Method of production and natural history of experimental posterior penetrating eye injury in the rhesus monkey. We developed an experimental model for a posterior penetrating eye injury that resulted in traction retinal detachment in 21 rhesus monkey eyes. The standard injury was an incision through the pars plana with vitreous prolapse and incarceration; the wound was then carefully closed with microsurgical techniques. At one to two weeks after injury, detachment of the posterior vitreous occurred and detachment of the retina occurred between seven and 11 weeks. The development of retinal detachment was related to traction on the peripheral retina over the vitreous base; and to the contraction of epiretinal membranes on the peripheral and equatorial retina. Our study supports clinical observations on the importance of blood in the vitreous in the development of vitreous traction and traction retinal detachment after a posterior penetrating injury.


Histology of wound, vitreous, and retina in experimental posterior penetrating eye injury in the rhesus monkey. We performed a histologic study to support our clinical observations on the mechanisms responsible for traction retinal detachment after a penetrating injury in the rhesus monkey eye. The monkey eyes (40 eyes; 40 monkeys) were characterized by intraocular fibrosis with the formation of a cyclitic membrane and epiretinal and subretinal membranes. The progression to a fibrous ingrowth from the wound occurred only in eyes with blood in the vitreous. The intravitreal fibroblastic proliferation had its origin mainly from the stroma of the ciliary body and choroid at the wound but probably also from the nonpigmented ciliary epithelium. A fibroblastic response was present within the vitreous as early as four days after injury, and had progressed to form a cyclitic membrane by six weeks. Epiretinal membranes were identified as early as four weeks after injury. They were most prominent over the peripheral retina anterior to the equator. It is likely that they are derived from multiple cellular sources including the fibrous ingrowth from the wound but they were also connected to the surface of the retina by bridges of tissue indicating a glial origin. The subretinal membranes appeared to be derived from both retinal pigment epithelium cells and glial cells.


Lysophosphatidic acids. Influence on platelet aggregation and intracellular calcium flux. Decanoyl-, palmitoyl-, and oleoyl-lysophosphatidic acid (LPA) were studied for their effects on platelet aggregation and intracellular calcium flux. Palmitoyl-LPA and oleoyl-LPA both caused a concentration-dependent aggregation of human blood platelets at concentrations of 12--300 microM. Aggregation by adenosine diphosphate (ADP) was enhanced at slightly lower concentrations. First-wave aggregation induced by these LPAs was not blocked by aspirin, indomethacin, or heparin, suggesting similarities to ADP aggregation. However, in washed platelets with a high calcium concentration, no serotonin secretion was observed, even though full aggregation occurred, suggesting that aggregation was not due to released ADP. This concept was supported by studies of platelets deficient in the storage pool of ADP and serotonin, which had a normal first-wave aggregation response to palmitoyl-LPA. Aggregation induced by palmitoyl LPA was inhibited by prostaglandin E1 (PGE1), theophylline, and ethylenediaminotetraacetate (EDTA), though in the presence of EDTA shape change occurred. Aggregation stimulated by palmitoyl-LPA or oleoyl-LPA was characterized by changes in the shape of the platelets with development of pseudopods and centralization of granules closely surrounded by contractile microfilaments and supporting microtubules. The addition of palmitoyl-LPA and oleoyl-LPA, but not decanoyl-LPA, caused the release of calcium from a platelet membrane fraction that contains elements of the intracellular calcium storage system and actively concentrates this cation in the presence of adenosine triphosphate (ATP) and magnesium. It is suggested that LPAs cause aggregation by stimulating the release of calcium intracellularly.


Susceptibility of the mammary gland to carcinogenesis: I Differentiation of the mammary gland as determinant of tumor incidence and type of lesion. The influence of age and mammary gland differentiation on the incidence of tumors induced by 7,12-dimethylbenz(a)anthracene (DMBA) was studied by correlating the development of the mammary glands of 20-180-day-old, virgin Sprague-Dawley rats with the number and type of tumors induced by DMBA administered at those various ages. The number of terminal end buds (TEBs), terminal ducts (TDs), and alveolar buds (ABs)/sq mm and their DNA-labeling indices (DNA-LI) were determined. Highest density of TEB occurred when the rats were 20 days old, decreasing thereafter. DNA-LI ranged between 25.2 and 29 in TEB of rats aged 30-55 days, which was coincident with the highest incidence of carcinomas. With aging, the number of TEBs and their DNA-LI decreased and the number of TDs and ABs increased, although with a low DNA-LI, which correlated with a lower incidence of carcinomas and higher incidence of benign lesions.


Interstitial anion distribution in striated muscle determined with [35S]sulfate and [3H]sucrose. The distributions of a charged and an uncharged extracellular tracer in the interstitial spaces of skeletal and heart muscles were examined in vivo by a double-labeling technique. 35SO4(2-) and [3H]sucrose were simultaneously injected intraperitoneally into rats and toads, and extracellular volume was determined in the rat gastrocnemius and left ventricle and in the toad semitendinosus. In nephrectomized rats and in toads with intact kidneys, sucrose and SO4(2-) spaces were constant for several hours. Sucrose and SO4(2-) spaces did not significantly differ in rat ventricle (P greater than 0.80); in rat gastrocnemius the sucrose space was much larger than SO4(2-) space (2P less than 0.0005), while in toad semitendinosus sucrose space was somewhat smaller than SO4(2-) space (2P less than 0.005). These observations suggest that fixed charges in the interstitial compartment can lead to extracellular anion exclusion in some tissues and perhaps to accumulation in others. The magnitude and direction of these effects differ for different striated muscles.


Kinetics of bicarbonate/chloride exchange in dogfish erythrocytes. A stopped-flow rapid reaction apparatus was used to monitor changes in extracellular pH in dogfish (Mustelus canis) erythrocyte suspensions under conditions where dpH/dt was determined by the rate of HCO3-/Cl- exchange across the red cell membrane. Experiments were performed on erythrocytes suspended either in their own plasma or in elasmobranch Ringer solution over a range of temperatures from 5 to 35 degrees C. The exchange fluxes at 25 degrees C for red blood cells suspended in their own plasma (2.03 nmol/cm2-s) or in Ringer solution (2.00 nmol/cm2-s) are not significantly different and can be compared to those obtained under similar conditions for human red cell suspensions (0.910 nmol/cm2-s). The flux for dogfish erythrocytes suspended in Ringer solution was reduced by 80% after exposure of the cells to SITS. An Arrhenius plot of the exchange rate constant yielded an activation energy of about 13.2 kcal/mol. We conclude that 1) plasma has no inhibitory effect of HCO3-/Cl- exchange across the dogfish erythrocyte membrane or on activity of intraerythrocyte carbonic anhydrase, 2) HCO3-/Cl- exchange probably occurs via the same mechanism in fish and mammalian erythrocytes, and 3) the conversion of plasms HCO3- to CO2 in dogfish can be catalyzed by intraerythrocyte carbonic anhydrase.


Cost-effectiveness evaluation of a home visiting triage program for family planning in Turkey. Graduate Turkish midwives were trained in triage rules for determining family planning home visit frequency based on risk of couples. In a sample of 542 couples followed for six months, modern contraceptive use increased 22 per cent among high-risk and about 15 per cent among moderate- and low-risk couples. After making assumptions about the fecundity, contraceptive success, and pregnancy complications, the estimated average cost per complication averted was $61 for high-risk, $177 for moderate-risk and $526 for low-risk couples.


Specific granules of the rat atrial muscle cell. The specific granules found in the atrial cardiac muscle cells of the normal rat were studied. The ultrastructural appearance of these granules demonstrated a fixative-dependent lability. Fixation with cacodylate buffered aldehydes yields three types of granules. However, fixation with phosphate buffered aldehydes or primary fixation with OsO4 yields granules of uniform appearance. The granules are found predominantly in the perinuclear zone; 78% of the granules are within ten linear micrometers of the center of the nucleus. Two independent methods of measurement demonstrate spherical diameters of these granules of 0.30 micron and 0.37 micron respectively. The granules are found in greater concentration at one pole of the nucleus than at the other. On the high density side there are 4.07 granules/micrometers3 which occupy 5.8% of the cytoplasmic volume. On the low density side there are 2.15 granules/micrometers3 which occupy 3.0% of the cytoplasmic volume. The granules at both poles are the same size. Atrial walls were incubated in a modified Tyrode's solution. One hour of incubation caused no change in the atrial granules. Addition of norepinephrine or L-Dopa resulted in the appearance of more granules but the size of the granules remained the same. Incubation with reserpine had no effect upon the atrial granules. Apparently the atrial myocardial cell is stimulated by exogenous catecholamine to synthesize more atrial granules which themselves do not appear to contain catecholamines.


Intracranial pressure in the cat during nitroglycerin-induced hypotension. Intracranial pressure measurements were made during nitroglycerin-induced hypotension in the cat anesthetized with halothane. A total of 48 individual observations were made in eight animals. The administration of sufficient nitroglycerin to decrease mean arterial pressure from a control value of 87 +/- 7 torr by 12 +/- 4 torr resulted in an increase in mean intracranial pressure from a control value of 7 +/- 2 torr to 12 +/- 2 torr. Larger decreases in mean blood pressure were associated with larger increases in intracranial pressure. The increase in intracranial pressure was similar to that previously reported for nitroprusside, and greater as well as more reproducible than that reported for trimethaphan. Thus, nitroglycerin may produce significant increases in intracranial pressure, and this may be a limiting factor in its clinical use.


Serologic study of Pasteurella aerogenes sp n. The antigenic attributes of Pasteurella aerogenes sp n were serologically compared with species of the genera Actinobacillus and Pasteurella. Examination included the tube-agglutination and double-immunodiffusion techniques. The results indicated the possibility of serologically different strains of P aerogenes. Antisera prepared from strains of P aerogenes also reacted well with antigens prepared from Yersinia pseudotuberculosis (P pseudotuberculosis) and P pneumotropica.


Bovine saccocystosis: patholgic features of naturally occurring infection with Sarcocystis cruzi. Naturally occurring bovine sarcocystosis caused death and illness in eight dairy heifers. Clinical disease was characterized by cachexia, peripheral lymph node enlargement, and anemia. Increased amounts of serum enzymes and anti-Sarcocystis antibody titers were present in affected animal. Macroscopic findings in two heifers at necropsy included emaciation and serous atrophy. Necropsied heifers (No. 1 and 2) contained different developmental stages of Sarcocystis cruzi; each stage was characterized by specific histopathologic findings. Heifer 1 had vascular endothelial schizonts in various soft tissues, with mild mononuclear cell infiltration, alveolar capillary fibrinous thrombi, and multifocal splenic necrosis. Heifer 2 had developing young S cruzi cysts, in myofibrils of cardiac and skeletal muscles, with a concurrent multifocal degenerative myositis. Marked lymphoid hyperplasia occurred in both heifers.


Immunization against bovine tropical theileriosis, using 60Co-irradiated infective particles of Theileria annulata (Dschunkowsky and Luhs 1904) derived from ticks. Portions of ground supernate material from Theileria annulata-infected and prefed adults of the Hyalomma anatolicum anatolicum were irridiated by 60Co source at 0, 3, 5, 6, 7, or 9 krads. These portions were injected subcutaneously into different groups of cross-bred calves. The calves injected with 0-, 3-, or 5-krad irradiated tick supernate had severe reactions (rectal temperature 39.8 to 41.6 C, two- to fourfold enlargement of prescapular lymph gland, mean peak parasitemia 27.3% to 32.5% infected erythrocytes, decreased PCV 41.7% to 60.7%, and hemoglobin concentration 37.5% to 50.8%), and many died, whereas those injected with 6- or 7-krad irradiated tick supernate had minimal reactions (rectal temperature 39.2 to 39.8 C, slight enlargement of prescapular lymph gland, parasitemia less than 1%, decrease packed cell volume 15.1%, and hemoglobin concentration 20.1%), with no mortality. All surviving calves injected with nonirradiated (0-) or 3-, 5-, 6-, or 7-krad irradiated tick supernate developed comparable indirect fluorescent antibody titers and were resistant to challenge exposure with infective material from 30 ticks. The calves injected with 9-krad irradiated tick supernate showed no reactions and did not develop indirect fluorescent antibody titers; they were also susceptible to challenge exposure with infective tick material.


Specificity in response of vaccinated swine and mice to challenge exposure with strains of Erysipelothrix rhusiopathiae of various serotypes. Swine and mice were vaccinated with standard erysipelas adsorbate bacterins made from Erysipelothrix rhusiopathiae of serotype 2 and were subsequently exposed to pathogenic strains of E rhusiopathiae, serotypes 1, 2, 4, 9, 10, and 11. Response to challenge of immunity in swine was determined by presence of urticarial lesions at the sites of intradermal injection of culture; response in mice was determined by the quantal (live-dead) method. After vaccination with standard bacterins, swine and mice were significantly more susceptible (P less than of equal to 0.01) to infection with strains of serotypes 9 and 10 than with strains of serotypes 1, 2, 4, or 11. An adsorbate bacterin made from the challenge strain of serotype 10 induced specific immunity to homologous challenge exposure in swine but not in mice. Bacterins made from the other challenge strains induced little or no immunity.


Frequency of Sarcocystis in pigs in Ohio and attempted transmission to cats and dogs. Tissues of 236 sows, obtained at slaughter in Xenia, Ohio, were examined microscopically after trypsin digestion. Sarcocystis bradyzoites were found in eight of 236 (3.4%) pigs (in 8 diaphragms, 7 esophagi, and 1 heart) and in three of 101 tongues. After these infected porcine tissues were fed to three dogs and three cats, none of the animals shed Sarcocystis sporocysts in their feces.


Evaluation of the enzyme-linked immunosorbent assay for detecting Brucella abortus antibodies. The specificity of enzyme-linked immunosorbent assays (ELISA) corresponds to conventional methods for detecting brucella antibodies in bovine serum. The ELISA test detected brucella antibodies early in only 12.5% of the cattle sera tested. Also, the sensitivity of ELISA was comparable to complement-fixation and Rivanol methods, but less sensitive than the standard tube agglutination method.


Alveolar macrophage migration. Influence of lung lining material and acute lung insult. Migration of alveolar macrophages collected by lavage from normal rhesus monkeys was tested in an under agarose migration system. Lung lining material and serum albumin obtained from normal rhesus monkeys enhanced the random migration of alveolar macrophages. A chemotactic effect for alveolar macrophages was demonstrated in response to lung lining material. Gel filtration of lung lining material using Sephadex G-200 indicated the presence of 4 distinct fractions. Fraction IV, which had a molecular weight of less than 5,000 daltons, had the greatest ability to enhance alveolar macrophage migration. Macrophages obtained from lungs of rhesus monkeys after they breathed an oxidant gas (ozone) for 7 days demonstrated decreases in both the number of cells randomly migrating and the distance they migrated. The addition of normal lung lining material to macrophages exposed to ozone enhanced their random mobility but did not restore migration values to control values. Ozonized lung lining material or rhesus monkey serum did not significantly alter alveolar macrophage migration from that of control lung lining material or serum. These data indicate that components of the acellular lining material of the lung can produce directional migration of alveolar macrophages and may serve to direct the central flow and clearance of macrophages from alveolar regions. Intraluminal alveolar macrophage accumulation during lung insult with ozone appeared to be related more to migration inhibition of resident cells than to recruitment of additional cells by chemotaxis.


[Role of the mycelium in the elimination of aflatoxin B1 from contaminated substrates]. When the aflatoxin-producing strain of Aspergillus flavus, nr 14409 developed in mixed cultures with non toxigenic strains, in solid or liquid media, it produced less aflatoxin than in pure culture. Investigations in view to elucidate the process promoting the toxin disappearance showed that the mycelium could immobilize a large amount of aflatoxin by adsorption on its walls.


Human obesity and some of its experimental counterparts. Human obesity is a manifestation of a positive energy balance. A variety of different factors influence this balance. The varieties of human obesity may be classified as follows: 1. Childhood onset with or without an increased number of adipocytes; 2. The syndromes of neuroendocrine dysfunction including hypothalamic obesity, Cushing's disease, and hyperinsulinism; 3. Dietary obesity; 4. Obesity due to physical inactivity; and 5. Genetic forms of obesity. Among the genetic form of obesity are the Laurence-Moon-Bardet-Biedl syndrome. Alstrom's syndrome, and possibly the Prader-Willi syndrome. Studies in experimental animals have increased our understanding of two of these forms of human obesity. These are: 1. Hypothalamic obesity associated with decreased sympathetic activity, hyperphagia and an increased secretion of insulin. Subdiaphragmatic vagotomy can reverse this syndrome; 2. Genetic forms of obesity inherited as recessive or dominant traits.


Pleiotropic control mutations affecting the sporulation of Bacillus subtilis. Mutations affecting quantitatively the production of the sporulation-associated extracellular alkaline protease were isolated and characterized. They fall into at least five genes, three of which, ScoA, B and C, were mapped in the argC-metC region. The pleiotropic effects of these mutations concern several or all of the following: rate and timing of protease production, synthesis of alkaline phosphatase, time-course of spore formation. Electron microscopic evidence indicates delayed switch from one morphological stage to another. The nature of the Sco mutations and the genetic regulation of sporulation are discussed.


Immunogenic activity of a cell wall fraction extracted from Brucella abortus in guinea-pigs. A cell wall fraction (F8) extracted by boiling sodium dodecylsulfate at 4 % from Brucella abortus 99S was used with oil adjuvant to vaccinate groups of ten guinea-pigs, at doses equivalent to 1 X 10(9) and 1 X 10(10) bacteria, once or twice at 3 month intervals. H38 vaccine, a total cell vaccine from formalized B. melitensis 53 H38, was used as a reference, at doses 3 X 10(8) and 3 X 10(9) bacteria. These doses were chosen since they have about the same vaccinal activity in mice being respectively equal to 10 and 100 mice optimal dose (MOD). One extra-group of guinea-pigs received two injections of 100 microgram of smooth-lipopolysaccharide (LPS-S) of B. melitensis 16M, in adjuvant. Control group received the adjuvant only. Guinea-pigs were challenged 3 months after the last vaccination with 5,000 colony-forming units of B. abortus 544, and autopsied 40 days later. The spleen and 8 lymph nodes were cultured: a guinea-pig is considered as protected if no Brucella was found in any sample. Protection afforded by the two vaccines is dose-dependent. H38 vaccine gives a better protection (infected 24 %) than F8 (46 %) since a higher dose is needed to obtain the same level of protection: i. e., 100 MOD of F8 is about equal to 10 MOD of H38 (35 and 37 % respectively). Contrary to what was previously shown in mice, recall does not improve the immunity and LPS-S does not vaccinate at all.


[Cutaneous manifestations observed during prolonged intravenous feeding: 3 cases. Review of the literature (author's transl)]. 3 patients (one infant and two adults) in prolonged intravenous feeding for digestive diseases developed cutaneous symptoms resembling acrodermatitis enteropathica. Essential fatty acid and hypozincemia (in 2 of 3 cases) are found. The dermatitis disappeared slowly with oral alimentation in 2 cases, and in a few days in the third one, with oral zinc sulfate. Review of literature shows that dermatitis occurring during prolonged intravenous feeding is attributed to essential fatty acid, zinc, or less often amino acid, deficiency. But resemblance of dermatitis with acrodermatitis enteropathica in most cases, high frequency of hypozincemia, and dramatic effects of treatment with zinc salts allow to think, that zinc is a key factor. Nevertheless, it is necessary to study simultaneously those different parameters and also vitamins A, E and B to conclude whether it exists or not many deficiencies (related or not) as an etiologic factor for cutaneous symptoms.


Enteral and parenteral nutrition in patients with head and neck cancer. Head and neck cancer patients present with special problems in nutritional homoeostasis because of local phayngeal discomfort and obstruction and difficulty with deglutition due to either the neoplasm or the surgical alterations in the upper aerodigestive tract. Pretreatment malnutrition and vitamin deficiency are only compounded by the nutritional stress imposed by radiation and surgery. Reduced wound complications occur if the patients are nutritionally replenished before treatment. While nasogastric feedings will suffice in many patients, rapid nutritional restoration by this method is limited, and positive nitrogen balance may be difficult to achieve in the severely malnourished patient. Intravenous hyperalimentation offers a rapid and efficacious alternative in selected cases. The case histories of two patients are presented to illustrate these concepts.


A critical comparison of the virus neutralizaiton, radioimmunoprecipitation and immunodiffusion tests for the serological diagnosis of BLV infection. Several serological tests are available for the detection of antibodies to BLV. Thus far, only the virus neutralization antibody (VNA) test, the immunofluorescence test, and the immunodiffusion test with the major internal virion protein have been critically evaluated as diagnostic methods for the identification of BLV-infected cattle. Of these tests, the VNA test is the most sensitive and specific. Therefore, in the present study the VNA test has been applied to evaluate the reliability of the radioimmunoassay for BLV p25 (RIAp25) and of the immunodiffusion test with BLV-associated glycoprotein antigen (IDgp). The results show a very close agreement between the RIAp25, and the VNA test. The IDgp test is less sensitive than the RIAp25, particularly for the detection of BLV antibodies in early stages of infection. The RIAp25 is more rapid than the VNA test and does not require tissue culture techniques. Thus, the RIAp25 seems to be the most practical and sensitive available method for the serolgical diagnosis of BLV infection in cattle.


[Periodic modifications of the preoptico-terminal LRH tract in the squirrel monkey during the estrous cycle (author's transl)]. The quantities of specific immunoreactive material along the preoptico-terminal LRH tract show important modifications during the estrous cycle in the squirrel monkey. During the late follicular phase and the peri-ovulatory period the preoptico-terminal LRH tract shows "low" or "very low" fluorescence intensity. A progressive but very important increase occurs during the luteal phase, followed by great variations during the early and middle follicular phases. These variations suggest a conspicuous release of LRH, especially during the middle follicular phase. It is supposed that the preoptico-terminal LRH tract (whose LRH is released into the capillaries of the vascular organ of the lamina terminalis and reaches the systemic blood) controls gonadotropic cell sensitivity to the preovulatory discharge of the hypothalamo-infundibular LRH tract, and perhaps also gonadotropins synthesis.


Blood groups and reproduction in Hebridean women. The distribution of ABO and RH blood groups was studied in 910 fertile women from the Isles of Lewis and Harris. The frequencies of group O mothers fell and of RH-mothers rose with increasing parity, but there were no significant changes in the ABO and RH blood group distributions among their offspring when they were subdivided according to their mothers' parity. When mother-offspring pairs classified according to their ABO and RH compatibility status it was found that RH incompatibility was associated with greater number of previous pregnancies and of abortions. Regression coefficients of birth weight on maternal stature and maternal age were significant only for doubly compatible female offspring and on number of previous pregnancies only for doubly compatible offspring of both sexes. When offspring were classified according to their own and their mothers' ABO blood groups, considerable variations in sex ratio were found. However, the only statistically significant finding was a deficit of A females among the offspring of O mothers. It is suggested that for the ABO blood groups system incompatibility selection, which favours homozygotes rather than heterozygotes, can be counterbalanced by selection for greater maternal tolerance of incompatible offspring with increasing parity. Hence the loss of heterozygotes in lower parity mothers may be compensated by an increase production in higher parity mothers. For the Rh system the same mechanism may occur, but there is evidence additionally of reproductive compensation.


Synthesis of high affinity antibodies in irradiated rabbits grafted with allogeneic cells from hyperimmune donors. Irradiated rabbits grafted with allogeneic lymph node, spleen and bone marrow cells from a donor rabbit hyperimmunized against TMV synthesize high affinity antibodies, displaying mainly recipient allotypic specificities, after antigen boosting. By contrast, recipient rabbits from non-immune donors synthesize antibodies of lower affinity. It is suggested that the differentiation of new emerging host B cells is specifically influenced by the presence of donor-memory cells.


Penetrability of the outer membrane of Neisseria gonorrhoeae in relation to acquired resistance to penicillin and other antibiotics. Acquired antibiotic resistance in Neisseria gonorrhoeae is principally associated with three genetic markers, penA, mtr, and penB. penA is a specific marker for penicillin resistance, whereas mtr and penB are nonspecific in conferring resistance to penicillin and several other antibiotics as well. It has been suggested that the nonspecific markers may cause a general decrease in the penetrability of the gonococcal outer membrane. To investigate this, antibiotic penetration of the outer membrane was studied in two isogenic strains-FA19 (susceptible parent) and FA140 (containing penA, mtr, and penB)-and also in a clinical isolate with multiple resistance. The method involved brief treatment of exponential cells with ethylenediaminetetraacetic acid at 5 degrees C to disrupt the outer membrane barrier. The 50% inhibitory concentrations of antibiotics for treated and normal cells were measured turbidimetrically, and from their ratios outer membrane penetration barriers were calculated. Small barriers were observed for actinomycin D and benzylpenicillin, and these were very similar in the susceptible and resistant strains. Also, in FA140 no significant barriers for rifampin, erythromycin, and tetracycline were detected. These results suggest that mechanism(s) other than reduced outer membrane penetrability underlie acquired resistance due to penA, mtr, and penB.


Plasmid-related transmissibility and multiple drug resistance in Streptococcus faecalis subsp. zymogenes strain DS16. Streptococcus faecalis subsp. zymogenes strain DS16 was found to harbor two plasmids, designated pAD1 (35 megadaltons) and pAD2 (15 megadaltons). pAD1 is transmissible and determines a hemolysin-bacteriocin, whereas pAD2 is non-conjugative and determines resistance to erythromycin, streptomycin, and kanamycin. pAD2 could be mobilized by pAD1, but usually involved formation of a pAD1-pAD2 cointegrate.


Isoniazid inhibition of the synthesis of monounsaturated long-chain fatty acids in Mycobacterium tuberculosis H37Ra. Isoniazid inhibited C(24) and C(26) monounsaturated fatty acid synthesis in Mycobacterium tuberculosis H37Ra. Time courses of this inhibition and that of mycolic acid synthesis were similar.


In vitro synthesis of peptidoglycan by beta-lactam-sensitive and -resistant strains of Neisseria gonorrhoeae: effects of beta-lactam and other antibiotics. The synthesis in vitro of peptidoglycan by Neisseria gonorrhoeae was studied in organisms made permeable to nucleotide precursors by treatment with ether. Optimum synthesis occurred at 30 degrees C in tris(hydroxymethyl)aminomethane-maleate buffer (0.05 M; pH 6) in the presence of 20 mM Mg(2+). The incorporation from uridine 5'-diphosphate-N-acetyl-[(14)C]glucosamine into peptidoglycan, measured after precipitation of the cells with trichloroacetic acid, was sensitive to the beta-lactam antibiotics, bacitracin, diumycin, and tunicamycin and relatively resistant to spectinomycin and tetracycline. Differences in sensitivity between preparations from a beta-lactamase producer and a laboratory segregant derived from it were not great. Synthesized peptidoglycan was also fractionated into sodium dodecyl sulfate-soluble and -insoluble portions. beta-Lactam antibiotics at concentrations equivalent to the minimal inhibitory concentrations for growth of the organisms did not inhibit peptidoglycan synthesis, but rather caused a small enhancement. At higher concentrations, above about 0.5 mug/ml, incorporation into sodium dodecyl sulfate-insoluble material was progressively inhibited, whereas the amount of sodium dodecyl sulfate-soluble product increased greatly, more than compensating for the loss of the precipitable fraction. Similar observations were made with three strains, and also with the beta-lactam clavulanic acid, normally considered as a beta-lactamase inhibitor rather than as itself an effective antibiotic.


Antibacterial activity of a new parenteral cephalosporin--HR 756: comparison with cefamandole and ceforanide. HR 756, a new parenteral cephalosporin that is beta-lactamase resistant, was tested against 271 bacterial isolates. Both agar and broth dilution testing were employed, using two media and two inoculum sizes of bacteria. Antibacterial activity of the drug was compared to that of cefamandole (CFM) and ceforanide (CFN). In agar, HR 756 was more active than CFM and CFN against all bacteria tested except isolates of Staphylococcus aureus, which were better inhibited by CFM. HR 756 exhibited some antipseudomonas activity in agar, although a marked inoculum effect was apparent. A comparison of median minimum inhibitory and bactericidal concentrations in broth showed again that HR 756 was the most active of these three drugs. HR 756 demonstrated enhanced antibacterial activity compared to CFM and CFN against bacteria sensitive to all three drugs as well as against more resistant isolates of Serratia marcescens, Enterobacter species, and indole-positive Proteus. As with other cephalosporins, results for most bacteria were affected by inoculum size, medium, and type of dilution test employed in in vitro studies.


In vitro comparison of rosamicin and erythromycin against urinary tract pathogens. The in vitro activity of rosamicin and erythromycin was compared at various pH values against 311 strains of bacteria representing common urinary tract pathogens. Alkalinization of the media consistently and significantly increased the antibacterial activity of rosamicin against all of the organisms tested. This was also true for erythromycin except when tested against strains of Proteus. At pH 8, rosamicin was two- to sixfold more active than erythromycin against Enterobacteriaceae. The activity of both antibiotics against Pseudomonas aeruginosa was very similar when tested at pH 8. Erythromycin was twice as active as rosamicin at pH 8 against group D streptococci. The activity of both antibiotics was bacteriostatic and inoculum size dependent, regardless of the organism tested or the pH of the test media. The greater activity of rosamicin against Enterobacteriaceae warrants clinical investigation.


Circular myotomy as an aid to resection and end-to-end anastomosis of the esophagus. Segments ranging from 40 to 70% of the thoracic esophagus were resected in 80 mongrel dogs. End-to-end anastomosis was effected after circular myotomy either proximal or distal, or both proximal and distal, to the anastomosis. Among dogs undergoing resection of 60% of the esophagus, distal myotomy enabled 6 of 8 animals to survive, and combined proximal and distal myotomy permitted 8 of 10 to survive. Cineesophagography was performed in a majority of the 50 surviving animals and showed no appreciable delay of peristalsis at the myotomy sites. When these sites were examined at postmortem examination up to 13 months after operation, 1 dog showed a small diverticulum but none showed dilatation or stricture. It is concluded that circular myotomy holds real promise as a means of extending the clinical application of esophageal resection with end-to-end anastomosis.


Study of two new non-steroid anti-inflammatory drugs having a pyrazole structure (LM 22070 and LM 22102). Two derivatives from a new heteroarylacetic series, 1,3,4-triphenylpyrazole-5-acetic acid (LM 22102) and 1-isobutyl-3,4-diphenylpyrazole-5-acetic acid (LM 22070), were selected on the basis of their anti-inflammatory, analgesic and antipyretic properties. In the mouse, LM 22102 and LM 22070 were respectively 15 and 30 times less active than indomethacin in Koster's test, but they were 9 and 13 times less toxic than the reference drugs. In contrast, they were very active in the rat and the guinea-pig. LM 22102 appeared to be as active as indomethacin in the various tests performed: Randall and Selitto's test for analgesic activity, hyperthermic rat, experimental models of inflammation (UV erythema, carrageenin-induced oedema, cotton granuloma, adjuvant-induced arthritis). In vitro, its inhibition of prostaglandin-synthetase in guinea-pig lung was appreciably more powerful than that of indomethacin. Like all potent non-steroid anti-inflammatory drugs it has ulcerogenic activity, similar to that of indomethacin, which accounts for its acute oral toxicity in the rat. The activity of LM 22070 is either the same as (antipyretic action) or inferior to (analgesic and anti-inflammatory activity and inhibition of prostaglandin-synthetase) that of indomethacin, but always markedly superior to that of phenylbutazone. Its ulcerogenic activity and oral acute toxicity in the rat are respectively 2.5 and 3 times weaker than those of indomethacin.


[Systematic study of ventriculo-auricular conduction and its importance in the detection of aberrant conduction pathways]. Ventriculo-atrial conduction was studied by ventricular pacing in three groups of patients: 34 cases with the preexcitation syndrome on surface ECG, 35 cases with documented paroxysmal atrial tachycardia but with otherwise normal ECGs and 120 cases without either of these two conditions. This conduction time was unchanged up to pacing rates of over 160/min in 88 p. 100 cases with preexcitation and was thus a sign of a nodal short-circuit. This phenomenon was also observed in 85 p. 100 cases with isolated paroxysmal atrial tachycardia and in 20 p. 100 normal cases which suggests the presence of a latent accessory pathway in these patients.


[Automatic activity of the pre-excitation pathways]. The possibility of preexcitation pathways exhibiting automatic activity was demonstrated in 3 cases: in two cases electrophysiological studies supported this diagnosis which was confirmed in the third case by histological examination of the preexcitation pathway. During sinus node dysfunction, spontaneous or induced (by rapid right atrial pacing or by a reciprocating tachycardia), the substitute rhythm arose from the Kent Bundle either transiently or for a longer period: rhythms arising from the Kent Bundle can only be diagnosed after eliminating the possibility of an atrioventricular junctional rhythm conducted to the ventricles by Mahaïm fibres.


[Detection of pulmonary embolisms by recording of the variations of thoracic impedance at each lung]. It is possible to record changes of volume caused by variations of the blood supply to each lung by measuring the transthoracic electrical impedance. A theoretical study was performed beforehand to define the variations of the impedance of the deep-lying structures. The form, number and distribution of the electrodes were determined by experiments on a model so that only variations of the impedance of the pulmonary parenchyma, and not of the mediastinum, were recorded. In this way the origins of the signals recorded were known. The validity of the method was tested on patients having undergone pneumonectomy and on patients with defects of pulmonary perfusion. Using the data obtained during the preceding experimental studies it was possible to defect perfusion defects caused by pulmonary embolism. Five cases of pulmonary embolism, confirmed by angiography and lung scan, of varying severity and chronicity, are reported. The amplitude of the impedance curve was reduced on the affected side, the difference of amplitude between the two being related to the degree of vascular amputation.


[1st degree and 2nd degree blocks (Wenckebach type) during right ventricular stimulation in the course of Prinzmetal's angina]. Right axial deviation and delay between stimulation and ventricular response was observed during pacing of the apex of the right ventricle in Prinzmetal angina. The degree of deformation of the ventricular complex and the length of this delay appear to be related to the severity of the anginan, the length of the preceding diastolic period and the amplitude of stimulation. This observation demonstrates the presence of conduction defects at the heart of ischaemic myocardium and may explain the failure of prophylactic pacing in Prinzmetal angina complicated by paroxysmal atrioventricular block.


[Prinzmetal's angina initiated by interruption of exercise. 5 cases with normal coronary radiograms]. Five male patients, aged between 31 and 58 years, presented with anginal chest pain with nausea and sweating after the interruption of exercise. Prinzmetal variant angina was observed during the recovery phase of exercise tolerance testing. Coronary arteriography and selective left ventricular angiography were normal in all cases. Ergonovine, used in one case, induced coronary artery spasm. The angina was eased by Nifedipine in three patients and passed off with time in the other two patients. In one case attack occurred with amiodarone therapy and in another with glyceril trinitrate, after normal exercise tolerance tests. Vagotonia, all the more pronounced when sympathetic tonus is increased, and hyperventilation seem to be the causative factors of what probably results from coronary artery spasm. Nifedipine, a calcium-blocking agent would appear to be the treatment of choice.


[Septal rupture after myocardial infarct. Early operation; 31 cases]. 31 survivors of a group of 49 patients with septal rupture during acute myocardial infarction were operated on average 8 days after the onset of necrosis. The operation was performed after a period of circulatory assistance in 23 cases and consisted of septal reinforcement, closure of the perforation and resection of necrotic tissue. The results were satisfactory in patients operated on early after effective resuscitation (91 p. 100 survival), and better than in the patients operated on after the maximum possible delay (50 p. 100 survival) and in patients in whom poor tolerance of the VSD led to an emergency salvage operation (29 p. 100 survival).


[Hemodynamic and cartographic study of intravenous trinitrin in the acute stage of myocardial infarct]. 12 cases of acute myocardial infarction were prescribed intravenous trinitrin. Haemodynamically, the drug invariably affected the pre-load whether the haemodynamic state was normal (group I), or disturbed by left ventricular failure (group II). Myocardial function was only improved in cases with left ventricular failure. Mapping studies, performed to assess, at least theoretically, the degree of ischaemia, only showed a transient lowering of the ST elevation compared to a control group, and limitation of the ischaemic area around the myocardial necrosis could not be proved.


[Effect of nitrate derivatives on the contractility and relaxation of papillary muscle in hypoxia and reoxygenation]. The direct action of nitrate derivatives on myocardial contractility is not fully understood. The effects of Glyceryl Trinitrate (1 mM/L.) and Sodium Nitro prussiate (3 X 10(-5) M/L.) on papillary muscle were studied during 30 minutes hypoxia followed by 60 minutes reoxygenation: Both conditions were analysed every 5 minutes: 1. Contractility was assessed by maximal shortening velocity with no load (Vmax), maximal isometric force (PF), number of active cross-bridges and peak time (TPF), a characteristic of the period of activity. 2. Relaxation was assessed by the relaxation velocity (V relax) and the 1/2 relaxation time (THR). The two nitrate derivatives had the same effects: during anoxia, a notable reduction of the maximal force was observed; myocardial depression continued during the first 15 minutes of reoxygenation. After the 30th minute of investigation all parameters increased significantly (107-110 p. 100, p less than 0,01); TPF and THR returned to normal. A positive inotropic effect and improvement of the relaxation phase were observed at the end of reoxygenation. This effect is not attributed to improved segmental performance especially as it occurred at dosages close to those used in therapeutics.


[Use of dopamine in sequelae of extracorporeal circulation. Apropos of 50 patients]. Dopamine was used after open heart surgery in a group of 50 patients. The therapeutic indications were: diffuse coronary insufficiency in 27 cases, myocardial infarction in 12 cases and early septicaemic shock in 6 cases. In the other 5 cases, dopamine was prescribed for short lasting circulatory insufficiency. The dosage varied between 3-15 gammas/kg/min. The variations of different parameters were studied over 12 hours. Improvement of cardiac efficiency was an early feature (less than 3 h) and was observed for all dosages (above 3 gammas/kg/min). It was accompanied by a marked diuresis. The chromotropic effects were non-existent at these dosages. At medium-term dopamine was effective in 40 patients (80 p. 100). Dopamine is effective in over 3 out of 4 cases after cardiopulmonary bypass. Its effect is immediate, and is observed in dosages less than 10 gammas/kg/min.


[Study of the long-term psychological consequences of heart valve prostheses]. The present follow-up period of cardiac surgery allows assessment of the long-term consequences of valvular prostheses, the short-term consequences having already been the object of many studies. 50 patients of both sexes, operated on for aortic or mitral valve disease between 1973 and 1974 were interviewed to assess their degree of psychological adaptation with regard to their cardiac status and the principal factors of adaptation. The position of the prosthetic valve (aortic or mitral) seemed to be of little importance and the prognosis depended rather on sex, age at operation, previous personality, intelligence quotient, postoperative psychiatric complications and the interval between diagnosis of the disease and operation.


Behavioral and endocrine responses of schizophrenic patients to TRH (protirelin). We studied the effects of intravenous protirelin (thyrotropin-releasing hormone) in 17 schizophrenic patients and 17 normal subjects. A total of 12 patients received protirelin, 0.5 mg, and, on another occasion, niacin, 2 mg, in a double-blind, crossover design. Both behavioral and endocrine data were collected. Five patients received protirelin in an open trial; only endocrine data were collected. Protirelin caused about a 50% prompt decrease in psychotic symptoms. Patients then tended slowly to experience a relapse. Side effects were about as infrequent after protirelin as after niacin. We assayed serum prolactin (PRL), growth hormone (GH), thyroid-stimulating hormone (TSH), L-triiodothyronine (T3) and thyroxine (T4). Free T4 (FT4) index was calculated. The values for PRL, GH, and TSH at baseline and after protirelin stimulation were normal. Patients showed lower T3 values at baseline, but a brisker T3 response to protirelin, than controls. Their FT4 indices were higher at baseline. Patients showed diminished T4 binding sites rather than increased total T4. The causes of these alterations in thyroid dynamics are unidentified.


The role of receptors of the autonomic system in regulation of glycogen synthetase activity in the heart and skeletal muscle in rats. By determining glycogen synthetase activity, rate of 14C-glucose incorporation and glycogen levels, using pharmacologic agents which act on the alpha, beta M and N receptors, the influence of the autonomic system on synthesis of this polysaccharide in heart and skeletal muscle was analysed. The results indicate that the autonomic system is involved in intracellular autoregulation of glycogen synthetase activity through tissue receptors. Drugs which stimulate the cholinergic system depress this enzyme activity in the heart and skeletal muscle indirectly by releasing endogeneous catecholamines (nicotine-gangliconic effect) and also inhibit utilization of energetic ATP and phosphocreatinine reserves in the heart (muscarinic effect). Stimulation of the alpha-adrenergic receptor enhances glycogen anabolism in both types of muscles depending on the stimulatory influence of nonsterified sugers released in the process of glycogen hydrolysis and depression of cAMP level and presence of glucosteroids. Stimulation of beta-adrenergic receptors induces opposite changes. Analysis of the influence of pharmacologic agents that stimulate and inhibit decomposition and synthesis of glycogen showed that hydrolytic decomposition is probably one of the main processes of intracellular autoregulation of glycogen synthetase activity.


New derivatives of 6-hyroxy-coumaranone-2-acetic acid with anti-prostaglandin activity. Sixteen new amide and ether derivatives of 6-hydroxy-coumaranone-2-acetic acid (1) were synthetized, some of which were screened pharmacologically for anti-prostaglandin activity.


Epidemiological markers for Pseudomonas aeruginosa. VII. Nosocomial occurrence in urological ward. Comparison of two phage typing sets, pyocine typing, and serogrouping. A comparison of two pyocine typing methods with serogrouping, and two phage typing sets has been made. In one instance, a contaminated bladder irrigation fluid of 0.05% silver nitrate solution caused a series of urinary tract infections. By all systems, fewer of the presentstrains were typable than usual. Among the phage typing sets the one developed by LINDBERG et al. typed only 66% whereas that selected by BERGAN typed 83%, both less than observed previously. The set of LINDBERG et al. also rendered longer pattern codes, and yielded more variable results with related strains. A set of pyocine indicator strains, selected among the strains to be typed, was more suitable than one developed elsewhere. Comparison of five different methods of epidemiological typing of Ps. aeruginosa indicated that phage typing alone is not entirely satisfactory for this species and should therefore always be combined with serogrouping.


Retarded ejaculation: a review.

Retarded ejaculation: a review. Retarded ejaculation is the persistent difficulty or inability to ejaculate despite the presence of adequate sexual desire, erection, and stimulation. The causes of this dysfunction may be organic, i.e., medical illness or drug ingestion (particularly medications with antiadrenergic effects), the result of surgical interventions, or secondary to inhibiting psychological factors. With regard to psychological determinants, fear, guilt, resentment, and passively have all been implicated, although objective studies are rare. The sexual object choice of men with retarded ejaculation has ben reported by several clinicians and investigators to be other than adult members of the opposite sex, while the marital relationship of these males has been considered etiological in other instances. Outcome assessment to date consists mostly of individual case reports or reports on small groups of patients treated without controls. To some extent, routine reliance on long-term traditional therapy has yielded to shorter, symptomatic learning-based treatments. While improved outcomes have been reported, many patients do not respond well. It is not yet possible to objectively predict succes or failure. Since it is our impression that this sexual dysfunction is more common than previously assumed (or is increasing in frequency), our present lack of data should soon be remedied.


Intrathoracic meningoceles and neurofibromatosis. We describe here four additional cases of intrathoracic meningoceles associated with neurofibromatosis, bringing the total number of reported cases of thoracic meningoceles to 88. Seventy-five (85%) have been associated with neurofibromatosis. Possibly, both dural and regional vertebral dysplasia are intrinsic to neurofibromatosis and contribute to the development of the meningocele.


Sorption and movement of pesticides on thin layer plates of Brazilian soils. The sorption from aqueous solution (Table II), and movement in water on thin layers plates (Figure 1) of 7 soils (Table 1) of 3 organochlorine, 2 organophosphorus and 1 carbamate insecticide was determined in the laboratory. Generally, all substances were sorbed most and moved least on soils richest in organic matter. However, sorption was not a function of organic matter content alone (Table III). Aldrin and DDT were most strongly sorbed and did not move from the point of application on the thin layer plates of any soil. On all 7 soils, carbaryl was the least strongly sorbed insecticide. On 5 soils, lindane, parathion and malathion were increasingly strongly sorbed, but on the other 2 soils lindane was mostly strongly sorbed. The apparent greater mobility of 14C-labelled malathion on thin layers of soils repeatedly leached could be explained by the formation of more polar substances.


Pseudomonas corneal ulcer. The causative role of contaminated eye cosmetics. The clinical significance of contaminated ocular cosmetics is illustrated by the case of a 47-year-old woman in whom a Pseudomonas corneal ulcer developed immediately after she sustained minor corneal trauma with a mascara applicator. Pseudomonas aeruginosa was cultured from the corneal ulcer and the mascara. In addition to the causative role in acute corneal ulcers, contaminated eye cosmetics contribute to chronic external eye infections. Retail eye cosmetics are typically free of contamination when purchased. The inoculation of the cosmetic occurs during normal use.


Alkaline phosphatase activity in the ganglion cells in and near the temporal bone. The distribution pattern of alkaline phosphatase was studied in the ganglion cells in and near the temporal bone of some mammals. No or extremely weak activity of alkaline phosphatase was observed in or near the spiral and vestibular ganglion cells of the bat, rat, cat, and monkey. However, intense to moderate enzyme activity was noted exclusively in the peripheral areas of the spiral and vestibular ganglion cells of the guinea pig. The enzyme activity was also demonstrated in the nerve fibers at some distance from both axonal and dendritic processes of the spiral and vestibular ganglion cells of the guinea pig. Trigeminal and geniculate ganglion cells of all mammals examined showed intense to moderate enzyme activity in their capsular cells. There is a marked difference in the phosphate metabolism in the capsular tissues of the ganglion cells in or near the temporal bone of various mammals.


Transformation of Pseudomonas aeruginosa strain PAO with bacteriophage and plasmid DNA. A procedure has been developed which allows transformation of P. aeruginosa strain PAO with plasmid and bacteriophage DNA at a frequency of 10(-6) per recipient cell. The method is similar in outline to that developed for Escherichia coli. It involves growing the recipient cells to 3-5 x 10(8) per ml in nutrient broth, washing the cells with 0.1 M MgCl2, resuspending in 0.175 M CaCl2 for 20 min, exposing to DNA for 1 h and then heat pulsing at 42 degrees C for 1 min. Some plasmid markers are expressed immediately, whereas others require time for phenotypic expression.


[Immunologic diagnosis of animal hydatidosis--Preliminary results]. Immunological reactions for diagnosis of Hydatidosis in cattle and swine are studied, such as Casoni, Latex agglutination and Serum-precipitation. The preliminary data shows that procedures may be useful in clinical practice of bovines. The same techniques in swine shows much promise, but requires further evaluation. The intradermal test for Hydatic disease, introduced by Casoni (1911) has been employed in some parts of the world and seems to be of high sensitivity in bovine. Latex agglutination and precipitation Test may be used in cases of weak skin reactions.


[Sensitization to E and C erythrocyte antigens]. The appearance of sentibilition on antigens E and c was described, noticed for the first time after many years identification on our sera.


Rabbit erythrocyte purine nucleoside phosphorylase. Initial-velocity studies. 1. Concave-downward double-reciprocal plots were obtained for rabbit erythrocyte purine nucleoside phosphorylase when the concentration of Pi was varied over a wide range at a fixed saturating concentration of either inosine or deoxyinosine. Similar behaviour was also displayed by the calf spleen enzyme. 2. The degree of curvature of double-reciprocal plots was greatly modified by the presence of SO42-, introduced into the assay mixture with the linking enzyme xanthine oxidase; competitive inhibition by SO42- was observed over a narrow range of high Pi concentrations. 3. Partial inactivation with 5,5'-dithiobis-(2-nitrobenzoic acid) resulted in a marked alteration in the kinetic properties of the enzyme when Pi was the variable substrate. 4. Initial-velocity data are expressed in the form of Hill plots, and the significance of such plots is discussed.


Rabbit erythrocyte purine nucleoside phosphorylase. Differential-inactivation studies. 1. Qualitative studies on the stability of rabbit erythrocyte purine nucleoside phosphorylase showed a marked decrease in the susceptibility of the enzyme to thermal inactivation and digestion by proteinases of different specificities in response to certain of its substrates. 2. The extent to which inosine stabilizes the enzyme against thermal and proteolytic inactivation is related in a quantitative manner to the concentration of this substrate; it is proposed that differences in the rates of inactivation of the enzyme may reflect substrate-induced conformational changes in the enzyme structure that could alter the binding properties of the enzyme in a kinetically significant way. 3. A synergistic effect in the stabilization of the enzyme is observed in response to both substrates, inosine and phosphate, when the enzyme is inactivated with Pronase. 4. In the presence of substrate an increased rate of inactivation after reaction with 5,5'-dithiobis-(2-nitrobenzoic acid) is reported. 5. Differential-inactivation studies were also carried out with calf spleen purine nucleoside phosphorylase, and the results are discussed in relation to the kinetic properties displayed by this enzyme.


Phospholipid-dependence of oestrone UDP-glucuronyltransferase and p-nitrophenol UDP-glucuronyltransferase. Hepatic UDP-glucuronyltransferase activity was resolved into two fractions, one exhibiting oestrone glucuronyltransferase activity and the other exhibiting p-nitrophenol glucuronyltransferase activity. Hydroxyapatite-column chromatography removed greater than 95% of the phospholipids from both preparations. The partially purified delipidated enzymes were essentially devoid of catalytic activity, but activities were restored by the addition of phospholipids or phosphatidylcholine mixtures containing various saturated and unsaturated fatty acids. Both oestrone and p-nitrophenol glucuronyl-transferase activities were reconstituted to similar degrees with the phosphatidylcholine mixtures. When purified phospholipids were tested, phosphatidylcholine and lysophosphatidylcholine were most effective in restoring activity, whereas phosphatidylethanolamine was the least effective. These results further suggest that oestrone and p-nitrophenol UDP-glucuronyltransferases are dependent on phospholipids for their activity.


The isolation and properties of a second glycoprotein (LGP-II) from the articular lubricating fraction from bovine synovial fluid. A high-molecular-weight glycoprotein (LGP-I) was shown [Swann, Sotman, Dixon & Brooks (1977) Biochem. J. 161, 473--485] to be the major constituent in the articular lubricating fraction from bovine synovial fluid. In addition to the LGP-I component, a second glycoprotein (LGP-II) was also present. After fractionation of bovine synovial fluid by sequential sedimentation in CsCl density gradients, the LGP-I and LGP-II components were separated by gel-permeation chromatography. The LGP-II component was then purified by chromatography on DEAE Bio-Gel A and Bio-Gel P-150. The molecular weight of the LGP-II component was 48,800 calculated from sedimentation-equilibrium measurements. Amino acids represented 53% (w/w) and carbohydrate constituents 36% (w/w) of the molecule. Glutamic acid and lysine (144 and 100 residues/1000 residues) were the major amino acids. Glucosamine, mannose, galactose and N-acetylneuraminic acid [representing 8.0, 6.6, 9.5 and 11.9% (w/w) respectively] were the only carbohydrate constituents detected. Immunodiffusion analysis showed that LGP-II component did not form a detectable precipitin line with antiserum to bovine serum. It appears likely, therefore, that this glycoprotein is synthesized by the joint tissues and is not derived from serum.


Purification of alcohol dehydrogenase from Drosophila by general-ligand affinity chromatography. A method for the purification of alcohol dehydrogenase from Drosophila melanogaster is described. The method makes use of 8-(6-aminohexyl)amino-5'-AMP, immobilized on Sepharose 4B, as an affinity ligand. Since alcohol dehydrogenase from Drosophila shows weak affinity for this column, a novel technique was developed to separate alcohol dehydrogenase from both unbound proteins and more strongly bound enzymes. The purification procedure is simple to operate and give a homogeneous preparation in good yield after only three steps.


Strain differences in rat liver (UDP-glucuronyltransferase activity towards androsterone. Male Donryu, Wistar King rats showed discontinuous variations in hepatic microsomal UDP-glucuronyltransferase activities towards androsterone, but not towards testosterone, bilirubin, phenolphthalein and 4-nitrophenol. Fresh microsomal fraction with a low transferase activity towards androsterone formed 0.049--0.080 nmole of glucuronide/min per mg of protein, whereas fresh microsomal fraction with a high transferase activity towards androsterone formed 0.335--0.557 nmol of glucuronide/min per mg of protein. The microsomal fraction with low enzyme activity towards androsterone was not stimulated by treatment with Triton X-100 or freezing and thawing. In contrast, male Long Evans and Sprague-Dawley rats did not exhibit such diversity.


Unfolding and refolding of phospholipase C from Bacillus cereus in solutions of guanidinium chloride. 1. Protein-fluorescence studies indicated that phospholipase C from Bacillus cereus is denatured in solutions of guanidinium chloride. The denaturation was not thermodynamically reversible and followed biphasic kinetics. 2. Guanidinium chloride solutions released the structural Zn2+ from the enzyme and rendered all histidine residues chemically reactive. In the presence of free Zn1+ the enzyme was much more resistant to denaturation. Also, the addition for free Zn2+ to the denatured enzyme induced refolding. 3. The Zn2+-free apoenzyme was much more sensitive to guanidinium chloride than was the native enzyme and the denaturation appeared to be thermodynamically reversible. 4. Guanidinium chloride denaturation was associated with a reversible inactivation of the enzyme. Heat-inactivated, coagulated enzyme was substantially re-activated on dissolution in guanidinium chloride solutions followed by dialysis against a Zn2+-containing buffer.


Conjugated and unconjugated bilirubins in humans and rhesus monkeys. Structural identity of bilirubins from biles and meconiums of newborn humans and rhesus monkeys. 1. Bilirubin-IXalpha monoglucuronide was the predominant bilirubin in biles and meconiums of newborn humans and rhesus monkeys. Rhesus-monkey baby biles contained slightly more diglucuronide than did human baby biles. 2. Bilrubin-IXalpha glucoside, bilirubin-IXalpha xyloside and bilirubin-IXbeta were also constituents of human and rhesus-monkey baby biles and meconiums. Bilirubin-IXalpha glucuronide glucoside was present in human and rhesus-monkey baby biles but not in meconiums. The identity of the bilirubins was confirmed by u.v.-visible and mass spectroscopy of the azodipyrroles obtained by treating the bilirubins with diazotized ethyl anthranilate. The resulting azodipyrroles were identical with the corresponding azodipyrroles obtained from human adult biles and also from reduced isomers of biliverdin. 3. Bilirubin-IXbeta was present in much higher proportions in the extracts of meconiums than in the extracts of biles from the same babies. 4. Oxidation of bilirubins to biliverdins occurs in utero to a small but undetermined extent. The resulting green pigments were present in meconiums collected from the lower small and large intestines of newborn babies and rhesus monkeys. 5. Butanol extracted most of the bilirubins present in biles. This modified method proved to be quick and easy. Little hydrolysis of bilirubins took place during extraction or separation by t.l.c.


Properties of salt-resistant lipase and lipoprotein lipase purified from human post-heparin plasma. Lipoprotein lipase and salt-resistant lipase were isolated from human post-heparin plasma. The proteins of human post-plasma lipoprotein lipase and salt-resistant lipase were identified and demonstrated to be immunologically different. Significant differences between the two enzymes in their relative amino acid composition were demonstrated, which indicates that the two enzymes are different proteins. When analysed by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, the enzymes seemed to have monomer molecular weights similar to that of lipoprotein lipase purified from bovine milk.


[Problems and possible errors in monitoring drug side effects at the hospital (author's transl)]. Special problems and possible errors in drug monitoring were discussed by analyzing three cases of hospital treated patients. The first one showed how easily side effects of drug can be falsely diagnosed and treated as a drug independent complicating disease. Furthermore, the active principle of the drug had to be differentiated from several potentially inducing substances. In the second case, the wrong diagnosis of a drug induced illness caused an intermission of a vital basic therapy. The lateron developing signs were interpreted as symptoms of the primary disease but they might also have been caused by drugs given later. For the third case it should be pointed out that side effects can be provoked during long- or short-term treatment by changing the diet. For drug monitoring it is therefore equally necessary to watch the drugs as well as the living circumstances.


Toxicity studies on lidamidine hydrochloride (WHR-1142A), a novel antidiarrheal agent. The acute oral LD50 of 1-(2,6-dimethylphenyl)-3-amidinourea hydrochloride (WHR-1142A, lidamidine hyrochloride) was 260 (208, 328) mg/kg in male mice, 267 (212, 336) mg/kg in male rats and 160 (130, 197) mg/kg in female rats. A daily oral dose of 10 mg/kg for 30 days was well tolerated in the rat and monkey. Histologic changes were reversible and for the most part could be explained on the basis of one or more of the several pharmacologic effects of WHR-1142A. A short-lived hyperglycemic effect was a prominent effect in mice and rats. This effect was seen occasionally in high doses in the monkey, suggesting a species difference.


Pharmacokinetics and disposition of lidamidine hydrochloride (WHR-1142A), a novel antidiarrheal agent, in rat and monkey. 14C-Labelled 1-(2,6-dimethylphenyl)-3-methylamidinourea hydrochloride (14C-WHR-1142A, lidamidine hydrochloride) was rapidly and quantitatively absorbed from the gastrointestinal tract of rat and monkey after a single oral dose of 5 mg/kg (base). Peak 14C levels occurred within 30 min and the radiolabel was found in both the plasma and cellular components of whole blood. The half-life of the parent compound was 30 min in rat and 1 h in the monkey. The label was essentially cleared from all tissues examined within 24 h in the rat. In both rat and monkey, the compound was extensively metabolized (greater than 90%) prior to excretion and eliminated primarily in the urine (95% of the 14C dose could be accounted for in urine within 24 h in the monkey and 65% within 24 h in the rat); about 15-20% of the dose was recovered in feces within 24 h in the rat. In rat, a significant portion of the dose was eliminated in bile, and enterohepatic recirculation of 14C excreted in bile occurred. In contrast, biliary elimination of 14C was not a major pathway in the monkey.


[Effects of molsidomine and nitroglycerin on the regional blood flow in the normal and acutely ischemic myocardium (author's transl)]. In anaesthetized dogs regional myocardial blood flow (radioactive particle distribution technique) and several haemodynamic parameters were measured before and after acute ligation of left descending coronary artery. By injection of N-carboxy-3-morpholino-sydnonimine ethylester (molsidomine, Corvaton) or infusion of nitroglycerin it was tried to influence blood flow of the infarcted areas of the myocardium. 1. Ligation of the coronary artery induces myocardial infarction of anterior wall, predominantly restricted to the endocardial portions of the heart muscle. 2. Molsidomine and also nitroglycerin do not change overall blood flow of the heart in the sense of vasodilation. 3. In the infarcted area the ratio: blood flow of endocardial layers to blood flow of epicardial layers, is improved by molsidomine. 4. The positive effect of molsidomine becomes clearer in the border zone of infarction. Nitroglycerin remains without effect. 5. The effects of the compound molsidomine are explained by stronger action on extravascular factors of colonary vascular resistance (decrease in enddiastolic pressure).


Comparative study of nitroglycerin and molsidomine. Effects on the integrated systemic venous bed and the arterial pressure in dogs. The effect of nitroglycerin, N-carboxy-3-morpholino-sydnonimine-ethylester (molsidomine, Corvaton), and its metabolite 3-morpholinosydnonimine upon the peripheral circulation was investigated in 38 dogs with cardio-pulmonary bypass. The three compounds increased the integrated systemic venous blood volume and decreased the mean arterial pressure. The time course of the action of nitroglycerin was different from that of molsidomine: The arterial and venous effects of nitroglycerin began immediately after the injection was started, reached a maximum, and had disappeared after 7 min. The effects of molsidomine started later and showed no tendency to decrease during the observation period of 30 min. When referred to the same decrease in arterial blood pressure, molsidomine acted more strongly upon the systemic venous bed than did nitroglycerin. The arterial and venous effects of the molsidomine metabolite could be antagonized by a dopamine infusion. It is concluded that the hypotensive effect of the three compounds observed in the intact circulation is due to the diminuation of peripheral resistance as well as to the dilatation of the systemic venous bed. The dilatation of the veins effects a decrease in the venous return and thereby in the cardiac output and the arterial pressure. It can be concluded that the antianginal effect of the three compounds is not only due to the diminution of the afterload of the heart; the diminution of the heart; the diminution of the preload also represents an important component of action.


Effects of progesterone on mammary carcinogenesis by DMBA applied directly to rat mammae. The effects and site(s) of action of progesterone on DMBA mammary carcinogenesis in the rat, when a small dose of the carcinogen was applied directly to the inguinal mammary gland, were investigated. No reduction in tumour yield was apparent when progesterone was administered s.c. for 18 days before dusting DMBA. This finding contrasts with a previously reported inhibitory effect on carcinogenesis when hormone treatment was followed by intragastric administration of DMBA. When progesterone injections were begun either 2 days before or 2 days after direct application of DMBA, and were continued until the end of the experiment (135 or 195 days) an enhancement in carcinogenesis was observed similar to that previously demonstrated after gastric intubation of DMBA. These findings, together with previously reported observations, suggest that progesterone may exert its inhibitory effect on carcinogenesis by acting at a site outside the breast, perhaps on the liver. However, it is likely that the hormone acts directly on the mammary tissue to exert its enhancing effect on tumorigenesis.


PUVA-induced repigmentation of vitiligo: a histochemical (split-DOPA) and ultrastructural study. Repigmentation induced by oral photochemotherapy (8-MOP + UV-A) in four patients with vitiligo has been studied by histochemical and ultrastructural techniques. Hypertrophic melanocytes were demonstrated both in the middle and deep portions of the hair follicles in the centre of islands of repigmentation and also in the epidermis of the expanding repigmenting border. Mitosis of melanocytes was absent in these areas. Ultrastructural study showed that the melanocytes of repigmented areas were hyperactive. The melanosomes were larger than those of surrounding healthy skin, although the mode of packaging was unaltered. These observations suggest that melanocytes repigmenting vitiliginous skin under the influence of oral photochemotherapy are derived from a melanocytic reservoir localized in the hair follicles.


Coagulation failure in babies with rhesus isoimmunization. Serial prospective studies of coagulation status have been undertaken on 73 babies with a positive Coombs test. No abnormalities were detected in the babies with mild haemolytic disease, but seven of the 36 babies with severe haemolytic disease (cord Hb less than 11 g/dl or cord bilirubin greater than 85 mumol/1) showed evidence of transient defibrination 1 d after birth and another six had evidence of coagulation failure at birth with a platelet count of less than 150 x 10(9)/1 and a severe deficiency of multiple coagulation factors. The level of factor II and factor X was less than a fifth of the normal cord blood level in these six babies and the level of I, VII and IX was severely reduced; the factor VIII level was normal or high. Exchange transfusion started within 1 h of birth corrected the immediate factor deficiency in these six babies, but evidence of defibrination then became apparent with afibrinogenaemia, a marked fall in factors II and V, less constant falls in factors VII, IX and X, and a raised fibrin:fibrinogen degradation product level. One of these six babies died with severe pulmonary hypoplasia within an hour of birth; the other five died from haemorrhage into the lung or brain 1 1/2--6 d after birth. The very low vitamin-K dependent factor levels in the cord blood of the babies who died are presumably the result of liver damage in utero, but the subsequent changes are those of a comsumption coagulopathy. Simple screening tests at birth served to indicate which babies were at risk and it is concluded that death due to haemorrhage might be reduced by more intensive factor replacement before there is overt evidence of haemorrhage in these babies.


Physical growth and neurointegrative performance of survivors of protein--energy malnutrition. 1. The anthropometric measurements and neurointegrative performance of seventy-nine children aged 6--12 years who had survived kwashiorkor in early childhood were compared to those of 142 children who served as controls. 2. For the boys the differences in height and weight between those who had survived protein--energy malnutrition (PEM) and the controls were significant (P less than 0.01). 3. For the girls the differences in height and weight between those who had survived PEM and the controls were not significant. 4. In the tests chosen, the performances of the survivors of PEM was significantly poorer than that of the controls. 5. There was no improvement in the performance when thirteen survivors were reassessed at 10 years of age. 6. There was a significant difference in scholastic performance between the survivors of PEM and the normal controls. The scholastic performance of the siblings of PEM survivors was also significantly better than that of the PEM survivors. 7. The dietary intakes at the time of reassessment were unsatisfactory in 25% of the survivors, but did not relate to their scholastic abilities.


Relation between erythrocyte selenium concentrations and glutathione peroxidase (EC 1.11.1.9) activities of New Zealand residents and visitors to New Zealand. 1. Erythrocyte, plasma and whole blood selenium concentrations and glutathione peroxidase (EC 1.11.1.9; GSHPx) activities were measured (1) in 104 healthy New Zealand residents living in Otago, a low-soil-Se area (2) in sixty-four surgical patients, including nineteen patients on total parenteral nutrition and twenty-three cancer patients (3) in fifty-two 'overseas subjects' (twenty-five visitors to Otago from outside New Zealand and twenty-seven Otago residents on return from overseas travel). 2. Blood Se concentrations reflected dietary Se intake; means for Otago patients, healthy subjects and overseas subjects were different 0.043, 0.059, 0.136 micrograms Se/ml blood respectively) and mean for overseas residents was greater than for New Zealand overseas travellers. 3. Erythrocyte Se concentration was always greater than plasma Se, and plasma Se was a smaller proportion of erythrocyte Se for patients compared with the controls. 4. GSHPx activities were different in the three groups, and varied directly with erythrocyte Se until a plateau was reached at approximately 0.14 micrograms Se/ml erythrocytes. 5. Overseas subjects showed no relationship between erythrocyte Se and GSHPx activity. This agrees with some overseas studies and the significance of this finding is discussed. 6. Plasma Se concentration remained the most sensitivie index of short-term changes in Se status, and erythrocyte Se and GSHPx activities for long-term changes in New Zealand subjects. Use of these measurements for overseas subjects with higher blood levels is discussed.


Thymidylate synthetase catalyzed exchange of tritiumfrom [5-3H]-2'-deoxyuridylate for protons of water. Thymidylate synthetase catalyzes an exchange of tritium of [5-3H]dUMP for protons of water in the absence of CH2-H4folate. The turnover number for this reaction is some 45,000-fold lower than that of dTMP formation and Km is 1.2 X 10(-5) M, similar to the dissociation constant of the enzyme-dUMP complex determined by equilibrium dialysis. The presence of 4 mM folate has no effect on Vmax but results in a decrease in the Km of dUMP to a value close to that in the normal enzymic reaction. The exchange reaction provides definitive evidence that the enzymic reaction involves attack of a nucleophile of the enzyme on the 6 position of dUMP to provide a 5,6-dihydro-dUMP intermediate which is covalently bound to the enzyme. Stereochemical considerations of the exchange reaction require proposal of a partial reaction which is not completely sterospecific or a complex reaction in which protons of water are handled with complete stereospecificity in a fashion similar to the one carbon unit of the normal enzymic reaction.


Phase separations in membranes of Anacystis nidulans grown at different temperatures. Freeze fracture electron microscopy studies were performed on samples of Anacystis nidulans quenched from different temperatures. Membrane lipid phase separations were observed to take place over the ranges 15--30 degrees C, 5--25 degrees C and -5--15 degrees C for cultures grown at 38, 28 and 18 degrees C, respectively. Differential scanning calorimetry heating curves showed endotherms which coincided with these temperature ranges. Variations of phase separation temperatures with growth temperature, and hysteresis effects in the calorimetric measurements, were related to changes in the fatty acid composition of membrane lipids.


Stimulation of chloride transport by fatty acids in corneal epithelium and relation to changes in membrane fluidity. The effect of altering cell membrane lipids on ion transport across isolated corneas was studied. Corneas mounted in Ussing-type chambers showed a rapid increase in short-circuit current following treatment with a variety of unsaturated fatty acids of varying chain length and unsaturation. Measurements of membrane fluidity which utilize immunofluorescence labelling of membrane proteins showed corneal epithelial cell membranes to be significantly more  fluid following linoleic acid treatment. Uptake studies indicate rapid incorporation of [14C]linoleic acid into corneal cell membranes. Highly unsaturated fatty acids were found to have the greatest ability to stimulate chloride transport. Saturated fatty acids were tested and were found to have no effect on chloride transport at any concentration. It is proposed that unsaturated fatty acids activate chloride transport by increasing membrane lipid fluidity. The relationship of these parameters is discussed in terms of a mobile receptor model. We speculate that an increase in membrane lipid fluidity promotes lateral diffusion of membrane receptor proteins and enzymes, increasing protein-protein interactions within the membrane, ultimately resulting in the enhancement of cyclic AMP synthesis.


Purification by affinity chromatography and some properties of microsomal galactosyltransferase from pig thyroid. Membrane-bound 4-beta-galactosyltransferase (lactose synthase; UDP galactose: D-glucose 4-beta-galactosyltransferase, EC 2.4.1.22) was purified 1500-fold to near homogeneity from pig thyroid microsomes with about 30% yield. The purified enzyme behaved as a lipophilic protein, rapidly losing activity and aggregating if not supplemented with either Triton X-100 or serum albumin (both of these were equally effective for long-term stabilization). The enzyme preparation showed an absolute requirement for Mn2+, which could not be replaced by other cations. Catalytic properties were very similar to those reported for soluble forms of the enzyme in biological fluids. The purified galactosyltransferase showed a major protein band of approx. 74,000 daltons on sodium dodecyl sulfate gel electrophoresis. On gel filtration, enzyme activity was eluted at approx. 70,000 daltons. It is concluded that the membrane-bound thyroid galactosyltransferase is a monomeric protein significantly larger than the soluble forms of this enzyme described earlier; but it resembles recently reported galactosyltransferases from sheep mammary Golgi membranes and liver microsomes.


Ribulose 1,5-bisphosphate carboxylase from the thermophilic, acidophilic alga, Cyanidium caldarium (Geitler). Purification, characterisation and thermostability of the enzyme. An an initial stage in the study of proteins from thermophilic algae, the enzyme ribulose 1,5-bisphosphate carboxylase 2-phospho-D-glycerate carboxylyase (dimerizing, EC 4.1.1.39) was purified 11-fold from the thermophilic alga Cyandium caldarium, with a 24% recovery. This purified enzyme appeared homogeneous on polyacrylamide gels and could be dissociated into two subunit types of molecular weights 55,000 and 14,900. The optimal assay temperature was 42.5 degrees C, whilst enzyme purified from Chlorella spp. showed maximum activity at 35 degrees C. The thermostability of Cyanidium ribulose 1,5-bisphosphate carboxylase was considerably greater than that of the Chlorella enzyme, and the presence of Mg2+ and HCO-3 further enhanced this heat stability. A break in the Arrhenius plot occured at 20 degrees C for Chlorella ribulose 1,5-bisphosphate carboxylase and 36 degrees C for the enzyme from Cyanidium. It is suggested that the thermostability of Cyanidium ribulose 1,5-bisphosphate carboxylase is a result of an inherent stability of the enzyme molecule which permits efficient CO2 fixation at high temperatures but results in low activity in the mesophilic temperature range.


Catabolism of taurine in Pseudomonas aeruginosa. Cell-free extracts of taurine-grown Pseudomonas aeruginosa catalyze the transamination of taurine and pyruvate resulting in the formation of L-alanine and sulfoacetaldehyde. The enzyme responsible for this activity has been partially purified in order to demonstrate its participation in a pathway of taurine degradation. Ethyl methane sulfonate treatment of Ps. aeruginosa yielded a mutant deficient in taurine transaminase and incapable of growing on taurine indicating that the enzyme is of physiological significance in this organism.


A NMR shift method for determination of the enantiomeric composition of hydroperoxides formed by lipoxygenase. A method is presented for determination of the enantiomeric composition of hydroxyperoxides formed by enzymic oxygenation of unsaturated fatty acids. After reduction of the hydroperoxy group with NaBH4, and esterification, the positional isomers of the resulting hydroxy compounds are separated by high performance liquid chromatography. The latter are subsequently subjected to a chiral derivatization to form diastereomeric alpha-methoxy-alpha-trifluoromethylphenylacetate esters. Determination of the diastereomeric composition by a NMR shift experiment furnishes the enantiomeric composition of the parent hydroperoxides. The method has been applied to the hydroperoxides formed by incubation of linoleic acid by corn germ or soybean lipoxygenase. Our results indicate that under the conditions used the hydroperoxides are mainly enantiospecifically formed.


Learning and behavioral abnormalities in the seizure-prone baboon. A high incidence of behavioral and learning difficulties has been found in juvenile seizure-prone baboons presented with a graded series of operant behavioral task challenges. The animals fell into two distinct groups based upon the rate at which their operant performance was able to develop, the amount of day-to-day variability in performance level, their ability to tolerate change, and the frequency of appearance of symptoms of emotionality. The association between learning problems and behavior problems in these seizure-prone baboons may correlate well with the deficits in both intellectual performance and social behavior that have been reported in some studies with human epileptics. In addition, the data suggest a relationship between familial factors and trainability, and between predisposition to seizures and trainability.


Effect of electric fields on the behavior of Drosophila melanogaster Meig. A constant and alternating electric field causes in fruit flies (Drosophila), placed between the plates of a capacitor, a cessation of movements. The percent of fruit flies reacting to the field is directly proportional to the field strength and inversely proportional to the humidity and, apparently, to the infrasonic background, is maximum at a frequency of variations of the field of 10 Hz, and does not depend on the polarity of the capacitor plates, contact of the fruit flies with them, ionization and electrical conductivity of the air, atmospheric discharges, atmospheric pressure or disturbance of the geomagnetic field. The reaction is absent in the winter. It is suggested that the fruit flies perceive the mechanical forces occurring when the body's charge interacts with the external field.


A less empirical method of representing megavoltage beams for use in rapid radiotherapy dose calculations. A large number of initial measurements are needed for accurate computation of radiotherapy dose distributions directly from stored data on the dose distribution of single radiation beams. Because of this, interest has been shown in alternative methods which use empirical formulae to represent the dose distributions of single beams. These can be easier to implement but are less directly related to measured quantities and may be of limited validity. A method of representing radiotherapy beams is proposed which closely approximates their radiation physics, in order to calculate the dose at any point by a simple algorithm directly from a small number of initial dose measurements. The method is of wide validity, probably including all megavoltage radiations for which Compton scattering is the dominant interaction in tissue. The accuracy of the method is demonstrated by application to an 8 MV linear accelerator and a cobalt 60 machine.


Activity of postcentral cortical neurons of the monkey during conditioned movements of a deafferented limb. Unit recordings were performed in the sensorimotor cortex of awake monkeys during performance of learned movements of the contralateral arm. The movements were triggered by a sound stimulus. The neuronal discharge in association with movement was observed before and after deafferentation (C2--T5) of the operant limb. Whereas neurons recorded in the motor cortex (area 4) and in the parietal association cortex (area 5) still modified their activity in relation to movement performed by the deafferented arm, the neurons recorded in the primary sensory cortex (areas3, 1 and 2) showed no activity change in relation to movement after deafferentation. This finding strongly suggests that modification of discharge of postcentral neurons seen during ballistic arm movement is mainly the result of input from the moving limb (peripheral feedback) and not the result of input from other structures of the central nervous system (internal feedback).


Serotonin synthesis and release in brain slices: independence of tryptophan. The purpose of the present study was to examine the role of substrate availability in the regulation of the release and synthesis of serotonin by brain slices. Electrical field depolarization of the brain slices stimulated the synthesis and release of serotonin in the absence of changes in intracellular tryptophan concentration, in the absence of tryptophan in the incubation bath, and in the absence of changes in total tryptophan uptake. Furthermore, electrical stimulation decreased the apparent Km for tryptophan required for synthesis of serotonin by the slices. Several conclusions were drawn. (1) Rates of serotonin release and synthesis in brain slices may increase independently of the tissue tryptophan concentration or tryptophan uptake. (2) There is little difference in the synthetic rate of serotonin in tissues exposed to pargyline or not at all. (3) Blockade of monoamine oxidase by pargyline appears to give estimates of the synthetic rates of serotonin which are comparable to estimates derived from [3H]-tryptophan incorporation. (4) Newly synthesized serotinin is preferentially released. (5) Only in tissue pretreated with pargyline do increasing concentrations of tryptophan increase the releasable pool of 5-HT. (6) Electrical depolarization may allosterically activate tryptophan hydroxylase; an effect which may be mimicked by homogenization of the tissue.


The amino acid sequences of the three heavy chain constant region domains of a human IgG2 myeloma protein. The amino acid sequences of most of the CH1, CH2 and CH3 domains of IgG Zie, a myeloma protein belonging to the IgG2 subclass, are presented. These data make possible a comparison of the sequences of residues 253-446 of all four subclasses of immunoglobulins: these residues make up almost the entire Fc regions. A comparison can also be made of the CH1 domain of IgG1 Eu and the CH1 domain of IgG2 Zie. Earlier sequence analyses of the Fc regions of subclass 1 and 3 proteins, and parts of the Fc regions of subclass 2 and 4 proteins showed that about 95% of these sequences were identical. The extended comparisons made possible by the data presented here show that this very high degree of identity is maintained throughout the four subclasses. Similarly, the CH1 domains of gamma 1 and gamma 2 chains were found to have about 93% sequence identity. It is unlikely that the few single amino acid changes within the constant region domains can account for the marked differences between subclasses observed in the region domains can account for the marked differences between subclasses observed in the biological effector functions of immunoglobulin Fc regions, especially since most of the changes are highly conservative. Rather, it seems probable that these functional differences are caused by conformational differences between the subgroups, which result from sequence differences in the hinge regions.


Clinical Oncology Program: a community cancer control model. The majority of cancer patients are diagnosed and treated in their local communities, making it imperative to upgrade cancer management at the community level. The Clinical Oncology Program has demonstrated that sophisticated cancer control programs are possible in a community setting. Moreover, if "quality of survival" data collection is included in such programs, valuable information emerges that can further improve cancer management in the community.


Cyanobacterial evolution: results of 16S ribosomal ribonucleic acid sequence analyses. We report here the sequences of oligonucleotides released by T1-ribonuclease digestion of the 16S ribosomal RNA's (rRNA's) of unicellular cyanobacteria Agmenellum quadruplicatum (strain BG-1) and Synechococcus 7502. We compare them with sequences previously obtained for the 16S RNA's of six other cyanobacteria and two chloroplasts, and conclude that: (i) Synechocystis-like unicells form a discrete cluster which also (and surprisingly) includes Agmenelium quadruplicatum, usually considered to be a Synechococcus; (ii) filamentous cyanobacteria of the genera Nostoc and Fischerella arose from within the Synechocystis group; (iii) phylogenetic diversity (and hence presumably evolutionary antiquity) within the Synechococcus group is very great; and (iv) red algal chloroplasts are of definite cyanobacterial origin, while Euglena chloroplasts are of separate and quite possibly noncyanobacterial origin. We also present the results of a computer-aided search among the 10 oligonucleotide 'catalogues' for families of related but nonidentical sequences. Examination of these families reinforces the above conclusions.


Effect of heparin on the metabolism of putrescine in vivo. Rats and guinea pigs which are given heparin metabolize intraperitoneally injected [14C]-putrescine to 14CO2 at reduced rates. The results have been considered in relation to the heparin-induced liberation of diamine oxidase from tissues into the blood stream.


Adsorption of Bacillus subtilis bacteriophage PBS 1. Bacteriophage PBS 1 adsorbs initially on the flagella of its host, Bacillus subtilis (stage I). The phage can adsorb to both active and inactive flagella. Flagellar attachment is nonspecific as PBS 1 was shown to attach to the flagella of Bacillus species other than the normal host B. subtilis. The phage particle then quickly moves down the length of the flagellum to its base, the final adsorption site. Flagellar motion is required for flagellar base attachment (stage II). After proper attachment at the flagellar base, the phage tail sheath contracts sending the tail core through the final adsorption site (stage III). The phage DNA is then injected at this site (stage IV). Stage I adsorption does not cause loss of motility in PBS 1 -- resistant bacilli. The loss of motility observed upon infection of sensitive cells by PBS 1 may be associated with either stage II or stage III of adsorption.


Physiological studies of a temperature-sensitive sporulation mutant of Bacillus cereus T. Growth of temperature-sensitive mutant Bacillus cereus T JS22-C occurred normally at the restrictive temperature (37 degrees C), but sporulation was blocked at stage 0. The production of extracellular and intracellular proteases and of alkaline phosphatase occurred at 37 degrees C, but the expression of a functional tricarboxylic acid cycle did not. At the permissive temperature (26 degrees C), the mutant sporulated at a slightly lower frequency (60%) and at a lower rate than the parent strain. The oxidation of organic acids, which accumulate in the growth medium began at T0 in cultures of the parent strain but was delayed until about T3 in cultures of the mutant. Later events in sporulation were also delayed in the mutant by about 3 h. Experiments in which the temperature of growth was shifted from 37 to 26 degrees C or from 26 to 37 degrees C at various times showed that the temperature-sensitive event began approximately 1 h after the end of exponential growth and ended when the cells reached the end of stage II (septum formation). The absence of a functional tricarboxylic acid cycle in cells of the mutant grown at 37 degrees C or shifted from 26 to 37 degrees C before T1 did not appear to be due to a lesion in one of the structural genes of the tricarboxylic acid cycle but was more likely due to the inability of the cells to derepress the synthesis of some of the enzymes of that cycle.


Transfer and integration of chromosomal genes from Pseudomonas glycinea into Pseudomonas aeruginosa. The plasmids FP2 and R68.45 were shown to function as chromosome-mobilizing plasmids in a series of interspecific crosses between the phytopathogen Pseudomonas glycinea and the human pathogen Pseudomonas aeruginosa. At least four of seven loci tested were transferred from P. glycinea donors to P. aeruginosa auxotrophic recipients. Transductional analysis indicates that a leu+ locus of the P. glycinea chromosome transferred is stably integrated into the P. aeruginosa chromosome.


A new plaque system for canine distemper: characteristics of the green strain of canine distemper virus. A Vero cell adapted Green strain of canine distemper virus (CDV) was tested for its plaque-forming capacity in different cell lines. Plaque formation was observed in HEp-2, BS-C-1, and HeLa cells but not in Vero or dog kidney cells even though replication and cytopathology were observed in the latter cell types. In the cells in which the virus was capable of producing plaques, the plaques were observed within 24 h post infection and continued to increase in size with subsequent cellular destruction such that by 72 h postinfection the size of the plaques approached 0.5 mm. With the use of the plaquing technique, it was possible to demonstrate the thermal lability of the virus as well as the kinetics of adsorption. Thus, it was shown that the half-life of the virus was 125 min at 25 degrees C, 75 min at 35 degrees C, and 65 min at 37 degrees C. The rate of adsorption of CDV to HEp-2 cells was 17.2% in 30 min at 37 degrees C and continued slowly for 4 h before completion. Application of this rapid plaque-forming assay to plaque-reduction tests for CDV antibody and for CDV-infected cells by the infectious center assay are described.


Stimulation of monocyte precursors in vivo by an extract from Listeria monocytogenes. A water-soluble monocytosis-producing activity (MPA) extracted from Listeria monocytogenes was found to stimulate proliferation of promonocytes in vivo. Mice were pulse-labelled for 2 h with tritiated thymidine ([3H]TdR) at various times after intraperitoneal injection of MPA. Autoradiography of bone marrow cells revealed an increased labelling index of promonocytes of MPA-treated mice which was maximum 8 h after the MPA injection. Mice labelled with [3H]TdR 8 h after MPA injection developed a monocytosis at the expected time (peak at 48 h) and the blood monocytes were found to be highly labelled. Both the generation time of monocyte precursors and the halftime of blood monocytes were found to be shorter than the corresponding values in control mice.


Immunological properties of partially purified material with monocytosis-producing activity from Listeria monocytogenes. A fraction rich in a monocytosis-producing activity (MPA) has been obtained by a two-stage chromatographic separation from a saline extract (SE) of Listeria monocytogenes. Like SE, the purified material elicits monocytosis and decreases the halftime of circulating monocytes. The purification of MPA eliminates the following found in SE: the in vitro mitogenic activity, the in vitro adjuvant activity, the immunosuppressive activity, and the granulocytosis-promoting and the lymphopenia-inducing activities.