[delta-9-Tetrahydrocannabinol (THC) inhibition of the membrane transport system for thymidine]. THC decreases 3H-thymidine uptake within 15 sec. after addition of the drug to the culture (L1210 murine lymphoma cells and human lymphocytes). Experiments performed at 0 degrees C indicate that THC has no action on thymidine binding to the carrier. THC in micromolar concentration inhibits DNA synthesis through a alteration of membrane configuration.


[Isolation in east Senegal of a yellow fever virus strain from a pool of Aedes belonging to the subgenus Diceromyia]. During an epidemiological survey of yellow fever in Eastern Senegal, one strain of yellow fever virus was isolated in December 1976 from wild Mosquitoes. This first isolate obtained in nature from Aedes subgenus Diceromyia shows the primordial part these vectors may have in the area studied. It corroborates the existence of a selvatic focus of yellow fever in this region. It also gives information on the transmission cycle in a dry area.


[Modulation of humoral immunity in the mouse by means of grafts carrying reticulated polysaccharides]. Synthetic reticulated polysaccharides grafted with linear amino-acids or amines have been submitted to the test of localized hemolysis in gel (Jerne). Some of them show a statistically highly significant immuno-stimulating power in Mice.


[Proliferative activity of the rat adrenal cortex during the estrous cycle and at the end of gestation]. The cell proliferation in the female Rat adrenal cortex undergoes rhythmic modifications which appear to be related to the estrous cycle. Significant variations appear likewise at the end of pregnancy. Such fluctuations of the proliferative activity raise the question of a possible endocrine regulation.


[Kinetics of insulin secretion in response to glucose by isolated islands of Langerhans from the fetal rat]. Isolated islets of Langerhans from 21.5 day-old foetal Rats were studied in a perifusion system in vitro. The overall dynamics of insulin release by the foetal islets in response to glucose 13.9 mM is biphasic and qualitatively similar to that obtained with islets of adult Rats. The magnitude of the initial phase of insulin secretion is similar for the foetal and adult islets. The second phase is fourfold higher in the adult than in the foetus. The response of foetal islets occurs, 45 to 60 sec. after the increase of glucose concentration in the medium and a maximum insulin release for the first phase is obtained with a lag period of 2 min. The difference between foetal and adult islets is essentially quantitative.


[Detection of human antigens on the surface of mouse cells transformed by chromosome transfer]. Mouse embryo cells, transformed in vitro by the transfer of chromosomes from HeLa human tumour cells, express a surface antigen (s) also found on HeLa cells. This antigen(s), which has been detected both by indirect immunofluoresence and by a 125I-protein A binding assay, is not an antigen(s) shared by both Human and Mouse cells.


[Sexual differences in the development of plasma thyroxine levels in the embryo and young chick]. Plasma thyroxine (T4) levels were separately ascertained in male and female embryo and young chicken from the 12th day of incubation till the 4th day after hatching by the thyroxine binding globulin technique. In both sexes, plasma T4 reach a peak the 20th day of incubation, but values are significantly higher in females. A sharp decrease occurred thereafter, plasma T4 tending toward adult values the 4th day after hatching.


[Leukocyte migration toward the alveoli]. Migratory processes of leukocytes toward alveolus have been studied after intratracheal injection of aluminium or beryllium hydroxide. Migrating cells could only be observed during the first three days following the injection. Three migrating processes were pointed out and especially an emperipolesis phenomenon. This morphological observation and cytokinetic study of septal cells, exclude the existence of a precursor septal pool involved in a maturation process of alveolar macrophages.


[Stereotype and plasticity of utterances in gibbons (Hylobates concolor leucogenys)]. The "great call" of adult male and female Hylobates concolor leucogenys was studied in different conditions of social stimulation, using quantitative (i. e. sonographic) analysis. Vocal sequences are generally made up of mixed sounds, appearing in a fixed order and constituting a species-specific character. Qualitative diversification appears in the repetition of sequences. Different social situations alter parameters of the calling pattern: especially the length and intensity of homologous modulated sounds, and the qualitative complexity of sequences. The capacity of controlling length and intensity of modulated sounds has been shown in earlier papers for H. c. gabriellae, and by several authors, in Cebus and Rhesus monkeys. The "great call" of H. c. leucogenys shows the two fundamental characteristics of instinctive (i. e. genetically determined) activity-patterns.


[Effect of concanavalin A on the palatine ridges in vitro]. Concanavalin A acts in three ways on palatal shelves cultivated in vitro: 1. it has a mitogen effect, particularly on the medio palatal epithelium; 2. this produces thickening of this epithelium; 3. a delayed fusion or no fusion of the palatal shelves. The renewed mitogen activity and loss of adhesion properties seem to be linked.


[Tele-electromyography of various quadriceps femoris muscle bundles during locomotion in a Madagascar lemur (Lemur fulvus)]. The vastus lateralis muscle is of primary importance in leaping inasmuch as it initiates the jumps; on the contrary the activity of the vastus intermedius does not increase during jumping, but it is the only one to be active in quadrupedal resting postures.


[Tissue specificity of testosterone fixation: demonstrated by ultrastructural immunocytochemistry after cryoultramicrotomy]. Testosterone can be detected by immunocytochemistry on ultrathin slices obtained by cryoultramicrotomy. Testosterone detected by this method is likely bound on a binding site having a high affinity. In order to study the tissue specificity of this binding, testosterone was tested in Rat pituitary gland, liver and adrenal glands. Immunoreactive testosterone was detected in the gonadotropic cells of the pituitary gland, in the hepatocytes. Testosterone was not detected by immunocytochemistry in the pituitary cells other than the gonadotropic cells and in the cells of the medulla of adrenal glands. These data testify in favour of tissue specificity of the testosterone binding.


[Water in keratin: electrical conductivity measurements]. Measurements of electrical conductivity of keratin fibers show that, for weak hydration (0-5%) interaction between water and protein is strong. This decreases the probability of charges-exchange taking place between them. During the first percentages of elongation, an increase of the percentage of "intermediate water" appears.


[Comparative oxidation of erucic and oleic acids by mitochondria isolated from heart auricle of living man]. Mitochondria were isolated from fragments of heart auricles, that were cut off during surgical intracardiac operations. They were incubated with either [14 14C] erucic acid or [10 14C] oleic acid as a control. In the experimental conditions used, the radioactive products soluble in perchloric acid, that are issued from the beta-oxidation reactions in mitochondria, were formed in much lower amounts from erucic acid than from oleic acid. These results show the very low capacity of human heart mitochondria to use directly erucic acid as a substrate for energy requirements, as has been observed before with other animal species. Activation of fatty acids, the preliminary step of their beta-oxidation, was also observed to be very much lower with erucic acid.


[Specific phosphorylation of a calf serum protein by a kinase from the cell surface]. A protein of molecular weight approximately 200,000, which exists in trace amounts in calf serum, is specifically phosphorylated by an enzyme located at the surface of cultured cells. The emzymatic reaction utilizes ATP, is enhanced by Mg++ and Zn++ ions, and is not dependent on cyclic AMP. This kinase activity is associated with normal growing fibroblasts but disappears when they are contact-inhibited. It remains high, however, in transformed and malignant cells, whatever their growth state.


[Inhibition of the fluorescence of acridine, 9-aminoacridine, and 9-amino-6-chloroacridine by human serum albumin]. Study of fluorescence quenching of acridine and some 9 amino acridines upon human serum albumin additions reveals a single protein fixation site. Characteristic values of thermodynamic functions are obtained from experiments at different temperatures.


[Genetic control by the HLA region of the immune response to factor VIII in hemophilic patients]. In 10 sibships of haemophilic A patients, every one including 1 haemophilic brother with an antibody to factor VIII and 1 haemophilic brother without antibody, pattern of HLA segregation was analysed. All sibships were HLA haploidentical or different and not HLA identical. This fact suggested a linkage between the major histocompatibility complex and an "Ir" gene to factor VIII.


Comparison of specific protein assays in biological fluids by radial immunodiffusion and laser nephelometer. Laser immuno-nephelometry is presently being used for measuring concentrations of specific proteins in biological fluids. Our findings have not substantiated the highly correlative results with radial immunodiffusion that have been reported. The reason for our poor correlation was found in the lack of uniformity in expressing concentrations of the different specific proteins in the calibrating standards. One value of the laser nephelometer was the greater precision obtained when comparing results to those measured by radial immuno-diffusion. Also, the laser was found to be more sensitive for measuring low level concentrations.


Myrtus communis L. phytohemagglutinins as a clarifying agent for lipemic sera. Phytohemagglutinins from sees of Myrtus communis L., either in solution or adsorbed by glutaraldehyde-treated erythrocytes, constitute an effective system for clarification of lipemic sera. It can be used in clinical analysis to avoid the interference produced by turbidity in spectrophotometric determinations. Parameters such as glucose, bilirubin, urea, uric acid, GPT, GOT, and LDH, amongst others, can be determined without interference. The content in triglycerides of 1 ml of serum can be decreased by more than seventy per cent by treatment with 50 mg of lyophilized glutaraldehyde-treated erythrocytes saturated with Myrtus communis L. phytohemagglutinins.


A fluorometric assay using 4-methylumbelliferyl alpha-L-iduronide for the estimation of alpha-L-iduronidase activity and the detection of Hurler and Scheie syndromes. Incubation of 4-methylumbelliferyl alpha-L-iduronide with whole cell homogenates prepared from cultured skin fibroblasts and amniotic cells, and peripheral blood leukocytes gave 4-methylumbelliferone which was easily measured fluorometrically. This reaction, presumably due to the action of alpha-L-iduronidase, has a maximum hydrolytic activity at pH 3.25. The apparent KM value of alpha-L-iduronidase in leukocyte whole cell homogenates for this substrate was 179 mumol/l compared to 353, 41 and 166 mumol/l for other alpha-L-iduronidase substrates phenyl alpha-L-iduronide, iduronosyl anhydrol[1-3H]mannitol 6-sulfate and iduronosyl anhydro[1-3H]mannitol respectively; the corresponding Vmax values were 617, 394, 158 and 10 pmol/min/mg protein respectively. Incubation of the 4-methylumbelliferyl alpha-L-iduronide with whole cell homogenates prepared from cultured skin fibroblasts and leukocytes from a Hurler patient gave 4-methylumbelliferone at a rate more than 20 times less than found for control normal preparations. 4-Methylumbelliferyl alpha-L-iduronide is a sensitive, convenient and superior substrate to phenyl alpha-L-iduronide for the assay of alpha-L-iduronidase activity, but is not a suitable replacement for the radiolabelled substrate iduronosyl anhydro[1-3H]mannitol 6-sulfate.


Identification and incidence of a urinary fragment of IgG. Urine from some patients, when concentrated approximately three hundred fold and immunoelectrophoresed against anti-IgG, shows an unexpected additional precipitin line in the alpha-globulin region. This reaction has been shown to be due to the presence of a low molecular weight (approximately 20 000) fragment of the heavy chain of IgG. A retrospective examination of immunoelectrophoretic plates run over a period of five years has revealed that this fragment was present in 30 out of 110 patients.


A new screening test for the diagnosis of mucopolysaccharidoses. A simple method for the electrophoretic separation of glycosaminoglycans from untreated urine is presented. It is shown that this rapid electrophoresis on specially shaped acetate cellulose strips gives more information than other screening tests used in laboratory for discriminating between normal and pathological samples. This technique is useful particularly with low levels of glycosaminoglycans which may give false-negative responses.


Immunichemical determination of cathodal elastase in human duodenal juice. In human duodenal juice enzymes hydrolysing the elastase substrate succinyl-trialanine-p-nitroanilide have both an anodal and cathodal mobility in agarose gel electrophoresis. The cathodal enzyme, also having an elastinolytic activity, was purified. An application of electroimmunoassay for separate determination of this cathodal elastase is presented. Parallel estimations of esterolytic, elastinolytic and immunochemical activities in duodenal juice from a group of children revealed discrepancies suggesting both variations in the distribution of the two forms of "elastases", and presence of inactive forms.


The diagnostic value of pharmacodynamic tests in the hyperprolactinaemic syndrome. Patterns of prolactin (PRL) secretion were studied in a group of 18 hyperprolactinaemic patients with galactorrhoea and menstrual disorders and in a control group of thirty-two women in the early puerperium (24 h after a normal delivery) following provocative (TRH and Chlorpromazine) and suppressive (L-Dopa and bromocriptine) stimuli. Five out of the eighteen hyperprolactinaemic patients tested had radiological evidence of a pituitary tumour, and two were treated surgically. The early puerperium patients with elevated basal PRL levels (100--700 ng/ml) demonstrated a significant PRL response to the various treatments. On the other hand, in the hyperprolactinaemic group, an impaired PRL response to TRH, Chlorpromazine and L-Dopa was noted in patients with basal PRL levels higher than 30 ng/ml, whereas bromocriptine suppressed effectively PRL levels in all the hyperprolactinaemic patients tested irrespective of their basal PRL concentrations. The ratio between the fall in PRL concentrations (as percent of the baseline) after L-Dopa administration (delta%L) versus the PRL decrement after bromocriptine treatment (delta%B) was calculated. In the early puerperium group with normal pituitary prolactin secreting cells this ratio was equal to 0.8. In the hyperprolactinaemic group, the five patients with radiological evidence of a pituitary tumour had significantly lower ratios ranging from 0.2 to 0.57. These data suggest that in terms of prolactin release, prolactin producing tumour cells are intrinsically refractory to hypo thalamic dopaminergic signals. The calculation of individual delta%L/delta%B ratios may serve, therefore, as a valuable indicator for early detection of autonomous pituitary prolactin secreting cells and for evaluation of the extent of the pituitary lesion.


The influence of bromocriptine on serum levels of growth hormone and other pituitary hormones and its metabolic effects in active acromegaly. The effect of treatment with bromocriptine for 12--18 months on serum GH and metabolic responses was studied in sixteen patients with active acromegaly. Of this group ten patients showing a sustained GH reduction of more than 50% during an 8 h bromocriptine test, proved to be responsive to long-term therapy. In the responding patients GH levels decreased to 38% of the pretreatment level after 12 months of therapy. A dose higher than 10 mg did not produce a significantly greater effect. Prolactin and LH levels decreased in all patients, FSH levels showed a significant rise. Testosterone levels in the male patients increased significantly, indicating that the state of hypogonadism can at least be partially reversed. The GH levels became normal in only one patient. We conclude that the role of bromocriptine in acromagaly is limited and selective pituitary operation and/or irradiation is preferred as definitive treatment in most patients.


Translocation 46XY, t (17;18) (q25;q21) in a mentally retarded boy with progressive eye abnormalities. A 10-year-old boy with reciprocal translocation between chromosomes 17 and 18- 46XY,t (17;18) (q25; q21), appeared cytogenetically balanced. The patient was a healthy, thriving boy whose main abnormal feature was moderate mental retardation. However, abnormal ocular signs were present, including macular "fibrosis", optic disc abnormalities with a traction retinal detachment, tapeto-retinal degeneration, and tilting of the disc to the nasal side. These changes are consistent with the ocular changes previously described in the 18q- syndrome, suggesting that there has been a minimal deletion of chromosome material at the 18q21 breakpoint. The case also demonstrates that the ocular changes of the 18- syndrome may be progressive.


Immunogenicity and kinetics of distribution and elimination of sheep digoxin-specific IgG and Fab fragments in the rabbit and baboon. To evaluate the relative merits of purified IgG and Fab preparations of defined specificity for potential clinical use, immunogenicity studies were carried out in baboon and rabbit experimental models. Distribution and elimination kinetics of purified sheep digoxin-specific IgG and Fab fragments were also studied following intravenous administration to baboons. Serial plasma and urine Fab concentrations were determined from trichloroacetic acid-precipitable 125I counts from pre-labelled preparations and also by measurement of the antibody's functional 3H-digoxin binding capacity. Results were compared with data obtained from IgG by 3H-digoxin binding. Kinetic data analysed by computer-fitted functions demonstrated that plasma Fab disappearance was best described by a tri-exponential function, whereas a bi-exponential function best described the IgG data. Initial distribution half-life (t 1/2) of Fab (0.28-0.32 hr) was considerably shorter than that of IgG (4.0 hr) and contributed a greater proportion of the total fall in plasma level over 24 hr. Fab elimination t 1/2 (9-13 hr) was also shorter than IgG (61 hr), but appreciably longer than earlier estimates in rabbits, guinea-pigs, rats and mice. The total volume of distribution of Fab was 8.7 times greater than that of IgG measured by the same method. Over the first 24 hr after administration 30-45% of administered Fab was recoverable in active form in urine, while 93% of total administered 125I counts from 125I-Fab preparations (bound and free) could be recovered. Less than 1% of administered IgG binding activity was recovered in urine during the initial 24 hr. The relative immunogenicities of sheep digoxin-specific IgG and Fab fragments were studied in six baboons. Both IgG and Fab elicited prompt immune responses when injected intramuscularly with Freund's complete adjuvant. Intravenous injection of soluble sheep IgG resulted in a prompt immune response in one baboon while repeated injections caused only a late, weak response in a second animal. Soluble sheep Fab fragments elicited only delayed and weak responses in the two baboons thus challenged. Further immunogenicity studies in ninteen rabbits showed significantly earlier and greater antibody responses to intravenously administered sheep IgG antigen than to Fab fragments derived from the same IgG population. These studies demonstrate that digoxin-specific Fab fragments undergo more rapid and extensive distribution to the extra vascular compartment and also more rapid renal excretion than IgG. Furthermore, Fab fragments are significantly less immunogenic than the parent IgG population. These data indicate potentially important therapeutic advantages for digoxin-specific Fab compared with IgG when administered for the reversal of life-threatening digitlis toxicity.


Relative importance of C3b inactivator and beta 1H globulin in the modulation of the properdin amplification loop in systemic lupus erythematosus. Serum concentrations of C4, C3, factor B (B), properdin (P), C3b inactivator (C3bINA) and beta 1H globulin have been measured by radial immunodiffusion in sixty-two samples from thirteen patients with systemic lupus erythematosus (SLE). Significant reductions in the mean serum concentrations of C4 (classical pathway) B and P (alternative pathway) and C3 were found. In addition, the mean level of the control protein beta 1H, but not C3bINA, was reduced. Sera from thirteen patients taking during disease exacerbation (low C3) showed significantly lower levels of both C3bINA and beta 1H than sera taken from the same thirteen patients during disease remission (high C3). Serum concentrations of C3bINA correlated with B (P less than 0.005) but not C4, C3 or P, whereas levels of beta 1H correlated with C4 (P less than 0.01), B (P less than 0.005) and properdin (P less than 0.01). Serial measurements of the serum concentrations of C3bINA and beta 1H showed that levels of these protein fell during exacerbation, and such falls were more closely associated with diseases in the serum levels of the alternative pathways proteins than C4. It is concluded from these observations that serum concentrations of the control proteins C3bINA and beta 1H, especially the latter, control the extent of turnover of the alternative pathway in SLE. Metabolic studies are required to determine the causes of the decreased serum concentrations of these control proteins.


Pulmonary function changes in normal rats induced by antibody against rat IgE. Changes in pulmonary function, as measured by airway conductance and dynamic compliance, in normal rats have been provoked by the administration of a rabbit antisera prepared against rat IgE myeloma protein. The response is specific in that neither anti-IgG nor normal rabbit serum induced pulmonary changes. Pre-treatment with disodium cromoglycate inhibits the bronchospasm in a dose related manner. In addition, drug protection can be demonstrated with as long 1 hr pre-dosing.


Do contraceptives influence the incidence of acute pelvic inflammatory disease in women with gonorrhoea? The influence of different contraceptive techniques on the incidence of pelvic inflammatory disease (PID) in 672 patients with gonorrhoea have been studied. The lowest frequency of PID was found in patients using hormonal contraceptives (Group A), 8.8 per cent compared to 23.5 per cent in patients using intrauterine devices (Group B) and 15.1 per cent in patients using neither technique (Group C). In comparable control groups no significant differences in background factors, such as age, marital status and sexual activity were demonstrated. It is therefore concluded that the significantly lower incidence of PID in patients using hormonal contraceptives compared to the other groups and the high incidence of PID in patients using intrauterine devices is related to the contraceptive technique per se.


Treatment of rhesus monkeys (Macaca mulatta) with intrauterine devices loaded with levonorgestrel. The effects of levonorgestrel-loaded plastic intrauterine devices on endometrial morphology were investigated in 15 rhesus monkeys for 14 weeks. The devices were designed to release 25 microgram of the hormone per day and were inserted in the uterus by hysterotomy. Control animals were sham operated or received inert placebo devices. With the levonorgestrel-releasing devices, widespread changes in endometrial morphology were seen. These changes included atrophy of the endometrial mucosal and glandular epithelium and decidualization of the endometrial stroma. With the inert placebo control devices, only minor changes in endometrial morphology were observed.


Insignificance of colonic bacteria in the sputum of patients in a new ICU. Over a 12-month period, 27% of patients in a new ICU grew bacterial pathogens from sputum or tracheal cultures. The commonest isolates were Pseudomonas aeruginosa and Klebsiella species. Endotracheal intubation, the length of time intubated, and antimicrobial therapy all predisposed to the isolation of organisms from sputum. No patient developed a gram-negative pneumonia, and there was no case of septicemia associated with a positive sputum culture. The presence of epithelial or pus cells in sputum was unrelated to the culture results. It was concluded that the growth of colonic bacteria from sputum or tracheal aspirates was of little prognostic or clinical significance. No significant common environmental site or cross-infection pathway was identified: sinks were contaminated by patients rather than vice versa. Most sputum isolates were probably endogenous in origin.


Cerebral tissue response to reserpine: a morphological study. The acute influence of reserpine injection on cerebral tissue was studied in baboon and rat models. Five h after the infusion of reserpine, bilateral cortical areas were found to contain perivascular changes only, whereas basal ganglia regions contained advanced oedematous responses. Mitochondrial swelling was commonly found in the latter regions, as were loci containing microvascular crenation with accompanying pericytic changes.


Cell wall biogenesis in Oocystis: experimental alteration of microfibril assembly and orientation. Cell wall biogenesis in the unicellular green alga Oocystis apiculata has been studied. Under normal growth conditions, a cell wall with ordered microfibrils is synthesized. In each layer there are rows of parallel microfibrils. Layers are nearly perpendicular to each other. Terminal linear synthesizing complexes are located in the plasma membrane, and they are capable of bidirectional synthesis of cellulose microfibrils. Granule bands associated with the inner leaflet of the plasma membrane appear to control the orientation of newly synthesized microfibrils. Subcortical microtubules also are present during wall synthesis. Patterns of cell wall synthesis were studied after treatment with EDTA and EGTA as well as divalent cations (MgSO4, CaSO4, Cacl2). 0.1 M EDTA treatment for 15 min results in the disassociation of the terminal complexes from the ends of microfibrils. EDTA-treated cells followed by 15 min treatment with MgSO4 results in reaggregation of the linear complexes into a paired state, remote from the original ends to which they were associated. After 90 min treatment with MgSO4, normal synthesis resumes. EGTA and calcium salts do not affect the linear complexes or microfibril orientation. Treatments with colchicine and vinblastine sulphate do not depolymerize the microtubles, but the wall microfibril orientation is altered. With colchicine or vinblastine, the change in orientation from layer to layer is inhibited. The process is reversible upon removal of the drugs. Lumicolchicine has no effect upon microfibril orientation, but granule bands are disorganized. Treatment with coumarin, a known inhibitor of cellulose synthesis, causes the loss of visualization of subunits of the terminal complexes. The possibility of the existence of a membrane-associated colchicine-sensitive orientation protein for cellulose microfibrils is discussed. Transmembrane modulation of microfibril synthesis and orientation is presented.


Maternal deprivation, 1972-1978: new findings, new concepts, new approaches. Research since 1972 in the field of "maternal deprivation" is critically reviewed. The results are used to reassess briefly the formulations proposed in 1972 and to discuss more fully the meaning and practical implications of fresh findings on new or recently revived topics. These include the development of social relationships and the process of bonding, critical periods of development, the links between childhood experiences and parenting behavior, influences on parenting, and the possible reasons why so many children do not succumb to deprivation or disadvantage.


Primate repetitive DNAs: evidence for new satellite DNAs and similarities in non-satellite repetitive DNA sequence properties. Repetitious DNA sequences have been isolated from a number of the primates in in both Suborders Anthropoidea and Prosimii by hydroxy-apatite chromatography at a Cot of 10. In addition to finding previously unreported possible AT-rich satellite DNAs in Orangutan, Gibbon, Rhesus and Slow Loris a clear similarity to human DNA was found in the nonsatellite repetitious DNA sequence properties of the primates in the Suborder Anthropoidea. This is based on the presence of the hydroxyapatitie isolated 1.703 and 1.714 g/cm3 DNA families in CsCl gradients in the analytical ultracentrifuge following renaturation and extensive DNA hyperpolymer network formation. Within the superfamily Hominoidea the amount of the 1.714 g/cm3 DNA family was greater than that of the 1.703 g/cm3 DNA family while the reverse situation was true within the Superfamily Cercopithecoidea. The orangutan 1.703 and 1.714 g/cm3 DNA families were shown to exhibit the same differential reassociation behavior demonstrated previously in human DNA (Marx et al., 1976a). These data are interpreted as preliminary evidence for a similar sequence organization in the Order Primates Suborder Anthropoidea.


The relationship between juxtapapillary diverticula and biliary calculi. An endoscopic study. A systematic prospective endoscopic study of the incidence of juxtapapillary diverticula in a variety of digestive disorders was undertaken in the Surgical Clinic at the Provincial Hospital, Port Elizabeth. The findings were related to conditions commonly encountered. The following frequency distribution was found: 33 diverticula out of 164 patients associated with gallstones (20.1%); 15 out of 668 patients not associated with gallstones (2.2%); 1 out of 39 patients with pancreatitis (2.6%); and 3 out of 146 patients with gastric ulcer (2.1%). No diverticulum was noted in 111 patients with duodenal ulcer. These findings suggest that juxtapapillary diverticula are nearly 10 times more common in patients with gallstones than in patients without. There is evidence to suggest that these diverticula tend to precede the gallstones. It is conceivable that juxtapapillary diverticula may predispose to gallstones. Alternatively, both conditions may be manifestations of another underlying disorder as yet to be defined.


Intraluminal duodenal diverticulum. Report of a case diagnosed by endoscopy. Intraluminal diverticulum of the duodenum is a very rare congenital anomaly arising in the second part of the duodenum in close relation to the papilla of Vater. 39 cases have been reported in our available literature. The clinical symptoms and signs are nonspecific, and characteristically the preoperative diagnosis has in all cases been based on the roentgenographic appearance of the lesion. In this paper we present a case diagnosed by duodenoscopy, the radiological studies including hypotonic duodenography revealing no pathology.


Effects of dietary cadmium on rhesus monkeys. Ten male rhesus monkeys, each weighing 3.5 kg, were divided into four groups of 3, 3, 2, and 2, and were fed daily with 100 g pelleted food containing 300, 30, 3, and 0 ppm cadmium, respectively. Urine samples were collected every 2 weeks and blood samples every 4 weeks. One monkey each of the 300 and 30 ppm groups was autopsied for pathological examination and tissue cadmium determination at the week 24 of the experiment; the remaining 8 animals were killed after 55 weeks. The lowest exposed group (3 ppm) did not show any specific biological response to cadmium over a period of 55 weeks. In the 30 ppm group, no significant changes were observed for up to 24 weeks, although cadmium concentration in the renal cortex and urine at 24 weeks were 300 mug/g wet weight and 18 mug/l., respectively. Plasma urea nitrogen and urine protein (quantitative determination) increased after 30 and 36 weeks. At 55 weeks of the experiment, qualitative tests were negative for low molecular weight proteinuria and glycosuria, and the results remained normal for renal and liver function tests and blood analysis, although cadmium concentrations in the renal cortex of two monkeys were 460 and 730 mug/g wet weight and those in the liver were 110 and 160 mug/g wet weight, respectively. In the highest exposure group (300 ppm), urine cadmium increased to 250 mug/l. by 11 weeks, and urine retinol-binding protein, plasma GOT, GPT, and LDH increased after 12 weeks. Proteinuria (quantitative determination), glycosuria, aminoaciduria (panaminoaciduria), and erythrocytopenia were observed after 16 weeks, when urine cadmium was 500-900 mug/l. Hypohemoglobinopathy and proteinuria (qualitative determination) were observed after 20 and 24 weeks, while cadmium concentrations in the renal cortex and the liver were 760 and 430 mug/g wet weight at 24 weeks, respectively. Slightly depressed tubular reabsorption of phosphate, increased urine beta(2)-microglobulin, increased plasma urea nitrogen, and increased plasma alpha(2)-globulin fraction (electrophoresis) were observed between 28 and 30 weeks of the experiment. Creatinine clearance and plasma cholinesterase decreased after 47 and 54 weeks, respectively. Cadmium concentrations in the renal cortex and the liver of two monkeys at 55 weeks were 350 and 580 mug/g wet weight and 410 and 630 mug/g wet weight, respectively. Pathological examinations revealed denaturation, destruction, and regeneration of the epithelial cells in renal proximal tubules, but no pathological changes in osseous tissues. Critical cadmium concentration in the renal cortex was estimated to be 380 mug/g wet weight for low molecular weight proteinuria and 470 mug/g wet weight for proteinuria, glycosuria, and aminoaciduria. Critical concentration in the liver was also estimated to be 210 mug/g wet weight. The apparent biological half-time of cadmium in monkeys at autopsied stage was calculated to be 0.66, 6.4, 5.2, and 22.4 years for the 300, 30, 3, and 0 ppm groups, respectively.


The presence of precipitating antibodies in the sera of horses with chronic obstructive pulmonary disease (COPD). The sera of horses affected and not affected with chronic obstructive pulmonary disease (COPD) were examined for precipitins to Micropolyspora faeni and Aspergillus fumigatus. Precipitins to both antigens were not restricted to COPD cases but occurred more frequently in animals affected with COPD. Many animals without detectable precipitins responded clinically to inhalation challenge with these antigens.


Comparative studies of penicillin-binding proteins in Pseudomonas aeruginosa and Escherichia coli. Penicillin-binding proteins in Pseudomonas aeruginosa were compared with those of Escherichia coli. These in P. aeruginosa were found exclusively in the cytoplasmic membrane fraction (fraction soluble in sodium N-lauroyl sarcosinate). Sodium dodecyl sulfate/acrylamide gel electrophoresis of the proteins bound to [14C]penicillin G resulted in the separation of six major bands and several minor bands. The proteins in these bands are referred to as proteins 1A, 1B, 2, 3, 4 and 5 in order of increasing electrophoretical mobility. The electrophoretic mobilities and other properties of penicillin-binding proteins in P. aeruginosa and E. coli were compared and correlated. Fundamentally they seem to be very similar in the two bacteria, but proteins 1A and 1B in P. aeruginosa seem to correspond respectively to proteins 1B and 1A in E. coli, and protein 6 seems to be missing or present in only small amount in P. aeruginosa. In addition, the affinities of currently developed beta-lactam antibiotics to each protein of P. aeruginosa and E. coli were examined in relation to the morphological changes of the cells induced by these antibiotics and their antibacterial potencies. Mecillinam showed high affinity to only protein 2 in both P. aeruginosa and E. coli. At a minimal inhibitory concentration, it converted cells of both P. aeruginosa and E. coli from rods to spherical cells, although its minimal inhibitory concentration was much higher for P. aeruginosa than for E. coli.


Protein synthesis in brine shrimp embryos. Dormant and developing embryos of Artemia salina contain equivalent amounts of chain initiation factors 2. Dormant and developing embryos of Artemia salina contain equivalent amounts of eIF-2, the eukaryotic initiation factor which forms a ternary complex with GTP and Met-tRNAf. The factor was purified from 0.5 M NH4Cl ribosomal washes by (NH4)2SO4 fractionation, followed by chromatography on heparin-Sepharose, DEAE-cellulose, hydroxyapatite and phosphocellulose. Purified preparations from dormant and developing embryos have similar specific activities and nucleotide requirements. The mobility of both proteins in dodecylsulfate gel electrophoresis is indistinguishable, and each contains three major polypeptide chains of molecular weight 52 000, 45 000 and 42 000. Both proteins are also immunologically identical, and each stimulates amino acid incorporation in a cell-free system of protein synthesis. The binding of [35S]Met-tRNAf to 40-S ribosomal subunits is catalyzed by eIF-2 isolated from dormant or developing embryos and is dependent upon GPT and AUG. Binding of [35S]Met-tRNAf to 40-S ribosomal subunits, and ternary complex formation with eIF-2, GTP, and [35S]Met-tRNAf is stimulated 2--3-fold by a factor present in the 0.5 M NH4Cl ribosomal wash and which elutes from DEAE-cellulose at 50 mM KCl. This protein does not exhibit GTP-dependent binding of [35S]Met-tRNAf. Binding of GDP and GTP was investigated with purified eIF-2 from developing embryos. The factor forms a binary complex with GDP or GTP, and eIF-2-bound [3H]GDP exchanges very slowly with free nucleotides. Our results suggest that eIF-2 does not limit resumption of embryo development following encystment, nor does it limit mRNA translation in extracts from dormant embryos.


Acidic ribosomal proteins from eukaryotic cells. Effect on ribosomal functions. Precipitation of Saccharomyces cerevisiae ribosomes by ethanol under experimental conditions that do not release the ribosomal proteins can affect the activity of the particles. In the presence of 0.4 M NH4Cl and 50% ethanol only the most acidic proteins from yeast and rat liver ribosomes are released. At 1 M NH4Cl two more non-acidic proteins are lost from the ribosomes. The release of the acidic proteins causes a small inactivation of the polymerizing activity of the particles, additional to that caused by the precipitation itself. The elongation-factor-2-dependent GTP hydrolysis of the ribosomes is, however, more affected by the loss of acidic proteins. These proteins can stimulate the GTPase but not the polymerising activity when added back to the treated particles. Eukaryotic proteins cannot be substituted for bacterial acidic proteins L7 and L12. We have not detected immunological cross-reaction between acidic proteins from Escherichia coli and those from yeast, Artemia salina and rat liver or between acidic proteins from these eukaryotic ribosomes among themselves.


Purification and some characteristics of the human coagulation factor VII. 1. A purification procedure for factor VII (proconvertin) from human plasma is described. The procedure involves barium sulphate adsorption and elution. DEAE-Sephadex column chromatography, barium sulphate adsorption and elution, heparin-Sepharose column chromatography, preparative disc gel electrophoresis and finally adsorption with antiserum to prothrombin coupled to Sepharose and antiserum to albumin coupled to Sepharose. This procedure gave an approximately 8 . 10(5)-fold purification. 2. The factor VII obtained from the electrophoresis step was mainly a single-chain protein with an apparent molecular weight of 53000 +/- 2000. 3. After the final purification step, additional forms of factor VII, resulting from a fragmentation of the factor VII molecule were detected. 4. Amino acid composition data of the purified factor VII are given. 5. Antisera were raised in two different rabbits by injection of the purified factor VII. The antisera obtained gave a good titre against the factor VII activity and were not directed against any of the three other vitamin-K-dependent coagulation factors.


Fluorescent derivatives of yeast tRNAPhe. The preparation of four fluorescent derivatives of tRNAPhe (yeast) and their characterization by chemical, spectroscopic, and biochemical methods is described. The derivatives are prepared by replacing wybutine (position 37 in the anticodon loop) or NaBH4-reduced dihydrouracil (positions 16/17 in the hU loop) with ethidium or proflavine; they are isolated by reversed-phase chromatography (RPC-5). All tRNAPhe-dye derivatives are aminoacylated by yeast phenylalanyl-tRNA synthetase to at least 80% of the charging capacity of the unmodified tRNAPhe with an unchanged Km (0.2 mucroM) and a V lowered by 30--50%. They exhibit good to excellent activity in the aminoacylation assay from synthetase from Escherichia coli. It is concluded that the insertion of the dyes does not seriously disturb essential elements of the native tRNAPhe structure. The dyes are bound via N-ribosylic linkages. The appearance of isomeric tRNAPhe-ethidium derivatives is attributed to the involvement of the different amino groups of ethidium in the condensation. In addition, there are indications for the existence of alpha and beta anomers of the tRNA-dye compounds. The dyes are rigidly fixed to their position in the tRNA molecule by stacking interactions with the neighboring bases. The ethidium probes show Mg2+-induced changes of the tRNA conformation which are paralleled by changes of the rate of aminoacylation. On the basis of this observation it is hypothesized that conformational flexibility of the tRNA molecule is a functionally important feature of the tRNA structure.


Binding of specific ATP citrate lyase and fatty acid synthetase antibodies to heavy populations of rat liver polysomes. The polysome fractions involved in the synthesis of the rat-liver inducible lipogenic enzymes, ATP citrate lyase and fatty acid synthetase, were identified by their binding of radioiodinated specific antibodies to enzyme. Both of these populations of specific polysomes were shown to be markedly heavier than specific polysomes involved in albumin synthesis. The quanity of antibody bound to the lipogenic enzyme-related polysomes was markedly affected by the dietary status of the animal. A dietary regimen which induced ipogenesis resulted in a tenfold increase in the hepatic activities of these enzymes found in normally fed animals. The radioactivity bound to hepatic polysomes of induced rats was likewise greater than tenfole higher, presumably reflecting an increase in the number of polysomes active in enzyme synthesis. The fasting state resulted in lower hepatic enzyme activity than normal and correspondingly less binding of ATP citrate lyase and fatty acid synthetase antibodies to the heavy polysomes of the sucrose gradient.


Flavanone synthase from Petroselinum hortense. Molecular weight, subunit composition, size of messenger RNA, and absence of pantetheinyl residue. Flavanone synthase from irradiated cell suspension cultures of parsley was purified to apparent homogeneity. Molecular weights of about 77 000 for the enzyme and about 42 000 for the subunits were determined respectively by sedimentation-equilibrium measurements and disc-gel electrophoresis in the presence of dodecyl sulfate. A specific antiserum was prepared for the enzyme and was used in an assay for flavanone synthase mRNA activity in partially purified RNA preparations. The apparent molecular size of flavanone synthase mRNA was estimated by sucrose gradient centrifugation and gel electrophoresis under partially denaturing conditions. Values of about 17 S and Mr = 0.62 X 10(6) were obtained. The fractionation patterns suggested that flavanone synthase mRNA was homogeneous in size. All together, the results support the idea that the enzyme is composed of two subunits which are probably identical. Amino acid analysis and a microbial assay were carried out to test the possible occurrence of cysteamine, beta-alanine, and pantothenate in the enzyme. The results were negative, indicating the absence of pantetheine or a similar residue. The possible similarity in mechanism between flavanone synthase and 3-oxoacyl-(acyl carrier protein) synthase is discussed.


Pharmacokinetics of cyclophosphamide after prolonged low dose treatment in ovarian cancer patients. We have studied Cyclophosphamide (Cy) pharmacokinetics in 9 patients after their first intravenous dose of 100 mg, and in 9 patients after 6--13 months of continual treatment with the same dose every day. The half-life of Cy was shorter (p less than 0.05) in the latter group, the Co was greater (less than 0.01) and the Vd was clearly less (p less than 0.01). The AUC was unchanged.


Rabbit allotype a locus subspecificities of homogeneous anti-streptococcal antibodies. Rabbits were immunized with group A-variant (Av) streptococcal vaccine to elicit antisera containing antibodies of "restricted heterogeneity" specific for Av polysaccharide. Antibodies that migrated as single bands in polyacrylamide gel isoelectric focusing were isolated on agarose block electrophoresis and preparative isoelectric focusing. These homogeneous antibodies were analyzed for content of the a locus markers by inhibition of allotype-anti-allotype radioimmunoassays. Both single-band preparations and preparations containing 2--5 bands were deficient in content of the a locus markers. These analyses were strongly influenced by the different anti-allotype antisera used. Single-band preparations, deficient in a 2 or a 3 markers, were further used to produce anti-allotype antisera, and these sera were assayed for reaction with pooled a2 or a3 molecules. The results, in contrast to the a1 allotype, failed to demonstrate common determinants on either a 2 or a 3 molecules indicating that each a allotype consists of a set of different Ig molecules. The data suggest different evolutionary pathways of the a 1, as opposed to the a 2 and a 3 molecules.


Norepinephrine elevations in cerebrospinal fluid after d- and l-amphetamine. We continuously collected cerebrospinal fluid (CSF) from the lateral ventricles of monkeys and gave them from 0.1 to 1.0 mg/kg d- or l-amphetamine intravenously. The norepinephrine (NE) content of their CSF had a small circadian rhythm and a large increase after amphetamine. 1.0 mg/kg amphetamine gave a four-fold rise in CSF-NE which remained elevated for 33 h, smaller doses gave proportionately lesser responses. Both d- and l-amphetamine caused similar NE elevations except for minor differences at the highest dose. If there are differences in behavioral effects of moderate doses of d- and l-amphetamine, they are probably not due to a general difference in central NE release from these stereoisomers.


Growth enhancement and serum replacement in cloning of murine mastocytoma and granulocyte/macrophage precursor cells: two distinct activities present in hemolysates. In the present study we investigated the serum replacing and enhancing activities of erythrocyte lysates, obtained from different animal species, on the growth of murine mastocytoma cells and normal granulocyte/macrophage precursor cells (CFU-C) present in bone marrow. The soft agar technique for cloning hemopoietic cells in vitro was used to quantitate the growth of these cells in culture. Rat, rabbit, guinea pig, mouse and sheep hemolysates were tested for their capacity to replace or to enhance serum as a growth promoter. All hemolysates except mouse were able to replace serum efficiently when mastocytoma cells were cloned. On the other hand, only rat hemolysate proved to be efficient for cloning normal murine CFU-C. Since increasing the concentration of hemolysates in the soft agar medium did not change these results, the differences in activity are unlikely to reflect quantitative variations. However, hemolysates with little or no serum replacing capacity enhanced the clonal growth of normal CFU-C when added to small amounts (2.5%) of horse serum. Trypsin treatment of rat hemolysate destroyed its serum replacing capacity but not its enhancing activity. No correlation was found between the amount of hemoglobin and the replacing activity of each hemolysate. The data obtained in the present study point to the presence of at least two distinct activities in hemolysate: serum replacing and growth enhancing capacities.


Projection of the cerebellar dentate nucleus onto the frontal association cortex in monkeys. Stimulation of the cerebellar dentate nucleus in monkeys elicited responses in the frontal association cortex (area 9) on the contralateral side to the stimulation, in addition to those in the motor (area 4) and premotor (area 6) cortices which were reported previously. The responses in the frontal association cortex were characterized by surface positive-deep negative field potentials in the cortex. They contrasted with surface negative-deep positive potentials in the motor and premotor cortices on the same dentate nucleus stimulation. In the rostral part of the premotor cortex (area 6) on the border of area 9, both types of responses were induced and admixed. The relay nucleus of the thalamus was suggested for the dentate-induced responses in the frontal association cortex.


Fusional vergence ranges of the monkey: a behavioral study. Fusional vergence ranges were behaviorally determined for two rhesus monkeys and two human subjects using random dot stereograms as stimuli. The subject performed a two-alternative forced choice form discrimination of discretely presented stimuli and the fusional vergence stimulus was changed during the intertrial intervals. The fusional vergence measurements for the monkey were similar to those for the human subjects.


Immunochemical identity of dipeptidyl aminopeptidase IV from pig serum, liver, submaxillary gland and kidney. The enzymes which were extracted by autodigestion from the microsomal fractions of the pig kidney, liver and submaxillary gland and from the serum showed an immunochemical identity by a double immunodiffusion test. But the kidney enzyme had a different pI-value from the pI-values of the enzymes of other organs.


Superoxide dismutase and life span of Drosophila melanogaster. Comparison of superoxide dismutase activity in homogenates of wild and vestigial strains of D. melanogaster revealed a lower enzyme activity in the short-living vestigial strain.


Is superoxide dismutase a physiological radioprotector? Prolonged treatment with relatively low doses of ionizing radiation did not induce synthesis of superoxide dismutase, either in Drosophila melanogaster or in mice liver.


Polyadenylate-polyuridylate enhancement of 7,12-dimethylbenz-anthracene skin carcinogenesis. Double-stranded polynucleotide polyadenylate-polyuridylate (Poly AU) enhanced skin tumor formation in Swiss mice by 75% when injected prior to a single application of 7,12-dimethylbenzanthracene (DMBA). When given after the carcinogen application Poly AU did not significantly enhance tumor formation.


[Effect of nitroglycerin on the tonus of isolated coronary arteries]. It has established on isolated ring-like strips of large coronary arteries of the dog that spasmolytic effects of nitroglycerin are related to its antagonistic action on Ca2+ and are not completely pharmacomechanic. The action of nitroglycerin is not related to beta-adrenoreceptors of the coronary arteries and apparently is not mediated through an increase in the intracellular pool of cyclic AMP.


Regional cerebral blood flow thresholds during cerebral ischemia. The development of methods of determining regional cerebral blood flow (rCBF) has made possible the determination of thresholds for the appearance of cerebral ischemia. These thresholds vary depending on the method used for assessing cerebral ischemia. The following thresholds have been determined in man and nonhuman primates: 20 cc/100 g per min, electroencephalogram (EEG) and evoked cortical potential abnormalities appear, paralysis seen in waking monkeys; 15 cc/100 g per min. EEG and evoked cortical potential are lost; 12 cc/100 g per min, flows at this level in excess of 120 min produce infarction in waking animals; and 6 cc/100 g per min, massive loss of intracellular [K+]. The residual rCBF and the duration of ischemia determine the appearance of infarction in waking Macaca irus monkeys.


Inhibition of ovarian, placental, and adrenal steroidogenesis in the rhesus monkey by trilostane. Trilostane inhibits adrenal, ovarian, and placental steroidogenesis when administered orally to rhesus monkeys. By inhibiting 3 beta-hydroxysteroid dehydrogenase activity, it causes an increase in circulating levels of pregnenolone. Trilostane reverses the stimulation of luteal progesterone production and the delay in onset on menstruation induced by human chorionic gonadotropin. In pregnant monkeys it reduces circulating progesterone levels and is an effective interceptive agent if given for 5 days beginning on day 16, 25, or 50 of gestation. Concurrent administration of progesterone prevents this interceptive effect. Trilostane reduces plasma cortisol levels at doses lower than those necessary to terminate pregnancy.


Cell surface changes in mouse peritoneal macrophages after induction with proteose peptone or thioglycollate. Some five to six per cent of mouse PEC spontaneously form rosettes with SRBC. This weak intercellular interaction is most likely mediated by a "receptor" for SRBC located on the surface of peritoneal macrophages. Manifestation of the receptor is influenced by the genetic background and the H-2 haplotype of PEC donors; a high proportion of RFC is associated with the H-2s haplotype. PEC derived from intact mice markedly differ in morphological and functional characteristics from those of PP- or TG-pretreated donors. Formation of rosettes by induced macrophages depends on the time interval between stimulation and PEC harvesting and on the type of the inducing agent; it is also radiosensitive and more responsive to the action of colchicine. TG-induced macrophages have a significantly reduced capacity to bind syngeneic lymphoid cells. The difference in adhesivity between intact and stimulated PEC can be abolished by glutaraldehyde prefixation. In vivo induction results in modified morphological and functional properties of macrophages, including transformation of their cell surface.


[Electron microscopic aspects of opportunistic fungi after pretreatment]. The ultrastructive of Aspergillus fumigatus, Aspergillus flavus and Aspergillus niger was studied when treated in vitro with 0.001, 0.01 and 0.1% econazole nitrate and econazole base. The very first morphological alterations appear faster than in normal-growing fungus and consist in a convoluted cytoplasmic membrane, large mesosomes and lomasomes and an extensive vacuolization. Acid phosphatase is found in the mesosomes and lomasomes and also in the center of the vacuoles. This is an early sign of fungus degradation.


[Saphrophytic life of opportunistic fungi]. Probably all pathogenic fungi can cause opportunistic infections in compromised hosts. This paper briefly reviews our knowledge on the saprophytic life - geographic distribution and habitat - of the most common pathogenic fungi. Some mycoses are of endogenous origin - e.g. Candida albicans is an endosaprophyte - others of epigenon origin - e.g. Pityrosporum ovale is an episaprophyte - but most mycoses are caused by fungi which have an exosaprophytic (or exosaprobic) life: one becomes infected after exposure to the saprobic source of the fungus. Nevertheless, it should be kept in mind that mycoses, e.g., cryptococcosis, coccidioidomycosis, and histoplasmosis, in compromised hosts are not necessarily the result of recent exposure but may be the result of the reactivation of latent or inactive forms.


[Opportunistic fungi in the atmosphere]. Our knowledge in aerobiology has considerably increased in the last 20 years due to new trapping methods. The use of volumetric spore traps permits to accurately analyze the particles suspended in the air and their evolution, while the deposition method gives an incomplete picture of the real air content. The air microflora changes considerably during 24 h: some groups of spores occur in the morning, others in the afternoon and yeast-like organisms during the night. The most common fungi in the atmosphere are Cladosporium sp., Sporodbolomyces considerably increase (20-10(3) times) the number of spores released in the atmosphere. Aspergillus flavus, thermophilic actinomycetes, Botrytis cinera and Didymella exitialis are cited as examples.


[Fungi in pulmonary pathology].

[Fungi in pulmonary pathology]. The author presents the most frequently observed pulmonary infections due to some opportunistic fungi (yeast, Aspergillus, Mucor). He describes the criterial for a correct diagnosis of pulmonary mycosis.


The effects of protein malnutrition on the behavior of rats during the suckling period. Observations of 2 groups of dams and their litters were made every 3 hr around the clock on Days 1-20 postpartum. The dams fed either an 8% or a 25% casein diet for 5 weeks before mating and during gestation and lactation. Dams on the low protein diet spent more time in the nest actively nursing their young than did high protein dams, and they exhibited no deficits in other maternal behaviors. Five of 11 kinds of behavior developed more slowly in the undernourished pups than in the well-nourished ones, but the developmental delays were no longer than a few days. Circadian fluctuations were apparent in all of the pups' activities during the 3rd postnatal week as well as in grooming and horizontal movement, 2 behaviors that were present earlier, by 6-10 days of age.


Home orientation in nursling rats: the effects of rehabilitation following intergenerational malnutrition. Rat pups with histories of intergenerational malnutrition were rehabilitated by cross-fostering at birth to well-nourished females. These pups weighed slightly less than well-nourished controls but significantly more than pups reared by malnourished females. Rehabilitated and control pups were both more active than malnourished pups reared by malnourished females. However, the percentage of nest returns by pups displaced to other parts of the cage was low among rehabilitated pups as compared with controls, but did not differ from that of pups with histories of intergenerational malnutrition reared by malnourished females. These data suggest that, although activity is a product of postnatal condition, home-orienting behavior is affected by a history of intergenerational malnutrition regardless of rehabilitation.


Angiographic diagnosis of a bleeding jejunal diverticulum. The authors report on the preoperative diagnosis of a bleeding jejunal diverticulum by selective arteriography. The angiographic findings, as well as the difficulties of the intraoperative localization of bleeding jejunal diverticula, are discussed.


Amino acid substitution: its use in detection and analysis of genetic variants. Techniques of chemical analysis, amino acid sequencing and autoradiography are being used to study the frequency of incorporation of normally noncoded amino acids into hemoglobins and seminal fluid proteins. We are studying, by the sequencing of radiolabeled proteins followed by the recovery of [3H]isoleucine phenylthiohydantoin by high-performance liquid chromatography, the frequency at which normally noncoded isoleucine is incorporated into hemoglobin because of base-substitution mutations versus translational errors. Irradiation increases the isoleucine content of human hemoglobin and the frequency of substitution of isoleucine for specific amino acids in rabbit hemoglobin. Studies to date indicate that these techniques have been developed sufficiently for initial analysis of the potential of drugs and environmental pollutants to induce base-substitution mutations in mammalian somatic cells.


Control of male reproductive behavior by the central nervous system of Drosophila: dissection of a courtship pathway by genetic mosaics. In gynandromorphs of Drosophila, a detailed examination was made of the association between male courtship behavior and the chromosomal genotype of various parts of the central nervous system. Mosaic flies that behave as males repeatedly show a shorter courtship than normal males. If there is to be male behavior, the posterior dorsal brain must be haplo-X on at least one side for occurrence of the early courtship events. Tapping, following of females and wing extension. Licking (proboscis extension) has nearly the same focus but is submissive; that is, male tissue must be present in both left and right dorsal brain. The next courtship step, attempted copulation, has a focus (especially for actual genital contact) located in the thoracic ganglia, though apparently not in a discrete region. Attempted copulation, which can occur even in mosaics with a gravid abdomen, may be correlated with the presence of sex combs. The role of courtship foci are interpreted in terms of known sensory inputs to and functions of the major insect ganglia.


[Biological characteristics of various strains of Pseudomonas aeruginosa isolated from human pathological matter]. According to the higher frequency of isolation of bacterial strains belonging to the genus Pseudomonas from various human phatologic materials, in was seemed interesting to study the biological characteristics of these bacteria, which are the most virulent and pathogenic Gram-microorganism. In the present work the results of cultural, biochemical, cytochemical and immunological tests are reported. In vivo tests were also carried out, using rabbits inoculated with whole cells or their products.


Evolution of polypyrimidines in Drosophila. We surveyed 101 different Drosophila species for the presence of a particular highly repetitive DNA sequence containing long tracts of polypyrimidine/polypurine DNA, first found in D. melanogaster. Out of 55 tested species in the melanogaster group, only the sibling species D. simulans and D. mauritiana, as well as one distant relative in the ananassae subgroup, D. varians, contained the same sequence. All four of these species have long pyrimidine tracts as shown by acid hydrolysis of labelled DNA. All four species have the same sequence, bu the amount of this polypyrimidine/polypurine DNA varies greatly. Four other species in the hydei subgroup were found to contain a polypyrimidine/polpurine sequence, with an oligonucleotide composition different from that of D. melanogaster. This polypyrimidine DNA varies from as much as 10% of the total DNA in D. nigrohydei, to as little as 0.4% in D. neohydei. The long pyrimidine tracts in the hydei subgroup are often more than a thousand nucleotides in length, representing exceedingly homogeneous repetitious sequences.--These results show a rapid but discontinuous pattern of evolution for polypyrimidine/polypurine DNA . These sequences are not species specific, yet closely related species have greatly different amounts of polypyrimidines. Drastic changes occur in the amounts of these satellite type DNA sequences, as if the sequence had no continuous selective advantage in evolution. The implications of these results with regard to the general function and evolution of satellite DNA are discussed.


Independent production of CO2 sensitivity by nuclear gene Dly and a transmissible agent from delayed-recovery Drosophila melanogaster. Flies of stocks designated delayed-recovery by McCrady and Sulerud (1964) remain temporarily paralyzed after exposure to carbon dioxide. This condition is similar to CO2-sensitivity, which occurs in flies infected with the maternally transmitted sigma viruus, but is due, at least in part, to the third chromosome mutant gene Dly. Because earlier work indicated that extracts of delayed-recovery flies could occasionally transmit CO2 sensitivity when injected into resistant recipients, we have tested the possibility that some delayed-recovery stocks contain a sigma-like transmissible virus, in addition to the Dly gene. We found that TDR-orange, a stock derived from the original delayed-recovery line, and temperature-cured populations of the same stock, both contain some agent that is transmissible by injection. TDR-BC3f, a stock derived by backcrossing through the male line to eliminate maternally transmitted factors, does not appear to contain such an infectious agent, but remains sensitive to CO2. These observations lead us to the conclusion that the originally described delayed-recovery stocks harbor an infectious extrachromosomal agent, in addition to possessing the Dly gene, and each is capable of producing a sensitivity to carbon dioxide.


Synaptonemal complex and recombination nodules in wild-type Drosophila melanogaster females. Electron microscope serial section reconstruction analysis of all zygotene-pachytene nuclei of meiotic cells from three wild-type germaria (a subunit of the ovary containing the early meiotic stages arrayed in temporal developmental sequence) of Drosophila melanogaster females corroborates and extends earlier observations (Carpenter 1975a) on the nature and sequence of ultrastructural events occurring during the time of meiotic recombination. Emphasis has been placed on (1) the time of appearance and disappearance of the synaptonemal complex (SC) and the changes in its dimensions that accompany a cell's progression through pachytene, and (2) the appearance, disappearance, number and chromosomal locations of recombination nodules (Carpenter 1975b). For both the SC and the recombination nodule the availability of several developmental series has provided an estimate of the biological variability in the properties of these recombination-associated structures. The much more extensive data presented here substantiate the earlier hypothesis that recombination nodules occur at sites where reciprocal meiotic recombination will occur, has occurred, or is occurring. A second morphological type of recombination nodule is reported; it is suggested that the presence of the latter type of nodule may correlate with sites of gene conversion. The hypothesis that there may be two types of meiotic recombination processes is discussed.


A new method to distinguish between meiotic and premeiotic recombinational events in Drosophila melanogaster. A new method is proposed to distinguish between meiotic and premeiotic exchange events in Drosophila melanogaster males associated with male recombination activities. The method was applied to data that have accumulated in this laboratory during the past five years, and it was concluded that a large fraction, perhaps the overwhelming majority, of the male recombinants were due to exchange events that took place before meiosis.


[Operon of riboflavin biosynthesis in Bacillus subtilis. XVI. Localization of the ribC-group markers on the chromosome]. Regulatory markers of ribC group were located on the chromosome of Bacillus subtilis by means of genetic transformation. Markers of this group controlling the regulation of riboflavin biosynthesis were mapped between markers of resistance to acriflavin and streptomycin (strC group). The value of cotransfer index between acriflavin-resistance markers and ribC markers was found to be 26--32%. Acriflavin inhibits the riboflavin biosynthesis. The level of inhibition depends on the genotype of riboflavin-producing strains, while the inhibition of the cell growth does not depend on it.


[Comparative study of the radiosensitivity of monkey chromosomes in cellular irradiation in vivo and in vitro]. Chromosome radiosensitivity was studied in the primary culture of peripheral blood lymphocytes and epithelial kidney cells of Macaca mulatta monkeys after gamma-irradiation in vivo and in vitro. The results of the experiments show that there are no differences in aberration yields produced in both types of somatic cells under gamma-irradiation in vivo and in vitro.


The growth and development of the squirrel monkey (Saimiri Sciureus). Squirrel monkeys of 2 subspecies, Bolivian and Colombian, were removed from their mothers on the day of birth and nursery reared for up to 2 years of age. Infants were tested weekly for 12 weeks, then monthly for 1 year, and at 2 years of age. Tests included morphology (body weight, crown-rump length, and head measurements), behavior (reflexes, activity, reaction to the surrogate), and physiology (heart rate, respiratory rate, temperature and optokinetic nystagmus). Data show some likenesses and some differences between the 2 subspecies.


Developmental changes of glycogen enzymes in fast and slow muscles of the rat. Glycogen synthase (GS), Branching enzyme (BE), Glycogen Phosphorylase (GPho) and the Debranching enzyme (DE) activities were studied in the white extensor digitorum longus (ELD) and in the red soleus (S) muscles of rats during the developmental period from birth to the young adulthood. During the first days of postnatal life all enzyme activities similarly increase in both ELD and in S. BE and DE seem to rise faster and reach the adult levels earlier than GS and GPho. Significant differences can be seen between ELD and S by age 14--21 days: glycogenolytic enzymes rise higher in the ELD, GS activity is similar in both muscles whereas BE activity is higher in S. All these develop changes are completed in 25 days. Thereafter, only GPho activity in the ELD continues to slowly increase.


Diverticular disease of the large intestine in Northern Norway. In 280 unselected necropsies on patients over 20 years of age in Northern Norway, diverticular disease was present in 25% of the males and 43% of the females. The frequency of diverticular disease increased in both sexes by age. Both the frequency of diverticular disease and the average number of diverticula per case with diverticular disease were higher in females than in males in all age groups. The sigmoid was the most frequent site of diverticula in both sexes and for all ages, and the average number of diverticula per diverticulum-bearing segment was also highest in the sigmoid for all ages and in both sexes. The average number of diverticula in the sigmoid of affected individuals increased with age and with the number of segments involved. Diverticular disease was not associated with adenomas of the large intestine or with malignant or benign neoplasms elsewhere in the body or with any of the common diseases thought to be related to a Western type of diet, except with cerebrovascular disease.


Distribution of the gut hormones in the primate intestinal tract. Reliable and specific radioimmunoassays have been developed for the gut hormones secretin, gastrin, cholecystokinin, pancreatic glucagon, VIP, GIP, motilin, and enteroglucagon. Using these assays, the relative pattern of distribution of the gut hormones has been determined using the same bowel extracts for all measurements. VIP occurred in high concentration in all regions of the bowel, whereas secretin, GIP, motilin, and CCK were predominantly localised in the proximal small intestine. Pancreatic glucagon was almost exclusively confined to the pancreas. Like VIP, enteroglucagon also exhibited a wide pattern of distribution but was maximal in the ileum. The acid ethanol extraction method that was used was found to be unsuitable for gastrin. On gel chromatography of the extracts, motilin and VIP eluted as single molecular species in identical position to the pure porcine peptides. CCK, pancreatic glucagon, enteroglucagon and GIP were all multiform.


Monooxygenase enzyme activity in alcoholics with varying degrees of liver damage. Monooxygenase enzymes are involved in the biotransformation of drugs and of environmental carcinogens. The activity of 7-ethoxycoumarin 0-deethylase and associated NADPH-cytochrome c reductase was determined in 9000 g supernatant from bioptically obtained liver specimens from patients with various liver diseases in order to study in vitro drug metabolising capacity. Monooxygenase and reductase activity was significantly higher in the livers of 21 patients with alcoholic liver disease (fatty liver, alcoholic hepatitis, cirrhosis of the liver) than in 22 normal controls or in six patients with chronic active hepatitis. The raised activity of drug-metabolising enzymes obtained from alcoholics with liver damage differs from normal values found in five alcoholics without liver disease. Both groups were comparable in respect to the amount of alcohol consumed and duration of abuse. A strikingly low monooxygenase activity was observed in eight patients with cirrhosis of the liver and ascites, with, however, no apparent effect on reductase activity. The results show that alcoholic liver disease is associated with enhanced monooxygenase and reductase activity, but alcoholism, per se, is not. This rise of drug-metabolising enzyme activity could lead to selectively increased rates of biotransformation in patients with alcoholic liver damage.


Cost-benefit evaluations in primary health care. Social work programs in primary health care (PHC) agencies have been well patronized and effective, but the expansion of social worker involvement in PHC depends on cost-benefit evaluations that satisfy the financial requirements of those who run PHC--the physicians. This article outlines a model for determining the cost-benefit performance of PHC social work programs.


Histochemical localization of enzymes in the stigma and style of Gossypium hirsutum L. during pre- and post-pollination stages. The distributional pattern of some enzymes (esterase, beta-D-galactosidase, succinate dehydrogenase and malate dehydrogenase) is described in the dry stigma and closed style of Gossypium Hirsutum L. during pre- and post-pollination stages. All the four enzymes indicated granular reaction and increased activity in the transmitting tissue and its surrounding cells during post pollinated stage. The possible physiological role of these enzymes in pollen tube growth in vivo in stigma and style is discussed.


The species of sakis, genus Pithecia (Cebidae, Primates), with notes on sexual dichromatism. Recognized species of sakis, South American monkeys of genus Pithecia (Cebidae), are P. hirsuta Spix, P. monachus E. Geoffroy, P. albicans Gray, P. pithecia Linnaeus. Evolutionary stages in sexual dichromatism in sakis and other primates are noted.


Population and territory stability of the Lemur catta at Berenty, Madagascar. Several Lemur catta troops at Berenty, Madagascar have been censused repeatedly since 1963. In 1972, the entire reserve was censused. A recensus in 1975 showed that although some minor changes have occurred in the number of animals in individual troops, the population of the reserve as a whole, the core areas of the lemurs' territories, and their home range boundaries have all remained stable ever since the first complete census 3 years earlier.


Female dominance in Indri indri.

Female dominance in Indri indri. A total of 15 months were spent on field research in eastern Madagascar studying the largest extant lemur Indri indri. Social relationships were analysed according to the frequency and direction of affiliative and agonistic behaviours, and with respect to the relative tree positions and behavioural synchrony of group members. The relationship between the adult male and adult female in each group was distinguished by the subordinance of the former. Between group variation in adults' relationships are examined with respect to the function of this behaviour.


Quantitative changes in the fundamental structural pattern of the diencephalon among primates and insectivores. The volumes of the main components of the diencephalon from 10 basal insectivores, 12 prosimians, and 15 simians including man were compared. The comparison of the percentage composition within the diencephalon shows that the thalamus and the subthalamus increase whereas the epithalamus and the hypothalamus decrease in relative size among primates. The allometric analysis reveals that, in spite of a relative reduction, the epithalamus and the hypothalamus are also progressive structures. However, their allometric size increase, being especially accentuated in earlier phyletic phases, is small in comparison to that of the thalamus and the subthalamus. These latter two components are characterized by a continuous phylogenetic growth from the basal insectivores to the simians. The correlation analysis shows that the strongest correlations and, in many cases, that isometric size increase exist between structures which belong to the same functional system. These findings indicate the existence of at least two major developmental gradients in the quantitative development of the diencephalon, a neencephalic and a limbic one.


Characterization of an in vitro method for demonstrating thyrotropin-releasing hormone-stimulated prolactin secretion. Anterior pituitaries of normal adult male rats were subjected to synthetic thyrotropin-releasing hormone (TRH) treatment in an acute incubation system which employed pretreatment of the glands with plasma obtained from the donor animals. Following a 60-min preincubation period in a 1:1 mixture of Krebs-Ringer bicarbonate buffer (KRB) and plasma, media and hemipituitary prolactin (PRL) concentrations were significantly (p less than 0.01) increased after a 40-min treatment with 500 pg TRH. The TRH effect was absent among hemipituitaries preincubated in KRB alone. Plasma obtained from older donors was more potent than was plasma from younger rats in this effect. TSH secretion was markedly increased by 500 pg TRH, whether or not plasma preincubation was employed. A dose response of PRL release to concentrations of TRH from 100 pg to 6.0 ng was observed. Crude extracts of median eminence also effected enhanced PRL release using the plasma preincubation technique. The results suggest that plasma preincubation of explanted pituitaries increases PRL cell sensitivity to TRH, perhaps by enzymatic inactivation of endogenous TRH bound to cellular membrane receptors.


In vitro release of prolactin by thyrotropin-releasing hormone: influence of dopamine, thyroxine, and cycloheximide. An acute incubation procedure, using explanted normal rat hemipituitaries pretreated with fresh plasma obtained from pituitary donor animals, was employed to further investigate the in vitro stimulation of prolactin (PRL release by thyrotropin-releasing hormone (TRH). Pretreatment with dopamine (0.1 microgram/ml) caused a 30-50% decrease in the amount of PRL released into incubation media; the inhibitory effect of dopamine was not reversed by treatment with 0.5-6.0 ng. TRH, although these TRH concentrations consistently stimulated PRL release from pituitaries not exposed to dopamine. Treatment with thyroxine (10(-6) to 10(-5) M) showed a competitive inhibition of thyrotropin release by TRH (0.5 ng), but was without effect on TRH-stimulated PRL release. Cycloheximide (100 microgram/ml) blocked a net increase in PRL levels. TRH, nevertheless, significantly increased PRL release in the presence of cycloheximide. The results indicate that neither dopamine nor thyroxine compete with TRH in causing PRL release, and that the TRH stimulation of PRL release is unrelated to ongoing levels of hormone synthesis.


Structure and function of L-lactate dehydrogenases from thermophilic and mesophilic bacteria. I) Isolation and characterization of lactate dehydrogenases from thermophilic and mesophilic bacilli. Lactate dehydrogenases from thermophilic bacilli (Bacillus stearothermophilus, Bacillus caldotenax) and from mesophilic bacilli (Bacillus X1, Bacillus subtilis) have been isolated by a two-step purification procedure. Only one type (LDH-P4) composed of four identical subunits (Mr 34 000 or 36 000) was found in each bacillus. The tetrameric enzymes were characterized with respect to thermostability, pH and temperature dependence of the pyruvate reduction and the L-lactate oxidation, substrate specificity, saturation kinetics (Km values of pyruvate, lactate, NAD, NADH), pyruvate and oxamate inhibition, and activation by fructose bisphosphate. The thermophilic and mesophilic enzymes differ characteristically in these parameters. Preliminary structural data (amino acid composition, comparative N-terminal sequence analysis) show the expected close phylogenetic relationship (high degree of sequence homology), but also typical differences between thermophilic and mesophilic dehydrogenases, a suitable basis for further comparative studies.


Intraperoxisomal and intramitochondrial localization, and assay of pyruvate (glyoxylate) aminotransferase from rat liver. Pyruvate (glyoxylate) aminotransferase is found in the peroxisomal and mitochondrial matrices, and in soluble fractions of rat liver homogenates. Soluble activity is from broken peroxisomes. Differential solubility of the mitochondrial and peroxisomal enzymes in digitonin can be used to assay the two activities separately.


[The complexing ability of gangliosides for Ca2, I. Influence of mono- and divalent cations and of acetylcholin (author's transl)]. The binding of Ca2 to single ganglioside species (GGtet1NeuAc, GGtet2aNeuAc, GGtet 3aNeuAc), to their free, reducing sialyl-oligosaccharides and to ganglioside mixtures from chicken brain was investigated by means of ion-sensitive electrodes (potentiometry). Unlike the sialyl-oligosaccharides and free N-acetylneuraminic acid, gangliosides were found to possess two different modes of binding for Ca2, depending on the total concentration of Ca2. This was mainly indicated by a release of up to 75% of previously bound Ca2 after raising the total Ca2-concentration above a critical level of about 5--9 X 10(-5)M. Addition of acetylcholin (9mM), Li, K, and Na, respectively, caused a release of Ca2 from ganglioside-Ca2-complexes (0.1mM Ca2, 0.1mM ganglioside-NeuAc) in the sequence: acetylcholin : Li : K : Na = 4 : 3 : 1 : 1 composed on molar basis (9mM).


Can quality of life be evaluated?

Can quality of life be evaluated? A multidisciplinary committee of the Veterans Administration sought to evaluate quality of life as related to long-term care by developing possible measurements of the concept.


[Parenteral feeding with varying amounts of nitrogen and calories in patients with esophageal carcinoma]. Eighteen male patients with operable esophagus carcinoma received parenteral nutrition during 4 preoperative and 14 postoperative days in three different infusion regimens. It was possible to demonstrate that a preoperative positive N-balance can be achieved in all patients of each group in comparison to 2 of the 3 groups postoperatively. Side effects were not observed in the course of this study.


[Lipid, nitrogen and aminoacid parameters in the operated patient relative to parenteral alimentation]. Three groups of patients who underwent Billroth II operation received infusions that differed in calory and amino-acid contents. In all groups the controlled parameters of serum and urine changes were similar and rarely abnormal. The elimination of amino-acids in urine is dependent on the kind of parenteral supply. The relation of the amino-acids in the different groups is, however, agreeable.


[Parameters of catabolism during long-term postoperative parenteral feeding]. In 26 adult patients of an intensive-care ward, the following parameters were controlled for 26 to 35 days under postoperative parenteral feeding: prealbumin, transferrin, and retinol-binding protein, the immunoglobulins IgA, IgM and IgG, total serum protein, Hb content, body-weight and urinary nitrogen elimination. In the early phase and also in the 2nd to 4th postoperative week, prealbumin and transferrin are apparently good indicators for the existence of a catabolic or anabolic metabolic condition.


[Adverse effects of administration of carbohydrates during long-term parenteral feeding]. Metabolic parameters of 26 adult patients were investigated for 26 to 35 postoperative days while being fed parenterally. Tolerable metabolic disturbances did not only occur in the phase immediately after surgery, but also in the late postoperative phase together with complications.


Nutritional assessment and treatment of hospital malnutrition. A thorough awareness of the nutritional and metabolic status of the hospitalized patient is crucial for all persons directly involved in patient care. The catabolic nature of the body's response to illness or injury induces a serious drain on vital organs and tissues. Therefore, a complete assessment of the body's various compartments must be carefully taken, and any nutritional depletion must be quickly alleviated. Due to the alarming incidence of often undetected severe malnutrition in hospitalized patients, if becomes imperative that attention be paid to nutritional status, to decrease unnecessary morbidity and mortality.


[Alternatives to peripheral-venous parenteral feeding]. The protein-sparing effect of different programs of peripheral-venous parenteral feeding was studied in 31 patients following abdominal surgery. 10 patients (group II) received 1 g amino acids/kgBW/day, 11 patients (group III) 1 g amino acids and 2 g carbohydrates/kgBW/day and 10 patients (group I, control) were infused only with water and electrolytes. Patients with simultaneous addition of amino acids and carbohydrates had significantly better nitrogen balances than patients given amino acids alone. The normalisation of amino acids metabolised and delivered predominantly by muscle, just as the significant improvement in serum levels of transport and acute-phase proteins demonstrated that the utilisation of added amino acids took place not only in peripheral but also in visceral tissues. Comparable positive effects could not be seen with sole amino acid infusion. Our study indicates that this program, being effective in the state of keto-adapted starvation, is of no use in the early postoperative period, because of lacking corresponding metabolic conditions.


Growth of Pseudomonas aeruginosa in normal and burned skin extract: role of extracellular proteases. Growth curves and mean generation times (MGT) were determined for Pseudomonas aeruginosa strain M-2 (protease +) and strain PA-103 (protease +/-) in burned skin extract (BSE) and in normal skin extract (NSE). Strain M-2 grew on NSE or BSE with an MGT of 30 min. Strain PA-103 grew in NSE at a similar MGT; however, PA-103 in BSE had a MGT of 65 min. When protease was added to BSE, PA-103 grew as rapidly as M-2. When ammonium sulfate was added to inhibit protease production, the MGT of M-2 slowed to that of M2 in both BSE in NSE. The MGT of PA-103 in amino acid-supplemented BSE was similar to that of PA-103 in BSE. The MGT of PA-103 in amino acid-supplemented BSE was similar to that of M-2 in both BSE andNSE. These data suggest that protease may serve as a virulence factor by modifying the available nutrients in burned skin. As a result, nutrients are formed that permit an enhanced growth rate and amore rapid establishment of the infection in the host.


Secretion of phospholipase C by Pseudomonas aeruginosa. The conditions necessary for the secretion of phospholipase C (phosphatidylcholine cholinephosphohydrolase) by Pseudomonas aeruginosa were studied. Enzyme secretion by washed cell suspensions required a carbon source and ammonium, potassium, and calcium ions. The calcium requirement could be substituted by magnesium and strontium but not by copper, manganese, cobalt, or zinc. During growth in liquid medium, cells secreted phospholipase C during late logarithmic and early stationary phases. Secretion was repressed by the addition of inorganic phosphate but not by organic phosphates, glucose, or sodium succinate. Studies with tetracycline indicated that de novo protein synthesis was necessary for the secretion of phospholipase C and that the exoenzyme was not released from a preformed periplasmic pool. Similarly, extraction of actively secreting cells with 0.2 M MgCl2 at pH 8.4 solubilized large quantities of the periplasmic enzyme alkaline phosphatase but insignificant amounts of phospholipase C. Bacteria continued to secrete enzyme for nearly 45 min after the addition of inorganic phosphate or rifampin.


Exposure of guinea pigs to Rickettsia rickettsii by aerosol, nasal, conjunctival, gastric, and subcutaneous routes and protection afforded by an experimental vaccine. Guinea pigs were inoculated with Rocky Mountain spotted fever by the aerosol, conjunctival, subcutaneous, intragastric, and intranasal routes. Rickettsial infection was produced by all routes except intragastric. All animals with clinical signs of disease developed agglutinating antibody, and most developed a cell-mediated immune response. Disease produced by all experimental routes (except intragastric) was indistinguishable. The tissue culture-derived inactivated vaccine produced in this laboratory protected guinea pigs against an aerosol challenge.


Complement components (C1, C2, C3, C4) in bronchial secretions after intranasal infection of guinea pigs with Mycoplasma pneumoniae: dissociation of unspecific and specific defense mechanisms. Shortly after intranasal infection of guinea pigs with Mycoplasma pneumoniae, the titers of the complement components increased significantly in bronchial secretions by the folllowing amounts, compared with the titer of a control group: C1, about 2-fold; C2, 1.6-fold; C3, 17-fold; and C4, 942-fold. Histopathological signs of inflammation were not apparent at this time. At 2 weeks after infection, when the titers of complement components in the bronchial secretions were at the level of control values or lower, the serum antibody titer increased, and it reached the highest level at 6 weeks after infection. Therefore, one can distinguish two phases of reaction of the macroorganism to intranasal inoculation. The increase in complement components shortly after infection may represent an earlyunspecific defense mechanism of the host before the specific immune response becomes effective, since the complement system can be activated by M. pneumoniae via the classical as well as the alternative pathway in the absence of antibodies.


Antigenic polypeptide complex from the Melvin strain of Neisseria gonorrhoeae: isolation and properties. An antigenic complex has been isolated in a highly purified from from the Melvin strain of Neisseria gonorrhoeae. The complex has a molecular weight of 9.3 x 10(6) and on sodium dodecyl sulfate-polyacrylamide gel electrophoresis was found to consist of several subunits; the most predominant had the following molecular weights: 110,000, 94,000, 68,000, a smear containing (52,000, 48,000, and 44,000), 42,000, 36,000, 29,000, 28,000, 26,000, and 12,000 comprising 89% of the total protein. With the exception of the subunit of molecular weight 110,000, no change in the content or the mobility of other subunits was observed when beta-mercaptoethanol was omitted from the denaturation solution of sodium dodecyl sulfate electrophoresis. Amino acid analysis of the complex showed a predominance of hydrophobic amino acids. These data implicated noncovalent interactions between the subunits. When the cells were labeled with fluorescamine it was possible to obtain a fluorescent complex with identical properties. Among several buffers used for the isolation of the complex, 0.2 M tris(hydroxymethyl)aminomethane buffer (pH 7.5) gave maximum yield with low amounts of lipopolysaccharide and phospholipid; the choice of the buffer for column chromatography did not seem to make any difference. The high protein content and low amounts of lipopolysaccharide and phospholipid are characteristic properties of the complex.


Action of bacterial endotoxin and lipid A on mitochondrial enzyme activities of cells in culture and subcellular fractions. Escherichia coli O127:B8 lipopolysaccharide (LPS), prepared by the Westphal procedure, caused a marked decrease in the activities of mitochondrial malate dehydrogenase, succinate dehydrogenase, and adenylate kinase in African green monkey kidney (Vero) cells and primary cultures of mouse liver cells within 2 h after exposure to 10 micrograms of LPS/ml of culture medium. These three enzyme activities leaked into the supernatant fraction, and cytochrome oxidase activity was lost from the mouse liver mitochondrial particulate fraction within 45 min after exposure to 10 micrograms of LPS/mg of protein. Loss malate dehydrogenase activity from isolated mitochondria was also accelerated by LPS from E. coli O26:B6 (Boivin preparation) or Salmonella typhosa O901 (Westphal preparation), and by lipid A from Salmonella minnesota or Shigella sonnei. In addition, LPS and lipid A inhibited state 3 respiration by isolated mitochondria with attendant loss of respiratory control, but adenosine 5'-diphosphate/O ratios were relatively unchanged. Impaired mitochondrial function is an early event after exposure to biologically relevant amounts of LPS or lipid A.


In vitro interaction between normal cynolmolgus monkey alveolar macrophages and Legionnaires disease bacteria. The interaction between normal cynomolgus monkey alveolar macrophages and Legionnaires disease bacteria was studied by transmission electron microscopy. After ingestion of Legionnaires disease bacteria, the organisms replicated within macrophages and destroyed the phagocytic cell.


Studies on Alternaria allergens. I. Isolation of allergens from Alternaria tenuis and Alternaria solani. Extracts of Alternaria tenuis and Alternaria solani were separated into dialyzable (molecular weight less than 10,000) and non-dialyzable forms. The latter was further fractionated by gel filtration through Sephadex G-100 followed by ion-exchange chromatography on DEAE-cellulose. The dialyzable material was fractionated by gel filtration through Sephadex G-50. The allergenic activities of the fractions obtained from the A. tenuis extract was measured in vitro by the radioallergosorbent test assay and the allergenic potency was measured by radioallergosorbent test inhibition assay. Allergenic activity was detected in most of the non-dialyzable fractions, the majority of the activity being in the last G-100 fraction (MW approximately 20,000) which was predominantly protein in nature. The same component may be responsible for the activity found in the dialyzate and its first G-50 fraction since the immunodiffusion studies indicated that the last G-100 fraction has antigenic components in common with those of the first G-50 fraction. In addition, cross-reactions between A. tenuis and A. solani extracts show that the two species share common antigenic determinants.


Interaction of disodium cromoglycate with calcium ions in 2-propanol. Spectral evidence is presented which indicates that calcium ions can complex with the cromoglycate anion in an organic medium containing a small amount of water. The implications of this finding for the antiasthmatic activity of disodium cromoglycate are discussed.


Transformation of feline embryo cells in culture by a chemical carcinogen. A feline embryo cell line was treated in vitro with various levels of 7,12-dimethylbenz[a]anthracene (DMBA) or dimethyl sulfoxide (control). Repeat treatment of DMBA only induced in vitro transformation of feline embryo cells following clonal growth and selection. The morphologically altered cells formed large cell aggregates and grew in this aggregate form when suspended in liquid growth medium above an agar base, formed colonies in soft agar, and grew to high saturation densities. However, no progressively growing tumors were produced when cells were inoculated into nude athymic mice. The transformed lines were negative for feline oncornavirus-associated cell membrane antigen (FOCMA).


The diffusion of medical techniques to less developed countries. This paper describes a study of the extent to which a set of eight modern medical techniques had been introduced in less developed countries in 1977. The results are presented for each country and related to the characteristics of the country. Many very poor countries were found to have introduced many very recent techniques. The reasons for this are discussed, and appropriate questions to be asked about any new technique are suggested.


Attenuation in central neurons: its relationship to increased intracytoplasmic free calcium, calcium binding and memory storage. A mechanism responsible for attenuation of dendritic spikes of nucleus reticularis gigantocellularis (NRG) origin was addressed. Stimulation of afferent neurons with pulses of 100 per sec frequency generated attenuation in specific neurons. Intrasomatic infusion of EGTA reversed the attenuation. The results suggest that attenuation results from intracytoplasmic accumulation of free Ca2+ due to differences in rate of Ca influx and Ca binding. This accumulation generates a concentration dependent prevention of Ca2+ (and Na+) influx that causes the attenuation. The free intracytoplasmic Ca2+ is removed mainly by binding on proteins and/or polypeptides, a mechanism that promotes memory storage.


Acute zinc depletion syndrome during parenteral hyperalimentation. Zinc is an essential trace element whose malabsorption in early childhood may result in a skin disorder known as acrodermatitis enteropathica. Cutaneous lesions typical of acrodermatitis enteropathica have been described during total parenteral nutrition on zinc-deficient intravenous solutions in both adults and children. This condition has been named the "acute zinc depletion syndrome." A case is described in which a patient, despite a zinc intake of double the daily requirement, manifested the acute zinc depletion syndrome during therapy with combined liquid diet plus parenteral hyperalimentation. Predisposing factors in this individual included a short bowel syndrome and a large oral load of calcium lactate. Zinc metabolism is reviewed with attention to alterations in disease and during hyperalimentation. The clinical manifestations, predisposing factors, therapy and prevention of the acute zinc depletion syndrome are discussed.