Activity of pre-entral neurones in conscious monkeys: effects of deafferentation and cerebellar ablation. After limb deafferentation, there was no gross alteration in the initiation and performance of a sound-triggered ballistic movement. The pattern of neuronal discharge in the arm area of the motor cortex was not significantly modified. In the absence of cerebellum, the reaction time of motor cortex cells was about 150 msec longer than the reaction time observed in normal and deafferented animals. This was associated with an equal retardation in the onset of ENG changes in the limb muscles. This observation is compatible with the idea that the motor cortex is normally situated downstream to the cerebellum in the initiation of some movements. However, the motor cortex is necessary for the initiation and execution of simple sound-triggered movements since its removal results in a permanent inability to perform the task. Finally, in the absence of peripheral feedback, the pattern of motor output to the agonistic and antagonistic muscles was initiated normally and thus appeared to be preprogrammed centrally. The importance of the motor cortex as a "reflex center" in the control of slower movements is obviously not challenged by these observations since the motor task that we have used depends very little or not at all on sensory feedback (Stark, 1968). What these results indicate, however, is that the execution of some voluntary fast ballistic movements can be entirely preprogrammed independently of peripheral and cerebellar influences, and that the program, which is mainly concerned with generating velocity signals, appears to require the integrity of the motor cortex for its execution.


Relation of slowly conducting pyramidal tract neurons to specific aspects of forearm movement. PT neurons were recorded from monkeys performing a trained motor task that included tonic maintenance of a limb position, slow and controlled and then quick wrist movements. The results suggest that many of slowly conducting PTNs have preferential relations with specific aspects of slow or tonic motor acts.


Visual tracking and neuron activity in the post-arcuate area in monkeys. 1. A visual tracking task from a predetermined zone to another predetermined zone with use of a hand was trained in 3 macaque monkeys. They rotated the handle at the wrist joint by flexing or extending. A total of 88 neurons in the posterior bank of the arcuate sulcus, contralateral to the hand used, was related to the task. These neurons were designated as (post-arcuate-) FB neurons, following von Bonin and Bailey's terminology. 2. The FB neurons were classified into 4 types according to their discharge patterns during the task; (1) non-reciprocally, visually coupled neurons (6 neurons); (2) non-reciprocally movement-coupled neurons (41 neurons); (3) reciprocally movement-coupled neurons (17 flexion type and 8 extension type); and (4) finally, non reciprocally movement-coupled depression type neurons (15 neurons). These activations started before the movement onset, as detected in the displacement trace, and were not correlated to the EOG. 3. A possible functional significance of these neurons was discussed. A suggestion was made that in the FB area, after receiving the visual cue information, a function for the later movement direction and tis initiation are produced and sent to the motor apparatus within the brain so that effective tracking task can be performed.


Supplementary motor area of the monkey: activity of neurones during performance of a learned motor task. 1. Recordings were made of the natural dischages of neurones in the supplementary motor area (SMA) of conscious monkeys trained to perform a stereotyped motor task with either hand. 2. Eighty % of the total population of cells showed modulation of their activity during particular movements of either limb. Two thirds of this group had a similar pattern of modulation regardless of whether the contralateral or ipsilateral hand was used. 3. The number of cells whose activity was related to movements of distal joints was approximately equal to that whose discharges occurred with proximal movements. 4. Only 5% of cells tested sent their axons into the pyramidal tract, and only 15% of units investigated showed responses to passive manipulation of the limbs. The effective afferent input usually was of a rather complex kind. 5. The findings suggest that the discharges of a large number of neurones in SMA are changing during particular movements of either arm, and that only a small number of cells receive afferent sensory input. These results contrast with those obtained in the primary motor area and suggest a different role for SMA the control of movement.


Does the supplementary motor area play a part in modifying motor cortex reflexes? Neuronal activity in the supplementary motor area was recorded from a monkey performing a trained motor task that required readiness for proper usage of sensory inputs. Thirty-two neurons exhibited activity changes, which supports the hypothesis that the SMA is part of the system involved in modulating responsiveness of the motor cortex to sensory inputs in association with learned movements.


Precentral neuron activity associated with ipsilateral forelimb movements in monkeys. Unit activity was recorded in motor cortex on one side, while monkeys were moving left or right fingers, wrists, or arms. On hundred and eighty five movement-related neurons were obtained from two monkeys. Of these, 122 were related to contralateral movements, 50 were to movements of both sides, and the remaining 13 to ipsilateral movements. It was found that ipsilateral-movement-related neurons tended to appear in groups of neurons that were related more to arm movements than to finger and/or wrist movements.


Wenyonella baghdadensis sp. n. from the bandicoot rat Nesokia indica in the Baghdad area. Oocysts of Wenyonella baghdadensis sp. n. were found in the feces of 2 of 12 bandicoot rats Nesokia indica Gray & Harwicke from the Baghdad area. Sporulated oocysts were subspherical to broadly ellipsoidal, 25.4 (18-22) x 20.8 (15-28) micrometer, with a 2-layered wall, the outer wall being mammillated, without micropyle, micropylar cap, residuum, or polar granule. Sporozoites were ovoid, 11.8 (9-15) x 8.4 (6-10) micrometer, with Stieda body and residuum. Two sporozoites in each sporocyst were elongate, with granular cytoplasm and  a refractile globule, the other 2 were bean-shaped, without granules or refractile globule. Sporulation time equalled 3 days at 22-24 C. Entamoeba coli and Giardia sp. cysts were also found in 3 rats each.


Ultrastructural observations on renal schizogony of Leucocytozoon dubreuili in the American robin. The schizogonic development of Leucocytozoon dubreuili in the kidney proximal tubule cells of the American robin, Turdus migratorius,  was studied by electron microscopy. Renal schizogony is initiated by the entry of certain hepatic merozoites into cells of the proximal tubules. Development  of the schizont consists of coordinated sequence of events including extensive mitotic nuclear division, multiplication of mitochondria, increase in endoplasmic reticulum and ribosomes, differentiation of membranes, microtubules, micronemes and rhoptries, and cytoplasmic segmentation (cytomere formation). Merozoites form by budding around numerous centers in the schizont and, when mature, are bounded by a single plasma membrane subtended by microtubules. Each merozoite contains a large nucleus, a mitochondrion, and well developed apical complex consisting of 3 polar rings, paired rhoptries, and numerous micronemes. An atypical nuclear division observed in some maturing schizonts was characterized by the multiple fission of a nucleus within a persistent outer nuclear membrane and the absence of mitotic spindle apparatus. Alterations in infected renal cells consisted of disorganization and loss of cytoplasmic organelles and the accumulation of lipofuscin-like inclusions.


Ultrastruct of red-sore lesions on largemouth bass (Micropterus salmoides): associattion of the ciliate Epistylis sp. and the bacterium Aeromonas hydrophila. Epizootic outbreaks of red-sore disease in several reservoirs in the southeastern United States have been reported to cause heavy mortality among several species of fish having sport and commercial value. The etiologic agent is said to be the peritrich ciliate Epistylis sp.; secondary infection by the gram-negative bacterium Aeromonas hydrophila produces hemorrhagic septicemia which results in death. However, in recent studies on the largemouth bass Micropterus salmoides, Epistylis sp. could be isolated from only 35% of 114 lesions from 114 fish, while A. hydrophila was found in  96% of the same lesions. Transmission and scanning electron microscopy of lesions associated with red-sore disease indicate that neither the stalk nor the attachment structure of Epistylis sp. have organelles capable of producing lytic enzymes. Since other investigators have shown that A. hydrophila produces strong lytic toxins, and in absence of evidence to the contrary, it is concluded that Epistylis sp. is a benign ectocommensal and that A. hydrophila is the primary etiologic agent of red-sore disease.


Particle-based axenic media for tetrahymenids. Autoclavable, natural particulate media simplify axenic cultivation of tetrahymenid ciliates and presumably favor selection for phagotrophy. Viability is at least 2 months at room temperature (24-26 C) for the lipid-sensitive tetrahymenids Tetrahymena setosa, T. corlissi, T. paravorax, T. limacis, and T. patula, also for T. rostrata and (at 12 C), for strains of the T. pyriformis complex and Glaucoma chattoni. A typical medium consists of crude soy "lecithin" + skim milk powder + Saccharomyces cerevisiae cells. Other useful particules readily available commercially are: whole liver powder, cells of Micrococcus lysodeikticus and Escherichia coli, and powdered residue of liver which had been extracted with 70% ethanol ("liver No. 2). Preliminary experiments indicate that some of these media are suitable for the maintenance of Paramecium octaurelia stock 299S and Colpidium campylum. Such mixtures may serve as points of departure for devising media for more fastidious phagotrophs.


The effect of glucose on the biochemical and ultrastructural characteristics of developing Euglena chloroplasts. Chloroplast development is inhibited in Euglena gracilis strain Z, when greened in a medium containing glucose. This inhibition is reflected not only in the pattern of chlorophyll accumulation but also in the chloroplast ultrastructure and activities of the 2 light reactions of photosynthesis. Chloroplasts of cells greening in the presence of glucose are delayed in developing certain structures. Photosystem I activity develops at about the same rate as that of the controls during the first 48 h of greening, after which it develops at a slower rate. The rate of development of photosystem II activity in cells greening in a glucose medium lags considerably behing that of the controls until the later hours of greening. There are similarities between glucose inhibition and chloramphenicol inhibition of chloroplast development. Glucose may inhibit a step in chloroplast development ultimately controlled by the chloroplast genome.


A stimulatory effect of the fluid from preimplantation rabbit blastocysts upon luteinization of monkey granulosa cell cultures. Blastocyst fluid was aspirated from Day 6 1/2--7 rabbit blastocysts and was added to cultures of granulosa cells obtained from preovulatory follicles of untreated rhesus monkeys or from follicles of monkeys or from follicles of monkeys treated with PMSG. The stimulation of progesterone secretion was measured and equated with that produced by hCG. The hCG-like activity was also measured in a radioreceptor assay using 125I-labelled hCG and porcine granulosa cells. In 8 out of 10 experiments with cultured cells from untreated monkeys, addition of 20% blastocyst fluid from Days 6--9 of culture stimulated progesterone secretion by 2- to 6-fold. Similar findings were obtained in 5 experiments with cultures from PMSG-treated monkeys except that the blastocyst fluid was added from Days 0 to 6 of culture. The granulosa cells in such cultures underwent morphological luteinization. Compared to a standard of purified hCG the blastocyst fluid contained about 0.76--2.5 ng hCG-like activity/ml which was non-dialysable. The radioreceptor assay indicated the presence of 0.5--2.5 ng hCG-like material/ml.


The oestrous cycle of the brown lemur, Lemur fulvus. Examination of vaginal smears and observations of the colour and tumescence of the genitalia and discharge of mucus of 9 brown lemurs indicated that the oestrous cycle lasted for 30 days and that cycles occurred between September and July. The timing of cycles of females housed in visual isolation differed from that of females able to see other lemurs, indicating that the oestrous cycle in this species can be influenced by different housing conditions.


Administration of extra-amniotic arachidonic acid and the suppression of uterine prostaglandin synthesis during pregnancy in the rhesus monkey. After extra-amniotic treatment of pregnant rhesus monkeys premature parturition was induced in 4 given 2.5 mg PGE-2; none of the 4 monkeys given 100 mg arachidonic acid were affected. The concentrations of PGE, PGF, or 13,14-dihydro-15-oxo-PGF did not change after arachidonic acid treatment, but all increased after PGE-2. It is suggested that the availability of substrate, arachidonic acid, is not a major factor governing the control of PG synthesis but that the latter is suppressed during pregnancy.


A structure-carcinogenicity study of 4-nitroquinoline 1-oxides using the SIMCA method of pattern recognition. Structure-carcinogenicity data for a series of 4-nitro- and 4-hydroxyaminoquinoline 1-oxides were analyzed using the SIMCA method of pattern recognition. Using physicochemically based substituent constants to describe each compound, a principal components model was derived for the carcinogens. This model was 82% successful in predicting the carcinogenic potential of the compounds. For the 6-substituted compounds, a significant relationship between those structural parameters associated with carcinogenic potential and ability to stimulate unscheduled DNA synthesis was observed. In addition, other problems unique to the classification of carcinogens were discussed.


Folate antagonists. 13. 2,4-Diamino-6-](alpha,alpha,alpha-trifluoro-m-tolyl)thio]quinazoline and related 2,4-diamino-6-[(phenyl- and naphthyl)thio]quinazolines, a unique class of antimetabolites with extraordinary antimalarial and antibacterial effects. An array of nonclassical thioquinazoline analogues (VIII) of methotrexate was prepared by cyclization of the requisite 2-amino-5-(arylthio)benzonitrile with chloroformamidine hydrochloride (28--79%). The aminonitrile precursors were obtained by SnCl2-HCl reduction (28--99%) of the corresponding 2-nitro-5-(arylthio)benzonitriles, which were synthesized by the condensation of the appropriate 5-chloro-2-nitrobenzonitriles with various arylthiols (36--83%). Many of the thioquinazolines (VIII) showed suppressive antimalarial activity comparable with or superior to chloroquine, cycloguanil, and pyrimethamine against drug-sensitive lines of Plasmodium berghei in mice and Plasmodium gallinaceum in chicks, and several displayed potent prophylactic activity with P. gallinaceum. Moreover, the thioquinazolines retained potent antimalarial effects against chloroquine-, cycloguanil-, pyrimethamine- and DDS-resistant lines of P. berghei in mice and against chloroquine- and pyrimethamine-resistant strains of Plasmodium falciparum in owl monkeys. The most active compound, namely, 2,4-diamino-6-[alpha,alpha,alpha-trifluoro-m-tolyl)thio]quinazoline, was designated for preclinical toxicological studies. Numerous substances exhibited in vitro activity against a broad spectrum of pathogenic bacteria at concentrations of less than 0.25 microgram/mL. The thioquinazolines also prove to be potent folate antagonists, causing 50% inhibition of Streptococcus faecalis R (ATCC 8043) at drug concentrations ranging from 0.2 to 2.0 ng/mL. Structure--activity relationships are discussed.


Synthesis and carcinogenic activity of 5-fluoro-7-(oxygenated methyl)-12-methylvenz[a]anthracenes. Treatment of 7,12-benz[a]anthraquinone (2) with methylmagnesium iodide or methyllithium yields mixtures of cis- and trans-7,12-dihydro-7,12-dihydroxy-7,12-dimethylbenz[a]anthracenes (3a,b), in which the ratio of cis to trans lies in the 3--4:1 region. Each isomer afforded high yields of 7-chloromethyl-12-methylbenz[a]anthracene (5) on treatment with hydrogen chloride in ethyl acetate. Similarly, 5-fluoro-7,12-benz[a]anthraquinone (8) afforded a mixture of cis- and trans-5-fluoro-7,12-dihydro-7,12-dihydroxy-7,12-dimethylbenz[a]anthracenes (9) which yielded 7-chloromethyl-5-fluoro-12-methylbenz[a]anthracene (10) on treatment with HCl. The chloromethyl compounds, 5 and 10, yielded 7-acetoxymethyl-12-methylbenz[a]anthracene (6) and 7-acetoxymethyl-5-fluoro-12-methylbenz[a]anthracene (11) on treatment with acetate ion. Hydrolysis of 6 and 11 yielded 7-hydroxymethyl-12-methylbenz[a]anthracene (7) and 5-fluoro-7-hydroxymethyl-12-methylbenz[a]anthracene (12), respectively. Since neither 11 nor 12 is appreciably carcinogenic, the carcinogenic metabolism of 7,12-dimethylbenz[a]anthracene (DMBA) probably does not involve attack at the 7-methyl group.


2-(Substituted phenyl)oxazolo[4,5-b]pyridines and 2-(substituted phenyl)oxazolo[5,4-b]pyridines as nonacidic antiinflammatory agents. Some 2-(substituted phenyl)oxazolo[4,5-b]pyridines and 2-(substituted phenyl)oxazolo[5,4-b]pyridines have good antiinflammatory and analgesic activity. A few possess activity comparable to phenylbutazone or indomethacin without producing the irritation in the gastrointestinal tract that acidic antiinflammatory compounds cause.


Synthesis and antihypertensive activity of 5-thio-2-pyridinecarboxylic acid derivatives. Synthesis of various substituted 5-thio-2-pyridinecarboxylic acids and their derivatives is described by three methods, i.e., displacement of nitrite from methyl 5-nitro-2-pyridinecarboxylate (10) by a thiol anion, alkylation of methyl 5-thio-2-pyridinecarboxylate derived from reaction of the diazotized methyl-5-amino-2-pyridinecarboxylate (5) with thiocyanate followed by borohydride reduction of the product, and alkylation of 5-thio-2-pyridinecarbonitrile followed by hydrolysis. 5-Thio-2-pyridinecarbonitrile was obtained from butyl 6-methyl-3-pyridyl sulfoxide (2) by nitrosation and dehydration of the oxime. Many of these 5-thio-2-pyridinecarboxylic acid derivatives were orally active antihypertensive agents in the spontaneously hypertensive rat. Optimization of the structural parameters for this activity yiedled 5-[m-trifluorobenzyl) thio]-2-pyridinecarboxylic acid (41) and its sulfoxide, 42. Further biological studies with these compounds are described.


N,N'-(Phenylene)dioxamic acids and their esters as antiallergy agents. A series of dialkyl N,N'-(m-phenylene)dioxamates was synthesized by treatment of the requisite m-phenylenediamines with an alkyloxalyl chloride in the presence of triethylamine. Hydrolysis with sodium hydroxide solution gave the corresponding N,N'-(m-phenylene)dioxamic acids. Several N,N'-(p-phenylene)dioxamic acids were synthesized also in the same manner starting with the requisite p-phenylenediamines. These compounds were tested in the rat passive cutaneous anaphylaxis (PCA) assay. When tested iv, activity was found in the N,N'-(m-phenylene) dioxamic acids up to 2500 times that shown by disodium cromoglycate [50% inhibition at 0.001 mg/kg for N,N'-(2-chloro-5-cyano-m-phenylene)dioxamic acid (compound 61)]. Oral activity was seen in this series of compounds with duration of activity up to 120 min. Oral activity was detected in diethyl N,N'-(2-chloro-5-cyano-m-phenylene)dioxamate (compound 38) at levels of drug as low as 0.1 mg/kg.


Antiallergic activity of tetracyclic derivatives of quinoline-2-carboxylic acid. 2. Some benzothienoquinolinecarboxylic acids. Some benzothienoquinolinecarboxylic acids were synthesized and tested in the rat passive cutaneous anaphylaxis (PCA) assay as potential antiallergic agents. Many of the compounds showed activity comparable to that shown by disodium cromoglycate (DSFG); two of them, 1,4-dihydro-4,6,6-trioxo-5-chloro[1]benzothieno[2,3-g]quinoline-2-carboxylic acid and 1,4-dihydro-1,7-dioxo[1]benzothieno[3,2-f]quinoline-3-carboxylic acid, showed potency approximately eightfold greater than that of DSCG in the PCA assay.


Synthesis of 2-substituted primaquine analogues as potential antimalarials. A series of 2-substituted primaquine analogues has been synthesized and evaluated against Plasmodium berghei in the mouse and Leishmania donovani in the hamster. Three members (3a,d,e) of the series were evaluated against Plasmodium cynomolgi in the rhesus monkey. One analogue (3d) was evaluated against Trypanosoma rhodesiense in the mouse, and two (3b,e) were evaluated against Schistosoma mansoni in the mouse. Several analogues possessed significant activity against P. berghei (3e,f) and L. donovani (3a,e).


Quantitative studies on competitive activities of skin bacteria growing on solid media. Earlier quantitative investigations of antagonism between skin bacteria were based on the use of liquid cultures, but a more realistic model has now been devised, based on the use of the surfaces of solid media. Pure or mixed inocula were spread evenly over suitable agar media in Petri dishes marked out with a standard grid. Growth curves were constructed from viable counts of the surface bacteria after they had been removed from excised squares of the agar media and dispersed. The method was highly reproducible, and competitive interactions were revealed more clearly than in studies with liquid media. An antibiotic-producing strain of Staphylococcus epidermidis (S6+) readily suppressed strains of Micrococcus, Corynebacterium and Streptococcus species. However, a Staphylococcus aureus strain which was less sensitive to the antibiotic effect of S6+ interacted in a complex manner, depending on the absolute and relative size of the S6+ inoculum.


Isolation of small viruses resembling astroviruses and caliciviruses from acute enteritis of calves. Small round viruses (SRV) were isolated from the faeces of diarrhoeic calves from three farms. All three SRV preparations caused diarrhoea experimentally in gnotobiotic calves. Each preparation contained viral particles of two morphological types, "astrovirus-like" and "calicivirus-like", and from one preparation the two particle types were separated from each other. The calicivirus-like agent ("Newbury agent") was 33 nm in diameter, and caused diarrhoea in gnotobiotic calves with villous atrophy and D-xylose malabsorption. This virus did not infect cell cultures. The astrovirus-like agent did not cause diarrhoea in two gnotobiotic calves; however, it infected cell cultures (primary calf kidney) and the infected cells immunofluoresced with convalescent gnotobiotic-calf antiserum. The astrovirus-like agents in the three preparations were antigenically related. Experiments in calves showed that there was a degree of cross-protection between the three SRV preparations, as judged by the presence or absence of diarrhoea, but that at least three unrelated pathogens were present.


Studies of the specificity of ureaplasmas for marmosets. Marmosets, from which endogenous ureaplasmas had been eradicated by treatment with minocycline, were tested for susceptibility to infection by ureaplasmas from the genital and respiratory tracts of other animal species. They could be infected with ureaplasmas of human and simian origin, but were resistant to bovine and canine ureaplasmas. The results indicated that human, marmoset and squirrel-monkey ureaplasmas may form a biological subgroup, distinct from bovine and canine ureaplasmas, and that host range should not be ignored as a parameter for classification.


Anomalous blood typing from impersonation. Biological factitious, and technical reasons have previously been reported for real or apparent changes in blood type. In two cases, an apparent change in blood type resulted from a previous impersonation of the patient by a different person.


Tuberculous meningitis.

Tuberculous meningitis. To evaluate modern treatment and identify important factors influencing the outcome of tuberculous meningitis, clinical and laboratory findings in 52 patients aged from 9 months to 68 years have been reviewed. Patients were classified by clinical criterions at admission and at the start of treatment. Delay in commencing treatment was associated with deterioration and consequently poorer prognosis, but some severely ill patients made a good recovery. Forty-four survivors (85%) recovered, and only two patients (4%) had severe residual disability; eight (15%) of the patients died. Treatment should commence as soon as possible on clinical grounds without necessarily waiting for demonstration of Mycobacterium tuberculosis, as the organism can often be demonstrated in CSF withdrawn after the start of drug therapy.


Pott's disease in heroin addicts.

Pott's disease in heroin addicts. Five cases of tuberculous vertebral osteomyelitis occurred in heroin addicts at St Luke's Hospital Center between 1955 and 1975. All patients were men, and four were between 19 and 33 years of age. In contrast with the indolent onset typical to pyogenic or fungal vertebral osteomyelitis in heroin addicts, patients with Pott's disease had an acute toxic reaction, with fever, back pain, weight loss, and night sweats. Neurologic abnormalities, uncommon with pyogenic or fungal vertebral infection, occurred in all patients with tuberculous involvement of the spine. Roentgenograms of the spine were atypical in four patients, including two with an "ivory vertebra." All patients had involvement of extravertebral sites, and one patient had infection with Mycobacterium tuberculosis and M avium.


The mode of action of contractile effects induced by external calcium and its related bivalent cations in the KCl-depolarized rat uterus. The cumulative log dose-response curve (DRC) isometrically produced by CaCl2 on depolarized uteri of rats in Ca2+-free KCl Ringer's solution (pH 7.8) showed a plateau-shaped type, when responses were plotted as a percent of the maximal tension of 50 micrometer acetylcholine, whereas those produced by BaCl2 or SrCl2 were a simple sigmoid type with the maximal response near the height of the plateau induced by Ca2+. The plateau phase of Ca2+ was inhibited competitively by Mg2+ (0.5--50 mM) and non-competitively by Mn2+ (30 micrometer--1 mM), whereas the maximal contraction of Ca2+ was not inhibited by either ion. Dantrolene (0.1 mM) inhibited both the plateau and the maximal contraction of Ca 2+ and retained the plateau-shaped type. EGTA (2mM) potentiated the plateau to the maximal response level and changed the DRC induced by Ca2+ to the simple sigmoid type. From these results, the plateau of DRC induced by Ca2+ seems to be mainly due to actions of external Ca2+ on the calcium binding of internal surface of cell membrane, suggesting that the internal surface is the site of the bivalent cations tested.


Developmental stage of the rat mammary gland as determinant of its susceptibility to 7,12-dimethylbenz[a]anthracene. Postnatal development of the mammary gland was studied in 80 noninbred Sprague-Dawley virgin rats ranging in age from 2 to 112 days, and the changes induced by 7,12-dimethylbenz[a]anthracene (DMBA) were studied in 60 noninbred Sprague-Dawley virgin rats that, at the age of 55 days, were inoculated intragastrically with 10 mg DMBA/100 g body weight. To correlate the sequential structural changes in the two groups, animals of both groups were killed weekly and their mammary glands removed and processed for wholemount. Terminal endbuds (TEB), terminal ducts (TD), alveolar buds (AB), and lobules per square millimeter were counted in wholemount preparations under a stereomicroscope. During postnatal development, the mammary gland tree grew by sprouting numerous ducts ending in club-shaped TEB. The density of TEB reached a peak when the rats were 21 days old (25 +/- 2 TEB/mm2), decreased sharply until the animals were 63 days old, and then decreased slowly until they were 84 days of age. The number of TEB decreased because of their differentiation mainly into AB or their evolution to TD. AB later differentiated into lobules. AB increased in number steadily to a plateau when the animals were 70--84 days old. After DMBA was administered to the rats at 55 days of age, the number of TEB remained higher than that in the control animals and the TEB became larger and had higher mitotic activities. Such TEB were called intraductal proliferations (IDP); they evolved to adenocarcinomas. DMBA increased the number of TD and decreased the number of AB and lobules in relation to the control animals. These findings led to the conclusion that DMBA administration to 55-day-old rats alters the differentiation of TEB leads to AB leads to lobules, inducing instead the sequence TEB leads to IDP leads to adenocarcinoma.


Resistance to tumor graft in mice treated with inactivated Brucella abortus cultured in smooth or rough phase. Because killed Brucella abortus organisms cultured in smooth (S) or rough (R) phase were known to differentially influence humoral and cellular immune responses and to differ in their effects on T-dependent responses, the antitumor properties of killed B. abortus organisms, cultured in S- or R-phase and then inactivated, were compared in (C57BL/6 X DBA/2)F1 female mice with the use of 6 different transplantable tumors. In solid tumors, the antitumor effects produced by S-preparations were never improved by R-preparations. However, in ascites tumors, R-preparations gave the best antitumor results. These findings suggested that the defense mechanisms acrivated by immunostimulants may differ according to the site of tumor implantation. Among the other experimental factors studied, the route of B. abortus administration had a prominent role. Local injection at the site of tumor implantation before or after the graft gave better results than did systemic treatment. Systemic treatment could enhance the growth of Lewis tumor when applied 5 or 10 days before tumor graft but generally had an antitumor effect when given 1 day after the graft.


Bicarbonaturic effect of lysine in the dog. The infusion of 55 mumoles/kg/min of L-lysine monohydrochloride increased mean fractional bicarbonate excretion (CHCO3/GFR) from 0.01 to 0.29. This massive bicarbonaturia was observed in the absence of any significant fall in GFR or kidney cortex ATP content. Kaliuresis and urinary PCO2 also increased markedly while phosphaturia remained minimal. CHCO3/GFR reached 0.52 during the infusion of 110 mumoles/kg/min of L-lysine monohydrochloride and 0.65 when carbonic anhydrase inhibition was superimposed. Bicarbonaturia remained minimal during the infusion of 55 mumoles/kg/min of L-lysine dihydrochloride. However the same amount of isoelectric L-lysine and sodium L-lysinate increased CHCO3/GFR to 0.68 and 0.76, respectively. In dogs with ligated renal pedicles, a 1:1 relationship was observed between cellular entry of lysine and the combined shift of sodium and potassium from cell to extracellular fluid. Marked accumulation of lysine was observed in the kidney following the infusion of either L-lysine monohydrochloride or L-lysine dihydrochloride. This study demonstrates that lysine inhibits in the proximal tubule the fraction of bicarbonate reabsorption which is not mediated by carbonic anhydrase activity. This effect is best explained by trapping of hydrogen ions in the tubular cell following luminal and antiluminal entry of lysine in unionized form. The possible role of lysine as a poorly reabsorbable cation is also recognized.


Establishment of small breeding colony of rhesus monkeys. A breeding colony of 22 female and 4 male rhesus monkeys (Macaca mulatta) was established in a controlled-environment building with an outdoor run. The animals were quarantined for 2 years prior to their release into the unit. The housing, release and management of the colony are described. During the first year 19 young were born of which 17 have survived to 6 months of age. The cost of production and maintenance of the colony when compared with the cost of importing rhesus monkeys would appear to be acceptable.


Provocation of pseudomoniasis with cyclophosphamide in mice. After treatment with cyclophosphamide, a fatal syndrome was found in mice contaminated with Pseudomonas aeruginosa. The syndrome seems to be caused by P. aeruginosa from the intestine, and the liver is suspected to be the most important target organ.


The influence of anaesthetics on the haematology of the patas monkey, Erythrocebus patas. The effects of phencyclidine, ketamine and an alphaxalone-alphadolone mixture on the haematology of the patas monkeys have been compared. In animals sedated with phencyclidine or ketamine the only significant difference detected was in the mean cell volume. Statistically significant differences in white-cell count and blood coagulation and fibrinolytic activity were found in monkeys which had received alphaxalone-alphadolone. It is suggested that ketamine is a suitable alternative to phencyclidine for haematological studies in these monkeys.


Effect of anticoagulants and glucose on refractometric estimation of protein in canine and rabbit plasma. The effect of ethylenediaminetetraacetate (EDTA) compounds on the refractometric estimation of plasma protein concentration was attributed largely to osmotic fluid shifts, as reflected in changes in hematocrit, and to addition of total solids to the plasma. With H4EDTA, these two mechanisms were additive and caused increased plasma protein readings of significant magnitude even at recommended (1--2 mg/ml) anticoagulant concentrations. For the potassium and sodium salts, the two mechanisms were partly compensatory, which ameliorated the effect at 1--2 mg/ml concentration. At higher concentrations, such as might occur if a blood collecting tube were incompletely filled, all of the EDTA compounds caused technically significant over-estimation of plasma protein. When dextrose (d-glucose) was added in-vitro to canine blood, in amounts analogous to clinical hyperglycemia, the effect upon plasma protein estimation was minimal.


Reproductive performance in a breeding colony of Brazilian squirrel monkeys (Saimiri sciureus). In a captive colony of Brazilian squirrel monkeys (Saimiri sciureus) a discrete birth season has been retained for 5 years although its duration increased from 3 months in 1972 to 6 months in 1976. The ages of breeder females in this colony ranged from 3 to 14 years, and within this range reproductive performance was not affected by age, although it was significantly better in feral than in colony-born females. The latter had a lower pregnancy rate and a higher incidence of neonatal and fetal deaths than did the feral monkeys. It is our belief that the reproductive and maternal capabilities of the colony-born females were adversely affected by the practice of removing neonates from their mothers at weaning and raising them with age-mates.


Comparative mitogen responses of lymphocytes from Colombian Panamanian, and Peruvian owl monkeys. A comparative study of lymphocyte responses to various mitogens, an index of cell-mediated immune competency, was made under various culture conditions using peripheral blood lymphocytes from Colombian, Panamanian, and Peruvian Aotus monkeys. Dose response curves were determined for each primate group to phytohemagglutinin, concanavalin A, and pokeweed mitogen stimulation. Considerable variation in mitogen response was observed. The influence of culture media supplemented with fetal calf serum or autologous plasma, the number of cells per culture, and the duration of incubation on mitogen responsiveness was also evaluated. Optimal lymphocyte culture conditions also differed among the three groups. Owl monkeys from the same location in South and Central America showed similar responses to physical condition and free of detectable disease, these differences probably reflect fundamental inherent biological differences between subpopulations of owl monkeys.


The influence of chemical restraining agents on cardiovascular function: a review. A review of selected experimental reports indicated that chemical restraining agents commonly used in experimental animals affected basal cardiovascular function and could influence the response of the cardiovascular system to physiologic-pharmacologic stimuli. Drugs that were considered included pentobarbital, halothane, alpha-chloralose, droperidol, fentanyl, and ketamine. In relation to effects on hemodynamics, anesthetic restraint produced by one drug was not necessarily equivalent to that produced by another.


Effects of prostaglandin E1 on platelet loss during in vivo and in vitro extracorporeal circulation with a bubble oxygenator. Temporary inhibition of platelet function with prostaglandin E1 (PGE1) prevents platelets loss and functional alterations during extracorporeal circulation with a membrane oxygenator. This study evaluated the ability of PGE1 to prevent platelet injury in circuits containing a bubble oxygenator. During in vitro recirculation of human blood, the circulating platelet count, expressed as a percent of initial levels, decreased to 29%; platelets became insensitive to adenosine diphosphate (ADP) and to epinephrine; and plasma levels of low-affinity platelet factor 4 (LA-PF4) progressively rose to 7.4 microgram per milliliter. With PGE1 (1.2 micron), platelet counts remained stable at 92%; platelet reactivity remained normal for 1 hour; and plasma levels of LA-PF4 rose to only 3.3 microgram per milliliter. In rhesus monkeys that underwent cardiopulmonary bypass using a bubble oxygenator without PGE1, platelet counts, expressed as a percent of the prebypass platelet count, declined to 38%; platelets became insensitive to ADP; plasma levels of LA-PF4 progressively rose to 8.4 microgram per milliliter; and the mean postoperative bleeding time was 4.6 minutes. In monkeys that received PGE1, platelet counts declined to only 65%; platelets remained threefold more sensitive to ADP; platelets demonstrated delayed release of LA-PF4 and the mean postoperative bleeding time was 2.7 minutes. This report demonstrates that in a bubble oxygenator system, PGE1 reduces platelet loss, mitigates platelet injury, and shortens postoperative bleeding times following extracorporeal circulation.


[Juvenile xanthogranuloma].

[Juvenile xanthogranuloma]. The clinical and histopathological picture of a case of Juvenile Xanthogranuloma present in a new-born, in which all the investigations and analytic results were normal, is commented upon. The patient presents a case of exclusive skin affectation.


Acidemia and insulin resistance in the diabetic ketoacidotic rat. Insulin sensitivity with respect to changes in blood glucose, lactate, and ketone body concentrations has been studied in normal and streptozotocin-diabetic rats. Insulin was infused at doses ranging from 0.03 to 100 U/kg/hr and dose response curves established. Maximal responsiveness was achieved at 1 U/kg/hr for glucose and 0.3 U/kg/hr for ketone bodies in normal rats. In diabetic rats, responsiveness and sensitivity were directly proportional to pH. When pH was less than 6.9, there was little or no response. Ammonium chloride administration to normal rats or to mildly acidotic diabetic rats caused almost total loss of responsiveness to insulin. The insulin insensitivity found in severely acidemic diabetic rats could be reversed by sodium bicarbonate administration. Liver and muscle metabolite patterns suggested that loss of responsiveness and sensitivity was due both to effects at the insulin receptor and direct effects on glycolysis, presumptively at phosphofructokinase. Reversal of these changes with bicarbonate was associated with a fall in hepatic ATP content. It is suggested that the insulin resistance of severe diabetic ketoacidosis in the rat is secondary to inhibitory effects of hydrogen ion; the exact mechanism remains to be established.


Inhibition by potassium ion of the pregerminative response to L-alanine of unactivated spores of Bacillus cereus T. The effect of potassium ion on L-alanine-inosine-induced germination of unactivated spores of Bacillus cereus T was studied. Unactivated spores germinated in 0.1 M sodium phosphate buffer (NaPB), but not 0.1 M potassium phosphate buffer (KPB), at pH 8.0 and at 30 C. Inhibition of germination was also observed on incubation of unactivated spores in NaPB containing potassium chloride. Previously it was demonstrated that germination of unactivated spores involves at least two steps, one induced by L-alanine, and the other by inosine. Potassium ion seems to inhibit the response of the spores to inosine, because: (1) Spores that had been preincubated with L-alanine in NaPB or KPB, germinated in NaPB but not KPB in the presence of inosine. (2) During germination in NaPB, incorporation of L-[14C]alanine showed bimodal kinetics with a rapid first phase and a second continuous phase, but in KPB the second phase of incorporation did not occur. The events occurring before germination of unactivated spores are discussed with reference to the initiation of germination.


[Hospital infections with pseudomonas aeruginosa. II. Intensive care units (author's transl)]. 72 newly admitted patients of three surgical intensive care units of the Medical School Hannover were examined bacteriologically for pseudomonas aeruginosa for a period of 7 months. A total of 810 specimens was examined during therapy. 95 strains of pseudomonas aeruginosa were isolated in 32 of 72 patients, taken either at the time of admission or during the stay of the patients in the hospital. The frequency of contamination increased with the duration of the stay of the patients in the hospital as follows: 20 per cent at the time of admission, 71 per cent after 8 to 10-day stay and up to 100 per cent for a duration of stay exceeding 14 days. The germs were mainly localized in the nose-throat region and in the respiratory tract. The results of phage typing suggested a hospital infection in about 50 per cent of the patients. The relationship between infection and infectious disease was discussed with respect to the epidemiologic characteristics of intensive care units. Furthermore, it was attempted to formulate recommendations for interrupting or abolishing the infection chains.


[Detection of pathogenic mycobacteria in the environment of the medical units and of the slaughter-house of an African town (author's transl)]. The authors have made investigations about the presence of pathogen mycobacteria in puddles of rain water and in rill waters of sanitary formations and municipal slaughter-house of Yaoundé. 19 strains of pathogen mycobacteria have been isolated from 84 water samples : 15 M. tuberculosis strains, especially present in the environment of sanitary formations, 4 M. bovis strains, especially present in the environment of the slaughterhouse. The third part of isolated M. tuberculosis strains belongs to the africanum variety of this species, although this variety is prevalent in the human pathologic products. 13 from 19 strains are I.N.H. susceptible.


[Experiences with the uripret-system in pediatric practice (author's transl)]. The present study reports on the application of the Uripret-System for identification and susceptibility testing of microbial agents causing urinary tract infections carried out in a pediatric outpatient clinic. The findings were compared with those determined with the conventional methods in an institute of medical microbiology. For the detected mono- and mixed-cultures, in 85% of the cases a concurrent result of both methods was found. Only in one case a different microbial agent genus was determined with Uripret from that found in the institute. The quota of concurrence of the antibiograms for the mono-cultures was highest at 100% for gentamicin and lowest at 85.07% for tetracycline. With the mixed-cultures the concurrence ranged between 81.25% for tetracycline and 96.88% for sulphamethoxazole-trimethoprim. With proteus in mono- and mixed-culture the antibiograms showed concurrence to a lesser degree compared to the other microbial agent geni. The application of the Uripret-System in pediatric practice can be recommended on the basis of the present results.


[A study of serotypes of Pseudomonas aeruginosa isolated in man in Saigon (Vietnam) (author's transl)]. The authors study the serological distribution of 143 strains of Pseudomonas aeruginosa isolated in hospital Grall (Saigon-Vietnam) according to the country (South Vietnam), the kind of pathological specimens and the various departments of the hospial. They describe a special distribution of serological groups in Vietnam with a large predominance of groups 0 = 6 and 0 = 11. They consider the possibility of adapting a polyvalent vaccine including the 10 serological groups now prevailing in Vietnam.


[Antibody response to somatic and flagellar antigens of Pseudomonas aeruginosa (author's transl)]. Using the indirect fluorescent antibody technique, the production of antiflagellar and antisomatic antibodies in rabbits immunized with different P. aeruginosa strains is measured. After 6 injections of formalinized cultures in graded doses over 3 weeks, the antiflagellar antibodies reach the peak in the 4th to 5th week, followed by a rapid fall. The antisomatic antibodies reacting with native and boiled cells show a plateau-shaped maximum from the 3rd to 5th/6th week and fell slightly up to the 11th week. A significant dissociation of antiflagellar and antisomatic antibodies, however, is not observed. The antisomatic antibodies are less absorbed by protein A (Staph. aureus) than are the antiflagellar antibodies.


Evaluation of assay methods for hepatitis B surface (HBsAg) antigen and its antibody (anti-HBs) in viral hepatitis B (VHB)-HBsAg-positive. The sensitivity of methods for the detection of HBsAg and its anti-HBs was compared in serial 1200 sera samples from 30 patients with VHB-HBsAg-positive. HBsAg was tested by gel-diffusion (GD), counter-immunoelectrophoresis (CIE), reversed haemogglutination (rHA), redioimmunoassay (RIA), and enzyme immunoassay (EIA). RIA and EIA methods are statistically significantly more sensitive compared with the other methods (P less than 0.0005). By these methods the minimal concentrations of HBsAg in sera can be proved. Although there is no statistically significant difference in the sensitivity between RIA and EIA, the latter is more sensitive if the subtype ay-HBsAg is considered (12 sera samples). In 24 patients the subtype was ay, in two ad, and in four it could not be differentiated. In 70% of patients anti-HBs was proved by RIA and in 10% by CIE, i.e., in 73% and 9% of sera samples, respectively. In 117 sera samples of these patients the sensitivity of RIA and EIA was compared for determination of anti-HBs. No statistically significant difference between the methods for determination of anti-HBs was found (50.42%: 40.17%). No immune response to HBsAg has been observed in 9 cases, but 6 of them have remained permanent carriers of this antigen.


Astrovirus gastroenteritis age distribution of antibody. Astrovirus antibody was detected by immunofluorescence using infected primary human embryo kidney cultures as antigen. Of 87 Oxford children aged 0--10 years, only 7% in the 6 to 12-month-old group had antibody. The percentage of children having evidence of past infection rose progressively in the 1--4 age range and 75% of the 5 to 10-year-old group possessed astrovirus antibody. Fifty-four (77%) of a group of 70 young adults likewise had antibody.


Threshold spectral sensitivity of single neurons in the lateral geniculate nucleus and of performing monkeys. A technique is described for controlling fixation within central mascular fields and locating and determining thresholds for single neural units in the afferent pathways on the same awake, performing monkey for the same stimuli and at the same retinal loci from which behavioral thresholds are obtained. Comparison of preliminary neural unit and behavioral thresholds appears to reject the hypothesis that the color-opponent LGN units can serve threshold detection. A type of broad-band LGN unit is described which could serve that function, having its absolute threshold within the variability of the behavioral threshold (+/- 1 standard deviation) for all wavelengths successfully tested.


Is the rhesus protanomalous?

Is the rhesus protanomalous? Comparison of rhesus, human trichromat, and human protanomalous subjects were made for measurements of spectral sensitivity involving Landolt ring acuity criteria from 0.11 to 1.11 min-1. At 0.11 min-1, rhesus spectral sensitivity was more similar to that of the normal human trichromats than that of the human protanomalous observers. However, as acuity criterion became finer (thereby involving more central retinal function), rhesus spectral sensitivity became markedly more similar to that of the human protanomalous observers than that of the normal human trichromats.


The ultrastructure of defective human platelets. Much of our current knowledge about the physiology of hemostasis has come from intensive study of platelets from patients with inherited and acquired bleeding disorders or an increased risk of thrombotic disease. Appreciation of the role of plasma proteins in platelet stickiness, of platelet surface membrane glyco-proteins in aggregation, of the substances stored in platelet organelles in cell-cell interaction, vascular injury and atherosclerosis, and of endoperoxides and thromboxanes in platelet intercellular communication have resulted largely from investigations on various types of defective platelets. While the techniques of physiology and biochemistry have generated critical details about abnormal platelets, electron microscopy and ultrastructural cytochemistry have provided an improved morphological framework in which to integrate the new discoveries. The present review has attempted to correlate physiological, biochemical and ultrastructural concepts as they relate to the current understanding of inherited platelet disorders.


Long-term changes in spectral sensitivity after low-level laser (514 nm) exposure. Changes in rhesus spectral sensitivity were induced at low-level (2.1 log td) repetitive exposure to a visible (514 nm) coherent source. Irradiation involved the entire retina. Long-term suppression of intermediate cones was evident in spectral sensitivity functions measured for a very fine photopic (1.85 min-1) acuity criterion. At slightly coarser acuity criteria (1.42 min-1) but still photopic, evidence of rod intrusion was obtained. Recovery from these effects was not obtainable 14 months post-exposure. Possible morphological correlates at photoreceptor ultrastructural levels are discussed. Optical coherency is implicated in these effects.


[The morphogenesis of chronic hepatitis]. The concept of chronic hepatitis is very complex. There is no generally recognized definition and no agreement on the nomenclature. In more recent times a subdivision into chronic persisting (CPH) and chronic active (aggressive or progressive) hepatitis (cah) has been proposed. Morphologically CPH has a mononuclear inflammatory infiltration of the portal fields with preservation of the lobules. In positive hepatitis B CPH, orcein-positive milkglass-shaped hepatocytes and washed-out nuclei have recently been established by immunofluorescence. Periportal inflammation (piecemeal necrosis) is characteristic of CAH. Severe forms show hepatocytolysis and confluent necroses in addition. Since there is not always a sharp division between CPH and CAH, an unequivocal diagnosis of clinical, biochemical, serologic and immunological data is required.


[Clinical enzyme diagnosis in chronic hepatitis. Possibilities and limitations (author's transl)]. The determination of enzyme activity in serum for the diagnosis of chronic hepatitis has become increasingly popular. According to the author's experience serum aminotransferase is raised in about 100% of cases of chronic active hepatitis and also in active cirrhosis, but in only about 70--80% of persisting hepatitis or in moderately active chronic hepatitis. They are frequently normal in inactive cirrhosis. After aminotransferases the alkaline phosphatase is of great importance for the differential diagnosis of icterus. If aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase are determined at the same time, every cholestatic icterus can be diagnosed with certainty.


[Chronic hepatitis B. Relationships between virus in the liver and immune response (author's transl)]. A combined histological examination with detection of virus antigens in liver tissue and blood and the corresponding antibodies in blood can give information on the following problems: Standardization of a hepatitis virus B infection, with diagnostic and prognostic information; determination of infectivity; effects of therapy can be monitored, possibly glimpses may be obtained into the mechanism of cancerization.


[Epidemiology of struma in ambulant patients (author's transl)]. The number of regional claims was obtained from data on 2408 patients. By the number of regional claims we mean the number of claims for a defined performance in relation to the population living in a certain region; in the present investigation the first claims for in vivo diagnostic thyroid examinations within the administrative area. We found a great reduction of the regional claims in the country administrative areas surrounding Marburg, which was accompanied by a relative increase in advanced disease findings which included some who should have sought medical advice earlier. The disparities demonstrated also show that conclusions should only be drawn on taking into account the area of origin of the disease statistics from the patient data from the facilities of the Department of Health.


[Atypical paraproteinemic hemoblastoses (author's transl)]. The symptomatology of typical paraproteinemic hemoblastoses (plasma cell myeloma, Wadenström's macroglobulinemia) are well known. Once suspected, diagnosis of these disorders can easily be established in the majority of cases. Differentiation of benign paraproteinemias requiring no treatment is likewise possible by careful observation of the course of disease and relevant clinical criteria. Very seldom, cases of paraproteinemic hemoblastoses are seen which differ from the usual immunoelectrophoretic analysis and clinical picture. Two very unusual cases of paraproteinemia are presented.


[Prevention of the caries through the application of fluoride]. About 90% of the populations of North and Central Europe and North America suffer from dental caries. A change of nutrition and intensive oral hygiene would make it possible to limit the attack of caries decisively. All measures which have been directed to this end have so far failed. It must be noted that our population will apparently not be re-educated in the foreseeable future. However, since it is entitled to the exhaustion of all possibilities for the preservation of health, the increased use of fluorides for caries prevention is to be encouraged. Until the introduction of fluoridated drinking water the administration of fluoride tablets, especially in kindergartens and schools, should be promoted to the fullest extent. Alternatively it should be considered how far fluoridation of salt would be possible. Furthermore the local use of fluorides for caries prophylaxis to the fullest extent should be recommended.


[Oral hygiene (author's transl)].

[Oral hygiene (author's transl)]. Appropriate oral hygiene is an essential and effective prophylactic measure against caries and periodontal disease. The most important aids for this purpose are suitable multi-tufted short-headed tooth brushes with suitable plastic bristles and suitable tooth-pastes. By means of a rational technique, as for instance the rotation method, teeth and gum margin should be systematically cleaned for at least three minutes if at all possible after every meal. A certain massage effect is exerted on the gingivae at the same time. All other aids to oral hygiene such as toothpicks, dental floss, interdental stimulators, mouthwashes etc. are only additional aids which certainly have their special indications.


[Burning tongue (author's transl)].

[Burning tongue (author's transl)]. Burning tongue mostly does not occur as a disease per se, but as a symptom primarily of internal but also of neurological, dermatological, psychiatric and dental diseases. To facilitate differential diagnostic considerations, a short description is given of the individual clinical pictures as well as of the pertinent findings. The knowledge of these diseases is a prerequisite to the causal and lasting treatment of patients affected by the obstinate and occasionally even painful symptom of the burning tongue.


[Swellings in the maxillofacial region (author's transl)]. The most frequent swellings in the maxillofacial region can be traced to odontogenic inflammations. Chronic dental foci exacerbate and break through the soft tissue layer surrounding the jaw. There the purulent material quickly spreads along the muscular pocket and simulates a phlegomonous inflammation. Inflammations of the individual soft part niches have characteristic symptoms. Because of the loose interconnections the infectious material can spread very quickly into the parapharyngeal space and from there downwards into the mediastinum or upwards into the base of the skull. Because of the danger of an advance in these spaces, it will be necessary to incise the swellings on time.


[Symptom: changes at the corners of the mouth (author's transl)]. The multiplicity of the pathological changes discussed have already been called many names: rhagades, perlèche, angular cheilosis, interlabial mycosis. It is often a poly-etiologic disease picture the causes of which must be recognized and then if necessary be clarified in greater detail by close interdisciplinary cooperation. Beside the common internal and dermatological diseases which may lead to changes at the angles of the mouth it is intended to show which dental and stomatological considerations are to be included in the differential diagnosis and therapy of this symptom complex.


[Cardiogenic shock following acute myocardial infarction. Pathophysiology and clinical aspects (author's transl)]. The starting point of cardiogenic shock is an extensive myocardial infarction. Through a backward and forward failure of the left ventricle a shock-specific disturbance of the microcirculation occurs with a reduction of the circulation in the periphery of the body and development of a tissue acidosis (metabolic acidosis). Fall in blood pressure and cardiac volume, congestion of blood in the region of the pulmonary vessels and signs of reduced circulation in the body periphery (severe physical weakness, apathy, cold and clammy skin, oliguria) determine the clinical picture of cardiogenic shock. Therapeutically, intra-aortal balloon counter-pulsation, possibly combined with a cardiosurgical intervention, has reduced the mortality of cardiogenic shock after acute myocardial infarction from 90--100% to 60--70%.


[Acute pancreatitis following gastric secretion analysis by pentagastrin stimulation (author's transl)]. A picture of acute abdomen developed in a 25-year-old patient with recurrent duodenal ulcers after subcutaneous injection of pentagastrin for a gastric secretion test. Laparotomy undertaken for suspected perforated ulcer revealed an acute hemorrhagic pancreatitis. Healing and freedom from complaint occurred rapidly with drug therapy. The following are to be considered as possible causes for pancreatitis after subcutaneous application of pentagastrin: exacerbation of the ulcer, an acute exacerbation of chronic pancreatitis, a direct effect of pentagastrin on the pancreas, increased pancreatic secretion due to the stimulation of gastric acid, reflux of duodenal contents or bile, arterial hypotension with local acidosis in the pancreas. Attention must always be paid to contra-indications of gastric juice analysis.


[Dupuytren's palmar fibromatosis (author's transl)]. The analysis of a total of 500 patients with Dupuytren's contracture is reported. In agreement with the literature it was found that 90% of the patients are men. 29.9% are in the 5th decade of life at the time of the operation. The disease usually begins on one side. But after up to 3 years the second hand is also affected in 51%. The preferred location, both in its entirety and also in relation to the initial manifestation, is the ulnar portion of the hand. Because of the progressive nature of the complaint, relapses are to be expected even after a successful operation. At the time of the follow-up, 26.2% of the patients had recurrences. A correlation between the clinical picture and the histological phase classifications is not possible with certainty.


[The indications for operative revascularization of acute and chronic renal artery embolism (author's transl)]. Renal artery embolism, which in our patients accounts for 0.4% of all arterial emboli and 6.5% of all operations on the renal arteries, demands rapid diagnosis and immediate operative revascularization. Three of our own cases of complete renal artery embolism which were successfully operated on and 5 with total chronic embolism of the renal arteries, also successfully operated, verify this indication. The importance of the collateral circulation in complete embolism of the renal artery for the maintenance of the organ is pointed out. This collateral circulation can prolong the revival time of the organ so that surgical restoration of the flow can be successful even after a long time. Intraoperative renal biopsy permits the prognosis to be assessed.


[The persistence of pathogens and its immunepathological consequences]. In principle the persistence of pathogens is favored by disturbances of the interplay between specific humoral and cellular defence mechanisms in the particular individual characteristic. Clinical secondary reactions in persistence of infection are in many cases not characterized by the infection as such but more decisively by the "terrain" which a particular organism encounters. This terrain is characterized by immunopathological secondary reactions which now become in turn the basis of the clinical secondary disease. In the individual case the manifestations are due to: acquired disturbances of immunotolerance; formation of neoantigens or induced autoimmune reactions; frequent immune complex reactions due to infectious or secondary antigens with corresponding antibody formation and complement activation.


[Nature and significance of persistent infections (author's transl)]. The "persistent" viral infections, besides "subclinical" infections, pertain to the vast group of "clinically inapparent" infections. They differ from subclinical infections by a temporally unlimited "co-existence" with the pathogen. Pathogenetically, three forms of development are possible: 1. latent infections, 2. tolerated infections, 3. occult infections. Persistent viral infections are the inexhaustible reservoir for many viruses. To the organism affected they may be of benefit (infection immunity, interference, paraimmunity) or of disadvantage (activation of the infection with conversion into a disease, cause of many chronic, slowly developing disease processes, immunopathogenic consequences), the disadvantages prevailing. To the environment, persistent infections are invisible sources of danger as they produce carriers and chronic carriers.


[Particular features of mycotic carriers (author's transl)]. Although we are all carriers of fungi, an infection is rare. Therefore, the following questions are discussed: Why do these actually saprophytic germs become pathogenic at all? Why have opportunistic fungus infections increased? The diagnosis of a fungus infection due to saprophytic pathogens is difficult, as the demonstration of a fungus does not necessarily imply disease. The case history with relevant predisposing factors is an essential clue to the diagnosis. As a matter of principle, the diagnosis of a systemic mycosis should only be established by exclusion.


A gene complex controlling segmentation in Drosophila. The bithorax gene complex in Drosophila contains a minimum of eight genes that seem to code for substances controlling levels of thoracic and abdominal development. The state of repression of at least four of these genes is controlled by cis-regulatory elements and a separate locus (Polycomb) seems to code for a repressor of the complex. The wild-type and mutant segmentation patterns are consistent with an antero-posterior gradient in repressor concentration along the embryo and a proximo-distal gradient along the chromosome in the affinities for repressor of each gene's cis-regulatory element.


Multiplicity of germline genes specifying a group of related mouse kappa chains with implications for the generation of immunoglobulin diversity. The number of germline genes specifying the variable sequences of the Vkappa21 group of light chains was determined by saturation hybridisation analysis to be four to six. This gene multiplicity is considerably less than the total variability in the group, indicating that kappa-chain diversity is generated by somatic mutations in both framework and complementarity-determining (hypervariable) regions.


Rearrangement of genetic information may produce immunoglobulin diversity. The nearly complete amino-acid sequences of 22 closely related immunoglobulin kappa variable (Vkappa) regions from the inbred NZB mouse are presented. This group of Vkappa regions is encoded by at least six germline Vkappa genes. These data also suggest that the mouse kappa gene is divided into three segments termed V or variable (residues 1 to 98 or 99), J or joining (residues 99 or 100 to 112) and C or constant (residues 113--219). Tonegawa et la. have recently described a similar J segment for mouse lambda chains. Inbred mice contain multiple Vkappa and Jkappa gene segments. Therefore, different combinations of V and J gene segments may be joined at the DNA level during the differentiation of individual lymphocytes to contribute to antibody diversity.


The arrangement and rearrangement of antibody genes. Cloned segments of mouse chromosomal DNA provide direct evidence for the somatic rearrangement of kappa variable and constant region genes in antibody producing cells. This rearrangement apparently affects only one member of an allelic pair of light chain genes.


[Colo-vesical fistulas in acute pathology of the colon]. A survey of the relevant literature and a statement of the acute diseases of the colon giving rise to urological complications are followed by a short account of the subjective and objective symptoms of colo-vesical fistulae. An assessment is also made of the advantages of careful diagnostic, clinical and instrumental appraisal. The classic management of such fistulae is described, and the main features of the surgical technique required are illustrated. Successful employment of total parenteral therapy in 13 cases of enteric fistula (including 2 colo-vesical cases) at the University of Genoa "R" Surgical Clinic is reported. The indications, contraindications and complications associated with this method are explained. The modalities whereby a gradual transition is made to feeding per os are described and the results obtained are evaluated.


[Jejunostomy for feeding purposes. Considerations on 100 cases]. Personal experience with 100 cases of jejunostomy for feeding purposes is reported. Stress is laid on the advantages of this feeding technique which include simple, surgical technique, easy administration of diet, speedy metabolic response and the moderate nature of the complications.


[Use of releasing hormones in endocrinological diagnosis]. The identification and synthesis of thyrotrophin-releasing hormone (TRH) and luteinising hormone releasing hormone (LHRH) has widened our knowledge of hypothalamo-hypophyseal-thyroid and hypothalamo-hypophyseal-gonad diseases. More precisely, administration of these two releasing factors, by permitting the evaluation of pituitary TSH, LH, and FSH reserves, reveals otherwise undefinable changes in hypophyseal function. An account of the manner of execution and measurement, the administration route, and side-effects related to TRH and LHRH tests is followed by a description of the main diseases in which they offer the greatest degree of diagnostic assistance.


[Sea-blue histiocytosis. Clinical and immunological study of a familial case]. This case (a young man) presented a clinical picture of a hard periorbital edema, hepatosplenomegaly and a mild bilateral pulmonary fibrosis. The histopatological pattern of our case (as well as his sister affected with the same syndrome) was characterized by the presence of macrophages full of blue staining granules and bone marrow macrophagic infiltrations. In the pulmonary function tests the volumes and compliance test and diffusing capacity were normal. The enzymatic deficit of the macrophage leads to the increase storage of phosphoglicerides and phosphosphingolipids responsibles for the blue staining with Wright-Giemsa stain. Our case fit into the specific pathology of the macrophage cell in accordance with the more recent views of the autonomy of the MPS (Mononuclear Phagocytic System). The known relationship between macrophages and T and B lymphocites have prompted us to study the cellular and humoral immunological behaviour of our case. We have observed an increased IgM immunoglobulins and an increase of IgM surface membrane receptors. Our results will be illustrated and compared with the until known 70 publicated cases.


The biochemical effects of a maternal hyperalimentation during pregnancy. Six patients each with a very low 24-hour urine oestriol excretion were infused with hypertonic dextrose and amino acids for 48 hours prior to delivery. Amniotic fluid samples were studied before and after infusion. Lecithin sphingomyelin ratios and insulin levels were increased following infusions in all patients. There was usually a fall in amniotic fluid glucose and an increase in ammonia, amino acid nitrogen and osmolality following infusions. Maternal plasma oestriol, human placental lactogen, cystyl aminopeptidase and urine oestriol excretion were unchanged during the infusions.


Effects of the epipodophyllotoxin derivative VM 26 in mitosis and in interphase. The epipodophyllotoxin derivative VM 26 inhibits entry of mouse mastocytoma cells into mitosis in cell cultures at drug concentrations of 0.01--1 microgram/ml, the cells being arrested in G2 phase of the cell cycle. At higher concentrations, the compound exhibits spindle poison activity which manifests itself in a shortlasting rise in the number of cells arrested in metaphase of mitosis. These cells then disintegrate after a short period of time.


Serum haptoglobin levels in mice with 7, 12-dimethylbenz[a]anthracene-induced tumors. Serum haptoglobin (Hp) levels were determined periodically in mice treated with the carcinogen 7, 12-dimethylbenz[a]anthracene (DMBA). The magnitude and duration of the Hp response to tumors induced by DMBA were dependent on the tumor type; lymphocytic lymphomas elicted a minimal response, whereas mice bearing mammary carcinomas and stomach squamous cell carcinomas had high Hp levels which remained elevated throughout most of the period of tumor development. In the majority of mice with mammary carcinomas, the initial rise in serum Hp coincided fairly closely with the first appearance of palpable masses. Some variation in the magnitude of the Hp response was observed between individual mice bearing chemically-induced tumors of similar histological types.


Brain disorders don't disqualify workers from job. A variety of neurological disorders afflict people in the workforce and the occupational physician faces tough decisions about them. Sometimes the afflicted individual is an applicant for a job. In other cases, he or she suffers a neurological disorder, ranging from epilepsy to senility, while an employee, often after long and valued service. Whether the decision pertains to hiring or to approval of a return to work, it's usually up to the occupational physician to make it. Often he or she is under strong pressure to make an expedient decision.


Intraspinal alumina injection: the relationship between epileptiform focus, root scarring and chronic pain. Intramedullary or subarachnoid injections of alumina cream were made in the lumbar region of 38 adult cats. The animals were observed for 3 to 12 months and then subjected to acute neurophysiologic and histologic analysis. Neuronal hyperactivity in the dorsal horns was reliably produced by either subarachnoid or intramedullary alumina; behavioral abnormalities were not produced unless some of the alumina was present adjacent to dorsal root fibers in the subarachnoid space. Neuronal hyperactivity does not predict cutaneous hyperesthesia or motor abnormality; alumina produces scarring in the subarachnoid space and probably causes pain by making the dorsal root fibers mechanosensitive. Subarachnoid alumina may be a good model for human arachnoiditis.


Persistent bacteriuria in the rat after reflux challenge with Pseudomonas aeruginosa. An experiment based upon reflux of culture suspensions of Pseudomonas aeruginosa into the rat kidney was set up to examine possible factors of importance in the development of ascending renal infection. We monitored the persistence of challenge bacteria in the rat urinary tract by quantitative culture of urine collected by spontaneous micturition, despite heavy contamination with commensal microflora. In most animals challenged, pseudomonads gave rise to bacteriuria of only limited duration. During bacterial persistence in urine, colony counts fluctuated widely from day to day.


Renal infection in the rat after reflux challenge with Pseudomonas aeruginosa. A rat-pseudomonad reflux model was employed to examine the effect of the size of inoculum on the emergence of renal infection. Widely varying degrees of renal disease observed in challenged animals indicated that a number of variables influenced the outcome of the host-parasite interaction. In this regard, animals in which there was a reduction of the colony counts below a threshold figure rarely gave evidence of renal infection when examined at autopsy on the eighth day following reflux. These results suggest that a threshold level of bacteriuria may also have to be exceeded if renal infection is to become established in patients with vesico-ureteric reflux.


Renal phosphate clearance in fetal lambs. The purpose of this study was to investigate the possible role of diminished phosphate clearance by the fetal kidney in production of relative fetal hyperphosphatemia. Stimuli known to affect renal phosphate clearance in adults were investigated in young fetal lambs. Our studies confirm that the fetal lamb kidney responds to exogenous and endogenous parathyroid hormone (PTH) with inhibition of tubular phosphate reabsorption. Renal tubular phosphate reabsorption in the fetus is in part related to sodium reabsorption. These studies indicate that so-called "immaturity" of renal phosphate clearance in utero is not a significant factor in production of fetal hyperphosphatemia.


Analgesic sensitivity in children with asthma. First described as a component of a triad seen among adults with nonallergic asthma and nasal polyps, aspirin sensitivity has subsequently been documented as a frequent concomitant of a wide range of patients with chronic asthma. Recent reports suggest that its incidence among children with asthma is higher than previously suspected. Among aspirin-sensitive asthmatics, indomethacin and newer, nonsteroid anti-inflammatory agents precipitate airway obstruction with a high frequency while phenylbutazone has a lesser effect. Reports related to acetaminophen among these patients have been inconsistent. Salicylic acid and salicylamide appear to be tolerated. A correlation between the potential for causing airway obstruction among asthmatic patients and the drug's in vitro prostaglandin synthetase activity has been suggested, and elevation of plasma histamine level at the time of the pulmonary reaction has been described. Aspirin and other analgesics may therefore mediate bronchospasm by means of their effects on prostaglandin production and the resultant effects on intracellular cyclic nucleotide activity, which modulates histamine release from mast cells in lung tissue.


Pursuit eye movements and their neural control in the monkey. 1. Single units in the 3. and 6. nerve nuclei were recorded, together with the stimulus and eye movements in trained macaques during pursuit eye movements. 2. The relationship between the impulse rate of an oculomotor motoneuron and the corresponding eye movements can be described by a first order differential equation only, if distinctions are made between the modes of the oculomotor system (e.g., fixation or pursuit) and between the agonist phase and the antagonist phase of the corresponding eye muscle. 3. The trained monkeys showed a frequency response during pursuit eye movements, which was comparable to that of humans and which clearly indicates the existence of a predictor mechanism. 4. After sudden stimulus disappearance in the pursuit mode, both the neural impulse rate and the eye movement performed smooth changes for more than 1s. These slow post-pursuit eye movements were related to the time course before stimulus disappearance. 5. Our findings lead to the hypothesis, that pursuit eye movements in primates, if elicited by small moving visual stimuli, are generated by means of a feedback system consisting of a predictor mechanism, the parameters of which are continuously corrected by an updating process in the afferent visual system.


[Ocular herpes. Therapeutic aspects (author's transl)]. The range of treatment proposed for ocular herpes regularly widens. In addition to the harmful effects of the herpes virus itself, there are local immunological mechanisms which render the use of antiviral substances all the more difficult. Those currently available (5 iodo 2'deoxyuridine, vidarabine, trifluorothymidine) are certainly of the greatest value in superficial forms but have little effect upon deep seated stromal and uveal involvement. In addition, they are toxic to the corneal epithelium. At all events, they offer treatment during acute exacerbations and cannot prevent recurrences. Treatment should thus often consist of corticosteroids and antiviral agents in alternation and the solution is sometimes to be found in the combined use of these two substances. Surgery is above all indicated in the treatment of the sequelae of ocular herpes, the results of operations performed during acute phases being less definite.


[The "e" antigen system in HBs antigen carriers (author's transl)]. Antigen e and its antibody were sought by radial immunodiffusion in 86 carriers of HBs antigen observed over a period of one year. The antigen was found in 3 cases out of 30 with acute viral hepatitis, 11 cases out of 33 with chronic active hepatitis, 1 case out of 6 with chronic persistent hepatitis and 1 out of 6 healthy carriers. It was not found in the serum of 6 patients with fulminating hepatitis. The presence of antigen e is associated with high titers of circulating HBs antigens (p less than 0,001). In this group, no difference in the course of the disease was found in cases of chronic active hepatitis with HBs antigen, according to the presence or absence of antigen e or its antibody.


Formation and characterization of antibody against 2'-(5"-phosphoribosyl)-5' AMP, the monomer form of poly(adenosine diphosphate ribose). Specific antibody against 2'-(5"-phosphoribosyl)-5'AMP (PR-AMP), a monomer of poly(adenosine diphosphate ribose) (poly(ADP-Rib)), was produced by immunizing a rabbit with PR-AMP coupled to bovine serum albumin (BSA). Antibody against PR-AMP was purified 53-fold from serum by (NH4) 2SO4 precipitation, and BSA-Sepharose 4B, DEAE-cellulose and (PR-AMP)-BSA-Sepharose 4B column chromatographies. Inhibition experiments show that the adenine ring, 5'-phosphate residue and ribose-ribose bond of PR-AMP were essential for the antigenic determinant of PR-AMP. Anti PR-AMP antibody bound, not only with PR-AMP, but also with poly(ADP-Rib) of various chain lengths, while anti poly(ADP-Rib) antibody bound with poly(ADP-Rib) but not with PR-AMP.


Creutzfeldt--Jakob disease.

Creutzfeldt--Jakob disease. The laboratory transmission to animals of an apparently degenerative disease of the nervous system, Creutzfeldt-Jakob disease (CJD), is now well established. Important questions arising from this observation are the possibility of natural transmission or infectivity and the existence of other similarly transmissible diseases. Epidemiological studies have revealed some possible clusters of CJD and also an association with previous craniotomy, but there is no definite evidence of natural infection. A few instances have been reported of experimental CJD in animals following inoculation with material from Alzheimer's disease, but apart from this there is so far no evidence of transmission of any other form of degenerative nervous disease.


Demeclocycline in the treatment of the syndrome of inappropriate antidiuretic hormone release: with measurement of plasma ADH. A patient with the syndrome of inappropriate antidiuretic hormone release (SIADH) following head injury and meningitis was studied during treatment with demeclocycline, a drug known to produce a reversible nephrogenic diabetes insipidus. No changes were observed during six days of demeclocycline 1200 mg/24 hr but urine output increased significantly, with the production of a dilute urine, when the dose was increased to 2400 mg/24 hr. The patient lost weight, and all biochemical features of the syndrome were rapidly corrected despite an unchanged fluid intake and despite the persistence of high plasma levels of ADH. The rise in serum sodium was accompanied by mild sodium retention, as measured by external balance and exchangeable sodium. A complication of treatment was the development of acute renal failure possibly induced by a nephrotoxic effect of high circulating levels of demeclocyline. On stopping demeclocyline renal function returned to normal and, after some delay, SIADH returned, and was still present 9 months after initial presentation. This confirms earlier reports of the efficacy of demeclocycline in SIADH; but the authors advise caution against increasing the dose above 1200 mg/24 hr.


[Serum aminoacid levels during aminoacid-free parenteral feeding (author's transl)]. 19 patients in a surgical intensive care unit were fed parenterally on an aminoacid-free diet and the serum aminoacid levels were determined chromatographically on ion exchange resins. The results were compared with those obtained in 150 normal persons. The significance of the findings is discussed.


[Biosynthesis of cellulolytic enzymes and xylanase during submerged cultivation of the fungus Aspergillus terreus 17P]. The fungus Aspergillus terreus 17P--producer of cellulolytic enzymes--was cultivated in the Biotec 10 l fermenter on the medium containing minced and heated (at 200 degrees) wheat straw aerated with a different rate. At the mixing rate of 350 rpm and aeration rate of 0.7 r/rpm on the fourth day the culture liquid was obtained whose filtrate contained an active complex of cellulolytic enzymes and xylanase: CI--3.4; APB--1.1, Cx--35.7, cellobiase--0.23, xylanase--73.8 units/ml. The fractionation of the culture liquid filtrate with ammonium sulphate showed that the fraction precipitated at an interval of saturation of 0.3--0.7 contained the largest portion of cellulolytic enzymes and xylanase. The isolated enzymic preparations had a cellulolytic and xylanase activity and contained lipase, pectinase, laminarinase. They also contained low quantities of amylase, protease, beta-1,4- and beta-1,6-glucanase. Enzymic hylrolysis by the Asp. terreus 17P preparation of straw yielded glucose and xylose, of cotton, Na-KMC, cellobiose--glucose, Xylane hydrolyzate contained xylose and arabinose.


[Use of blockers and stimulators of prolactin secretion in the syndrome of persistent lactorrhea--amenorrhea]. The results of use of rifathyroin (the Soviet preparation thyroliberin), a stimulant of prolactin secretion, and of L-DOPA and cholstylbegit, blockers of prolactin secretion, in patients with various forms of the persisting lactorrhea-amenorrhea syndrome are presented in this work. Reaction of rifathyroin proved to be disturbed in these patients, i.e. decreased in adenomas and hypothalamic disturbances and exceedingly increased in combination of primary hypothyroidism and lactorrhea. L-DOPA and chlostylbegit were capable of reducing prolactin level in patients with the persisting lactorrhea-amenorrhea syndrome, this being accompanied by restoration of biphasic menstrual cycle in some of the patients. The use of estrogens led to increase of the serum prolactin level. Problems of diagnostic value of the test with rifathyroin, and of the efficacy of various therapeutic methods applied in lactorrhea-amenorrhea are discussed.


A major serine protease in rat skeletal muscle: evidence for its mast cell origin. The physical, chemical, and immunologic properties of a protease from rat skeletal muscle, proposed to function in the degradation of certain intracellular enzymes, are identical to those of a chymotrypsin-like serine protease isolated from peritoneal mast cells. The results of polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and 8 M urea indicate that the two rat proteases have identical mobilities corresponding to a molecular weight of 26,000. The relative amino acid compositions of the proteases are nearly identical. Immunodiffusion tests for crossreaction between the muscle protease and antisera directed toward mast cell protease indicate that the former is immunologically identical to mast cell protease. The first 35 amino-terminal residues of the two enzymes are identical and indicate homology of these proteins to other mammalian serine proteases. The sequence analysis of the protease from muscle was extended for an additional 16 positions, and comparison of this amino-terminal sequence with that of a similar enzyme from small intestine showed approximately 75% sequence identity. In contrast, only 40% of the residues in this region of bovine chymotrypsin A were found at corresponding loci in rat muscle protease. It is concluded that the protease from muscle or mast cells is closely related to the enzyme from small intestine which recently was localized in the "atypical" mast cells of gut mucosa [Woodbury, R. G., Gruzenski, G. M. & Lagunoff, D. (1978) Proc. Natl. Acad. Sci. USA 75, 2785-2789].


Identification of four trans-3,4-dihydrodiol metabolites of 7,12-dimethylbenz[a]anthracene and their in vitro DNA-binding activities upon further metabolism. Trans-3,4-dihydrodiols of 7,12-dimethylbenz[a]anthracene (7,12-Me2BA), 7-methyl-12-hydroxymethylbenz[a]anthracene (7-Me-12-OHMeBA), 7-hydroxymethyl-12-methylbenz[a]anthracene (7-OHMe-12-MeBA), and 7,12-di(hydroxymethyl)benz[a]anthracene [7,12-(OHMe)2BA] have been identified as metabolites of the potent carcinogenic and adrenocorticolytic agent 7,12-MeBA. The four trans-3,4-dihydrodiols were identified by their (i) ultraviolet-visible absorption and fluorescence properties, (ii) different retention times on both reversed-phase and normal-phase high-pressure liquid chromatography, (iii) mass spectral analysis, and (iv) inability to form vicinal cis-acetonides. Upon further metabolism by liver microsomes, the trans-3,4-dihydrodiols of 7,12-Me2BA, 7-Me-12OHMeBA, and 7-OHMe-12-MeBA were found to give rise to products that bind more strongly to DNA in vitro than do the products of 7,12-Me2BA. The evidence suggests that one or more of the four trans-3,4-dihydrodiols may be the proximate carcinogenic and adrenocorticolytic metabolites.


Introduction of antigenic phospholipids into the plasma membrane of mammalian cells: organization and antibody-induced lipid redistribution. Phosphatidylethanolamine bearing the 2,4,6-trinitrophenyl hapten was introduced into the surface membrane of mammalian fibroblasts by incubating the cells with small unilamellar vesicles containing this hapten-conjugated lipid. Consistent with integration of the antigen into the plasma membrane lipid bilayer, the exogenously supplied lipid was observed by immunofluorescence to diffuse rapidly (D greater than or equal to 0.6 X 10(-8) cm2/sec) over the surface of polykaryons formed between vesicle- and non-vesicle-treated cells. Association of the exogenous lipids with cells via adsorption of vesicles to the plasma membrane was rigorously excluded by a combination of ultrastructural and immunofluorescence studies. The distribution of the integrated antigenic lipid in the plasma membranes of vesicle-treated cells was followed by immunofluorescence microscopy. The exogenously supplied hapten-conjugated phospholipid was observed to be uniformly distributed and remained so for up to 1 hr at 37 degrees C. However, upon the addition of bivalent, but not monovalent, antihapten antibodies, the phospholipid underwent a rapid temperature-dependent redistribution, forming small patches that eventually coalesced into one or more large aggregates. This unexpected finding is discussed in terms of the mode of insertion of the lipid into the cell surface and the possible mechanisms by which bivalent ligands might alter the mobility and distribution of cell surface phospholipids.


Fibronectin synthesis by epithelial crypt cells of rat small intestine. Synthesis of fibronectin in an epithelial cell line (IEC-6) established from rat small intestine was demonstrated by using immunofluorescence, radioimmunoassay, and collagen-binding. Internally labeled radioactive fibronectin isolated from the IEC-6 cells gave a single main band in sodium dodecyl sulfate/polyacrylamide gel electrophoresis under reducing conditions. Fibronectin isolated from rat plasma gave two closely spaced bands. The slower one had the same mobility as the epithelial cell fibronectin. The distribution of fibronectin in IEC-6 cells as detected by immunofluorescence was different from that described for fibroblasts and other cell types; fibronectin was present exclusively in regions of cell-to-cell contact. No fluorescence was detected on the surface membrane facing the culture medium or underneath the cells. This suggests that fibronectin may not be involved in the adhesion of the epithelial cells to the growth surface but could mediate cell-to-cell contacts. In microscopic sections of the small intestine, immunofluorescent staining with antifibronectin serum was strong in the basement membrane underlying the epithelial cells in the crypts. The in vitro synthesis of fibronectin by the crypt cells and its abundant presence in the basement membrane underlying the same cells in vivo suggests that fibronectin is a structural component of the basement membrane, and that it may be, at least in part, synthesized and deposited by the intestinal epithelium.


Ecdysone-inducible functions of larval fat bodies in Drosophila. Late in the third instar larval stage of Drosophila melanogaster, the titer of the steroid hormone ecdysone increases sharply. This increase is blocked in the temperature-sensitive mutant ecd(1) after a temperature shift from 20 degrees C to 29 degrees C. The mutant was used to prepare three samples of late third instar larvae with different titers of ecdysone; the titer was low in one sample because of an earlier temperature shift, high in a second sample because the larvae were subsequently transferred to ecdysone-supplemented food, and also high in a third sample that was kept at 20 degrees C, providing a control for normal development. The effect of the high titer of ecdysone on proteins of the larval fat bodies was examined by comparing two-dimensional gel electrophoresis patterns of total proteins in stained gels. There were proteins at five positions in the gels for the high-ecdysone samples that were not detected at the corresponding positions in the gel for the low-ecdysone sample. The effect of ecdysone on these proteins was further studied by injecting [(35)S]methionine into the larvae at both early and late third instar stages, in order to label proteins synthesized before and after the increase in ecdysone titer. The results indicate that ecdysone induces two major responses in the fat bodies; certain proteins that were synthesized earlier in the fat bodies and secreted into the hemolymph are incorporated back into the fat bodies, and other proteins are newly synthesized. Attempts to induce prematurely the synthesis of the new proteins by exposing early third instar larvae to exogenous ecdysone were unsuccessful, suggesting that development must proceed further before the fat bodies can respond to ecdysone. By in vitro translation of RNA isolated from fat bodies of low-and high-ecdysone samples of larvae, it was shown that ecdysone greatly increases the amount of translatable messenger RNA for one of the newly synthesized proteins. A clone of DNA complementary to the induced messenger RNA has been isolated from a population of lambda bacteriophage carrying segments of the Drosophila genome. Using the cloned DNA to measure amounts of complementary poly(A)-RNA in the fat bodies by DNA.RNA hybridization, we detected about 50 times more complementary poly(A)-RNA in the high-ecdysone sample of larvae than in the low-ecdysone sample. This finding provides direct evidence that ecdysone induces an increase in the amount of the messenger RNA. The ecdysone-induced appearance of a major messenger RNA in late third instar larval fat bodies represents a developmental response to ecdysone that appears to be gene-specific, tissue-specific, and stage-specific, and it has exceptionally favorable features for further molecular studies of the control of gene expression by a steroid hormone.


Structural analysis of the ADHS electromorph of Drosophila melanogaster. Population geneticists have often determined the fitness differences that account for the dynamics of naturally occurring genetic polymorphisms. However, to understand causal aspects of evolutionary processes requires, in addition, investigation of the physiological and molecular structural differences underlying adaptively significant genetic polymorphisms. The characteristics of the alcohol dehydrogenase gene--enzyme system in Drosophila melanogaster make it well suited for this kind of study. Natural populations of this species are polymorphic for two electrophoretically detectable variants, ADHF and ADHS, of the enzyme. Structural studies reported here reveal that the two variants differ by (at least) a single amino acid replacement, threonine in ADHF for lysine in ADHS.


Sequence organization and transcription at two heat shock loci in Drosophila. The heat shock loci of Drosophila melanogaster chromosome subdivisions 87A and 87C have been studied by using cloned DNA. Both sites contain a number of copies of a 2,4-kilobase (kb) region homologous to mRNA for the 70,000-dalton heat shock protein. In situ hybridization to chromosomal RNA shows that transcripts of this sequence accumulate at both sites after temperature elevation. At 87C there is a 1.5-kb repeated sequence homologous to another heat shock RNA. One cloned segment includes two to three tandem copies of this sequence located 0.8 kb from the beginning of a 2.4-kb message region. RNA complementary to the 1.5-kb repeat acccumulates at 87C after temperature elevation, but does not code for any known heat shock protein. In the sibling species D. simulans, there are sequences located and transcribed at 87A and 87C that are homologous to the melanogaster 2.4-kb message sequence. The 1.5-kb repeat, however, is absent from 87C in simulans and no heat shock RNA homologous to it can be detected.


Immunization against malaria with antigen from Plasmodium falciparum cultivated in vitro. Aotus monkeys, which are generally killed when infected with the human malaria parasite Plasmodium falciparum, have been identified and grouped by karyotype. These animals were immunized with parasite material obtained from P. falciparum cultivated in vitro which had been maintained in culture for over a year. When sufficient amounts of this antigenic material were used with a synthetic muramyl dipeptide (MDP), protective immunity was induced without presenting the antigen in complete Freund's adjuvant.


Histochemically distinct compartments in the striatum of human, monkeys, and cat demonstrated by acetylthiocholinesterase staining. We here report observations on the distribution of acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7) in the striatum of the adult human, the rhesus monkey, and the cat. By the histochemical staining methods of Geneser-Jensen and Blackstad and of Karnovsky and Roots, compartments of low cholinesterase activity were identified in parts of the striatum in all three species. In frontal sections, these enzyme-poor zones appeared as a variable number of weakly stained approximately 0.5-mm-wide zones embedded in a darkly stained background. The zones varied in cross-sectional shape from round to elongated and were sometimes branched. They were most prominent in the head of the caudate nucleus. Three-dimensional reconstructions of serial sections through the caudate nucleus in the human and cat suggest that over distances of at least several millimeters, the zones of low enzyme activity form nearly continuous labyrinths.


Phosphatidic acid releases calcium from a platelet membrane fraction in vitro. A platelet membrane fraction which actively sequesters calcium in the presence of ATP was prepared and the influence of phosphatidic acid evaluated. At 10--60 micrograms/ml phosphatidic acid caused a concentration dependent release of calcium from the membrane fraction. The calcium was released from inside the vesicles, since release occurred in the presence of EGTA used to bind calcium outside the membrane vesicles. Aspirin failed to inhibit release of calcium by phosphatidic acid. Our results may explain, in part, the prostaglandin and thromboxane independent calcium release which occurs in response to certain aggregating agents. Thus, phosphatidic acid, or a metabolite, may have an important role intracellularly in platelets in promoting calcium movement.