Membrane recycling at the cytoproct of Tetrahymena. Exocytosis and membrane recycling at the cytoproct (cell anus) of Tetrahymena pyriformis were studied using thin-section electron microscopy. Single cells were fixed at specific times relative to the elimination of the vacuole's contents--before elimination, at elimination, 3--5 s and 10--15 s following elimination. The closed cytoproct is distinguished from other pellicular regions by a single membrane at the cell surface which is circumscribed by an electron-opaque flange that links or welds the plasma membrane to the underlying alveolar margins. Microtubules originating in the flange pass inward where they lie over, and possibly guide, the approaching food vacuoles to the cytoproct. Food facuoles near the cytoproct are also accompanied by coats of microfilaments. These microfilaments appear to be active in the channelling and endocytosis of food vacuole membrane. Upon cytoproct opening the plasma membrane and food vacuole membrane fuse. Elimination seems to be essentially passive and is accomplished by re-engulfment of the old food vacuole membrane which is constantly associated with microfilaments. Reengulfment of all the food vacuole membrane requires 10--15 s and results in a closed cytoproct. The membrane remnants embedded in microfilaments form a cluster under the closed cytoproct. At the periphery of this cluster remnants take the shape of 70--130-nm spherical vesicles or 0.2-micrometer-long flattened vesicles.


Mechanisms of cellular adhesion. IV. Role of serum glycoproteins in fibroblast spreading on glass. We have investigated the exogenous factors required for the transition from the round shape of suspended fibroblasts to the characteristic spread shape on serum-coated glass. Following the evidence of others that the transition is facilitated by adsorbed component(s) related to CIG/LETS (cold-insoluble globulin/large external transformation-sensitive) proteins, we have isolated 2 such preparations from chick serum. Their influence has been investigated on fibroblast adhesion, spreading and growth and they have been characterized by gel electrophoresis, immunological cross-reactivity, amino acid and carbohydrate residue analysis, sedimentation velocity behaviour and circular dichroism spectroscopy. The preparations have molecular weights of 225/215,000 and 140,000 Daltons respectively and are closely similar in composition and secondary structure. The 225/215 000 Dalton doublet is probably a product of limited proteolysis which almost certainly occurred in the avian circulation. For cells seeded on glass precoated in different ways and in different supplemented media we could detect no change in the extent of attachment but there were profound influences on cell shape following this initial adhesion. We confirm that prior adsorption of either CIG-related preparation to glass does indeed promote fibroblast spreading in the absence of other serum components and that CIG is the sole serum component with this type of activity. We now add 2 important qualifications: (i) the presence of substrate-adsorbed serum CIG is not essential for spreading when other serum components are present in the medium; and (ii) the adhesive organization shown by interference reflexion microscopy is incompletely formed unless the additional serum components are present in the medium. We therefore conclude that 16C fibroblasts have the ability when given the stimulus of soluble serum components other than CIG, but not otherwise, to synthesize all the components necessary for the highly organized contacts with glass, including endogenous CIG/LETS proteins.


The mechanism of K-cell (antibody-dependent) mediated cytotoxicity. III. The ultrastructure of K cell projections and their possible role in target cell killing. The cytotoxic interaction between lymphoid K cells from normal rat spleen and antibody-coated P815 mastocytoma cells has been studied in conditions under which the number of cytolytic events occurring at the time of observation was at a maximum. Electron micrographs of material fixed during the first 15 min after contact between the target and effector cells had been initiated by centrifugation showed that the K cells produce long projections which push deeply into the P815 cells, causing infoldings of the plasma membrane and distortion of the nucleus. The plasma membranes of the effector and target cells, and the nuclear membrane, remain intact. Subsequently the target cells undergo violent cytoplasmic blebbing (zeiosis) which is the first stage of cell lysis. The evidence for the hypothesis that projections from lymphoid K cells develop as a result of contact between receptors on the K cell surface and antibody bound to the target cell, and that the projections are involved in the cytotoxic mechanism is discussed.


[Operative trauma of the common bile duct. Report of eight cases (author's transl)]. The authors report eight cases of operative trauma to the common bile duct; seven patients were sent up for reoperation often during the late stages following an attempt at immediate or secondary repair. Emphasis was placed on the interest of extensive resection of the stenosis and wide and high opening of the common bile duct for construction of the bilio-jejunal anastomosis, and furthermore the late risk of onset of portal hypertension requiring portacaval anastomosis, finally the possible degradation of the good initial results requiring difficult reoperations.


[Diverticulosis of the small intestine (author's transl)]. The authors report two cases of acquired diverticulae of the small intestine with complications and study of pathological, clinical and therapeutic characteristics of this rare disease. Usually latent, these diverticulae were recognised generally during diverticulitis, intestinal obstruction, perforation or hemorrhage. The treatment was either removal of the diverticulum or segmental resection of the small intestine. Diverticulitis of the terminal ileum may lead to right ileo-colectomy.


Normal adults and subjects with hypogonadotropic hypogonadism respond differently to D-Ser(TBU)6-LH-RH-EA10. Daily administration of 5microgram of D-Ser(TBU)6-LH-RH-EA10 for one week produced a significant increase in the LH response to GnRH in hypogonadotropic hypogonadal subjects and a significant decrease in the response of normal male adults. Basal plasma testosterone concentrations fell in normal controls but were unchanged in the hypogonadal group.


Rapid micro-carbohydrate test for confirmation of Neisseria gonorrhoeae. A rapid carbohydrate utilization procedure for the confirmation of Neisseria gonorrhoeae and identification of other Neisseria species has been developed. This method utilizes both preformed enzymes, introduced in a heavy inoculum, and enzymes formed by the microorganisms as a result of growth in a small volume of super-enriched medium. Expected carbohydrate reactions were produced by 383 clinical isolates of neisseriae and were clearly visible within 4 h of incubation. The combined use of disposable glass tubes (6 by 50 mm) and microamounts of media (0.05 ml) make this method not only rapid, but also low in cost.


Rapid diagnosis of septic arthritis by quantitative analysis of joint fluid lactic acid with a monotest lactate kit. The Monotest Lactate Kit (MLT) was compared with gas-liquid chromatography (GLC) for the rapid detection of septic arthritis. A total of 36 joint fluids were tested. Specimens were obtained from patients with septic arthritis (17 cases), inflammatory arthritis (18 cases), and degenerative arthritis (1 case). Specimens from 15 patients with bacterial arthritis had lactate levels above 65 mg/dl (mean, 318 mg/dl with the GLC method and 378 mg/dl with the MLT method). Three specimens from patients with gonococcal arthritis had levels that were not above 30 mg/dl (mean, 21 mg/dl with either the GLC or the MLT methods). Patients with inflammatory or degenerative disease yielded levels lower than 65 mg/dl (mean, 48 mg/dl with the GLC method and 46 mg/dl with the MLT method). Both methods proved to be equallly reliable in detecting septic arthritis, except for the gonococcal cases. Both methods are fast and easily adaptable to clinical laboratories; however, MLT was more definitive when quantitation was needed, required less fluid per speciment, and could be readily done at the bedside.


Three variants of Corynebacterium diphtheriae subsp. mitis (Belfanti) isolated from a throat specimen. Three variants of a Corynebacterium diphtheriae subsp. mitis strain belfanti, two toxigenic (phage types 7 and 11) and one nontoxigenic (phage type 7), were simultaneously isolated from the throat of an adult.


An autoradiographic examination of the central distribution of the trigeminal, facial, glossopharyngeal, and vagal nerves in the monkey. The central distributions of primary afferent axons in cranial nerves V, VII, IX, and X have been re-examined autoradiographically after 3H-proline injections into their peripheral ganglia. Fiber-labeling after subtotal injections of the trigeminal ganglion, besides confirming earlier classical descriptions, suggests that trigeminal fibers of the ophthalmic and mandibular (but not maxillary) branches enter the ventrolateral part of the nucleus of the solitary tract (NST). Injection of VII's geniculate ganglion labels fibers which both ascend and descend upon reaching NST. The ascending fibers distribute in a compact and circumscribed zone immediately dorsal to the spinal V nucleus as far rostral as the caudal pole of the principal trigeminal nucleus. The descending fibers distribute to the lateral NST rostral to the level at which X joins the solitary tract. For a short distance caudal to this level, sparse label is confined to a small part of lateral NST ventral to the solitary tract, which corresponds to the zone receiving direct trigeminal afferents. Fiber-labeling after injections of the ganglia of nerves IX and X suggest the following. Although, upon reaching NST, a few fibers of either IX or X ascend as far rostrally as had those of VII, both have a much larger descending component which distributes to more caudal levels of NST. Most of IX's axons appear to end in the lateral NST; only a few travel as far as the obex. Fibers of X, on the other hand, are abundant in the medial and commissural parts of NST. Moreover, only X appears to have a crossed projection in the commissural nucleus and caudal portion of the contralateral NST. A few fibers of vagal origin also appear to enter the area postrema. Whereas fibers of X appear to constitute the solitary tract, few if any fibers of VII or IX travel within that fascicle. A significant descending components of labeled fibers appears in the spinal V tract when the superior ganglion of either IX or X is injected. These fibers distribute mainly in the pars caudalis of the spinal V nucleus and, to a lesser degree, the cuneate nucleus.


Anatomical organization of the primary visual cortex (area 17) of the cat. A comparison with area 17 of the macaque monkey. Golgi and axonal transport techniques have been used to examine the organization of neurons within primary visual cortex, area 17, of the cat. This organization has been compared to that of the primate cortical area 17 as described in previous studies and it is discussed in relationship to the distribution of afferents from the dorsal lateral geniculate nucleus (dLGN). The visual cortex of the cat and monkey show strong similarities in the laminar positions of neurons projecting extrinsically and also in the restriction of spiny stellate neurons to a central lamina (lamina 4) receiving input from the dLGN. However, lamina 4B in the monkey, which contains spiny stellate neurons but does not receive direct input from the dLGN, has no direct counterpart in cat area 17. Axon projections of spiny stellate neurons in the other divisions of lamina 4 differ in cat and monkey: the small, closely packed neurons in the lowermost division of lamina 4 (4B in the cat, 4Cbeta in the monkey) project chiefly within lamina 4 in the cat whereas in the monkey they have a strong projection to lamina 3. In the cat, spiny stellate neurons of lamina 4A project upon lamina 3 whereas in the monkey those in the apparently equivalent zone, 4Calpha, project upon lamina 4B. Most non-spiny stellate neurons examined have precisely organized interlaminar axonal projections which differ from the axon trajectories of neighboring spiny neurons.


Computed tomography in a primate stroke model using selective balloon catheter arterial occlusion. Ten heparinized nonhuman primates (rhesus monkeys and Papio maryumaya baboons) were subjected to temporary occlusion of an insular branch of the middle cerebral artery with a balloon catheter. An infarct was created. The lesions were monitored in vivo by computed tomography performed at intervals for 1 year. Animals were sacrificed and the lesions examined histologically. The technique obviates the disadvantages of surgical reaction, intravascular thrombosis, and gross cerebral edema observed in prior animal stroke models.


Biological evaluation on glass ionomer cement. Biological properties of a new dental cement of glass ionomer cement were compared with other types of conventional cement. The biological test was carried out by tissue culture method and animal examination. The culture cells showed weaker reaction to the glass ionomer cement than zinc oxide-eugenol or polycarboxylate cement. Pulp tissue reaction showed no significant difference between glass ionomer and zinc oxide-eugenol cement from in vivo experiments using monkeys.


The effect of protein-energy malnutrition on the growth of tooth germs in newborn rats. The effect of protein-energy malnutrition on the growth of molar and incisor tooth germs was studied. Significant differences were found between control and malnourished groups in the weights and calcium contents of both tooth germs. The data point to the importance of the effect of nutrient deficiency on the critical growth period of an oral structure.


Disinfection of nitrous oxide inhalation equipment. Cross-infection by contaminated equipment is a potential hazard associated with conscious sedation with nitrous oxide and oxygen . Nosocomial infections have occasionally been linked wih the use of unsterile inhalation devices; microbial contamination of sterile nasal hoods routinely occurs during administration of nitrous oxide; and in vitro experiments indicate that subsequent use of contaminated nasal masks may lead to aspiration of microorganisms. Although the incidence of respiratory disease after such contamination is unknown, it is clear that disinfection of the nitrous oxide apparatus between patients is desirable. A simple cleaning method involving alkaline glutaraldehyde is described that provides adequate disinfection of the rubber goods used in the administration of gas. Superiority of this technique over previously recommended cleaning methods is shown.


Psychotropic drug use among institutionalized and noninstitutionalized Medicaid aged in California. Previous research has shown that prescription drug use is higher for the aged than for the general population. The present study uses the California Medicaid data base to compare the amount and pattern of prescription drug use among the aged to that of the general population and then compares, within the aged population, drug use by the institutionalized and noninstitutionalized. It was found that prescription drug use was higher for the aged as compared to the general population; among the aged, however, prescription drug expenditures were almost three times as high for the institutionalized as compared to the noninstitutionalized. The bulk of the difference in prescription drug expenditure among the aged subgroup was found to be due to a much higher level of psychotropic drug use among the institutionalized. Data from a sample of aged in a day health program raises questions about the appropriateness of this level of psychotropic drug use.


Aging in the rhesus monkey: debilitating effects on short-term memory. The performance of aged rhesus monkeys (18 years and older) was compared to that of young control monkeys (three to five years old) in three experiments designed to define and evaluate the presumed short-term memory impairment associated with aging. An automated, indirect delayed-response procedure was used with special emphasis directed toward controlling or eliminating potentially confounding variables such as attention, motivation, learning disabilities, etc. It was shown that the aged monkeys do suffer from a profound a specific impairment in short-term memory (STM), performing normally on the shortest dealy interval and showing progressively greater impairment as the retention interval was increased. A subsequent study varied deprivation level and demonstrated that it is unlikely that differences in motivation could account for the age-related STM deficits observed on the delayed-response task. Further studies indicated that alterations in stimulus availability did not differentially affect the performance of the two age groups to any measurable extent, suggesting that differences in stimulus processing abilities are neigher necessary nor sufficient conditions for the deficit found in the first experiment. These results suggest that the delayed-response deficity in old monkeys is directly related to age-associated changes in those areas of the nervous system which are important for the expression of short-term memory.


Heterotopic free skeletal muscle autotransplantation with utilization of a long nerve graft and microsurgical techniques: a study in the primate. In six monkeys the lateral head of the gastrocnemius muscle was transplanted to the dorsum of the forearm after removal of the extensor muscles to the fingers. Microsurgical techniques were used to anastomose the artery and vein of the transplant to vessels in the forearm, and a 12 cm sural nerve graft was used to connect the thoracodorsal nerve in the axilla with the nerve of the transplanted muscle. There was evidence of function in this nerve graft in five of the six animals. Recovery in the transplanted muscles was evaluated by comparisons of muscle weight, electrophysiological measurements of contraction, and histological examination.


Low-residue diets: a reappraisal of their meaning and content. Dietary fibre appears to be the only constituent of food that markedly affects faecal weight and probably total colonic content in normal individuals. It is proposed that low-residue diets intended to reduce large-bowel contents should be renamed low-dietary-fibre diets and be put on a quantitative basis. A low-dietary-fibre diet would contain 10 g or less. Other dietary modifications may also be necessary in diseases causing malabsorption.


The relationship between energy-dependent phagocytosis and the rate of oxygen consumption in Tetrahymena. The induction of high rates of food vacuole formation in Tetrahymena pyriformis increased the rate of respiration in exponentially growing cells by 17% and in starving cells by 47.5%. The increased rate of oxygen uptake was caused by phagocytosis itself, as shown by comparing the rates of respiration of a Tetrahymena mutant exposed to particles at the permissive or restrictive temperatures for food vacuole formation. During cell division, heat-synchronized cells in rich, particle-supplemented medium showed a significant decrease in the rate of respiration. Furthermore, dimethyl sulphoxide, in concentrations sufficient to block food vacuole formation, suppressed the rate of respiration to a level similar to that of starved cells. Cytochalasin B, fowever, did not reduce the rate of oxygen uptake despite the inability of the cells to complete the formation of food vacuoles during treatment; a possible explanation for this finding is discussed. There was a strong correlation between formation of food vacuoles and a high metabolic rate in Tetrahymena.


[Lithium and pregnancy (author's transl)]. The problem has been considered of the action of Lithium salts on the progress of pregnancy and on the product of the conception. Lithium can bring about serious troubles in morphogenesis in invertebrate animals. The results obtained in mammals in laboratory experiments differ from species to species but it seems that these animals can be given about 8 to 9 times the levels of Lithium that are used in man without causing teratogenic effects. A statistical review of the children born to human mothers taking Lithium in pregnancy shows up an increase in the incidence of cardio-vascular abnormalities. (7.8% instead of 0.04%). The infants that have received Lithium and have not been anatomically affected show no more developmental problems later than others.


The scrapie agent: evidence against its dependence for replication on intrinsic nucleic acid. Exposure of the scrapie agent to u.v. light at various wavelengths has shown that light of 237 nm is 4 to 5 times as effective in inactivating it as 'germicidal' wavelengths (250 to 270 nm); whereas with systems that depend on RNA or DNA for function, inactivation is most effective by wavelengths in the germicidal range and there is a minimum of response in the wavelength region round 240 nm. The action spectrum for the scrapie agent is reminiscent of the absorption spectrum for purified bacterial endotoxin, identified as a lipopolysaccharide complex. Dilute aqueous suspensions of scrapie agent were exposed to ionizing radiations in the presence or absence of oxygen. In dilute suspensions of test systems depending on the integrity of nucleic acid or protein, oxygen is almost invariably protective, but it was extremely sensitizing for inactivation of the scrapie agent, to an extent approached only in the case of membranous systems like lysosomes. Results of these two methods argue against dependence of the scrapie agent on an intrinsic nucleic acid moiety for ability to replicate. They suggest that a lipid fraction is an important component and to that extent provide additional support for the 'membrane hypothesis'.


Studies on transduction process by SPP1 phage. The conditions for optimal transduction efficiency of the Bacillus subtilis phage SPP1 have been investigated. By irradiating transducing lysates with u.v. light we have been able to obtain a fivefold increase in the number of transductants and to reduce strongly the interference caused by infective particles. Any dependence of SPP1 transduction on PBSX induction has been ruled out by the use of xin mutants, which are unable to induce the defective phage. SPP1 mediated transduction is susceptible to the restriction and modification system of B. subtilis. The rec functions involved in the recombination of the SPP1 transduced DNA fragment are probably identical to those required in DNA transformation and heterologous PBS1 transduction.


Effect of calcium ions on the infection of Bacillus subtilis by bacteriophage SF 6. Infection of Bacillus subtilis 168Wt by SF 6 resulted in a rapid reduction in the number of phages. This could be counteracted by the addition of calcium, barium or strontium ions. At the optimum concentration of 7.5 x 10(-2) M, the number of p.f.u. remained constant until lysis began. Although cultures of another host. B. subtilis 31 try- his-, at the end of the logarithmic growth phase produced a substance which inactivated free phages, this was not the major cause of the reduction in the numbers of p.f.u. during infection experiments at low Ca2+ concentrations. The diminution of the number of p.f.u. was therefore attributed to the fact that at least one of the steps of the lytic cycle was calcium dependent. Adsorption of SF 6 was equally effective in media containing high or low concentrations of calcium ions. Infection experiments with phages whose DNA had been labelled radioactively revealed that, at high concentrations of calcium ions, the label remained associated with the host cells until lysis commenced. At low concentrations, however, a dissociation between phage DNA and the host was found, although adsorption took place at a normal rate. From these experiments we concluded that a high concentration of calcium ions was required for the penetration of phage DNA. Similar experiments with phages whose protein coat had been labelled showed the same results, indicating that desorption of the inactivated phages occurred. Both electron microscopy and column chromatogarphy with hydroxyapatite showed that a considerable fraction of the inactivated phages had ejected their DNA into the medium. A hypothesis explaining these results is presented.


Disorders in somesthesis following lesions of parietal lobe. 1. We determined the effects of lesions of the parietal lobe on the capacities of monkeys to detect and discriminate between mechanical sinusoids delivered to the hand. Tests of discrimination measured the capacity to discriminate between frequencies of flutter (24--36 Hz) and the capacity to make gross discriminations of frequency of flutter-vibration over the range of 10--50 Hz. 2. A unilateral removal of the parietal lobe impaired sensory capacities only on the contralateral hand; detection threshold was elevated, the capacity to discriminate between frequenceis of flutter was permanently lost, and the capacity to discriminate between and identify frequencies of 10--50 Hz was grossly impaired. No defects were found on the hand ipsilateral to the lesion. Detection thresholds, but not discrimination thresholds, decreased during postoperative testing, but in most cases did not recover to preoperative values. The impairments in frequency discrimination remained through the last day of postoperative testing. 3. A unilateral, subtotal parietal lesion that completely destroyed the primary and secondary somatic areas and Brodmann's area 5 resulted in the same sensory impairments as those produced by total removal of the parietal lobe. In most cases, detection threshold was elevated; flutter-frequency discrimination was lost, and the capacity to discriminate between frequencies of 10--50 Hz over the extended range of flutter and vibration was impaired. 4. The loss in discriminative capacity following lesions of the somatosensory cortex is interpreted as due to the absence of a cortical mechanism that determined differences in the temporal pattern of cyclically entrained activity in the somatic afferent pathway. This loss was dissociated from the remaining capacity, although impaired, to detect the presence of any neural activity in the afferent pathways or to determine gross differences in the frequency of mechanical sinusoids by a mechanism of coding by the labeled line.


Effects of dexamethasone on tumor-induced brain edema and its distribution in the brain of monkeys. A human choriocarcinoma was successfully adapted to grow in the brain of monkeys (Macaca mulatta), thus providing a model of tumor-induced brain edema. Four animals were given dexamethasone (3 mg/kg/day) during 3 to 5 days after the onset of clinical signs, and the other five received no treatment for the same period. Tissue water and electrolyte content of treated and untreated animals were compared in cortex and white matter at various distances from the edge of the tumor. In untreated animals, 67.9% and 23.6% swelling was detected in adjacent and remote white matter, respectively, but only 11.8% swelling was noted in adjacent cortex. In animals treated with dexamethasone these percentages of swelling were improved to 32.4% and 11.9% in the corresponding white matter, and to 4.9% in adjacent cortex. The electrolyte changes shown in edematous brain of control animals also demonstrated significant improvement in the dexamethasone-treated group. Tissue radioactivity of 3H-dexamethasone at 60 minutes after intravenous injection was high in the periphery of tumor, adjacent cortex, and white matter, but low in the center of tumor, remote cortex, and white matter. The sites with high concentrations of dexamethasone also showed significant improvement of brain edema after dexamethasone treatment, suggesting that dexamethasone may act directly at these loci.


Detailed monitoring of the effects of mannitol following experimental head injury. The experimental model of a cerebral missile injury developed by Crockard was used in three groups of Rhesus monkeys treated with mannitol. One group received mannitol 15 minutes after being injured with a BB pellet at 90 m/sec impact. Another group was wounded identically, but mannitol treatment was delayed until 1 hour after injury. The last group was wounded with the missile traveling at 180 m/sec, and mannitol was started 15 minutes after trauma. The data were contrasted with the results from the original model. After receiving mannitol, all groups showed marked improvement in mean blood pressure, cerebral perfusion pressure, cerebral blood flow, and cerebral metabolic rate of oxygen consumption out of proportion to the degree of reduction in intracranial pressure (ICP). The authors conclude that the therapeutic value of mannitol may, in some injuries, be directly related to its effects on blood flow and metabolism, as well as to its better known effects upon ICP.


Cerebrovascular responses to subarachnoid blood and serotonin in the monkey. Preliminary in vitro experiments were performed to determine the serum concentration of serotonin in the monkey, and the ability of cyproheptadine to block serotonin and serum-induced contractions in monkey cerebral arteries. Thirty-four cynomolgus monkeys were subsequently used to study changes in regional cerebral blood flow (CBF) obtained by the intracartoid 133Xe technique, and in the angiographic cerebral arterial caliber resulting from subarachnoid injection of artificial cerebrospinal fluid (CSF), blood, and serotonin. Five animals in each injection group were given 1.0 mg/kg intravenous cyproheptadine (a serotonin-blocking agent) during the post-injection period. Subarachnoid injection of artificial CSF produced no change in CBF or arterial caliber. Post-injection administration of cyproheptadine also had no effect on these parameters. A subarachnoid injection of fresh autogenous blood produced a significant but transient (less than 1 hour) decrease in CBF and moderate vasospasm, which lasted at least 3 hours. This vasospasm was essentially unaffected by intravenous cyproheptadine. The CBF and arterial caliber were unchanged following a subarachnoid injection of serotonin at concentrations (5 x 10(-6)M) present in normal monkey serum. In contrast, 5 x 10(-6) M serotonin invariably produced near maximal contractions in the in vitro cerebral artery preparations. Higher (x10) serotonin concentrations caused a transient CBF response similar to that obtained with blood. However, the cerebral vasospasm induced was of shorter duration than that obtained with blood. These results do not support a major role for serotonin in the production of post-subarachnoid hemorrhage vasospasm. Moreover, our data indicate that in vitro experiments do not reflect the ability of serotonin to constrict cerebral arteries in the intact animal.


Acromegaly with normal growth-hormone levels and pituitary histology. Case report. In rare cases, acromegalic patients have normal basal concentrations of growth hormone, and their acromegaly results from abnormal growth-hormone secretory patterns. A patient is reported with the clinical features of acromegaly, who had elevated somatomedin levels and an enlarged sella turcica, but whose serum growth-hormone levels on continuous monitoring were in the normal range, with levels of 2.8 to 8.9 ng/ml. Dynamic studies of growth hormone revealed normal responses to hypo- and hyperglycemia, but abnormal responses to L-dopa and thyroid-releasing hormone. At surgery, neither a pituitary adenoma nor eosinophilic hyperplasia was present. It is likely that this patient's acromegaly resulted from the presence of chronically high normal levels of growth hormone.


Technical aspects of hepatic portal dissection in biliary atresia. During the past 8 yr, 37 patients with a noncorrectable type of biliary atresia have undergone hepatic portoenterostomy or portocholecystostomy at the Kobe Children's Hospital. The hepatic portal dissections employed in this series were classified as "supraportal" (9 procedures), "portal" (25 procedures), and "infra-portal" (3 procedures) based on the level at which the fibrous mass at the porta hepatis was transsected as determined by the operative record and the pathologic findings. Successful biliary drainage was achieved in 19 out of 25 patients (76%) with a "portal" type of dissection, while 1 out of 9 with "supra-portal" and none out of 3 with "infra-portal" type dissections were successful in this respect. Of the 19 patients who achieved significant biliary flow, 8 have lived for 2--7 yr without jaundice and 3 others are jaundice-free for shorter intervals.


Fetal heart rate during a maternal grand mal epileptic seizure. Although maternal ingestion of antiepileptic drugs is strongly suspected of causing congenital defects, particularly oral clefts, the effect of epilepsy itself or a combined effect of drug intake and epilepsy have not been excluded as etiological factors. Very little is known about fetal oxygenation during a maternal grand mal epileptic seizure. We describe two cases in which fetal heart rate was recorded during a maternal epileptic seizure during labor. The first fetus became clearly asphyctic as judged from the fetal heart rate recording: immediately after the epileptic seizure there was a 13-minute continuous bradycardia wave with decreased short-term variability. After the bradycardia a phase of tachycardia with decreased short-term and long-term variability occurred. In the other fetus there was only a short period of bradycardia, which was followed by a phase of tachycardia and decreased short-term and long-term variability. Both fetuses were vigorous at birth 43 and 87 minutes, respectively, after the epileptic seizures of their mothers. We conclude that a maternal grand mal epileptic seizure can be ominous to the fetus. It is therefore important that epileptic seizures are controlled by optimal medication throughout pregnancy.


Isolation and identification of morphine n-oxide alpha- and beta-dihydromorphines, beta- or gamma-isomorphine, and hydroxylated morphine as morphine metabolites in several mammalian species. New morphine metabolites in the urine of guinea pigs, rats, rabbits, cats, monkeys, and humans were isolated with column chromatography, solvent extraction, and TLC and identified with TLC, GLC, and GLC-mass spectrometry. In addition to the known morphine metabolites, morphine N-oxide was isolated from the urine of guinea pigs, and alpha- and beta-dihydromorphines were isolated or detected in the urine of guinea pigs, rats, and rabbits. Monohydroxymorphine was identified tentatively in the urine of guinea pigs, rats, rabbits, and cats. Dihydroxymorphine was identified tentatively in the urine of guinea pigs, rats, and possibly, rabbits. Finally, beta- or gamma-isomorphine was identified tentatively in the urine of guinea pigs. The newly described morphine metabolites may be involved in some long lasting pharmacological effects of morphine.


Sensitivity of Pseudomonas aeruginosa envelope mutants to alkylbenzyldimethylammonium chlorides. A series of stepwise polymyxin-resistant envelope mutants of Pseudomonas aeruginosa was used to test the activity of a homologous series (C10-C18) of alkylbenzyldimethylammonium chlorides. A sterilization kinetics procedure in deionized water was devised to avoid amounts quaternary compound above the critical micelle concentration. In all cases, there was a linear relationship between the logarithm of the rate of change of the colony count with time and the logarithm of the homolog concentration. For all strains, there was a linear relationship between alkyl chain length and the concentration required to reduce the colony count to 10% in 2 hr. The stepwise series of polymyxin-resistant strains increased in resistance to polymyxin about threefold for each step. In general, this increase resulted in a similar increase in resistance to the quaternary compound. It is proposed that death in this system may primarily be a consequence of damage to the outer membrane rather than to the cytoplasmic membrane.


Specific high-performance liquid chromatographic assay for nitroglycerin in dosage forms. A specific assay for nitroglycerin dosage forms using high-performance liquid chromatography was developed. Sublingual nitroglycerin tablets are dissolved in 25 ml of water and injected directly into the chromatograph. Chromatographic conditions are: mobile phase, 60% methanol in water; flow rate, 2 ml/min; column, microparticulate reversed phase; and detection, 200 nm. The glyceryl mononitrate and dinitrate degradation products of nitroglycerin are separated from nitroglycerin and can be identified by altering the mobile phase composition of methanol.


Individualizing gentamicin dosage regimens in burn patients with gram-negative septicemia: a cost--benefit analysis. Services provided by a clinical pharmacokinetics laboratory were evaluated in terms of an accepted cost--benefit model, and a model to evaluate clinical services provided by the pharmacist is presented. A retrospective study was conducted to evaluate the impact, in terms of patient outcomes, of individualizing gentamicin dosage regimens in severely burned patients. Analysis was conducted using multivariate statistical techniques and appropriate nonparametric and parametric tests to determine significant differences. This analysis provided the necessary data to quantify the impact of the pharmacokinetic service. The findings suggest that significant differences do exist in comparing individually dosed patients against those who were not, based upon discriminant and multiple regression analyses and/or nonparametric tests. Furthermore, the results will be useful for insurance companies, third-party payers, and government agencies in deciding which innovative clinical services should be reimbursed.


Breeding macaques for research.

Breeding macaques for research. A breeding programme or rhesus macaques was established to produce animals with minimal disease and satisfactory behavioural patterns. Problems of design, management, health care and dietary requirements are described.


The Lesser Bushbaby (Galago senegalensis) and the Chacma baboon (Papio ursinus) as laboratory research animals. The 2 species are evaluated as far as adaptibility, economics, reproductive performance and behaviour are concerned. An important limitation is availability which makes conservation and breeding programmes imperative.


Social contact influences on the menstrual cycle of the female Chacma baboon (Papio ursinus). The menstrual cycle characteristics of 2 groups of adult female Chacma baboons were compared. Out of a group of 27 female baboons, 41% (11/27) failed to cycle during the 6 month study period but were all under the stresses of fairly severe experimental manipulation. Data on the menstrual cycles of the remaining 16 unmanipulated females was collected and carefully analysed. These 16 females were individually caged and denied social contact with other baboons. Their menstrual cycles were then contrasted to those of a group of 8 individually caged females which received 24 minute mating tests with vasectomized males on alternate days during their cycles. The females denied the social contact of the mating tests showed significantly longer cycles as a result of significantly lengthened periods up to the time of perineal detumescence.


A semi-synthetic diet for growing baboons. A semi-synthetic diet capable of sustaining good growth in young baboons and containing casein as the only protein source, is proposed. Growth rate data and problems encountered, such as soft stools and hair loss, are discussed. The main shortcomings of the diet are its lack of bulk (fibre) and the amount of time and effort which its preparation requires.


Blood chemical and haematological changes in diarrhoeic baboons (Papio ursinus). Blood was collected for blood chemical and haematological determinations from untreated surviving and non-surviving diarrhoeic baboons. The significance of changes in blood chemical and haematological values is discussed and the importance of supportive treatment is emphasized.


Tuberculosis in laboratory animals.

Tuberculosis in laboratory animals. Tuberculosis can cause great losses in captive colonies of various animal species. In South Africa the culprit is the human type of tubercle bacillus. Interspecific transmission of tuberculosis infection amongst laboratory animals, notably primates, is known to occur, and often handlers and caretakers act as the source of infection. The need for preventive measures in laboratory colonies and procedures for case finding and treatment of tuberculous animals are discussed. Indiscriminate destruction of diseased animals is opposed. The South African situation as revealed by questionnaire survey is described.


The induction and transplantation of hepatomas in Wistar and BD IX rats. Hepatomas were induced by feeding rats laboratory chow containing 0,6375 g of 3'-methyl-4-dimethylaminoazobenzene per kg for 3 to 5 months. DAB-1 was a hepatoma induced in randomly bred Wistar rats and was transplanted for 3 years after which it failed to grow in vivo but not in vitro. DAB-2 and DAB-3 are new transplantable hepatoma lines established in highly inbred DBIX rats. DAB-3 has a metaplastic morphology showing, inter alia, goblet cells, cartilagenous areas, duct-like structures and glandular follicles. This is unlike DAB-1 and DAB-2 which showed poorly differentiated trabecular or anaplastic carcinomatous patterns.


Development of ethyl 3,4-dihydro-4-oxopyrimido[4,5-b]quinoline-2-carboxylate, a new prototype with oral antiallergy activity. Structural modification of 3,4-dihydro-4-oxoquinazoline-2-carboxylic acid leading to ethyl 3,4-dihydro-4-oxopyrimido[4,5-b]quinoline-2-carboxylate, a new prototype with oral antiallergy activity of the disodium cromoglycate type, is described. This prototype is 10 times more potent than disodium cromoglycate in the rat passive cutaneous anaphylaxis test. Structure-activity studies indicate that a carboxylic acid moiety directly attached to the 2 position of the pyrimidine ring is most favorable for intravenous activity while esters of this acid are preferred for oral activity. The oral activity of ethyl 3,4-dihydro-4-oxopyrimido[4,5-b]quinoline-2-carboxylate (ED50 = 3 mg/kg) places this ester among the more potent orally active antiallergy agents reported to date.


Studies on analgesic agents. 1.1a Preparation of 1,2-diphenyl-2-(4-substituted 1-piperazinyl)ethanol derivatives and structure-activity relationships. The preparation and analgesic activity of a series of the title compounds (8-55 and 57) are described. The intermediates, 2-phenyl-2-(1-piperazinyl)acetophenones 5 and 6, were prepared from benzyl phenyl ketones 3 via their bromides 4. On reduction, compounds 5 afforded the titled compounds 8-12, 16, and 26-48. Compounds 13-15 and 17-25 were obtained by alkylation or benzylation of 1.2-diphenyl-2-(1-piperazinyl)ethanols 7 derived from 6 by reduction. The reduction of 5 and 6 with metal hydrides predominantly gave the erythro isomers. The erythro isomers were remarkably more active than their threo isomers. The more active members in this series of compounds were 16 and derivatives 35 and 37-44 of dl-erythro-1-phenyl-2-(substituted phenyl)-2-[4-(p-methoxybenzyl)-1-piperazinyl]ethanol. Compounds 16, 43, and 44 were the most active with a potency of about two to three times that of codeine. Racemates 16 and 38 were resolved into their optical isomers and it was found that (-)-16 and (+)-38 were more potent than their antipodes. Structure-activity relationship are discussed.


Synthesis of steroidal nitrosoureas with antitumor activity. Four steroidal nitrosoureas with structures which may permit specific binding to estrogen receptor were synthesized. Inhibitory activity was observed against the growth of the DMBA-induced transplantable rat mammary tumor 13762.


Enzyme affinity of the 5,6-dihydro derivatives of the substrate and product of thymidylate synthetase catalysis. The 5,6-dihydro derivatives of 2'-deoxyuridine 5'-phosphate (2) and 2'-deoxythymidine 5'-phosphate (3) were synthesized and characterized. The affinities of 2 and 3 were compared to those of the substrate (2'-deoxyuridine 5'-phosphate) and product (2'-deoxythymidine 5'-phosphate) of the reaction catalyzed by thymidylate synthetase. In both cases, the enzyme affinity of the 5,6-dihydro derivatives was 50 times less than that of the substrate or product. The conclusions from this study are that a noncovalent complex of enzyme and a dihydro substrate or dihydro product is improbable in thymidylate synthetase catalysis and the covalent enzyme--substrate complex is more reasonable.


Report of a mucopolysaccharidosis occurring in Australian aborigines. The first 2 reported cases of a mucopolysaccharidosis occurring in an Australian aboriginal family are presented. Though these children had the characteristic morphological features of the Hurler syndrome, enzyme assay of cultured fibroblasts showed normal levels of alpha-L-iduronidase and decreased activity of arylsulphatase B. Thus, they represented the Hurler syndrome clinically,  while they had the enzyme defect of the Maroteaux-Lamy syndrome, and they may represent a new severe form of the Maroteaux-Lamy syndrome. The parents of these children were first cousins. Though the children were not full blood aborigines, examination of the pedigree indicates that the gene originated in the common aboriginal family.


Orientation of medial smooth muscle in the wall of systemic muscular arteries. The study was undertaken to determine the pattern of alignment of muscle cells in the tunica media of muscular arteries. Brachial and femoral arteries from two small Rhesus monkeys and renal arteries from two rabbits were fixed under pressure with formalin, or glutaraldehyde followed by formalin. Sections were cut at 7 micron thickness at specific angles varying from zero to 30 degrees, and then stained with haematoxylin and eosin. The end coordinates of the medial muscle nuclei (appearing dark with the H & E stain) were recorded using a digitizer. Analysis was done as suggested by a previous modelling study by one of the authors; lengths of the individual nuclei as they appeared on the section were plotted as a function of the distance around the perimeter of the vessel. The distribution of lengths was consistent with a truly circumferential pattern of alignment for the muscle nuclei in the wall of muscular arteries. The standard deviation about the average circumferential pattern was +/- 13 degrees in the plane of the histological sections cut in cross section. The number density Nv of 4.4 x 10(5) mm-3 was higher than determined previously for human brain arteries and the nuclear length was 20% shorter (30 micron).


Remote afterloading endocurie therapy for carcinoma of the cervix. Since October 1975, 41 cancer patients were treated with a remote afterloading device using fractionated high dose-rate intracavitary radiation. Nineteen of these 41 patients were treated for carcinoma of the cervix. Remote afterloading high dose-rate fractionated intracavitary radiation was given in combination with external irradiation. The dose fractionation and rad equivalent therapeutic (RET) values and various points of interest are discussed.


Cannabis sativa: ultrastructural changes in organelles of neurons in brain septal region of monkeys. Ultrastructural studies of layer V pyramidal neurons of the septal region of rhesus monkeys exposed to smoke of active marihuana and of those exposed to intravenous delta-9-THC revealed low volume density and various degrees of fragmentation and disorganization of rough endoplasmic reticulum. In contrast, no changes were observed in these neurons of the septal region of control monkeys (unexposed monkeys and one monkey exposed to smoke of inactive marihuana). There were no significant differences in volume density of mitochondria or golgi apparatus between exposed animals and controls.


Effects of various compounds on lipid peroxidation mediated by detergent-solubilized rat liver NADPH-cytochrome C reductase. A reconstituted lipid peroxidation system containing NADPH-cytochrome c reductase isolated from detergent-solubilized rat liver microsomes was used to determine the effects of several compounds, including drugs, on the lipid peroxidation activity. EDTA and ferrous ion were essential requirements for reconstitution of the activity. The addition of 1,10-phenanthroline to the system containing both EDTA and ferrous ion further enhanced the activity. Pyrocatecol, thymol, p-aminophenol, imipramine, p-chloromercuribenzoate (PCMB) and alpha-tocopherol exhibited strong inhibition, aniline, N-monomethylaniline, aminopyrine, benzphetamine, SKF 525-A and NADP exhibited moderate inhibition, and phenol, benzoic acid, acetanilide and nicotinamide exhibited less or no inhibition at the concentrations lower than 1000 micron M. Metal ions such as Hg+, Hg2+, Co2+, Cu2+, Mn2+ and U6+ inhibited lipid peroxidation strongly. In addition, Cd2+, St2+ and Ca2+ exhibited less potent to moderate inhibition, and Ba2+ and Mg2+ were without effects on the activity. Among sulfhydryl compounds tested, dithiothreitol inhibited lipid peroxidation to a greater extent than did the other three compounds, glutathione, cysteine and mercaptoethanol.


Polychlorinated biphenyl-induced morphologic changes in the gastric mucosa of the rhesus monkey. The early morphologic events in polychlorinated biphenyl-induced lesions of the gastric mucosa of immature male rhesus monkeys (Macaca mulatta) were studied in serial biopsies taken during consumption of diets containing 3, 10, 30, and 100 mg. per kg. (p.p.m.) of Aroclor 1242. The severity of the lesions correlated directly with both the duration and the level of exposure. The first changes were seen after ingestion of 30 and 100 mg. per kg. for 2 weeks; changes were not seen until 10 weeks at 3 and 10 mg. per kg. The principal effect was an apparent arrest of the differentiation of generative cells of the isthmus and neck regions into parietal and zymogenic (chief) cells. Mature parietal and zymogenic cells were found only in the bases of the glands, where the oldest cells are normally found, and these showed signs of injury including dilation of the rough endoplasmic reticulum in zymogenic cells, irregularity of the mitochondria in parietal cells and irregular luminal membranes, and an increase in the number of large autophagic vesicles in both cell types.


The composition and calcium transport activity of the sarcoplasmic reticulum from goats with and without heritable myotonia. Studies were conducted on purified sarcoplasmic reticulum isolated from myotonic goats, an animal model of heritable myotonia. When compared to sarcoplasmic reticulum from normal goats, fragmented sarcoplasmic reticulum from the myotonic goat had (1) increased levels of calcium, (2) increased rates of calcium uptake and efflux, (3) an increased sialic acid content, and (4) an increased content of saturated fatty acids. These differences support the concept of a structural and functional defect as a basis for the abnormal contraction-relaxation characteristics of myotonia.


Dietary polyunsaturated fat versus saturated fat in relation to mammary carcinogenesis. High levels of dietary fat have been shown to promote the development of mammary tumors induced in rats by 7,12-dimethylbenz(alpha)anthracene, and polyunsaturated fats were found to be more effective than saturated fats. In further studies it was found that diets containing 3% sunflowerseed oil (polyunsaturated fat) and 17% beef tallow or coconut oil (saturated fats) enhance tumorigenesis as much as a diet containing 20% sunflowerseed oil. Rats on these diets developed at least twice as many tumors as those fed diets containing either 3% sunflowerseed oil or 20% of the saturated fats alone. These results are in accord with human epidemiological data which show that breast cancer mortality in different countries is positively correlated with total fat intake but not with intake of polyunsaturated fat. Total fat intake varies greatly in different countries, but most human diets probably contain levels of polyunsaturated fat at least equivalent to 3% sunflowerseed oil.


The effect of 5,8,11,14-eicosatetraynoic acid on lipid metabolism. The purpose of this presentation is to review the current state of knowledge regarding 5,8,11,14-eicosatetraynoic acid (ETYA, Ro 3-1428) and its effects on lipid metabolism. Accordingly, the topics discussed include hypocholesterolemic and dermatological studies involving ETYA in both animals and man, as well as the effects of ETYA on desaturase enzymes. Metabolic studies involving ETYA are also noted. Primary interest is focused on the effects of ETYA on selected processes of arachidonate metabolism, and the effect of ETYA on inflammation, platelet aggregation and tumor growth are discussed, keeping in mind the relevance of arachidonate metabolism to these processes.


[Antibioprophylaxis of meningococcal meningitis: reality or utopia? (author's transl)]. After restating the activity of the various antibiotics on Neisseria meningitidis, the authors review the results of 18 experiences of germ-carriers control by antibiotics, which were rather deceiving. Conditions for such a control are exposed but question of its real necessity is raised.


[Biological control of vectors of human and tropical diseases. Present means and prospects (author's transl)]. Biological control is "direct or indirect use of natural enemies of the injurious species to increase its mortality" (W.H.O., 1963). The more and more frequent apparition of resistant insects populations, the fears as regards the environment, the increase cost of hydrocarbur products and also some technic and operational difficulties to stop transmission by the use of only insecticide pulvérisation, impose this process. Nevertheless, practic use of natural enemies of vectors is yet unusual in spite of important research. (Identification problems, dynamic of species, insufficiency of ethology knowledge particulary of the host specificity, difficulties of application on the vectors which are the most usually widely scattered). For control of insects of medical importance (mosquitoes, black flies, tse-tse flies) it has been used either pathogen agents such as virus bacteria, microsporida or parasit agents such as fungi, mermithid nematods or at last, predators, essentially larvivorus fish. Actually, no biological agent is able to take the place of chemical and physical "traditional" means. In case of mosquito control which is more advanced, the only biological mean which is operational is the use of larvivorus fish and specially Gambusia.


[Electrophoretic differences in the proteins of the species Pseudomonas aeruginosa and Pseudomonas denitrificans capable of oxidizing n-alkanes]. Pseudomonas aeruginosa and Ps. denitrificans are capable of growing on n-alkanes, but differ in assimilation of higher and lower alkanes. The proteins of their cell-free homogenates were analysed by disc-electrophoresis in a system containing SDS. The "preliminarily adapted" strain of Ps. aeruginosa did not differ from the "non-adapted" to n-hexane strain, though both differed considerably from Ps. denitrificans in the composition of protein spectrum. Therefore, disc-electrophoresis of total proteins has shown that Ps. aeruginosa and Ps. denitrificans are not genetically identical; they exhibit certain common physiological properties, but apparently oxidize n-alkanes via different pathways.


[Chemotaxonomic markers of several coryneform bacteria and the "Rhodochrous" group]. Chemotaxonomic characters (the monosaccharide composition and diaminopimelic acid (DAP) of cell hydrolysates, the type of lipid LCN-A) were studied with bacteria of the "rhodochrous" complex and the Arthrobacter genus isolated from natural substrates as well as with collection strains of the genera Arthrobacter, Brevibacterium and Corynebacterium. If arabinose, galactose and meso-DAP were present in cell hydrolysates of these bacteria, they always contained lipid LCN-A. Bacteria of the "rhodochrous" complex can be differentiated from Corynebacterium sensu stricto by location of lipid LCN-A spots on chromatograms, and from the genera Brevibacterium (B. linens) and Arthrobacter, by the presence of arabinose, meso-DAP and lipid LCN-A in the cells. The representatives of two latter genera do not contain arabinose and lipid LCN-A in their cells.


[Nomenclature of obligate methylotrophs]. The nomenclature of obligate methylotrophs, i. e. bacteria using only reduced monocarbon compounds (methane, methanol, methylamines) as a carbon source, is dicussed. The chronology of naming taxons of methane oxidizing bacteria is presented and the rightfulness of their names is analyzed according to the rules of the International Codex of Bacterial Nomenclature. Such names as Methylomonas and others which are employed while describing various physiological groups of bacteria are used in the nomenclature of obligate methylotrophs, and this may be the source of errors. Therefore, only the genus of methane oxidizing bacteria should be referred to as Methylomonas whereas obligate methanol and methylamine assimilating bacteria should be classed as individual genera. The described species of methane oxidizing bacteria can be included into the genera Methylomonas, Methylococcus, Methylosinus, and Methylocystis. One should avoid such names as Methanomonas margaritae, Methanomonas immobilis, Pseudomonas methanica etc. since they do not possess the nomenclature status. All bacteria that depend obligatorily on the presence of reduced C1-compounds should be included into the family Methylomonadaceae. The taxonomy and nomenclature of facultative methylotrophs must be based on principles accepted for other organotrophic microorganisms as it has been suggested at the II International Symposium on the Growth of Microorganisms on C1-compounds (Pushchino, USSR, 1977).


[Isolation and general characteristics of a group of Pseudomonas aeruginosa temperate phages]. Eighteen temperate phages were isolated from 38 natural strains of Pseudomonas aeruginosa. The phages belong to five heteroimmune groups according to the ability of lysogenic variants of the strains PAO1 and PAT2 to exclude the growth of the superinfecting phage. Phages of the II and V immunity groups are serologically similar; the remaining phages are not inactivated by antisera against phages B26 (II group) and K1338 (V group). Prophages of the II, IV, and V groups are induced by UV for vegetative growth. Phages belonging to different immunity groups vary in their morphology and particle size as was found by electron microscopy. Phages of the I, II, IV and V groups comprise one morphological type, those of the III group are of another morphological type. Phages of the IV group are not adsorbed on the bacterial mutants resistant to phages of the II and V immunity groups.


[Linuron breakdown by fungi of the genus Aspergillus]. Aspergillus flavus isolated from soil as well as museum cultures from the genus Aspergillus transform linuron to 3,4-dichloroaniline by the reaction of demethylation with following hydrolysis of the amide bond; 3,4-dichloroaniline is then acetylated yielding 3,4-dichloroacetanilide. These products regulate the enzymes involved in demethylation and hydrolytic elimination of the side chain. Carbon sources added to a buffer mixture inhibit decomposition of the side chain.


[Xerophytic microorganisms multiplying under conditions close to Martian ones]. The xerophytic cultures Bacillus megaterium and Mycococcus ruber can grow in the imitated Martian conditions. Therefore, they are resistant to the extreme factors of the environment: the composition of atmosphere, low pressure, the maximum hygroscopicity of a substrate, periodic freezing-thawing.


[Results of measuring the modulus of elasticity of microorganism cell walls]. The elasticity modulus of Escherichia coli cell walls was found to change in the course of growth of the culture. It decreased in the middle of the exponential phase, apparently as a result of intensification of biosynthetic and related to them transport processes at this period. If the cells were treated with EDTA, their elasticity modulus was lower, by an order of magnitude, than that of the control cell walls. If the cells were treated with lysozyme, the elasticity modulus of their walls decreased by three orders of magnitude. The elasticity modulus of cell walls was less in gram-positive rods than in E. coli. The elasticity modulus of spherical cells cannot be determined using this technique.


[Effect of emulsifiers on the hydrolysis of solid fats by microorganism lipases]. The object of this work was to select emulsifiers and techniques for preparing emulsions of triglycerides of saturated fatty acids. It was found that not only the degree of dispersity of an emulsion influenced the activity of lipase with respect to a lipid being emulsified, but also the nature of an emulsifier affected hydrolysis of solid fats by microbial lipases.


An unstable donor-recipient DNA complex in transformation of Bacillus subtilis. In re-extracted DNA obtained shortly after uptake of transforming DNA by Bacillus subtilis, increased amounts of donor DNA radioactivity banding at the position of donor-recipient DNA complex (DRC) are observed in CsCl gradients, if the cells are irradiated with high doses of UV prior to reextraction of the DNA. Qualitatively, the same phenomenon is observed if lysates of transforming cells are irradiated. UV-irradiation of lysates of competent cells to which single-stranded DNA is added after lysis, does not result in linkage of this DNA to the chromosomal DNA. Two observations argue in favour of the formation of a specific labile complex between donor and resident DNA during transformation. Firstly, heterologous donor DNA from Escherichia coli, although being processed to single-stranded DNA in competent B. subtilis, does not seem to be linked to the recipient chromosome upon UV-irradiation, and secondly, the labile complex of donor and recipient DNA can be stabilized by means of treatment of the lysates of transforming cells with 4, 5(1), 8-trimethylpsoralen in conjuction with long-wave ultra violet light irradiation. This indicates that basepairing is involved in the formation of the complex. On the basis of these results we assume that the unstable complex of donor and recipient DNA is an early intermediate in genetic recombination during transformation.


[Experimental verification of the results of the mathematical modeling of the process of formation of alpha-amylase-nonproductive mutants of Bacillus subtilis under continous cultivation]. When Bacillus subtilis produces alpha-amylase in the course of continuous cultivation, it is difficult to maintain the activity at a constant level. This may be due to the formation of nonproductive mutants. Individual cells in the population have been analysed in the course of the continuous process. The composition of the population changes depending on time and the composition of the growth medium. Semisynthetic media cause selection of mutants which synthesize the enzyme at a low rate. In contrast, complex media which are more enriched in the sources of carbon and nitrogen induce accumulation of mutants with a high activity.


Autoantibodies to the insulin receptor activate glycogen synthase in rat adipocytes. Autoantibodies to the insulin receptor mimic the effects of insulin on glycogen synthase and phosphorylase. The interaction of antibodies with adipocyte cell surface insulin receptors seems sufficient to promote stable changes in the activities of these intracellular enzymes, suggesting that internalization or processing of insulin is not important in the generation of these biological responses.


[Endocrine disorders in children with neurofibromatosis von Recklinghausen (author's transl)]. Endocrine disturbances have been studied in 4 children with neurofibromatosis von Recklinghausen, aged 5.0-10.5 years. Hypothalamic precocious puberty was seen in three boys; growth hormone deficiency was diagnosed in a girl. After TRH stimulation one boy and the girl showed a diminished TSH-response. Another boy showed a relatively high basal level of TSH and an elevated TSH-response to TRH. All children were euthyroid. Two boys had a hyperprolactinemia even under basal conditions; the one with elevated TSH-response showed an excessive response of prolactin as well. In all our patients a suprasellar tumor caused the endocrine disorders described.


[Ultrasonic doppler technique in angiology (author's transl)]. The ultrasonic Doppler technique is a simple, non-stressing and harmless method of angiological investigation requiring little time. Today it is considered to be the best-suited procedure among the non-invasive instrumental methods in angiological diagnosis. It provides well reproducible data with regard to peripheral arterial blood flow and highly valuable information on functional conditions in the area of carotid flow and in the iliofemoral venous system. This method can be recommended unreservedly for use in general practice as well.


[Regulatory region of the MS2 phage RNA replicase cistron. Accesibility of MS2 RNA specific fragment to T1 RNAse digestion and chemical modification with kethoxal]. Partial digestion with T1 RNAase and chemical modification with kethoxal were used to study stability of two hairpin in the proposed secondary structure of the functionally active MS2 RNA fragment MS2 R(--53 leads to 6), containing the regulatory region of the phage replicase cistron. Analysis of the products obtained after the above treatments showed that T1 RNAase and kethoxal attacked predominantly the guanosine residues in the hairpin b of the MS2 R(--53 leads to 6). This implies that in contrast to the structurally stable hairpin a of the polynucleotide, hairpin b appears to be more labile and may exist under the present experimental conditions in equilibrium with its open form. The data of the competition experiments demonstrated that the kethoxal modified MS2 R(-53 leads to 6) and shorter polynucleotide MS2 R(-53 leads to-11) obtained from MS2 R(-53 leads to 6) after T1 RNAase digestion failed to bind with MS2 coat protein. The relatively unstable hairpin b region in the polynucleotide MS2 R(-53 leads to 6) is suggested to play essential role in the complex formation.


[Pathogenesis of coli enteritis (author's transl)]. The pathogenic mechanisms of E. coli in diarrheal diseases were largely obscure up to now. The discovery of an enterotoxin which corresponded with the cholera enterotoxin in its mode of action and is also largely identical with this molecule immunologically provided essentially new aspects of the pathogenic importance of E. coli in diarrheal diseases. The detection of enterotoxin formation depends on the biological test model and presently it is still expensive and unsuitable for routine laboratory use. The serological identification of coli bacteria is meaningless for the detection of enterotoxin formation. Enterotoxic coli are more frequently found (12%) in the large group of hemolytic organisms. In 1978 we isolated enterotoxic coli from the stools of 12 infants under one year old with stubborn diarrhea.


[Conceptions and facts on difficult primary dentition (author's transl)]. The appearance of the first teeth is often regarded as a particular effort of the child and associated with various complications. On the basis of clinical observations and histological investigations the statements and conceptions were looked into and the process of growth followed up closely for the purpose of clarifying physiological and pathological events, thus also differentiating facts from opinions and assumptions. Appropriate modes of behaviour are recommended.


[Problems of alloplastic joint replacement (author's transl)]. Nowadays artificial joint substitution can be assessed as a definite part of orthopedic surgery. The good primary results must not obscure the fact that in spite of great progress in the field of endoprosthesis, numerous problems must still be considered unsolved. Most important are the problems associated with anchoring the implant into living bone tissue. New ways of cement-free anchorage are being sought. The presentation of possible alternatives and their indicative limitation to alloplastic joint substitution shows that there are possibilities which can be carried out before a possible artificial joint substitution or instead of it. Since joint substitution is still in a phase of development, further advances may be expected in the future.


[Chronic bronchitis, inguinal hernia and other health disorders. Correlation with heaviness of occupation (author's transl)]. 68.8% of the workers of a metal factory have at least one pathological finding out of 11 parameters checked. The number of sick people increases from 57.1% in sedentary workers, to 64.5% in workers doing light or medium physical work, and 77.2% in heavy physical workers. The strongest trend, postulating a positive correlation between work and disease, can be found with the objective signs "chronic bronchitis", "inguinal hernia", and "pathological urine". Contrary to this positive trend in most medical findings, only hypertension and electrocardiographic changes are less frequent in heavy physical workers. The results obtained suggest, on the whole, an interrelationship between sickness and heavy physical work.


[Lymphogranulomatosis in siblings (author's transl)]. In two similar pairs of siblings a histologically confirmed lymphogranulomatosis appeared at an interval of several years in each case. Such observations do not arise through purely coincidental familial frequency but siblings of granulomatosis patients have in fact a much higher risk of contracting Hodgkin's disease than other persons. This gives rise to important considerations for the etiology and pathogenesis of lymphogranulomatosis which are discussed in detail in the light of recent literature.


[Suicide in Bavarian prisons (author's transl)]. The rate of suicides of prisoners in Bavaria from 1945-1974 was investigated. It was shown that only for prisoners awaiting trial was the rate higher than in the normal population or of soldiers of the Bundeswehr. A much higher risk of suicide was found for the first day of imprisonment. The most common method was by hanging in solitary confinement. A sure prevention by confinement with more prisoners is not possible.


[Dose-effects studies with bezafibrate in patients with hypercholesterolemia and hypertriglyceridemia (author's transl)]. The dose-effect relationship of bezafibrate, a new clofibrate derivative, was investigated in 24 outpatients with a primary hyperlipidemia and a Type lla lipoprotein pattern. The patients were divided into two groups at random and in each case received 3 X 50, 3 X 100, 3 X 150 and 3 X 200 mg bezafibrate daily in increasing or falling dosage for four weeks. For rising doses a statistically significant dose-effect relationship could be demonstrated for cholesterol and triglycerides. This was only true for cholesterol with falling doses while triglycerides remained at a low level. The optimal dose was found to be 600 mg bezafibrate daily. The substance was well tolerated, and the usual laboratory parameters remained within the normal range in all patients.


Azo reduction of trypan blue to a known carcinogen by a cell-free extract of a human intestinal anaerobe. The azo reductase activity of a cell-free extract of Fusobacterium sp. 2 is characterized using trypan blue as a substrate. Either chemical reduction of this dye with sodium hydrosulfite or reduction by the cell-free extract produces a mutagenic product, o-tolidine. The o-tolidine is mutagenic in the Ames Salmonella/mammalian-microsome mutagenicity test when activated by a rat liver S9 preparation.


Absence of mutagenicity of praziquantel, a new, effective, anti-schistosomal drug, in bacteria, yeasts, insects and mammalian cells. Praziquantel (Embay 8440, Droncit) a new, effective anti-schistosomal drug, was tested in various short-term assays that have shown a predictive value for the detection of potential carcinogens. Indicator organisms S. typhimurium strains, S. pombe, S. cerevisiae, cultured V79 Chinese hamster cells or human heteroploid cells and Drosophila melanogaster were treated with Praziquantel. The induction of reverse and forward mutations, mitotic gene conversions, X-linked recessive lethals, sister-chromatid exchanges and unscheduled DNA-repair synthesis was scored; rodent-liver microsome-, cell- and host-mediated assays were also performed. Hycanthone, another schistosomicide was included as a positive control. The absence of a genetic activity of Praziquantel uniformly observed in such a battery of tests (i) confirms the assumption that the anti-schistosomal effectiveness of this drug is not related to the mutagenic activity and (ii) should encourage the implementation of extended clinical and field trials.


Mutagenicity of benzotrichloride and related compounds. Benzotrichloride (BTC), benzal chloride (BDC), benzyl chloride (BC) and benzoyl chloride (BOC) were surveyed for their mutagenicity in microbial systems such as rec-assay using Bacillus subtilis and reversion assays using E. coli WP2 and Ames Salmonella TA strains with or without metabolic activation in vitro. BTC and BDC required metabolic activation for their mutagenic activities in several strains of E. coli and Salmonella. The mutagenic metabolites of these compounds may not have been produced by hydrolysis. BC was weakly mutagenic without metabolic activation. Only BOC exhibited no mutagenic activity in the detection procedures used. The mutagenic metabolite of BTC might be very unstable under our experimental conditions. The strain E. coli WP2  try hcr was more sensitive than E. coli B/r WP2 try (hcr+) with regard to the mutagenicity of BTC.


Mutagenic effects of thioacetamide in Drosophila melanogaster. Thioacetamide, which is carcinogenic in mice and rats, has been reported as negative in Ames's test on Salmonella his- with and without liver microsomal fraction (S 9 mix). Tests on Drosophila reported here showed a significant increase in sex-linked recessive lethals after treatment with thioacetamide, both after injection and after feeding of males.


Mutagenicity studies with x-ray-contrast media, analgesics, antipyretics, antirheumatics and some other pharmaceutical drugs in bacterial, Drosophila and mammalian test systems. As part of our investigation into mutagenic effects of environmental compounds, we studied 21 pharmaceuticals most frequently sold in West Germany: 6 X-ray-contrast media, 13 analgesics, antipyretics and antirheumatics, 1 central stimulant, and 1 antidepressant. They were studied in different bacterial, Drosophila and mammalian test systems. 4 of these 21 compounds could be detected as mutagens in one of the test systems. namely: 1,2-dichloroethane induced an increase in the frequency of recessive sex-linked lethal mutations in Drosophila melanogaster, quinine dihydrochloride and dimethylaminophenazone were mutagenic in the Salmonella typhimurium tester strain TA98 in the presence of S-9 liver fraction derived from Aroclor-induced rats, and trilithium citrate caused a significant effect in the micronucleus test on bone marrow of NMRI mice.


Induction of sex-linked recessive lethals and autosomal translocations by beta-propiolactone in Drosophila: influence of the route of administration on mutagenic activity. Beta-propiolactone (BPL) was tested for the induction of sex-linked recessive lethals and autosomal translocations in Drosophila melanogaster. The compound was administered to adult males either by oral application or by abdominal injection. When injected, BPL was a potent inducer of sex-linked recessive lethals. When BPL was given by feeding, its mutagenic activity was detectable only when the flies were starved and when the BPL-containing solutions were renewed several times. Nevertheless, the recessive-lethal frequency was one order of magnitude higher with injection. This difference in effects is attributed to (1) rapid decomposition of the compound in aqueous feeding solutions, and to (2) rapid degradation in vivo which restricts the activity of BPL mainly to the site of application. These data are compared with other studies in which both routes of application were applied. BPL induced translocations in stored spermatozoa when injected, but not when fed. This finding seems a logical consequence of (1) the difference in effectiveness of the two routes of application for BPL, and (2) the existence of different LECs for mutation induction (recessive lethals) and for chromosome breakage (translocations). In Drosophila, the breakage capacity of BPL was one order of magnitude lower than that of MMS, when a comparison was made on the basis of equal recessive-lethal frequencies.


Comparison of the in vitro mutagenicity and metabolism of dimethylnitrosamine and benzo[a]pyrene in tissues from inbred mice treated with phenobarbital, 3-methylcholanthrene or polychlorinated biphenyls. Homogenates of liver, lung, kidney, stomach, small intestine and colon from 8 strains of mice were compared for their ability to metabolize benzo[a]pyrene (BP) and dimethylnitrosamine (DMN) to mutagens. Females of strains CF1, AKR/J, AU/SsJ, DBA/2J, SWR/J, A/J, C3H/HeJ, and C57BL/6J were either untreated or received phenobarbital (PB), 3-methylcholanthrene (MC) or polychlorinated biphenyls (AR) to induce drug-metabolizing enzymes. The effects of these drugs on organ weight and on the amounts of DNA, S-10 protein, and microsomal protein per unit weight of tissue are reported. Salmonella typhimurium TA92 and TA98 were used as indicators of the formation of mutagens. For each organ there was an optimal balance between amount of tissue homogenate and concentration of test compound for maximal yield of revertants. A sensitive radiometric assay of DMN demethylase (DMND) is described which permits measurement of the enzyme in liver, lung and kidney. DMN at 1 mM is used as substrate. Aryl hydrocarbon hydroxylase (AHH) was measured in all tissue using BP as substrate. AR and MC are very good inducers of AHH activity in livers of mice classified as aromatic hydrocarbon responsive, but not in those classified as hydrocarbon nonresponsive. Responsiveness is strain-specific and genetically regulated. Metabolism of BP to mutagens by liver homogenates was correlated with extent of AHH induction. This dimorphism of response of AHH to inducers was present, but less pronounced, in non-hepatic tissues. Basal activities of AHH and DMND were correlated in livers and lungs from untreated mice. DMND activities were increased less than 2-fold by PB, MC or AR treatments. Metabolism of DMN to mutagens was not closely correlated with DMND activities. Strain of mouse, type of tissue and test substance are important variables in assessing the potential effect of microsomal enzyme-inducing agents on the metabolism of mutagenic substances.


Multimodality treatment of narcotic addiction: an overview. In closing, it seems important to add that, when viewed longitudinally, addiction resembles a chronic medical disease. Rehabilitaiton may take several years and improvement rather than cure may be the most reasonable goal. Disappointment at the lack of success in finding an effective cure is common, but a relapsing and remitting course does not necessarily imply failure. Return to treatment may signal continuing efforts and progression toward abstinence. Improvement in current techniques may make remissions longer and relapses shorter. Current work on endogenous opiates (endorphins) may lead to tests which will identify those patients who can achieve drug-free status and those who can function only when maintenance opiates are applied.


Early clinical studies of levo-alpha acetylmethadol (LAAM): an opiate for use in the medical treatment of chronic heroin dependence. Opiate maintenance with methadone has been demonstrated to be an effective treatment modality for many chronic heroin-dependent individuals. However, the many clinical and societal advantages of a longer-lasting medication prompted the development of LAAM, which could be administered three days a week rather than daily. Early Phase II clinical trials of LAAM in about 750 patients have been reviewed and have demonstrated the safety and effectiveness of this drug and confirmed its usefulness for treatment of this chronic disease.


Domains and the hinge region of an immunoglobulin heavy chain are encoded in separate DNA segments. A 6.8-kilobase DNA fragment containing the sequence coding for the constant region of the mouse immunoglobulin gamma1 heavy chain was cloned from total cellular DNA. Electron microscopic and nucleotide sequencing studies showed that the three protein domains and the hinge region are encoded in separate DNA segments.


(+)-Cyanidanol-3 as inhibitor of prostaglandin synthetase. Studies on renal medulla and liver of the rat in vitro and in vivo. (+)-Cyanidanol-3 inhibits the prostaglandin synthetase of the renal medulla and of the liver of rats in vitro and after treatment of the animals with 200 mg/kg. A half-maximal inhibition of the enzyme was obtained with 5 . 10(-5) M cyanidanol. If the microsomal inhibitor CFT1201 is first applied, the inhibitory effect in vivo of 50% is increased to 80%. It is supposed that cyanidanol is converted to metabolites which, according to our earlier studies, activate the enzyme system. An enzyme activity of the rat liver was measured which - with a turnover of 18-20% - was significantly higher than the values obtained by other authors.


Interaction of cations and chelators with the intestinal absorption of tetracycline. The influence of certain compounds on intestinal absorption of tetracycline was tested, using two different in vivo techniques: a) Disappearence of the drug from perfused intestinal segments of the rabbit; b) Measuring urinary excretion in the rat after oral dosage. Ca2+ and Fe2+ ions both reduced the permeation rate of tetracycline by about 30%. In presence of Ca2+ and salicylate ions, leading to ion-pair formation with the antibiotic, intestinal uptake was significantly increased in comparison to experiments where only calcium was present. A more pronounced increase was observed with EDTA. Phosphate ions had different effects on the uptake of the antibiotic in both experimental techniques. Possible mechanisms are discussed.


Effect of antithymocyte globulin on islet of Langerhans transplantation. Lewis rats were treated with streptozotocin to induce hyperglycemia and glycosuria (400-600 mg/dl). Transplantation of approximately 1,000 dissociated islets obtained from collagenase-treated pancreases from 4 donors will promptly correct induced diabetes. Functional survival of islet allografts is related to genetic disparity between donor and recipient strains. In the closely matched Fisher-to-Lewis combination, islets functioned for a mean of 4.2+/-1 days while in the AgB-incompatible Wistar/Furth-to-Lewis combination, islets functioned for a mean of only 2.1+/-0.5 days. Treatment of recipients with antithymocyte globulin (ATG) for 3 days extended islet survival to a mean of 11.8 +/- 1.9 days in the Wistar/Furth-to-Lewis combination and to as long as 184+/-87.5 days in the Fischer-to-Lewis combination. ATG may have a role in trials of clinical islet transplants.


Pyrogenic renal hyperemia: the role of prostaglandins. The intravenous administration of triple typhoid vaccine to anesthetized dogs resulted in a significant increase in renal blood flow accompanied by a modest decline in systemic blood pressure. This renal hyperemia was associated with elevated renal secretory rates of renin and prostaglandin E and F. Measurements of the intracortical distribution of radiolabeled microspheres revealed a progressive decrease in outer cortical blood flow rates and a progressive increase in inner cortical flow rates. When meclofenamate, an inhibitor of prostaglandin synthetase, was administered concomitantly with triple typhoid vaccine renal hyperemia did not develop. The renal renin secretory rate increased modestly and intracortical renal blood flow was not redistributed. The increased renal blood flow after triple typhoid vaccine administration to unanesthetized dogs was also reversed by meclofenamate. The marked increase in prostaglandin secretion by the kidney during renal hyperemia following triple typhoid vaccine administration (pyrogen), and the effect of meclofenamate, is consonant with a role for increased renal synthesis and release of prostaglandins.


The influence of early protein-calorie malnutrition on neuronal and glial protein synthesis. An experimental study on rats. The effect of pre- and postnatal undernutrition, produced according to the method of Chow and Lee (3), on the rate of protein synthesis in the brains of rats 11, 21, 34 and 90 days of age was studied by measuring the incorporation of L-[14C]valine in vivo and L-[3H]lysine in vitro. Both in vivo and in vitro experiments were performed with high concentration of the precursor to decrease the effects of pool variations and protein degradation. Particular interest was given to the effects of this form of early protein-calorie malnutrition (PCM) on neuronal and glial cells which were isolated from the brains by gradient centrifugation. Brain protein synthesis measured in vivo which showed a peak at 21 days in both animal series, was depressed by PCM at 11 days but stimulated at 34 days of animal age. Small effect was observed in the 90-day-old animals. A similar response as in whole brain was seen for neuronal cells, while glial cells showed a different reaction. Studies of in vitro protein synthesis did not reveal appreciable effects of undernutrition in whole brain. Both neuronal and glial cells showed a moderate but not statistically significant elevation of protein synthesis in animals subjected to early PCM.


[A case of cerebral tuberculoma (author's transl)]. A 27-year-old woman was admitted to other hospital for acute pleuritis in May 1977. She suddenly had a focal epileptic seizure in the face with loss of consciousness on July 10, 1977. The same episodes of seizure occurred on Aug. 8, on Oct. 26, on Nov. 22, 1977. She was admitted to our hospital on Dec. 12, 1977. Neurological examinations showed no abnormality. Chest X-ray film showed bilateral severe thickening of the pleura. Plain skull films showed normal findings. Enhanced CT scanning showed a homogenous irregular contour of high density area surrounded by low density area in the right frontal region. The lateral ventricle was slightly shifted to the left side. 99mTc brain scan also detected a spherical abnormal uptake in this area. Right carotid angiography showed no abnormal vessels and increased vascularities. On Nov. 22, 1977, a craniotomy was made over the right fronto-temporal bone, and a walnut sized tumor in the frontal subcortex was totally removed successfully. Histologically, the tumor was diagnosed as brain tuberculoma. The antituberculous therapy (AB-PC, INAH, Rifampicin), high doses of gammabenin, and steroid were given. About four months later, she was in good health without neurologic deficits and returned to her work. The literature was reviewed, and the value of CT scan and RI scan in the diagnosis of cerebral tuberculoma was emphasized.


[Benign infantile epilepsy].

[Benign infantile epilepsy]. The authors describe clinical and electroencephalographic analysis of 23 cases of banign infantile epilepsy. The characteristic features of seizures, the clinical course, and the EEG findings with presence of spikes and/or spikes and slow waves in leads from the motor and midtemporal areas are discussed. Frequent influence of factors releasing the first and subsequent seizures and a history of risk factors during pregnancy, and perinatal period, and early acquired predisposition were demonstrated. Follow-up showed that seizures disappeared at the age of puberty. All observations suggest the possibility of separation of benign infantile epilepsy as a particular form of this disease.


Posttraumatic epilepsy and CT scan.

Posttraumatic epilepsy and CT scan. Among 83 head-trauma cases examined by CT scan in a later year, 41 were included in a seizure group of those who clinically showed late epilepsy and who obviously showed epileptic discharge such as spike or spike and wave in EEG after trauma, and 42 were included in a nonseizure group of those who had some sequelae such as abnormal findings in EEG or neurologic defects: the CT findings of these 83 cases were collected and compared with clinical findings, EEG, and other data. The CT findings of these cases were divided into five groups: (A) a normal group; (B) a group showing partial or unilateral ventricular dilatation; (C) a group showing porencephaly in the cerebral parenchyma; (D) a group suspected of cortical atrophy; (E) a group of other cases. Group D contained 44.3% of the cases, and was the largest group; the frequency of seizure was highest in Group C. The CT classification reveals the contradiction of the conventional definition of posttraumatic epilepsy and also poses some problems concerning the disease. CT scan is mostly applied to head trauma in the acute stage, and as for trauma in the chronic stage there are a few reports on chronic subdural hematoma and post-traumatic hydrocephalus. We noticed posttraumatic epilepsy among the sequelae of trauma, and then analyzed CT findings of the epilepsy: the results are reported here.


Studies of cultured human and simian fetal brain cells. I. Characterization of the cell types. Explant cultures of the cerebral subventricular zone and cerebellar external germinal layer were established from fetal human, rhesus and cynomolgus monkey brains. Using comparable gestational ages, the morphogenesis of the cultures from these three sources was almost indistinguishable. Four cell types were distinguished by electron microscopy. Germinal cells or neuroblasts were confined largely to the primary explant and extended into a transitional outgrowth region. Astrocytes, which stained for glial fibrillary acidic protein, grew out of the explants and these could be distinguished from the large, mesenchymal epithelioid cells. A fourth cell type, not identified in previous studies, had the ultrastructural characteristics of an oligodendrocyte, but did not produce myelin in these culture conditions.


Neuroradiology of ossification of the posterior longitudinal spinal ligament. Comparative studies with computer tomography. Comparative neuroradiologic studies of the posterior longitudinal spinal ligament were performed in 15 cases showing myelopathy. On visualizing the ossified foci CT scan was found to be superior to the conventional roentgenograms, and detailed evaluation of the constricted spinal canal with related neurologic deficits became possible. CT analysis must be performed to differentiate spondylotic myelopathy, which is essential when considering operative intervention.


The cellular origin of lysosomal enzymes in the plaque in multiple sclerosis: a combined histological and biochemical study. Using a combined biochemical and histological approach certain conclusions can be drawn as to the origin of the increase in lysosomal enzymes in white matter from MS brains. Firstly, there is a gradient of lysosomal enzyme activity, plaque greater than periplaque greater than macroscopically normal white matter, which appears to be independent of the stage of evolution of the plaque. The most consistent change in cellular composition within and around all plaques is a marked astrocytosis. It thus appears that the increases in lysosomal enzymes can be mainly attributed to reactive astrocytes; macrophages and the cells of the perivascular infiltrate making only a limited contribution. Secondly, only one of the enzymes tested was significantly elevated in histologically normal white matter, i.e. n-acetyl-beta-D-glucosaminidase. Since this enzyme appears to be a particularly sensitive marker for astrocytes this may be indicative of proliferation of astrocytes in so-called normal white matter.


Catheter cervical vertebral venography.

Catheter cervical vertebral venography. Cervical vertebral venography using catheterzation via the femoral vein was carried out in 78 cases. In disc disease the internal vertebral venous plexus (IVVP) are interrupted at single or multiple levels, and sometimes completely blocked. In ossification of posterior longitudinal ligament, the IVVP are separated bilaterally and interrupted at multiple levels due to centrally situated ossification and associated osteophytes. Venography helps to determine the upper and lower limits of laminectomy, and the necessary sites of facetectomy. The IVVP in the thoracic region were clearly opacified in 86% of 37 normal selective azygograms.


Secondarily generalized convulsive seizures induced by daily amygdaloid stimulation in rhesus monkeys. Amygdaloid kindling in rhesus monkeys resulted in development of secondarily generalized convulsive seizures in an average of 196 days. Prior pharmacologic (bemegride) kindling accelerated this seizure development in one animal. None of the animals reached the stage 5 primary generalized seizure of baboons (Papio papio), even after 400 daily amygdaloid stimulations. Seizure stage instability, with frequent regression to an earlier stage, and the difficulty of establishing a generalized seizure triggering threshold in most of the rhesus monkeys, contrasts with our experiences in Papio papio. Thus, differences in the speed of kindling and in the quality of kindled convulsion between rhesus monkeys and epileptic baboons probably reflect the presence or absence of an epileptogenic predisposition in these two species. The difficulty of developing convulsive seizure in rhesus monkeys suggests that this species is particularly suited for the study of partial complex seizure. These studies indicate that the abrupt onset of human epilepsy with a fully developed convulsive seizure must represent and overwhelming central pathophysiologic event resulting from an endogenous, exogenous or a combined insult interacting with a genetically predisposed seizure susceptibility.


Quantitation of IgG, IgA and IgM in the CSF by radioimmunoassay. A radioimmunoassay (RIA) for quantitating IgG, IgA and IgM in unconcentrated CSF has been developed. The amounts and percentages of these immunoglobulins in CSF from 31 normal individuals were determined. Using these values as normal, CSF from patients with syphilis, encephalitis, subacute sclerosing panencephalitis (SSPE), and multiple sclerosis (MS) was studied. Abnormalities were detected, indicating the potential relevance of more extensive study of the CSF immunoglobulins. CSF from patients with myotonic dystrophy and myasthenia gravis was normal. RIA was compared with rocket electroimmunodiffusion (EID) for the quantitation of IgG. Although RIA consistently gave lower absolute values, both assays reliably detect elevated IgG in CSF. However, an advantage of RIA is its capacity to quantitate IgA and IgM.


Pyruvate dehydrogenase deficiency in spinocerebellar degenerations. To study the incidence of abnormalities of the pyruvate (PDH) or ketoglutarate (KGDH) dehydrogenase complexes in patients with spinocerebellar degenerations, we measured the activities of PDH and KGDH in platelet-enriched preparations from the blood of 14 patients. Low PDH was found in 6 of the 14 patients; low KGDH was found in 2 of the 6. PDH-normal and PDH-abnormal patients could not be distinguished by clinical criteria. These results extend previous studies, which suggested abnormalities of pyruvate oxidation in patients with hereditary ataxias. The data imply that deficient activity of the PDH complex may be associated with spinocerebellar degenerations, and that the clinical phenotypes of the inherited ataxias can be associated with several genotypes.


Effects of protein deficiency and food restriction during gestation in rats on maternal and fetal plasma and pituitary thyrotropin levels. The effects of protein deficiency and food restriction during pregnancy on maternal and fetal plasma and pituitary thyrotropin (TSH) levels were investigated on day 20 of gestation. The same parameters were also determined following administration of exogenous thyrotropin-releasing hormone (TRH). Maternal plasma and pituitary basal TSH concentrations were significantly elevated in protein deficiency. TRH injection to protein-deficient dams caused a marked reduction in pituitary TSH concentration, suggesting that the elevated plasma TSH seen in uninjected dams might be due to decreased metabolic clearance rather than to hypersecretion by the pituitary. Food restriction resulted in significant lowering of plasma TSH, but did not alter pituitary TSH in comparison to that of control dams. TRH administration had no effect on pituitary TSH concentration in food-restricted and control dams. Pituitaries of fetal young of protein-deprived dams were significantly smaller and contained significantly less total TSH, accompanied by a slight reduction in circulating plasma TSH. These observations are suggestive of developmental and functional retardation of the fetal pituitary. Fetal pituitary TSH was unaffected by TRH administration to control and food-restricted dams whereas, in young of protein-deprived females, total gland TSH was reduced.


Some biochemical observations on biotin deficiency in the rat as a model for human pyruvate carboxylase deficiency. Biotin deficiency was induced in newborn rats by feeding pregnant rats a biotin-deficient, avidin-rich diet. Signs typical of biotin deficiency are seen as soon as the young rat develops its fur. Deficiency of pyruvate carboxylase (PC) activity in the brains of the young animals (70%) is higher than has been reported before. The highest PC activity is found in the brain stem of control and biotin-deficient rats. Normally fed rats show, shortly after birth, a maximum in liver PC activity, which is absent in biotin-deficient animals. The biochemical changes observed in these rats seem to indicate that a specific deficiency of PC activity was induced as exemplified by hyperlactatemia and hypoglycemia and the absence of increased plasma concentrations of propionic acid and beta-methylcrotonic acid. This offers the possibility to use biotin deficiency in the rat as an animal model for patients with lactic acidosis in whom PC deficiency has been postulated.