Compartmental syndromes in which the skin is the limiting boundary. Following closed fasciotomy, skin may become the limiting boundary of extremity swelling. The resulting increase in pressure within the limb may threaten its survival. Realizing this potential complications, we reserve closed fasciotomy for those cases in which only moderate swelling is anticipated. Following this procedure the patient is observed closely for evidence that decompression dermotomy is indicated. Patients in whom severe swelling is present or anticipated are treated with fasciotomy and primary dermotomy. Wounds are closed by either primary or delayed skin graft. This approach has proven useful in the management of traumatized or vascularly embarrassed limbs in which swelling may compromise extremity viability.


Effects of metiamide on the human stomach. 1. The effect of metiamide on gastric acidity in man has been studied. Solutions of hydrochloric acid or glucose were instilled into the stomach and the subsequent rates of gastric secretion and emptying, and the disappearance of acid within the stomach, were measured. 2. Metiamide inhibited the gastric secretory response to the instilled acid and glucose solutions but did not change the overall pattern of emptying of the instilled solutions. 3. During administration of metiamide, there was a net loss of acid from within the gastric lumen. The rate of disappearance of acid from the instilled acid solution was small and not sufficient in magnitude to account for the metiamide-evoked decrease in the concentration of acid secreted in response to pentagastrin. 4. We conclude that metiamide does not inhibit gastric secretion by altering the 'barrier' function of the gastric mucosa.


Effect of chlorhexidine on dental plaque and gingivitis in mentally retarded children. The purpose of the investigation was to determine the effect of chlorhexidine mouthrinses as a supplement to toothbrushing in the plaque control of mentally retarded children. Fifty-four mentally subnormal children 7-14 years of age took part in the investigation. During the first period, half of the children rinsed their mouths with 0.2% chlorhexidine gluconate solution twice a day. The rest of the children used a placebo mouthrinse. After a n 8-week interval a "cross-over" experiment was carried out during which a 0.1% chlorhexidine solution was used. Plaque and gingival indices were scored at the beginning of each period, after 3 weeks, and at the termination after 6 weeks. The results revealed that mouthrinses with 0.1% as well as 0.2% chlorhexidine gluconate reduced plaque and gingivitis in mentally retarded children. The results were statistically significant (P is less than 0.05) for both concentrations. Furthermore, the investigation confirmed the occurrence of certain side effects such as discoloration of teeth and tongues.


Clinical evaluation of the effect of a proteolytic enzyme mouthwash on plaque and gingivitis in young adults. One hundred and thirty-one young adults were used in a controlled study to determine whether a proteolytic mouthwash produced from B. subtilis could help remove existing plaque, decrease the rate of plaque accumulation or reduce the clinical signs of gingivitis. These subjects were stratified by means of the Gingival Index and the Shaver-Schiff Plaque Index into severe or mild groups. These groups were further divided in a random fashion into treatment and placebo groups. The treatment group rinsed with a proteolytic mouthwash consisting mainly of neutral and alkaline proteases and amylase. A placebo mouthwash was used by the control group. The results of this investigation indicate that there is no statistically significant reduction either in existing plaque or in the rate of plaque accumulation when this proteolytic enzyme mouthwash is used. Furthermore, in the treatment group the degree of gingivitis as measured by the GI was not reduced.


Variables and criteria in prevalence studies of dental anomalies of number, form and size. Prevalence studies of dental anomalies of number, form and size have varied greatly in their findings. The purpose of this paper is to demonstrate from published studies the effect of variables in sampling techniques and examination methods and to suggest diagnostic criteria. In sampling the ethnic background, the sex distribution, age and derivation of the group studied are shown to be important, but the consumption of near optimum concentrations of fluoride in drinking water does not appear to influence findings. For the examination, a dental history is important and full radiographic coverage essential. Findings should be recorded separately for each dentition, while these anomalies should be studied as a group rather than singly. Diagnostic criteria are proposed for supernumerary teeth, hypodontia, invaginated teeth, double teeth, megadontia and microdontia.


Natural language storage and retrieval of medical diagnostic information. Experience at the UCLA hospital and clinics over a 10-year period. A natural language storage and retrieval system initially designed for pathology reports has been in operation for ten years at UCLA Hospital and Clinics. The original system has been improved to provide a thesaurus processor with added capabilities for expanding search request terms and a newly developed set of search programs with user options that make complex and more accurate retrievals possible. Summarized diagnostic statements or impressions from five specialities (Surgical Pathology, Bone Marrow, Autopsy, Nuclear Medicine, and Neuroradiology), are automatically encoded by referencing a master computer dictionary containing a unique numeric code for each English word. Input and retrievals are batch, off-line operations in free text, and are currently processed on the IBM 370/145. User acceptance is high, quality of retrievals improved, and cost is nominal. This paper describes an expanded natural language system which in now providing a viable form of information storage and retrieval for research, medical education, patient care, quality control, statistics and administrative purposes.


Computer aided nystagmus analysis.

Computer aided nystagmus analysis. The electronystagmogram (ENG) is analyzed with the assistance of a PDP-8 minicomputer for calculating the instantaneous slope, average slope, lead frequency, lag frequency and cycle frequency of both the fast and slow wave components of the ENG. The ENG data is first digitized and displayed on a storage scope in order to permit the operator to select an epoch of data. The results are then displayed on the scope, and the mean and variance of the important parameters are outputted on the teletype. The programs include a system for storing a large library of records.


Computer graphics--three dimensional reconstruction of thalamic anatomy from serial sections. This paper describes an interactive program which uses computer graphics techniques to reconstruct a three dimensional representation of thalamic anatomy from two dimensional serial secretion. Figures traced on a Rand tablet, connected to a DEC-340 display, are digitized and scaled. The three dimensional display capabilities of the Adage AGT-30 are used to present the reconstructed structures. Two dimensional cross sections of an arbitrary plane may also be displayed. The program has applications in stereotaxic surgery, teaching neuroanatomy, and may be used to reconstruct other anatomic structures from serial sections.


Hematology of the neonatal calf. II. Response associated with acute enteric infections, gram-negative septicemia, and experimental endotoxemia. The hematological responses of neonatal calves with acute enteric infections were compared to the responses of calves with septicemia and experimentally induced endotoxemia. The mean hematocrit of septicemic calves (45.0% +/- 7.8) was similar to that of calves with primary enteric infections (45.3% +/- 7.0) but the total plasma protein concentration of septicemic calves (5.8g/100 ml +/- 0.69) was significantly lower than that of calves with primary enteric infections (8.6 g/100 ml +/- 1.5). The difference in total plasma protein concentration was due primarily to the hypogammaglobulinemia observed in septicemic calves. The leukocytic response to septicemic calves was similar to that of nonsepticemic calves with enteric infections. In most calves of both groups, moderate but significant leukocytosis and neutrophilia were observed. Marked leukopenia was observed terminally in 2 of 9 septicemic calves but in only 1 of 26 calves with primary enteric infections. Leukopenia was a characteristic finding in calves with experimental endotoxemia. Leukopenia developed within 5 minutes following intravenous administration of endotoxin and persisted until death in most calves. In calves which lived 12 hours or longer, there was a biphasic leukocytic response with leukocytosis being observed 24 hours following endotoxin administration.


Glucose-insulin-potassium (GIK) therapy for ischemic heart disease. In 1912 Goulston advocated glucose therapy for several different kinds of heart disease, and in 1933 Shirley-Smith recommended glucose and insulin for coronary artery disease. Thirty years later, Laborit noted that treatment of rabbits with glucose and insulin prevented ventricular fibrillation induced by potassium chloride solutions. Sodi-Pallares et al, pioneers in glucose-insulin-potassium (GIK) therapy for heart disease, showed not only that potassium may be a major excitant in the genesis of ventricular tachycardia in the ischemic heart but that GIK solution was capable of enhancing oxidative phosphorylation in the ischemic heart. Interest in GIK therapy for ischemic heart disease has been renewed as the effects of GIK solutions on myocardial infarct size, metabolism and electrical properties are better understood. In this paper, selected new information regarding the actions of GIK and the clinical applications will be reviewed.


Pneumoperitoneum following tension pneumothorax. Report of two cases. Two cases of pneumoperitoneum following tension pneumothorax are described. Lungs in both patients had identifiable pathology and were ventilated with high inflation pressure and moderate positive end-expired pressure (PEEP). Laparotomy was performed in both patients with no evidence of intra-abdominal viscus perforations. A possible mechanism for the production of pneumoperitoneum is discussed.


The diagnosis of brain depression in the presence of severe multisystem disease--a case study. Brain depression in a patient with severe multisystem disease can be a diagnostic challenge, particularly when the patient is maintained on artificial life-support systems. A case report is presented of a 13-year-old girl with severe pneumonia who was treated with prolonged cardiopulmonary bypass during which time she developed a clinical picture simulating brain death with marked depression of cerebral cortical activity on two successive EEGs. Following correction of some of her metabolic defects, the patient showed marked improvement of cortical function. Multisystem disease can be so severe as to produce a clinical picture of brain death. We wish to emphasize that brain hypofunction of depression is best evaluated by both clinical examination and the EEG, and that neither one alone is sufficient to conclude that cerebral death has occurred.


A method for preparing chromosomes from peripheral blood in the mouse. We have developed a simple, reproducible microtechnique for obtaining metaphase chromosomes from peripheral blood of live mice. The method has been successful with mice of several different genetic backgrounds and has been repeated in three other laboratories.


Isosorbide dinitrate and cardiovascular adaptation to exercise. Sixteen men with well-documented angina pectoris and without previous myocardial infarction performed a multistage exercise stress test to determine their levels of exercise-induced limitations, characterized by onset of chest discomfort or electrocardiographic ischemic changes, or both. Following a control study, each subject was assigned randomly to either a placebo- or vasodilator-treated group, received chewable medication, and was retested 30 minutes after chewing the medication. Blood pressure, heart rate, and electrocardiographic changes were measured during rest, peak exercise, and recovery. A phonocardiogram, carotid-pulse contour, and single-lead electrocardiogram were recorded simultaneously at supine rest before and immediately after exercise, and systolic time intervals were measured. Results indicated that chewable isosorbide dinitrate reduced systolic blood pressure and the triple product (systolic blood pressure X heart rate X ejection time) significantly during rest and reduced the left ventricular ejection time corrected for heart rate both at rest and peak exercise; no significant differences were observed in the placebo group. The ability to achieve an increased workload was observed in both groups, and the threshold for ischemic manifestations occurred at comparable triple-product levels in both during pretreatment and posttreatment studies.


Unilateral lung function. Comparison of the lateral position test with radionuclide ventilation-perfusion studies. Twenty-seven patients underwent studies of unilateral lung function by the lateral-position test (LPT) and by computer-analyzed radionuclide imaging of ventilation and perfusion. The patients were divided into two groups, symmetric or asymmetric, on the basis of the physical examination of the chest and the chest radiograph. In patients with symmetry, the estimate of unilateral lung function by the LPT and isotopic estimates for unilateral lung volume, unilateral distribution of tidal volume, and unilateral perfusion, agreed within 2 percent, 4 percent, and 3 percent, respectively. In patients with asymmetry, the differences were 9 percent, 8 percent, and 13 percent. In settings of marked unilateral ventilation-perfusion imbalance, the LPT primarily reflected ventilation. Prediction of unilateral ventilatory function based upon the LPT and spirometric measurements agreed closely with unilateral ventilation determined isotopically by 133xenon, even in the presence of chronic obstructive lung disease. Our results confirm that the LPT provides valid information about unilateral lung function.


A systems approach toward the functional connections of attachment and fear. Proceeding from J. Bowlby's attachment theory and W.A. Mason's arousal theory, a control model is developed that is capable of accounting for basic processes of mammalian social behavior. In particular, the model simulates the transition from a state of attachment to familiar conspecifics and fear of strangers to a stage of detachment from the familiar and exploration of the stranger. Some of the model's predictions were tested in animal experiments and proved to be in satisfactory correspondence with the behavior actually observed.


Distribution of 18+28S ribosomal genes in mammalian genomes. In situ hybridization with 3H 18S and 28S ribosomal RNA from Xenopus laevis has been used to study the distribution of DNA sequences coding for these RNAs (the nucleolus organizing regions) in the genomes of six mammals. Several patterns of distribution have been found: 1) A single major site (rat kangaroo, Seba's fruit bat), 2) Two major sites (Indian muntjac), 3) Multiple sites in centromeric heterochromatin (field vole), 4) Multiple sites in heterochromatic short arms (Peromyscus eremicus), 5) Multiple sites in telomeric regions (Chinese hamster). - The chromosomal sites which bind 3H 18S and 28S ribosomal RNA correspond closely to the sites of secondary constrictions where these are known. However, the correlation is not absolute. Some secondary constrictions do not appear to bind 3H ribosomal RNA. Some regions which bind ribosomal RNA do not appear as secondary constrictions in metaphase chromosomes. - Although the nucleolus organizing regions of most mammalian karyotypes are found on the autosomes, the X chromosomes in Carollia perspicillata and C. castanea carry large clusters of sequences complementary to ribosomal RNA. In situ hybridization shows that the Y chromosome in C. castanea also has a large nucleolus organizing region.


The function of the retina in the perfused eye. The data show that the enucleated eye of the cat can be maintained in apparently physiologically functioning condition by appropriate arterial perfusion. Under appropriate conditions, photically evoked electrical mass responses can be recorded from various parts of the isolated, perfused eye for 8 to 10 hours. ERGs as well as responses from axonal bundles of the optic nerve exhibit shapes, amplitudes and time courses comparable to their counterparts in vivo. Homeostasis of the perfusion ensures the stability of these light-evoked electrical responses. Transient changes in biophysical parameters of the perfusate rapidly induce marked, although reversible, changes in the amplitudes of b-waves of the ERGs. Increases or decreases in the flow rate of the perfusate induce parallel increases or decreases in the amplitudes of the b-waves as well as of the optic nerve responses. Similar alterations in the oxygen concentration of the perfusate induce similar and proportional changes in the amplitudes of the b-waves. It is concluded, that low flow rates of hemoglobin-free perfusate induce hypoxia; consequently, acceleration of the flow can compensate for hypoxia in a certain range. Previous studies on the effects of and recovery after transient hypoxia in mammalian retina are in concordance with the present data. Progressive decrease of temperature induces gradual and reversible reductions in the amplitudes of the b-waves and increases their latencies and peak-times. It is suggested, that initial hypothermia, which occurs during the period of cannulation, reduces the deliterious effects of the coincident unavoidable hypoxia on retinal neuronal elements. Since light-evoked electrical responses can be maintained for many hours in these preparations and since movements of cardiovascular and respiratory origin, invariably present to varying extent in the in vivo experiments, are eliminated, this preparation is suitable for intracellular recordings from neuronal elements of the retina. Potentials were recorded from cells in various layers of the retina of the cat; intracellular recordings from horizontal cells (S-potentials) are described in detail. Spectral analysis of S-potentials allowed to distinguish between three types according to their inputs: a mixed, rod-cone type, which was most frequently encountered, a pure cone- and a pure rod-type. Light- and electronmicroscopic investigation of the retina after perfusion revealed that (1) the extent of cellular damage depends on the flow rate of the perfusate; (2) little cellular damage is observed if medium flow rates, which maintain physiologic responsiveness of the isolated eye to light, were applied for two hours; (3) high flow rates applied for two hours, or medium flow rates applied for 7 hours appear to induce cystic changes in the pigment epithelium, but only minor changes in the cells of the inner nuclear layer.


[Etofibrate and clofibrate in a double-blind trial on patients with raised serum-lipid levels (author's transl)]. In a clinical trial of 21 patients with hypercholesteraemia and (or) hypertriglyceridaemia, the effects of etofibrate and clofibrate were compared with one another and against a placebo: both drugs lowered triglyceride levels significantly, but etofibrate also had a stronger cholesterol-lowering effect. Both substances were well tolerated.


[T and B lymphocytes in skin changes of cutaneous lymphoma (author's transl)]. In 30 patients with benign or malignant lymphoreticular proliferation of the skin (38 skin biopsies) the percentage of immunoglobulin-bearing (B) and of spontaneous rosette-forming (T) lymphocytes was determined in cell suspension from homogenized tissue. Four main classes of cutaneous lymphoma could be differentiated: lymphocyte-rich (more than 50% of the infiltrate cells, predominantly B-lymphocytic, predominantly T-lymphocytic, mixed B and T-lymphocytic), lymphocyte-depleted (less than 50% of infiltrate cells), reticulo-histio-monocytic infiltrates, and reticulo- or lymphosarcoma. A definite statement was not possible (other than in leukaemic processes) if the accumulation of lymphocytic cells represented the primary malignant process rather than a concomitant inflammatory reaction. A clinically useful differentiation was into hyperplasia, paraplasia and neoplasia, as this takes into account different histopathological characteristics of cutaneous lymphomas (reactive hyperplastic/autonomic proliferative: benign/malignant; reversible/irreversible; systemic/nonsystemic; metastasizing/nonmetastasizing).


[Localization of urinary-tract infection by demonstrating antibody-coated bacteria in urine (author's transl)]. The immunofluorescence test for demonstrating antibody-coated bacteria as a direct method of localizing urinary-tract infection was performed on 34 patients, results being compared with the Fairley test. Mid-stream urine contained at least 10(5) bacteria/ml in all patients. The direct localization method revealed upper urinary-tract infection (renal bacteriuria) in 18 patients, lower urinary-tract infection (cystitis) in eight. Presence of antibody-coated bacteria correlated well with renal bacteriuria, such antibody having been demonstrated in all of the eighteen patients with renal bacteriuria but in none of the eight with lower urinary-tract infection (cause located in the bladder). The test has proved to be highly sensitive method for differentiating between upper and lower urinary-tract infection.


[Scanning electronmicroscopic studies on the behavior of so-called caustic-adhesive composite resins]. Two new caustic-adhesive composite resins (Concise-Enamel-Bond and Nuva-Seal/Nuva-Fil) were tested in experimentally prepared flat cavities in extracted human teeth under the scanning electron microscope. On the basis of the findings, possible failures with this filling technique resulting from insufficient adhesion of the "sealer" at the enamel are discussed, and practical proposals worked out (utilization of rubber dam, final coating with the sealer to improve surface quality and prevent marginal gaps).


[The position of the sublingual bar].

[The position of the sublingual bar]. Improper preparation of sublingual bars favors the development of caries and periodontal disease. It is tried to find methods for determining optimum shape and location of the bars.


[Clinical studies on the short term use of "Kavosan"]. The inflammation and plaque-inhibiting effect of KAVOSAN was tested in 43 probands with gingivitis in two test series. Irrespective of the type of oral care, a statistically significant improvement in the degree of inflammation and a reduction of plaque were observed after application of the active agent when compared to a placebo preparation, both in cases where plaque was removed as well as cases where plaque was not removed.


[The usefulness of lateral teleradiographs in prosthodontics]. Studies in 56 dentulous and 48 edentulous patients (the latter having total dentures) showed that in addition to data that can be determined accurately, less informative data can be found that is, however, significant for prosthetics.


[Mesenchymal tumors of the mouth].

[Mesenchymal tumors of the mouth]. The author describes rare cases of malignant tumors of mesenchymal origin in the oral cavity. These tumors have a poor prognosis and the majority is unresponsive to radiation. Primary therapy must always be surgery. Radiation therapy may only be applied for palliative purposes in inoperable cases, or as a postoperative treatment. An exception is the nongeneralized reticulum cell carcinoma originating from the alveolar process in which radiation may be regarded as the primary therapy of choice.


Post-coital contraceptive and uterotrophic effects of luteinizing hormone releasing hormone. LRH, administered subcutaneously (s.c.) or orally (p.o.) to female rats, was capable of interfering with pregnancy when given on various days of gestation. A 100% inhibition of pregnancy was demonstrated at daily s.c. doses of 1000 mug/rat administered over days 1-7; LRH also was effective as an interceptive, terminating pregnancy in 100% of rats when delivered from days 7-12 of pregnancy at a daily dose of 1000 mug/rat s.c. or p.o. An 80% inhibition also was observed in rabbits administered LRH from days 1-7 at a total dose of 1000 mug/kg, s.c. Uterotrophic studies demonstrated that LRH, administered s.c. to intact immature mice, produces a dose-related increase in uterine and ovarian weight and initiates vaginal opening. The hypothalamic hormone also produced a dose-related increase in uterine weight in ovariectomized mice and hypophysectomized rats. The data suggest that LRH has a post-coital contraceptive effect, presumably acting via hyperstimulation of the hypophysial-ovarian steroid-uterine axis, and/or by a direct extrapituitary (uterine) effect.


Ultrastructural localization of somatostatin in pancreatic islets of the rat. In order to determine the precise localization of somatostatin (SRIF) in the pancreas, electron microscopic immunocytochemistry was performed on thin sections of whole pancreas and isolated pancreatic islets of the rat using the peroxidase anti-peroxidase technique. SRIF was localized in secretory granules concentrated in cells sparsely distributed near the periphery of the islet. The granules were closely applied to their limiting membrane, exhibited moderate electron density, and were smaller than those in other islet cells. The location and relative number of SRIF-containing cells as well as the morphology of the granules suggest that SRIF is present in delta cells or a subgroup with small granules. These results provide evidence that SRIF is present in a discrete granule population in a specific type of secretory cell in the pancreatic islets.


Immediate release of prolactin and biphasic effects on growth hormone release following electrical stimulation of the median eminence. The median eminence (ME) region of the hypothalamus was electrically stimulated through permanently implanted electrodes in 1 unanesthetized sheep. Plasma concentrations of GH and prolactin (PRL) were measured at 10-min intervals before, during and after 30-min periods of electrical stimulation or sham procedures. The onset of ME stimulation decreased plasma GH in all 17 cases in which prestimulation GH levels were 1.0 ng/ml or higher. In all 27 cases of ME stimulation, plasma GH never increased during the 30-min stimulation period. However, spontaneous GH increases were noted during sham procedures in 9 of 31 cases. The termination of ME stimulation was followed within 10--20 min by markedly increased GH levels in 24 of 27 cases. All 4 ewes responded to electrical stimulation with comparable biphasic effects on GH release even though electrode locations varied slightly. These results indicate localization and stimulation-induced release of endogenous neurohormones in the ME region with activities inhibiting the release of GH (GHIF). The secondary increase in plasma GH following the end of ME stimulation indicates a reversal of conditions unfavorable to GH release. This reversal may represent a rebound from the inhibitory action of GHIF or the post-inhibitory action of a hypothalamic GH-releasing factor or both. In 3 ewes with electrodes implanted in the region of the anterior ME, the onset of stimulation increased plasma PRL within 10--20 min in 17 out of 20 cases. The electrode in the fourth animal was located in the posterior ME, and when all cases were considered, stimulation through this electrode did not significantly increase or decrease plasma PRL. However, in 5 out of 7 cases stimulation of the posterior ME decreased plasma PRL. In summary, these results indicate the presence in the anterior ME of andogenous neurohormones with PRL-releasing activity (PRF). Conclusions about the posterior ME are equivocal, but this region may contain a PRL-release inhibiting compound in combination with PRF.


Prostaglandin E2-induced release of LHRH into hypophysial portal blood(1). Prostaglandin E2 (PGE2) was infused into a lateral ventricle of adult male rats or infused into a hypophysial portal vessel. Intraventricularly administered PGE2 stimulated the release of LH, FSH, and prolactin but not TSH. Intraventricular infusion of the control solution did not alter the basal release of any of these hormones. PGE2 was found to be a potent stimulator of LH release, but larger quantities were needed to stimulate the release of FSH or prolactin. In addition, lateral ventricle infusion of 5 mug or 20 mug of PGE2 stimulated a 2- to 3-fold increase in the concentration of LHRH in hypophysial portal plasma but did not affect LHRH levels in arterial plasma. PGE2 infused into a hypophysial portal vessel at a rate of 0.167 mug/min for 30 min, or infusion of the control solution, resulted in similar changes in the concentration of FSH, LH, and prolactin in arterial plasma. The results of this investigation suggest that PGE2 stimulates the release of gonadotropins in vivo by enhancing the release of LHRH. The portal vessel infusion studies do not support a direct stimulatory effect of PGE2 on the pituitary gonadotrophs.


Evidence of sequential metabolic cleavage of proglucagon to glucagon in glucagon biosynthesis. Following a 30 min preincubation in medium containing no isotopes, anglerfish islet tissue was incubated in the presence of [3H]tryptophan and [14C]isoleucine for 20 min. A portion of the tissue was removed for immediate extraction. The remainder was washed thoroughly with unlabeled medium and post-incubated in medium containing an excess of unlabeled tryptophan and isoleucine for varying periods of time. The distribution of radioactive proteins in alcoholic tissue extracts was analyzed by gel filtration and polyacrylamide gel electrophoresis. The distribution of immunoreactive glucagon was determined by radioimmunoassay. Following the 20 min pulse incubation, only proinsulin was labeled with [14C]isoleucine. Two glucagon immunoreactive molecules, one larger than proinsulin (mol wt near 11,400) and the other slightly smaller than proinsulin (mol wt near 9,000), were the primary proteins labeled with [3H]tryptophan following the 20 min. pulse. During chase incubations of increasing duration, 3H-radioactivity appeared in a glucagon immunoreactive molecule with the approximate molecular size of glucagon and increased with chase time while radioactivity in the 11,400 mol wt tryptophan-labeled molecule decreased. With increasing chase time, the 3H-radioactivity attributable to the 9,000 mol wt tryptophan-labeled molecule initially increased and subsequently decreased which is consistent with the pattern that would be expected for a conversion intermediate. The presence of glucagon immunoreactivity in [3H]tryptophan-labeled molecules having molecular weights near that of proinsulin was established by radioimmunoassay of alternate gel slices following electrophoresis of labeled proteins recovered from the proinsulin containing portions of gel filtration eluates. That [14C]isoleucine became incorporated into insulin and [3H]tryptophan became incorporated into glucagon was established by determination of the distribution of radioactivity in polyacrylamide gels following electrophoresis of labeled proteins recovered from the insulin and glucagon containing portions of gel filtration eluates. These results provide preliminary evidence for sequential metabolic cleavage of proglucagon in glucagon biosynthesis.


Nucleotide and nucleoside stimulation of glucagon secretion. The effects of various nucleosides and nucleotides upon glucagon secretion from the isolated perfused rat pancreas were studied. Increasing glucagon secretion was found with increasing concentrations of exogenous cyclic AMP (2 X 10(-4) M, 2 X 10(-3) M and 1 X 10(-2) M). Stimulation of alpha cell secretion was also found with 2 X 10(-3) M 2'AMP, 3'AMP, 5'AMP, ADP, Adenosine, NADP, and NADPH. One X 10(-3) M cyclic GMP elicited significant glucagon secretion. The pattern of glucagon release was similar in all cases with peak secretion occurring during the 30- to 90-s time period following initiation of the stimulus. No significant increase of glucagon secretion was found in response to ATP, guanosine, 2'GMP, 3'GMP, 5'GMP, GTP, xanthosine, inosine, adenine, xanthine, thymidine, cytidine, ribose, nicotinamide, and uric acid. On the basis of the above results, the structural requirement for stimulation of glucagon secretion appears to be adenine linked to ribose, with phosphate groups being unnecessary. The conclusion of this study is that a new class of compounds capable of stimulating glucagon secretion has been identified, and important questions are thus raised about the mechanism of the action of exogenous cyclic AMP.


Changes of hypothalamic LH-RF content during the rat estrous cycle. Anti-LH-RF serum was produced in rabbits by synthetic LH-RF-BSA conjugate prepard with bis-diazotized benzidine. Employing this antiserum, a radioimmunoassay for LH-RF was established with the assay range from 0.8 to 10 ng/ml. Acid extracts of hypothalami from 4 day cycling rats through various stages of the estrous cycle particularly in the afternoon of proestrus were measured for their LH-RF contents. The hypothalamic LH-RF content was high at 10:00 on the day of proestrus and declined until 17:00 and thereafter, the content gradually increased to reach the basal level. Serum LH showed the highest level at 17:00 on the day of proestrus and fell at 21:00 on the same day. Accompaning this change of serum LH level, pituitary LH content began to decrease at 17:00 of proestrus. These results indicate that LH-RF released in the afternoon of proestrus may participiate to stimulate the preovulatory discharge of LH in the rat.


Two ribose-5-phosphate isomerases from Escherichia coli K12: partial characterisation of the enzymes and consideration of their possible physiological roles. Two physically and genetically distinct forms of ribosephosphate isomerase have been identified in Escherichia coli K12. The constitutive ribosephosphate isomerase A has a Km for ribose 5-phosphate (4.4 +/- 0.5 mM) six times greater than that of the inducible ribosephosphate isomerase B (0.83 +/- 0.13 mM). Treatment of the enzymes with 1.25 mM iodoacetate resulted in 100% loss of activity for ribosephosphate isomerase B, whereas ribosephosphate isomerase A was unaffected. Various cellular metabolites were tested and found to be without significant effect on either enzyme. The two enzymes could be separated by filtration on Sephadex G75 superfine and their apparent molecular weights were 45000 for ribosephosphate isomerase A and 32000-34000 for ribosephosphate isomerase B. Under certain conditions the two enzymes showed different patterns of heat inactivation but the results with ribosephosphate isomerase A varied in an unusual way with the protein concentration. Ribosephosphate isomerase B was formed inducibly in a mutant lacking ribosephosphate isomerase A but there was no evidence for the production of ribosephosphate isomerase B in wild-type cells. The formation of ribosephosphate isomerase B was not a consequence of the ribosephosphate isomerase B mutation, since strains could be constructed which formed both enzymes constitutively in the anticipated amounts. The ribosephosphate isomerase formed by a secondary mutant obtained from a ribosephosphate-isomerase-A-negative strain was identified as ribosephosphate isomerase B on the basis of its Km, elution profile from Sephadex G75, inhibition of iodoacetate, and heat inactivation. The ribosephosphate isomerases of another Escherichia coli K12 strain, X289, were investigated, since their properties were reported to be different from many of these described here for ribosephosphate isomerases A and B. In our hands strain X289 contained two ribosephosphate isomerases apparently identical to ribosephosphate isomerases A and B. The evidence to date suggests that ribosephosphate isomerase A catalyses the formation of ribose 5-phosphate from ribulose 5-phosphate and also participates in the reverse reaction during ribose and adenosine catabolism. The normal physiological role of the inducible ribosephosphate isomerase B is still uncertain.


The energy-coupling controlled efflux of 2-keto-3-deoxy-D-gluconate in Escherichia coli K 12. Experiments were devised to test the plausibility and the predictions of a efflux rate equation which was previously derived [10]9 1. 2-Keto-3-deoxy-D-gluconate transport system conforms with universal laws relating zero-trans influx, influx at steady-state, steady-state levels of accumulation to external and internal substrate concentrations. 2. Full-time-course uptake kinetics fit the linearized graphical representation that can be inferred from the integrated rate equation. 3. Influx does not depend upon internal substrate concentration nor upon energy-coupling. 4. Zero-trans outflux (leak inot empty medium) is a first-order process (rate constant: 0.02 min-1) and not mediated by the carrier. Absence of cis-competition with D-glucuronate is in agreement with a simple diffusion mechanism. 5. Outflux increases when external substrate concentration is raised (counterflow). Outflux at steady-state equilibrates influx, and is a first-order process (rate constant: 0.15 min-1). 6. Uncoupling with azide leads to accelerate zero-trans outflux by a factor of 2-3. No further acceleration is obtained when other classical uncouplers are used. The process remains first-order,  independent of the amount of carrier, and is accelerated by the presence of internal D-glucuronate as a result from trans-inhibition of the recapture. 7. Exchange outflux is all the more accelerated by azide as the carrier is less saturated. The process is clearly carrier-mediated and the outflux rate obeys a Michaelis law with respect to internal concentration. V is equal to V for influx. 8. Homo and hetero-overshoot experiments are in agreement with the participation of the carrier for mediating influx as well as outflux. 9. The kinetics of D-glucuronate outflux in a strain lacking the specific hexuronate permease but carrying the 2-keto-3-deoxy-D-glucuronate permease are similar to those obtained with 2-keto-3-deoxy-D-gluconate. We draw the conclusion that energy-coupling promotes the adjustment of outflux without interfering with influx rate. It apparently acts by reducing, in a continuous range, the affinity of the carrier facing inwards. The discussion is focused on the comparison with previously published models and on possible molecular mechanisms.


Altered alpha subunits in phenylalanyl-tRNA synthetases from p-fluorophenylalanine-resistant strains of Escherichis coli. Three different phenylalanyl-tRNA synthetases have been purified to near homogeneity, one from a wild-type strain of Escherichia coli and the others from two independently isolated p-fluorophenyalanine-resistant strains. The mutant enzymes were not able to use p-fluorophenylalanine as a substrate for activation and attachment to tRNA. They proved to be indistinguishable from the wild-type enzyme by several electrophoretic and immunological criteria. The alpha and beta subunits of all three enzymes have been prepared by a method described in this paper. The isolated subunits per se did not reveal any significant enzyme activity, but combined they were able to form active phenylalanyl tRNA synthetase after a defined reconstitution process. Mixed reconstitution experiments between wild-type and mutant subunits indicate that the mutant alpha subunit is responsible for p-fluorophenylalanine resistance and therefore seems to carry the phenylalanine-binding site or to participate in its formation.


Tertiary structure of tRNAPhe (yeast): kinetics and electrostatic repulsion. Conditions were established that allowed the observation of the unfolding of the tertiary structure of tRNAPhe (yeast) without the interference of either secondary structure or low salt aberrant structures. Relaxation kinetics of tertiary structure melting show that the reaction proceeds according to co-operative all-or-none mechanism. The negative activation enthalpy of formation (delta H+ + R = -14 +/- 5 kcal/mol, -59 +/- 21 kJ/mol) implies a fast pre-equilibrium preceding the rate-limiting step. The ionic strength dependence of the corresponding rate constant demonstrates that most of the electrostatic repulsion characteristic of tertiary structure folding is overcome before the rate-limiting step is reached. On the other hand, most of the stabilizing enthalpy change occurs after the rate-limiting step. At the usual ionic strength (0.1 M Na+) tertiary structure folding is about 100 times slower than double-helix formation. Extrapolation of the rate constants to high ionic strengths, however, indicates that the dynamic differences between secondary and tertiary structure are only due to electrostatic repulsion. The stabilization of tertiary structure by alkaline salts is increased by decreasing the cationic radius. Double helices show virtually no dependence on the radius of monovalent cations. This indicates considerable geometric restrictions for the stabilization of tertiary structure.


Clonazepam in facial neuralgia and cluster headache. Clinical and electrophysiological study. Clonazepam seems to be an effective drug in idiopathic trigeminal neuralgia. Electrophysiological investigations support the idea that this neuralgia is due to a loss of central inhibition. During the first 1-2 weeks of treatment marked drowsiness is observed in the majority of cases. In one case, presence of a synergism between Clonazepam and L-dopa+ inhibitor was also observed.


Use of atrial and bifocal cardiac pacemakers for treating resistant dysrhythmias. Several permanent cardiac pacing techniques have been utilized to control resistant cardiac arrhythmias. SA block, sinus arrest and intermittent ventricular tachycardia was controlled by the use of an atrial 'J' catheter and a rate programmable demand pacemaker. When these arrhythmias were associated with AV conduction delay they were managed with an AV sequential pacemaker with the additional insertion of a ventricular pacing lead. Appropriate adjustment of the AV sequential interval inhibited reciprocal AV or VA reentry thus controlling reciprocal tachycardia. Frequent ventricular premature systoles or intermittent ventricular tachycardia with in appropriately delayed sinus or subsidiary escape cycle lengths appear best managed by an AV sequential pacemaker by adjusting the atrial return cycle. Intractable atrial reentry tachycardias appear best managed by paired or rapid atrial stimulating pacemakers. Development of variable atrial rate, AV sequential and atrial return cycle activating pacemakers offer an effective control of resistant cardiac arrhythmias.


Range of xenogeneic donors whose hematopoietic cells can form colonies on macrophage layer of mice. The colony-forming ability of hematopoietic cells derived from 18 species of rodents was examined on the mouse macrophage layer which formed on a cellulose acetate membrane inserted into the peritoneal cavity of mice. Bone marrow cells of 12 xenogeneic species made a considerable number of colonies on the mouse macrophage layer. However, there was no parallelism between the colony-forming ability of the cells and donor's taxonomic relationship to the mouse.


The role of a thymus humoral factor in the proliferation of bone marrow CFU-S from thymectomized mice. The colony forming capacity of bone marrow cells from thymectomized mice was shown to be reduced as compared to that of bone marrow cells from normal donors. A further indication of changes in the proliferative capacity of colony forming cells (CFU-S), following thymectomy, was given by examination of the sensitivity of these cells to chlorambucil and by 3H-thymidine 'suicide' experiments; both showed that CFU-S from thymectomized mice were not cycling at the same rate as normals. It was also found that in late pregnancy of thymectomized females, there is an elevation in the number of bone marrow CFU-S and an increase in cell cycling. Such an increase could also be achieved by implantation, into thymectomized mice, of thymus lobes in closed diffusion chambers. Finally, in vitro administration of a thymus hormone (THF) reversed the suppressive effect of thymectomy on DNA synthesis in bone marrow CFU-S. Since the action of THF was restricted to bone marrow cells of thymectomized mice it is plausible that normal bone marrow contains at least two subpopulations of CFU-S, one of which is dependent upon a humoral product of the thymus.


In situ hybridization of chromosome loci. In situ hybridization is potentially the most powerful technique available for gene mapping, and has already been proved to be useful for these studies. By a combination of the isolation of pure protein-specific mRNA and the synthesis of high specific activity radioactive cDNA to it, this procedure should rapidly increase our knowledg of gene locations, linkages, and possible even heretofore undetectable minor deletions. Studies with in situ hybridization are summarized and some of the questions regarding specificity, grain development, and the like are considered.


Different effects of bacterial lipopolysaccharide on neonatal immunological tolerance to HSA in rabbits and chickens. Addition of bacterial lipopolysaccharide to HSA during repeated immunization of rabbits neonatally rendered tolerant to HSA led to anti-HSA antibody formation in 4 out of 5 animals. In all 6 tolerant animals immunized with HSA alone tolerance persisted after cessation of the immunization series, as shown by non-immune elimination of 125I-HSA. On the other hand, immunization with HSA together with different doses of LPS did not increase anti-HSA antibody levels in tolerant and control chickens.


Distribution of LH-RH in subcellular fractions of the basomedial hypothalamus. Subcellular fractionation of the mediobasal hypothalamus (MBH) and other brain structures was achieved by differential and sucrose gradient centrifugation. The fractions were monitored by measuring lactate dehydrogenase (LDH) activity (a marker for the soluble cytoplasmic fraction) and by electron microscopic examination. The luteinizing-hormone-releasing-hormone (LH-RH) content of the fractions was evaluated both by bioassay and radioimmunoassay. Significant amounts of LH-RH were found only in the MBH and in an anterobasal location corresponding to the organum vasculosum of the lamina terminalis. Within these areas, LH-RH activity was present in the first supernatant (homogenate with the exclusion of the nuclear pellet). Seventy percent of the LH-RH activity was recovered in the crude mitochondrial fraction. After further fractionation on a sucrose gradient, the distribution of LH-RH was parallel with that of LDH activity. Since LDH is predominantly located in the synaptosomal soluble fraction, it is concluded that the vast majority of LH-RH is contained within nerve endings. This finding is consistent with cyto-immunological data on the distribution of the neuropeptide in the rat hypothalamus.


Insulin secretion in the spiny mouse (Acomys cahirinus). Dose and time kinetic studies with glucose in vivo and in vitro. Plasma insulin responses to the intravenous injection of glucose in the doses of 0.5, 1.5, and 3.0 gm./kg. were compared in spiny mice (Acomys cahirinus) and weight-matched Swiss albino mice. The mean early (two-minute) plasma insulin response was significantly lower in Acomys at all doses of glucose injected; whereas, at later times (5, 15, and 30 minutes), differences in plasma insulin concentrations in the two species of mice were smaller or nonexistent. Plasma glucose clearance was significantly less in the Acomys. In terms of glucose dose kinetics, there was a decreased capacity of the mean plasma insulin response in Acomys compared with albino mice at two minutes; whereas, at later times, the mean dose response curve for Acomys was shifted to the right of that for albino mice, indicating a decreased sensitivity to glucose in the Acomys. There was, however, a large variation between the plasma insulin responses of the eight individual Acomys mice tested. There was a significant correlation in individual Acomys between the plasma insulin response, expressed as an insulinogenic index, integrated over the thirty minutes after injection of glucose 3.0 gm./kg. in vivo, and the insulin released from pancreatic islets obtained from the corresponding Acomys and perifused for thirty minutes with glucose 1,000 mg./100 ml. in vitro (r = 0.77, p less than 0.05). It is concluded that the rate and magnitude of the insulin response to glucose in an individual Acomys reflects mainly the degree of sensitivity to glucose of the pancreatic beta cells in that animal.


Amylase, isoamylase and macroamylase.

Amylase, isoamylase and macroamylase. Hyperamylasaemia has long been regarded as pathognomonic of acute pancreatitis. However, recent work has revealed a number of conditions where a gross elevation may be an incidental finding, notably diabetic ketoacidosis. The recent discovery of 'macroamylase', a high molecular weight amylase-protein complex capable of producing hyperamylasaemia with low urine amylase, has further complicated diagnosis and has led to the introduction of the ratio of amylase clearance to creatinine clearance as a diagnostic aid. Serum amylase may be resolved, by most electrophoretic media, into bands which correspond to those obtained when pancreatic homogenates or saliva are electrophoresed. The initial promise of this technique has not been realised at the routine diagnostic level. Duodenal juice amylase has been the classical enzyme used in assessing exocrine pancreatic function and although it is still of value it is being amplified by other enzyme tests.


Recent advances in the endoscopic retrograde cholangiopancreatography. Endoscopic retrograde cholangiopancreatography can become a safe and easy procedure by means of sterilization of the instruments. Administration of antibiotics or chemotherapeutic agents, both systemically and mixed with the contrast material, and measurement and control of the injection pressure of the contrast medium using a manometer are employed to achieve as aseptic an operation as possible. For diagnosis of pancreatic cancer in its early stage, as well as diagnosis of minimal and moderate chronic pancreatitis, opacification should extend into not only the main pancreatic duct, but also branches of the pancreatic duct and fine pancreatic ducts. The procedure is one of the most reliable methods for the detection of diseases of pancreatic and biliary systems, especially for the diagnosis of space-occupying lesions such as malignant tumors, and chronic inflammatory changes of the pancreas, as well as differential diagnosis in jaundiced patients.


Comparative nutritional analysis of chemically defined diets. Low residue, chemically defined diets containing all essential nutrients in a readily assimilated form, require minimal digestion and are almost entirely absorbed in the upper gastrointestinal tract. Within the past decade, these diets have been reported to provide nutritional support in a variety of clinical situations. The chemically defined diets presently available commercially differ in several respects. In order to provide optimal nutritional care utilizing chemically defined diets, the physician should compare the diet formulas and make the most appropriate choice for each individual patient. A comparative nutritional analysis of the currently available chemically defined diets is given.


The role of endotoxin in liver injury.

The role of endotoxin in liver injury. Evidence is present that a common pathway for hepatic injury by a variety of agents may result from impairment of the liver's ability to detoxify bacterial endotoxins from the gastrointestinal tract. Many factors may structurally, metabolically, or hormonally alter the normal liver's ability to render innocuous the small amounts of lipopolysaccharide ordinarily presented to it. This impairment may accentuate existing hepatic damage by allowing toxic levels of endotoxin to develop in the liver tissue, and by allowing endotoxin entry into the systemic circulation, may also lead to extrahepatic effects. Studies are cited that: (1) support a role for intraintestinal endotoxin in the development of experimental cirrhosis. (2) demonstrate how liver injury alters endotoxin detoxification, (3) examine the role of intestinal production and absorption of bacterial lipopolysaccharides in liver disease, and (4) point to a role for endotoxemia in extrahepatic manifestations of liver injury as well. Studies are also reviewed that suggest possible mechanisms for modifying endotoxicity in hepatic damage.


Polarity in segments of the Escherichia coli trp operon with deleted intraoperonic translational initiation signals. The effect of deletion of the operator-distal genes of the trp operon, including the trpE-trpD intercistronic punctuation point, on the degree of transcriptional polarity (in this case the effect of a nonsense mutation on the level of mRNA from the distal part of the very gene where the mutation is located) was investigated. Double mutants which contain a nonsense mutation and a deletion in trpE were constructed, and the degree of transcriptional polarity was estimated by the decrease in messenger RNA for the operator-distal trpE beyond the nonsense mutation, as well as by the production of truncated messenger RNA for the region of trpE proximal to the nonsense mutation. The content of mRNA of operator-distal trpE and the size of the mRNA of operator-proximal trpE of the double mutants show that transcriptional polarity is not relaxed as a function of distance of the nonsense mutation from the operator-distal end of the trpE segment (at which the subsequent high efficiency translational initiation signal has been deleted). These findings are consistent with the conclusion that the degree of polarity depends on the distance of the nonsense mutation from the subsequent translation initiation signal, but not on its distance from the operator-distal end, including possible translational or transcriptional termination signals.


Effects of glucose repression of the transmission and recombination of mitochondrial genes in yeast (Saccharomyces cerevisiae). Matings of a number of Saccharomyces cerevisiae stocks give different output ratios of mitochondrial genotypes depending on whether the cells are glucose-repressed or derepressed. The effects of glucose repression are independent of cellular mating type and mitochondrial genotype, and take place at least in part after zygotes are formed. An explanation is proposed in terms of changes in the relative numbers of mitochondrial DNA molecules contributed by the a and alpha parents, modified by selective replication or destruction of molecules inside the zygote.


Antibodies to Escherichia coli in chronic liver diseases. Patients with chronic active hepatitis or alcoholic cirrhosis have serum antibodies to many more serotypes of Escherichia coli than do patients with primary biliary cirrhosis or cryptogenic cirrhosis, or normal controls. They also have antibodies against more serotypes than cirrhotic patients with a portacaval shunt. These observations suggest that factors other than shunting of blood away from the liver are responsible for the increased range of antibodies. These factors are discussed. There was no correlation between the number of serotypes to which antibodies were present and the serum immunoglobulin concentration. In three patients, each with chronic active hepatitis, the antibodies were predominantly of the IgM class, while the elevation of globulin in general was mainly due to increased IgG and IgA levels. Antibodies to Escherichia coli, therefore, probably contribute only a small part of the increased globulin levels found in patients with chronic liver disease.


Prednisone for chronic active liver disease: dose titration, standard dose, and combination with azathioprine compared. Among 120 consecutive patients with chronic active liver disease (CALD) randomized to different treatments, those receiving maintenance doses of prednisone 20 mg daily (Pred), prednisone in doses given on alternate days and titrated to secure resolution of clinical and biochemical abnormalities (Pred-Titrad), or a combination of prednisone 10 mg and azathioprine 50 mg daily (Comb) survived and underwent resolution of clinical and biochemical features of disease more often than a control group receiving placebo or azathioprine 100 mg daily. Histological remission occurred significantly more often with Pred and Comb than with other regimens. Major side-effects of therapy were commoner with Pred than with Comb or Pred-Titrad, which did not differ. We conclude that Comb is the initial treatment of choice for CALD, since clinical, biochemical, and histological resolution of disease activity occurs as often as with Pred, whereas early side-effects are significantly less frequent.


Effect of urogastrone on gastric secretion and plasma gastrin levels in normal subjects. Purified human urogastrone was given by intravenous infusion to 12 normal volunteer subjects and measurements made of gastric acid, pepsin and intrinsic factor secretion, and of plasma gastrin concentration. Clinical, haematological, and biochemical screening tests were made throughout the period of study. Urogastrone inhibited acid and intrinsic factor secretion whether stimulated by pentagastrin, histamine, or insulin, but had a much less marked effect on gastric pepsin output. Plasma gastrin levels did not alter significantly. Limited dose-response studies showed that 0-25 mug urogastrone kg--1 hr--1 resulted in inhibition of acid output of 80% and was not associated with clinical side-effects. No significant alteration in any of the haematological or biochemical measurements was observed in any of the subjects.


The agglutinating antibody response in the duodenum in infants with enteropathic E. coli gastroenteritis. The agglutinating antibody responses in duodenal fluid and serum were measured serially in 15 infants with enteropathogenic E. coli gastroenteritis. Peak levels of duodenal agglutinins were recorded eight to 18 days after the onset of symptoms, and the titres fell within the next seven to 14 days. These antibodies were mainly of the IgA class but IgM antibodies were detected early in the response, especially in the youngest infants. Serum antibody responses were detected in eight patients, but they correlated poorly with the titres of intestinal antibodies. No rise in serum antibodies was found in six infants. Further studies are required to determine whether these differences are host-derived or whether they reflect different pathogenic properties of the infecting organisms.


Detection of antibody in white mice infected with Plasmodium berghei by means of the indirect immunofluorescence test. Experiments have been conducted in order to test the efficacy of the immunofluorescence test in the detection of antibody in mice infected with Plasmodium berghei Vincke et Zips, 1948. This method enables the detection of antibody in subclinical and latent cases when an occasional parasite only is present in the blood cells. Of the various methods used for the preparation of antigen, and of the various fixatives, a satisfactory immunofluorescence reaction was obtained if unfixed erythrocytes without their plasma were used as the antigen.


[Metabolism of arsenic (15). Influence of arsenic antidotes on intestinal absorption of arsenic trioxide]. A loop ligated at both sides was made in the ilecoecal portion of rabbit intestine. As2O3 solution was infused into this loop and the blood circulating around this loop was collected from the cannulated vein. As2O3 content absorbed in blood as well as that remaining in this loop were determined. In control rabbits on no drugs, approx. 30% of As2O3 infused was absorbed into the blood in 60 minutes. However, in rabbits on parenteral dimercaprol (BAL) or thioctic acid (TA), the content of As2O3 absorbed into the blood decreased remarkably while the content of As2O3 remaining in the loop increased. On the other hand, even when BAL or TA were added directly into thip loop containing As2O3, the content of As2O3 absorbed in blood decreased markedly, compared with that of the control group. Thus it was demonstrated that BAL or TA combined with AsO3(3-) after being excreted into the intestinal tract from the bile-duct, bringing about inhibition of the enteral absorption of As2O3.


The chitin-glucan complex of Saccharomyces cerevisiae. III. Electron-microscopic study of the prebudding stage. Differentiation of the cell wall of Saccharomyces cerevisiae at the site of the future bud was followed. A lentil-like structure originates on the inner side of the cell wall during the first phase. At the same time, an electron-dense layer occurs at the boundary between the inner layer of the cell wall and the lentil-like structure. During the second phase granular material is accumulated at the lower side of the lentil-like structure. During the third phase the lentil-like structure is split apart due to proliferation of the granular material resulting in formation of the base of the encircling region. The marked electron-dense layer observed from the first phase is attached to the surface of the encircling region during differentiation of the latter. During the budding proper the outer layers of the cell wall protrude and the end of the encircling region, together with the adjacent electron-dense layer, acquire their definitive appearance of rings, observed as marked electron-transparent and electron-dense tears on ultrathin sections.


Possibilities of the conjugation process in mycobacteria. Results obtained when studying conjugation in mycobacteria by means of different methods are summarized. The method of conjugation on surface of a solid complete medium was tested with different auxotrophic mutants of different strains of Mycobacterium smegmatis. It was not possible to obtain positive results even by means of the above method. This was probably due to unsuitability of the chosen strains of Mycobacterium smegmatis. Preparation of the donor strain by transfer of the F factor from Escherichia coli F'ORF 1 ade+ lac+ pro+ to Mycobacterium phlei PA ade Stmr by means of sexduction is described. Frequency of the phenotype PA ade+ Stmr increased in the average by two and a half orders of magnitude with respect to the control, however, a further transfer from cultures of the cells ade+ Stmr to cells ade could not be demonstrated. Experiments aimed at transferring the R factor from strains Escherichia coli K-12 to Mycobacterium phlei were unsuccessful.


Effect of tweens on the production of ergot alkaloids by Aspergillus fumigatus. Tween 80, which caused increased biomass formation, also produced the highest increase in the uptake rate of all components of the medium. The fatty acid components of the respective Tweens, i.e. palmitic acid (Tween 40), stearic acid (Tween 60), and oleic acid (Tween 80), have no effect either on alkaloid production or on substrate uptake. The fatty acid composition was different in the cell membrane of the culture supplemented with Tween 60 and facilitated the transport of metabolites into the cells.


The role of immune pig colostrum, serum and immunoglobulins IgG, IgM, and IgA, in local intestinal immunity against enterotoxic strain in Escherichia coli O55 in germfree piglets. The protective effect of pig immune colostrum, serum and immunoglobulins IgG, IgM and IgA against the enterotoxic strain of Escherichia coli O55, was studied in newborn germfree piglets. This strain produced accumulation of fluid and dilatation of intestine when injected into the ligated ileal segment of germfree piglets, which is considered to be the typical effect of enterotoxins. Erosion of the intestinal epithelium and penetration of bacteria into the submucosa were also observed. Immune serum, colostrum and all the immunoglobulin classes used produced a local protective effect, IgA being most effective. The mechanism of protection conferred by these immunoglobulins is discussed with respect to the possible pathogenic action of enterotoxic Escherichia coli O55 in the intestinal tract of immunologically virgin germfree piglets.


Attempt to enhance resistance to infection in 6-mercaptopurine treated mice by lysozyme administration and immunization with Escherichia coli O86 antigen. Long-term immunosuppressive therapy of mice with 6-mercaptopurine (6-MP) for 2 and/or 3 weeks results in partial lethality, decrease of total leukocyte count, of serum lysozyme level and in bacteremia. The adverse effect of 6-MP treatment could not be prevented by lysozyme administration; immunization with Escherichia coli O86 antigen further increased the lethality of 6-MP in mice. The results stress the potential danger of immunization with bacterial antigens during immunosuppressive therapy.


[Treatment of sinusitis in childhood].

[Treatment of sinusitis in childhood]. The cause of "colds" is frequently an unrecognized sinusitis. The importance of x-ray diagnosis is stressed. In therapy of sinusitis the phytotherapeutic Sinupret is a valuable adjuvans besides antibiotics, local and physical therapy. Sinupret is especially suitable for treatment after the acute phase of sinusitis during intervalls and as prophylaxis during the cold months with frequent infections of the upper respiratory tract.


[Problems of plastic and reconstructive surgery in the face]. For reconstruction of extensive skin defects on the face two techniques can be suggested: the sliding graft from the area of the skin adjacent to the defect (technique of the sliding graft and rotation) and the technique of distant flaps. If possible preference should be given to the first technique, as it certainly leads to better results regarding function, form and structure of the skin.


[The long-range analysis of the chrombiological structure of some cases of manic-depressive illness (author's transl)]. Within the group of endogenous psychoses manic-depressive illness is a subgroup which can be explicitly described. The psychopathologic phenomena of their current status (Momentagefüge) are disorders of drive and mood. The time structure generally exhibits the characteristic sequence of acute phases and "free" intervals, while in detail there are numerous variations of intensity, such as siurnal variation of mood etc. An essential of the definition of endogenous psychoses has always been their periodicity. However, in the majority of cases that periodicity was not conclusively proved. On the basis of one representative case factor analyses of a long and complete series of daily self-rating scales were performed. A dichotomy of time series of mood scores and of drive scores was used for autocorrelation. Thereby two different multiday periods were established. Two periods of this type combine to produce an interferential period, which does not generally occur on a continual scale, but only in a systematic selection. This was the subject of investigation. From 100 phase schedules (Phasenkalender) of manic-depressive psychoses 18 cases with long periods were selected by means of a special technique of cross-correlation, which were re-analyzed under methodologically more stringent conditions. Such re-analyses confirmed the initial hypothesis. The entire phase schedule is composed of interferential periods...


[Studies on the extracorporeal circulation. Especially on changes in acid-base balance, serum electrolytes and S-GOT during rapid perfusion cooling (author's transl)]. Experiments were made using 47 mongrel dogs under normo-and hypothermic perfusion employing the DeWall-Lillehei and Kay-Cross oxygenator. The purpose of this study is to find the ideal method of extracorporeal circulation as an adjunct of cardiac surgery. In this report, the changes of acid-base balance, serum electrolytes and S-GOT during perfusion were investigated. The results obtained were as follows. 1) In spite of the hypothermia, the changes of pH and buffer base in 10 degrees C hypothermic circulatory arrest indicated the gradual progress of the tissue metabolism. After the circulation restarted uncompensated metabolic acidosis without decrease of H2CO3 ensued. The circulatory arrest for 30 minutes in 10 degrees C hypothermia was thought to be hazardous to the preservation of life. 2) In case of ventricular fibrillation, hyperkalemia in the systemic venous blood was often found. It was also observed in the coronary venous blood. In accordance with the fact of hyperkalamia during anoxia, it is presumed that the cardiac anoxia is the important factor for the development of ventricular fibrillation. 3) The value of S-GOT in the arterial blood was not influenced by perfusion time, cardiac arrest and temperature, so far as the perfusion was performed smoothly. S-GOT was elevated when cardiotomy was carried out.


A review of token economy treatment programs for psychiatric inpatients. The author has reviewed outcome studies of token economy programs for psychiatric inpatients. Only studies that employed some control procedures in their evaluation were included. Token economies were most effective in modifying inhospital work, personal care, and some psychotic behaviors. Studies that assessed token programs to prepare patients for community living and reduce recidivism generally affirmed the effectiveness of token procedures, but the studies were poorly designed, and they lacked systematic follow-up data. Almost all studies failed to examine possible interactions between chemotherapy and the token economies. The author suggests the need for studies using token economies with psychiatric patients other than chronic schizophrenics, who have been studied almost exclusively to date.


Lymphomatoid granulomatosis in a renal transplant recipient. Lymphomatoid granulomatosis, as defined by Liebow et al. in 1972, is an angiocentric, angiodestructive, lymphoreticular proliferative disorder of uncertain relationship, if any, to malignant lymphoma. This report describes the rapid development and progression of lymphomatoid granulomatosis in a 33 year old recipient of an immunosuppressed renal transplant. The report further discusses the differences between lymphomatoid granulomatosis and malignant lymphoma with respect to both histology and natural histor.


Cardiac pathologic findings in patients treated with bone marrow transplantation. Cardiac pathologic findings were analyzed in 22 necropsy cases from a series of 29 patients with leukemia, aplastic anemia, or metastatic cancer who had been treated with ablative therapy followed by bone marrow transplantation. Some cardiac alterations were similar to those that occur in patients with hematologic and neoplastic diseases not treated with bone marrow transplantation, and consisted of cardiomegaly, cardiac atrophy, hemorrhage, foci of necrosis due to shock associated with sepsis or hepatic failure, myocardial abscesses secondary to systemic candidiasis or staphylococcal infection, fibrinous pericarditis, and hemosiderosis. Other cardiac alterations were more specifically related to factors associated with transplantation procedure. Six patients exhibited a distinctive interstitial reactive change characterized by the presence of (1) moderate to large numbers of Anitschkow cells, occurring alone or in small cellular aggregates and histiocytes, histiocytic cells with nuclei of the Anitschkow type, lymphoid cells, and plasma cells, and (2) nuclei of the Anitschkow type in cardiac vascular and endocardial smooth muscle, endothelial and Schwann cells, and occasional cardiac muscle cells. This alteration may have been induced by abnormal immune mechanisms, as suggested by the observation that five of the six patients with interstitial change had clinical evidence of graft-versus-host disease. Two patients developed fatal congestive cardiac failure in the early post-transplant period and exhibited myocardial damage with histologic and post-transplant period features indicative of severe acute injury. Findings in these two patients consisted of necrotic muscle cells, which exhibited multiple contraction bands, diastase-resistant PAS staining, and intracellular fibrin deposits; microthrombi, which were composed of fibrin and occasionally of fibrin and platelets; and extravasated erythrocytes and fibrin strands in the interstitium. One of the two patients also exhibited unusual nuclear alterations, which were characterized by replacement of normal chromatin by palely stained fibrous and filamentous material. Clinicopathologic analysis strongly suggested that the fatal cardiotoxicity in both patients resulted primarily from effects of high doses of cyclophosphamide, which were administered as part of a four drug regimen that provided tumor ablation and immunosuppression for bone marrow transplantation. Our findings emphasize the need for less toxic antineoplastic and immunosuppressive therapy for use in bone marrow transplantation procedures.


Culture of cells in beem capsules: a new technique for electron microscopic study of monolayer cultures. A method is described for the monolayer cultivation of primary cell suspensions and established cell lines directly in carbon-coated BEEM capsules, BEEM capsules are routinely employed by electron microscopists in tissue embedding procedures; growing monolayer cultures directly on the lids of inverted BEEM capsules presents the obvious advantage of maintaining cell to cell and cell to substratum conthaets with a minimum of stress and damage in the preparative steps for electron microscopy.


Local immune response in experimental pyelonephritis in the rabbit. II. Lymphocyte stimulation by lipopolysaccharide of infecting organism. The response of circulating and kidney lymphocytes from rabbits with experimental haematogenous pyelonephritis to somatic (O) antigen (lipopolysaccharide) from the infecting organism was evaluated. Lymphocytes were cultured for 3 days in the presence and absence of lipopolysaccharide from the infecting organism, Escherichia coli O75 and a heterologous organism. Circulating lymphocytes showed a significant response to the homologous lipopolysaccharide by day 5 of infection, and kidney lymphocytes responded by day 19 of infection but failed to respond after day 33. The lipid moiety of somatic antigen was required for the stimulation of lymphocytes since antigen preparations in which lipid was low or absent did not activate lymphocytes. B lymphocytes from kidney were stimulated by this antigen whereas both T and B circulating lymphocytes responded. Thus, pyelonephritis in rabbits is associated with the activation of a subpopulation of circulating cells which have specific receptors for the homologous antigen. B lymphocytes that are specifically activated by the homologous or O antigen then localize to the infected site.


Mechanism of termination of immunological tolerance. Mice were rendered tolerant to bovine serum albumin (BSA) by means of cyclophosphamide. The effect of immunization with sulphanilated BSA with different degrees of hapten conjugation on this tolerant state was examined. It was shown that the tolerant state was readily terminated with sulphanilated BSA with a low degree of chemical modification. Specificities of antibodies produced in response to sulphanilated BSA were tested by absorption and PHA inhibition test, demonstrating that there were antibodies directed to new antigenic determinant(s) on sulphanilate BSA as well as those reacting with unmodified BSA. To explore the cellular mechanism of termination, lethally irradiated syngeneic mice were reconstituted with thymus-derived cells (T cells) together with bone marrow-derived cells (B cells) from either normal mice or mice rendered tolerant to BSA, and were immunized with BSA or sulphanilate BSA. Tolerance termination was clearly observed in the recipient mice reconstituted with tolerant T cells plus normal B cells. From these experimental data, it was proposed that the termination was effected by means of the co-operation of the T-cell population tolerant to BSA but capable of responding to new antigenic determinant(s) on sulphanilated BSA, with non-tolerant B cells responsive to BSA.


Experimental murine leprosy: induction of immunity and immune paralysis to Mycobacterium lepraemurium in C57BL mice. Two series of reinfection experiments were carried out using C57BL mice. In the first series, the mice were inoculated with Mycobacterium lepraemurium (MLM) in one hind footpad and reinoculated in the contralateral footpad, two or four weeks later. Compared with normal mice of the same strain, the mice reinoculated after four weeks showed an increased local reaction to the bacilli and the bacilli did not multiply at the injection site. The responses of mice reinoculated after two weeks were intermediate to those of the other two groups. In the second series, a systemic infection was established by intraperitoneal innoculation of either a large or small dose of MLM. Twenty-two weeks later the mice were reinoculated in one of the hind footpads. Upon reinoculation, mice receiving the small intraperitoneal dose reacted more strongly than normal mice to MLM, whereas mice receiving the large dose were unable to mount any local reaction to the mycobacterium. The experiments have shown that the local reaction which develops in the C57BL strain of mice approximately four weeks after subcutaneous injection of MLM is accompanied by the onset of systemic immunity. Such systemic immunity lasted for more than 20 weeks after intraperitoneal injection of a small dose of bacilli, but was completely abolished during the course of a heavy systemic MLM infection.


Effect of thymectomy and antilymphocyte serum on Mycobacterium leprae infection in mice. BALB/c mice thymectomized at 3 to 5 days of age were studied to determine if this procedure would result in enhanced susceptibility to infection with Mycobacterium leprae and, if so, whether or not administration of antilymphocyte serum would further increase this susceptibility. The plateau for growth in the footpads of intact mice occurred 4 months after inoculation, whereas in the thymectomized and thymetocomized plus antilymphocyte serum-treated groups the plateau occurred between months 11 and 12 after inoculation. Thymectomy resulted in at least a 10-fold increase in the number of M. leprae found in the footpads. Antilymphocyte serum did not appear to further enhance the M. leprae infection in the thymectomized mice. Although growth of M. leprae in the testes of both intact and thymectomized mice was erratic, the number of organisms reached a higher ceiling in the thymectomized groups. M. leprae harvested from all groups was passaged into intact mice at various intervals after inoculation to test for viability. Viable M. leprae were found at all intervals tested including 22 months after infection in the intact mice, suggesting that a chronic infection occurred that probably lasted during the entire life of the animals.


Cellular location of streptolysin  O.

Cellular location of streptolysin  O. Streptolysin O was measured in subcellular fractions of group A streptococci obtained after preparation of protoplasts in a hypertonic buffer containing raffinose. Most of the activity was located in the periplasm (the region between cell wall and membrane) and did not differ in several characteristics from that of extracellular streptolysin O. Of the enzymes used as subcellular markers, aldolase and maltase (cytoplasmic) and acid phosphatase (membrane associated) were in the same fractions as found in other bacteria. However, the location of alkaline phosphatase differed from that of other bacteria in the most of the activity was in cytoplasm rather than in the periplasm.


Nonspecific resistance to Escherichia coli in mice. Nonspecific cell-mediated immunity to a relatively virulent strain of Escherichia coli was studied in mice infected with Staphylococcus aureus and elicited with specific antigens. The infected and elicited mice were protected against as intraperitoneal challenge by E. coli for an observation period of 7 days, whereas normal mice, given the same number of bacteria, died within 18 to 24 h. However, the amount of time elapsing between elicitation and challenge greatly affected the rate of protection. Little or no protection was observed in mice injected with S. aureus but not elicited or in mice injected with staphylococcal antigens but not infected with staphylococci.


Adherence of enteropathogenic Escherichia coli to intestinal epithelium in vivo. Two porcine strains of enteropathogenic Escherichia coli, one possessing K88 antigen and one lacking K88, were orally inoculated into conventional neonatal piglets. Athough both strains caused severe diarrhea, only the K88-possessing strain was able to proliferate in the anterior small intestine. Both K88-possessing and K88-lacking strains were found in large numbers in the posterior small intestine and, using fluorescent antibodies and scanning and transmission electron microscopy, were found adhering to the epitheial surface in these regions. The presence of an unusual surface structure on the bacterial cell of the K88-lacking strain was described.


Characterization of group A streptococcal R-28 antigen purified by hydroxyapatite column chromatography. Purified R-28 antigen from an M-protein-poor, R-antigen-rich strain of group A Streptococcus was prepared by sequential treatment of an acid extract of whole cells with ammonium sulfate fractionation and hydroxylapatite (HA) column chromatography. Purified R-28 antigen was eluted only with 0.10 M sodium phosphate, pH 6.7. Findings on quantitative amino acid composition, polyacrylamide gel electrophoresis pattern, and HA column elution pattern were similar but not identical to those previously reported for streptococcal M-proteins. Rabbits immunized with either HA-purified R-28 antigen or heat-killed cells developed two pepsin-sensitive, trypsin-resistant immunodiffusion lines of identity against HA-purified R-28 antigen but failed to form bactericidal antibody. One of these two lines formed a line of identity with R-28 antigen prepared by trypsinization of whole cells. The other line remained undefined, although it appeared not to be either streptococcal group A carbohydrate, M-protein, T-antigen, polyglycerophosphate, E4 antigen, or M-associated protein; by enzymatic criteria it is an R-antigen. Polyacrylamide gel electrophoresis of HA-purified R-28 antigen revealed multiple serologically active charge and size isomers. These findings suggest possible structural similarities between group A streptococcal M-proteins and R-antigens and also indicate that the same purification techniques may be utilized to study these protein antigens if the proper strain of Streptococcus is chosen.


Extension of the mean time to death of mice with a lethal infection of Venezuelan equine encephalomyelitis virus by antithymocyte serum treatment. The mean time to death of mice infected with Venezuelan equine encephalomyelitis (VEE) virus was increased 2 days by antithymocyte serum (ATS) treatment given 1 day before and 1 day after virus inoculation. Virus assays of blood, brain, and spleen indicated that VEE virus replication was delayed by ATS. Additionally, mice treated with ATS exhibited neurological signs later than untreated mice. During the infection, the percentage of splenic B lymphocytes as determined by surface immunoglobulin staining increased. ATS treatment caused a further elevation of the percentage of splenic B lymphocytes. These results show a selective depletion of the non-immunoglobulin-bearing lymphocyte population during VEE virus infection and support the hypothesis that ATS destroys or alters an important population of cells associated with the normal course of pathogenesis and the replication of VEE virus to high titers in the mouse.


Carbon sources utilized by virulent Treponema pallidum. Carbon sources utilized by virulent Treponema pallidum organisms extracted from infected rabbit tissue have been investigated. Utilization of 14C-labeled compounds by T. pallidum was monitored by degradation of these compounds to 14CO2. Experiments have consistently shown that of 22 carbon sources examined, [14C]glucose and [14C]pyruvate are selectively degraded to 14CO2 under the experimental conditions employed. When [1-14C]pyruvate, [2-14C]pyruvate, and [3-14C]pyruvate are tested, virulent T. pallidum preferentially degrade and release the carboxyl group as 14CO2. End product analyses indicate that CO2 and acetate are the major products of pyruvate degradation by T. pallidum.


Retention of motility and virulence of Treponema pallidum (Nichols strain) in vitro. A maintenance medium for Treponema pallidum was designed to hold its Eh at the optimum for that organism, -10 to -110 mV. After 100% motile (freshly harvested) T. pallidum was inoculated into the medium, the motility of the treponemes decreased to 80% after 2 days, 50% after 3.5 days, and 0% after 9 days during incubation at 34 C. Full virulence was retained for 2 days, but it dropped rapidly thereafter, and the treponemes became avirulent by day 5.


Isolation and purification of two antigenically active, "complimentary" polypeptide fragments of tetanus neurotoxin. Tetanus neurotoxin (molecular weight approximately 160,000) was purified from bacterial extracts (intracellular toxin) and mildly trypsinized and from culture filtrates (extracellular toxin). Both purified preparations could be dissociated reversibly into two polypeptide chains, with molecular weights of 53,000 (fragment alpha) and 107,000 (fragment beta), by treatment with 100 mM dithiothreitol (DTT) and 4 M urea with concomitant loss of toxicity. Upon removal of DDT and urea from the dissociated toxin preparation by dialysis, these fragments reassociated, forming the whole toxin. The two fragments were isolated and purified from the dissociated toxin by gel filtration on an Ultrogel AcA 44 column equilibrated with buffer containing 2 M urea and 1 mM DTT. The preparation of fragment alpha was nontoxic whereas that of fragment beta was slightly toxic. Immunodiffusion analyses, using horse antitoxin, showed that the antigenicities of fragment alpha and fragment beta were distinct from each other but were partially identical with that of undissociated toxin. The abilities of these fragments to precipitate antitoxin were lost on heating at 60 C for 5 min. The molecular substructure of tetanus neurotoxin is discussed on the basis of these findings.


Relationship of two arthropod-borne rhabdoviruses (kotonkan and Obodhiang) to the rabies serogroup. Indirect immunofluorescence confirmed the antigenic relationship between kotankan and Obodhiang viruses and Mokola virus that had originally been shown by complement fixation test. This relationship suggests inclusion of these two arthropod isolates in the rabies subgroup of the Rhabdoviridae family. Cross-reactivity with Mokola virus was also demonstrated by direct immunofluorescence but was easily eliminated when conjugates were diluted. No crossreactivities were found by neutralization tests or by surface immunofluorescence. Other than these immunological ties to the rabies serogroup, other biological characteristics of kotonkan and Obodhiang viruses were distinct. Maximum yield of infectivity of kotonkan and Obodhiang in cell culture was at 30 C, antigen usually filled the cytoplasm of infected cells diffusely, and syncytia were formed before severe cytonecrosis. By electron microscopy, virus particles and their nucleocapsids appeared cone shaped (mean lengths: kotonkan, 182 nm; Obodhiang, 170 nm). Viral morphogenesis took place on plasma membranes of cells in culture, mouse brain neurons, and inflammatory cells (macrophages) in brain lesions. All of these characteristics of the two viruses, and the known association of kotonkan virus with an acute, febrile illness of cattle in Nigeria, suggest a biological relationship with bovine ephemeral fever virus. The latter is known to exist in the same geographic area but exhibits no serological cross-reaction with either kotonkan or Obodhiang virus. The question of whether these two viruses deserve placement in an expanded rabies subgroup (at the cost of a less precise definition of the subgroup) or in a separate subgroup (which would include bovine ephemeral fever virus) of the Rhabdoviridae family will only be answered by further physicochemical characterization and comparison.


Siderochrome production by Yersinia pestis and its relation to virulence. P+ plague strains contained more siderochrome-producing organisms than P-. Siderochrome enhanced the mouse virulence of an F1+Vw+P1+P-Pu+ strains, inhibited P1 activity, and could be assayed by a paper disk titration method.


Adjuvant effect of Bordetella pertussis vaccine to sheep erythrocytes: enhancement of antibody formation by using subcutaneous administration of adjuvant and antigen. The subcutaneous route (s.c.) was used to study the adjuvant effect of Bordetella pertussis vaccine (pv) on the primary antibody response to sheep erythrocytes. The reasons for using the s.c. route are discussed. PV, besides enhancing the hemagglutinin response, also markedly increased the number of plaque-forming cells in the draining lymph nodes. A heated preparation of PV was tested and found to possess significant adjuvant activity. Interestingly, the enhancement occurred in the absence of marked enlargement of the lymph nodes, which was characteristic of the unheated preparation. In addition, a crude solubilized cell-free preparation of PV was tested and also found to possess significant adjuvant activity. The activity was only partially abolished by heat. Hence, it was concluded that both heat-labile as well as heat-stable factors contributed to the adjuvanticity of PV. The studies also support the view that the draining lymph nodes represent a principal locus of action of PV and that the s.c. route of administration of adjuvant and antigen provides a suitable model for studying and assaying the adjuvanticity of PV.


Chitin assay used to demonstrate renal localization and cortisone-enhanced growth of Aspergillus fumigatus mycelium in mice. Aspergillus fumigatus mycelium in untreated mice (N-mice) and cortisone acetate-treated mice (C-mice) has been quantified by chemical assay of fungal chitin. Cortisone pretreatment rendered mice more susceptible to infection by A. fumigatus (mean lethal dose at 20 days, congruent to 10(6) for N-mice; less than 10(4) for C-mice). In both N- and C-mice there was renal localization of mycelial infection at conidial doses less than the mean lethal dose. At a conidial dose greater than the mean lethal dose, mycelial infection was found in the kidneys and brain of N-mice and in the kidneys, liver, and heart of C-mice. Chitin assay results showed that A. fumigatus mycelium grew more rapidly in C-mice. It is suggested that the resistance of N-mice to mycelial development may be an important mechanism whereby natural resistance to A. fumigatus is conferred.


Effect of lipopolysaccharide and lipid A on mouse liver pyruvate kinase activity. Several investigators have reported lipid A as the biologically active unit in the lipopolysaccharide (LPS) molecule. To determine if lipid A was responsible for the reported increases in pyruvate kinase, mice were injected with endotoxin from Salmonella typhimurium SR-11, the Re mutant of Salmonella minnesota R 595, and lipid A-bovine serum albumin conjugate. The livers were homogenized and the activity of pyruvate kinase was measured. Similar increases in enzyme were obtained with all three preparations. These data imply that the lipid portion of the LPS molecule was responsible for alterations in host enzyme activity. To further determine if the lipid portion was the active unit, a lipid-degraded endotoxin (endotoxoid) prepared by potassium methylate treatment was inoculated into mice. An initial increase in liver pyruvate kinase activity was observed with all preparations. The marked increase observed at 16 h with the native product and lipid A conjugate was not obtained with the endotoxoid. These experiments extend and confirm previous observations that lipid A is responsible for the effects associated with LPS. Animals tolerant to endotoxin from S. typhimurium SR-11 were challenged with endotoxin from the Re mutant. A significant increase in pyruvate kinase activity was not obtained, suggesting that anti-O antibodies are not important in the development of tolerance.


Specific responsiveness of leukocytes to soluble extracts of human tumors. The leukocyte adherence inhibition (LAI) method was studied with respect to its specificity in detecting responses to extracts of tumor tissues or normal lymphocytes. Responses of cells from normal persons were within 10% of each other whether incubation was carried out with culture medium alone or with any of the extracts. The same was true of cells from 78 cancer patients unless the cells were incubated with extracts of the same histologic type as their own. In the latter case, statistically significant responses occurred in 95% of the 110 analyses done. Negative responses were given by cells from 14 patients tentatively diagnosed as having breast carcinoma but whose lesions later proved benign. There was one positive response inconsistent with the diagnosis. Of 29 normal individuals known to have been exposed to tumors or tumor extracts, 11 responded positively and specifically to the relevant tumor extract. Cells from 12 of 30 multiparous female breast-cancer patients responded to extracts of pooled normal lymphocytes. The results establish that the LAI analysis is an extremely specific means of detecting systemic responses to malignant diseases. In addition, analyses have proven positive in 95% of the cases studied.


Antibodies and antigen expression in human melanoma detected by the immune adherence test. By means of a modified immune adherence (IA) technique, sera from melanoma patients were tested for the presence of antimelanoma antibodies. In total 13/73 sera tested showed a positive IA reaction of which 4/6 sera showed a positive reaction in the autologous situation. Sera from 33 patients with other tumors, 7 patients with non-neoplastic diseases and 50 healthy individuals did not show any IA reactivity towards melanoma cells. The reaction seemed to be selectively directed against tumor-associated antigens (TAA) on melanoma cells. No correlation with the stage of the disease could be found. Longitudinal studies indicated that conversions in antibody activity did not correlate with the clinical state of the patients. There was also no correlation with the corresponding in vitro data obtained in cell-mediated immunity tests. Cell lines and short-term cultures originating from tumors from different melanoma patients shared a common antigenicity. The expression of TAA on cells from a melanoma cell line fluctuated significantly during prolonged culture. The expression of TAA was influenced by the culture conditions and the growth state of the cells. A relation between TAA-expression and cell cycle phase was demonstrated.


Drug abuse during the Civil War (1861-1865). The Civil War (1861-1865) has long been blamed as the catalyst for the spread of drug addiction in America. This paper attempts to examine this hypothesis through an extensive review of pertinent literature, and to clarify misconceptions concerning addiction problems associated with the war.


Kif in Morocco.

Kif in Morocco. Chronic cannabis intoxication of a significant fraction of the male population still prevails in Morocco. The preparation used (kif) is a powder made from the dried flower of the female plant. It contains 2 to 3% THC and is smoked mixed with tobacco (1/3 of the mixture). Cultivation of kif is tolerated in an area of 60 square miles in the high Rif mountain of Northern Morocco, where it constitutes the main cash crop of the local farmers. A significant percentage (50%?) of the men in the area also consume kif regularly. This cultivation is spreading to neighboring areas. Moroccan health authorities claim that cannabis intoxication represents a major health hazard. There exist little data correlating chronic usage of kif with pathological states in these areas of large production and consumption. This dearth of information due to lack of local medical personnel could be alleviated by a combined medical and ethnological study.


Would healing: a brief review.

Would healing: a brief review. The biology of wound healing is indeed a complex process. From phase 1 to phase 3, an orderly progression of events take place in the repair process. Various factors influence the rapidity and cosmetic appearance of this phenomenon. Physical, microbial, nutritional and environmental factors all have some role in the end result.


Pathogenesis of staphylococcal infections of the skin. Staphylococcus aureus does not grow readily on normal skin, where an important factor inhibiting its growth is the resident flora. Hydration of the stratum corneum favors the growth of S. aureus. Before lesions of staphyloderma are produced, organisms multiply on the surface. Substances produced as the result of multiplication enter the skin and produce an irritant reaction characterized by necrobiosis, spongiosis followed by perivascular infiltration, exocytosis and intraepidermal vesicle formation. A technique was used whereby the skin surface was separated from growing S. aureus by a filter. Pustules were produced through the filter.


Evaluation of "chemical isolation" in 1,168 leprosy patients' homes. "Chemical isolation" (treatment of open cases as a measure of control for transmission between contacts) is evaluated by a retrospective study of 7,232 household contacts of 1,168 leprosy patient homes. Contacts comparable in age and type of exposure were arranged in subgroups according to whether they were born before (Group A) or born after (Group B) beginning treatment of the index cases had begun. Additionally, the whole group of contacts, both of open (LL & BB) and closed (TT & I) cases were evaluated. Among comparable contacts of LL and BB cases, the infection rate in the contacts before initiation of treatment is higher than in that of contacts after initiation of treatment. The protection afforded by the treatment to the exposed group (Group B) is on the order of 66%. The morbidity occurring in the group born after the initiation of index case treatment apparently results from partial persistence of infectiousness of the case under treatment.