[Complications of pregnancy in female anesthesiologists (author's transl)]. A questionnaire was sent out to the members of the German Society of Anesthesiology and Reanimation with the purpose to clarify whether there is an increased incidence of certain complications during pregnancy among anesthesiologists. The results obtained allow the tentative conclusion that there is a higher abortion rate. There was also an increase of premature deliveries and congenital malformations. Surprisingly, a significant increase in births of females was observed among female anesthesiologists (with or without exposure) and among the offspring of male anesthesiologists (with or without exposure). Therefore this observation cannot be related to the exposure in operating rooms. On the basis of these results and reports from literature it is not permissible to relate the incidence of these complications exclusively to the chronic inhalation of narcotic gases. Other covariables which might cause the complications were not considered in this study. Nevertheless in spite of these limitations narcotic gases should be removed from the atmosphere of operating theatres as completely as possible.


[Donor cervical mucous in the treatment of the persistent cervical factor in infertility (author's transl)]. A case of persistent infertility due to a cervical factor is reported which did not respond to several treatment regimes to make the cervical mucous penetrable for the sperms of the husband. Intra-uterine insemination was equally unsuccessful, however the in-vitro incubation of the semen of the husband in donor cervical mucous and subsequent intra-uterine insemination of this incubated mucous resulted in a pregnancy.


[The treatment of carcinoma in situ of the breast (author's transl)]. The management of 63 carcinomas in situ of the breast is reviewed. These 63 carcinomas in situ occurred among 575 carcinomas of the breast from 1969 to 1973. The treatment consisted of simple mastectomy. In cases of early invasion the axilla was explored by palpation of the adipose tissue for enlarged lymph nodes. None were found and no extirpation of the axillary nodes was carried out. Of 59 patients with carcinoma in situ of the breast, 3 later had a local recurrence. Two patients later died of distant metastases. In view of these inadequate results of simple mastectomy it is recommended that a modified radical mastectomy should also be done in all cases of carcinoma in situ of the breast.


[Endometrial cyto-histology by PISTOLET-aspiration technic (author's transl)]. A modified intrauterine aspiration technic for detection of endometrial adenocarcinoma and its precursors has been described. This method which is simple, inexpensive and requires neither anaesthesia nor analgesia, allows cyto-histologic diagnoses of endometrial lesions. A correct cytologic or cyto-histologic diagnosis was made in 93.9% of the 277 cases examined. Of the premalignant and malignant endometrial lesions, the diagnostic accuracy was 100%.


[The ultrasonic diagnosis of breast prosthesis implanted after operative treatment of tumors or augmentation plastic of the breast (author's transl)]. The ultrasonic diagnosis as a method of recognising postoperative subprosthetical breast pathological changes (respectively of simulated tumor recidivs and implanted breast prosthesis) located near the thorax and therefore difficult to detect by external palpation and mammography examination have been described in a follow-up study, and further possibilities of application suggested.


[Estimation of fetal weight by ultrasound (author's transl)]. In attempt to estimate birth weight in utero several dimensions of fetal head and trunk cross-sections, obtained by ultrasonic A- and B-scan techniques (Kretz-Technik), were related to postnatal weights in 108 normal and abnormal pregnancies. Abdominal parameters showed better correlation with weights than did head parameters. Evaluations derived from mean diameter, circumference or area yielded more accurate estimations than those derived from single diameter. In addition, the combination of both head and abdomen measurements increased accuracy. The best results were obtained by planimetric determination of head and trunk cross-sectional areas. Using this method the standard error of estimates was 233 gm. as compared with 423 gm. employing biparietal diameter alone.


[Early ultrasonic diagnosis of anencephaly and iniencephaly (author's transl)]. The routine and repeated ultrasonic examination during pregnancy gives the possibility of observing fetal malformation, especially of the head and the spinal column, at an early stage of pregnancy. One case of anencephalus and two cases of iniencephalus diagnosed by ultrasonic between the 16th and 28th week of pregnancy are described. The method is compared with other diagnostical possibilities and the consequences for the further pregnancy are discussed. The ultrasonic examinations were done with the Vidoson 635 from Siemens Company/Erlangen.


[Malignant ovarian neoplasms in young women (author's transl)]. 15 cases of malignant ovarian neoplasms of the period 1948-1974 are being reported. All these women were less than 30 years of age. The youngest patient was 15 years old and 7 were less than 25 years old. These 15 cases represent 2,2% of all ovarian neoplasms with primary surgical treatment at the I. University Clinic of Obstetrics and Gynecology in Vienna in this period. Anamnestic datas, symptomatology and clinical aspects of these cases are reported. Surprisingly high was the rate of 9 cases of primary stage cancer Ia in these young women and girls, which was significant higher than in the total material of the clinic. Therefore it seems intelligible that in spite of the high rate of conservative surgical treatment 9 patients have survived 5 and more years without any symptoms. The possibility of conservative surgical treatment of malignant ovarian neoplasms in young women and teenaged girls of primary stage of cancer Ia is discussed.


[Infantile and hypoplastic uterus: a contribution to overcome the confusion of terms (author's transl)]. The confusion of terms between the radiological literature and the gynaecological and anatomical literature regarding the definitions of the infantile and the hypoplastic uterus are described. The history of this confusion is traced. The two types of uterus were clearly defined by K. Menge and K.v. Oettingen in 1930. The infantile uterus shows an abnormal relationship between the length of the cervix and the length of the uterine cavity of 1:1 or 2:1, whereas the hypoplastic uterus shows a normal relationship between the length of the cervix and the length of the uterine cavity of approximately 1:2.


[The excretion of chorionic gonadotropin in ectopic pregnancy (author's transl)]. In 244 cases of ectopic pregnancy the excretion of chorionic gonadotropin in the urine was determined in 459 tests. In 88% of the cases an immunologic pregnancy test (pregnosticontest) was positive. The mean quantitive excretion of chorionic gonadotropin in the urine was 20 +/- 13% of the values for normal pregnancy. In 11.4% of the cases, values compatible with the chorionic gonadotropin excretion in normal intra-uterine pregnancy were observed. Repeat quantitative tests on the same patient showed a decrease of the mean chorionic gonadotropin titre in the urine with increasing gestational age. The results are shown in diagrams.


A new type of mutation in Schizosaccharomyces pombe: vegetative iodine reaction. Colonies of Schizosaccharomyces pombe that contain ascospores (e.g., colonies of homothallic strains) turn black after treatment with iodine vapors. Heterothallic strains of S. pombe normally do not show this reaction. In experiments with the latter strains we found mutants which exhibit a positive iodine reaction though they do not contain ascospores. This phenotype is due to mutations in a new gene, vir1 (vegatative iodine reaction). The vir1 locus is not linked with the mating-type genes.--Strains of mating-type h-S are known not to give any spontaneous mating-type mutations. Mating-type mutations were also not found after treatment with nitrous acid.


Population genetics of allozyme variation in Neurospora intermedia. Electrophoretically detectable variation in the fungus Neurospora intermedia has been surveyed among isolates from natural populations in Malaya, Papua, Australia and Florida. The principal result is a pattern of genetic variation within and between populations that is qualitatively no different than the well documented patterns for Drosophila and humans. In particular, there is a high level of genetic variation, the majority of which occurs at the level of local populations. Evidence is presented which argues that N. intermedia has a population structure analogous to that of an annual vascular plant with a high level of vegetative reproduction. Sexual reproduction appears to be a regular feature in the biology of the species. Substantial heterokaryon function seems unlikely in natural populations of N. intermedia. Theoretical considerations concerning the mechanisms underlying the observed pattern of variation most likely should be consistent with haploid selection theory. The implications of this constraint upon the theory are discussed in detail, leading to the presentation of a model based upon the concept of environmental heterogenicity. The essence of the model, which is equally applicable to haploid and diploid situations, is a shifting distribution of multiple adaptive niches among local populations such that a given population has a small net selective pressure in favor of one allele or another, depending upon its particular distribution of niches. Gene flow among neighboring populations with differing net selective pressures is postulated as the principal factor underlying intrapopulational allozyme variation.


What influence does age have on rehabilitation of amputees? A study of 194 male lower extremity amputees, with an average age of 56.8 years, showed that vascular disease is the most common cause of limb loss at all ages. Increasing age was correlated with an increasing incidence of bilateral amputation and arteriosclerotic and pulmonary problems, lower goals and levels of achievement, increased mortality during therapy, fewer amputees who were able to return home, an increased number of aids (cane, crutches, wheelchair), and a longer rehabilitation period. Many patients over age 65 required nearly a year of rehabilitation to achieve maximum benefit.


Impaired anamnestic cellular immune response in patients with Crohn's disease. The cellular immune system was studied in patients with Crohn's disease (CD), not receiving corticosteroids, or azathioprine, by means of in vitro and in vivo methods. It was found, that the in vitro lymphocyte reactivity of 54 CD patients after stimulation with a cocktail of antigens (varidase, trichophyton, candida, mumps, and PPD) was significantly depressed when compared with the response of 20 simultaneously cultured healthy controls (p less than 0-001) or a group of 54 separately cultured healthy controls, matched for age and sex (p less than 0-001). The lymphocyte response of a control group of 18 patients with malnutrition or malabsorption without any evidence of inflammatory bowel disease, was higher than the response of an equal number of CD cases, although the difference failed to reach significance. Intradermally injection of the same five antigens, as used in the antigen cocktail, showed a failure to react to any antigen in 13 out of 48 CD patients, in comparison with three of 48 matched healthy controls (p less than 0-01). In both CD patients, as well as in healthy controls a significant correlation could be demonstrated between the number of positive skin tests, the area of skin induration, and the in vitro lymphocyte responsiveness after stimulation with the antigen cocktail. In the CD group no correlation was found between in vitro responsiveness and disease activity, as defined by a score of clinical and biochemical parameters. The depressed skin reactivity and the hyporesponsiveness in the lymphocyte transformation test after stimulation by an antigen cocktail suggest that depression of the anamnestic cellular immune response is a basic feature in patients with Crohn's disease.


Viral antibody studies in pancreatic disease. Viral studies were performed on sera from 54 patients with recent acute pancreatitis, 10 with recurrent acute pancreatitis, seven with chronic pancreatitis, and 10 with pancreatic carcinoma, and on sera from 81 age- and sex-matched controls. In 29 of the acute pancreatitis patients from whom paired sera were obtained no convincing evidence of recent viral infection was found. A higher incidence of raised antibody titres against Coxsackie B3 and B4 was observed in the group of acute pancreatitis patients compared with their controls. The possible signficance of these observations and their relationship to the aetiology of the pancreatitis and to other immunological findings are discussed.


Importance of the site of endoscopic gastric biopsy in ulcerating lesions of the stomach. Twenty freshly resected stomach specimens, each containing an ulcerated carcinoma, were studied in an attempt to determine the best site for gastric biopsy. Using endoscopic biopsy forceps multiple biopsies were obtained from various sites around the ulcer. Carcinoma was detected with similar frequency in biopsies from the slough and from the rim of the ulcer. The positive biopsy rate was increased to 95% when the results from the rim and the slough were combined. It is suggested that the diagnostic accuracy of endoscopic gastric biopsy can be improved by taking biopsies from both the rim and the slough of an ulcer.


Bile acids and colonic motility in the rabbit and the human. Colonic motor activity was initiated by infusions of bile salts into the caecum or rectum of the anaesthetized rabbit. Primary bile acids were examined proximally and distally in the colon and elicited marked motor responses. Sinc dihydroxy bile acids are known to be potent inhibitors of electrolyte and water absorption in the colon, the secondary bile acid deoxycholic acid, the dihydroxyl compound most related to cholic acid which is the main bile acid in the rabbit, was examined distally and was also active, but to a lesser extent than cholic acid conjugates in this species. In man, a relationship was found between the faecal bile acid excretion and colonic motility: the introduction of bile acids directly into the human sigmoid colon and rectum also stimulated colonic motility. In man, the dihydroxy compound chenodeoxycholic acid was slightly more active than conjugates of cholic acid.


Alterations in tissue ferritins in iron storage disorders. Purified tissue ferritins isolated from Bantu subjects with gross haemosiderosis, from a patient with idiopathic haemochromatosis (HC) treated by phlebotomy, and from rats with experimental iron overload were studied in order to determine the significance of the abnormality previously demonstrated in tissue isoferritins in patients with IHC. The isoferrin profile of the tissues from the Bantu subjects and the iron-loaded rats showed a similar abnormality to that previously found in patients with untreated IHC--that is, an abnormally uniform distribution of iron-containing isoferritins with an increase in the more basic isoferritins and an apparent absence of the more acidic ones. In contrast, tissues from the patient with treated IHC, who was iron depleted at the time of death, showed the normal organ-specific isoferritin distribution. These findings strongly suggest that the abnormal distribution of tissue isoferritins in IHC is an acquired phenomenon and unlikely to be related to an underlying genetic defect in ferritin or iron metabolism.


Jaundice due to carbimazole.

Jaundice due to carbimazole. On three occasions, a 63 year old housewife with hyperthyroidism developed a reaction which included fever, pruritus, malaise, and, on one occasion, jaundice one to 17 days after taking carbimazole. Challenge with carbimazole was followed within 12 hours by abdominal pain, pruritus, and increased serum transaminase levels. Light microscopy of a liver biopsy showed increase of portal zone cellularity over the control and the electron microscopy revealed fine structural changes compatible with drug-related liver injury.


Studies of intestinal lymphoid tissue. I. Electron microscopic evidence of 'blast transformation' in epithelial lymphocytes of mouse small intestinal mucosa. The morphology of epithelial lymphocytes in osmium-fixed, Epon-embedded jejunum of adult mice was studied by light and electron microscopy. Toluidine blue-stained 1 mum 'thick' plastic sections were compared with adjacent thin sections, thereby permitting precise ultrastructural identification and description of selected epithelial lymphocytes. Their size and appearances varied considerably, ranging from typical small lymphocytes through medium-sized lymphocytes to large immunoblasts. A high proportion of medium-sized epithelial lymphocytes (mean diameter 6-9 +/- 1-1 mum) contained several lysosomes, extensive Golgi complexes, prominent centrioles and abundant ribosomes. Their appearances, therefore, corresponded directly to mitogen-stimulated lymphocytes. In contrast, immunoblasts were big cells (mean diameter 11-0 +/- 0-8 mum) with large, euchromatic nuclei and prominent nucleoli. The majority had pale-staining, ribosome-studded cytoplasm and thus resembled type I, or T blasts. Very rarely, densely staining blasts containing ribosomes and well developed rough endoplasmic reticulum were observed; these corresponded to type II or B blasts. These observations indicate that transformation of lymphocytes occurs within the interepithelial cell spaces of the small intestinal mucosa, suggesting that epithelial lymphocytes are immunocompetent cells which may be responsive to local antigenic stimulation.


Studies of intestinal lymphoid tissue. II. Aspects of proliferation and migration of epithelial lymphocytes in the small intestine of mice. Mice were given either intraperitoneal tritiated thymidine (3H-Tdr) or colchicine to study proliferation and migration of intestinal epithelial lymphocytes. Both labelled medium and large lymphocytes ('immunoblasts') were observed throughout the epithelium, crossing the basement membrane and within villous lymphatics for at least seven days after 3H-Tdr administration. Epithelial lymphocytes are predominantly young cells, actively dividing at the rate of 1% per hour. They do not migrate along the villi, unlike epithelial cells, but circulate rapidly through the epithelium, returning to the lamina propria at the rate of approximately 3 epithelial lymphocytes/1000 epithelial cell nuclei/hour. The labelling pattern of epithelial lymphocytes and intralymphatic cells with time was very similar suggesting that epithelial lymphocytes therefore may directly enter adjacent lymphatics and hence gain access to thoracic duct lymph.


The cellular infiltrate of the jejunum in adult coeliac disease and dermatitis herpetiformis following the reintroduction of dietary gluten. The cellular infiltrate of the jejunal mucosa has been studied in patients with both treated and untreated adult coeliac disease and dermatitis herpetiformis and serially in treated patients before and after the reintroduction of gluten to the diet. In adult coeliac disease and dermatitis herpetiformis the jejunal mucosa showed similar abnormalities of the cellular infiltrate which was characterized by an increase in intraepithelial lymphocytes and lamina propria plasma cells and eosinophils, with the greatest numbers of cells occurring in untreated patients. At 24-48 hours following a single 25-g gluten challenge there was an increase in lamina propria plasma cells, lymphocytes and eosinophils and intraepithelial lymphocytes. This rise was sustained after seven days on a gluten-containing diet for all of these cell groups except lamina propria lymphocytes. These responses were essentially similar in both adult coeliac disease and in those dermatitis herpetiformis patients who had jejunal lesions before treatment. In dermatitis herpetiformis patients with normal jejunal morphology on a normal diet there was an upward trend in lamina propria plasma cells and intraepithelial lymphocytes within one to three weeks of taking extra dietary gluten. These results are compatible with the view that more than one immunological mechanism may be responsible for the pathogenesis of the jejunal lesion of coeliac disease and dermatitis herpetiformis.


Postoperative motility of the large intestine in man. Motor activity of the colon in the immediate postoperative period has been studied in human subjects using radiotelemetering capsules, radioopaque markers and serial abdominal radiographs. Following operations outside the abdomen there is a delay of about 16 hours before colonic activity returns. After abdominal operations the delay is from 40 to 48 hours. The length of an operation has no significant effect upon the duration of colonic ileus. The amount of postoperative analgesia has no significant effect upon the duration of colonic ileus. Gaseous distension after laparotomy is confined to the colon.


A relation between the energy of food and gastric emptying in men with duodenal ulcer. Using information about the volume and energy density of meals, results from the literature on gastric emptying for healthy men can be marshalled into a consistent body. The same process applied to the published papers on men with duodenal ulcer shows that they have abnormally rapid gastric emptying, especially for meals of high-energy density. This provides confirmation of the view of Shay (1944) that the slowing of gastric emptying by duodenal receptors is less in men with duodenal ulcer than it is in healthy men.


The pseudomembranous colitis associated with clindamycin therapy--a viral colitis. Four patients are described who developed pseudomembranous colitis in association with clindamycin therapy. Rectal biopsies from two patients were studied with the electron microscope and compared with the ultrastructural appearance of the rectal mucosa from seven normal people. Ultrastructural evidence for a viral colitis was obtained. The significance of the clindamycin therapy to the viral colitis and the contribution of the viral colitis to the clinical state are discussed.


Factors relevant to the prognosis of chronic gastric ulcer. The factors that determine the recurrence rate of chronic gastric ulcer were studied in 105 patients. It was found that complete healing of the ulcer significantly reduced the recurrence rate and subsequent need for hospital admission because of ulcer symptoms when this group was compared with those who left hospital with their ulcers unhealed. Those admitted with large ulcers also had a higher recurrence rate. The age and sex of the patient, ingestion of analgesics and cigarette smoking did not influence recurrence. The initial healing rate of the ulcer also had no effect on the subsequent course of the patient.


Quantitative liver imaging using 131-I Rose Bengal as an index of liver function and prognosis. A technique for assessing quantitatively hepatic function by direct measurement of liver parenchymal cell uptake of 131I Rose Bengal using a scintillation camera with a digital store and retrieval system is described. Ninety-four studies were performed on 84 patients with a variety of hepatic disorders over a two-year period, the diagnosis in each case being established by liver biopsy or laparotomy. The results were compared with the clinical, biochemical and histological assessment of the patients. A good correlation was found between the half-time for hepatic uptake of 131I Rose Bengal and the histological changes, as well as with clinical prognosis measured in terms of clinical improvement or deterioration to death. The rate of liver uptake was found to be a better index than the clearance of radioisotope from the blood and was superior to conventional biochemical investigations in both icteric and anicteric patients. The test was not shown to be of clinical value in discriminating between intra- and extrahepatic causes of jaundice. It is suggested that this technique may provide a safe and sensitive method for assessing the severity of liver dysfunction and also for monitoring clinical progress, especially in situations where liver biopsy may be unreliable or hazardous.


Influence of intravenously administered acetylsalicylic acid on platelet functions. A pharmacodynamic and pharmacokinetic study. The influence of intravenously administered acetylsalicylic acid (ASA) on the kinetics of platelet function was examined in 10 patients. Simultaneously, assays of salicylate in plasma were performed. A significant inhibition of platelet aggregation as well as PF 3 and PF 4 availabilities could be demonstrated 2 min after injection. A decrease of platelet adhesion was significant after 15 min. The inhibition of platelet functions was still present after 24 h and was partially demonstrable after 72 h. The concentration of salicylate in plasma 2 min after injection of ASA was only about two thirds of the level calculated from mere distribution in circulation. After 1 h, half of the initial salicylate had disappeared from plasma. No salicylate could be found after 24 hours. ASA also depressed platelet functions when added to platelet-rich plasma in vitro in a concentration of 100 mug/ml. Inhibition of platelet aggregation and of PF 4 availability were dependent on the time of incubation. Their onset was much slower in vitro than in vivo. No inhibition of the PF 3 availability could be found in vitro. The inhibition of platelet functions by ASA is demonstrable almost immediately after injection while the duration of this inhibition is considerably longer than the elimination time of salicylate from plasma. This allows the conclusion that a direct intravascular reaction between ASA and platelets occurs and that the inhibition of platelet functions is irreversible.


Adenine nucleotide metabolism during the aggregation of human platelets by bovine factor VIII. Human platelets, prelabelled with [3H]-adenine in vitro, were aggregated biphasically by bovine fibrinogen/factor VIII, and the amounts and specific radioactivity of ADP and ATP as well as the radioactivity of ATP, ADP, AMP, IMP and hypoxanthine + inosine were determined intracellularly and extracellularly. During the second phase of aggregation, ATP and ADP were released (50% of total) with a specific radioactivity 15-20 times lower than that of the ATP and ADP retained in the cells. The specific radioactivity of the ATP and ADP in the cells increased during release. Radioactive ATP was converted to radioactive hypoxanthine during release. These findings correlated well with those obtained with collagen, and indicate that bovine factor VIII induces the platelet release reaction whereby the storage (non-metabolic) pool of ATP and ADP is released while the metabolic pool is retained.


Electroencephalography in haemophilia and Christmas disease. Electroencephalography has been performed in a series of patients with haemophilia and Christmas disease because of the suggestion by other authors of a high incidence of abnormality. In an adult population of haemophiliacs no difference was found in the incidence of abnormalities compared with the general hospital population.


Studies on catabolism of 125I-labelled fibrinogen in normal rabbits and in rabbits with indwelling intravenous catheters: methodologic aspects. The catabolism of rabbit fibrinogen labelled with radioactive iodine was studied over a period of 7-9 days in normal rabbits and in rabbits with indwelling intravenous catheters. The labelled fibrinogen was highly clottable and homogeneous on immunoelectrophoresis and disc electrophoresis. The protein-bound 125I-activity amounted to at least 99%. Normal rabbits with a weight between 1.6 and 2.2 kg exhibited a mean plasma volume of 41.65 ml/kg. A mean half-life time of 1.69 days and a mean fractional catabolic rate of 59.8% of the plasma fibrinogen pool per day was computed by tracing labelled fibrinogen. The absolute catabolic rate revealed a mean value of 58.7 mg/kg body weight/day. Comparable results were obtained for all three labelled fibrinogen batches. A siliconized polyvinyl tubing with an outer diameter of 2.0 mm inserted into a jugular vein up to a length of 10-12 cm and indwelling for more than 10 days did not significantly influence the parameters studied for controlling the fibrinogen catabolism except for the absolute catabolic rate of 112.8 mg/kg/day which differed significantly from that of the control group. Thus, the indwelling intravenous catheter had no or only a minor effect on the activation of intravascular coagulation.


Fibrinogenolytic substance (hementerin) of Brazilian blood-sucking leeches (Haementeria lutzi Pinto 1920). The fibrinogenolytic activity of the salivary gland extract from the Brazilian blood-sucking leech Haementeria lutzi Pinto 1920 is characterized. The substance, named here hementerin, is stable and active at very low protein concentration, does not exhibit direct proteolytic activity on casein, fibrinogen, or fibrin, and is able to activate the human plasma fibrinolytic system in the presence of a serum cofactor and/or calcium. This indirect activation mechanism distinguishes hementerin from hirudin and shows a similarity with streptokinase. The effect on blood coagulation tests is reported.


The effect of 5-fluorouracil on the mitotic cycle and DNA synthesis in the epithelium of mouse small intestine. The examinations were performed on 42 mice of the Porton strain. The experimental animals were injected intraperitoneally with the dose of 75 mg of 5-fluorouracil per kg body weight. The first experimental group received injections of [3H]thymidine within 48 hours and the second group within 96 hours of the injection of 5-fluorouracil. Two mice from each group were killed at within 1, 2, 4, 8, 12, 24, and 48 hours of the [3H]thymidine injection. Calculations of the mitotic index and time of duration of individual phases of the mitotic cycle in epithelial cells of the small intestine were based on application of the autoradiographic method. These studies lead to the conclusion that 5-fluorouracil disturbs the course of metabolic processes in the cell, which are also related with the distribution of the genetic material. Histological examinations show that 5-fluorouracil produces profound morphological changes in the intestine, which affect both the intestinal epithelium and the connective tissue stroma. The autoradiographic tests revealed a considerable suppression of the mitotic activity of the epithelium of intestinal crypts. Moreover, it was shown that 5-fluorouracil inhibits the mitotic activity of the intestinal epithelium by diminishing the number of cells capable of entering into mitosis. Nevertheless, by 96 hours following introduction of a single dose of 5-fluorouracil normal morphological structure and mitotic activity of the intestinal wall cells are restored.


Ingestion and digestion of erythocytes by non-irradiated and irradiated macrophages. The effect of X-rays (1300 R) and gamma irradiation (3000 R) on phagocytic activity of mouse peritoneal macrophages cultivated in vitro was studied using human glutaraldehyde-fixed red blood cells. The peroxidative activity of haemoglobin was cytochemically detected by the DAB method. The obtained results indicate that the applied dose of X-irradiation does not affect the phagocytic activity of macrophages. On the contrary, the gamma irradiation (3000 R) causes acceleration of phagocytic activity of macrophages with concomitant impairment of intracellular digestion of ingested material. Weakened cytochemical reaction for acid phosphatase suggests that sufficiently high doses of irradiation cause some disturbances in the biosynthesis of lysosomal enzymes in exposed macrophages.


Oxidative enzymes in the development of Fasciola hepatica L. II. Dehydrogenase activity of miracidium. Histochemical methods were used to detect succinate, isocitrate, malate, lactate, alpha-glycerol phosphate' L-glutamate, alcohol, glucose-6-phosphate, 6-phosphogluconate, and beta-hydroxybutyrate dehydrogenases in miracidium--a free living larva of Fasciola hepatica. Examinations were carried out on miracidia which had just left egg covers and on those which had survived for 18 and 24 hours, respectively. Differences were observed regarding the occurrence and intensity of the enzyme activity depending on the age of the larvae. On the basis of the localization of dehydrogenases and persistence of their activity in the miracidia in various periods of their lives, the author concludes that in young larvae there exist three parallel modes of oxidation: glycolytic, in the tricarboxylic acid cycle, and in the pentose cycle. Moreover, there occur processes of amino acid metabolism and of fatty acid oxidation. The 18-hour larvae exhibit a marked predominance of oxidation in the Krebs cycle, the remaining modes being less pronounced, and after 24 hours the only way to obtain energy in the miracidium is oxidation in the Krebs cycle. Likewise noteworthy is the enhancement of the processes of fatty acid oxidation, this being evidenced by an intensified activity of beta-hydroxybutyrate dehydrogenase. The role of each enzyme in the metabolism of the larva is discussed.


Oxidative enzymes in the development of Fasciola hepatica L. III. The activities of oxidases and dehydrogenases in the sporocyst. The object of the study was the investigation of the occurrence and distribution of some oxidative enzymes in the sporocyst of Fasciola hepatica L. The samples were examined for the presence of cytochrome oxidase, peroxidase, NADH and NADPH tetrazolium reductases, as well as succinate, isocitrate, malate, lactate, alpha-glycerophosphate, glyceraldehyde-3-phosphate, glucose-6-phosphate, beta-hydroxybutyrate, L-glutamate and alcohol dehydrogenases. All of them save cytochrome oxidase were found to occur in the sporocyst. The presence and localization of these enzymes were examined by histochemical methods in various stages of development of the sporocyst. These investigations permitted it to be established that glycolytic processes are the principal way of release of energy for all developmental groups of this larva. Moreover, the functions of the tricarboxyl acid and pentose-phosphate cycles were detected and found to play a less important part in processes of energy production in the sporocyst. In addition, the functioning and metabolism of each larval organ in various stages of its development were discussed in so far as was possible on the basis of the analysis of the above-mentioned oxidative enzymes.


Synthesis of glucuronoglucans in chicken cartilage cultured in synthetic medium. Cartilaginous femur and tibia rudiments from 10-day-old chick embryos were grown in vitro for 4 days in Parker's solution without protein added, and subsequently fixed and extracted successively with 0-2 N HClO4 at 4 degrees C (fraction A), 5 per cent trichloracetic acid (TCA) at 4 degrees C (fraction B), and 5 per cent TCA at 90 degrees C (fraction C). The residue after extraction was dissolved in 1 N NaOH at room temperature (fraction D). Fraction C containing most of hexuronic acids and aminosugars of the cartilage was used to study the quantitative changes of glucuronoglucans throughout the culture period. The amount  of hexuronic acids and aminosugars was increased after 24, 48, 72 and 96 hours of culture. After 96 hours the level of hexuronic acids was twice that found prior to establishing the culture. The increment was statistically significant.


Interaction between macrophages of various origin and Toxoplasma gondii under conditions in vitro. The study of proliferation of a virulent strain of Toxoplasma in cultures of macrophages of various origin revealed a certain sequence in the development of the pathogen: penetration and phagocytosis of the parasite, the stage of disintegration of one part of population and active proliferation of the other, resulting in the destruction of host cells. It was found that the penetration and phacocytosis were more active if macrophages from resistant animals (rats) were used, in comparison with those isolated from susceptible animals (white mice, guinea pigs). The activity of proliferation of a virulent strain of Toxoplasma also differs with the host cells: the toxoplasma multiply more rapidly in macrophages from susceptible animals than in those from resistant animals. The following changes of macrophages due to proliferation of the parasite were observed: change of form of the cell accompanied with the loss of cytoplasmatic processes, vacuolation of the cytoplasm, displacement of the nucleus towards the periphery followed by its pycnosis and rupture of the cell.


[Serological studies of cestode cysts. P1 blood-group activity in cysts of zoo animals]. The cyst fluid of cestodes from various animals kept in zoological gardens was examined for the presence of A-, B-, H- and P1-blood group activity. While the results in the ABH-system were negative, the cysts from 2 of 13 animals examined (1 elk and 1 reindeer) presented P1-blood group activity.


Population structure and dynamics of the house dust mite Dermatophagoides farinae (Acarina: Pyroglyphidae) in Czechoslovakia. The relationship between the room microclimate and population dynamics of the house dust mite Dermatophagoides farinae Hughes, 1961 was studied. A distinct increase of the mite population density in mattresses was observed only in the period, when the monthly means of relative air humidity in rooms were higher than 47-50%, denominated by the author as critical air humidity. This is a considerably lower value than that relevant to Dermatophagoides pteronyssinus (Trouessart, 1897) from the paper by Bronswijk et al. (1971) (critical air humidity 60-65%). The climatic humidity affecting the room microclimate is consequently the main reason why one species or another is predominant under different geographical conditions. From October till May the D. farinae population is primarily composed of protonymphs, in the period of maximum population density (May-October) the presence of adults is predominant. Protonymphs are considered to be least resistant to the humidity decrease in their environment.


Parasitic mites of Surinam. XXXII. New species of feather mites (Sarcoptiformes, Analgoidea). Seven new species of feather mites belonging to families Analgidae, Falculiferidae, Pterolichidae, Pteronyssidae and Xolalgidae are described from Columbiformes, Cuculiformes, Piciformes and Passeriformes of Surinam.


Intestinal helminths from grey mullets, Mugil capito Cuv. and M. cephalus L., of Lake Borullus, A.R.E. Helminthological examination of grey mullets, Mugil capito Cuv. and M. cephalus L. from brackish Lake Borullus in the Nile Delta in the Lower Egypt revealed that these fishes are infected with two species of digenetic trematodes, Haplosplanchnus pachystoma (Eysenhardt, 1829) and Saccocoelium obesum Loos, 1902 and one acanthocephalan species, Neoechinorhynchus agilis (Rudolphi, 1819). On comparing the incidence and intensity of infection of individual fish samples it was found that after migration from the sea to the lake the grey mullets lose gradually their intestinal trematodes.


Biological changes in the rhizosphere of wheat after foliar application of chlorocholinechloride, urea and 4-chloro-2-methylphenoxyacetic acid. In field experiments wheat in the phase of shooting was sprayed with solutions of chlorocholinechloride (CCC) and urea, CCC and ammonium salt MCPA (Aminex) or CCC, urea and Aminex. The effect of the treatment on dry weight of overground parts of wheat, number of bacteria, production of carbon dioxide, urease activity and content of ammonium in the rhizosphere soil was investigated. In all cases evolution of carbon dioxide in the rhizosphere soil was higher than that in the control soil. Highest numbers of bacteria were found in the rhizosphere soil of plants treated with urea, the herbicide and their mixtures. Content of ammonium was higher in the control soil than in the rhizosphere soils, the urease activity was highest in the rhizosphere soil of plants treated with the solution of the herbicide and with the combination of the herbicide with urea.


The Azotobacter flora of some Czechoslovakian watercourses. The occurrence of Azotobacter in some Szechoslovakian watercourses has been investigated. Several strains belonging to A. chroococcum and A. beijerinckii were isolated from 7 out of 18 samples. A. insignis has been isolated from the flowing water of Lake Machovo at Doksy. This is first report of this strictly aquatic Azotobacter species in Czechoslovakian watercourses. The taxonomy of the genus Azotobacter was discussed against the background of the existing knowledge resulting mainly from other taxonomic techniques than those based on the phenotypically expressed characters.


Genetic variability of Chlamydomonas reinhardtii induced by six urea derivatives. The lethal and mutagenic effect of six urea derivatives applied to the cells of Chlamydomonas reinhardtii Dang was investigated. The mutagenic effect of two N-alkylnitroso derivatives (N-methyl-N-nitroso- and N-ethyl-N-nitrosourea), two monoalkyl derivatives (N-methyl- and N-ethylurea) and two dialkyl derivatives (N,N'-dimethyl- and N,N'-diethylurea) was compared at equal molar concentrations and different cell survival or at equitoxic concentrations, i.e. at equal survival. The former type of appraisal shows the alkylnitroso derivatives to be strong mutagenic agents, exceeding in their effect several times both monoalkyl- and dialkyl derivatives. MNU is seen to be a stronger mutagen than ENU. Alkyl derivatives are generally weak mutagens, the strongest being DEU and the least potent DMU. On using the latter type of evaluation MNU is seen to be clearly the strongest mutagen while the other five compounds, including ENU, have, at equitoxic concentrations, approximately the same effect.


Transport properties of membrane vesicles from Acholeplasma laidlawii. III. Evidence of active nature of glucose transport. Membrane vesicles obtained from Acholeplasma laidlawii accumulate glucose as well as maltose and fructose against their concentration gradient in the absence of exogenous energy sources. Glucose uptake by membrane vesicles is inhibited by anaerobiosis and by electron transfer inhibitors, such as rotenone and amytal, but not by 2-heptyl-4-hydroxyquinoline N-oxide, antimycin A, cyanide and azide. Rotenone, cyanide and amytal also produce a rapid efflux of glucose from the membrane vesicles. Arsenate, oligomycin and N,N'-dicyclohexylcarbodimide do not inhibit glucose transport. Transport of glucose is markedly inhibited by proton conductors such as CCCP and pentachlorophenol. It is concluded that glucose transport can be driven by a high-energy state of the membrane or by the membrane potential.


Serum lysozyme in mice subjected to combined immunosuppression with 6-mercaptopurine and hydrocortisone. Simultaneous peroral administration of 6-mercaptopurine (80 mg/kg per day) and subcutaneous injection of hydrocortisone (1 mg/mouse per day) for ten days results in increased lethality and more pronounced decrease in total peripheral leukocyte count and serum lysozyme levels as compared with mice receiving each drug separately. The possible mechanism of this effect is discussed.


[Alcoholism in school-age children].

[Alcoholism in school-age children]. Curiosity motivated consumption of illegal drugs by young people decreased during the last 5 years. At the same time the problem of school-children abusing alcohol increased. This has to be seen against the background of more general epidemiological data of alcohol consumption in the Federal Republic of Germany: --between 1961 and 1974 the expenditure for alcoholic beverages more than doubled; --according to serious estimations there are between 700,000 and 1 million of alcoholics in this country (from these about 8-10% being minors); --the average age of inmates of clinics for alcoholics dropped considerably during the last decade. Main findings of a follow-up survey conducted (size of sample: about 10,000 school-children in Hamburg, age 13-20, representative of a total of 110,000) are: --more than 25% of the above mentioned 110,000 school-children showed a rather excessive drinking behaviour (i.e. having been drunk 1-5 or more than 5 times during a period of 2 months prior to the interviews); --positive correlations were found to exist between excessive drinking habits and certain psycho-social variables (i.e. broken home, suicide-attempts, excessive consumption of alcohol by the parents, etc.); --the subgroup of those school-children who were users of illegal drugs: about 60% of them belong also to the category of "excessive alcohol user". Reasons for the general increase of alcohol consumption in Western Germany are for instance: --a change of drinking habits (more frequently, drinking at home and alone); --a shift of preferances (from relatively low percentage-beverages like beer and wine to so-called hard liquors); --an increase of alcohol consumption among those societal groups--the young and women--who formerly were almost abstinent. Some reasons and causes for the increase of alcohol consumption among school-children are: --being exposed to negative model-behaviour of adults and especially of parents; --peer-group pressure; --the discovery of school-children by the industry as an important consumer group, i.e. shape of images through advertisement (for example "drinking makes you appear strong" etc.); --the increasing loss of functions of traditional agents of socialization (i.e. family, school and religion).


[Problems of toxic psychosis as illustrated on the example of the so-called LSD psychosis]. The effects of LSD are characterized by a number of disturbances of perception and experience, which can be observed in the fields of visual, spatial and temporal perception and of affectivity. We also see disturbances of experience, which can otherwise be observed only in psychoses, for example reduction or change of cognitive functions, but also depersonalization and euphoria. In atypical courses of intoxication ("horror-trips") anxiety and excitement are predominant. Atypical courses of intoxication may be interrupted by "talk down" and additional application of tranquilizers. In a certain number of LSD-users in our clinic we saw psychoses. We classify them into flash-backs, exogenic (toxic) psychoses and so-called "endoform psychoses". The latter implies three possible constellations: accidental coincidence of LSD-use and psychosis; pre-existing psychosis with symptomatic use of LSD as an attempt of self-treatment; finally the onset of a psychosis may be triggered by the use of the halluzinogen. From the symptomatological cross-section they cannot reliably be distinguished from real schizophrenia. An independent nosological unit "LSD-psychosis" does not seem to exist.


[Prenatal diagnosis].

[Prenatal diagnosis]. Not less than 4% of live-born individuals suffer from some genetic or partly genetic condition. The risk in genetic high risk pregnancies is dependant on the mode of inheritance. Genetic-counselling and in some severe disorders prenatal diagnosis can help to avoid genetic diseases. Indications, technique and results of amniocentesis for prenatal diagnosis of genetic diseases are discussed.


[Pregnancy with an intrauterine pessary in the placenta]. A case of a 23 year old patient which had become pregnant with a copper-T-IUD in situ is presented. After a pregnancy without many complications a healthy child was born. The copper-T-IUD was partially embedded in the placenta. Usually the delivery of a living and healthy child will not take place if a foreign body is situated in the placenta. If a woman becomes pregnant in spite of an IUD in situ, the IUD should be removed, even if this removal should terminate pregnancy. The risk of septic abortion in a pregnant woman with an IUD in situ is 1 in 15 to 1 in 30.


[Legal abortions at the University-Gynecological Clinic Mannheim during 1971-1974]. Between 1971 and 1974 142 legal abortions were performed. Methods used were determined by gestational age, size of the uterus and whether or not abortion in conjunction with sterilization was indicated. Dilatation and evacuation was employed in 46% of cases; in 8% of these sterilization was performed at a later date. A further 55% were treated by means of primary hysterectomy, 38% via the vaginal route, 17% via the abdominal route. Complications were observed in 4 cases (3 perforations, 1 post-operative haemorrhage, 1 case of endometritis). The complication rate was not higher than in non-pregnant women.


[Potency disorders in the aging men. Psychiatric aspects]. Based on experiences gained in psychiatric counselling for patients with problems specific to climacterium virile, the climacterium virile as a time of crisis is compared to the period of puberty. Suggestions are given to provide a crisis management for this particular period of life in order to improve the chances for a satisfactory development during the subsequent years of life.


[Exo- and endocrine testicular function in the aging man]. In males over 60 years of age FSH excretion remains within the same range, whilst LH secretion increases significantly. Plasma testosterone and the biological active testosterone fraction decreases whilst at the same time the percentage of protein bound biological inactive testosterone increases. The androgen dependent target tissues become less sensitive to testosterone. The metabolic clearance rate for testosterone decreases. Spermatogenesis seems to stay intact in male senescence but exhaustive research in this field is not available.


[Testicular histology in the aging man]. In aged men beyond 50 years--regardless of claims of impotence or infertility--testicular biopsies are discussed. Generally speaking all biopsies show more or less histological changes due to old age. Reduced spermatogenesis, fibrosis of tubule walls and retrogression of Leydig cells are mostly seen. The morphological changes in Leydig cells reflect the usual cell failure more convincably than the decrease in number. Selected microphotographs represent characteristic biopsies in old age. These findings confirm the previous results of other investigators. The various histological changes explain the different intensity and the variety of the claims in aged men as definite signs for male climacteric.


[Qualitative and quantitative determination of proteins in the seminal plasma of the aging man]. A short review on the origin of the human spermaplasma proteins and their different methods of examination is given. It follows a description of the results of 44 men over 50 years of age concerning albumin and immunoglobulin IgA and IgG. These results were obtained with an immunodiffusion technique.


[Foreign proteins in the blood and lymph after oral administration. Giant molecular foreign proteins in the blood and lymph of adult animals and men and their biological effectiveness after enteral administration]. With isotopic and immunological methods it could be demonstrated that: 1. Rabbit- and horse-proteins can be absorbed from the gut into blood and lymph of rats and dogs in highmolecular form. 2. The highmolecular part after the passage of the intestinal wall was calculated between 5 and 20%. 3. The increase of the lymphocytotoxicity in the lymph of rats from 1:2 to 1:16 after enteral application of horse-antihuman-lymphocyte-gammaglobulin indicates the biological activity of the protein after the penetration through the gut. Furthermore the immunosuppressive effect of ALS after oral application could be demonstrated on the survival time of allogeneic skin transplants. A significant lymphopenia could be induced in dogs after the oral application of horse-antidog-gammaglobulin. From these findings far reaching consequences must be drawn concerning nutritional and immunological aspects. By the enteral absorption of proteins for example a natural tolerance must be induced which is broken in food allergies. Furthermore it is conceivable that the immunocompetent cells of the gastro-intestinal tract can be manipulated for the purpose of immunization or desensibilization within therapeutical programs of prophylactic medicine.


[Anemia in chronic renal insufficiency]. Anemia is known as one of the earliest manifestations of chronic renal insufficiency. Anemia begins at a serum creatinine level of 2 mg/100 ml. There is no correlation between the degree of anemia and the etiology of renal disease. Patients on chronic hemodialysis shown an average hematocrit of 23%. In the pathogenesis of renal anemia various factors may be discussed, especially a deficiency of iron and erythropoietin. A method of conservative therapy which would allow optimal treatment of renal anemia is not yet available. Successful renal transplantation has to be considered the best therapeutic measure in terminal renal insufficiency.


[Sonographic thyroid diagnosis].

[Sonographic thyroid diagnosis]. Sonography is suitable for the examination of thyroid glands respectively goiters. This method particularly gains in the differentiation of cold nodules or cold regions. In more than 50% of patients with cold nodules sonography showed cystic lesions. In addition, ultrasonically guided percutaneous fine needle biopsy is employed for emptying cysts or gaining material for cytological examination.


[Modification of infectious-allergic processes by oral administration of antigens]. The oral administration of appropriate antigens causes a decrease in sensitization as shown by the models of tuberculin allergy in guinea pigs and of the sensitization of guinea pigs and rabbits to corynebacterium acnes antigens.


The relationship between mitochondrial heterogeneity and gluconeogenesis in liver mitochondria of the rat, pigeon and guinea pig. Isolated mitochondria of pigeon and guinea pig liver were subjected to zonal centrifugation. With pigeon liver mitochondria there was uniform distribution of pyruvate carboxylase, phosphoenolpyruvate carboxykinase, malate dehydrogenase, aspartate aminotransferase and glutamate dehydrogenase activities. Guinea pig liver mitochondria demonstrated two pyruvate carboxylase and phosphoenolpyruvate carboxykinase maxima but only one maximum with aspartate aminotransferase, malate dehydrogenase and glutamate dehydrogenase. Mitochondrial enzyme levels in rat, pigeon and guinea pig indicate different roles of certain gluconeogenic enzymes in the transport of carbon and hydrogen in and out of mitochondria.


Hypoxanthine phosphoribosyltransferase and hypoxanthine uptake in human erythrocytes. A system of hypoxanthine uptake and IMP retention was studied and characterized in human erythrocytes. It follows closely the system already described for rabbit erythrocytes[7]. IMP formation and retention are dependent on the activity of hypoxanthine phosphoribosyl-transferase and on intracellular availability of phosphoribosyl pyrophosphate (P-Rib-PP), which is one of the substrates. In the extrecellular medium, neither P-Rib-PP nor GMP -- a potent inhibitor of the enzyme in vitro -- has any influence on IMP retention. The amount of residual hypoxanthine phosphoribosyltransferase in erythrocyte ghost preparations is directly related to the residual hemoglobin content. Thus the enzyme is characterized as typically soluble and "loosely bound" to membranes. There is a slight difference in the kinetic properties of the ghost-bound and the free soluble enzyme. The possible importance of these results for purine uptake and utilization in human red cells is discussed.


Drug-induced foam cell reactions in rats, II. Chemical analysis of lipids stored in lungs and foam cells after treatment with chlorphentermine, 5-[p-(fluoren-9-ylidenemethyl)phenyl]-2-piperidineethanol (RMI 10.393) and 1-chloramitriptyline. Lipidosis and foam cell reaction was induced in rat lungs by repeated administration of chlorphentermine, RMI 10.393 (=5-[p-(fluoren-9-ylidenemethyl)phenyl]-2-piperidineethanol), and 1-chloramitriptyline. Foam cell and lung lipids were extracted and separated in classes by thin-layer chromatography. Phospholipids were determined by phosphorus analysis, while neutral lipids were measured densitometrically. In lungs of drug-treated rats lecithin, phosphatidyl glycerol, phosphatidic acid, phosphatidyl inositol and free fatty acids accumulated in varying amounts. All other lipids were present in normal or reduced concentrations. Foam cells of chlorphentermine- and RMI 10.393-treated rats contained mainly phospholipids, i.e. lecithin and only small amounts of neutral lipids, i.e. cholesterol. Foam cells induced by 1-chloramitriptyline contained besides phospholipids also large amounts of neutral lipids, i.e. cholesterol, free fatty acids and cholesterol esters. This study and recent reports of others show that certain drugs produce a generalized metabolic disturbance characterized by accumulation of various lipids in several tissues. The distribution patterns of lipids induced by various drugs may differ considerably. This indicates that several biochemical mechanisms may be involved in the pathogenesis of drug-induced lipidosis.


[Accumulation of basic amino acid residues, rate of autolysis and relative length of gut during trypsin evolution (author's transl)]. The study of six trypsins (crayfish, dogfish, horse, pig, sheep, bovine) showed that among these the highest lysine + arginine content and the highest inactivation rate occur in specialized herbivorous animals with extreme length of gut. Since the autocatalytic degradation in trypsins can take place only at lysine or arginine residues, an accumulation of basic amino acids, the increase of the autocatalytic inactivation rate and the relative length of gut might be correlated during the evolution of mammalian trypsins.


A survey of factors related to mental hospital readmissions. The authors followed up 107 patients selected at random from those discharged from a southern state mental hospital in fiscal year 1972-73. They attempted to differentiate those who were readmitted to the hospital from those who were not on the basis of 52 factors, both personal and environmental, and also compared those who misused alcohol with those who did not. In their sample, 36 of the patients returned to theinstitution, and 71 did not. One of the findings was that in both the total sample and in the nonalcoholic subsample, those readmitted more often received income ffrom sources other than their own employment or the employment of someone in their household. They also tended to be single, separated, or divorced. In both the alcoholic and nonalcoholic subsamples, those readmitted reported more contacts with the community mental health center after their discharge than those not readmitted. In the total sample, the readmitted patients engaged in fewer leisure-time activities and were more likely to report a drinking problem.


Follow-up of mentally retarded adults successfully and unsuccessfully placed in community group homes. State hospital staff members compared 72 retarded adult patients who had been successfully placed in group homes in the community with 13 patients who had been placed but rehospitalized. No significant differences were found between the groups on the four variables of sex, age at the time of the study, age at first admission to the hospital, and time spent in the hospital. A comparison of preplacement problems listed in the patients' hospital records with the reasons for rehospitalization of the unsuccessfully placed group suggests that both hospital staff and group home parents find aggressive behaviors a problem, but that group home parents are more concerned than hospital staff with deficiencies in self-care.


Human triploid cell strain. Phenotype on cellular level. The complex investigation of the bilogical properties of the triploid cell strain derived from a spontaneous abortus was carried out. Cytomorphological, autoradiographic, cytochemical, biochemical and immunochemical investigation showed that, according to most of the investigated properties, triploid cells did not differ from normal diploid cells. The cells had normal form, were well orientated, revealed expressed fibrillar apparatus and viability in the culture during 15--17 passages. The decrease of the alkaline phosphatase level, increase of acid phosphatase, lactate and malatdehydrogenase and greater nuclei area were the essential differences from the control. The cells had normal mitotic cycle parameters and the antigenic spectrum was practically identical to the normal cells.


Tandem duplication q14 and dicentric formation by end-to-end chromosome fusions in ataxia telandiectasia (AT). Clinical and cytogenetic findings in 5 patients. Chromosome studies on lymphocyte cultures were performed in 5 patients with AT, 2 of whom had been followed for 4 years. Four out of these patients showed an increased incidence of chromosome-type aberrations. A clonal development was present in one patient, 96% of his metaphases containing a tandem duplication of almost the entire long arm 14. Four years earlier the proportion of these cells was 80%. Two other patients presented a small proportion of cells with an unidentified abnormally long D chromosome. In a total of 724 metaphases from 4 patients 31 dicentric chromosomes were observed, all of a peculiar type; in their formation no chromosome material was lost and they all seem to have arisen by end-to-end fusions. The incidence of chromatid-type aberrations was normal or at the upper limit of control values in all 5 cases. The sister chromatid exchange rate studied with BUDR in 3 patients was found to be normal.


The human leulocyte test system. VII. Further investigations concerning micronucleus-derived premature chromosome condensation. Premature chromosome condensation (PCC) from X-ray induced micronuclei shows a dose-effect relationship in human leukocytes in vitro. Preparations at different culture times without colcemide treatment reveal complex variations of the frequencies of micronuclei and PCC correlated with the fixation time. The positions of PCC patches in the metaphase plate and the frequencies of different PCC types (S and G2) ar independent on the X-ray dose. The latter indicates that the slowing down of the micronuclei in the cell cycle, which is the reason for the formation of PCC, may be an outcome rather of a regulatory phenomenon than of an unspecific physiological damage of the chromatin included in the micronuclei. This is especially evident from labeling experiments with tritiated thymidine, showing that the extent of asynchrony between main nuclei and micronuclei is independent on the X-ray dose. Labeling experiments with tritiated uridine reveal a X-ray dose dependent suppression of RNA synthesis in cells with main nuclei and micronuclei. THE S-phase nature of "pulverized" PCC patches could be verified by incorporation of tritiated thymidine in aound 50%. Staining of centromeric heterochromatin in micronuclei reveal a frequency of micronuclei with centromeric heterochromatin resembling the frequency of G2-phase PCC found in mitoses.


The metaphase chromosome ultrastructure. II. Helical organization of the basic chromosome fiber as revealed by acute angle metal deposition. The acute angle metal depositon technique, discloses a helical chromosome fiber substructure. The microdensitometric analysis of the fiber parameters shows that a fibril 152 A in diameter coils to form the basic chromosome fiber 295 A in diameter with a pitch of 247 A. These figures should be corrected because of the thickening due to metal deposition, the real dimensions would be closer to 112 A for the fibril diameter and 255 A for fiber diameter. The real pitch value is probably somewhat smaller than 247 A (approximatively 200 A) as the values were obtained by analysing slightly stretched fibers. These results support the helical model of the chromosomes fiber organization and show that, most probably, the metaphase chromosome fiber as seen in electron microscopy is the second order of helical packing.


An abortus with a normal/trisomy 16 mosaicism: instability of trisomic cells in vitro. A 46,XX/47,XX,+16 mosaicism was demonstrated in cultured chorionic cells obtained from an abortion material. By tracing polymorphic fluorescent chromosome markers in the abortus and the parents, the karyotypically normal component was confirmed to be non-maternal in origin. The trisomic cells showed a growth disadvantage, and were overtaken by the normal cells in prolonged cultivation.


Hexokinase isozymes in human neoplastic and fetal tissues: the existence of hexokinase II in malignant tumors and in placenta. The distribution of electrophoretic fractions of hexokinase (HK E.C. 2.7.1.1) in extracts of 53 human primary tumors, homologous normal tissues and fetal organs was investigated. It was found that the fraction HK II is present in every malignant tumor and in placenta tissue.


Predominance of the haemoglobin E gene in a Mongoloid population in Assam (India). A high frequency of the haemoglobin E gene (HbbetaE) had been found in 1972 in the Ahom, a mongoloid population in Upper Assam. The present study confirms frequencies between 0.3 and 0.35 for this population in a larger sample from different areas. An even higher frequency near 0.5 was found in the Kachari of Upper Assam, a tribe of the tibetoburman Bodo group. HbbetaE frequencies in these groups are compared with the frequencies in the general Assamese population and the austroasiatic Khasi of Meghalaya.


Y-chromatin positive cells in the smear preparations of the gonad from a XX male. An ambisexual male infant showed a normal female karyotype by the leukocyte culture technique in two different occasions. Cultured fibroblasts from the right gonad had also a 46, XX complement. They were Y-chromatin negative. To our surprise, Y-chromatin was observed in 96% of the nuclei in smears from the uncultured gonad. It is emphasized that the examination of the uncultured gonad by the quinacrine technique is mandatory in the study of "XX males".


[Trisomy 4p. Three new observations (author's transl)]. Three new observations of trisomy 4p are reported. Two are due to a maternal translocation t(4;15). The third is due to a "mirror" duplication, it is the first case of trisomy 4p without balanced parental rearrangement. The very characteristic phenotype is compared to that of 13 other patients already reported in the literature.


Control of the immune response. I. Depression of DNA synthesis by immune lymph node cells. The DNA response in the regional lymph nodes draining the site of immunization with contact sensitizing agents was assessed by measuring the uptake of radioactive iododeoxyuridine. The DNA response in the regional lymph nodes reached a peak on day 3 after immunization and fell to pre-immunization levels by day 6. The hypothesis was tested that lymph node cells from mice immunized with picryl chloride might depress the DNA response to the same antigen. Immune lymph node cells were injected intravenously and the recipient mice were immunized with picryl chloride on the same day. The immune cells depressed the DNA response on day 4 by an average of about 60 per cent. Smaller but significant depression also occurred on day 3. The cells responsible for the depression appeared in the regional lymph nodes 3-4 days after immunization and disappeared by day 21. The transfer of small numbers of immune cells (less than 2-5 X 10(6)) increased the DNA response in recipients 4 days after immunization with picryl chloride. The depression of the DNA response was largely specific. Pooled data from ten experiments showed that cells immunized with 4-ethoxymethylene-phenyl oxazolone ('oxazolone') caused no depression of the DNA response to picryl chloride, although in two of these experiments significant depression of about 21 per cent was seen. Similar results were obtained when immune cells were injected into mice immunized with 'oxazolone'.


Immune plasma-dependent cytotoxicity of immune and non-immune peripheral lymphoid cells for target cells coated with bacterial outer unit membrane. The development of a model system for use in the study of lymphoid cell cytotoxicity to bacterial membrane antigens was attempted. In this system 51 Cr-labelled chicken red blood target cells were coated with pieces of the outer unit membrane of leptospirae rather than with soluble antigens. Using the model system to study dog peripheral immune lymphoid cell cytotoxicity to coated target cells we found that both immune and non-immune lymphocytes are antibody dependent for the expression of their cytotoxicity. It was also found that the unit membrane preparation from leptospirae can serve as a good antigenic stimulant to immune dog lymphoid cells as measured by increased [3H]thymidine uptake.


Autoimmune New Zealand mouse. Alterations in C3 receptors, complement-induced clumps and follicular adherence of immune complexes. Lymphocytes with free complement receptors are markedly diminished in autoimmune mice, probably as a reflection of a receptor blockage by immune complexes. There is also a slight decrease in Fc receptor-bearing cells and an increase in complement-induced clumps. These alterations may be related to a lack of immune complex fixation onto germinal centres and also may play a part in possible defects in T-B-cell co-operation, follicular localization of immune complexes and immune response control in autoimmune mice.


Investigation of the binding site of mouse IgG subclasses to homologous peritoneal macrophages. The binding of mouse myeloma IgG1, IgG2a, IgG2b, IgG1 Fc, IgG2b Fc and a pepsin produced C-terminal subfragment of IgG1 Fc and IgG2b Fc (provisionally identified as pFc') to mouse peritoneal macrophages was investigated. The high affinity cytophilic antibodies belonged to IgG2 subclasses and the binding site of these antibodies was located in the CH3 homology region.


N-bromosuccinimide oxidation of anti-DNP and anti-DNP-p-aminobenzoylglutamate antibodies in the presence and absence of protecting hapten. The reagent N-bromosuccinimide (NBS) has been employed to investigate the role of tryptophan in hapten binding in anti-DNP (H-1) and anti-DNP-p-aminobenzoylglutamate (DNP-ABG) (I-13) antibodies. In 0-1 M acetate (pH 4-0) buffer fifteen and sixteen moles of tryptophan in the anti-DNP and anti-DNP-ABG antibodies respectively were reactive toward NBS. The hapten DNP-lysine protected 1 tryptophan in antibody H-1 and three tryptophans in antibody I-13 from NBS modification. DNP-ABG protected three tryptophans in antibody H-1 and five tryptophans in antibody I-13 from NBS oxidation. NBS treatment of the unprotected antibodies resulted in a significant, but not total inhibition of hapten binding, while in the hapten protected antibody preparation no significant loss of binding occurred due to NBS treatment. The binding activity of the anti-DNP antibody H-1 was more sensitive to NBS oxidation than was the anti-DNAP-ABG antibody I-13. This was apparently due to the larger number of oxidizable tryptophans in I-13 making it less sensitive to overall tryptophan modification. The results of these investigations are discussed in terms of the antibody combining site model proposed by Haselkorn et al. (Haselkorn, Friedman, Givol and Pecht, 1974) derived from kinetic mapping of the antibody-combining site by chemical relaxation spectroscopy.


Anti-galactan activity in Tridacna maxima (Röding) haemolymph. Calcium dependence of the haemagglutinins and precipitins. A powerful natural agglutinin with haemagglutinating and precipitating properties has been found in the haemolymph from the elongate clam Tridacna maxima (Röding). The agglutinin shows anti-galactan properties and reacts with a variety of bacteria-, plant-, invertebrate- and vertebrate-derived galactans, glycopeptides and polysaccharides. Previous studies which showed that the agglutinin-combining sites were inhibited by 2-acetamido-2-deoxy-D-galactose and D-galactose also revealed some anomalies in the reactions of the agglutinin with different saccharide-containing macromolecules. In an attempt to resolve these anomalies, the present study further examines the precipitating and haemagglutinating properties of the agglutinin and illustrates a requirement of the agglutinin for Ca2+. The ability of the T. maxima agglutinin to precipitate with structures containing terminal beta-linked 2-acetamido-2-deoxy-D-galactopyranosyl or D-galactopyranosyl groups suggests that the Tridacna haemolymph and purified lectin will find considerable application in the study of many biologically important carbohydrates.


Studies on phagocytosis in fish. I. In vitro uptake and killing of living Staphylococcus aureus by peripheral leucocytes of carp (Cyprinus carpio). The clearance and uptake of Staphylococcus aureus were studied in vitro in whole blood of immunized and non-immunized carp. Bacterial numbers were determined by : (1) counting viable cells in agar plates; (2) counting radioactivity of 14C-labelled bacteria. Similar results were obtained by these two methods. Neither the bacterial growth nor the ingestion of bacteria into the cells seem to be influences by immunization. In both immunized and non-immunized groups the number of intracellular bacteria increased rapidly during the first 120 minutes, then progressed at a slow rate during the next 60 minutes, after which there was a rapid decrease in the number of bacteria only in the immune blood. It is concluded that the phagocytic cells of immune blood are more effective in activating or killing bacteria.


Relationship between age of allogeneic thymus donor and immunological restoration of athymic ('nude") mice. In nude mice back-crossed a minimum of five times to BALB/c, solid thymus grafts from C57Bl donors 3 days of age or younger restored both the humoral immune response against sheep erythrocytes and cellular immunity as tested by rejection of CBA skin grafts. Donor thymus placed under the renal capsule at a dose of 0-5 mg/g of recipient resulted in normal humoral immunity, while a minimum dose of 1-5 mg/g was required to reconstitute cellular competence. None of the various amounts of allogeneic thymus tissue transplanted affected the immunological status of nude recipients when grafts were obtained from donors 4 days of age or older. Histological findings correlated with the humoral and cellular responses observed. In nudes grafted with neonatal tissue, the thymus implant proliferated and developed normal architecture. The density of lymphocytes in thymus-dependent regions of peripheral lymphoid organs was near normal. On the other hand, most grafts from older (3-week-old) donors were resorbed by 90 days after implantation. In a number of cases, however, Russell bodies and numerous blast and plasma cells were seen in the graft site. Our observations suggest a possible cytotoxic rejection of implants from older allogeneic donors, while the survival and restorative capacity of transplants from 3-day-old or younger donors may have been due to a tolerogenic effect of the graft on the nude recipient.


Type specificity of complement-requiring and immunoglobulin M neutralizing antibody in initial herpes simplex virus infections of humans. Studies comparing the enhancing effect of guinea pig complement on homotypic and heterotypic neutralizing antibodies produced in initial herpes simplex virus (HSV) infections of humans indicated that antibodies to HSV type 1 and HSV type 2 were enhanced to about the same extent, and there was no signigicant difference in the degree to which complement enhanced homotypic and heterotypic HSV-neutralizing antibody. Homotypic and heterotypic immunoglobulin G neutralizing antibodies were enhanced by complement to as great, or greater, an extent as immunoglobulin M (IgM) HSV antibodies in the same sera. In patients with initial HSV type 1 infections, the IgM neutralizing antibody response was type specific. On the other hand, patients with initial HSV type 2 infections produced both homotypic and heterotypic IgM neutralizing antibody. An initial HSV type 2 infection in an individual previously infected with HSV type 1 elicited the production of IgM neutralizing antibody to both HSV type 1 and HSV type 2. However, patients with recurrent HSV type 1 infections failed to produce IgM antibody to either HSV type during reactivation of the virus.


Characterization of extracellular glucosyltransferase activity of Steptococcus mutans. The extracellular glycosyltransferase activity of Sterptococcus mutans GS-5 has been resolved into two non-overlapping fractions after gel filtration chromatography on Bio Gel A-15 columns. The activity eluting in the void volume, fraction A, was highly aggregated and synthesized both soluble and insoluble glucans. The activity retarded by the resin, fraction B, synthesized only soluble glucan. Almost all of the extracellular glucosyltransferase activity was eluted in the void volume when the cells were grown in Todd-Hewitt medium. However, most of the activity migrated as the lower-molecular-weight species when cells were grown under conditions which inhibit insoluble glucan formation. The activities in both fractions had identical temperature and pH optima as well as similar Km values for sucrose. Fraction A synthesized both alpha-1,3- and alpha-1,6- linked glucans, whereas fraction B catalyzed alpha-1,6-glucan formation. Fraction B has been purified to near homogeneity and is also aggregated with a subunit molecular weight of 45,000. The properties of the glucosyltransferases in both fractions are discussed in terms of the role of the enzymes in both soluble and insoluble glucan formation.


Experimental measles encephalitis: a genetic analysis. The encephalitogenic potential of nine temperature-sensitive mutants of measles virus was determined in newborn golden Syrian hamsters. The parental virus produced acute encephalitis without any prior adaptation. Six of the mutants were attenuated, two were virulent, and one was associated with hydrocephalus with acute onset. The attenuated mutants, blocked before measles virus antigen and ribonucleic acid synthesis at 39 C, were all members of one complementation group. The virulent temperature-sensitive mutants, defective in hemolysin antigen synthesis at 39 C, were members of a second complementation group. The hydrocephalus-inducing mutant was genetically distinct from the other mutants. The mechanism of attenuation most probably does not involve a temperature-induced inhibition of virus replication, but rather appears to be related to the partial defectiveness of the mutants under permissive conditions.


Immunological properties of glycolipids from membranes of Acholeplasma laidlawii. Glycolipids, the predominant class of lipids in the membranes of Acholeplasma laidlawii, are the haptenic determinants that react with anti-A. Laidlawii serum to fix complement. The predominant complement-fixing activity of the membrane glycolipids was associated with the monoglucoysyl diglyceride, diglucosyl diglyceride, glycerlphosphoryl diglucosyl diglyceride (GPDD), and an unknown lipid B, which did not react with ninhydrin but release glucose and glycerol and traces of phosphorus upon hydrolysis. The glycolipids monoglucosyl diglyceride and diglucosyl diglyceride or GPDD and unknown lipid B were paired as a result of their cross-reactions with selective antisera prepared with the aid of reconstituted membrane complexes containing membrane lipids. Reconstituted membrane complexes assembled from [14C]monoglucosyl diglyceride and delipidated membrane proteins gave optimal complement fixation titers before saturation of the complexes with the ]14C]monoglucosyl diglyceride. The phosphoglycolipid of the membrane, GPDD, was anticomplementary as a pure lipid, a cholesterol liposome, and a reconstituted membrane complex. This anticomplementary activity, which was caused by 3 mug of pure GPDD, affected both human and guinea pig complement. Although human C1, C4, C3, and C5 were not inhibited by GPDD, C2 was inhibited 10-fold by reconstituted membrane complexes containing 150 mug of GPDD. A role for this phosphoglycolipid is discussed in the hypothetical mechanism of inhibition of C2 attachment to SAC1, 4 sites.


Pathogenicity of an attenuated, temperature-sensitive mutant of western equine encephalitis virus induced by a chemical mutagen. To know the pathogenicity of the chemically induced, temperature-sensitive (ts) mutant of western equine encephalitis virus, designated tsNG39, the lethality for mice injected with tsNG39, virus yield, interferon production, and histological changes in the brains of these mice were examined in parallel with those of mice inoculated with the parent strain (PS). All of the mice injected intracranially with PS died within 3.5 days after injection irrespective of the inoculum size of virus, whereas the lethality of the mice inoculated with tsNG39 varied from 94.3 to 65.5% among groups of mice and this variation seemed to be correlated with the inoculum size of virus rather than with the maximum virus titer in the brain. By histological examination, two types of changes in the brain were distinguished, inflammatory and degenerative ones. Inflammatory changes were more prominent in the brains injected with tsNG39 than in those receiving PS. Degenerative changes were dominant in the brains injected with PS, but they were slight in the earlier phase of infection by tsNG39 became prominent only later. The degree of degenerative change was well correlated with both the virus titer in the mouse brain and the death pattern of mice injected with PS or tsNG39. Since degenerative changes are thought to be caused by the direct effect of injected virus, these results indicated that the factor responsible for the low virulence of tsNG39 was the slow viral growth in the brain.


Effect of glucocorticosteroids on phagosome-lysosome interaction. The effects of hydrocortisone on fusion of thorotrast-labeled lysosomes with phagosomes containing killed toxoplasmas was studied. Mouse peritoneal macrophages from glucocorticosteroid-treated animals fromed phagolysosomes just as effectively as macrophages from untreated animals (72% thorotrast-positive vacuoles in hydrocortisone-treated animals; 78% in controls). The electron microscopic appearence of macrophages from treated or untreated animals was similar. This observation complements studies which show no change in intracellular microbicidal activity in macrophages treated with glucocorticosteriods.


Cell-associated subacute sclerosing panencephalitis agent studied in organotypic central nervous system cultures: viral rescue attempts and morphology. Organotypic cultures of hamster cerebellum were exposed to the IP-3-Ca cell line , which contains a cell-associated subacute sclerosing panencephalitis agent. Central nervous system (CNS) cultures were examined by light and electron microscopy as well as standard virological techniques from 3 to 46 days postinfection. The results indicate that although viral nucleocapsid material was transferred to elements of the CNS, cell-free virus could not be detected by virological techniques and by electron microscopy, and budding viral particles were not observed. Attempts to recover cell-free virus from hamster CNS tissue exposed to IP-3-Ca cells were generally negative. However, 2% of the cultures yielded low levels of infectious virus. IP-3-Ca cells were able to transfer the cell-associated viral material to all cell types found in the CNS cultures and were capable of inducing polykaryocytes in the CNS cultures. The role of cell-associated virus-like agents in subacute sclerosing panencephalitis and other chronic CNS infections is discussed.


Inhibition of hemolytic activity of the thermostable direct hemolysin of Vibrio parahaemolyticus by ganglioside. The hemolytic activity of the thermostable direct hemolysin produced by Vibrio parahaemolyticus was inhibited by a ganglioside mixture. The ganglioside component which inhibited the hemolysin was not FM1 ganglioside.


Production of elevated levels of dextransucrase by a mutant of Streptococcus mutans. A mutant (S19) of Sreptococcus mutans strain 6715 which produces elevated levels of dextransucrase (EC 2.4.1.5) was isolated. Soluble enzyme in culture supernatant solutions from S19 polymerized the glucosyl moiety of sucrose into alcohol-insoluble and water-insoluble glucans at a rate three to six times greater than that of the parent strain. Washed-cell suspensions of S19 also contained increased amounts of cell-associated enzyme. Adherence of S19 to glass in the presence of sucrose occurred at twice the rate of strain 6715. The Km values for sucrose and primer dextran were similar for the mutant and parent enzymes. Mutant S19 should facilitate studies on the mechanism of adherence of S. Mutans and the control of dextransucrase production by this bacterium.


Mitogenicity of formalinized toxoids of staphylococcal enterotoxin B. Staphylococcal enterotoxin B is a potent mitogen for mouse and human lymphocytes. Mitogenic activity was retained after detoxification of the enterotoxin by formaldehyde at pH 5.0, 7.5, OR 9.5. The most active toxoid (pH 7.5) was separated into a monomeric, a dimeric, and a polymeric fraction (1 x 10(5) to 3 x 10(5) molecular weight) by gel filtration, and although each fraction demonstrated mitogenic activity, the polymeric fraction was clearly the most efficacious. These data show that mitogenicity of staphylococcal enterotoxin B does not depend on toxicity. This suggests that the mitogenic and toxic activities are effected by different sites on the molecule.


In vivo and in vitro stimulation of mouse spleen leukocytes by BL-20803, a low-molecular-weight interferon inducer. BL-20803, a low-molecular-weight compound, although able to elicit circulating interferon in the mouse, failed to protect cultured cell lines in vitro from infection by interferon-sensitive viruses. Of the tissues analyzed for interferon content after oral administration of the drug to mice, spleen and lung contained the largest amounts of the virus inhibitor. Spleen cells from such dosed animals when isolated into in vitro cultures elaborated small amounts of interferon into the culture medium. The time sequence of acquisition by spleen cells of the ability to produce interferon closely correlated with the kinetics of development of the circulating interferon response in the intact mouse. When spleen cells were separated on the basis of adherence or nonadherence to a plastic surface, the bulk of the interferon activity was found to be associated with the adherent cells. Upon exposure to BL-20803 in cell culture, adherent cells and, to a lesser extent, nonadherent cells from untreated mice were stimulated to produce interferon-like activity. The biological behavior of BL-20803 is shown to have striking similarities with that of the structurally different low-molecular-weight inducer tilorone hydrochloride.


Arthritis of mice induced by Mycoplasma pulmonis: humoral antibody and lymphocyte responses of CBA mice. Peak arthritis occurred 14 days after intravenous injection of Mycoplasma pulmonis and persisted in some mice at low levels for 84 days. A marked lymphocytosis occurred during the first week of infection  with only a slight increase in polymorphonuclear leukocytes. Complement-fixing antibodies appeared in low titer 3 days after infection and moderate levels persisted for 84 days. The metabolic-inhibiting and mycoplasmacidal antibody responses were absent or minimal. M. pulmonis appeared to be mitogenic for mouse lymphocytes as evidenced by (i) increased uptake of [3H]thymidine for normal lymphocytes exposed to various concentrations of nonviable M. pulmonis antigen, and (ii) a 13-fold increase in [3H]thymidine uptake in lymphocytes taken from mice 3 days after infection with M. pulmonis in the absence of added antigen. Lymphocytes taken from infected mice transformed significantly more at all time periods than control lymphocytes when exposed to M. pulmonis antigen. This response was maximal at 3 days and minimal at 21 to 35 days after infection. Lymphocytes sensitized to M. pulmonis did not transform when exposed to M. arthritidis antigen or vice versa. M. pulmonis infection had no effect upon the mitogenic responses of lymphocytes to phytohemagglutinin or lipopolysaccharide. There was no statistically significant correlation between persistence of arthritis and degree of humor antibody or lymphocyte responses. However, persisting arthritis was associated with a higher incidence of mycoplasma isolations.


Delayed-type hypersensitivity responses to a cell wall fraction of the mycelial phase of Coccidioides immitis. A skin test-active fraction was isolated from the mycelial-phase cell walls of Coccidioides immitis. This alkali-soluble, water-soluble antigen (C-ASWS) elicited positive reactions in 22 of 24 (92%) of the Coccidioides-sensitized guinea pigs whereas only 14 (54%) of the same guinea pigs reacted to commercial coccidioidin (BioCox). None of the 21 Histoplasma-sensitized guinea pigs cross-reacted with the C-ASWS antigen. Footpad tests in mice actively infected with Coccidioides further established the efficacy of the C-ASWS antigen in eliciting a delayed-type hypersensitivity response. One-microgram doses of C-ASWS produced reactions comparable to 100-mug doses of nondialyzable coccidioidin (Smith's lot 64 D4). The C-ASWS fractions isolated from three different C. immitis strains showed similar reactivity in terms of the number of positive reactions produced in Coccidioides-sensitized guinea pigs. However, the induration responses (diameter in millimeters) elicited by the C-ASWS fraction of one strain were significantly less than those elicited by the C-ASWS fractions of the other two C. immitis strains.


Enhanced resistance to Corynebacterium pseudotuberculosis infections associated with reduced serum immunoglobulin levels in levamisole-treated mice. The effect of levamisole (1-2,3,5,6-tetrahydro-6-imidazo[2,1-b]thiazole monohydrochloride) treatment on the course of a Corynebacterium pseudotuberculosis infection and the ability of either vaccinated or unvaccinated randomly bred mice to resist challenge were investigated. It was found that either a double treatment of levamisole administered with or without a sublethal inoculation of C. pseudotuberculosis or a single treatment of levamisole alone had a significant effect on the ability of mice to resist challenge with virulent C. pseudotuberculosis. This prolonged, enhanced nonspecific and specific resistance was associated with a quantitative reduction in the geometric mean serum immunoglobulin levels, with the immunoglobulin G2 and immunoglobulin A levels being more severely affected. As the enhanced nonspecific resistance to C. pseudotuberculosis was associated with depressed serum immunoglobulin levels in the mice pretreated with levamisole alone, it was suggested that the cell-mediated immunity may play a more important role than the humoral immunity in the resistance to C. pseudotuberculosis infection.


Intrauterine infection of mice with St. Louis encephalitis virus: immunological, physiological, neurological, and behavioral effects on progeny. Intravenous injection of pregnant mice with St. Louis encephalitis (SLE) virus at 8 days of gestation resulted in infection of the fetus. Progeny developed no antibody or tolerance to SLE virus since the viral antigen was cleared by maternal antibody before antibody-forming competence developed in the young. Temporary growth retardation was observed in a number of young at 3 weeks of age. After the initial setback the growth rate increased, indicating that early runting was due to an inability to adjust adequately to extrauterine life, which was subsequently overcome. In most other young there were no significant effects on growth, reproduction, or life expectancy. A few young died at or shortly after birth; in these, neurological changes ranging from gross defects such as encephaloceles and hydrocephalus to histological evidence of necrosis and congestion were observed. Neurologically related behavioral changes were detected by using the open field test and the rotating-rod test, which indicated neurological damage and memory impairment in the surviving intrauterinely infected animals.


Analysis of growth rate in sucrose-supplemented cultures of Streptococcus mutans. In the presence of sucrose, Streptococcus mutans grows in large glucan-containing aggregates. Because of reports of linear rather than exponential growth of sucrose-grown cultures, the kinetics of growth of sucrose-grown cultures of S. mutans strain OMZ-176 were compared with those of glucose-grown cultures. Culture turbidity measurements indicated that growth of sucrose cultures was slower, did not follow exponential kinetics, and slowed and stopped at lower absorbance values than did glucose-grown cultures. However, measurements of the rates of accumulation of deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and protein using fully equilibrated radioactively labeled precursors of each of these macromolecular species in sucrose and glucose-grown cultures showed that: (i) for glucose cultures the synthesis of each of the three informational molecules occurred at the same exponential rate, which was identical to the rate of turbidity increase; (ii) for sucrose cultures each macromolecular species was synthesized at the same exponential rate and these rates were identical to the rate of increase of turbidity of the glucose-grown culture for periods of up to 7 h. Furthermore, the ratios of DNA to RNA, RNA to protein, and protein to DNA for the sucrose cultures were identical to those for the glucose cultures for up to 10 doublings. From these data it was concluded that in the presence of sucrose S. mutans grows in a balanced fashion at the same exponential rate as it does in glucose. The deviation from an exponential growth model of the absorbance in sucrose cultures was attributed to an optical artifact due to the formation of large glucan-containing aggregates of cells. The addition of dextranase to sucrose cultures resulted in cultures which increased in turbidity at the same exponential rate as glucose-grown cultures, without affecting the rate or extent of macromolecular synthesis.


Production, purification, and chemical characterization of Staphylococcus aureus exfoliative toxin. Methods for the production and isolation of exfoliative toxin are described. Fermentation conditions were established under which large quantities of the crude material can be produced. Column chromatography methods, including carboxymethyl cellulose and hydroxyapatite, were utilized to purify the toxic protein. The pure toxin had a molecular weight of 26,000 as determined by polyacrylamide gel electrophoresis in sodium dodecyl sulfate. The pure toxin is a simple protein composed of 17 amino acids. Tests for carbohydrate and for alpha- and beta-hemolysin were negative. The mean effective dose of the purified toxin was 0.5 mug per newborn mouse.


Induction of resistance with heat-killed compact-type strains of Staphylococcus aureus against challenge with the diffuse variant of the Smith strain of Staphylococcus aureus. Active immunization of mice with high doses of heat-killed and autoclaved vaccine of unencapsulated strains of Staphylococcus aureus, which was grown in brain heart infusion media, protected against challenge with the Smith diffuse strain of Staphylococcus aureus. These organisms were capable of absorbing the protective antibody in rabbit hyperimmune sera prepared with the Smith diffuse strain. Also, mice treated with rabbit hyperimmune sera prepared with these strains (four out of six strains) protected against challenge with the Smith diffuse strain. Protective activities of these rabbit hyperimmune sera were assumed to be essentially identical to the protective antibody induced by the Smith diffuse strain.


Effect of the antitumor antibiotic chromomycin A3 on the humoral immune response in rats. Chromomycin A3 (250 mug/kg) suppressed the humoral immune response in rats against sheep erythrocytes when administered 48 h or later after antigenic stimulus. The antibiotic at this dose enhanced immunity when given along with or before antigen administration. The natural heterohemagglutinin levels in rabbits and guinea pigs were not affected by the antibiotic (10 mug/kg per day x 7).


Localized immunity in experimental bovine mastitis caused by Mycoplasma dispar. Development of immunity to reinfection with Mycoplasma dispar occurred in the bovine mammary gland and appeared to be confined to the quarter or quarters previously infected with this mycoplasma; it was not generalized throughout the gland. Immunity followed the inoculation of virulent strains of M. dispar but not of an avirulent strain. The immunity engendered protected against both homologous and heterologous strains of M. dispar. Challenge of immune quarters with virulent M. dispar resulted in a transient polymorphonuclear cell response greater than that observed in previously uninoculated quarters.


Stimulation of human lymphocytes by a vaccine strain of Francisella tularensis. An immune response to Francisella tularensis was demonstrated in man by the lymphocyte stimulation test. Peripheral blood lymphocytes were obtained from 26 individuals vaccinated with a viable tularemia vaccine, from 29 unvaccinated individuals, and from two patients who had recently undergone tularemia. The lymphocytes were incubated in the presence of various dilutions of heat-killed bacteria of the vaccine strain. The bacteria induced a deoxyribonucleic acid synthesis in the lymphocytes from 18 of the vaccinated individuals and from the two patients which was higher than that in the lymphocytes from any of the unvaccinated individuals. The deoxyribonucleic acid synthesis was maximal after about 6 days of incubation irrespective of concentration of bacteria. Lymphocytes from vaccinated and unvaccinated individuals were stimulated by two unrelated agents, tuberculin purified protein derivative and pokeweed mitogen. Lymphocytes from the vaccinated individuals did not show a higher response to these agents than did those of the unvaccinated. This suggests that the lymphocyte response to the Francisella bacteria was not due to a nonspecific activation. The vaccine-induced lymphocyte stimulation did not correlate with serum antibodies agglutinating F. tularensis antigen.