Cross-linking of DNA in L1210 cells and nuclei treated with cyclophosphamide and phosphoramide mustard. Phosphoramide mustard, formed from cyclophosphamide in vivo and in vitro, may be the active metabolite of this drug. We have found phosphoramide mustard to be at least 100 times more potent than cyclophosphamide in inhibiting growth of two strains of the L1210 lymphoma in culture. Phosphoramide mustard also produced enlargement of cells, an effect not seen with cyclophosphamide. Phosphoramide mustard significantly increased the amount of cross-linked DNA after incubation with intact LM4 cells or nuclei isolated from these cells. Cyclophosphamide had a similar effect only in the isolated nuclei. These findings strengthen the proposed role of phosphoramide mustard as the active metabolite of cyclophosphamide. The effect of cyclophosphamide on nuclei is unexplained.


Cellular and nuclear volume during the cell cycle of NHIK 3025 cells. The distribution of cellular and nuclear volume in synchronous populations of NHIK 3025 cells, which derive from a cervix carcinoma, have been measured by electronic sizing during the first cell cycle after mitotic selection. Cells given an X-ray dose of 580 rad in G1, were also studied. During the entire cell cycle the volume distribution of both cells and nuclei is an approximately Gaussian peak with a relative width at half maximum of about 30%. About half of this width is due to imperfect synchrony whereas the rest is associated with various time invariant factors. During S the mean volume of the cells grows exponentially whereas the nuclear volume increases faster than for exponential kinetics. Hence, although cellular and nuclear volumes are closely correlated, their ratio does not remain constant during the cell cycle. Volume growth during the first half of G1 is negligible especially for nuclei where the growth appears to be closely associated with DNA-synthesis. For unirradiated cells the growth of cellular and nuclear volume is negligible also during G2 + M. In contrast, the X-irradiated cells continue to grow during the 6 hr mitotic delay with a rate that is constant and about half of that observed in late S. Hence, radiation induced mitotic delay does not appear merely as a lengthening of an otherwise normal G2. During G1 and S the irradiated cells were identical to unirradiated ones with respect to all the parameters measured.


Morphogenesis of larval cuticle in the polychaete Phragmatopoma lapidosa. A correlated scanning and transmission electron microscopic study from egg envelope formation to larval metamorphosis. The development of the egg envelope and its incorporation into the larval cuticle of the polychaete Phragmatopoma lapidosa, was studied by correlative scanning and transmission electron microscopy. The mature egg possesses an envelope composed of five zones including an outer granular zone formed by the tips of the egg microvilli. The formation of the granules is described and their functions are discussed. The entire egg envelope is retained as the larval cuticle up to the 16 h trochophore stage. From this stage to about the 60 h larval stage, the envelope is gradually lost and replaced by a cuticle consisting of branching microvilli. The cuticle of the 20 day larva is composed of highly branching microvilli penetrating a homogeneous electron opaque cuticle. The possible functions of the cuticle among the Annelida are discussed.


DNA synthesis in a multi-enzyme system from Xenopus laevis eggs. Cytoplasm from unfertilized eggs of the frog Xenopus laevis was separated by DEAE-cellulose column chromatography into nine fractions. Supercoiled pXir 11 DNA molecules (pXir 11 is a Col El-based recombinant plasmid containing part of the Xenopus laevis 18S and 28S ribosomal genes and transcribed spacer region) were incubated with each fraction singly and in various combinations. After incubation for 4 hr at 26 degrees C, the pXir 11 DNA was reisolated and examined by electron microscopy. Using appropriate reaction conditions (pH 7.2, 10 mM Mg2+, 250 micron NTP, 50 50 micron dNTP, 50 MM KCl, fractions III and IV or VI), at least 5-10% of the input DNA was converted to theta structures (presumed intermediates in DNA replication).


Apex echocardiography. A two-dimensional technique for evaluating congenital heart disease. We have evaluated apex echocardiography, using an 80 degrees phased array sector scanner, in 368 patients with congenital heart disease. With the patient lying with the left side dependent, the transducer is placed over the apex of the heart and cross sectional images are obtained in the plane perpendicular to the cardiac septa and through the orifices of the mitral and tricuspid valves. In this view, the chambers are side by side and both atria and ventricles are separated by their respective septa and atrioventricular valves. Defects in the region of the septa can be detected. Congenital defects involving the atrioventricular valves, such as endocardial cushion defects, tricuspid atresia, and Ebstein's anomaly, can be defined. The location of the baffle after Mustard's operation for aortopulmonary transposition and intra-atrial structures, such as the membrance in cor triatriatum, can be seen. The position of the apex of the heart can be located in dextro, levo, or mesocardia by definition of the apex image. The relative size of the ventricular septum can be identified with the apex image. We have found this technique to be valuable in patients with congenital heart disease who are undergoing cross sectional echocardiography.


Echocardiographic assessment of left ventricular filling and septal and posterior wall dynamics in idiopathic hypertrophic subaortic stenosis. In order to study left ventricular function in idiopathic hypertrophic subaortic stenosis (IHSS), left ventricular echograms were analyzed by computer and compared with results in normal subjects. Systolic function was consistently normal or above normal even in the presence of severe diastolic abnormalities. Wide variation in diastolic function in IHSS allowed separation of patients into three groups on the basis of the left ventricular peak filling rate. Because of the severe septal hypertrophy and hypokinesia, peak left ventricular filling rate is predominantly determined by the rate of free wall thinning. Patients in group 1 had rapid left ventricular filling rates, those in group 2 had normal filling rates, and those in group 3 had slow filling rates. With reduction in left ventricular peak filling rate caused by impaired free wall thinning, there was progressive increase in 1) duration of the rapid filling phase, 2) delay of mitral valve opening, 3) asynchrony between septum and posterior wall, 4) incidence of angina, and 5) incidence of atrial fibrillation.


Left ventricular outflow tract obstruction due to systolic anterior motion of the anterior mitral leaflet in patients with concentric left ventricular hypertrophy. Patients with hypertrophic cardiomyopathy (i.e., asymmetric septal hypertrophy) may show obstruction to left ventricular outflow under basal conditions or with provocative maneuvers. The presence of dynamic left ventricular outflow tract obstruction in patients with concentric ventricular wall thickening (but without abnormalities of the aortic valve) has been less well appreciated. Clinical and morphologic features of five patients with nondilated left ventricles and with left ventricular outflow obstruction are presented. In each patient peak systolic pressure gradients between left ventricle and systematic artery were measured at cardiac catheterization and ranged from 60-140 mm Hg under basal conditions or with provocation. Each patient had echocardiographically documented systolic anterior motion of the anterior mitral leaflet, which was apparently responsible for the outflow obstruction, and concentric left ventricular wall thickening (septal-free wall thickness ratio of less than 1.3). Two of the five patients had evidence of genetically transmitted hypertrophic cardiomyopathy, as evidenced by disorganized muscle cells in the ventricular septum or asymmetric septal hypertrophy in first degree relatives. Hence, left ventricular outflow tract obstruction associated with systolic anterior motion of the anterior mitral leaflet may occur in some patients with concentric left ventricular hypertrophy who do not have typical hypertrophic cardiomyopathy.


Measurement of whole body calcium in chronic renal failure: effects of 1alpha-hydroxyvitamin D3 and parathyroidectomy. In vivo neutron activation analysis was used to measure changes in whole body calcium in patients with chronic renal failure. Eight patients, not treated by haemodialysis, showed losses of calcium in contrast to increases noted in twenty-one patients treated by haemodialysis. Changes in whole body calcium were independent of pre-existing renal bone disease. Treatment of bone disease by total parathyroidectomy (six patients) or 1alpha-hydroxyvitamin D3 (eleven patients) resulted in large increases in total body calcium. In patients given 1alpha-hydroxyvitamin D3, changes in total body calcium correlated with histological and radiological indices of response but variable changes in forearm bone mineral content were observed. Neutron activation analysis provides a convenient method for measuring skeletal mass and may also be useful in the assessment of response to 1alpha-hydroxyvitamin D3 of patients with osteitis fibrosa and osteomalacia.


Ultrastructural observations on the in vitro interaction between rat eosinophils and some parasitic helminths (Schistosoma mansoni, Trichinella spiralis and Nippostrongylus brasiliensis). Rat eosinophils form an intimate association with the surfaces of parasitic helminths, in vitro, in the presence of immune serum. The parasite presents a non-phagocytosable surface to the cell. The initial response of the eosinophil is degranulation which leads to the formation of large cytoplasmic vacuoles. Peroxidase, an enzyme localized in the matrix of the crystalloid secretion granules, is discharged into these vacuoles as a consequence of degranulation. The vacuoles eventually become connected to the adherent basal plasma membrane of the eosinophil, and peroxidase is secreted directly onto the surface of the parasite. There is no morphological evidence to suggest that this particular secretion affects the integrity of the parasite surface.


Unusual chest X-ray appearances in hypertrophic cardiomyopathy. The plain chest X-ray of 12 patients with hypertrophic cardiomyopathy were found to be grossly abnormal and atypical of this disease. Four patients presented with enlarged globular shaped hearts suggesting dilatation of all cardiac chambers. In a further four this appearance was seen to develop over a period of years and four patients were found with marked left atrial enlargement. On reviewing the echocardiographic, angiographic and necropsy data it was noted that the cardiac enlargement was produced by dilation of the atria and the right ventricle but not the left ventricle.


A purine N1-C6 hydrolase activity in the chicken egg yolk: a vestigial enzyme? All attempts to prove the presence of xanthine oxidase and uricase in yolk preparations failed. We were able instead to show that yolk preparations could hydrolyze the N1-C6 bond of certain purine bases. In the case of xanthine, 4-ureido-imidazole-5-carboxylic acid and 4-ureido-imidazole are formed. Activity only becomes apparent during purification. An analogous enzyme was described earlier in Clostridium cyclindrosporum. The liver and the blood plasma of actively laying hens do not contain the enzyme. A scheme for the degradation of egg ribonucleic acids is presented.


The use of netropsin with CsCl gradients for the analysis of DNA and its application to restriction nuclease fragments of ribosomal DNA from Physarum polycephalum. Netropsin binds to DNA in caesium chloride density gradients and reduces the density of the DNA. The DNA is saturated at a netropsin/DNA weight ratio of about 6 and the change in density, deltarho, at saturation is given by deltarho = -109 (dA + dT content)1.87 mg/ml for the six DNAs tested covering dA + dT contents from 0.28 to 0.69. At lower netropsin/DNA ratios the observed density shifts are consistent with a two-site model for netropsin binding to DNA. Netropsin approximately doubles the resolution of Physarum polycephalum nucleolar satellite DNA from main-band DNA. The fragments of P. polycephalum nucleolar satellite DNA obtained with the restriction endonuclease HindIII do not separate on CsCl gradients, even in the presence of netropsin, which shows that the transcribed and non-transcribed sequences in this DNA have similar nucleotide compositions.


Quantification of myosin heavy-chain mRNA during myogenesis. Complementary DNA (cDNA) was synthesized from a 26-S poly(A)-containing RNA fraction consisting predominately of myosin mRNA, and used to quantitate the amounts of myosin mRNA during development. RNA . cDNAmyosin hybridizations were performed with RNA isolated from tertiary cultures of chick fibroblasts, and the proportion of myosin RNA determined. The levels of myosin RNA present in primary chick myoblast cultures undergoing development were also analyzed by RNA . cDNAmyosin hybridizations. Correlation of these values with the rate of myosin heavy chain synthesis indicates that myosin mRNA is subject to post-transcriptional or translational control.


The role of serum albumin in the uptake of fatty acids by cultured cardiac cells from chick embryo. Fatty acids enter the cultured cardiac cells from chicken embryo through two mechanisms, one involving a saturable process, the other resembling passive diffusion. Studies of the saturable component, at fixed concentrations of palmitate or of oleate and at increasing concentrations of albumin, show that this protein increases the rate of palmitate uptake with a maximum at palmitate/albumin molar ratios between 7 and 10 while it decreases the rate of oleate uptake under all conditions. Albumin cannot be replaced by other serum proteins; its effect is specific to saturated fatty acids, can be mimicked by the detergent Tween 40 and involves the binding of the fatty acid to the protein, prior to its delivery to the cell. Both with labelled saturated and unsaturated fatty acids the presence of albumin lowers the proportion of unesterified fatty acids and enhances the proportion of esterified fatty acids recovered in the cardiac cell after uptake. A similar effect of albumin was also found with hepatocytes and permanent cell lines. A specific role for serum albumin is presented, which assumes a 'dispersing' effect of this protein towards dimers (or higher aggregates) of saturated fatty acids and the entry of fatty acids into the cell as monomers.


Frequency analysis of the electromyographic activity in striated pelvic floor muscles: a preliminary report. A power spectrum of the electromyographic signals in urethral and anal sphincters has been analyzed in 25 patients. Different spectra are observed in each muscle, with higher frequencies in the urethral sphincter. The high frequencies are manifest at short brisk contractions (e.g. cough) and disappear quicly during a sustained voluntary contraction. High frequencies are less pronounced in stress incontinence, but increase in spastic syndromes. The hypothesis is advanced that the proportion of active tonic and phasic motor units determines the efficiency of sphincter reactions.


Congenital absence of the female urethra: surgical cure of case. A case of congenital absence of the urethra in a women suffering from total incontinence was cured by constructing a sphincteric tube from the lateral and posterior (trigone) walls of the bladder.


Behavioral consequences of dietary vitamin deficiency in young and middle-aged rats. The behavioral correlates of vitamin A and B 6 dietary deficiency in young adult rats (Experiment 1) and middle-aged, retired breeder rats (Experiment 2) were examined. Male and female rats received either vitamin A deficient, vitamin B6 deficient, or normal control diets for two and a half months. Body weight, eating, and drinking of water and adulterated fluids were monitored. Pyridoxine deficiency generally had greater effects on consummatory behavior and weight gain than vitamin A deficiency, but this effect was influenced by the rats' age and sex. Wheel running, (Experiment 1), increased above control levels in both the vitamin delete groups. Vitamin A and B 6 deplete diets may affect behavior before an animal displays classical physical signs. Furthermore, such behavioral changes are not restricted to young, rapidly growing male rats; instead, their character is influenced by both the sex and age of the animal.


Toxicity of Phytophthora infestans and Alternaria solani to chick embryos. None of the extracts and culture filtrates from growth of 9 races of Phytophthora infestans on living potato tissue and potato dextrose broth are toxic to chick embryos. Chloroform extracts of 4 out of 10 isolates of Alternaria solani grown on potato dextrose broth showed some toxicity to chick embryos.


Relationship between plasma unbound-bilirubin concentration and cerebellar bilirubin content in homozygous Gunn rat sucklings. Suckling increases and starvation (16 h) decreases plasma unbound-bilirubin concentration in 15-day-old homozygous Gunn rats. The effect of suckling-induced increase of plasma unbound-bilirubin concentration on cerebellar bilirubin content was examined. Cerebellar bilirubin content of the suckled rats did not increase, but rather decreased, in spite of the elevated concentration of plasma unbound-bilirubin . There were significant negative correlations between cerebellar bilirubin content and b. wt both in the suckled and starved groups.


[Oleum hippophaë, a stabilizer of biological membranes]. Toxic lesion of the liver was reproduced in albino rats by way of a separate and combined intragastric administration of a 20 per cent ethanol (in doses of 0.65 ml/100 g of mass) and of a 20 per cent CCl4 oil solution (in amounts of 0.3 ml/100 g of mass), thrice in a week for 3 months. Subject to investigation were the intensity of the lipids peroxidation with reference to the diene conjugates level in the liver tissue and peroxide resistance of the peripheral blood erythrocytes, P-450 cytochromes in the supernatant fluid after precipitation of the nuclei and mitochondria, total liver protein and subcellular structures, water-soluble liver protein. The activity of the P-450 cytochrome and the content of the total and water-soluble liver protein were found to change antibathmically to the lipids oxidation intensity, especially in animals receiving both poisons. Oleum hippopheae causes a well-marked anabolic effect which manifests itself in an increased proportion of tissular and serumal proteins. It lowers the free radical oxidation of the lipids, protects the cytochromes P-450 against damage. The mechanisms of the results, obtained are discussed.


[Change in the biogenic amine content in rats in acute and chronic alcohol poisoning]. In Wister line rats subject to determination were the epinphrine, norepinephrine, DOPA, dophamine, serotonin conents and monaminoxidase activity in the blood, liver and brain in acute alcohol poisoning. Acute alcohol poisoning did not produce any substantial changes in the content of biogenic amines in the blood, liver and brain of the rats. With chronic poisoning the content of catecholamines, serotonin increased while the monaminoxidase activity in the study organs declined, this bearing witness to the effect of alcohol on the metabolism of biogenic amines.


[Effect of m-cholinoblockaders and physostigmine on emotional reactivity and catecholamine metabolism in the brain of rats]. In experiments on male albino rats m-choline blocking agents, atropine and benactyzine potentiated the stimulating effect of l-DOPA on emotional reactivity and aggressiveness, while physostigmine antagonized behavioral effects of l-DOPA. Both the choline blocking agents and physostigmine lowered the brain dopamine accumulation rate after introduction of l-DOPA, at the same time raising the level of homovanilic acid dopamine metabolite. It is suggested that the effect of cholinergic compounds on emotional reactivity and aggressiveness of the animals depends in part on the activity of the brain dopaminergic system.


Scleroderma-inducing glycosaminoglycan in the urine of patients with systemic scleroderma. A glycosaminoglycan with scleroderma-inducing effect was isolated and partially purified from the urine of patients with systemic scleroderma. The glycosaminoglycan was an N-sulfated glycosaminoglycuronan and its high total sulfate and 2,5-anhydromannose contents suggest that the glycosaminoglycan is a degradation product of heparin or polysulfated heparin sulfate. Furthermore, the composition of the above glycosaminoglycan was similar to that of the N-sulfated glycosaminoglycan which we observed previously in uninvolved skin of scleroderma.


Treatment of post-pill amenorrhea.

Treatment of post-pill amenorrhea. Post-pill amenorrhea, a relatively rare but important sequela of oral contraceptive use, is often accompanied by galactorrhea. A review of women with post-pill amenorrhea-galactorrhea (PPAG) showed that it has more than one cause. Clinical and laboratory methods of evaluation are reviewed, and appropriate methods of treatment are suggested.


[The role of the physician in female sexual councelling (author's transl)]. In this investigation 100 women were asked by multiple choice questionnaire where they expected help with sexual problems. The female population of the area sees a need for sexual councelling and expects help primarily from physicians and more so from gynaecologists than general practitioners. Physicians are thought to be sufficiently trained and competent for sexual advice by the majority. 25% of the respondents had doubts about the competence and availability of sexual advice from physicians. The majority would seek sexual advice from physicians or husbands. Gynaecologists are preferred for sexual advice because of their specialization and greater anonymity than family physicians. Most patients dislike routine questions on sexuality and would prefer to open the subject themselves. The majority thinks of physicians as having normal sexual adjustment. Sexual councelling does not appear to be available as readily as desirable. Lack of available advice does not appear to be as urgent a problem as depicted in the mass media.


Viral antigens and impurities in influenza vaccines. Evaluation by immunoelectrophoretic methods. Laurell electrophoretic methods were used to evaluate internal influenza virus antigens and immunogenic impurities (from the fertile egg) in influenza whole virus and subunit preparations. It could be found that subunit preparations obtained after selective solubilization of the surface antigens with cetyltrimethylammoniumbromide are essentially free from internal structure proteins, ribonucleoprotein, and matrix protein. In addition impurities (non viral antigen substances) are considerably reduced in comparison with whole virus preparations, when the core particle is separated by centrifugation. By testing hyperimmune sera against whole virus and subunit preparations, concerning antibody specificities to host components, it could be demonstrated that whole viruses stimulate more antibodies to the host components, than subunit preparations. This is especially true if antigens are tested which are associated with the chorioallantoic membrane.


Experience with monovalent and bivalent influenza vaccines in Canada 1976. Laboratory examination of vaccines from four manufacturing companies and prepared with A/New Jersey/8/76 and A/Victoria/3/75 strains (clinical results, cf. these proceedings, pp. 267-272). When diluting the concentrated suspensions of vaccine, loss of activity can be avoided by adding a small amount of Tween 80 to the diluent.


Hemostatic complications in leukemic patients. With clinical vigilance and laboratory tests of platelet and coagulation factor function, the clinician can promptly recognize and treat hemostatic disorders in leukemic patients. For example, laboratory values are strikingly abnormal in disseminated intravascular coagulation. Prompt neutralization of the underlying cause of the coagulopathy is essential. Platelet and coagulation factors may have to be replaced if the disorder is severe. Diffuse petechiae, purpura, mucous membrane bleeding, and hemorrhage around venipuncture or infusion sites indicate thrombocytopenia. Vigorous platelet replacement is necessary to prevent massive intracranial of gastrointestinal hemorrhage. Platelet dysfunction may cause spontaneous bleeding or immediate or delayed hemorrhage after surgery. The abnormality is often evident in peripheral blood smear or indicated by bleeding time or aggregation studies. If possible, sufficient autologous platelets should be infused to return the bleeding time to normal. Immune thrombocytopenic purpura may be easy to diagnose when the reduction in the circulating platelet count is compared with the normal number of marrow megakaryocytes. But attempts to increase platelet count by platelet transfusions may be frustrating. Treatment involves high doses of corticosteroids, followed by splenectomy if necessary.


Growth and development of gastrocnemius muscle in S 5B/PL and Osborne-Mendel rats overfed during nursing. Three techniques for overfeeding rat pups were used from birth to 24 days of age to assess their effect on growth and development in an obesity susceptible (OM) and an obesity resistant (S 5B/P1) strain of rat. These included: (1) Feeding a semi-purified high fat rather than low fat diet to the dams (alters the energy content of milk); (2) Raising pups in litters of 3 rather than 6; and (3) Force feeding of milk in lieu of any force feeding. In OM rats there was no difference in lean body mass (excludes heart, liver and kidney) (LBM) gastrocnemius muscle weights, cell number and protein content of muscle. Body weights and gastrocnemius muscle triglycerides were significantly higher in OM rats fed the high fat diet than in those fed the low fat diet. S 5B/P1 (S) rats treated in the same manner as OM, showed no significant differences in body weight, LBM, gastrocnemius muscle weight or content of DNA, protein or triglycerides. Protein and DNA for 100 g fresh gastrocnemius muscle were similar for the two strains even though the muscle was 1 1/2 times heavier in OM than in S rats. Muscle triglycerides were higher in OM than in S rats.


Destruction of Ascaris suum eggs during their feeding to various species of beetles. Eggs of Ascaris suum (Linné, 1758) were fed to nine species of beetles of the families Scarabacidae, Carabidae and Histeridae in order to ascertain the dependence of egg penetration on the structure of mouth parts of the beetle. The mouth parts of some beetle species have various filtration apparatuses preventing the helminth eggs from penetrating into the digestive tract. Geotrupes stercorosus (Scriba) was found to possess a crushing apparatus which destroys a great number of helminth eggs penetrating into the digestive tract.


Effect of metabolic inhibitors on growth and brefeldin A formation in Curvularia lunata. Arsenite as opposed to azide exerted a stronger inhibitory effect on brefeldin A production than on mycelial growth of cultures of Curvularia lunata. However, azide was a more potent inhibitor of mycelial growth than arsenite at 0.5 mM and 1.0 mM. The inhibitory effects of iodoacetate on growth and brefeldin A formation were significantly less potent than those of iosoacetamide. Increases in the levels of fluoride elicited a variable inhibitory effect on brefeldin A production and a corresponding decrease in biomass.


Exogenous regulators in the mycelium of Pleurotus ostreatus after exogenous application. The mycelium of the fungus Pleurotus ostreatus was cultured on a synthetic medium with growth regulators. Best growth was observed on media with 100 ppm IAA, 200 ppm GA3 and 200 ppm of kinetin. Growth of terminal hyphae and the appearance of colonies differed characteristically. Auxin bio-assays showed that the content of substances in younger mycelium slowly increased during cultivation without conspicuous changes in the medium. After exogenous application of IAA the content of auxins in younger mycelium increased and the content of IAA decreased gradually in the culture medium. Gibberellin bio-assays showed their content in the mycelium fell during cultivation and while it increased in the medium. Application of GA3 to the medium leads to a significant increase in these substances in the young mycelium and in the medium their level remains the same. Cytokinin bio-assays showed their content to vary during cultivation. An addition to kinetin to the nutrient medium results in an increase of cytokinins in the mycelium while in the medium the level of cytokinins is maintained. Addition of one substance thus influences the levels of other endogenous regulators.


2,2'-dimethoxy-4a,4a'-dehydrorugulosin (rugulin), a minor metabolite from Penicillium rugulosum. A new metabolite was isolated from the culture of Penicillium rugulosum and its structure was determined from physico-chemical data. Accompanying metabolites skyrin and rugulosin were characterized by UV, IR, CD, mass and NMR spectra.


Infant killing and cannibalism in free-living chimpanzees. Male chimpanzees at the Gombe National Park were twice seen to attack 'stranger' females and seize their infants. One infant was then killed and partially eaten: the other was 'rescued' and carried by three different males. Once several males were found eating a freshly killed 'stranger' infant. A similar event was observed in Uganda by Dr. Suzuki and Dr. Nishida reports an incident from the Mahali Mountains, Tanzania. A different kind of killing occurred at Gombe when a female and her daughter killed and ate three infants of other females of the same community during a 2-year period. There is evidence suggesting that other infants may have died in this way. The paper draws attention to puzzling aspects of infant killing and cannibalism in chimpanzees.


Agonistic interactions of captive female orang-utans with infants. Female orang-utans with infants were pair-tested for dominance (displacement behavior) and for competitive food-getting. Dominance was quickly established in the first test for each pair, displacements were unidirectional in all tests and dominant animals obtained essentially all food incentives in 3 of the 4 series of tests. Agonistic interactions were similar in most respects to those of monkey, but were not influenced by location of testing, i.e. home cage. Aggressive behavior and food-getting were related to body weight but displacement was not. This development of dominance relationships is similar to those reported for many territorial vertebrates confined to restricted spatial conditions.


[Surgical refertilization by means of laser technic. Animal experimental study]. Animal experiments on rabbits with a CO2 laser concerning end-to-end-anastomosis of cornua uteri are reported. The rate of success of this laser technique by a before investigated optimal energy density of 64 Watt sec/cm2 (8 Watt,0,2 sec) was about 70% deliveries without any complication. This method could be an alternative to the presently used microsurgical methods of refertilisation in human tubar sterility.


[Carcinogens in the food].

[Carcinogens in the food]. It is estimated that in the Western hemisphere approximately 50% of all carcinoses in females and approximately 30% of all carcinoses in males are influenced by dietary factors. The most frequent carcinogenic dietary compounds are the polycyclic aromatic hydrocarbons, the nitrosamine combinations and the mycotoxins. Exact data on the carcinogenic risk of these dietary compounds is, however, not yet available for humans. Epidemiological investigations also support the assumed dietary carcinogenesis. It is known that the contracting rate for carcinoma of the stomach is considerably higher in Japan than in Europe or in the USA and that the morbidity rate for carcinoma of the colon is considerably lower in Third World countries. The positive incidence between dietary fat uptake and carcinoma of the breast seems to be well established.


Evidence for a role of androgens in the growth and maturation of ovarian follicles in rats. Changes in the morphology and steroid content of ovaries were studied after 48 h of intravenous injection of 100 microgram of cyproterone acetate or flutamide to diestrus or estrous rats. Treatment with cyproterone acetate at diestrus caused a decrease in the number of small follicles (less than 200 micrometer), freshly formed corpora lutea and the levels of estradiol-17beta in the ovary, suggesting inhibition of ovulation. Following flutamide administration at diestrus, the number of follicles at all stages of development were reduced with a concomitant decrease in the ovarian levels of the hormones. Thus, flutamide suppressed the growth and maturation of follicles. On administration of these drugs at estrous, the steroid content of ovaries was more pari passu with the increase in the number of mature and medium follicles. The differential effects of the two drugs are discussed in the light of these observations.


Preparation and application of Nalpha-B1,Nepsilon-B29-bis (ter.-butyloxycarbonyl)insulin. Two methods are described for the preparation of NalphaB1,Nepsilon29-Boc2-insulin from Nalpha A1-trifluoroacetyl-insulin and Nalpha A1-citraconyl-insulin in 80 - 90% and 65% yields, respectively. Removal of the Boc protections afforded the fully active insulin. Application of this derivative was demonstrated by the preparations of des-GlyA1-insulin and [A1-guanidinoacetyl]insulin. The former compount exhibited 2% activity in the in vitro free fat cell assay and the latter 88 +/- 5% while NalphaB1-NepsilonB29-Boc2-insulin showed 45 +/- 3% activity only.


Dyslexia revisited. A review.

Dyslexia revisited. A review. Specific developmental dyslexia, a condition characterized by reduced reading, spelling, and writing abilities combined with normal intellectual capacity, has challenged geneticists and 'environmentalists.' Although most of the strikingly controversial results can be traced to differences concerning diagnostic decision-making, there are many hints of a genetic contribution. Twin studies and extensive pedigree analysis substantiate this view, but it is too early to infer a definite mode of inheritance from the available data.


Rupture of the urethra in a female child with a fractured pelvis: a case report. A case of complete rupture of the urethra in a female child is reported. The condition is very uncommon and some possible explanations are given to account for its rarity.


Role of endogenous interferon in the anti-tumor effect of poly I-C and statolon as demonstrated by the use of anti-mouse interferon serum. We have determined the effect of sheep anti-mouse interferon globulin on the anti-tumor effects of poly I-C, statolon, tilorone, pyran copolymer and BCG in mice inoculated with Ehrlich ascites or L 1210 lymphoma cells. Whereas the anti-tumor effects of poly I-C and statolon were nulified when mice were injected with immunoglobulins, the anti-tumor effects of pyran copolymer and BCG were not modified by this treatment. We conclude that interferon mediates the anti-tumor activity of poly I-C and statolon in these experimental systems. It is suggested that anti-interferon serum provides a direct method of determining whether other biologic effects attributed to viruses, poly I-C, statolon, tilorone, pyran copolymer (and possibly other interferon inducers) are mediated or not by interferon.


Experimental observations on the integration of bladder and urethral function. Bladder and urethral pressure responses to pelvic sympathetic and pudendal nerve stimulation 60 anesthetized cats were studied. Results show that urethral resistance is composed of smooth and skeletal musclar components, which relax with pelvic nerve stimulation. Reciprocal inhibition of the detrusor-external sphincter is a spinal-mediated reflex that can be elicited by pelvic or pudendal nerve stimulation. Urethral smooth muscular pressure loss with pelvic nerve stimulation can be blocked with propranolol, suggesting that beta-receptors are involved in this response.


[Microsporum persicolor, an easily misinterpreted dermatophyt]. Trichophyton persicolor was described by Sabouraud in 1910, and was mistaken by most mycologists for Trichophyton mentagrophytes. Recently the infection in wild rodents was discovered and the independence of this fungus proved by its perfect form (Nannizzia persicolor) which is called at the present time Microsporum persicolor.


Ultrastructural aspects of bilirubin encephalopathy in cochlear nuclei of the Gunn rat. The cochlear nuclei of homozygous Gunn rats aged 2 days to 7 months were examined. Ultrastructural abnormalities were observed in all age groups studied, including 2 and 4 days old animals. Mitochondrial alterations are amont the earliest manifestations of bilirubin encephalopathy (2 days). In mitochondria of large neurons, vacuoles were found which contained increasing (with age) collections of alpha and beta glycogen particles. Some of the larger 'ex-mitochondrial sacs' appear to have been caught at the point of disruption, with glycogen-filled vacuoles in close proximity. Dilated profiles of rough ER also contained glycogen particles. In the cytoplasm of the same large neurons, elaborate myelin figures surrounded tongues of cytoplasm, vacuoles and degenerative elements. Reconsideration of previous morphological and biochemical observations in the light of the present findings makes it appear very likely that bilirubin primarily affects membrane function, especially in mitochondria.


Histochemical studies on genetical control of hormonal enzyme inducibility in the mouse. I. Non-specific esterase activity and regional histology of the epididymis. As a base line for future cell genetical studies the authors record the distribution of non-specific esterase reaction in the various histologically distinguishable cell types of the mouse epididymis. The findings are correlated with previous descriptions of the lobar structure of the organ. Assuming the sequence of lobes of the head to be as implied in these classical descriptions, the esterase activity of the epithelial cells gradates between strong to weak several times along the length of the epididymal duct. The relationship of the lobes to each other, as seen in transverse sections, is described. Methodological studies using different fixatives indicate that apparent similarity of esterase reaction at different sites may camouflage an underlying difference in the nature of the esterases at these sites.


The diurnal variation of mitotic response in the epithelium at the edge of acute ulcers in the rectal mucous membrane of guinea-pigs. The mitotic response to wounding was examined in ulcers resulting from the excision of small pieces of rectal mucous membrane in two groups of guinea-pigs. One group was wounded at 09.00 hours and a second group at 21.00 hours. Mitotic counts were carried out in the glandular epithelium at the ulcer edges at 2 hourly intervals over a period of 24 hours. Mitotic activity increased in 2--4 hours and thereafter showed a peak-and-trough pattern. The wounded rectal epithelial cells exhibited a diurnal variation with a peak of activity during the day and low activity at night. It would appear that such diurnal rhythmicity is not species-specific because it was similar in both the guinea-pig and rat. The evidence suggests that there is not a chalone-adrenaline complex in the rectal epithelium as the diurnal variation was similar in the nocturnal rat and in the diurnal guinea-pig, and was not abolished by wounding. Mitotic activity was lower in the glands at the immediate wound edge, and in the upper cells of the glands. The cells in these situations are probably designated for migration to close the defect, for migration excludes mitosis. It seems possible that the mechanisms responsible for the circadian rhythm of mitosis are different from those which induce the bursts of mitotic activity after wounding; if so this would be contrary to the chalone concept.


Multiple forms of glucokinase from Dictyostelium discoideum. A single form of glucokinase with an apparent Km value equal to 0.12 mM glucose was detectable in extracts prepared from aggregating cells, whereas kinetic and electrophoretic evidence indicated the presence of this form as well as a second glucose-phosphorylating enzyme with a Km value of about 0.01 mM glucose in extracts from culminating cells.


(Lysyl-Glycyl-Glycyl)5 and (Lysyl-Glycyl-Glycyl)10 as models of histone. Interaction with DNA and acetylation by calf thymus enzyme. Sequential polypeptides (Lys-Gly-Gly)5 and (Lys-Gly-Gly)10 were synthesized as models for the N-terminal region of H4 histone and their interactions with DNA were studied. The ability of (Lys-Gly-Gly)10 to precipitate DNA was found to be much higher than that of (Lys-Gly-Gly)5. For example, at the physiological salt concentration, (Lys-Gly-Gly)10 precipitates DNA but (Lys-Gly-Gly)5 does not. Both peptides could be acetylated by a partially purified histone acetyltransferase preparation derived from calf thymus. epsilon-Amino groups of lysyl residues were the sites of the acetylation. DNA-cellulose chromatography of the products indicated that acetylation weakened the interaction of the peptides with DNA.


Amino acid sequences of fragments I and II obtained by cyanogen bromide cleavage of rat serum albumin. The amino acid sequences of fragment I, the N-terminal cyanogen bromide fragment, and fragment II, a fragment between the first and second methionine residues, of rat serum albumin were determined by conventional methods in consideration of the sequences of human and bovine serum albumin. These sequences were compared with those of human and bovine serum albumin.


Purification and characterization of calcium-binding protein from chick chorioallantoic membrane. A procedure is described for the purification of the calcium-binding protein (CaBP) from the chorioallantoic membrane of the chick embryo. With this scheme, a 180- to 200-fold purification was achieved with a 40% yield. Characterization of the CaBP revealed that its properties differ from those of previously studied calcium-binding proteins. The CaBP has a molecular weight of 95,000 to 100,000 and appears to be composed of four subunits of identical molecular weight (22,000 to 25,000). The CaBP is a basic protein as indicated by its high electrophoretic mobility under acidic conditions and its relatively high isoelectric point of 8.06. The calcium-binding activity of the CaBP is sulfhydryl dependent and highly specific for calcium ions (10 high affinity sites, ka = 2.35 X 10(7) m-1; 100 to 120 low affinity sites, ka = 2.00 X 10(5) M-1). Amino acid analysis indicated that the CaBP contains 2 to 10 residues of a modified amino acid, gamma-carboxyglutamate (gamma-CGlu). The presence of gamma-CGlu residues suggested that vitamin K may be involved in the expression of the CaBP in the chorioallantoic membrane.


Sodium-dependent amino acid transport in reconstituted membrane vesicles from Ehrlich ascites cell plasma membranes. Plasma membranes, isolated from Ehrlich ascites tumor cells, were dissolved in 2% cholate, 4 M urea and then reformed into liposomes upon dialysis at 4 degrees with exogenous phospholipids. Reconstituted vesicles regain the ability to transport amino acids. Na+ was shown to accelerate the uptake of alpha-aminoisobutyrate, phenylalanine, and methionine, but not leucine or epsilon-aminohexanoic acid. With the reconstituted vesicles, methionine, but not leucine, inhibited the uptake of alpha-aminoisobutyrate. An apparent Km value for alpha-aminoisobutyrate uptake of 3.0 mM was obtained. This value is close to that observed with the intact cells and the native membrane vesicles. A Na+ gradient (high Na+ outside) increased alpha-aminoisobutyrate uptake, whereas a reversed gradient (high Na+ inside) increased alpha-aminoisobutyrate efflux. The latter flux was increased by valinomycin, suggesting electrogenic transport. A modest extent of coupling between a Na+ gradient and uphill flow of alpha-aminoisobutyrate was observed.


The aetiology of Perthes' disease. Genetic, epidemiological and growth factors in 310 Edinburgh and Glasgow patients. The aims of this survey were to establish the familial incidence of Perthes' disease, to note any associated developmental anomalies and to collect information on preceding trauma or synovitis, on the pregnancy and birth, and on various sociological factors. Height and weight measurements were obtained for 217 patients, and comparisons made with those of their parents, unaffected sibs and (local) controls. Results showed an extremely low frequency of Perthes' disease among relatives, with no obvious pattern of inheritance. As genetic factors were not apparent, environmental and sociological causes were sought. The disease occurred particularly in children who were third-born or later in the family, and had older than average parents. Many came from low-income families and one in ten had been a breech birth, shown other malposition or had had a version late in pregnancy. Many children were already undersized at the time of developing Perthes' disease and remained short than average throughout life. Neither their parents nor sibs were shorter than normal, indicating that the patients' short stature was not familial. The child who is going to develop Perthes' disease is already constitutionally and socially at a disadvantage, and during the perinatal period and the first few years of life is perhaps more susceptible to trauma than is a normal child.


Studies on pulse-labelled RNA during the mitotic cycle of Physarum polycephalum by subnuclear fractionation. A method is described for the isolation of pulse-labelled RNA from nuclei and subnuclear fractions of Physarum polycephalum. At all times during interphase the nucleolar RNA consisted mainly of a 34-S rRNA precursor with only small amounts of 26-S and 19-S rRNAs. The nucleoplasmic RNA consisted of predominantly mature 26-S rRNA with small amounts of 19-S rRNA and a 30-S RNA species. The 30-S RNA component displayed different labelling kinetics from the rRNA precursors. A low molecular weight RNA fraction (4-8 S) appeared to accumulate in the nucleus as interphase progressed.


Thin-layer chromatographic separation of the 3-O-methylated metabolites of noradrenaline. The use of sodium borate impregnated thin-layer silica gel plates for the separation of noradrenaline and its 3-O-methylated metabolites is described. Its application to studies of the metabolism of tritiated I-noradrenaline by isolated tissues is illustrated for the rabbit uterus.


Variation of food intake and body weight with estrous cycle, ovariectomy, and estradiol benzoate treatment in hamsters (Mesocricetus auratus). Food intake and body weight of hamsters fluctuated systematically with the estrous cycle. Food intake and body weight were lowest when elevated endogenous estrogen levels were expected. Ovariectomized hamsters gained a significant amount of body weight compared with sham-operated animals. Replacement therapy with estradioal benzoate reduced the body weight and food intake of ovariectomized animals relative to oil-injected, ovariectomized control animals. The results are compared with similar data from rats and support the concept that in females of both species estradiol operates to regulate food intake and body weight.


Behavior of the rat after removal of the neocortex and hippocampal formation. After surgical removal of the neocortex and hippocampal formation, rats retained most of the movement patterns of locomotion, climbing, grooming, feeding, and fighting. However, forepaw immobility during swimming was abolished. Feeding behavior was suppressed temporarily but recovered partially. The distinctive postures of sleep and walking and a circadian rhythm of motor activity were retained. However, behaviors were often not performed at the appropriate time and place. The normal sequence of grooming behavior was disrupted; food hoarding and social behavior were essentially abolished. Removal of the neocortex alone had much the same effect as removal of neocortex and hippocampus together. Removal of hippocampus alone produced only a mild disruption of behavior. It is suggested that ascending nonspecific projections to the cerebral cortex play an important role in the moment-to-moment control of behavior but are not essential for the sleep-waking cycle.


Differential influence of stereoisomers of estradiol on sexual behavior of female hamsters. Morphological and behavioral responses to estradiol-17 beta (E2-17 beta) and estradiol-17 alpha (E2-17 alpha) were examined in a series of three experiments. The E2-17 beta augmented uterine growth in hamsters to a greater extent than did E2-17 alpha. Lordosis in ovariectomized adults was elicited by treatment with E2-17 beta but not with E2-17 alpha (each tested in combination with progesterone). When administered neonatally only E2-17 beta disrupted estrous cyclicity in the intact female and induced the ability to mount in ovariectomized, androgen-treated adults. These results suggest the existence of a stereospecific response to estrogenic stimulation in neural tissue comparable with that occurring in the uterus.


Alterations of male sexual behavior by learned aversions to hamster vaginal secretion. Male hamsters poisoned after their first adult exposure to the vaginal secretion of female hamsters became hesitant to approach and ingest the secretion. The same aversion-training procedure also altered the responses of males to estrous females, changing the latency, frequency, and duration of a variety of behaviors that are commonly taken as indexes of sexual attraction or arousal and of copulatory performance. The effects suggest that the aversions to vaginal secretion alter the perceived meaning of the secretion for male hamsters, and analysis of the correlations between various measures of sexual arousal and performance support the hypothesis that separate mechanisms underlie the effects of the secretion on appetitive and consummatory sexual behavior.


The supply of optometric manpower.

The supply of optometric manpower. Approaches to determining health manpower requirements are reviewed. The paper identifies a source of error in determining the present supply of optometric manpower which will ultimately influence any policy or program intended to either correct or adjust future health manpower supplies. The study also demonstrates a need to refine the data on health manpower supplies with particular reference to the characteristics and practices of the optometrist.


Circulating plasma levels of pregnenolone, progesterone, estrogen, luteinizing hormone, and follicle stimulating hormone in young and aged C57BL/6 mice during various stages of pregnancy. Young (3-5 mo of age) and senescent (12-15 mo of age) multiparous C57BL/6 mice were mated with young males (3-6 mo of age) and the numbers of preimplantation embryos and implantation sites determined on days 1 (day of plug), 4, 9, and 16 of pregnancy. The numbers of viable embryos were significantly lower (p less than 0.02 to p less than 0.001) in senescent females compared with young females on all days except day 1 of pregnancy. Plasma samples tested by radioimmunoassay indicated circulating estradiol-17B was significantly lower (P less than 0.05) on day 1 and higher (p less than 0.05) on day 4 in older females, whereas FSH was higher on days 4, 9, and 16 (p less than 0.02 to p less than 0.001) in senescent females when compared with samples from young females. Levels of pregnenolone, progesterone, estrone, and LH were not significantly different at any stage of pregnancy in the two age groups. From the hormonal data it did not appear that degenerating corpora lutea were responsible for the declining litter size in this strain of aged mouse.


Some immunological findings in silicosis. Results of an experimental study of the effect of quartz [DQ 12a1 administered intratracheally to Wistar line rats on the status of their immunological reactivity. The results obtained showed that a significant inhibition of antibody formation to human albumin took place in animals with experimental silicosis in comparison with control rats that were given physiological saline or corundum as established by passive haemagglutination reaction according to Boyden as well as enhancement of the intensity of the delayed-type hypersensitivity to tuberculin. That became manifest by stronger inhibition of macrophage migration from spleen fragments.


Purification of mouse cell interferon induced by isotopically labelled double-stranded f2 phage RNA. The dynamics of interferon formation by an established cell line of mouse fibroblast (L cells) and by mouse peritoneal leukocytes induced by double-stranded RNA extracted from E. coli f2 phage is described. The L cells produced interferon at a lower rate, the maximum values were obtained at 12 to 20 hours after induction, and the production was ultimately dependent on the established cell line used and on the presence of DEAE-dextran during induction. The mouse peritoneal leukocytes (MPL), on the other hand, did not require DEAE-dextran and the maximum of interferon production was reached between 6 and 12 hours after induction. Both the L cell- and the MPL-interferons were purified and concentrated so that the final specific biologic activity was 100-to 300-fold higher than that of the initial preparations (1 to 5 X 10(6) interferon units per mg protein). Polyacrylamide gel electrophoresis showed similar migration profiles for the preparations of both interferons. The smaller part of the activity was situated in a broader, slow-moving peak and the greater part formed a sharp, high and fast-moving peak. Using 3H uridine-labelled f2 ds-RNA for induction of interferon it was found that one of the radioactivity zones coincided with the fast-moving activity peak of the purified and concentrated interferon.


Anticomplementary properties of 043/63 and 043/13 two new antiinflammatory drugs. The anticomplementary properties of two indandione derivatives were studied in vitro on fresh human serum and in vivo on rabbits. In vitro the two substances block immunohemolysis and have direct effect on serum complement activity. One substance blocks the activation of the first complement component and the other the fourth complement component. In vivo, single doses, lower or block complement activity of rabbit serum.


Immunity status of Czech population with regard to poliomyelitis in 1970--1975. The results of examination of antibodies against all three types ofthe poliomyelitis virus from the period of systematically performed multipurpose immunological survey in the Czech Socialistic Republic (1970--1975) are presented and evaluated. The analysis of these results indicates that the status of immunity in the Czech population, systematically vaccinated against poliomyelitis, is good, as all requirements of collective protection against this disease have been met. At the same time, the results demonstrated that immunological surveys are at present the most suitable method of verifying the immunity of the vaccinated population and should be consistently performed.


The mechanism of group differences in the character of the vaccinal process in immunization against natural smallpox. The effect of antigenic polymorphism of the ABO-system blood groups on the character of the vaccinal process after immunization against natural smallpox was investigated. The increased susceptibility of persons possessing A antigen to the harmful effect of smallpox vaccine virus is due to hereditary rather than to acquired factors. The leukocytes of peripheral blood of these persons showed a poorer binding capacity with respect to the smallpoxvaccine virus; they also exhibited a high rate of chromosomal aberration after vaccination, resulting to some extent from increased proliferative ability of the cells.


Serum immunoglobulin levels in various forms of meningococcal infection and in meningococcus carriers. The levels of serum IgG, IgA and IgM were examined in 191 adults including 103 patients with various forms of meningococcal infection, 32 meningitis convalescents and 56 carriers, in order to elucidate the causes of different susceptibility to the meningococcal infection. The IgD level was determined in 54 meningitis patients as well as in convalescents and carriers. The amount of immunoglobulins was determined by radial immunodiffusion. The level of IgG at the beginning of the disease in patients with the generalized forms of meningococcal infection (meningitis, meningitis combined with meningococcaemia, meningococcaemia) was found to be considerably lower than in healthy subjects. The levels of all immunoglobulins, particularly of IgA and IgM, increased in the course of the disease. The levels of IgG, IgA and IgM in meningitis convalescents a year after recovery were found to be the same as in the controls. The levels of IgG, IgA and IgM in patients with meningococcal nasopharyngitis were significantly lower than in healthy subjects. The carriers showed a decreasd level of IgA and a considerably increased level of IgG while the levels of IgM and IgD did not differ from the control.


Lysis of C1Q-coated chicken erythrocytes by human lymphoblastoid cell lines. Human lymphoblastoid cells lysed chicken erythrocytes (E) that carried cell surface bound human C1q. Antibody to E(A) was not required for the C1q-dependent reaction. The effect of C1q was inhibited by Fab'2 anti-C1q and by the serum C1q inhibitor. The action of the lymphoblastoid cells was inhibited by anti-metabolites and by pretreatment of the cells with trypsin which is known to destroy their C1q receptor. Lymphoblastoid cell lysate was inactive. The time course of the C1q-dependent lysis was comparable to that of the antibody-dependent cellular cytotoxic reaction of human K-cells. Lysis of EA by human peripheral lymphocytes was enhanced up to 50% by human C1q.


Safety of influenza vaccination in allergic children. One hundred forty-two allergic children aged three to 18 years were studied for evaluation of the usefulness of skin testing with influenza vaccine as a means of identifying those children who could be immunized safely despite their allergies to chickens, eggs, or feathers. One hundred twenty-eight children were fully immunized with bivalent influenza A/New Jersey/76-A/Victoria/75 vaccine. Twelve children had positive skin tests and were not immunized, and two developed positive skin tests after their first injection. One child had urticaria 8 hr later, one had a nonspecific reaction, and one had a self-limited erythema multiforme reaction eight days after the second injection. All others tolerated the procedure well. History of sensitivity to eggs was not as reliable an indication of vaccine sensitivity as skin testing with vaccine. A negative result of an intradermal skin test with a 1:100 dilution of the vaccine in saline appeared to be a reliable indicator of allergic subjects who could be immunized against influenza without fear of life-threatening acute allergic reactions.


An otorhinological study of children with cleft palates. An otorhinological study of 245 children with cleft palate was carried out in two groups from two different hospitals. The incidences of deafness and exudative otitis media were much higher in the group where each child was seen by an otologist and hearing tested by audiogram. The lower incidence in the second group could be explained by the fact that a large number of children with exudative otitis media and deafness were missed as they were neither routinely seen by an otologist nor were they screened by audiograms. We found 37% of asymptomatic children were deaf. It is important therefore that all children with clefts of the palate should be seen by an otologist and investigated by audiogram and impedance test. The incidence of deafness was less if the cleft involved soft palate only and if the palate was repaired early. The incidence was also less in children who had their tonsils and adenoids removed. Infracture of the pterygoid hamulus during the repair of the soft palate failed to show any increase in the incidence of deafness. In this study we found a higher incidence of deafness amongst children with nasal escape. Fifty per cent of the children with clefts of the palate and lip had deviated nasal septum producing nasal obstruction.


Use of meclofenamic acid to investigate the role of prostaglandin biosynthesis during induced parturition in sheep. The maternal administration of meclofenamic acid (a prostaglandin synthetase inhibitor) to pregnant sheep prevented the dexamethasone-induced delivery of live lambs and delayed delivery after foetal death in utero. Administration of meclofenamic acid had no effect on the changes in the levels of progesterone and oestrogen in the plasma which occur before lambing in response to foetal glucocorticoid. Despite normal maternal endocrine changes, increased uterine activity did not occur at the expected time, although it could be elicited by vaginal distension or by administration of oxytocin. The rates of cervical ripening and dilatation were reduced by meclofenamic acid and lambing was frequently associated with some degree of cervical dystocia. Withdrawal of meclofenamic acid did not immediately result in an increase in the level of prostaglandin F in the plasma despite the appearance of co-ordinated uterine contractions; the concentration of prostaglandin in the plasma was not raised until vaginal passage of the lambs. It is concluded that the synthesis or release of prostaglandins mediates the effects of changes in the levels of steroids in the maternal plasma on uterine contractility in sheep.


Increases in steroid binding globulins induced by tamoxifen in patients with carcinoma of the breast. The effects of tamoxifen on cortisol binding globulin (CBG) and sex hormone binding globulin (SHBG) were studied in 25 women and one man with breast cancer. These patients were in various endocrine states according to age (15 post-menopausal women) or previous endocrine surgery (ovariectomy, two patients; ovariectomy plus adrenal surgery, five patients; hypophysectomy, three patients; ovariectomy plus hypophysectomy, two patients). The administration of tamoxifen (20-40 mg/day) resulted in increases in the level of CBG in all patients (mean rise in binding capacity 10.8 microgram cortisol/100 ml plasma) and in the level of SHBG in 21 patients (mean rise in binding capacity 0.79 microgram dihydrotestosterone/100 ml plasma for all patients). These increases were positively correlated. They were not associated with any alteration in the association constants of the steroid binding globulins. The effect of tamoxifen on CBG diminished with increasing age. The changes in the levels of CBG and SHBG were independent of the endocrinological state of the patient. It is inferred that tamoxifen has a direct oestrogen-like action on the liver which results in increased production of CBG and SHBG. Tamoxifen therapy for carcinoma of the breast appeared to be least effective in those patients in whom the drug caused the highest increase in the concentration of CBG.


Release of growth hormone in lactating and non-lactating goats in relation to behaviour, stages of sleep, electroencephalograms, environmental stimuli and levels of prolactin, insulin, glucose and free fatty acids in the circulation. Recording electrodes were implanted in contact with the dura mater overlying the parietal cortex of six female goats, four of which were lactating. After recovery from surgery and complete familiarization with the housing conditions, the personnel and the recording technique, each goat was observed continuously for 24 h with simultaneous recording of the cortical electroencephalogram (EEG). Remote blood sampling was carried out every 30 min without disturbing the animal. Apart from the release of growth hormone (GH) associated with morning milking in two of the goats, there was no consistent relationship between the apparently spontaneous, episodic release of GH and behvaiour, stages of sleep, cortical EEG, air temperature, time of day or night, obvious environmental stimuli which arose from the normal husbandry routine, or the levels of porlactin, insulin, glucose or free fatty acids in the blood. There was also no relationship between the release of prolactin and the stages of sleep.


Mouse spleen lymphoblasts generated in vitro. Recovery in high yield and purity after floatation in dense bovine plasma albumin solutions. Mouse spleen lymphoblasts, stimulated to divide in vitro, acquired a low cell density and could be separated by isopycnic techniques. Cultured cells were suspended in BPA columns, rho = 1.080, and spun to equilibrium. The method was simple, fast, accomodated large numbers of cells, and was reproducible. It provided lymphoblasts in high yield and purity (at least 80% of the low density cells were blasts). It allowed for the recovery of proliferating cells in their first cell cycle, and did not alter the subsequent ability of cells to proliferate when recultured in vitro. Certain properties of mouse spleen lymphoblasts were analyzed in detail. Lymphoblasts induced by LPS, FCS, con A (tetravalent and succinylated), and MLC were very similar except in the absolute numbers that were induced. The blasts exhibited the classic cytologic features of enlarged nucleoli and abundant cytoplasmic polyribosomes (basophilia). As a population, they were enlarged in size relative to nondividing cells, but this seemed to apply primarily to cells in the S and G2+ M phase of the cell cycle rather than G1. The cell cycle distribution of lymphoblasts was analyzed by flow microfluorometry. By analyzing low density cells obtained at varying intervals after mitogen stimulation, FMF indicated that lymphoblasts enter the S phase of their first cell cycle beginning at 20-24 h after stimulation.


Leishmania donovani. Hamster macrophage interactions in vitro: cell entry, intracellular survival, and multiplication of amastigotes. An in vitro system was developed for studying host-parasite cellular interactions in visceral leishmaniasis with amastigotes isolated from infected spleens of hamsters and their peritoneal macrophages maintained by an improved method. The culture system supports the growth of Leishmania donovani amastigotes with different parasite/macrophage ratios for up to 2 wk, yielding results more consistent and reproducible than previously possible. Results indicated that the "forms" of the amastigotes (with or without adherent host membranes) and the "state" of the macrophages (with or without stimulation in vivo by thioglycollate or in vitro by aging) had no effect on the growth rate of the parasites, which, however, seems to vary with the macrophage subpopulations. An electron microscope study suggests that amastigotes are ingested through phagocytosis by the macrophages and become lodged in loose phagosomes. Additional evidence with quantitative data is presented to support the earlier findings that phagosome-lysosome fusion occurs after the interiorization of the parasites and that they not only survive but multiply in these vacuoles. During the postinfection periods, reorientation of amastigotes in vacuolar space results in the appearance of three types of parasitophorous vacuoles (parasites in loose vacuoles, in tight-fitting vacuoles or abutting in part against the inner lining of vacuoles). The last category may be the predominant type giving rise to the variations observed. Exogenously introduced dense marker accumulated in these parasitophorous vacuoles of the macrophages infected for several days indicating a continuous accessibility of amastigotes to the ambient mestruum via phagosome-lysosome vacuolar system of the host cells. This finding may have significant implications in parasite nutrition, host immunity, and chemotherapy of leishmaniasis.


Mouse spleen lymphoblasts generated in vitro. Their replication and differentiation in vitro. Mouse spleen lymphoblasts induced with lipopolysaccharide and fetal calf serum were obtained in high yield and purity in their first proliferative cell cycle by floatation in dense bovine plasma albumin columns (3). The blasts were maintained in vitro for 3 more days. The cultures were examined in bulk on each day, and in addition, those cells in S phase initially were tagged with [(3)H]thymidine and followed continuously in vitro. Grain count dilution data indicated that most blasts divided but twice over a 2- to 3-day interval in vitro. [(3)H]Thymidine pulse radiolabeling and flow microfluorometry suggested that at least 50-70 percent of the proliferating blasts withdrew from proliferative activity after 2-3 days of culture. Morphologic studies demonstrated that lymphoblasts persisted as such for 1-2 days in vitro and then matured into typical plasma cells. Many of the blastprogeny had small nuclei and considerable basophilic cytoplasm on Giemsa-stained cell smears; abundant rough endoplasmic reticulum by electron microscopy; and readily detectable cytoplasmic Ig by immunocytochemistry. Reversion of blasts to small lymphocytes could not be detected; however, some blasts persisted even after 3 days of culture. The viability of the cultured lymphoblast was followed by initially tagging the cells with [(3)H]thymidine as well as several other techniques. Little cell death was documented during the first day of culture. The number of labeled progeny increased twofold whereas the grain count halved. But 40- 50 percent of the cell-associated label was lost during each of the second and third days, and fewer labeled progeny than predicted by grain count dilution were identified. The culture medium could not be implicated in this loss of lymphoblast progeny, and we suggest that the maturation of the lymphoblast to a short-lived plasma cell was responsible. Therefore mitogen-stimulated B blasts seem to mature into typical plasma cells after just two cycles of cell division. The plasma cells resemble those produced in situ during an immune response in their cytologic features, withdrawal from active proliferative activity, and short life-span.


Association of virus specific replicative ribonucleic acid with nuclear membrane in chick embryo cells infected with japanese encephalitis virus. Using high resolution electron microscopic autoradiography and velocity sedimentation, RNA synthesis was examined in chick embryo cells infected with Japanese encephalitis virus (JEV). RNA was labelled with 3H-uridine for 5 min or 10 min at 15 h after infection in the presence of actinomycin D and D-glucosamine. Microautoradiography showed significantly numbers of silver grains on the nuclear membranes of 5 min pulse-labelled thin cell sections. The RNA species in membrane fractions obtained from the nucleus and cytoplasm of the infected cells were analysed by sucrose density gradient sedimentation. Radioactive 23S replicative form RNA and 8-12S RNA were obtained from the outer membrane fractions of the nuclear envelope. Labelled 42S virus RNA was obtained from the fractions containing large vesicle membranes and plasma membranes. These results suggest that JEV-RNA synthesis is initiated in the perinuclear region in close association with the outer membranes of the nuclear envelope.


The effects of colony differences on muricidal behavior in rats within one strain. Two experiments were performed to investigate the origin of colony differences in muricidal behavior within the same strain of rat. In the first experiment (N = 52 male Long-Evans rats), the first generation offspring of parents from two different colonies were reared under identical conditions and tested for muricide. No differences were found, indicating that an environmental effect accounted for previously observed differences. The second experiment (N = 36 male Long-Evans rats) examined the effects of the presence or absence of mice in the rearing quarters. Again, no differences in muricidal rates were found. Overall, the offspring of killer mothers killed significantly more often than the offspring of nonkiller mothers.


The effect of an aversive imprinted stimulus on aggressive behavior. The hypothesis that aggression is affected by varying the affective value of the imprinted stimulus was tested with 12 Bardrock chicks. The affective value was defined as a hypothetical response of the animal which was inferred from observable events such as distress calls and flight responses. An aggressive response was defined as an imprinted bird's peck at a socialized bird. In order to vary the value of the imprinted stimulus, different shock frequencies were paired with the simultaneous withdrawal of the imprinted stimulus. The difference in aggressive responses between the experimental and control S s was significant (p less than or equal to .01). The present experiment suggests that only moderate levels of aversive stimulation when added to the imprinting process served to maximize both imprinting and aggression. Shock intensities either above or below this level resulted in reduced aggression--in the former case because of interference due to overstimulation, in the latter because of incomplete excitation.


Effects of combining pilocarpine, d-amphetamine, and either a free feeding schedule or cyclic food deprivation on mouse killing by rats. The combination of a drug which suppresses mouse killing by rats (d-amphetamine) , a drug which activates mouse killing (pilocarpine), and either ad-lib food or a 24-hour cyclic food deprivation schedule were examined for their effects on the mouse-killing response by rats (N = 53). Results showed that the presence of d-amphetamine prevented the activating effects of pilocarpine in rats with a fairly high killing propensity regardless of whether they were on the ad-lib food or the deprivation schedule. The study suggests that a drug which affects both eating behavior and mouse killing is more effective in determining behavioral outcomes than a drug which affects only mouse killing.


Blood-group antigens and antibodies in human brain-tumor cysts. Cyst fluids from 12 human brain tumors were studied for their blood-group content and compared to autologous saliva, serum, and cerebrospinal fluid (CSF). Lewisa substance, which is a fucolipid, was present in four of 12 cysts studied. Lewisb, which differs from Lewisa by a single fucose, was found in eight of 12 sera and/or saliva and in one CSF specimen; Lewisb substance, however, was not detected in any corresponding cyst fluids. Isohemagglutinins, blood-group antibodies anti-A and/or anti-B, were present in nine of nine cyst fluids studied, were of lower titers as compared to autologous serum, and occurred as either IgG or IgM immunoglobulins. The results further delineate the biochemical requirements necessary for molecular penetration into human brain-tumor cysts.


Hepatic transaminase in protein-restricted rats: development of a controlled model. A marginal protein malnutrition model which makes allowances for the increasing nutritional requirements of the growing rat and the effects of dietary manipulation on diurnal rhythms, while still rigidly controlling the level of protein restriction, is reported. A predetermined, constantly increasing intake of four purified diets, providing approximately 40 to 160% of the National Research Council protein requirement for rats was fed to rats receiving a nitrogen-free energy source adlibitum. This standardization reduced within-group variation and allowed precise growth reproducibility. Biochemical parameters were measured at evenly spaced intervals throughout the day to remove diurnal differences from between-group comparisons. Growth, nitrogen balance, and 24-hour means of liver weight, DNA, RNA, protein, and glutamate-oxaloacetate and glutamate-pyruvate transaminases reflected protein intake. However, when growth was depressed 10, 30, or 60%, liver GPT/DNA was depressed 40, 49, or 67%, respectively. Hepatic GPT appears to be a sensitive and accurate indicator of marginal protein malnutrition.


Biological availability to the rat of intrinsic and extrinsic iron with soybean protein isolates. Evaluations were conducted to assess the biological availability of iron in three food grade isolated soybean proteins and to evanuate the influence of these proteins on iron added to the diet from a source of known high biological availability. Ferrous sulfate was used as the standard iron source in all experiments. The biological availability was measured by a 14-day hemoglobin repletion after a 4 week depletion period using multiple dose response and comparing the test samples and standard iron source by the slope ratio assay procedure. The relative iron bioavailability for three isolated soybean proteins was A = 60%; B = 64% and C = 59% with a mean value of 61%. Autoclaving isolated soybean protein B at 108.4 degrees improved iron bioavailability over the unheated samples while isolated soybean protein A was unaffected by this treatment. Iron added to the diets containing isolated soybean protein had bioavailabilities similar to that of iron present in the soybean which supports the common dietary iron pool hypothesis. The high iron content (0.18 mg/g protein) coupled with the bioavailability data make the isolated soybean proteins a good dietary iron source.


Examination of the structure of an unknown green fluorescent compound, compound G2, accumulated in non-growing cells of Eremothecium ashbyii by the addition of dimeric diacetyl. The addition of dimeric diacetyl to Eremothecium ashbyii caused simultaneous accumulation of two green fluorescent compounds with the inhibition of riboflavin formation in non-growing cells. One compound, referred to as Compound G1, was identified as 6, 7-dimethyl-8-ribityllumazine as reported previously and the other is referred to as Compound G2. The latter compound was considered to be 6-methyl-7-(2-hydroxy-2-methyl-3-oxobutyl)-8-ribityllumazine because a violet fluorescent compound, 6-methyl-7-hydroxy-8-ribityllumazine was derived from Compound G2 in the presence of p-quinone and because the known action mechanism of dimeric diacetyl as a trapping agent of possible intermediates in the biosynthetic pathway. The results indicate that an immediate intermediate to 6, 7-dimethyl-8-ribityllumazine in the biosynthetic pathway of riboflavin is 4-ribitylamino-5-amino-2, 6-dihydroxypyrimidine, whose pyrimidine portion is derived by the elimination of a dimeric diacetyl fragment from the molecule of the isolated lumazine.


Two species of Entamoeba from white-tailed deer, Odocoileus virginianus, from Georgia. Large numbers of 2 species of Entamoeba, Entamoeba coli and Entamoeba bovis, were recovered from captive white-tailed deer from Georgia. The trophozoite of the first ameba was a large form with a well-defined vesicular nucleus bearing a prominent eccentric endosome, abundant peripheral chromatin, and numerous periendosomal granules. Cytoplasmic vacuoles containing bacteria and other substances were common. Mature cysts were octonucleate. Glycogen vacuoles and irregularly shaped chromatoids were frequently present. This ameba was identified as Entamoeba coli. The trophozoite of the second ameba was small, with a typical Entamoeba nucleus. Cysts were uninucleate, containing numerous chromatoids resembling bars, splinters of wood, and irregular masses. There was occasionally a glycogen vacuole. This ameba was identified as Entamoeba bovis.


The failure to separate human X-and Y-spermatozoa by the millipore filtration technique. Millipore filtration of motile human spermatozoa with the use of a pore size of 5 micrometer without applying high or low pressure results in a small but statistically significant increase of Y-spermatozoa in the filtrate. Immobilized spermatozoa do not pass through the membrane.


Hemolytic anemia and thrombocytopenic purpura: two related subsets of systemic lupus erythematosus. Systemic lupus erythematosus patients who develop hemolytic anemia or thrombocytopenic purpura differ from other lupus patients and are similar enough to be considered two related subsets with a more benign course. Thirty-one lupus patients with either or both these hemocytopenias were found to be significantly younger, more often males, and had less frequent fever, polyarthritis, serositis, cutaneous vasculitis, nephropathy, neurologic manifestations, and persistent hypocomplementemia than 62 lupus patients without any of these hemocytopenias. They also had lower index scores of overall disease severity and required less treatment. It seems important to subdivide lupus patients in subsets for therapeutic and prognostic purposes.


Preparation and biological actions of some symmetrically N,N-disubstituted dopamines. The title compounds have been synthesized and evaluated for emetic effects in the dog, actions on the cardioaccelerator nerve in the cat, pecking in pigeons, and for behavioral effects following both peripheral and direct intracerebral injection into the nucleus accumbens and caudate-putamen of the rat. Generally, in the series studied, the N,N-diethyl and N,N-di-n-propyl congeners of dopamine displayed notably high degrees of activity. However, the test compounds exerted differing effects on peripheral and central dopamine receptors and in the area postrema. Differentiations of the activities of the different homologues within the brain were also shown.


Imidazo[4,5-f]quinolines. 4. Synthesis and anthelmintic activity of a series of imidazo[4,5-f]quinolin-9-ols. A series of 2-arylimidazo[4,5-f]quinolin-9-ols has been prepared by a multistep procedure from various 5-aminobenzimidazoles. These compounds possess a significant degree of anthelmintic activity against the mouse tapeworm Hymenolepis nana. The most active compound is the 2-(2-furyl) analogue. Additional anthelmintic testing is reported for this compound.


Synthesis and antitumor properties of some isoindolylalkylphosphonium salts. Antitumor evaluation of 2-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)ethyltriphenylphosphonium bromide (1) revealed significant activity in P-388 lymphocytic leukemia (T/C = 160%). As a follow-up to this chemical lead, a series of closely related phosphonium salts was prepared in which the 1,3-dihydro-1,3-dioxo-2H-isoindole ring system was maintained or in which it was replaced by other moieties such as maleimido, bromo, methoxy, and isoindoline. Syntheses generally involved treatment of the appropriate N-(bromoalkyl)phthalimide with the required phosphine or condensation of the K salt of the substituted imide with beta-(bromoethyl)triphenylphosphonium bromide (12). From the biological data obtained for these compounds, several requirements can be defined for substantial antileukemic activity. Of utmost importance is the presence of a triarylphosphonium halide moiety, coupled to an alkyl chain of two or three carbon atoms. The preferred terminus of the alkyl chain is the 1,3-dihydro-1,3-dioxo-2H-isoindole ring system, although the observed activity of beta-(bromoethyl)-triphenylphosphonium bromide (12) (T/C = 127%) would suggest that a superior carrier molecule could be developed.


Lack of erythroid characteristics in Ia-positive leukemia cell lines induced by Friend murine leukemia virus: brief communication. A group of mouse leukemia cell lines induced by the Friend murine leukemia virus (F-MuLV) was examined for a cell membrane antigens (regulated by the I-region of the H-2 complex), as well as for erythroid characteristics. Erythroid traits tested were hemoglobin synthesis, incorporation of 59Fe into heme, and presence of globin mRNA. Of 19 lines, 13 were positive for erythroid characteristics. All of these 13 lines were a-negative. Of 19 lines, 6 were negative for erythroid characteristics, and 5 of the 6 were a-positive. The data suggested that F-MuLV-induced leukemogenesis may operate in more than 1 cell type. In addition to the primitive erythroid type of cell usually involved in leukemia induced by F-MuLV, nonerythroid Ia-positive cells may also be transformed. The exact origin of the Ia-positive leukemia cells is unknown.


Chronic idiopathic thrombocytopenic purpura. A familial immunodeficiency syndrome? We studied three children with chronic idiopathic thrombocytopenic purpura (ITP) and their immediate families. All three patients and 10/13 family members manifested at least one immunologic defect, eg, decreased numbers of T lymphocytes (1/3, 5/13), diminished in vitro response to phytohemagglutinin (2/3, 6/13), dysgammaglobulinemia (2/3, 4/13), altered autoantibodies (1/3, 5/13), and decreased serum properdin levels (3/3, 2/13). In addition, one parent and two asymptomatic siblings of two of the propositi had shortened platelet life spans with normal platelet counts. The HLA antigens A3 and B7 were identified in all three families. There also appeared to be an association between a familial haplotype and the immunologic defects. Chronic ITP appears to occur in families with underlying immunologic defects, which are genetically related.


Clinical study on the acoustic phenomena in coronary venous system with intracardiac phonocardiography. In order to study the intracardiac murmurs in coronary venous system, right heart catheterization was carried out on 35 patients with or without mitral regurgitation. The double-lumen phonocatheter of A. E. L. was used for 33 cases but for 2 the microtip phonocatheter of Millar was employed. As a rule, simultaneous recording of intracardiac and external phonocardiograms was made with the pressure tracing in the majority of cases. The examined subjects were divided into 3 groups; 9 cases with mitral regurgitation confirmed by left ventriculography (Group I), 20 without mitral regurgitation (Group II), and 6 with functional systolic murmur (Group III). In Group I, a loud systolic murmur was recorded in 7 cases (MR 5, MR + AR 1, ECD 1), but in none of IHSS in the coronary sinus or great coronary vein. In Group II, no systolic bruit was noted in VSD and other lesions except ASR in the coronary venous system. The same was true in patients with functional systolic murmur (Group III). Intracardiac phonocardiography is thought to be useful to record mitral regurgitant murmurs in the coronary venous system, since the latter is in the close proximity to the mitral posterior commissure or mitral annulus.


[Treatment of a case of coloboma-like papillar excavation and maculopathy with photo-coagulation (author's transl)]. A study is presented of a case of serous detachment of the mucula secondary to congenital pit of the optic disc. We observed during fluorescein angiography a late leakage of dye at the temporal margin of the disc. A lasercoagulation of this lesion gave a favourable result. All these findings support Gass' explanation implicating a mechanical defect in the region of the pit that permits spinal fluid to seep beneath the retina.


Establishment of an albino sand rat (Psammomys obesus colony and comparison with the natural coloured animal. The lifespan and fertility of albino sand rats were found to be severely reduced in comparison with a laboratory colony of brown sand rats. The albinos were also much more susceptible to diabetes, as judged by their glucose tolerance. In fact, untreated albinos had a higher incidence of diabetic response than coloured sand rats fed a diabetogenic diet. The albino sand rats reproduced poorly because of a reduction in male fertility. Circulating testosterone levels and seminal vesicle weights were reduced in the albinos. It is speculated that the reduction in reproductive capacity is related to diabetes.


Prolongation of G1 and S phase in C-6 glioma cells treated with maple syrup urine disease metabolits. Morphologic and cell cycle studies. Metabolites accumulating in maple syrup urine disease, a disease attributable to an inborn error in the catabolism of branched-chain amino acids, were administered to rat C-6 glioma cells maintained in monolayer culture in order to study the morphologic and cell kinetic changes caused by these metabolites. Computer analysis of fraction-labeled mitoses in combination with flow microfluorometric analysis was used to analyze the effects of these metabolites on the cell cycle. The maple syrup urine disease metabolites, i.e., L-leucine, L-isoleucine, and L-valine and their corresponding ketoacids caused a prolongation of the G1 and S phases, when administered in combination at concentrations corresponding to approximately the highest recorded plasma levels in patients with the disease (1 x level). This effect was not reversible. Ketoleucine (alpha-ketoisocarproic acid or AKICA) alone, the compound that accumulates in maple syrup urine disease and that has previously been shown to be the most important metabolite associated with it, caused marked prolongation of the G1 and, to a lesser extent, the S phase at concentrations of 200 mg. per 100 ml. Return of the AKICA-treated growth-arrested cells to a standard medium caused complete reversal of grwoth inhibition. Consistent fine structural changes were found in cells treated with AKICA at concentrations of 300 mg. per 100 ml. or with the combined maple syrup urine disease metabolites at a 2 x level. These included marked cell process elongation and the appearance of numerous bundles of cytoplasmic filaments.


Leukocyte recruitment to airways by aldehyde-carbon combinations that mimic cigarette smoke. Exposure of Syrian golden hamsters to formaldehyde (3 to 250 p.p.m.) evaporated onto carbon (21 to 805 mg. per cu. m.) recruited polymorphonuclear (PMN) leukocytes to the epithelium of tracheas and intrapulmonary airways which peaked at 24 to 48 hours. Acrolein (less than 6 p.p.m.) on carbon (593 mg. per cu. m.) caused PMN recruitment which was maximal at 12 hours. The vapor phase of cigarette smoke produced PMN leukocyte recruitment of the same magnitude and with the same time course. In contrast, exposure to formaldehyde at doses of 2 to 250 p.p.m. and acrolein at 6 p.p.m. was cytotoxic to airway cells and caused prompt and delayed exfoliation but no recruitment of PMN leukocytes. There was no difference in cytotoxicity when carbon was present. Leukocyte recruitment occurred only when carbon was present, either given simultaneously wiht aldehydes or with adsorbed aldehydes. Thus, aldehyde vapor simulates the cytotoxic effects of particle-free cigarette smoke vapor. Of greater significance is the finding that an aldehyde, formaldehyde or acrolein, inhaled adsorbed on carbon or simultaneously with carbon to hamster airways is chemotactic for PMN leukocytes just as is the vapor phase of cigarette smoke when given simultaneously with carbon particles.


Pancreatic acinar cell changes induced by caerulein, vinblastine, deuterium oxide, and cytochalasin B in vitro. The effects of caerulein, vinblastine (VB), deuterium oxide (D2O), and cytochalasin B upon both the structure and the function of the pancreatic acinar cell were studied in vitro using rat pancreatic fragments. Caerulein (10 ng. per ml.) stimulates the release of enzymes and induces the appearance of numerous exocytotic images at the apical part of the acinar cell. Whereas VB (5.10(-5) M) and D2O (55 per cent) inhibit the secretory response to caerulein, they do not affect the general ultrastructure of the acinar cell. Prolonged incubation in the presence of VB provoked the disappearance of microtubles and the massive precipiation of microcrystalline material in all parts of the cytoplasmic space. Numerous microtubules were found in the acinar cell after exposure to D2O. Although VB and D2O do not alter the microfilamentous network localized at the apical part of the cell, cytochalasin B (2.10(-5) M) disrupts it. This drug decreases the number of microvilli projecting into the enlarged acinar lumen. Whether cytochalasin B is used alone or in association with VB or D2O, it inhibits the secretory response to caerulein and prevents the process of exocytosis. Thus, it is suggested that microfilaments act on a later step of the secretory cycle, i.e., exocytosis, than microtubules. The probable site of action of these latter organelles in the migration of zymogen granules toward the acinar lumen is discussed.


Involvement of membrane sulfhydryls in the activation and maintenance of nutrient transport in chick embryo fibroblasts. At 5 microgram/ml, insulin stimulates hexose, A-system amino acid, and nucleoside transport by serum-starved chick embryo fibroblasts (CEF). This stimulation, although variable, is comparable to that induced by 4% serum. The sulfhydryl oxidants diamide (1-20 micrometer). hydrogen peroxide (500 micrometer), and methylene blue (50 micrometer) mimic the effect of insulin in CEF. PCMB-S,1 a sulfhydryl-reacting compound which penetrates the membrane slowly, has a complex effect on nutrient transport in serum- and glucose-starved CEF. Hexose uptake is inhibited by 0.1-1 mM PCMB-S in a time- and concentration-dependent manner, whereas A-system amino acid transport is inhibited maximally within 10 min of incubation and approaches control rates after 60 min. A differential sensitivity of CEF transport systems is also seen in cells exposed to membrane-impermeant glutathione-maleimide I, designated GS-Mal. At 2 mM GS-Mal reduces the rate of hexose uptake 80-100% in serum- and glucose-starved CEF; in contrast A-system amino acid uptake is unaffected. D-glucose, but not -L-glucose or cytochalasin B, protects against GS-Mal inhibition. These results are consistent with the hypothesis that sulfhydryl groups are involved in nutrient transport and that those sulfhydryls associated with the hexose transport system and essential for its function are located near the exofacial surface of the membrane in CEF.


Hemodynamic and clinical evaluation of the Hancock xenograft bioprosthesis of aortic valve replacement (with emphasis on management of the small aortic root). One hundred twenty-nine consecutive patients underwent isolated aortic valve replacement with the Hancock porcine xenograft between July, 1974, and December, 1976. The hospital mortality rate was 3.9 percent. No patient was treated with anticoagulants, and valve-related complications were extremely rare. The smaller prosthetic sizes (19 and 21 mm. stent diameter) should be used with extreme caution, and the 19 mm. prosthesis should probably never be used in the audult patient. Two methods of managing the small aortic root are emphasized: one to avoid using the smaller prosthetic size in adults and the other to alter greatly the root size in children who have a hypoplastic aortic annulus. Acceptable calculated orifice sizes and left ventricular--aortic (LV-Ao) pressure gradients may be obtained with the 23 mm. or larger prostheses. Actuarial survival curves show 92 percent of patients alive and well at 24 months' follow-up.


Middle ear effusions in neonates.

Middle ear effusions in neonates. Suppurative middle ear effusions (MEE) have been shown to occur commonly in neonates. In spite of this, otoscopy is not routinely performed on septic infants in the neonatal intensive care unit (ICU). This is clinically significant since unrecognized suppurative MEE may act as a focus for dissemination of bacteria into the circulation and/or central nervous system (CNS). We have completed a prospective study in an attempt to define the prevalence, bacteriology, and response to therapy of MEE in neonates. To facilitate this, the normal micro-otsocopic appearance of the newborn TM was established by systematically examining 50 normal infants under 24 hours old. MEE was present in 30% of 125 consecutively examined infants in the neonatal ICU. Bacteriologic data are drawn from tympanocentesis performed on 34 neonates. Nasotracheal intubation of longer than seven days is highly associated with suppurative MEE. Suppurative MEE in the neonatal ICU is often refactory to treatment and may require prolonged therapy and repeated tympanocentesis.


One hundred and eighty-seven cases of child abuse and neglect. The case histories of 187 abused and neglected children, admitted to the Royal Alexandra Hospital for Children over a three-year-period, were reviewed. Multiproblem families from the lower socioeconomic groups predominated, reflecting the hospital's geographic catchment area. Eight children died and 30 were made state wards. A high proportion of mothers described problems during the pregnancy, a difficult delivery and neonatal problems. The majority of parents in this study were married and had small families. First-born male infants of young isolated mothers were found to be at greatest risk of child abuse and neglect.


Heritability of UV-sensitivity and photo-reactivation ability in Drosophila embryos. In Drosophila the UV sensitivity at the zygote stage and PR ability of damage induced by UV irradiation at 290-380 nm are heritable characters. The heritability of those characters is matroclinal. Resistance to UV irradiation dominates over sensitivity, and high PR ability is dominant over low. These characters are not associated with the pleiotropic action of any of the genes in question.


Purification and properties of human serum dopamine-beta-hydroxylase. 1. Two different molecular forms of dopamine-beta-hydroxylase were isolated from human serum; a major component (Peak I enzyme) with a molecular weight of 368000 and with a higher specific activity and a minor component (Peak II enzyme) with a molecular weight of 188000 and with a lower specific activity. 2. Both forms require ascorbic acid for the activity, and are stimulated by fumarate. Addition of N-ethylmaleimide or copper also increased the activity. The optimal pH of both forms in the presence of 20mM tyramine as substrate is 5.0. 3. Km values toward tyramine of Peak I enzyme and Peak II enzyme were 1.67 mM and 14.2 mM respectively. 4. Both Peak I enzyme and Peak II enzyme are glycoprotein.


Three-dimensional structure of the lipovitellin-phosvitin complex from amphibian oocytes. Microcrystals of the lipoprotein-phosphoprotein complex which are found in the oocytes of Xenopus laevis were examined using electron microscopy. Analysis of Fourier transforms of the images of the (010) and (001) projections showed the space group to be P2(1)22(1). Ten projections were combined to produce a map of the complex having about 20 A resolution. The lipoprotein complex consists of two subunits related by a local twofold symmetry axis. The density was averaged around the local symmetry and reasonably well defined structural domains can be seen in the resulting model.