HLA antigens and hereditary hemorrhagic telangiectasia. HLA antigens (27 HLA alleles of the A and B loci) were determined in 20 subjects of the same family, covering three generations; 6 of them were suffering from hereditary hemorrhagic telangiectasia. The haplotype HLA A2, Bw17 was found in all the sufferers. The same haplotype was not found in clinically health members except two of the generation III, but a visceral angiomatosis without clinical evidence cannot be excluded. An association of hereditary hemorrhagic telangiectasia with the haplotype HLA A2, Bw17 can be suspected in this family.


HLA antigens and erythrocyte glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in Sardinia. The frequency of 17 HLA antigens from locus A and locus B has been evaluated by microlymphocytotoxicity test in a population of 233 subjects (157 normal and 76 with deficiency of glucose-6-phosphate dehydrogenase [G-6PD]in red cells) from a village of Sardinia, a mediterranean island relatively close to continental Italy. It appears that G-6-PD-deficient people show a frequency of some HLA antigens (A2, A10, B12, BW35) significatively different from normal Sardinian subjects but close to (A10, BW35) or higher (A2, B12) than that of subjects from peninsular Italy.


A new allergen from the perienteric fluid of Ascaris suum with respect to charges. A NEW ALLERGEN WITH PI in the 6.0 region was obtained from the perienteric fluid of Ascaris suum through isoelectric focusing techniques. This new allergen shows strong allergenicity, at a concentration of 10(-9) microgram/ml, in rats passively sensitized with the reaginic antiserum produced against Ascaris perienteric fluid.


Effect of phenytoin on the immune response in rabbits. Rabbits treated with phenytoin in various ways, were immunized with human serum or with sheep erythrocytes. The antibody response in rabbits injected with the antigen mixed with phenytoin differed distinctly from the response obtained in animals having received the antigen alone or mixed with diluent. The effect of phenytoin on the antibody response depended on the nature of the antigen. The response to some antigens was suppressed, to some potentiated, and to some potentiated in the early phase and then suppressed. The effect comprised both IgM and IgG responses. Skin hypersensitivity tests did not reveal any effect on the cellular immune response. These findings may explain why particularly IgA is affected in patients taking phenytoin by the oral route, and why either reduction or elevation of IgA may occur.


Relationship between mitogenic factor and in vitro lymphocyte stimulation during guinea pig immune response to KLH. Lymphocyte stimulation and production of the lymphokine mitogenic factor (MF) in response to specific in vitro challenge were studied in parallel using lymphocytes from animals sensitized with different doses of keyhole limpet haemocyanin at various times after sensitization. Overall, agreement between the two assays of cellular response was good. However, examination of the antigen dose-response characteristics in each experimental situation revealed dissociation in some cultures. Blood leucocyte responses developed later than those of lymph node cells. The latter gave good MF but were poorly stimulated at day 60, when both responses were maximal for blood leucocytes, indicating a possible redistribution of responsive cells from the nodes to the blood. Treatment of guinea pigs with cyclophosphamide affected lymphocyte stimulation to a greater extent than MF production. Only a part of the antigen-induced stimulation of lymph node cells could be attributed to MF elicited in culture.


Norepinephrine uptake in guinea pig lung. Effects of anaphylaxis, phenoxybenzamine and cocaine. Lungs from control and sensitized guinea pigs were perfused via the pulmonary artery with Tyrode's solution. Infusion of equimolar concentrations (3x10(-9) to 3x10(-6 M) of 3H-1-norepinephrine (NE) and 14C-urea was started 1 min after injection of 1 ml 0.9% NaCl or 50 mg ovalbumin in 1 ml 0.9% NaCl and continued for 15 min. Anaphylactic lungs retained more urea, NE, and NE metabolites than control lungs at all NE concentrations and the proportion of unchanged NE was higher. Phenoxybenzamine decreased the 3H/14C ratio due to decreased 3H accumulation. Cocaine affected predominantly the control lungs. The results indicate that anaphylaxis increased the net uptake of NE in the lung and decreased the metabolism of retained NE.


Platelet migration inhibition test for platelet antibodies. Parameters and simplified methodology. A simplified methodology and parameters associated with the performance of a platelet migration inhibition test for the detection of antiplatelet-associated antibodies is described.


Mast cell numbers and passive cutaneous anaphylaxis in irradiated mice. IgE antibody levels in irradiated mice immunized with primed spleen cells are significantly higher than those measured in actively immunized intact mice. The possible role of mast cells in this elevated IgE response was assessed by the enumeration of mast cells and by determining their capacity to give rise to passive cutaneous anaphylactic (PCA) reactions in the skin of irradiated mice. The number of mast cells was found to be not significantly depleted over a period of 11 days by the irradiation doses used. Furthermore, the capacity of these mast cells to give PCA reactions was unimpaired. Radiation effects on mast cells in adoptively immunized mice therefore do not contribute to the high IgE levels observed in such animals.


Effect of aluminium hydroxide gel on the secondary response in mice. The necessity of using A1(OH)3 gel as an adjuvant in the IgE secondary response to a low dose of ovalbumin in mice was studied. Our results demonstrated that a good secondary response can be obtained independent of the presence of A1(OH)3 gel.


Assessment of the older person in the community. The Cross-National Geriatric Community study is being conducted by the United States-United Kingdom Cross-National Project. Semi-structured interviews have been completed with over 850 community residents over the age of sixty-five years randomly selected from the metropolitan regions of New York and London. The assessment techniques described in this section may be of interest not only to other research workers conducting geriatric community surveys but also to health professionals concerned with the clinical examination of the older ambulatory patient and the early detection and appropriate referral of the need for health and social services.


Loss of specific natural cell-mediated cytotoxicity with absorption of natural antibodies from serum. When effector cells from most individuals are tested directly against a number of target cells for cell-mediated cytotoxicity, most of the reactivity is non-selective. This apparent non-selectiveness is a result of specific activity against multiple antigens on target cells by each effector suspension. The specific reactions can be demonstrated through competitive inhibition of natural cell-mediated cytotoxicity. The specific inhibition of cytotoxicity by competitor cells directed our attention toward the determination of specificity to the effector cell surface. Natural cell-mediated cytotoxicity was decreased when effector cells were treated with proteolytic enzymes or low pH and regained when these cells were incubated in serum, suggesting an antibody on cell surfaces of the effector cell. Reconstitution of trypsinized effector cells with absorbed serum resulted in selective loss of cytotoxicity against the absorbing cell. To determine the role of the effector cell and the role of antibodies in natural cell-mediated cytotoxicity, effector cells from two different persons were reconstituted in the same absorbed sera. The selective pattern achieved was similar. When effector cells from the same individual were reconstituted with two different sera absorbed in the same way, the selective pattern achieved showed greater differences. We concluded that natural antibodies loosely attached to effector cells provided the specificity of natural cell-mediated cytotoxicity.


Assessment of mental health and social problems during multiple friendly visits: the development and evaluation of a friendly visiting program for the isolated elderly. The Friendly Visitor Program was designed to reduce social isolation. Visits were made by a pair of trained visitors to twenty-three isolated, elderly New York City residents. Pre- and post-testing visits to experimental and control Ss collected data on measures of isolation, adjustment, cognitive impairment and mental state. The major procedure was an hour long structured visit every two weeks for six months and a six month follow-up. For the experimental group only apartment upkeep and mental state improved and isolation diminished at the time of follow-up, indicating friendly visiting probably was therapeutic.


Evaluation study of the exploratory visit: an innovative outreach activity of the ILGWU's friendly visiting program. The exploratory visit to recent retirees, an outreach component of the International Ladies Garment Workers Union Friendly Visiting Program, was evaluated during a ten month period beginning in September 1973. An operations analysis found that need identifying activities of Friendly Vistors by type of service need. A post-test only control group effect study revealed exploratory visits were effective in establishing a link between the program and the retiree although they had no significant impact on the retirees' service needs.


K cell mediated lysis of cultured colon carcinoma and urinary bladder carcinoma cells induced by monospecific antisera against carcinoembryonic antigen (CEA) and two CEA-related normal glycoproteins. Antibody dependent lymphocyte (K cell) mediated lysis of tumor cells in vitro was used to assay for cell surface associated carcinoembryonic antigen (CEA) and two CEA-related normal tissue components, "normal glycoprotein" (NGP) and biliary glycoprotein I (BGP I). Three tumor cell lines were used as target cells. These were HT-29, colon carcinoma, T-24, urinary bladder transitional cell carcinoma and Mel-1, malignant melanoma. To induce lysis we used the IgG-fraction of specific rabbit and monkey anti-CEA sera and of specific rabbit anti-NGP and anti-BGP I sera, respectively. Purified human lymphocytes were used as effector cells. HT-29 was efficiently killed by low concentrations of rabbit anti-CEA and less efficiently by monkey anti-CEA. T-24 and Mel-1 were not lysed by anti-CEA, HT-29 and T-24 were lysed by low concentrations of anti-BGP I. In contrast only HT-29 was lysed by anti-NGP. Only a fraction of the tumor cells was killed by the different antisera although kinetic studies showed that the lytic reaction was complete well before the end of the eighteen hour incubation period used in the assay. Anti-CEA and anti-BGP I gave 30-40% corrected lysis of HT-29. With anti-NGP the corresponding figure was 10-20%.


Familial leukemia and inherited chromosomal aberration. This communication contributes a family with 12 cases of cancer and two cases of leukemia. Chromosomal analysis was performed on three occasions, 9 months apart. In unaffected first-degree relatives, we have demonstrated high frequency of tetraradial figures: in parents, 1:243 mitoses, and in all first degree relatives, 1:328 mitoses. The rate of chromosomal breakage was moderately elevated in comparison with carefully matched controls, mainly in father (6.17), mother (4.01) and one sister (4.07). G-banded and C-banded karyotypes revealed no structural chromosomal abnormality in relatives of leukemic children. This family is one of five leukemic families investigated. Analogous methods of chromosomal analysis have been employed in all, but chromatid exchange figures and elevated chromosomal breakage were detected only in the presently reported pedigree. It has been postulated that in this family there exists a possible relation between increased incidence of chromatid exchange figures and increased tendency to leukemia.


The human element in survey research.

The human element in survey research. This paper addresses itself to issues related to data collection in survey research with a community population. Areas discussed related to practical human problems in conducting a community survey of a stratified random sample of people sixty-five years of age and over in New York City. Some of these problems occur in most large scale community surveys, but some are a result of special features of this particular study. Topics covered include difficulties encountered in obtaining interviews, maintaining the staff, and coordinating the research team in the ongoing U.S.-U.K. Cross-National Project.


Competition for cytotoxic immune capacity against a 'syngeneic' mouse tumour distributed at two sites. Normal C3H mice will develop fatal ascites after the intraperitoneal injection of as few as 100 BP8 cells. However, mice can be immunized so that they can specifically reject an intraperitoneal challenge of 10(7) of these C3H-derived tumour cells. This paper investigates a phenomenon in which the capacity of immunized mice to reject an intraperitoneal challenge of tumour cells is lost between two to seven days after tumour cells have been given subcutaneously. Investigation of this temporary loss of capacity to reject the intraperitoneal challenge of tumour suggests that this might be due to the attraction of cytotoxic immunity to the site of subcutaneous injection. The possibility that this phenomenon is due to blocking factors, tumour overload, suppressor cells or enhancing antibody has been investigated but experimental results are given which do not favour these explanations.


[Estrogen and progestogen cytosol receptors in human breast carcinoma (author's transl)]. The authors have studied Estrogen (RE) and Progestin (RP) cytosol receptors in 379 human breast carcinomas: 281 tumors suitable for surgery, 26 pseudo-inflammatory tumors, 52 metastases and 20 recurrences. They have used an exchange technique with estradiol for RE and a synthetic compound, R 5020, for RP. The results point out that high rates of RE correlate with post-menopausal women and high rates of RP with pre-menopausal women. Tumours are considered receptor-positive when the binding sites concentration exceeds 100 fmoles/g tissue. Using this as a base 32% of the tumors are RE and RP negative. Considering only the positive tumors, 54% contain both receptors, 31% only RE and 15% only RP. The percentages are also given in terms of the hormonal state of the patients. The results are discussed in terms of McGuire's hypothesis that both receptors are necessary to obtain a positive response to hormonal therapy. Correlation between histology and receptors is also discussed.


Transformation of normal hamster cells by benzo(a)pyrene diol-epoxide. The frequency of cell transformation was determined after treatment of normal hamster embryo cells with benzo(a)pyrene (BP) and six of its metabolites. These metabolites included the trans 4,5-, 7,8- and 9,10-dihydrodiols; the 4,5-epoxide; and two stereoisomers of the non-K-region diol epoxides r-7, t-8-dihydroxy t-9, 10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene (diol-epoxide 1) and r-7, t-8, dihydroxy c-9, 10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene (diol-epoxide 11). The trans 7,8-dihydrodiol was more active than the other two dihydrodiols tested and was also more active than the parent hydrocrabon BP. Of the three epoxides tested, the diol-epoxide 1 was more active than the 4,5-epoxide and diol-epoxide 11. The results suggest that diol-epoxide 1 is a major cell-transforming metabolite of BP.


The metabolic activation of 7-methylbenz(a)anthracene: the induction of malignant transformation and mutation in mammalian cells by non-K-region dihydrodiols. Four different dihydrodiols derived from 7-methylbenz(a)anthracene have been tested, together with the parent hydrocarbon, for their ability to induce the in vitro malignant transformation of mouse M2 fibroblasts and mutations in V79 Chinese hamster cells. In the transformation tests withe the non-K-region dihydrodiols, the 3,4-diol was the most active dihydrodiol tested and the 8,9-diol was also more active than 7-methylbenz(a)anthracene itself; the 1,2-diol showed only slight activity. The K-region dihydrodiol, the 5,6-diol, which cannot be directly metabolized to a vicinal diol-epoxide, was inactive. These differences in biological activity were similar to those apparent in the results from the mutagenicity tests. The data support the general hypothesis that non-I-region dihydrodiols, which can be metabolized to vicinal diol-epoxides, are important in the metabolic activation of the carcinogenic polycyclic hydrocarbons and, when taken together with other results, indicate that 3,4-dihydro-3,4-dihydroxy-7-methylbenz(a)anthracene is most probably involved in the metabolic activation of 7-methylbenz(a)anthracene presumably following conversion into the related diol-epoxide, 3,4-dihydro-3,4-dihydroxy-7-methylbenz(a)anthracene 1,2,-oxide.


Drug sensitivity studies on clonal cell lines isolated from heteroploid tumour cell populations. I. Dose response of clones growing in monolayer cultures. Drug sensitivity of a heteroploid tumour cell line and three clones isolated from it was studied in tissue culture. Cells of the parent line P0, and of clone P1 were fibroblast-like and pseudo- and hypodiploid. Cones P3 and P4 consisted mostly of epithelial and round cells, respectively, and were hypotetraploid. In dose-response experiments, P1 and P4 clones were more sensitive to dianhydrodulcitol than tp0 or P3 clones. Adriamycin was more toxic to P3 than to the other three cell lines. P3 and P4 clones were more sensitive to vincristine than P0 or P1 clones. N-formyl-leurosine, a new derivative of the Vinca alkaloids, was least toxic to P4 cells, and the other three cell lines were equally sensitive. It was concluded that relative sensitivity of the clones depended on the particular drug. Presence of clones of lower sensitivity in heteroploid cell populations may have some bearing on regrowth of tumours after chemotherapy.


The Comprehensive assessment and Referral Evaluation (CARE)--rationale, development and reliability. The Comprehensive Assessment and Referral Evaluation (CARE) is a new assessment technique which is intended to reliably elicit, record, grade and classify information on the health and social problems of the older person. The CARE is basically a semi-structured interview guide and an inventory of defined ratings. It is designated comprehensive because it covers psychiatric, medical, nutritional, economic and social problems rather than the interests of only one professional discipline. The style, scope and scoring of the CARE makes it suitable for use with both patients and non-patients, and a potentially useful aid in determining whether an elderly person should be referred, and to whom, for a health or social service. The CARE can also be employed in evaluating the effectiveness of that service if given.


Biological characterization of a tumour-growth-promoting factor from ascitic fluid of tumour-bearing mice. Tumour-growth-promoting activity has been observed in ascitic fluids of mice with progressively growing SV40- and chemically induced tumours. Administration of ascitic fluid to animals together with a normally non-tumorigenic dose of SV40- transformed tissue culture cells (TU-5) will cause these cells to grow progressively and eventually kill the animals. Also, the mKSA-specfic, immunologically non-responsive state (the eclipse phase) of mice bearing large mKSA tumours can be maintained by administration of ascitic fluid or serum from tumour-bearing animals after the tumours have been surgically removed. Normally, complete immunity to a secondary tumour cell challenge is re-established approximately 10 days after removal of the primary tumour, but daily injections of ascitic fluid or serum will maintain sclipse so that a secondary challenge of tumour cells will grow progressively. The active component apparently acts non-specifically, since ascitic fluid from an unrelated tumour also is able to maintain the mKSA-specific eclipse phase. Thascitic fluid has no apparent immunosuppressive activity in vivo.


A system for studying biorhythms in domestic sheep in confinement. A system is described for studying biorhythms in domestic sheep. One animal in each of four temperature and light controlled rooms can be studied in pens designed to permit continuous monitoring of eating, drinking, walking, resting, body temperature and cardiac rate. Automated data acquisition, including analog-to-digital conversion, is controlled with a minicomputer. Digitized data are recorded on magnetic and punched paper tape. Data processing on large scale computers includes editing, summarisation, machine plotting and time-series statistical analysis of the period, amplitude and phase of the biorhythms.


Vaginal temperature rhythms in sheep.

Vaginal temperature rhythms in sheep. Six ovariectomized adult sheep were tethered in a temperature--and light--controlled room and given feed and water ad lib. Vaginal temperatures were recorded at 10m intervals for 12 or 17d. Hourly means were calculated and subjected to statistical anlayses by time--series procedures. Initial analysis revealed a positive linear trend in most animals suggesting a low frequency rhythm with a period greater than the 17d experimental period. All subsequent analyses were, therefore, conducted on data adjusted for a linear trend. The periodogram, correlogram and spectral density analyses revealed a predominant circadian rhythm in 5 of the 6 animals. Ultradian rhythms, with periods of 12 and 8h, were also present in some animals. The magnitude of the rhythmic change in vaginal temperature, as estimated from the amplitude of the circadian component, varied from 0.05 degrees to 0.16 degrees C. Calculation of the external acrophase indicated that the daily maximum temperature occurred between 0851 and 1727.


Estimating a population in need of alcoholism services: a new approach. A new approach for estimating a population at risk of alcoholism and problem drinking is discussed. Its advantages include specification of planning-relevant social-demographic characteristics of a population at risk and the identification of a population base in terms of which alcoholism programs, services, and resources can be comparatively evaluated.


A survey of Thai student use of illicit drugs. In a survey of drug use by 1,506 Thai students, about one-fourth report having used illicit drugs and 6% report current use. Point prevalence of drug use in this population appears to be much lower than that reported by local news media. Prevalence and patterns of drug use among Thai and American students are remarkably similar. The authors conclude that easy availability of drugs of abuse does not necessarily lead to endemic or epidemic use. The isolation of high risk groups and study of cultural factors which may help to maintain low levels of drug use are suggested for future research.


Heroin addicts with a history of glue sniffing: a deviant group within a deviant group. Sociodemographic, drug-taking history and psychological test data were collected from 133 male heroin addicts in treatment programs. Those addicts who had ever sniffed glue (26.4%) were characterized by a unique orientation toward death. Not only were they significantly more likely to have attempted suicide, but also they more often fantasized about death both while on heroin and when clean, and they acknowledged less fear of the pain/deterioration involved in dying as measured by the Collett-Lester Scales. In addition, they had on the average abused more than twice as many different substances as addicts without a glue use history.


Patterns of alcohol and multiple drug use among rural white and American Indian adolescents. This study examined the attitudes and practices of sample of White (N=667) and American Indian (N=280) adolescents in regard to the use of alcohol and other drugs. The findings lend general support to the hypothesis of Whitehead et al. that users of any one drug will show increased probability to use another drug when compared to those not using that drug. Additionally, it was found that rural Indian youth are somewhat more likely than rural White youth to be involved with alcohol, marijuana, and hard drugs.


Small group dynamics and drug abuse in an Army setting: a case study. Drug abuse has been subjected to a myriad of empirical and theoretical explorations which have attempted to explicate its occurrence as a sociobehavioral phenomenon. The study of the organization of drug-related behavioral manifestations requires the investigation of variant psychosocial, situational, environmental, and structural variables. Small groups within the military establishment are relatively numerous and vitally important. A sense of comradeship exists within such groups and troop morale is frequently facilitated by their existence. The purpose of this paper is to present a descriptive case study of the role of the small group as a central organizing locus around which drug abuse in an army setting revolves. The data presented were collected from subpopulations identified in the course of an epidemiological study of drug and alcohol use at a military post. The paper describes the small group observed in terms of its functional relationships and interactive dynamics. The case study data are presented relative to role differentiation within the group, group norms, values, boundaries, identity, sanctions, and controls. These concepts are examined with a view toward assessing the manner in which drug abuse is initiated, maintained, and controlled via small group dynamics.


Prediction of treatment effectiveness in a drug-free therapeutic community. Treatment effectiveness for drug dependance is evaluated and compared with success rates reported in the literature. Program differences and varying follow-up procedures make assessment difficult. Identical pre- and posttreatment quantitative adjustment indices are recommended in order to improve the measurement of improvement. Education and length of stay in treatment are among the most important predictors of posttreatment drug usage and work akjustment. Education and improved treatment success with lower class youth are discussed.


Preliminary observations on an intervention program for heavy smokers. Each of 571 smokers selected one of three methods of smoking cessation: group therapy, individual counseling, and hypnosis. One-year results suggest little difference between the three methods in producing ex-smokers. All methods produced an average success rate of approximately 20%. It should be noted, however, that with all types of verbal or verbally related therapy it is not known precisely how these techniques work or whether  the outcomes are really a function of what is put into the therapy by the treatment agent and/or the recipient. It was generally found that younger, more educated smokers chose hypnosis; older, more educated smokers chose group therapy; and older, less-formally educated smokers chose individual counseling while the youngest and generally less educated smokers chose to become nonattenders and not take part in therapy. These results have important implications for designing optimal treatment programs which will be acceptable and effective for the greatest number of smokers.


Satiation and sensory deprivation combined in smoking therapy: some case studies and unexpected side-effects. Two promising techniques for smoking reduction, sensory deprivation and stimulus satiation, were applied in combination to five smokers. All were successful initially in achieving abstinence and four ultimately in maintaning abstinence. The issue of possible side-effects is worth considering. Quitting per se and both satiation and sensory deprivation may be stressful and as a result may potentially produce negative side effects. The observation of positive side-effects in these cases balances this possibility to some extent.


Psychological test and demographic variables associated with retention of narcotic addicts in treatment. The relationships of psychological and demographic variables to retention in treatment of narcotic addicts were examined. Age and race were not related to retention. The IQ's of subjects retained longer seemed to be higher but the relationship did not reach statistical significance with this sample size. Legal pressure was clearly associated with longer retention as were higher scores on the Suitable for Treatment Scale. Legal pressure seemed to exert its major influence early in treatment. Treatment center variables and patient variables probably interact to determine retention.


The usefulness and reliability of a drug severity scale. This paper reports on the interrater reliability of a previously developed method for measuring severity of multidrug use. This method is based on interviewer's ratings of the number of different drugs used, the frequency of use, and the length of use of each drug. The results show that relatively unsophisticated raters in comparison with trained and experienced raters are able to utilize the drug severity form with a minimum of error.


Measuring various drug use dimensions with a calendar method. This note presents a technique used to acquire a variety of time-specific data on drug use. The calendar technique involves self-reported patterns of consumption and any changes therein, including cessation. Advantages of this technique over other approaches are discussed, and examples of the variety of use measures that can be derived from the calendar method are  illustrated.


The consequences of osmotic diuresis in residual nephrons for urinary drug excretion. The renal clearance of chloramphenicol (calculated per 100 ml of inulin clearance) increased in linear relation to fractional sodium and water excretion. The renal excretion of chloramphenicol may be influenced by changes in fractional water excretion without changes in fractional sodium excretion. The low sodium diet did not significantly change chloramphenicol urinary excretion in patients with chronic renal insufficiency. The results obtained are compatible with the view that osmotic diuresis in residual nephrons, the development of which is in part accounted for by an adaptive decrease in tubular sodium reabsorption, affects urinary excretion of drugs, the tubular transport of which depends on fractional water reabsorption.


Validation of plasma and urinary canrenone for determination of bioavailability of spironolactone--comparison of tablets with solution/suspension. Data showing a linear relationship between spironolactone dose and the levels of canrenone in plasma and urine are presented to support the use of canrenone levels as a measure of the bioavailability of spironolactone. The bioavailability of a selected batch of spironolactone 25 mg tablets was compared to that of an oral aqueous suspension of spironolactone in a separate balanced cross-over study involving 10 healthy subjects. The tablets were equivalent to suspension as regards area under the plasma concentration-time curve and total urinary excretion of canrenone, the prinicipal unconjugated metabolite of spironolactone. Peak plasma concentrations of canrenone were higher, and were attained significantly earlier, after treatment with spironolactone in suspension. The results indicate that spironolactone was absorbed more rapidly from the suspension, but that the total absorption did not differ between the two formulations.


A survey of drug interaction.

A survey of drug interaction. A survey is presented of the interaction phenomena between two or more simultaneously used drugs. The well known mechanisms of drug interaction, like chemical incompatibility, displacement of protein binding, enzyme induction, etc., are summarized and illustrated by means of practically relevant examples. Attention is paid to the fact that drug interaction can sometimes be advantageous from the clinical point of view, although in many cases it is an unwanted phenomenon in practical pharmacotherapy. Furthermore, the predictability and detection of interaction phenomena are mentioned briefly, together with the possibilities of distributing appropriate information to physicians and pharmacists.


The significance of the simultaneous determination of carbamazepine and its 10,11-epoxide from plasma and human erythrocytes. The distribution of carbamazepine and its 10,11-epoxide derivative into human erythrocytes was studied in child and adult epileptics on long-term therapy. Firstly, it was found that carbamazepine penetrated into erythrocytes, where the mean concentration of the drug was in rational agreement with the unbound fraction in plasma. Secondly, the relationship between the percentage of carbamazepine concentration in red cell and the drug level in plasma resembled the relationship between the percentage of unbound carbamazepine and the drug level in plasma, which relation has been described in literature recently. This similarity favors this: by determining the ratio of carbamazepine in red cells to the drug in plasma, the unbound fraction can be deduced. Thirdly, carbamazepine-10,11-epoxide was not found in red cells.


Pharmacokinetics of papaverine in man.

Pharmacokinetics of papaverine in man. A retrospective pharmacokinetic analysis was done of papaverine plasma level data in man reported in the literature. Upon i.v. administration the plasma level vs time curve can best be described by an open two-compartment model, and upon p.o. administration by open-compartment model. The biological half-life of papaverine varies between 1.5 and 2.2 hours, and has a volume of distribution of approximately 15% of the body weight. Papaverine is practically completely metabolized and underlies the first-pass effect upon p.o. administration.


Eye color in skin cancer.

Eye color in skin cancer. In Spain, 2175 patients with skin disease were studied for eye color; 425 had skin cancer and 1750 had other skin conditions. Of the skin cancer patients, 359 had light-colored eyes (blue, green, gray or light brown). Of the others, 60% had dark-colored eyes (black or dark brown).


New uses for benzoyl peroxide: a broad-spectrum antimicrobial agent. Benzoyl peroxide is a useful agent in the treatment of acne, chronic ulcers, tinea pedis, and tinea versicolor, probably because of its antimicrobial power. 2.5% concentration is almost as active as 5%. Although potential irritancy and allergic reaction have not been a problem on the face, benzoyl peroxide should be used judiciously in chronically inflamed or ulcerated skin. Several potential uses are mentioned.


Nonsuture surgery for basal cell carcinoma: an alternative method. Eighty-seven basal cell carcinomas were treated by surgical excision. Sites of removal were allowed to heal by secondary intention. Advantages of this method include histologic monitoring of the adequacy of incision, a less formidable surgical procedure, and a cosmetically acceptable scar.


Maintaining spontaneous respiration in the postoperative phase of cardiac surgery. With the described technic we were able to eliminate the use of a ventilator with its attendant problems. No ventilator can adjust to the body's demand for ample ventilation as correctly as the body itselt. All anesthetic agents used are without depressant effect on the respiratory and cardiovascular systems. The most important result of this technic is that at the end of surgery the patient is quite awake and breathing normally. There is therefore no need for a ventilator in the postoperative phase. An illustrative case is presented.


Esophageal atresia with tracheoesophageal fistula. Our experience in treating ten full-term and six premature infants with esophageal atresia and distal tracheoesophageal fistula was reported. Fourteen cases were treated by a one-stage procedure and two cases by a two-stage procedure. One patient died due to pulmonary infection following the one-stage procedure and one died of septicemia after the two-stage procedure. Anastomotic stricture developed in four cases and was treated successfully by dilatation.


Rational use of operation in pericardial constriction. The most appropriate operation for constricting pericardial disease must be selected to provide optimum chance for permanent recovery of myocardial function with minimal morbidity. Our 18 patients demonstrate the changing cause of pericardial constrictive disease and the application of newer surgical treatments. Good results were obtained in 16 patients.


Pyloric origin of gastric and duodenal ulcers: surgical connotations. A new theory on cause and treatment of peptic diseases proposes that these disorders result from dysfunction of the pyloric muscle causing delay in gastric emptying of solids. It emphasizes the separate function of the duodenal sphincter and the gastric sphincter components of this muscle. Dysfunction of either results in delayed gastric emptying of solids. Peritoneal patch pyloroplasty (PPP) has been devised to correct delayed gastric emptying. Testing of gastric emptying by the barium burger meal is essential to proper diagnosis. One hundred consecutive patients who required surgery for peptic diseases during the past five years have undergone PPP, the first 20 with, and the next 80 without, vagotomy. Results included two deaths and 94 favorable results. Follow-up studies in these patients continue.


Legg-Calvé-Perthes disease in Nigerians. Ten new patients with Legg-Calvé-Perthes disease were seen in the University College Hospital, Ibadan, in ten years, out of a hospital pediatric population of 550,000, giving an incidence of 1:55,000. This result is consistent with previous reports that Legg-Calvé-Perthes disease is less common in Negroes than in Caucasians but Negroes are not immune.


Enchondroma of the hand.

Enchondroma of the hand. Thirty-three patients with enchondroma of the hand underwent operation for removal of the enchondroma and filling of the cavity with bone meal. Twenty-six patients had pathological fractures of the phalanges or metacarpals.


Parietal cell vagotomy and omentopexy as definitive surgery for perforated duodenal ulcer. We recommend a definitive procedure as initial management for acute perforated duodenal ulcer. In the two patients herein reported, the parietal cell vagotomy with omentopexy and without drainage was performed as a definitive procedure for perforated duodenal ulcer. No wound infection, dumping symptoms or diarrhea occurred in the early postoperative period. Gastrointestinal follow-up study in one patient showed normal passage. These early favorable results with minimal morbidity encourage us to broaden the indications for definitive operation for acute perforation.


Gait study in evaluation of results in intramedullary nailing for femoral shaft fractures. The present preliminary investigation conducted on six adult males whose femur shaft fractures had been fixed internally by means of Hansen-Street intermedullary nails indicated that our gait study technic helps confirm the clinical findings in such cases. Five patients, although their fractures had united and they had resumed their usual activities, were not deemed quite normal as yet and the causes for their gait abnormality were identified in the clinical examination. The gait study technic thus provided fairly accurate quantitative support of the clinical findings.


The surgical gallbladder.

The surgical gallbladder. A series of 412 personally performed cholecystectomies is analyzed and discussed. Surgical cases were divided into groups based on whether or not the gallbladder was visualized by cholecystography. A third group required immediate surgery without attempting radiologic investigation. We do not accept the diagnosis of dyskinesia which is a radiological finding as an indication for surgery and no such cases are included in the series. Quite a number of cases operated on for "chronic cholecystitis" were found at surgery to have other less common pathological lesions, as proved by later histologic examination of the excised gallbladders. Bilharzial gallbladder disease is discussed and the new terms bilharzial cholecystitis and bilharzioma of the gallbladder are suggested for the lesions described. We stress the need to explore, inspect and aspirate the common bile duct in every case of calculous cholecystitis as the only alternative to operative cholangiography. By so doing biliary fistulas were completely eliminated from the series.


Prophylactic lithium and personality variables. An international collaborative study. 61 patients - 28 suffering from bipolar, and 33 from unipolar psychotic affective disorders - completed two personality inventories, one before and one about 6 months after starting lithium treatment to prevent relapses. On the basis of empirical observations it had been assumed that personality characteristics would change more in bipolar than in unipolar patients and that these changes would concern mainly those personality characteristics which reflect sociability and impulsivity. The inventories used were the EPI and the MNT. The results were in agreement with the predictions. Moreover, a significant decrease in N-scores was found both in bipolar and unipolar patients. It is assumed that these changes reflect both the therapeutic effect of lithium and an effect upon the personality characteristics of patients who suffer from bipolar or unipolar affective disorders.


A controlled study of a dopa decarboxylase inhibitor (benserazide) in the treatment of schizophrenic patients. In a double-blind controlled study lasting 6 weeks, 32 schizophrenic patients were randomly assigned to one of two treatments: chlorpromazine or benserazide, a dopa decarboxylase inhibitor. Results on each measure were subject to multifactorial analysis of covariance. Benserazide did not appear to be as effective an antipsychotic medicaiton as chlorpromazine. In fact, chlorpromazine was significantly better on measures of tension, excitement, hallucinatory behavior, thinking disturbance, social interest, and drop-out rate. At the relatively low dosages used in this study, it would seem that benserazide had little effect on the cerebral dopa decarboxylase, and it would be worthwhile trying higher dosages.


Clinical study with bromperidol, a new butyrophenone derivative. 20 psychotic - predominantly schizophrenic - patients underwent treatment with the new butyrophenone derivative bromperidol for a period of 4 weeks; the drug was administered in the form of 1 mg tablets. The daily dose (initial dose: 1 mg; mean dose at the end of the trial: 4.47 mg) was always administered in one single dose. 19 patients finished the trial, and in 18 cases the therapeutic result was considered very good to good. These results were confirmed by statistical analysis. Nine patients exhibited mild to moderate extrapyramidal concomitant symptoms; no other side effects were observed. The results of detailed laboratory tests and evaluations of various quantitative and qualitative tolerability parameters were not indicative of toxic effects. The therapeutic value of this new substance will be demonstrated by a double-blind study.


[Psychopathometric methods for the testing of psychopharmaceuticals. Efficiency increase]. The rentability of tests of psychopharmacological drugs can essentially be influenced by psychopathometric procedures. Shortness and simplicity of the test decisively adds to the rentability and the validity of the examination. Procedures considering patients' demands, also demand a high amount of variation and robustness by which (1) the validity is increased and (2) the rentability is decreased. Investigations in time series make further economizing of tests possible, if - valid for reversible physically caused psychosis and cyclothymical depression - symptoms and syndromes will be changed in a rectifying manner. This is shown in a study with the antidepressant Mefexamid given to depressive patients. From these patients were taken one objective and three self-rating scales. In these cases each test on its own gave 84% of the information which it had given together with a second scale.


Open trial and double-blind clinical trial of the antidepressant Ro 8-1998 in comparison with imipramine. Based on the results of an open trial with Ro 8-1998 (chemic name: N,N-dimethyl-3-(1-methyl-5H-dibenzo(a,d)cycloheptene-5-ylidene)-propylamine N-oxide hydrochloride) in 11 endogenous depressed outpatients a double-blind trial with imipramine was proposed. Therapeutic efficacy and side effects of Ro 8-1998 and imipramine were compared in a double-blind trial with 30 patients who were newly hospitalized. Most of them suffered from endogenous depression. On days 0, 5, 10, 15 and 20 the patients were examined and the symptoms were documented with the AMP system, the Hamilton scale for depression, a behaviour rating and the "global depression rating Zurich". Ro 8-1998 caused a decrease of systolic blood pressure, an increase of heart frequency and urea. Twelve out of 15 patients showed a decrease of white blood cells. In four patients the number of white blood cells dropped below 4,000. Statistical analyses proved both substances to be potent antidepressants. The therapeutic efficacy of Ro 8-1998 was at least equal to that of imipramine. Further trials with bigger groups of patients are necessary to show whether the trend towards a better antidepressant efficacy of Ro 8-1998 can be reproduced.


Plasma renin activity during lithium treatment of patients. Plasma renin activity (PRA) was determined in patients given lithium treatment. In a longitudinal study PRA was determined in 9 patients before the start of lithium treatment and at intervals during 3 months of treatment. The activity was increased significantly above pretreatment values on day 8 of the treatment; thereafter it fell to pretreatment values. In a transversal study 18 patients given lithium treatment for 2-20 years were compared with 11 control persons. PRA did not differ significantly between the two groups. The results indicate that PRA rises transiently shortly after start of lithium treatment and thereafter falls to pretreatment values where it remains even under prolonged lithium administration.


The normal and abnormal human corneal epithelial surface: a scanning electron microscope study. The surface morphology of 108 corneal buttons obtained at keratoplasty showed specific patterns for each disease process. The surface over a traumatically scarred cornea was identical to that of undamaged sites, showing microvilli and microplicae in various numbers and combinations. Keratoconus specimens showed many dark cells, frequently noted to have surface blebs 0.25 to 3 micrometer in size over the entire cone in the nipple type, and in a broad basal band inside the cone or over the entire button in the sagging-cone type. Some blebs contained cytoplasm and 250 A glycogen-like granules. In larger, dark cells, holes were found in the blebs and the plasma membrane was degenerated. Corneal epithelial edema was manifested by a large irregular surface caused by the anterior bulge of edematous cells, many attached by only a small area, and variable-sized depressions, often the size of epithelial cells. More than a year after stromal scarring from herpetic keratitis, many epithelial cells lay loosely on the surface whereas other epithelial cells were edematous and partially detached from the surface cell sheet. Localized heaping of rounded epithelial and inflammatory cells persisted in some areas.


Pseudomonas eye infections in cyclophosphamide-treated mice. Swiss-Webster mice challenged intracorneally with varying doses of P. aeruginosa exhibit eye infection within 24 hr. as detected by corneal opacity. The infection remains localized and spontaneously heals within 4 to 6 weeks. However, when mice are pretreated with a single i.p. injection of cyclophosphamide 4 days prior to either intracorneal or anterior-chamber challenge with various bacterial cell suspensions (10(1) to 10(8)), 83% of the anterior chamber and 54% of the intracorneally challenged mice (most at higher dilutions of the bacteria) died of Pseudomonas septicemia within 48 hr. Corneal damage was histochemically and ultrastructurally observed in surviving animals by 24 to 48 hr. following challenge by either route.


Simplification of glutathione-bicarbonate-Ringer solution: its effect on corneal thickness. Glutathione and adenosine can safely be omitted from glutathione-bicarbonate-Ringer solution (GBR) which is used as an irrigating solution during vitrectomy, without significant reduction in the solution's efficacy or increase in corneal toxicity. Bicarbonate appears to be an essential ingredient and should not be omitted from the Ringer solution.


Acoustic microscopy of the human retina and pigment epithelium. An acoustic microscope uses sound waves rather than light to image a sample, and displays viscoelastic rather than optical properties. The Stanford instrument, operating at frequencies near 1,000 MHz, achieves resolution and magnification that is comparable to a light microscope. Using this instrument, we examined sections of normal human retina and pigment epithelium and found that characteristic degrees of acoustic attenuation or phase shift were produced by structures such as cell nuclei, rod and cone outer segments, Bruch's membrane, red blood cells, and ocular pigment. Resolution was better with thin than thick sections, and fixation did not significantly alter the acoustic properties of the tissues studied. A comparison of iris tissue from albino and pigmented rabbits showed that melanin was a particularly strong acoustic attenuator. Acoustic microscopy may provide a new and direct means of probing the physical structure of tissues and cells.


Double-membrane arrays in type II fibers of mouse extraocular muscle. Double-membrane arrays were observed in singly innervated type II fibers of the global region of mouse superior rectus. These arrays were selectively confined to the endplate region of such cells. Close associations and continuities between the cisternae of the arrays with those of the intermyofibrillar sarcoplasmic reticulum suggest derivation of the former from the latter. These proliferations of the cellular smooth membranes might be related to the specialized functional requirements of the innervation site.


Electro-oculography in infants.

Electro-oculography in infants. To record the electro-oculogram in infants without using general anesthesia and passive globe rotation, we used the static vestibular reflex in which compensatory eye movements occur in response to angular rotation of the semicircular canal. To produce these eye movements, we placed the infant in a supine position in his mother's arms in a rocking chair and, while he nursed from a bottle, directed his attention to a distracting stimulus. We recorded the electro-oculogram during rocking under conditions of light and dark adaptation. We used the electro-oculograms to calculate the conventional light-to-dark amplitude ratio.


Fusing human rod outer segments from an eye enucleated for choroidal melanoma. In the retina from an eye enucleated for choroidal melanoma apposed rod outer segments were seen by transmission electron microscopy to be fusing together in groups by the confluence of their plasma membranes and the formation of cytoplasmic bridges between adjacent outer segments. These fusions were seen in areas distant from the melanoma but where the retina was not normal in appearance.


Unfocused ultrasound for localized tissue destruction in rabbit kidneys. The rabbit kidney was subjected to exposure from an unfocused ultrasound source in an effort to create a relatively large volume of ultrasound-damaged tissue in the rabbit kidney. The results of this exposure were followed for 1 year. An insignificant change in blood pressure was noted up to 1 month after exposure to ultrasound and no persistent hypertension was noted thereafter. Marked gross, histologic, and vascular changes were found in the area of exposure culminating in marked absorption of renal substance (in excess of 25 per cent of total kidney weight). Calcific stones formed in the pelvis of the kidney in virtually all animals observed from 6 months to 1 year after ultrasound exposure. These stones appeared to be related to the calcification within the transitional epithelium of tubules at the junction of normal and ultrasound-damaged tissue. The marked ability of the absorptive processes to ablate large volumes of physically damaged tissue is demonstrated.


Castration effects on tumor specific immunity. Using two immunogenic methylcholanthrene-induced fibrosarcomas in CD2F1 male mice, initial observations suggested that the rate of tumor growth might be enhanced by castration. For confirmation, tumor transplantation experiments using more than 500 mice were carried out in order to compare tumor specific transplantation immunity in castrate and in control male mice. Inbred mice bearing a 3-methylcholanthrene-induced fibrosarcoma transplant underwent surgical excision of the tumor; and specific resistance to subsequent challenges using varying doses of that tumor cell line were compared in castrate and in noncastrate groups of mice. Although castration influenced the rate of tumor growth, castration had no apparent effect on tumor specific immunoresistance. Mechanisms of host-tumor immunorelationships are discussed.


Quantitation of urinary immunogloublins by a double antibody technique. A double antibody method for quantitation of urinary immunoglobulins that is sensitive enough to avoid the need for urine concentrations has been developed. The first antibody is goat antiserum monospecific for the heavy chains of IgA, IgG, and IgM. The second, and precipitating, antibody is developed in rabbits made tolerant to human IgG. Normal values for male and female children and adults are presented. Elevated levels of urinary IgA and IgG were found after urinary tract infection.


Dynamics of the continent ileal bladder. An experimental study in dogs. A continent ileal bladder was constructed in six dogs. The most important requirements for a continent ileal bladder as a reliable mechanism of continency and for prevention of back flow in the ureters could be achieved by two intussusception valves (nipples) of small bowel in opposite directions. The dynamics of these "nipple valves" were studied electromanometrically and radiologically. These experiments showed that these intussusception valves did not binder a free flow in the isoperistaltic direction and did prevent reflux in the antiperistaltic direction.


Excretion of 4-pyridoxic acid and oxalic acid in patients with urinary calculi. Urinary excretion of 4-pyridoxic acid and oxalic acid was investigated in 75 patients with urinary calculi and in 50 normal subjects on regular diet. Mean excretion of 4-pyridoxic acid was 0.85 and 0.90 mg per day, respectively, and mean excretion of oxalic acid was 27.5 and 28.0 mg per day, respectively. Statistically there was no difference between the two groups in 4-pyridoxic acid excretion or in oxalic acid excretion. There was a weak positive correlation between the urinary excretion of 4-pyridoxic acid and oxalic acid. Patients who were on ascorbic acid supplementation during the urine collection period excreted increased amounts of oxalic acid. It was concluded from this investigation that most patients with urinary calculi had 4-pyridoxic acid excretion and oxalic acid excretion within normal limits. Low 4-pyridoxic acid values were not combined with high excretion values of oxalic acid, and the nutritional state of vitamin B6 in patients with urinary calculi was assumed to be satisfactory in order to control the endogenous oxalic acid production. The significance of high excretion values of 4-pyridoxic acid and oxalic acid is discussed.


Spectrophotometry of the canine bladder. Canine bladders were subjected to spectrophotometric analysis in order to choose a laser for experimental endoscopic use. Percentages of transmission and reflection were obtained; these allowed derivation of an absorption curve throughout the wavelength range of water transparency. We conclude that the argon laser was the most appropriate system available at the present time.


Carbon urinary conduits. Animal experiments. A new type of urinary conduit utilizing pure carbon has been used in dogs. It appears to be inert with respect to urine, acts as an adequate conduit in dogs, and theoretically should work in humans. Twelve vesicostomies and two ileal-bladder using carbon as a conduit were performed in dogs. Evaluation of the biocompatibility of the carbon material, a report on the experimental animal testing procedures showing protocol and results, and detailed description of the surgical technique are shown. Carbon conduits, so designed, functioned well and should be tolerated in humans as long term urinary conduits obviating the need for indwelling catheters and bulky adhesive dressing.


Induction of Venezuelan equine encephalitis (Mucambo) virus by iododeoxyuridine in chronically infected 'cured' cultured mosquito cells. Infection of cultured Aedes aegypti mosquito cells with Venezuelan equine encephalitis virus (Mucambo subtype) results in the establishment of a chronic non-cytopathic infection. Infected cells could be 'cured' when they were grown in the presence of immune serum for 3-4 passages. 'Cured' cells could then be subcultured repeatedly, in the absence of immune serum, without showing any indication of infectious virus production. When 'cured' cells were exposed to 50 microgram/ml of 5-iodo-2-deoxyuridine for 24 h, efficient induction of virus was observed. The enhancement of virus replication could not be related with increased susceptibility of the uninfected cell population. The phenotype (plaque size and virulence) of the induced virus resembles more closely that of the standard virus than the phenotype of the virus produced in chronically infected mosquito cells. These findings indicate that virus information can be maintained in chronically infected mosquito cells in a latent inducible form, and constitute indirect evidence suggesting the existence of a DNA provirus in this system.


Cell fusion by canine distemper virus-infected cells and their plasma membranes. Cells first gain detectable fusion induction ability 4-6 h after infection with canine distemper virus even though mature virions are not released until about 10 h. Plasma membranes isolated from cells as early as 6 h after infection also have the ability to induce early fusion. While protein synthesis is not required for fusion in the early fusion assay itself, it is required in infected cells for induction of fusion ability. Early cell fusion by infected cells is apparently the result of synthesis of a virus-induced protein that is found in association with the cell plasma membrane.


Effects of thymectomy on the endocrine glands of the rat. The effects of thymectomy on the thyroid gland, the adrenal cortex, the testes and the lymph nodes of the rat follow the same pattern as those observed in guinea pigs but in a very attenuated form. Thymectomized rats do not show the wasting observed in thymectomized guinea pigs. The effects on the adenohypophysis are approximately the same in rats and guinea pigs, but the sequence of the changes is different. Injections of thymic extract or of presumably pure thymic hormone suppressed all the effects of thymectomy on the endocrine glands of the rat. In  rats, thymic hormone was found in the thymus, the lymph nodes and the spleen. It disappeared from the lymph nodes and the spleen within three days of thymectomy and did not reappear, although most of the changes in the endocrine glands were transitory. The implications of the observations for understanding the consequences of thymectomy are discussed.


Mammalian embryo: a model for congenital prolonged QT syndrome. The QT interval has been studied in ECG in mouse and rat embryos during two stages of development. The QT interval during the early stage of development is prolonged and an ST segment clearly exists. Both disappear during fetal development and do not exist in adult animals in which the T wave immediately follows the QRS. Mammalian embryos have therefore been proposed as a model for the study of QT prolongation. It is suggested that the origin of the QT prolongation in the young embryos is caused by the prolonged duration of the action potentials of the primordial cardiac tissue. During embryonic development this tissue becomes organized as a conductive system surrounded by "neomyocardial" tissue with a shorter duration of action potential, which causes the shorter QT interval at this stage. Our working hypothesis is that the pathogenesis of the prolonged QT syndrome in children could be interpreted as an incomplete or delayed differentiation between the primordial or primordial-like myocardium retaining prolonged action potential duration, and "neomyocardium" with short duration.


Leptospirosis among dairy workers in the valley of Jezreel: first recorded isolation of Leptospira hardjo in Israel. Five cases of leptospirosis among dairy farmers in the Valley of Jezreel are described. The disease was caused by leptospirae of serotype hardjo and available epidemiological evidence suggested infection due to contact with cows. This is the first time that Leptospira hardjo has been isolated and identified in Israel. Infection with L. hardjo should be regarded as a significant occupational risk and this strain should be included in the group of antigens used for screening sera for leptospira antibodies in Israel.


Prenatal diagnosis of genetic disease. A report on 200 amniocenteses. The results of 200 prenatal diagnoses following amniocentesis are summarized. The routine withdrawal of 40 to 45 ml amniotic fluid caused no increase in maternal morbidity, fetal loss, prematurity or congenital malformations. There were no culture failures and in all cases in which amniotic fluid was obtained the prenatal diagnosis was subsequently confirmed. Electron microscopy was used in the prenatal diagnosis of a newly described metabolic storage disease (mucolipidosis IV). Eleven abnormal fetuses and one male fetus at risk for hemophilia A were diagnosed and aborted.


The association of HL-A-B8 and childhood celiac disease in an Israeli population. The frequency of histocompatibility antigens (HL-A) was studied in 33 children with celiac disease. HL-A-B8 phenotype was detected in 27.3% of the celiac patients and 7.5% of 395 carefully matched control subjects (X2 for heterogeneity=14.23; P less than 10(-4)). HL-A typing, especially in children, is advocated both as a diagnostic and a prognostic measure. The importance of ethnically matched control subjects is discussed together with a proposal for the construction of such control groups.


Thrombosis on Björk-Shiley aortic valve prosthesis. A case report and review of the literature. A patient who developed thrombosis on a Björk-Shiley aortic valve prosthesis is reported. The patient presented with severe angina pectoris and the main physical findings were absence of the closing click of the prosthetic valve and the presence of systolic and diastolic aortic murmurs. Echocardiography showed early closure of the mitral valve and depressed left ventricular function. An emergency operation was performed and the clot was removed. The patient's recovery was uneventful and he is well one year after surgery. Awareness of the possibility of valve thrombosis is necessary in view of the need for emergency surgical treatment. The literature on the subject is reviewed.


Meteorologic factors and temporal variations of cardiac mortality in an urban setting in a desert climatic zone. The aim of this investigation was to study, by use of the unbiased and rigorous techniques of lagged cross-covariance and spectral analyses, the associations between daily cardiac mortality and weather conditions in Beersheba, an urban center situated in a hot and dry climatic zone. The results of the analyses point to the existence of seasonal differences in mortality, with a peak in winter. Of greater interest is the statistical documentation of temporal associations between short-term increases in daily mortality and certain weather situations corresponding to the transitional periods of turbulent atmosphere with below normal air temperatures, strong gusty winds and a drop in relative humidity, i.e., conditions accompanying the intrusion of a winter cold wave. The crests in short-term mortality occurred most often within a week of the intrusion of the cold air masses. No consistent cross association was found between high summer temperatures and mortality. The results of this investigation are discussed in the light of those previously reported for Tel Aviv (a coastal city) and Jerusalem (a city situated at a high altitude).


Low cortisol and growth hormone secretion in response to methoxamine administration in obese subjects. To investigate the hypothalamic responsiveness in obesity, changes in the levels of plasma cortisol and growth hormone (GH) were studied in 11 obese and six normal-weight subjects after hypothalamic alpha-adrenergic stimulation with methoxamine, 20 mg i.v. To allow for dose/body weight differences, five additional obese subjects received 30 mg methoxamine. Plasma GH, cortisol, insulin, free fatty acid and glucose levels were determined during the 3-h infusion of methoxamine. The responses of cortisol and GH were reduced in the obese subjects as compared with the normal-weight subjects. No significant changes in plasma glucose, free fatty acids or insulin were observed in any of the groups. The reduced responses of plasma cortisol ang GH in the obese subjects are considered to be an expression of hypothalamic underresponsiveness, since the stimuli for the secretion of these hormones are at least partially controlled by an alpha-adrenergic mechanism.


Elective cervical suture in preventing premature delivery in multiple pregnancies. Of 133 pregnancies conceived after ovulation induced by menotropins and chorionic gonadotropins, a group of 20 women with multiple gestations--15 twins, three triplets and two quadruplets-had elective cervical suture during the 12th to 15th weeks of pregnancy. A comparable group 20 women with multiple pregnancies without cervical suture served as the control for comparing the mean duration of pregnancy, fetal survival rate and mean length of hospitalization. Duration of pregnancy was significantly longer in the sutured group (P less than 0.05). The perinatal loss was significantly lower--16 of 47 infants in the sutured patients, as compared with 25 of 47 infants in the control group. The mean hospitalization period was shorter in women who underwent cervical suture (P less than 0.025).


Triploidy in man: a clearly recognizable syndrome? Complete triploidy in a 13-week-old fetus and in a full-term liveborn infant is described. A previous pregnancy of one of the mothers had resulted in a hydatidiform mole. Hydatidiform degeneration of the placenta of triploid abortuses and newborn infants may be responsible for the intrauterine growth retardation and fetal death often observed. Although many phenotypic features are common in triploidy, a review of the literature indicated that a pathognomonic syndrome could not be delineated. Nevertheless, a certain combination of findings may be suggestive of the diagnosis.


Mother and child health in Africa: the role of health education. Research and practical experience clearly indicate that most mother and child health problems in Africa are preventable. Most are associated with poor personal hygiene and environmental sanitation, ignorance, poverty, and inadequacy or nonutilization of available health services. Improved health planning can either alleviate or totally abolish many of these problems. Health education is an integral part of mother and child health and other medical care programs. Because the reaction of the individual to medical intervention is largely determined by the sociocultural and community environment, health education should not be directed towards the health-deficient target population alone, but towards the community as a whole.


Maternal, perinatal and infant health in Bedouin and Jews in southern Israel. A study has been made of 3,745 Bedouin and 9,422 Jewish babies born in 1972-73 to residents of the Beersheba district of southern Israel (the Negev). Newborn infants weighing less than 1 kg were excluded. Thirty-seven percent of the Bedouin babies were born at home; their mothers tended to be older and of higher parity than those choosing to deliver in hospital. Less than 6% of Bedouin mothers had been to school, compared with 90% of the Jews; 30% were aged under 20 or over 34 years, compared with 18% of the Jews, and 23% were having their seventh or later baby, compared with 12% of the Jews. Mean birth weight of babies born in hospital was about 200 g lower in Bedouin than in Jews, and 11.4% of Bedouin and 6.5% of Jewish infants weighed less than 2.5 kg. There was little variation in complications of labor between the 1,959 Bedouin and 8,877 Jewish women delivered in Beersheba's Soroka Medical Center. The cesarean section rate was 1.8% in Bedouin and 4.3% in Jews, while in 0.3% of Bedouin and 1.4% of Jews labor was induced. Monozygous twinning rates were similar in the two ethnic groups (4.8 and 4.5 sets/1,000 deliveries, respectively) but dizygous twinning was twice as common among the Bedouin as among the Jews (13.0 vs 6.0 sets/ 1,000). Male births accounted for 0.526 and 0.512 of the total in Bedouin and Jews, respectively. Perinatal mortality rates for hospital births were 31.1 and 18.3/1,000 in Bedouin and Jews, respectively. Infant deaths among Bedouin (31.0/1,000) were underreported; the rate was 16.8/1,000 for Jewish infants. Although rates of all specific causes of death were higher in Bedouin than in Jews, patterns of mortality in subgroups based on birth weight, sex, twinning and maternal age were quite similar in the two ethnic groups. There were six reported deaths from tetanus among Bedouin babies. For the cohort of babies born in 1972, admissions to the Soroka Medical Center pediatric wards were recorded in 366 (195.5/1,000) Bedouin and 787 (174.3/1,000) Jewish babies younger than the age of one year. Bedouin admission rates were higher than those of Jews for gastroenteritis (119.1 and 64.5/1,000 respectively), infectious and parasitic diseases (29.4 and 21.9), malnutrition (25.6 and 8.0) and external causes (10.1 and 4.4). Admission rates for bronchitis and pneumonia were, however, lower among Bedouin than Jews in the first six months of life.


[Metastizing basalioma. A case contribution]. A case of a metastasizing basal cell carcinoma that began 24 years earlier as a rodent ulcer on the back is reported. Histologically there were strands of characteristic basal cell type cells and, in addition, areas of squamous cell differentiation. The problem of "epithelioma metatypique" is discussed. The autopsy showed pure basal cell metastases in the lungs, the paraaortal lymph nodes and penetration of the tumor masses into the vena cava inferior. The unsufficient treatment by X-ray seems to be a conditioning factor by injuring the surrounding stroma.


[Linear pigmentation of nails].

[Linear pigmentation of nails]. A case of linear pigmentation of three fingernails is reported. Following extraction of the nail of the thumb the matrix displayed a 2X4 mm circumscribed pigmented area. Histologic examination revealed a junction nevus.


[Unusual garland-like lichen planopilaris of the face]. Report about two male patients with uncommon lichen planopilaris of the face. The disease resolved with garland-like vermiculate scars.


[Treatment of molluscum contagiosum].

[Treatment of molluscum contagiosum]. Puncture with a toothpick dipped in phenolum liquefactum is a suitable method for the treatment especially of small mollusca contagiosa in children. The danger of phenol intoxication through resorption during the treatment of multiple molluscs always must be borne in mind. Comparable studies in rats' nipples using the puncture technique showed that up to 0.7 mg phenol can be applied to one molluscum.


[Malignant melanoma of penis].

[Malignant melanoma of penis]. Two cases of malignant melanoma of the penis are reported. A further case report of a naevus caeruleus of the glans penis is presented with regard to the differential diagnosis of malignant melanoma of the penis. A comprehensive review of the literature has revealed 41 case reports of malignant melanoma of the penis. A brief characterisation of malignant melanoma of the penis is given.


[Elastic globes].

[Elastic globes]. After a short compilation of the descriptions of the elastic globes offered in the literature, the results of 446 tissue specimens of five different dermatoses (lichen planus, erythematodes chronicus discoides, tuberculosis cutis luposa, basal cell carcinoma, and nervus cell nevi). An increased appearance of elastic globes was found in erythematodes chronicus discoides and tuberculosis cutis luposa, compared with the other dermatoses. Elastic globes were not limited to special areas of the body, but there were topographical preferences. Elastic globes are common in the aged. The histopathology is descripted.


[Effect of topical drug vehicles on wound contraction]. The effect of vehicles of medical preparations upon wound contraction was tested in animals. The detraction of experimental skin defects on the back of guinea pigs was used which is caused first of all by wound contraction. Wound contraction is more favourably influenced by vaselinum flavum than by pasta zinci mollis and amylum maydis. The influence of pasta zinci mollis was more favourable than the influence of amylum maydis. The comparison of the three unspecific powder constituents lactose, amylum maydis and talcum revealed differences. These investigations do not allow the general recommendation of the use of fatty vehicles in the treatment of ulcers but they do show that such a recommendation can be made when the ulcer is in a region where wound contraction plays an important part in wound healing and when there is no super infection of the ulcer.


[Ascher's syndrome].

[Ascher's syndrome]. A case of Ascher's syndrome with blepharochalasis and double upper lip is described. It is emphasized that the combined appearance of these two symptoms is essential for the definition of this syndrome.


[Oligozoospermia in Klinefelter's syndrome]. Case report of a 31 year old male with a 47-XXY-Klinefelter-syndrome which showed a maximum of 4,0 million spermatozoa/ml with a motility of up to 51% in his ejaculate. No rise of spermatozoa counts could be observed after 3x25 mg mesterolone/day over 8 weeks.


The clinical significance of Acinetobacter species. Of 50 consecutive patients from whom Acinetobacter species were isolated, only one had an infection due to the organism which required antibiotic therapy. Fourteen of the isolates were associated with minor body surface infections and the remainder occurred as the result of either colonization without infection or culture contamination. The taxonomy, natural occurrence and antibiotic sensitivity of Acinetobacter species and their differentiation from more pathogenic organisms are reviewed.


Wisconsin's laboratory evaluation and certification program. A review of methods used in the evaluation of test performance and certification of laboratories in Wisconsin.


An evaluation of four telemedicine systems for primary care. In an evaluation of the efficacy of four two-way telecommunication systems for use in primary care, more than 1,000 patients seeking care at a community health center received an additional remote examination by use of either color television, black and white television, still-frame black and white television, or hands-free telephone. The diagnosis, clinical tests and X rays requested, and proposed patient management were compared to the actual care received by the patients at the health center. There were no significant differences between any of the modes in relation to diagnostic accuracy, time for the diagnostic interview, tests requested, or referral rates. Furthermore, patient attitudes did not vary significantly. Thus the relatively inexpensive telephone proved to be as efficient and effective a means for delivery of remote physician care as did any of the visual communication systems.


Multiple prescriptions and drug appropriateness. The relationship between number of prescriptions per office visit and the appropriateness of the prescribed drugs is examined, using data on more than 20,000 prescriptions purchased for a low-income rural population during 1973 and 1974. Criteria for drug appropriateness are based on an AMA evaluation of drugs. The results show that greater numbers of prescriptions per visit are associated with lower percentages of appropriate drugs prescribed and that patients whose prescriptions were written by specialists received a higher percentage of appropriate drugs than did those whose prescriptions were written by general practitioners. It is concluded, in support of other researchers, that a better knowledge of drugs leads to more conservative use of them.


A microscope stage sample holder for microfluorometric measurements of biological specimen in the range of temperature between 3.5 to 300 K. A cryostat was constructed, which permits measurements of the intracellular fluorescence within a range of temperature between 3.5 to 300 K. The cooling unit operates in accordance with the "Continuous Flow Principle" and allows the application of objectives up to a numerical aperture of 0.6. It results from measurement of BAO Feulgen stained nuclear DNA, that a decrease of fluorescence intensity is caused by two different mechanisms: (1) There is a highly temperature dependent effect, originating from phenomena of solid physics, and (2) a second effect, which is almost temperature independent, and can be explained as a photochemical reaction.


Fluorescence histochemical demonstration of dopa thioethers by condensation with gaseous formaldehyde. The usefulness of the formaldehyde (FA) and glyoxylic acid (GA) methods for the fluorescence histochemical demonstration of dopa thioethers has been tested using protein droplet models. Similar fluorescence intensities were recorded from these compounds after either FA or GA treatment. Cysteinyldopa gave a high fluorescence yield similar to that obtained from dopamine and dopa in the FA reaction, whereas gluatitodopa showed a lower, although clearly visible fluorescence. Since the FA method seemed to be the most useful one for demonstration of catechol thioethers, the FA-induced fluorophores of these compounds were further characterized by microspectrofluorometry. The spectral characteristics of the thioether fluorophores (excitation maxima at 420 nm and emission maxima at 480-485 nm) distinguish these substances from dopa and other compounds fluorogenic in the Falck-Hillarp method. Dopa thioethers are proposed to form fluorophores with FA in a manner analogous to that of the primary catecholamines i.e. via low-fluorescent tetrahydroisoquinolines, along two different pathways, to strongly fluorescent 3,4-dihydroisoquinolines and 2-methyl-dihydroisoquinolinium compounds. These dihydroisoquinolines are in a pH-dependent tautomeric equilbrium with their quinoidal forms as reflected by a characteristic spectral shift upon acidification. The results of this study provide the guide-lines for the characterization of fluorogenic compounds in pigment-forming cells.


Flow microfluorometric monitoring of the interaction of lipid vesicles with cells. Flow microfluorometric techniques have been applied to experiments concerned with the penetration of cells by lipid vesicles. The high sensitivity of laser flow systems enables to measure the weak fluorescence emitted by individiual liposomes tagged with perylene, inserted into their multilamellar layer. The total fluorescence of cells which habe incorporated such perylene-loaded liposomes could be measured and well separated from that unbound liposomes. Significant differences in the incorporation rates of cationic and anionic liposomes were shown by means of time-course analyses of cellular fluorescence spectra. The advantages of the rapid data analysis by flow fluorescence techniques is discussed in comparison with conventional radio-isotopic methods.


Effects of physical characteristics of milking machines on teats and udders. A milking machine must remove milk from a cow thoroughly and rapidly but not impose excessive stress or contaminate teats with bacteria. The machine removes milk by applying vacuum to the exterior of the teat until it stretches sufficiently to open the streak canal. Periodic collapse of the teat cup liner relieves tension on the teat sphincter and aids circulation of blood through the teat. The milking machine may affect the likelihood of mastitis by directly implanting pathogenic organisms into the streak canal, by engendering long-term deterioration of the teats, and by serving as a reservoir of pathogens.


Role of teat dips and hygiene in mastitis control. The primary sources of mastitis pathogens are infected quarters, chapped, sore, or eroded teat ends, and the environment. The major means of transfer of the most predominant mastitis pathogens is the milking routine. Methods are available to reduce the number of organisms normally transferred during each of the procedures. However, with the exception of teat cup pasteurization, the application of hygienic procedures in herds where teat dipping is practiced did not result in additional beneficial effects. Effectiveness of 4% chlorine, 0.5 and 1% iodine, and 0.5% chlorhexidine teat dips has been demonstrated in field trials and should be the preferred products in a mastitis control program. Most gram-negative organisms get on teats by direct contact with the bedding. In herds with clinical coliform mastitis, changing the bedding material has been associated with fewer clinical mastitis cases.


The leukocyte as a defense mechanism.

The leukocyte as a defense mechanism. Within the udder, neutrophil polymorphonuclear (PMN) leukocytes are capable of phagocytosing a wide variety of particles (microorganisms, milk fat globules, casein). Studies of PMN leukocyte function indicate that milk fat globules and casein are perhaps significant deterrents to phagocytosis and destruction of Staphylococcus aureus by PMN leukocytes in milk. These deterrents could be a major factor in establishment of intramammary infections by invading mastitis pathogens. Elimination of fat and casein from milk during clinical or subclinical mastitis may free PMN leukocytes to function properly and may remove infection from the mammary gland. Further observations on PMN leukocyte function indicate that considerable variation exists among cows in the ability of whole milk and skimmed milk to support phagocytosis and in the ability of PMN leukocytes to phagocytose. Variation in this basic defense mechanism could account for the differences that exist in susceptibility to infection by mastitis pathogens.


Immune response of the mammary gland and role of immunization in mastitis control. It has been mentioned that IgG1 is the major secretory immunoglobulin class in mammary gland secretions; in addition, most immunoglobulins of all classes in these secretions are of humoral origin. A transport mechanism selectively favors IgG1. A lesser amount of immunoglobulin is produced locally in the gland, this local contribution apparently increasing after antigenic stimulation. Therefore, systemic and local stimulation would be likely to contribute to the presence of specific antibodies in secretions. The role of cellular immune phenomena as it relates to the mammary gland has not been determined. There is evidence for the influence of phagocytic cells in the mammary gland. Published reports have established that a state of heightened resistance to mammary gland infection can be induced. Research workers have clearly shown that immunized animals resist challenge exposure to infection to a greater degree than do nonimmunized animals. This resistance, being not absolute, causes reluctance to use the term immune. It is apparent that reexamination must be made of the correct conditions, i.e., effective antigenic preparation, proper inoculation route, dose, and duration necessary to stimulate an immune response in the mammary gland.


Western equine encephalomyelitis in horses in the Northern Red River Valley, 1975. In mid-July, 1975, western equine encephalomyelitis (WEE) virus was isolated from mosquitoes collected in flooded areas of eastern North Dakota and western Minnesota. Inasmuch as clinical manifestations of WEE are usually observed in horses before human cases of encephalitis are recognized, surveillance of equine disease was initiated. Sixty-one practicing veterinarians from the are under surveillance reported 281 cases of WEE in horses from June through September, with peak incidence in late July. The high percentage of sero-positive, clinically normal, unvaccinated horses in one region suggested that many horses had developed non-clinical infections. The efficacy of vaccines used by the practitioners appears to have been execllent, as none of the horses vaccinated before the epizootic became ill during the period of surveillance. It was concluded that data collected from routine surveillance of encephalomyelitis in horses could be used to predict epidemics of WEE.


Epidural melanoma causing posterior paresis in a horse. An aged gray stallion was examined because of fullminating posterior paresis, bladder paralysis, and perineal anesthesia. Lower motor neuron dysfunction was detected at the lumbosacral level of the spinal cord, and cerebrospinal fluid was yellow. After brief supportive treatment, the horse died. Necropsy revealed a single epidural melanoma at L5-6. The absence of cutaneous melanotic growth, absence of organ involvement, and extensive vertebral remodeling indicated the neoplasm to have been primary and to have been present for an extended period. Neurologic dysfunction was acute and progressive, as a result of spinal cord compression by the neoplasm.


Diaphragmatic hernias in the horse: a review of the literature and an analysis of six additional cases. Eighteen cases of equine diaphragmatic hernia were reviewed. Most of the cases were of long duration, with an additional factor  precipitating acute abdominal crisis. History and physical examination were of little diagnostic significance. Radiography, if available, and exploratory laparotomy were the most useful diagnostic procedures. The prognosis for successful surgical repair and recovery was poor.


Coccidia and intestinal nematodes of East Central Illinois cats. In a fecal examination survey (1975-1976) of 217 cats from laboratory colonies, a humane society shelter, and homes in east central Illinois, Toxocara mystax eggs were found in 32%, Toxascaris leonina eggs in 6%, Ancylostoma eggs in 9%, Capillaria eggs in 4%, Isospora felis oocysts in 23%, Isospora rivolta oocysts in 24%, and Toxoplasma or Besnoitia oocysts in 1%. The laboratory and humane shelter cats were the most heavily infected. Isospora felis and I rivolta could not be transmitted to 2 pups by feeding oocysts from the cat or to 2 other pups by feeding the organs of mice that had been fed the oocysts.


Tracheal osteochondroma in a dog.

Tracheal osteochondroma in a dog. A young female Labrador Retriever-type dog had a 4 1/2-month history of respiratory distress, which eventually became severe, leading to cyanosis. Physical examination suggested an upper airway obstructive lesion, which was confirmed by bronchoscopy and radiography to be a mass in the thoracic portion of the trachea. The mass was removed surgically and, on histologic examination, was found to be an osteochondroma. Six months after surgical extirpation, there was no indication of recurrence of tumor.


Evidence for the presence of phosphoriboisomerase and ribulose-1,5-diphosphate carboxylase in extracts of Desulfovibrio vulgaris. Cell extracts of Desulfovibrio vulgaris were found to incorporate 14CO2 into acid-stable products when ribose-5-phosphate or ribulose-1,5-diphosphate was used as a substrate. This CO2 fixation required adenosine triphosphate and produced 3-phosphoglyceric acid as one of the products. The assimilation of CO2 by pentose phosphates was unrelated to the pyruvate-CO2 exchange reaction. The pyruvate-CO2 exchange did not require adenosine triphosphate, did not produce phosphorylated compounds, and, unlike the pentose phosphate system, required an acidic protein fraction for activity.


Structural analysis of the surface polysaccharide of Staphylococcus aureus M. The chemical structure of the surface polysaccharide from Staphylococcus aureus M was investigated by a combination of methanolytic, hydrolytic, and chromatographic techniques. The repeating unit that was most consistent with the data was a hexasaccharide composed of N-acetyl-D-aminogalacturonic acid, N-acetyl-D-fucosamine, and taurine in molar ratios of 4:2:1. A disaccharide was isolated and characterized, by combined gas-liquid chromatography-mass spectrometry, as N-acetyl-D-aminogalacturonyl-(1 leads to 3)-N-acetyl-D-fucosamine. Taurine is linked to a carboxyl group of N-acetyl-D-aminogalacturonic acid via an amide bond.


Detection and characterization of plasmids in Pseudomonas glycinea. Pathogenic strains of Pseudomonas glycinea were shown to possess plasmid deoxyribonucleic acid by dye-buoyant density gradient centrifugation. The size and number of plasmids of four different isolates were determined by neutral sucrose gradient centrifugation. Two isolates were found to harbor a single plasmid; however, they differed in size, having molecular weights of 43 X 10(6) and 54 X 10(6). Two other isolates each contained two different plasmids. Plasmids with molecular weights of 43 X 10(6) and 73 X 10(6) were observed in one isolate, and the other carried plasmids with molecular weights of 25 X 10(6) and 87 X 10(6). An auxotrophic mutant derived from the latter strain was found to contain plasmids of identical size. The plasmids were found to be under stringent control of replication, having plasmid copies of 1.0 to 2.7 per chromosome equivalent. By the dye-cesium chloride technique, the mutant showed twice as much covalently closed circular deoxyribonucleic acid as did the parental strain.


Characterization of a plasmid from Streptomyces coelicolor A3(2). Covalently closed circular deoxyribonucleic acid (DNA) with a molecular weight of 20 X 10(6) was identified in strains of Streptomyces coelicolor A3(2) of various fertility types. Hybridization studies and digestion by various restriction endonucleases indicated that the circular DNAs (pSH1) were identical regardless of the fertility type (UF, IF, or NF) of the strain from which it was isolated. The pSH1 DNA was cleaved to many fragments by the endonucleases HincII, SmaI, and SalI and to three or four fragments by BamHI and PstI. Plasmid pSH1 carries single sites for each of the two restriction enzymes, EcoRI and HindIII. These sites are 7.6 X 10(6) daltons apart. Attempts to isolate the fertility factor SCP1 as covalently closed circular DNA were unsuccessful. These data suggest that the biochemically isolated plasmid pSH1 is not identical to the genetically characterized fertility factor SCP1, which has been identified in an autonomous state in IF-type strains and in an integrated state in NF-type strains.


Stalkless mutants of Caulobacter crescentus. A stalk, a single falgellum, several pili, and deoxyribonucleic acid (DNA) phage receptors are polar surface structures expressed at a defined time in the Caulobacter crescentus cell cycle. When mutants were isolated as DNA phage phiCbK-resistant or ribonucleic acid (RNA) phage phiCp2-resistant, as well as nonmotile, strains, 5 out of 30 such mutant isolates were found not to possess stalks, but did possess inactive flagella. These stalkless mutants were resistant simultaneously to both DNA and RNA phages and did not possess pili and DNA pendent stalkless mutants. All motile revertants simultaneously regained the capacity to form stalks and susceptibility to DNA and RNA phages. It is suggested that a single mutation pleiotropically affects stalk formation, flagella motility, and coordinate polar morphogenesis of pili and DNA phage receptors. The stalkless mutants grew at a generation time similar to that of the wild-type strain at 30 degrees C. Cell size and morphology of a stalkless mutant, C. crescentus CB13 pdr-819, were also similar to those of the wild-type strain, except for the absence of a stalk. In addition, the CB13 pdr-819 predivisional cells were partitioned into smaller and larger portions, indicating asymmetrical cell division, as in the wild-type strain. From these results, it is suggested that swarmer cells undergo transition to cells of a stalked-cell nature without stalk formation and that the cell cycle of the stalkless mutant proceeds in an ordered sequence similar to that defining the wild-type cell cycle.


Ultrastructural surface changes associated with dextran synthesis by Leuconostoc mesenteroides. When Leuconostoc mesenteroides NCDO 1875 was grown in MRS broth and fixed for electron microscopy in the presence of ruthenium red, the cell wall appeared as a triple-layered structure similar to other, gram-positive bacteria. When such logarithmic-phase cultures were exposed to sucrose, the appearance and growth of a uniform layer of electron-dense material was evident on the surface of the cell wall. After 2 h in the presence of sucrose, the formation of this surface coat (110 to 130 nm thick) was complete. For 85 to 90% of the cells, continued exposure to sucrose did not produce any further change in their appearance, but the rest of the population began to accumulate insoluble capsular dextran at the surface of their coat material. Within 18 h, these cells had produced a large capsule (maximum diameter, 6 micrometer) composed mainly of an extensive reticulum of fine filaments. Periodate-reactive carbohydrate was localized cytochemically in the capsular dextran and in the surface coat of all cells. It is suggested that the surface coat of sucrose-grown cells represents a cell-bound dextran-dextransucrase complex and that the acapsulate cells produce the relatively soluble S dextran reported by previous workers.


Morphology and ultrastructure of Crenothrix polyspora Cohn. Naturally grown cell material of Crenothrix polyspora from the well of a waterworks was studied by means of phase-contrast and Nomarski interference microscopy as well as by transmission electron microscopy. The material consisted of clusters of sheathed filaments up to 2 cm long. Propagation forms observed were nonmotile, spherical cells that arose by simple ("macrogonidia") or multiple ("microgonidia") septation of the filamental tips. Ultrastructural analysis revealed Crenothrix to be procaryotic and gram negative, with several layers of sheath material surrounding the filaments. On thin sections, individual cells had elaborate membrane systems in the form of lamellar stacks. They resembled thylakoids of photosynthetic bacteria. Spectrophotometric analysis gave no indication of photosynthetic pigments. The cells also contained large hexagonal bodies, rod-shaped fibrillar elements, and polyphosphate granules.


Characterization of bdellocysts of Bdellovibrio sp. Bdellovibrio sp. strain W will infect and produce resting cells, termed bdellocysts, in a variety of gram-negative bacteria. Bdellocysts appeared to be produced only within susceptible prey and never in their absence. Optimum conditions for encystment included infection of stationary-phase prey cells in 0.05 M potassium phosphate buffer (pH 7.5) at concentrations of prey and bdellovibrios of 2 X 10(9) cells per ml with a multiplicity of infection of unity. Bdellocysts contained more deoxyribonucleic acid, ribonucleic acid, protein, and carbohydrate per cell than did vegetative cells. Poly-beta-hydroxybutyrate and dipicolinic acid were not detected. Bdellocysts were more resistant than vegetative cells to effects of elevated temperatures, sonic treatment, and desiccation. Bdellocysts remained viable for extended periods when incubated in the absence of prey, whereas vegetative cells lost viability rapidly under the same conditions. Their survival under starvation conditions may be due to the low rate of endogenous respiration by the bdellocysts. Bdellocysts are capable of germination in the presence or absence of prey cells in rich medium such as peptone-yeast extract.


Ultrastructural changes during encystment and germination of Bdellovibrio sp. Under proper conditions, Bdellovibrio sp. strain W cells develop into bdellocysts in appropriate prey bacteria. After attachment and penetration of the prey cell, the encysting bdellovibrio began to accumulate inclusion material and increase in size, and was surrounded by an outer layer of amorphous electrondense material. The cytoplasm of the encysting cell appeared more electron dense, and nuclear areas appeared more compact. During germination of bdellocysts, the outer wall was uniformly broken down the inclusion material changed shape and affinity for the heavy metal stain, and the nuclear areas expanded. As the outer wall was dissolved, outgrowth began with the elongation of the germinant as it emerged from the prey ghost as an actively motile cell.


Caulobacter crescentus pili: structure and stage-specific expression. Pili are functionally expressed during the predivisional and swarmer stages of the Caulobacter crescentus differentiation cycle. They appear on the developing swarmer pole and at the same cellular location as flagella and the phiCbK receptor sites. Pili disappear when the swarmer cell differentiates into a stalked cell; this occurs with the loss of flagella and the disappearance of phage receptor sites. C. crescentus CB13B1a pili have been purified and characterized. Monomeric pilin is a protein with an apparent molecular weight of 8,500 that stains weakly with periodic acid-Schiff reagent. The amino acid composition of purified pilin reveals very low quantities of basic amino acids and a complete absence of methionine. Pilin is synthesized throughout the C. crescentus differentiation cycle. Neither free pili nor pilin monomers are detectable in the growth media, suggesting that loss of piliation in the swarmer- to stalked-cell transition occurs via pilus retraction.