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The standard complement fixation (CF) test, a commercial agarose gel immunodiffusion (AGID) test (ImmuCell Corporation, Portland, Maine), and two commercial enzyme-linked immunosorbent assays (ELISAs; Allied Laboratories, Glenwood Springs, Colo. [Allied ELISA], and the CSL, Limited, [Parkville, Victoria, Australia] enzyme immunoassay [CSL ELISA]) were evaluated by using sera from the Repository for Paratuberculosis Specimens. The case definition of subclinical bovine paratuberculosis was isolation of Mycobacterium paratuberculosis from fecal samples or internal organs of dairy cattle without diarrhea or weight loss. Animals designated as free of the disease originated exclusively from certified paratuberculosis-free herds in Wisconsin. None of the cattle evaluated had been vaccinated for paratuberculosis. Among 177 M. paratuberculosis-infected cattle, the CF test, the AGID test, the Allied ELISA, and the CSL ELISA had test sensitivities of 38.4, 26.6, 58.8, and 43.4%, respectively, and specificities of 99.0, 100.0, 95.4, and 99.0%, respectively. Only 108 of the infected cattle were confirmed by culture or by a commercial DNA probe (IDEXX Corporation, Portland, Maine) to be shedding the organism in fecal samples at the time of serological testing. Among the 108 M. paratuberculosis fecal shedders, the CF test, the AGID test, the Allied ELISA, and the CSL ELISA were positive for 54.6, 40.7, 65.7, and 56.5% of the cows, respectively; and among the 69 cows that were nonshedders, the tests were positive for 14.5, 4.3, 47.8, and 24.6% of the cows, respectively. There was a significant difference (P < 0.05) in the rate of positive test results for all four tests between these two groups of animals. The CF test performed well when it was compared with the other serological tests if a titer of >/- 1.8 was classified as a positive test result.

To evaluate the usefulness of pulsed infrared solid-state Holmium:Yttrium-Aluminum-Garnet (Ho:YAG) laser in neurosurgery, acute responses of brain tissue to Ho:YAG irradiation and to investigate the healing processes in rats and rabbits.Animals were divided into groups according to different survival time and laser irradiation mode. Craniotomy was made and laser energy was delivered to the brain surface by two irradiation modes: 1) contact mode with the fiber in contact with the brain surface; and 2) non-contact mode with the fiber tip 5 mm above the brain surface. Gross observations were made and histological changes were studied.Acute responses were studied on rats' brain. The contact mode produced a crater lined with less than 1 mm thick thermally coagulated layer of brain tissue. The non-contact mode effectively vaporized the brain tissue even with water irrigation. Good homeostatic effect was achieved. The shock waves generated by the pulsed delivery of laser energy, however, impacted on the brain resulting in debris spreading and brain vibration. The healing processes were studied on rabbits' brain one day to six weeks after irradiation. The lesions produced by the contact mode were narrow and sharply defined. With the non-contact mode, the thickness of the coagulated layer at the bottom of the crater varied between 0.8 and 1.1 mm.Ho:YAG laser should be a clinically useful tool in neurosurgery because of its good ablation effect, shallow penetration and convenient optic fiber transmission system. Meanwhile, a continuously waved Ho:YAG laser is desired to reduce the shock wave impact.

To use an on-farm recording form to quantity the effect of specific management practices on apparent prevalence of Mycobacterium paratuberculosis in dairy cattle herds.Epidemiologic survey.26 commercial Wisconsin dairy farms.An instrument was developed on the basis of literature review and expert interviews to quantify on-farm management practices associated with increased apparent prevalence of M paratuberculosis. On-farm visits were conducted to assess how specific management practices were conducted. Apparent prevalence of M paratuberculosis infection was measured for all animals20 months old on all farms, using a commercial ELISA. Regression analysis was used to identify management variables that were significantly associated with apparent prevalence of M paratuberculosis.Regression analysis (R2 = 0.90) identified that high scores for environmental conditions, newborn calf care, grower calf care, bred heifer care, and manure handling were significantly associated with M paratuberculosis apparent prevalence in Wisconsin dairy herds.Environmental conditions, newborn calf care, grower calf management, bred heifer management, and manure handling factors may serve as a prioritized checklist for instructing owners and managers where to place emphasis in changing management practices to limit M paratuberculosis prevalence. Likewise, the factors identified as having low association with apparent prevalence may be de-emphasized in control programs, allowing dairy managers to focus time and finances on more effective components of an M paratuberculosis control program.

A random sample of Wisconsin dairy herds, stratified by herd size, were tested for paratuberculosis by use of an absorbed ELISA procedure. The ELISA was optimized for overall accuracy by means of receiver operating characteristic curve analysis, and had a sensitivity and specificity of 50.9 and 94.9%, respectively. Herd prevalence was analyzed for correlation with responses to a management practices questionnaire completed by the herd owners. One hundred and fifty-eight herds and 4,990 cattle were tested. Of these, 50% of herds and 7.29% of cattle had positive test results. Calculation of true prevalence from the apparent prevalence indicated that 4.79% of cattle and 34% of the Wisconsin dairy herds tested had serologic evidence of paratuberculosis. Among the 54 herds classified as positive on the basis of true prevalence estimation, the mean number of test positive cattle was 20.3%. The geographic distribution of herds with positive results was not uniform. More infected herds were found in the southern and western districts of Wisconsin than in the eastern district. The west-central district had a larger number of infected herds than did other districts. By use of chi 2 analysis, the only management factor found to be significantly associated with herd prevalence was housing of calves after weaning (P = 0.03). Specifically, in herds with higher prevalence, calves were separated after weaning into calf barns and hutches rather than into pens in the cow barn more often than in herds with lower prevalence. This factor was also considered significant by use of logistic regression analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

The frequency of thioguanine-resistant, hypoxanthine phosphoribosyltransferase-deficient lymphocytes in the peripheral blood of human subjects was used to study the genotoxic effects of smoking. Sixty-two nonsmokers and 58 smokers, aged 19 to 45 years with average ages of 30 and 32 years, respectively, and with no other known exposures, were studied using an in vitro assay of the frequency of mutant lymphocyte clones. Analysis of variance explained 68% of the variation in the mutant frequencies. Mutant frequency was dependent upon lymphocyte cloning efficiency, length of smoking history, age, and interactions between these variables. Four nonsmokers and three smokers had high mutant frequencies that were not explained by these variables. Mutant frequencies were inversely related to lymphocyte cloning efficiencies; the effect was twice as great for smokers as for nonsmokers. The time-dependent effect of smoking dominated, with mutant frequency increasing 10%/year of smoking as compared with an independent 1%/year of age. Smoking had a greater effect on young smokers' lymphocytes. Heterogeneity of mutant frequency among both smokers and nonsmokers and its implications for use of lymphocyte mutation assays as biomarkers are discussed.

Commercial laying hens were examined microbiologically at necropsy 31 or 42 weeks after aerosol vaccination with the F strain of Mycoplasma gallisepticum (MG). Mycoplasma isolates were studied in Western blots probed with polyclonal antiserum raised in rabbits to F strain immunogen. The persistence of the vaccine strain was demonstrated by detection of a 75-kilodalton immunoreactive protein, which was present in all MG isolates and thought to be a unique marker of the F strain. Use of PCA-F to probe Western blots allowed simultaneous identification of non-MG isolates, non-F strains of MG, and the F strain of MG.

In a prospective study of 1,046 male medical students, those who later committed suicide showed a heightened sensitivity in stressful situations as assessed by the Habits of Nervous Tension Questionnaire (HNT). Survival analyses specified 2 of the 25 HNT items as the strongest suicide predictors: Irritability (relative risk 5.5; 95% confidence interval 1.76-17.17) and Urinary Frequency (3.3; 1.07-10.32). No other risk factors for suicide emerged from family background measures or individual medical school measures. It appears that types of sensitivity reflect psychological characteristics that are long-term precursors of suicide.

Medical records from 333 cats with diabetes mellitus were studied retrospectively, using epidemiologic methods to determine the incidence of and risk factors for diabetes mellitus in this species. Abstracts were derived, using the Veterinary Medical Data Program with its 17 participating academic institutions in the United States and Canada. A reference population of 135,651 cats was derived from the same hospital population and time span (July 1980 to June 1986). The incidence of diabetes mellitus in cats was determined to be 2.45 cases/1,000 cat-years-of-risk during the 6-year study period. Breed had no detectable effect on risk for diabetes mellitus. In contrast, body weight, age, gender, and neutering had a significant (P less than or equal to 0.01) effect. Body weight of cats was categorized as being less than or greater than or equal to 6.8 kg. The higher body weight, probably indicating obesity, contributed a 2.2-fold increase in risk, even after adjustment for age and gender (adjusted odds ratio). The etiologic fraction for high body weight was 3.8%, suggesting that an estimated 3.8% of cases of diabetes mellitus was attributable to this factor alone. Over 50% of diabetic cats were greater than 10 years old, and the etiologic fraction for age greater than 7 years alone was 73.5%. Age was a significant (P less than 0.001) and the most important single risk factor for development of the disease in cats, with adjusted odds ratios of 8.3 and 14.4 for age 7 to 10 years and greater than 10 years, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

The California Dairy Herd Improvement Association records of 29 California dairies which experienced clinical mycoplasmal mastitis between January 1975 and December 1977 were examined and compared to the records of selected control herds. A 15-fold greater risk of clinical mycoplasmal mastitis was found among large herds as compared to small herds. On average, herds with clinical mycoplasmal mastitis culled 5 % more cows than did control herds (33 % vs 28 %). No difference was found in average milk production. These findings compare closely with the findings of a previous report where infected herds were identified by the presence of pathogenic mycoplasma in bulk tank milk. The similarity of results support the use of frequent bacteriologic culture of bulk tank milk as a routine surveillance strategy for mycoplasmal mastitis in endemic areas. The similarity of results also supports the use of routine clinical diagnostic data in the study of the epidemiology of diseases of veterinary importance.

The effect of vaccination on milk production was evaluated in vaccinated and control cows experimentally challenged in two of four quarters with live Mycoplasma bovis. During the first three weeks after experimental challenge, six of eight unchallenged quarters on vaccinated cows and seven of eight unchallenged quarters on control cows became infected. Most of these quarters secreted normal milk, with negative California Mastitis Test scores and maintained normal milk production throughout most of the study (although some quarters on control cows remained infected). All challenged quarters became infected, had strong California Mastitis Test reactions, and had a drastic (greater than 85%) loss in milk production. Thereafter, four of eight challenged quarters on control cows remained infected, had mostly positive California Mastitis Test scores, produced mostly normal-appearing milk, and recovered some productive capabilities. By the end of the study no M. bovis could be recovered from challenged quarters on vaccinated cows and the milk appeared mostly normal. The California Mastitis Test scores on these quarters, however, remained elevated and milk production remained very low.

In the context of a longitudinal study, we explored factors contributing to midlife career achievement among 108 women physicians. Three groups were formed, based on medical specialty, specialty board certification, and professorial appointment. Using analysis of variance procedures, the career groups were compared on measures obtained during medical school and on marital status, family size, and three health measures in midlife. Of the youthful measures, academic standing, father's socioeconomic status, and early family (specifically father-daughter) relationships were found to be associated with midlife achievement. Furthermore, a clear association was observed between success and good health in midlife. Married women formed the majority in all groups; no differences in family size were found. We conclude that career achievement among women physicians is influenced less by marriage and family size than by motivational and personality factors shaped in early life.

In an ongoing longitudinal study of former medical students, now physicians in midlife, the prevalence of cancer among relatives of 46 probands affected by cancer has been compared with that of two control groups of cancer-free probands. Overall, the prevalence of cancer among relatives of the three groups of probands was similar. However, male probands with cancer appeared to have a greater prevalence of cancer among their relatives than did male cancer-free probands, while the corresponding comparisons for the smaller groups of female probands showed the opposite tendency. Among the relatives of cancer probands of either sex, there was evidence of familial clustering of cancer. Where two relatives in a proband's family had the same type of cancer, the two relatives were usually on the same side (paternal or maternal) of the family. Ages at onset of cancer and types of cancer in relatives of the cancer and cancer-free probands did not reveal any significant differences.

Patterns of habits of nervous tension (HNT) recorded by medical students who later developed cancer, coronary occlusion, hypertension, or mental illness, or who committed suicide, were compared with those of students who remained healthy 15 to 30 years later. Data came from the 25-item HNT Questionnaire previously reported. Unpaired t tests and two-group discriminant function analyses were the chief statistical methods used. Compared with those of the healthy group, the overall HNT patterns were significantly different for the cancer, coronary occlusion, mental illness and suicide groups. The overall pattern for the hypertension group did not reach significance. It therefore appears that youthful reactions to stress as self-reported in a checklist of habits of nervous tension reflect individual psychobiological differences that are linked with future health or disease.

Four cows were vaccinated with Mycoplasma bovis five times at two week intervals: three times subcutaneously in Freund's complete adjuvant, and two times with M. bovis alone in two of four quarters by intramammary infusion. The effect of vaccination on the immune response was evaluated in the serum and whey of the four vaccinated and control (placebo) cows experimentally challenged in two of four quarters with live M. bovis. Vaccination resulted in markedly increased M. bovis-specific, serum IgM, IgG and IgG2, but not IgA, reactivity. Challenge exposure with live M. bovis by intramammary infusion resulted in high specific serum IgM, IgG1 and IgG2 reactivity and a noticeable IgA response in both vaccinated and control cows. Whey from quarters on vaccinated cows had elevated, specific IgG1 reactivity at the time of challenge but no other differences were observed. Challenge exposure with live M. Bovis resulted in high antibody levels of all isotypes in quarters which were challenged, but highly elevated reactivities in unchallenged quarters occurred only with IgG1 and IgG2. These results indicate that vaccination elevated M. bovis-specific IgG1 but not other immunoglobulin reactivity in quarters on vaccinated cows, and that live organisms are necessary to elicit a local, specific IgA response.

Enzyme-linked immunosorbent assay, using monoclonal antibodies, was used to detect Mycoplasma bovis in milk samples from a dairy experiencing an epizootic of mastitis. This method was specific (100%) for M bovis. Broth enrichment increased the sensitivity from 65% to 86%, compared with standard culture methods.

Most bovine mastitis due to mycoplasmas is initiated by passage of mycoplasmas through the teat canal into the teat and gland cisterns. Within a few days, mycoplasma numbers increase to as much as 10(6) or 10(8), and the cows react with a strong inflammatory response. Alveolar epithelium undergoes degenerative changes and exudate replaces milk secretion. The interstitium between alveoli is invaded with lymphocytes, macrophages, plasma cells and fibroblasts. The extent and duration of these changes vary greatly. In milder cases, they may be reversed within days or weeks with a return to normal or reduced milk production. Often, destruction and atrophy of alveoli are complete with extensive fibrosis throughout the udder. Milk ducts may undergo invasive and obliterative fibrosis. Cell-mediated responses are suppressed, while hypersensitivity is suspected of enhancing the adverse responses. Immunity in cows that recover is variable and of limited duration.

We studied 22 twin pairs in which one or both twins had dementia of the Alzheimer type (DAT). In four twins, diagnosis was confirmed by autopsy. Seven monozygotic (MZ) pairs were concordant for DAT; 10 MZ pairs were discordant. Two dizygotic (DZ) pairs were concordant for DAT, and 3 DZ pairs were discordant. The current concordance rate was 41% for MZ twins and 40% for DZ twins. The study supports the belief that, etiologically, DAT cannot be entirely accounted for by a single autosomal dominant gene. The data also suggest that in certain genetic circumstances, disease expression may be delayed in females.

An enzyme-linked immunosorbent assay (ELISA) was adapted to detect Mycoplasma californicum-specific antibodies in bovine serum. Cross-reactive antibody was found in the M californicum-positive reference serum when assayed against each of 7 solid-phase antigens of heterologous mycoplasma species. Cross-reactivity was further demonstrated by inhibition of ELISA reactivity to M californicum solid-phase antigen by incubation of sera with antigen suspensions of each heterologous species. Incubation of test sera with a cross-reacting antigen mixture containing equal proportions of the 7 cross-reactive mycoplasmas was used to minimize cross-reactivity in the M californicum-specific ELISA. Specificity of antibody reactivity to M californicum, as measured by ELISA, was determined by enzyme-linked immunosorbance inhibition, in which sera were incubated with M californicum antigen suspensions before determining ELISA reactivity to M californicum solid-phase antigen. Seropositive and suspect sera (n = 55) were obtained from 3 dairies that had bacteriologically verified epizootics of M californicum mastitis. The percentage of inhibition demonstrated in enzyme-linked immunosorbance inhibition was determined for each serum. Inhibition percentages below the 15th percentile (61% inhibition) of this distribution were classified as nonspecific.

This study characterized the immune responses in four vaccinated and four control cows in response to vaccination and experimental intramammary inoculation with Mycoplasma bovis. Specific antibody responses occurred in serum and milk in response to vaccination and experimental infection. Lymphocytes from peripheral blood, but not from the mammary gland of vaccinated cows had increased responsiveness to mitogens. No lymphocytes tested were responsive to M. bovis antigen. Both vaccination and experimental infection resulted in skin test reactivity. These results imply that vaccination results in immune responses which may alter the course of experimental M. bovis mastitis, but may contribute to cellular inflammation.

In a study of the circulatory characteristics of 78 male medical students who later developed hypertension, no relationship was found between response to the cold pressor test and subsequent hypertension. Casual and resting blood pressure and heart rate measurements were all significantly higher in medical school in subjects who later developed hypertension than in two groups of control subjects who have remained in good health. Of the circulatory characteristics measured, a casual systolic pressure value greater than or equal to 125 mmHg in medical school was found to be the most predictive of future hypertension. A significant positive association was also found between parental hypertension and the presence of hypertension in the subject. When the two risk factors--higher casual systolic pressure in youth and parental hypertension--occur together, their predictive power is shown by the odds ratio of 12.65 (x2 = 12.87, 1 d.f., p less than .001).

The effect of vaccination on mycoplasmal infection and the cellular inflammatory response was evaluated in 4 vaccinated and 4 control cows experimentally challenged in 2 of 4 quarters with live Mycoplasma bovis. In unchallenged quarters during the first three weeks after experimental challenge exposure, 6 of 8 quarters on control cows, and 7 of 8 quarters on vaccinated cows became infected with low numbers (10(2)-10(4) cfu/ml) of M bovis. During the same period all challenge-infused quarters on both control and vaccinated animals became infected with high numbers (10(9) cfu/ml) of M bovis. Thereafter, all quarters on vaccinated cows became culture-negative for M bovis, while 2 of 8 unchallenged quarters, and 4 of 8 challenged quarters on 3 of 4 control cows remained infected. A cellular inflammatory response as measured by the California Mastitis Test accompanied the experimental infection in proportion to the infection level except in challenged quarters on vaccinated cows after the first three weeks post challenge in which the cellular inflammatory response remained high despite the advent of negative M bovis culture results. This study indicates that the course of experimental M bovis mastitis can be affected by vaccination, and that vaccination results in an adverse cellular inflammatory response in challenged quarters.

In the cohort of 1337 former Johns Hopkins medical students from the classes of 1948 through 1964, there were 1248 graduates and 89 nongraduates. In follow-up studies of this cohort, 49 subjects, 3.1% of the graduates and 11.2% of the nongraduates, have been found to have died prematurely. Incipient mental illness and emotional disturbance appear to have contributed substantially to academic failure, poor performance during and after medical school, and premature death. These findings underscore the need for learning to identify and help medical students who are especially vulnerable to stress. Such insights would contribute to the prevention of premature disease and death, not only from mental illness but from other disorders.

The DNA alkaline elution technique provides a sensitive assay for the effects of DNA-damaging drugs in mammalian cells. We have adapted this method to permit measurements of effects on DNA in solid tumors. Human colon carcinoma xenografts in nude mice were treated with a single i.p. injection of 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea, and the effects on the DNA were followed for 19 hr. Drug doses in the pharmacological range produced significant reductions in DNA alkaline elution rates in assays in which X-ray was used to introduce a standard frequency of single-strand breaks. These changes in alkaline elution rate were attribute to the production of both DNA interstrand and DNA-protein cross-links, which were distinguished from each other on the basis of the extent to which the effect on elution could be reversed by proteinase K. Crosslinking increased for about 8 hr after treatment with little change thereafter up to 19 hr. A drug-resistant tumor line exhibited substantially less cross-linking than did a drug-sensitive line at all time points examined.