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Biomedical subjects

E S Johnson

Publications and source records attributed to E S Johnson.

At least 73 records · Page 4Linked to original sources

Bias on withdrawing lost subjects from the analysis at the time of loss, in cohort mortality studies, and in follow-up methods.

Cohort mortality studies may differ from morbidity and other follow-up studies in that, in many of the methods of follow-up employed, the identification or follow-up process and the process of determination of outcome (death) are essentially the same. Furthermore, some of the methods may involve preferential identification of deaths over live persons, or vice versa. This latter area of difference is particularly problematic in situations in which the comparison group (the general population) has not been subjected to tracing, and in which certain persons who are being traced are not covered by the universe defined by the follow-up method. Because of these peculiarities, it is shown that, during the analysis, the usual practice of withdrawing persons lost to follow-up at the time of loss can lead to seriously biased results when follow-up rate is not very high.

Bias↗

Novel astrocytic protein in multiple sclerosis plaques.

Monoclonal antibody J1-31 (MAb J1-31, isotype IgG 2b) was raised against crude homogenate of brain tissue from a multiple sclerosis (MS) patient (autopsy sample; Malhotra et al.: Microbios Letters 26:151-157, 1984). In human brain, MAb J1-31 recognizes an intracellular protein antigen (J1-31 antigen), which bands at approximately 30,000 daltons under reducing conditions for sodium dodecyl sulfate gel electrophoresis (Singh et al.: Bioscience Reports 6:73-79, 1986). By immunofluorescence microscopy, MAb J1-31 stains those cells that are also stained by antiserum to glial fibrillary acidic protein (GFAP), namely astrocytes, retinal Müller cells, and tanycytes in the ependyma (Predy et al.: Bioscience Reports 7:491-502, 1987). In addition, MAb J1-31 stains ciliated ependymal cells that do not express GFAP. Using a model system for gliosis (laceration-type injury of rat spinal cord), we were able to show that astrocytes responding to central nervous system injury exhibit greatly enhanced staining for J1-31 antigen (Predy et al.: Journal of Neuroscience Research 19:397-404, 1988; Predy and Malhotra: Brain Research Bulletin in press, 1989). In this article, we demonstrate that immunofluorescence staining owing to MAb J1-31 is greatly enhanced in MS plaques, as compared to adjacent "apparently normal" white matter. (This is consistent with previous results as MS plaques characteristically show an astroglial response [reactive gliosis] leading to the formation of a glial scar [McKhann: Annual Review of Neuroscience 5:219-239, 1982].) In addition, we present further evidence that J1-31 antigen is distinct from GFAP, although these two proteins may be associated spatially with one another.

Animals↗

Active reduced-size hexapeptide analogues of luteinizing hormone-releasing hormone.

A series of reduced-size hexapeptide analogues of LH-RH were synthesized that contain the residues corresponding to amino acid positions 4-9 and are linked to various carboxylic acids in place of residue 3. These compounds were tested in vitro in the rat pituitary receptor binding and LH release assays. A wide range of binding affinities was obtained up to and exceeding that of LH-RH. Both agonists and antagonists were obtained. From the SAR studies, it appears that a very precise size, length, and shape of the substituent at position 3 is required to achieve agonist activity, whereas the structural requirements for antagonist activity appear to be much less stringent. Depending on the nature of the substituent at positions 6 and 4, the biological response switches from antagonist to agonist or vice versa. The results suggest that conformational changes at position 6 or 4 feed back to the substituent at position 3, which induces the change from agonist to antagonist. The most potent compounds in the series were tested in vivo and found to be active.

Animals↗

Mortality among nonwhite men in the meat industry.

Mortality among 5145 nonwhite men in a local meatcutters' union in Baltimore who were observed between July 1949 and December 1980, was compared with that of nonwhite men of the United States general population, through the estimation of standardized mortality ratios. The study population had potential for exposure to viruses that cause leukemia and lymphoma in cattle and chickens, and other harmful agents. Statistically significant standardized mortality ratios of 2.1 for lung cancer and 3.1 for cancer of the esophagus were observed among workers in abattoirs and meatpacking plants, respectively. The results obtained are consistent with findings for white male and female members of the same union, and with other published data.

Abattoirs↗

A feline model for experimental studies of peritumor brain edema.

An in vivo model for correlative imaging studies of intracerebral glial tumors and peritumor brain edema has been developed. Adult male and female cats implanted with 1 x 10(6) or 5 x 10(5) 9L glioma cells had parietal tumors of 4 mm or greater in diameter and showed signs of increased intracranial pressure 13.7 +/- 1.9 days or 19.2 +/- 1.3 days after implantation. No immunosuppression was required and the success rate for tumor growth after implantation was 88%. Histologically, the tumor resembles a malignant astrocytoma. The tumor contained the highest water content (85.94%); peritumor white matter was more edematous (73.01%) than white matter in the contralateral hemisphere (69.04%), sham-operated (69.41%) and control brain (68.76%). There was no correlation between the size of the tumor and water content in tumor or white matter. Increased tissue albumin in peritumor white matter indicated blood-brain barrier dysfunction within the tumor and confirmed the vasogenic origin of the edema. Proton magnetic resonance imaging provided good spatial and contrast resolution with increased signal intensity in edematous white matter, decreasing with distance from the tumor. The large brain of this animal model allows the use of serial imaging and regional correlative biochemical measurements in a single animal. Other advantages of this model are its predictability and the short time required to produce tumors with marked peritumor edema.

Animals↗

Nimodipine in migraine prophylaxis.

Nimodipine is a compound that is thought to block the influx of calcium through channels in vascular smooth muscle. This paper describes a double-blind parallel-group comparison of 40 mg nimodipine three times a day and placebo. Sixty-eight patients received treatment after a run-in period of 2 months, and of these, 57 completed 8 weeks or more of the trial. All but five of these completed the full 6-month trial. The nimodipine and placebo groups showed no significant differences in the frequency of attacks, severity or duration of headache, or gastrointestinal or other symptoms.

Adolescent↗

Neurofilamentous abnormalities in motor neurons in spontaneously occurring animal disorders.

Cytoskeletal proteins have a characteristic distribution within neurons when immunocytochemical techniques are used on conventional paraffin sections. For example, phosphorylated neurofilaments are located within axons but are not normally present in the majority of perikarya of the central nervous system. This pattern can be altered in disease, and neurofilaments that accumulate within perikarya can be phosphorylated inappropriately. To determine whether retained neurofilaments were phosphorylated inappropriately, we used immunocytochemical techniques to examine several diseases in animals in which neurofilaments accumulate within neuronal perikarya. Our investigations of diseases with disparate etiologies show that, whenever neurofilaments are retained within the neuronal perikarya, they are phosphorylated. These results suggest that phosphorylation of neurofilaments in an inappropriate location, i.e. perikarya, may be a nonspecific disease-related response of neurons that can be initiated by a variety of cellular injuries.

Animal Diseases↗

Amdinocillin: interaction with other beta-lactam antibiotics for gram-negative bacteria.

Amdinocillin was studied alone and in combination with three other beta-lactam antibiotics (aztreonam, cefoperazone, and ceftriaxone) for activity against gram-negative bacilli. These antibiotic combinations failed to show synergy by the checker-board double-dilution test or by killing kinetic studies. However, amdinocillin did show additive killing action when combined with the other beta-lactam antibiotics studied. Amdinocillin failed to induce or inhibit beta-lactamase production in species of Enterobacteriaceae, but with Pseudomonas aeruginosa, beta-lactamase production was induced. It is concluded that the activity of amdinocillin alone or in combination with another beta-lactam antibiotic should not be more effective in the treatment of infections by gram-negative bacilli than just using the beta-lactam antibiotic alone at a higher dose.

Amdinocillin↗

Chromosomal aberrations and sister chromatid exchanges in lymphocytes and urine mutagenicity of migraine patients: a comparison of chronic feverfew users and matched non-users.

1. Thirty migraine patients who had taken the leaves, tablets or capsules of feverfew daily for more than 11 consecutive months were compared to 30 feverfew non-user migraine patients who had been individually age- and sex-matched. 2. The frequency of chromosomal aberrations and sister chromatid exchanges (SCE) were determined from lymphocyte cultures established from blood samples taken over a period of several months. Matched pairs were sampled on the same date for two-thirds of the cases, and the greatest difference in sampling time of the remainder was 20 days. Also, the mutagenicity of urine samples from 10 feverfew user migraine patients was compared to that from 10 matched non-user migraine patients using the Ames Salmonella mutagenicity test system. Paired samples were given on the same date. 3. The mean frequency of chromosomal aberrations in the feverfew user group was lower than that in the non-user group both in terms of cells with breaks (2.13% vs 2.76%) and in terms of cells with all aberrations (4.34% vs 5.11%). However, this difference was small and not significant. 4. The mean frequency of SCE in the feverfew exposed group was lower than that in the control group (8.78 vs 8.80 SCE/cell), but, this difference was not significant as determined by factorial analysis of variance (P = 0.897). There was a highly significant variance between the frequencies of SCE in the matched pairs of migraine patients but this was not related to age, sex or feverfew exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Treatment of subjects lost to follow-up in the analysis of mortality studies.

In the analysis of retrospective cohort mortality studies, persons lost to follow-up are either withdrawn at the time of loss or are assumed to be alive at the end of the study. It has been advocated that the former method does not give a biased estimate of expected mortality in this group, and is therefore the preferred method. In this paper, it is argued that this approach is not always the best one, and that in certain situations, depending on the method of follow-up used, assuming that persons lost to follow-up are alive may give more accurate results than withdrawing them at the time of loss. Data from a recent study are used for illustration.

Data Interpretation, Statistical↗

Review of the experience with nabumetone in clinical trials outside of the United States.

Nabumetone, a new nonsteroidal anti-inflammatory agent, has undergone extensive clinical evaluation in a number of countries. There have been over 4,000 patients treated, including nearly 1,000 elderly patients and over 1,100 patients who have received nabumetone for more than one year. A total of 2,400 of these patients with a variety of rheumatic disorders have been investigated in studies outside of the United States. Studies in rheumatoid arthritis and osteoarthritis have demonstrated that nabumetone is effective in the treatment of these conditions and that this effectiveness is maintained in many patients in the long term. Nabumetone appears to be well tolerated and there is no evidence from patients receiving treatment for 12 months or more of any clinically significant adverse effects on hematologic or biochemical parameters. Thus, these studies support the use of nabumetone in the treatment of rheumatoid arthritis and osteoarthritis.

Aged↗

Developmental patterns of spatial ability: an early sex difference.

Over 1,800 public school students (grades K-12, ages 6-18) took a battery of 7 spatial tests tailored to their respective developmental levels. Analyses of resulting data indicate that it is feasible to measure spatial ability throughout this developmental range with modified versions of adult paper-and-pencil tests, that a male advantage in spatial performance appears reliably by age 10, and that the magnitude of the advantage remains constant through age 18. Analysis of covariance suggests that an early female precocity in language skills may mask a male advantage in spatial ability during the primary school years. There is no indication of a sex difference in kindergarten children.

Adolescent↗

Mortality from non-malignant diseases among women in the meat industry.

A mortality follow up study was conducted among 7261 white female members in a local meatcutter's union in Baltimore, Maryland, between July 1949 and December 1980. The group was divided into four main job categories within the meat industry and a control group of non-meat workers belonging to the same union. Mortality in each of these subgroups was compared with that of white women in the United States general population through the determination of cause specific standardised mortality ratios. No increased risk of death from non-malignant causes was observed in any job category within the meat industry. Some caution should, however, be exercised in interpretating this finding, as few workers in chicken slaughtering plants died.

Female↗