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Biomedical subjects

A Johnson

Publications and source records attributed to A Johnson.

At least 541 records · Page 30Linked to original sources

Complotype genetic loci segregate more frequently with HLA-DR than with HLA-B.

The loci for BF, C2, C4A, and C4B are very closely linked to each other so that alleles of these plasma protein markers occur in populations in linkage disequilibrium and are inherited as single genetic units called complotypes. These complotypes are coded by a DNA region of the short arm of chromosome 6 embracing approximately 100 kilobases, which serve as a marker of the major histocompatibility complex. We have studied the complotypes of nine families with known HLA-B/DR crossovers. In seven families, the complotypes were inherited with HLA-DR, including in one family with a double recombination. The haplotype HLA-A28, Cw1, B27, FC3, 20, DR4 of JTr resulted from two recombinations between HLA-A2, Cw1, B27, SC42, DR7 and HLA-A28, Cwx or Cw1, B37, FC3, 20, DR4. In the remaining two families (Ro and Lo) the complotypes were inherited with HLA-B. The haplotype A2, Cw5, Bw44, SC30, DR3 of StLo resulted from paternal recombination between the haplotypes A2, Cw5, Bw44, SC30, DR4 and A24, B8, SC01, DR3, and the haplotype A24, Cw4, Bw35, SC31, DR3 of NaRo resulted from maternal recombination between A24, Cw4, Bw35, SC31, DR4 and A26, Bw41, FC31, DR3. Our data suggest that the complotype region maps closer to HLA-D than to HLA-B.

Complement C2↗

A parallel study of enalapril and captopril and 1 year of experience with enalapril treatment in moderate-to-severe essential hypertension.

Angiotensin converting enzyme (ACE) inhibitors, enalapril (5 to 20 mg twice daily) or captopril (25 to 100 mg thrice daily) and matching ACE inhibitor placebos were given to 32 moderate-to-severe essential hypertension patients who were already on 50 mg hydrochlorothiazide daily. Alpha-methyldopa (250 to 500 mg twice daily) was given to 16 patients following 6 weeks of ACE inhibitor therapy. Both enalapril and captopril significantly (p less than 0.05) lowered the supine and upright blood pressures (BPs) (acutely and long-term) without significant reflex heart rate changes. The BPs of enalapril patients were, however, significantly lower (supine diastolic p less than 0.03, supine systolic p less than 0.05, and upright diastolic p less than 0.04) than those of captopril patients when compared by repeated measures of analysis of variance. Eleven enalapril patients have been followed for 1 year with continued BP control. Skin rash occurred in one captopril patient and reversible renal insufficiency developed in two enalapril patients during the first 16 weeks. It is concluded that (although both ACE inhibitors lowered BP, enalapril was more effective than captopril and twice-daily enalapril was well tolerated during 52 weeks of treatment.

Blood Pressure↗

Changes in total RNA, polyadenylated RNA, and actin mRNA during meiotic maturation of mouse oocytes.

The total RNA content of mouse oocytes, as measured by ethidium bromide fluorescence, was found to decrease by 19% during meiotic maturation (ovulated eggs contain 19% less RNA than full-grown oocytes). Consistent with these results, prelabeled stable RNA of full-grown oocytes decreased by about 20% during in vitro maturation. Polyadenylated RNA represented 19% of total prelabeled RNA in full-grown oocytes and 10% in oocytes matured in vitro, confirming previous results on in vivo prepared material. To distinguish between deadenylation and degradation for one mRNA, the amount and state of adenylation of actin mRNA was examined using Northern blots of oocyte RNA probed with a nick-translated beta-actin cloned chicken cDNA. The results showed that the amount of actin mRNA remained similar during maturation, but its molecular weight decreased slightly. Experiments in which RNA was treated with oligo(dT) and RNase H demonstrated that the actin mRNA was deadenylated during maturation, when actin synthesis is known to decline. These results indicate that the previously defined loss of bulk RNA and changes in the state of adenylation of mRNA during the first 11/2 days of embryogenesis actually begin during the 12 hr of meiotic maturation preceding fertilization.

Actins↗

Behçet syndrome.

Behcet syndrome, a multisystem disorder characterized by ocular, mucocutaneous, articular, vascular, gastrointestinal, and neurologic abnormalities, is described in six pediatric patients. The patients ranged in age from 2 months to 11 years at time of onset. Several years were usually required before additional manifestations of the disease occurred. Aphthous ulceration was present in all six patients, arthritis in three, erythema nodosum in four, sterile cellulitis in three, gastrointestinal manifestations in five, neurologic manifestations in two, and genital or perianal ulcerations in three; ocular involvement was present in only one. There were no diagnostic laboratory studies, and, as in the adult population, no cause for Behçet syndrome was found. Patients had a variable response to corticosteroid therapy. Two patients who had significant morbidity and who responded poorly to corticosteroid therapy also received chlorambucil therapy, which appeared to provide improved control of signs and symptoms. Based on the prolonged interval between onset and the appearance of complete manifestations, Behcet syndrome may be more common in children than previously reported.

Arthritis↗

Flow cytometric light chain analysis of peripheral blood lymphocytes in patients with non-Hodgkin's lymphoma.

Peripheral blood lymphocytes from 96 patients with non-Hodgkin's lymphoma were studied, either at primary staging, during treatment or in follow up. The amount of surface immunoglobulin light chain per cell was determined by direct immunofluorescence staining analysed by flow cytometry. Discrepancy between kappa and lambda fluorescence profiles in the sample was considered to indicate the presence of monoclonal cells i.e., circulating lymphoma cells. The results were correlated with routine haematological findings, histopathology of the lymphoma and tumour burden. Using routine haematological methods leukaemic spread was evident in 24% of the patients in our study. Using kappa/lambda distribution analysis evidence of circulating lymphoma cells was found in an additional 27%. As expected, the major diagnostic gain was in the low grade malignant group, where 30% of the patients with normal peripheral blood according to standard procedures showed evidence of circulating lymphoma cells in the kappa/lambda distribution analysis. The corresponding gain in the high grade malignant group was 19%. In patients with active disease but without morphological evidence of leukaemia, 37% showed abnormal kappa/lambda distributions. In patients in complete remission the corresponding figure was 18%. The clinical significance of small numbers of circulating lymphoma cells is not yet understood, but a possible outlook is to use kappa/lambda distribution analysis to increase staging precision and in the early detection of relapse.

Flow Cytometry↗

A study of serum antibody activity in workers with occupational exposure to diphenylmethane diisocyanate.

The prevalence of sensitization was studied in a group of 76 foundry workers with occupational exposure to diphenylmethane diisocyanate (MDI). Ten workers had clinical evidence of asthma, 40 had non-asthmatic respiratory symptoms, and 26 were asymptomatic. Specific IgE antibodies to MDI were found in two workers (2.6%) and specific IgG antibodies, in five workers (6.6%). The prevalence of IgE and IgG antibodies was higher in the 10 subjects with asthma than in the non-asthmatic group. The prevalence of anti-paratolyl-monoisocyanate antibodies was not significantly different from that of anti-MDI antibodies, and both haptenic determinants displayed a high degree of cross-reactivity in the RAST inhibition test. The role of humoral immunological mechanisms in MDI-induced asthma is unclear in view of the rather low prevalence of these serum antibodies in this group of workers.

Antibodies↗

Psychological, nutritional and physical status of olympic road cyclists.

Six members of the Irish Olympic Road Cycling Squad underwent a comprehensive medical, nutritional, psychological and biochemical assessment in January 1983. They were given specific medical and dietary recommendations and were reassessed in January 1984 after a period spanning the competitive racing season. The cyclists' diets at both sessions were comparable and generally conformed with recommended daily intakes. Supplementary ingestion was unnecessary to attain recommended daily intakes of vitamins. Serum levels of HDL-cholesterol increased and triglyceride decreased during the period of the study. The squad had characteristics indicating traits of self-sufficiency, toughness and practical mindedness. At the second assessment there was evidence of heightened ambition and competitiveness and an improvement in mood states with reduced ratings for confusion and tension.

Adult↗

Respiratory abnormalities among workers in an iron and steel foundry.

A study of the health of 78 workers in an iron and steel foundry in Vancouver, British Columbia, was carried out and the results compared with those found in 372 railway repair yard workers who were not significantly exposed to air contaminants at work. The foundry workers were exposed to PepSet, which consists of diphenyl methane diisocyanate (MDI) and phenol formaldehyde and their decomposition products as well as to silica containing particulates. A questionnaire was administered by trained interviewers, and chest radiography, allergy skin tests, pulmonary function tests, and methacholine inhalation tests were carried out as well as measurement levels of dust and MDI. Compared with the controls, the foundry workers had more respiratory symptoms and a significantly lower mean FEV1 and FEF25-75% after adjustments had been made for differences in age, height, and smoking habit. Three workers (4.8%) had radiographic evidence of pneumoconiosis and 12 (18.2%) had asthma defined as presence of bronchial hyperreactivity, cough, and additional respiratory symptoms such as wheeze, chest tightness, or breathlessness. Sensitisation to MDI is probably the cause of asthma in these workers.

Adult↗

Pulmonary transvascular fluid and protein exchange after thrombin-induced microembolism. Differential effects of cyclooxygenase inhibitors.

We studied the effects of cyclooxygenase inhibitors (indomethacin, meclofenamate, and ibuprofen) on the increases in pulmonary transvascular fluid and protein fluxes that occur after thrombin-induced intravascular coagulation. Each drug-pretreated group was compared with a control group receiving the same amount of alpha-thrombin (alpha-T), the native enzyme used to induce intravascular coagulation. Studies were made in the following groups of anesthetized sheep prepared with lung lymph fistulas: low dose-indomethacin (bolus injection of 5 mg/kg and infusion of 3 mg/kg/h, high-dose indomethacin (bolus injection of 20 mg/kg and infusion of 12 mg/kg/h), meclofenamate (bolus injection of 5 mg/kg and infusion of 3 mg/kg/h), low-dose ibuprofen (bolus of 6.2 mg/kg and infusion of 3.1 mg/kg/h), and high-dose ibuprofen (bolus of 25 mg/kg and infusion of 12.5 mg/kg/h). The concentrations of the arachidonic acid metabolites, thromboxane B2 and 6-keto-prostaglandin F1 alpha, did not increase in the treated groups. Infusion of alpha-T increased the mean pulmonary arterial pressure and pulmonary vascular resistance in the control and treated groups, but to higher levels in the indomethacin and meclofenamate groups. In the control group, alpha-T increased pulmonary lymph flow (Qlym) and lymph protein clearance (Qlym X lymph/plasma protein concentration ratio), a measure of lung vascular permeability. In the indomethacin, meclofenamate, and low-dose ibuprofen groups, alpha-T resulted in delayed increases in Qlym and lymph protein clearance, but these lymph parameters attained the same levels as the control groups. However, the high-dose of ibuprofen significantly attenuated the increases in Qlym and lymph protein clearance after alpha-T.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Histopathology of the temporal bone in osteogenesis imperfecta congenita: a report of 5 cases.

The histopathologic findings in 8 temporal bones from 5 patients with osteogenesis imperfecta congenita are reported. The otic capsule, bony walls of middle ear, and ossicles showed evidence of both deficient and abnormal ossification. Microfractures were found in the otic capsule and in the anterior process and handle of the malleus, in addition to their common location at the crura of the stapes. The cochlear and vestibular end-organs appeared normal. Pathologic changes compatible with otosclerosis were not seen. The possible implication of these changes on hearing and balance is discussed.

Ear, Inner↗

Carbamoylation of glutathione reductase and changes in cellular and chromosome morphology in a rat cell line resistant to nitrogen mustards but collaterally sensitive to nitrosoureas.

A Walker 256 rat carcinoma cell line (WR) with acquired resistance to nitrogen mustards has been found to lack cross-resistance to nitrosoureas. Although total cellular glutathione pools were similar in the parent (WS) and resistant cell lines (WS, 2.5 X 10(-6); WR, 2.0 X 10(-6) mol/mg protein), glutathione reductase activity was 3.98 in WR compared to 8.67 nmol reduced nicotinamide adenine dinucleotide phosphate oxidized per microgram protein per min in WS cells. Treatment of cells with a carbamoylating nitrosourea, N,N'-bis(trans-4-hydroxycyclohexyl)-N'-nitrosourea, produced a dose-dependent inhibition of glutathione reductase and depletion of thiols in both cell lines. The drug caused no direct DNA strand breakage, but a differential mitotic spindle-chromosome stain showed that spindle formation was inhibited in WR cells at N,N'-bis(trans-4-hydroxycyclohexyl)-N'-nitrosourea concentrations of greater than 50 microM. In WS cells, mitotic figures were still visible at 100 microM. Chromosomal damage was expressed in both cell lines at concentrations of 25 microM. The number and extent of these aberrations were greater in WR than WS. Observed karyotypic abnormalities included polyploidy, chromosome decondensation, and endoreduplication. In interphase cells, transmission electron microscopy showed that the most prevalent drug-induced lesions included (a) disappearance of plasma membrane filopodia, (b) appearance of membrane blebbing, and (c) development of irregular crescent-shaped nuclei. These morphological and cytogenetic changes correlate with cytotoxic responses of these cell lines to N,N'-bis(trans-4-hydroxycyclohexyl)-N'-nitrosourea and would be consistent with drug-induced inhibition of glutathione reductase.

Animals↗

Clinical and histological evidence for the presence of the vomeronasal (Jacobson's) organ in adult humans.

One hundred adult humans were examined specifically for the presence of the opening of the vomeronasal organ (VNO) on the antero-inferior part of the nasal septum. This was found in 39% of patients. Twenty-seven human septums were removed at post mortem, examined macroscopically, sectioned coronally and examined microscopically. In 70% of these specimens, vomeronasal structures were identified. Histological examination failed to reveal any evidence that these organs may be functional. The human embryology and comparative anatomy of the VNO are reviewed. The physiological function in different vertebrates is also considered, and the significance of the findings in this study is assessed in the light of this evidence.

Adolescent↗

Cell shape in the migratory epidermis of the external auditory canal.

The shapes adopted by cells migrating within tissues and in cell cultures are related to both the direction and mechanism of migration. The skin on the tympanic membrane and deep external auditory canal is unique in its ability to migrate from the tympanic membrane to the junction between the deep and superficial parts of the ear canal, where it desquamates. Observations on 24 surface preparations of skin, obtained from 17 human temporal bones, revealed that the basal cells of the epidermis were spindle-shaped, and their long axes were aligned in the direction of migration. This cellular asymmetry and orientation did not persist in the more superficial layers of the epidermis. These findings are important in the consideration of the mechanism of migration, and the level within the epidermis at which it occurs.

Adult↗

An ultrastructural study of the skin of the tympanic membrane and external ear canal of the guinea pig.

The ultrastructure of the skin covering the tympanic membrane and external ear canal has been studied in eight guinea pigs, to identify any features which could be related to the rapid movement of the epidermal surface at this site. Migratory epidermis showed evidence of reduced intercellular adhesion in the deeper layers and reduced differentiation in all layers. Differentiation was more evident in cell ridges found at the junctional zone between migratory and non-migratory skin. The findings agree with those of previous authors, and indicate that migration is most likely to occur within the deeper layers of the epidermis.

Animals↗

Isolation, characterization, and propagation in vitro of human glomerular endothelial cells.

Human glomerular endothelial cells have been isolated, cloned, and characterized. They appeared as the first outgrowth from human glomeruli in the presence of platelet-derived growth factor, which was also a requirement for continuous growth. By phase microscopy they appeared as monolayers of polygonal cells. Von Willebrand's factor (VWF) was detected in the cytoplasm of all clones. Their intermediate filaments differed antigenically from that present in human umbilical vein endothelial cells. Like other endothelial cells, they demonstrated high levels of membrane-associated angiotensin-converting enzyme (ACE).

Cell Division↗

Prophylaxis of fever and infection in adult cancer patients. A placebo-controlled trial of oral trimethoprim-sulfamethoxazole plus erythromycin.

Oral trimethoprim-sulfamethoxazole (Bactrim) plus erythromycin (TMZ-E) was tested versus placebo (P) as prophylaxis for bacterial infection in a randomized, double-blind trial in adult cancer patients receiving cytotoxic chemotherapy expected to result in significant neutropenia. The incidence of adverse reactions attributable to TMZ and/or E was higher in drug-treated episodes (18 of 28 vs 3 of 29 for P, P less than 0.0005) resulting in poorer compliance. The incidence of fever was not significantly different between episodes treated with TMZ-E (18/27) and those treated with P (17/29), nor was there a significant difference in the median interval between the onset of neutropenia and the onset of fever. However, 14 of 18 fevers in TMZ-E recipients were without a documented infectious source compared with only 6 of 17 in P recipients (P less than 0.05). The same patterns were apparent even when episodes in which compliance with the regimen was either excellent or good were considered separately. There was no significant difference in the number of deaths from infection between TMZ-E and P recipients (3/27 vs 1/29). It is concluded that TMZ-E prophylaxis is of no practical benefit, may mask the cause of infection in febrile neutropenic cancer patients, and is associated with substantial toxicity.

Adolescent↗