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Biomedical subjects

N A Johnson

Publications and source records attributed to N A Johnson.

At least 55 records · Page 3Linked to original sources

An empirical test of the meiotic drive models of hybrid sterility: sex-ratio data from hybrids between Drosophila simulans and Drosophila sechellia.

Recently, there has been much discussion regarding the hypothesis that divergence of meiotic drive systems in isolated populations can generate the patterns of reproductive isolation observed in animal hybridizations. One prediction from this hypothesis is that the sex ratio of hybrids with heterospecific sex chromosomes should greatly deviate from the Mendelian expectation of 50% female. From sex-ratio data in our Drosophila hybridization studies, we find no such deviation: the sex ratio of offspring of males with introgressed heterospecific Y chromosomes with various autosomal backgrounds does not differ from that of the pure species. We also discuss other aspects of the current meiotic drive models.

Animals↗

T cell receptor gene segment usage in a panel of hen-egg white lysozyme specific, I-Ak-restricted T helper hybridomas.

We have studied the relationship between MHC-restricted, Ag-specific recognition and TCR structure in a panel of seven Th-hybridomas specific for the foreign protein Ag, hen egg-white lysozyme, and the I-Ak class II MHC molecule. The fine specificity of these Th cells had been determined previously by their reactivity to a panel of APC lines bearing mutant I-Ak molecules and to proteolytic fragments of HEL. TCR gene segment composition was determined by cDNA cloning and DNA sequencing. A heterogeneous, yet repetitive usage of gene segments was observed within the panel. The same V alpha C10-J alpha MD13 rearrangement was used in three of the hybridomas, two with identical Ag and MHC-restriction fine specificities. The prevalent usage of the V beta 14 gene segment and members of J beta 2 cluster was noted. Inasmuch as gene segment usage did not correlate with MHC-restriction or Ag fine specificity alone, these results favor an interactive Ag model of T-cell recognition, in which Ag and MHC are recognized as a bimolecular complex.

Amino Acid Sequence↗

Sequence conservation in potential regulatory regions of the mouse and human leukocyte common antigen gene.

The leukocyte common antigen is a family of glycoproteins uniquely expressed by cells of hemopoietic origin. The family is generated by alternative splicing of 3 exons, and individual members are expressed in a cell type-specific fashion. The glycoprotein consists of a heavily glycosylated exterior domain of approximately 100 kDa, a single membrane spanning region, and a cytoplasmic domain that has homology to a protein tyrosine phosphatase of 83 kDa. To further understand the regulation and structure of this family of molecules, genomic clones were isolated from mouse lambda and cosmid libraries. The genomic organization was determined from 20 genomic clones. Eighteen of the clones clustered within a 75-kilobase region, whereas the promoter region, the exons for the 5'-untranslated region, and the leader domain are located an unknown distance further 5' within in an unlinked clone. The gene is composed of 34 exons: two 5'-untranslated exons, 1a and 1b, and 32 exons that encode protein sequence. Exon 2 contains part of the 5'-untranslated region and encodes the 23 amino acids of the leader sequence. Exons 3-15 encode amino acid residues 1-538 of the external domain, exon 16 encodes residues 539-574, encompassing the membrane-spanning domain, and exons 17-33 encode residues 575-1268 of the cytoplasmic domain. Exon 33, the largest exon, contains the 1.1-kilobase 3'-untranslated region. A comparison between mouse and human (Hall, L.R., Streuli, M., Schlossman, S.F., and Saito, H. (1988) J. Immunol. 141, 2781-2787) promoter regions reveals significant homologies 5' to the transcription start site. The relationship between exon structure and glycoprotein structure is discussed.

Amino Acid Sequence↗

Evaluation of antibiotic therapy following penetrating abdominal trauma.

Postoperative infection accounts for significant morbidity and mortality following penetrating abdominal trauma. During a 2 1/2-year period, December 1980 through June 1983, 257 patients sustaining penetrating abdominal injury were initially treated at Parkland Memorial Hospital in Dallas. Following the patient's written consent, they were prospectively randomized to receive, prior to surgery, intravenous clindamycin 600 mg every 6 hours and tobramycin 1.2 mg/kg every 6 hours (CT), or cefamandole 1 gm every 4 hours (M), or cefoxitin 1 gm every 4 hours (C). The antibiotics were continued for 48 hours. Major organ injuries in the three groups were comparable. The overall infection rate was significantly less in the cefoxitin group (13%), compared to cefamandole at 29%, and was comparable to the combination of clindamycin/tobramycin at 20%. The most significant difference followed colon injury. There were 96 patients who sustained colon injuries and the infection rate was CT 33%, M 62%, and C 19% (p = 0.002). If nonoperative wound infections were excluded from the colon group and only severe infections were evaluated, the infection rate was CT 18%, M 38%, and C 13% (p = 0.021). The infection rate was higher in the shock patients and tended to increase as age increased. Enterococcus, Escherichia coli, and Klebsiella pneumoniae were the most frequent aerobes isolated along with anaerobes. Five of six Bacteroides isolates from major infections occurred in the cefamandole group; two of which were in bacteremic patients. The hospital stay corresponded with infection rates, being 11.4 days (CT), 13.1 days (M), and 9.4 days (C). The results of this study indicate that cefoxitin is comparable to the combination of clindamycin/tobramycin and superior to cefamandole when used before surgery in patients sustaining penetrating abdominal trauma. The study suggests that antibiotic coverage should be against aerobes and anaerobes. Routine administration of an aminoglycoside is unnecessary.

Abdominal Injuries↗

Effects of mutagenized X chromosomes of Drosophila melanogaster on viability and fitness in males.

Drosophila melanogaster males were treated with different doses of X-rays or ethyl methanesulfonate (EMS) and mated so that mutagenized X chromosomes could be recovered and tested for lethal mutations and for less drastic mutations affecting viability and other aspects of fitness. The lethals were detected in standard X-linked lethal tests. The less drastic mutations were detected in one generation tests for effects on viability and in multigeneration tests for effects on overall fitness. The Poisson-corrected frequencies of the lethal mutations increased linearly with dose for both X-rays and EMS. Based on the data, 1 Krad X-rays given acutely induces the same number of lethals as 0.55 mM EMS administered by feeding. For some of the X-ray and EMS doses, the mutagenized chromosomes that were nonlethal reduced the viability of their carriers by a small amount, but there was no discernable dose-effect relationship. However in every case where a viability effect was seen, the percentage reduction was less than the corresponding frequency of lethals. All the groups of mutagenized nonlethal chromosomes reduced overall fitness by a significant percentage. Wherever a meaningful comparison was possible, this reduction was 2-3 times the reduction in viability, but, as in the viability data, no dose-effect relationship was discernable.

Animals↗

A comparison of mutation rates for specific loci and chromosome regions in dysgenic hybrid males of Drosophila melanogaster.

The mutation rates of specific loci and chromosome regions were estimated for two types of dysgenic hybrid males. These came from crosses between P or Q males and M females in the P-M system of hybrid dysgenesis. The M X P hybrids were the more mutable for each of the loci and chromosome regions tested. The Beadex locus was highly mutable in these hybrids but did not mutate at all in the sample of gametes from the M X Q hybrids. The singed locus had 75% of the mutability of Beadex in the M X P hybrids; it was also mutable in the M X Q hybrids. The white locus was only slightly mutable in the M X P hybrids and not at all mutable in the M X Q hybrids. The mutations in singed and white probably arose from the insertion of P elements into these loci; the mutations at Beadex probably involved the action of a P element located near this locus on the X chromosome of the P strain that was used in the experiments. Mutations in two chromosome regions, one including the zeste-white loci and the other near the miniature locus, were much more frequent in the M X P hybrids than in the M X Q hybrids. These mutations also probably arose from P element insertions. The implication is that insertion mutations occur infrequently in the M X Q hybrids, possibly because most of the P elements they carry are defective. In M X P hybrids, there is variation among loci with respect to P element mutagenesis, indicating that P elements possess a degree of insertional specificity.

Animals↗

Linkage of beta 2-microglobulin and ly-m11 by molecular cloning and DNA-mediated gene transfer.

beta 2-Microglobulin (beta 2m) is expressed on the cell surface after introduction of a beta 2mb (C57BL/6N) genomic clone into thymidine kinase-deficient mouse L cells by cotransformation using the calcium phosphate precipitate method. Stable transformant cell lines were identified that express the beta 2mb allele, as determined by reaction of the cells with appropriate monoclonal antibodies and by two-dimensional gel electrophoresis of endogenously labeled immunoprecipitates of cell extracts. These beta 2mb transformants now express ly-m11.2, as detected by an indirect radioimmunoassay. A plasmid subclone of the beta 2mb gene that contains an 8.4-kilobase insert, after introduction into mouse L cells, similarly directs the synthesis of both the beta 2mb and the ly-m11.2 antigens. Thus, the beta 2mb and ly-m11.2 determinants most likely represent sites on the same protein structure.

Animals↗

Biphasic effects of ethanol on open-field activity: sensitivity and tolerance in C57BL/6N and DBA/2N mice.

Male C57BL/6N (C57) and DBA/2N (DBA) inbred mice were found to differ in open-field behavior after an acute ip injection of ethanol and in the development of tolerance to repeated injections. DBA mice showed only increased activity for 28 min after ethanol doses up to 2.67% g/kg when compared with saline-injected controls. Under the same conditions, C57 mice showed dose-related increases in activity during the first 4 min, followed by dose-related decreases in activity. The effects endured for at least 60 min after injection in both strains. In a third experiment, mice were injected daily with saline or 2.0 g/kg ethanol and tested on Days 1, 5, 9, and 13 for open-field activity. On the 17th day, all mice were tested after an ethanol injection. Neither strain showed tolerance to the activity-stimulating effect of ethanol. Some evidence for tolerance to the effect of ethanol to reduce activity in C57 mice was found. In a fourth experiment, twice-daily injections of ethanol for 10 days produced marked tolerance to the depressant effect of an injection on the 11th day in C57 mice, compared with those in a control group given ethanol for the first time on the 11th day. No tolerance to the stimulant effect of ethanol was seen in C57s. DBA mice were injected twice daily for 19 days but did not display tolerance when tested on Day 10 or on Day 20, Indeed, DBA mice chronically treated with ethanol exhibited more marked stimulation of activity after ethanol than mice treated chronically with saline. Differences in blood ethanol concentrations between the strains could not account for any of the observed differences. Implications for the genetic control of responses to ethanol are discussed.

Animals↗

High mutability in male hybrids of Drosophila melanogaster.

The frequencies of sex-linked lethal mutations arising in hybrid male offspring from crosses and in nonhybrid controls were determined. The hybrids were produced by crossing representative strains of the P-M system of hybrid dysgenesis in all possible combinations. Males from the cross of P males x M females had a mutation rate about 15 times higher than that of nonhybrid males from the P strain. Genetically identical males from the reciprocal cross had a mutation rate 3 to 4 times that of the nonhybrids. For crosses involving a Q strain, a significant increase in the mutation rate was detected in males produced by matings of Q males with M females. No increase was observed in genetically identical males from the reciprocal mating. Crosses between P and Q strains gave male hybrids with mutation rates not different from those of nonhybrids. Many of the lethals that occurred in hybrids from the cross of P males x M females appeared to be unstable; fewer lethals that arose in hybrids from the cross of Q males x M females were unstable. The relationship between P and Q strains is discussed with respect to a model of mutation induction in dysgenic hybrids.

Animals↗

Energy well spent fighting the diabetes epidemic.

As the global burden of type 2 diabetes increases, medical science races to comprehensively understand its molecular aetiology. We suggest that the apparent struggle to seek a pharmacological or molecular victory to the diabetes epidemic is a flawed strategy given that evolution has already provided us with the best medicine. Recent molecular evidence highlights the interaction between muscle fatty acid kinetics in dictating whole body insulin action. Insights from an evolutionary perspective suggest that the ability of the body to evoke insulin resistance and store energy as fat within muscle cells is a normal physiological response to aid our survival during food or carbohydrate scarcity, but this 'hunter-gatherer physiology' predisposes to diabetes in a modern environment characterized by ample food availability and muscle inactivity. We contend that the true value of physical activity in the prevention and treatment of insulin resistance has been missed by the medical community because scientific investigation has been constructed upon physical activity recommendations that were never intended for this purpose. These recommendations provide a level of metabolic stress insufficient to be compatible with the expectations of our genes.

Diabetes Mellitus↗

Prediction of patient nonadherence with home-based exercise for cardiac rehabilitation: the role of perceived barriers and perceived benefits.

BACKGROUND: The aim of this study was to determine whether cardiac patients' perceptions of the barriers to and benefits of home exercise while in hospital and 6 weeks after discharge are predictive of nonadherence with regular home exercise 6 months after discharge from hospital. METHODS: A prospective longitudinal study of 459 patients age 75 years or less and discharged from any of six public hospitals in the Lower Hunter Region of New South Wales, Australia, with a diagnosis of acute myocardial infarction or angina was conducted. RESULTS: Multivariate logistic regression analysis, using data provided by 281 (61.2%) patients, showed that cardiac patients' perceptions of the benefits of and the physical environment and time barriers to home exercise while in hospital were predictive of nonadherence with regular home exercise 6 months after discharge from hospital, after adjustment for potential confounders. Six weeks after discharge from hospital, patients' perceptions of the enjoyment and time barriers to home exercise were predictive of nonadherence at follow-up, after adjustment for potential confounders. CONCLUSIONS: Cardiac patients' perceptions of the barriers to and benefits of home exercise may be modifiable sources of nonadherence. A randomized controlled trial is required to confirm and extend upon these findings.

Adult↗

A lament by women for "the people, the land" [Nishnawbi-Aski Nation]: an experience of loss.

In response to a hunger fast by five members of the Sandy Lake Band at the Sioux Lookout Zone Hospital in Northern Ontario (Canada)--a cultural protest of the status of health care services in the Zone--the Federal Minister of Health agreed to establish a Panel to review the region's health care system. The year-long study involved hearings in each of the 28 remote communities of the Zone, and interviews with elders and chiefs, women, and health care providers. A consultation team from McMaster University (Faculty of Health Sciences) assisted the Panel with epidemiological survey research, literature reviews, and the interpretation of the data collected in the proceedings. This paper offers our interpretation of data collected from the qualitative study component. Specifically, it provides an interpretation of the discourse of the native women of the Nishnawbi-Aski Nation on their experience of health and health care. An "idiom of loss" captures, we feel, the depth of their concerns, dilemmas and frustrations.

Attitude to Health↗

Patients' perspectives of a physician-delivered smoking cessation intervention.

Forty-three patients--recipients of a highly structured, physician-delivered smoking cessation intervention--were interviewed using ethnographic (anthropological) research methods. We conducted interviews with patients after visits with the physician, then audiotaped and transcribed them. Discourse analysis of interview texts identified features and components of the physician maneuver most effective from the patients' point of view. Patients discussed two general areas of physicians' preventive activities: an interventionistic component (in which professional, diagnostic, and authoritative features were emphasized) and a personalistic component (in which physicians were experienced as equals, supportive, caring, empowering, and challenging). From the perspective of patients, the personalistic component of the physician-delivered smoking cessation maneuver appeared most effective. We conclude that, in clinical preventive medicine generally, patients (1) evaluate the kind of support they receive from their physician (e.g., degree of empathy, encouragement, and sincerity), (2) respond favorably to positive imagery in the challenge to alter their lifestyle, (3) look for a balance in the relationship established with their physician (negotiation, respect, mutual understanding, and rapport), and (4) remember the consistency and regularity of their physician's health promotion messages.

Female↗

Determination of maduramicin by liquid chromatography with atomic absorption spectrometric detection.

A liquid chromatograph was interfaced to an atomic absorption spectrometer for the detection and quantitation of maduramicin in feed matrixes at the 1-8 ppm level. Ionophores in general form strong 1:1 products with various metal cations, yielding complexes that are insoluble in water but very soluble in organic solvents. Maduramicin, a carboxylic, polyalcohol, polyether antibiotic, is labeled with the sodium cation and analyzed by atomic absorption spectroscopy (AAS). The lower limit of detection is approximately 100-200 ng maduramicin sodium salt. Feeds containing 1-8 ppm maduramicin are extracted with acetone, the extract is passed through an alumina column, the column is eluted with acetonitrile-water (90 + 10), and the eluate is analyzed for maduramicin by liquid chromatography-AAS after concentration and conversion of maduramicin to the sodium salt. Recoveries of maduramicin averaged 89.5%. Liquid chromatography with AAS detection has been shown to be a sensitive and highly specific technique for the determination of ionophores in general and maduramicin in particular.

Animal Feed↗

Liquid chromatographic method for rapid determination of total avermectin B1 and 8,9-Z-avermectin B1 residues in apples.

A liquid chromatographic method has been developed and validated for the rapid determination of avermectin B1 and 8,9-Z-avermectin B1 residues in apples. The avermectins are extracted from the crop matrix with an acetonitrile-water-hexane mixture; the extract is cleaned up on an aminopropyl solid-phase extraction column. The avermectins are derivatized with trifluoroacetic anhydride and analyzed by reversed-phase liquid chromatography with fluorescence detection. Recoveries of avermectins from apples fortified with about 2-77 ppb avermectin B1a or 2-27 ppb 8,9-Z-avermectin B1a averaged 85%. The limit of quantitation is 2 ppb (signal-to-noise [S/N] ratio, 12) and the limit of detection is 1 ppb (S/N ratio, 6) for each analyte. The assay is a simple, rapid, and sensitive method for monitoring the total amount of avermectin residues in apples.

Chromatography, Liquid↗

Liquid chromatographic fluorescence method for multiresidue determination of thiabendazole and 5-hydroxythiabendazole in milk.

A novel liquid chromatographic multiresidue method has been developed for quantitation of thiabendazole (TBZ), the metabolite 5-hydroxythiabendazole (5-OH-TBZ), and the sulfate conjugate of 5-hydroxythiabendazole (5-HSO4-TBZ) in raw cow's milk. The 5-HSO4-TBZ is hydrolyzed quantitatively under acidic conditions to 5-OH-TBZ. TBZ and 5-OH-TBZ are extracted from milk at pH 8.0 with ethyl acetate followed by cleanup of the extract on a cation-exchange solid-phase extraction column. Analytes are quantitated by liquid chromatography with a cation-exchange stationary phase and fluorescence detection. Recoveries from raw cow's milk samples fortified with TBZ and 5-OH-TBZ or TBZ and 5-HSO4-TBZ at 0.05 to 2 ppm ranged from 87 to 103% for TBZ, 98-109% for 5-OH-TBZ, and 96-115% for 5-HSO4-TBZ (quantitated as 5-OH-TBZ). The assay provides a simple, rapid, and sensitive multiresidue method for monitoring total residues of TBZ, 5-OH-TBZ, and 5-HSO4-TBZ in milk.

Animals↗