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Biomedical subjects

M Young

Publications and source records attributed to M Young.

At least 109 records · Page 6Linked to original sources
PubMed1998

Loss of glucose transporter-2 precedes insulin loss in the nonobese diabetic and the low-dose streptozotocin mouse models: a comparative immunohistochemical study by light and confocal microscopy.

Glucose transporter-2 (glut2) is underexpressed in beta cells of several rodent models of non-insulin-dependent diabetes mellitus (NIDDM). This may also be true for rodent models of insulin-dependent diabetes mellitus (IDDM). The present study examines two murine models of autoimmune IDDM, the nonobese diabetic (NOD) and the low-dose streptozotocin (stz) murine models for changes in the expression of glut2 by double-label light and confocal microscopy during various stages of the disease. The spatial distribution of glut2 cells was also examined in relation to insulin immunoreactive cells and the islet inflammatory cells during these stages. In both the female NOD mouse and the female Swiss mouse without stz treatment, glut2 colocalized with insulin in virtually all the beta cells. In the NOD mouse, islets with moderate to advanced insulitis showed either an absence or considerably reduce expression of glut2 in insulin-containing beta cells. Cells with reduced glut2 expression were usually located adjacent to the region of insulitis. At onset of diabetes, glut2 immunolabeling was reduced despite the preservation of weak insulin immunoreactivity. In Swiss mice treated repeatedly with stz, glut2 labeling began to decline in select Beta cells after the fourth injection in approximately 50% of the islets, despite the lack of insulitis. At this stage expression of glut2 fell in a small number of islets with evidence of early macrophage infiltration. Loss of glut2 became more pronounced in nondiabetic Swiss mice after the fifth injection. At this stage glut2 labeling in the plasma membrane appeared diffuse and variable. At onset of stz-induced diabetes, glut2 expression significantly fell, despite weak immunoreactivity for insulin. This loss was associated with an enhanced influx of both macrophages and T lymphocytes within the islets of diabetes mice. In both the NOD and the low-dose stz mouse models, loss of glut2 thus occurs from an early stage and precedes hyperglycaemia. This loss may be mediated by immune and nonimmune mechanisms.

Animals↗
PubMed1998

Effects of glutathione depletion on oxidant-induced endothelial cell injury.

Ischemia-reperfusion produces edema in vivo by disrupting endothelial cell junctional integrity. A cultured rat pulmonary artery endothelial cell (RPAEC) model was used to analyze the effects of oxidants and ischemic plasma in vitro. RPAEC cultures were treated with ischemic human plasma from transverse rectus abdominis musculocutaneous (TRAM) flaps following mastectomy or with an equal quantity of nonischemic plasma taken peripherally. Endothelial cells treated with ischemic plasma rounded and formed gaps within 5 min, then ruffled and blebbed after 10 min. Cultures treated with human nonischemic plasma had no gross morphological changes. Additionally, cultures treated with human ischemic plasma demonstrated an increase in diffusion rate of 125I-albumin across monolayers while monolayers treated with human nonischemic plasma had no increase in diffusion rate. RPAEC monolayers were treated with malic acid diethyl ester (DEM) or L-buthionine-[S, R]-sulfoximine (BSO) to decrease cellular stores of glutathione before exposure to oxidant stress. Cultures depleted of cellular glutathione stores were significantly (P < 0.05) more susceptible to 50 microM H2O2 than controls, as determined by an increase in diffusion rate of 125I-albumin across monolayers. To determine if ischemic plasma effects were mediated by oxidants, cultures were depleted of glutathione by DEM or BSO pretreatment before exposure to plasma from the ischemic hind limbs of Sprague-Dawley rats. Glutathione-depleted RPAEC monolayers were significantly (P < 0.05) and substantially (2-3 X) more susceptible to the effects of ischemic plasma than were cultures with normal glutathione levels. Glutathione depletion had no effect on cultures treated with an equal amount of nonischemic plasma from sham-operated rats. These data strongly suggest that ischemic plasma in the absence of any cellular component are able to induce an oxidant injury in endothelial cells and thereby compromise junctional integrity.

Animals↗
PubMed1998

Is utility in the mind of the beholder? A study of ergonomics methods.

This paper reviews the use of ergonomics methods in the context of usability of consumer products. A review of the literature indicated that there is upward of 60 methods available to the ergonomist. The results of the survey indicated that questionnaires, interviews and observation are the most frequently reported methods used. Ease of use of the methods was dependent upon type of method used, presence of software support and type of training received. Strong links were found between questionnaires and interviews as a combined approach, as well as with HTA and observation. However, a questionnaire survey of professional ergonomists found that none of the respondents had any documented evidence of the reliability and validity of the methods they were using. A study of training people to use ergonomics' methods indicated the different requirements of the approaches, in terms of training time, application time and subjective preferences. An important goal for future research is to establish the reliability and validity of ergonomics methods.

Adult↗
PubMed1998

Early extubation after abdominal aortic reconstruction.

OBJECTIVE: To assess the safety of early (<2 hrs) extubation after elective infrarenal aortic surgical procedures. DESIGN: A retrospective chart review of 192 consecutive elective infrarenal aortic surgical procedures from January 1990 to March 1994 at Mayo Clinic Scottsdale was undertaken. MEASUREMENTS AND MAIN RESULTS: Combined general and epidural anesthesia was used extensively (187 patients; 97.4%). Early extubation was accomplished in 166 (86.5%) patients. Time to extubation was dependent on clinical factors and not by protocol. All early extubations occurred in the operating room or recovery room with a median time from skin closure of 12 minutes. Ten patients were extubated from 2 to 12 hours after the procedure, 14 patients more than 12 hours after the procedure, and 2 patients were not extubated and subsequently expired. Of the 166 patients extubated within 2 hours, 8 (4.8%) required reintubation. Factors found univariantly to be significantly associated with failure of early extubation include obesity, abnormal chest x-ray postoperatively, prior myocardial infarction, and prior coronary revascularization (p < 0.05). CONCLUSION: Early extubation (<2 hrs) after elective infrarenal aortic procedures may be performed safely and should be undertaken unless clinical features suggest failure of extubation.

Aged↗
PubMed1998

Characterization of oligosaccharides from an antigenic mannan of Saccharomyces cerevisiae.

Mannans of the yeast Saccharomyces cerevisiae have been implicated as containing the allergens to which bakers and brewers are sensitive and also the antigen recognized by patients with Crohn's disease. A fraction of S. cerevisiae mannan, Sc500, having high affinity for antibodies in Crohn's patients has been characterized by NMR spectroscopy followed by fragmentation using alkaline elimination, partial acid hydrolysis and acetolysis. The released oligosaccharides were separated by gel filtration on a Biogel P4 column and analyzed by fluorescence labeling, HPLC and methylation analysis. The relationship between structure and antigen activity was measured by competitive ELISA. The antigenic activity of the original high molecular weight mannan could be ascribed to terminal Manalpha1-->3Manalpha1-->2 sequences which are rarely found in human glycoproteins but were over-represented in Sc500 compared to other yeast mannans.

Antigens, Fungal↗
PubMed1998

Allelic imbalance in familial and sporadic prostate cancer at the putative human prostate cancer susceptibility locus, HPC1. CRC/BPG UK Familial Prostate Cancer Study Collaborators. Cancer Research Campaign/British Prostate Group.

A recent report has provided strong evidence for a major prostate cancer susceptibility locus (HPC1) on chromosome 1q24-25 (Smith et al, 1996). Most inherited cancer susceptibility genes function as tumour-suppressor genes (TSGs). Allelic loss or imbalance in tumour tissue is often the hallmark of a TSG. Studies of allelic loss have not previously implicated the chromosomal region 1q24-25 in prostate cancer. However, analysis of tumour DNA from cases in prostate cancer families has not been reported. In this study, we have evaluated DNA from tissue obtained from small families [3-5 affected members (n = 17)], sibling pairs (n = 15) and sporadic (n = 40) prostate tumours using the three markers from Smith et al (1996) that defined the maximum multipoint linkage lod score. Although widely spaced (12-50 cM), each marker showed evidence of allelic imbalance in only approximately 7.5% of informative tumours. There was no difference between the familial and sporadic cases. We conclude that the incidence of allelic imbalance at HPC1 is low in both sporadic tumours and small prostate cancer families. In this group of patients, HPC1 is unlikely to be acting as a TSG in the development of prostate cancer.

Aged↗
PubMed1998

Ultrasonographically-guided fine-needle aspiration cytology in the diagnosis of colonic lesions.

BACKGROUND: The use of fine-needle aspiration cytology (FNAC) in the diagnosis of colonic lesions was investigated. METHODS: Some 22 patients (median age 71 years) with a colonic lesion identified on abdominal ultrasonography underwent ultrasonographically-guided FNAC using a 21-G needle. The sample was checked immediately by a cytopathologist for adequacy. RESULTS: Eighteen patients had colonic carcinoma; aspiration cytology detected malignant epithelial cells consistent with colonic carcinoma in 17 patients and severely dysplastic cells in one patient. The sensitivity and specificity of ultrasonographically-guided FNAC in the diagnosis of colonic carcinoma was 94 and 100 per cent respectively. The remaining four patients had a diagnosis of ileocaecal tuberculosis, ileocaecal Crohn's disease, and metastatic adenocarcinoma in the liver with no identifiable primary (two patients). One demonstrated granulomata, grew acid-fast bacilli and the patient was treated for tuberculosis. One had inflammatory cells and the patient was found to have Crohn's disease on histology. The remaining two patients had confirmed metastatic adenocarcinoma in the liver on aspiration cytology but suspected colonic lesions were found to be benign on cytological examination and no primary lesion was subsequently demonstrated. There were no complications of FNAC and patients complained of minimal discomfort. There has been no evidence of tumour recurrence with a median follow-up of 12 (range 1-25) months. CONCLUSION: Ultrasonographically-guided FNAC is a valid method for the diagnosis of colonic tumours.

Adult↗
PubMed1998

DNA sequence sampling of the Streptococcus pneumoniae genome to identify novel targets for antibiotic development.

We initiated a survey of the Streptococcus pneumoniae genome by DNA sequence sampling. More than 9,500 random DNA sequences of approximately 500 bases average length were determined. Partial sequences sufficient to identify approximately 95% of the aminoacyl tRNA synthetase genes and ribosomal protein (rps) genes were found by comparing the database of partial sequences to known sequences from other organisms. Many genes involved in DNA replication, repair, and mutagenesis are present in S. pneumoniae. Genes for the major subunits of RNA polymerase are also present, as are genes for two alternative sigma factors, rpoD and rpoN. Many genes necessary for amino acid or cofactor biosynthesis and aerobic energy metabolism in other bacteria appear to be absent from the S. pneumoniae genome. A number of genes involved in cell wall biosynthesis and septation were identified, including six homologs to different penicillin binding proteins. Interestingly, four genes involved in the addition of D-alanine to lipoteicoic acid in other gram positive bacteria were found, even though the lipoteicoic acid in S. pneumoniae has not been shown to contain D-alanine. The S. pneumoniae genome contains a number of chaperonin genes similar to those found in other bacteria, but apparently does not contain genes involved in the type III secretion commonly observed in gram negative pathogens. The G+C content of S. pneumoniae genomic DNA is approximately 43 mole percent and the size of the genome is approximately 2.0 Mb as determined by pulsed-field gel electrophoresis. Many of the genes identified by sequence sampling have been physically mapped to the 19 different SmaI fragments derived from the S. pneumoniae genome. The database of random genome sequence tags (GSTs) provides the starting material for determining the complete genome sequence, gene disruption analysis, and comparative genomics to identify novel targets for antibiotic development.

Amino Acyl-tRNA Synthetases↗
PubMed1998

Tuftelin--aspects of protein and gene structure.

The acidic enamel protein tuftelin has now been cDNA cloned, sequenced and characterized in a number of vertebrate species. Recently, the bovine tuftelin gene structure was elucidated. Cloning of the human tuftelin gene and partial sequencing of a number of exons have also been achieved. Immunologically, the protein has been shown to be conserved throughout 550 million years of vertebrate evolution. The gene has been localized to the long arm of the autosomal chromosome 1. The mapping of the human tuftelin gene to a well-defined cytogenetic region could be important in understanding the etiology of autosomally inherited amelogenesis imperfecta, the most common hereditary disease of enamel. The present paper reviews the primary structure, mRNA/cDNA structure, and gene structure of tuftelin. It describes its immunolocalization at the light microscope level and at the ultrastructural level in both the ameloblast cells and in the extracellular enamel matrix. The timing of tuftelin expression and its possible roles in enamel formation are discussed.

Ameloblasts↗
PubMed1998

Truncation of peptide deformylase reduces the growth rate and stabilizes solvent production in Clostridium beijerinckii NCIMB 8052.

The wild-type strain of Clostridium beijerinckii NCIMB 8052 tends to degenerate (i.e., lose the ability to form solvents) after prolonged periods of laboratory culture. Several Tn1545 mutants of this organism showing enhanced long-term stability of solvent production were isolated. Four of them harbor identical insertions within the fms (def) gene, which encodes peptide deformylase (PDF). The C. beijerinckii fms gene product contains four diagnostic residues involved in the Zn2+ coordination and catalysis found in all PDFs, but it is unusually small, because it lacks the dispensable disordered C-terminal domain. Unlike previously characterized PDFs from Escherichia coli and Thermus thermophilus, the C. beijerinckii PDF can apparently tolerate N-terminal truncation. The Tn1545 insertion in the mutants is at a site corresponding to residue 15 of the predicted gene product. This probably removes 23 N-terminal residues from PDF, leaving a 116-residue protein. The mutant PDF retains at least partial function, and it complements an fms(Ts) strain of E. coli. Northern hybridizations indicate that the mutant gene is actively transcribed in C. beijerinckii. This can only occur from a previously unsuspected, outwardly directed promoter located close to the right end of Tn1545. The Tn1545 insertion in fms causes a reduction in the growth rate of C. beijerinckii, and, associated with this, the bacteria display an enhanced stability of solvent production. The latter phenotype can be mimicked in the wild type by reducing the growth rate. Therefore, the observed amelioration of degeneration in the mutants is probably due to their reduced growth rates.

Amidohydrolases↗
PubMed1998

A steroidogenic factor-1-binding site and cyclic adenosine 3',5'-monophosphate response element-like elements are required for the activity of the rat aromatase promoter in rat Leydig tumor cell lines.

Although transcription initiation within CYP19 (cytochrome P450 aromatase) occurs immediately 5' to the initiator methionine (proximal promoter) in two rat Leydig tumor cell lines (R2C and H540) that express high aromatase activity and in rat ovary, the patterns of aromatase expression in the two cell types are distinctive. To define mechanisms controlling different patterns of expression of the rat aromatase proximal promoter, we performed transient transfection and gel mobility shift assays. Transfection experiments using different sized promoter fragments fused to a reporter gene were used to identify regions that are functionally important for transcriptional regulation in steroidogenic cell lines [R2C, H540, and Y1 (mouse adrenocortical cells that express low aromatase activity)]. These experiments indicate that the cAMP response element (CRE) at -231 and the steroidogenic factor-1 (SF1) motif are both required for expression of the reporter gene in each steroidogenic cell line and that the CRE at -169 is similarly required in R2C cells. Gel mobility shift assays confirm binding of nuclear proteins from the steroidogenic cell lines to the SF1 motif and to CRE (-231). Leydig tumor cells also contain nuclear proteins that bind to the CRE (-169), but nuclear extracts from R2C cells produce a uniquely shifted band compared with H540 cells. These results suggest that differences in proteins that bind to distinct elements within the rat aromatase promoter may be responsible for different patterns and levels of aromatase expression in these steroidogenic cell lines.

Animals↗
PubMed1998

The Women's Interagency HIV Study. WIHS Collaborative Study Group.

The Women's Interagency HIV Study comprises the largest U.S. cohort to date of human immunodeficiency virus (HIV)-seropositive women (N = 2,058) with a comparison cohort of seronegative women (N = 568). The methodology, training, and quality assurance activities employed are described. The study population, enrolled between October 1994 and November 1995 through six clinical consortia throughout the United States (totaling 23 sites) represents a typically hard-to-reach study population. More than half of the women in each cohort were living below the federally defined levels of poverty. The women ranged in age from 16 to 73 years; approximately one-quarter self-identified as Latina or Hispanic, over one-half as African-American not of Hispanic origin, and less than 20% as white, non-Hispanic origin. Self-reporting of HIV exposure risk included injection drug use by 34% of the seropositive women and 28% of the seronegative women, heterosexual contact (42% vs 26%), transfusion risk (4% vs 3%) and no identified risk (20% vs 43%). Demographic and HIV exposure risk characteristics of the seropositive cohort were comparable with characteristics of nationally reported AIDS cases in U.S. women. This well characterized cohort of HIV-seropositive and high-risk seronegative women represents a rich opportunity for future studies of HIV disease progression and pathogenesis.

Adolescent↗
PubMed1998

Exercise after acute hyperbaric oxygenation: is there an ergogenic effect?

The purpose of this study was to determine the effects of a 1-h exposure to 2.0 atm abs (202.6 kPa) and 100% oxygen on subsequent maximal O2 consumption (VO2max), ventilation threshold (VT), lactate threshold (LT), and muscle oxygenation (%Mox) during incremental exercise to maximum on a cycle ergometer. Two baseline exercise tests (T1 and T2) were performed on separate occasions without prior exposure to hyperbaric oxygen (HBO2) and a third test (T3-HBO2) was performed after (22.5 +/- 5.6 min) HBO2 Near infared spectroscopy was used to monitor oxygenation of the left vastus lateralis muscle during T2 and T3-HBO2. No significant differences were observed between VO2max VT, or LT among any of the exercise tests. There was no significant difference in %Mox between T2 and T3-HBO2 except at 235 W where there was a significant elevation in %Mox during T3-HBO2 relative to T2. These results suggest that prior exposure to HBO2 (100% O2 at 2 atm abs for 1 h) has no ergogenic effect on subsequent incremental exercise performance.

Adult↗