Decline in deaths from AIDS due to new antiretrovirals.
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Biomedical subjects
Publications and source records attributed to B Yip.
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UDP-GlcNAc: alpha-3-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I (EC 2.4.1.101; GlcNAc-T I) is a medial-Golgi enzyme which catalyses the first step in the conversion of oligomannose-type to N-acetyl-lactosamine- and hybrid-type N-glycans and is essential for normal embryogenesis in the mouse. Previous work indicated the presence of at least two exons in the human GlcNAc-T I gene MGAT1, exon 2 containing part of the 5' untranslated region and the complete coding and 3' untranslated regions, and exon 1 with the remainder of the 5' untranslated region. We now report the cloning and sequencing of a human genomic DNA fragment containing exon 1, which is between 5.6 and 15 kb upstream of exon 2. Transient transfection, ribonuclease protection and reverse transcriptase-mediated PCR indicated the absence of transcription start sites in intron 1 between exons 1 and 2. Northern analysis, ribonuclease protection, primer extension analysis and rapid amplification of 5'-cDNA ends showed that there are multiple transcription start sites for exon 1 compatible with the expression by several human cell lines and tissues of two transcripts, a broad band ranging in size from 2.7 to 3.0 kb and a sharper band at 3.1 kb. The 5' flanking region of exon 1 has a GC content of 81% and has no canonical TATA or CCAAT boxes but contains potential binding sites for transcription factors Sp1, GC-binding factor and epidermal growth factor receptor-specific transcription factor. Chloramphenicol acetyltransferase (CAT) expression was observed on transient transfection into HeLa cells of a fusion construct containing the gene for CAT and a genomic DNA fragment from the 5' flanking region of exon 1. It is concluded that MGAT1 is a typical housekeeping gene although there is, in addition, tissue-specific expression of the larger 3.1 kb transcript.
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To identify associations between HIV-related experience and patterns of service provision, physicians across Canada were solicited by mail to register in a national network of HIV/AIDS care givers. Respondents provided data about: personal, demographic and practice characteristics; the number of HIV-positive patients ever seen; the nature of the HIV-positive client population; and services provided to HIV-positive patients. Univariate techniques provided a demographic and professional profile of participating physicians. Logistic regression was used to identify associations between level of HIV-related experience and the provision of patient services. The 566 registered physicians have provided care to 56,378 HIV-infected persons and represent every province and territory in Canada. Multivariate analysis revealed that highly experienced physicians were more likely to provide all 3 types of services considered, to practise in Montreal, Vancouver or Toronto, and to be medical specialists (all P < 0.001).
BACKGROUND: Diabetic papillopathy is a benign unilateral or bilateral optic neuropathy with transient optic disk edema and minimal reduction in visual function. The optic disk edema typically resolves in a few months with no resulting optic atrophy and minimal or no decrease in acuity. The exact etiology of the disk edema is unknown, but theories include retinal vascular leakage into and surrounding the optic nerve and disruption of axoplasmic flow resulting from microvascular disease of the optic nerve head vasculature. CASE REPORTS: Two adult patients receiving insulin for type II diabetes mellitus manifested bilateral disk edema and minimal visual dysfunction. Both patients showed funduscopic evidence of mild-to-moderate nonproliferative diabetic retinopathy O.D. and O.S., and one patient had clinically significant macular edema in both eyes. The diagnosis in both cases was diabetic papillopathy. Both patients had significant resolution of their disk edema in 3 to 6 months, with stable acuities and no signs of optic atrophy. CONCLUSIONS: Although diabetic papillopathy is a well-known clinical entity in patients with type I diabetes, the clinical profile can be expanded to include individuals with type II diabetes.
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A semi-automated method has been developed for the simultaneous analysis of two micro-satellite repeat polymorphisms located in intron 13 and 22 of the Factor VIII gene. The fluorescent dyes, 6-FAM-and HEX-phosphoramidites were used to 5'-end label the respective 5' primers of these two microsatellite repeats and a multiplex polymerase chain reaction (PCR) devised for amplification. The PCR product was loaded onto the gel with DNA size marker labelled with ROX. A total of 24 samples could be analysed simultaneously on an automated DNA sequencer. The results were computed using a dedicated software, with assignment of PCR product size in basepair. This method compares well with the conventional manual procedure using radio-labelled primers, but at the same time overcomes many of the inherent disadvantages associated with the latter method.
A group of 222 residents in NHS continuing care were studied in order to assess the prevalence of joint contractures in the very disabled elderly and to establish whether there was an association between the presence of contractures and functional ability; 121 (55%) had at least one contracted joint. There was no clear linear relationship between length of stay in continuing care and the presence of contractures. Those with upper limb contractures were nearly twice as likely to be unable to feed themselves as those without contractures (p < 0.0001). The presence of at least one lower limb contracture was significantly associated with reduced mobility (p < 0.0001). An association was also demonstrated between the presence of lower limb contractures and frequency with which the patient walked. The role of disease and immobility in the development of contractures is discussed as well as the potential for the prevention and treatment of contractures.
Patients who smoke have higher complication rates than nonsmokers following many surgical procedures. It is not known if the adverse effects of smoking are caused by a nicotine effect or by some other potentially harmful agents that exist in tobacco smoke. It is also not known if these vasoactive effects are mediated through sympathetic nerve fibers (via nicotinic receptors in ganglia) or through elevated circulating levels of vasoactive hormones. We designed a 5-day protocol to measure relative blood flow both before and after a digital sympathetic block in the digits of subjects who were regular smokers following both smoking and wearing of a transdermal nicotine patch. Suitable pulse/wave tracings were recorded on 23 subjects. We also measured serum levels of nicotine, cotinine, vasopressin, norepinephrine, epinephrine, dopamine, and carboxyhemoglobin on each test day. Data for these serum levels were available in 30 test subjects. Digital sympathetic block had a significant beneficial effect in reversing the decreased digital blood flow that occurred after smoking (and also with use of the nicotine patch), despite the elevated circulating levels of vasopressin and norepinephrine seen with smoking. The vasoactive effects of smoking are probably due to the nicotinic effects on sympathetic fibers at the ganglionic levels.
Patients who smoke have higher complication rates than nonsmokers in the postoperative period. The authors designed an experimental protocol for habitual smokers (n = 30) to determine the specific hemodynamic and hematologic adverse effects possibly caused by nicotine and whether the method of nicotine delivery and systemic nicotine levels achieved might influence these adverse effects. During the 5-day study, subjects were asked to refrain from smoking, and testing sessions were conducted as follows: on day 1, the subjects smoked two cigarettes immediately before testing; on day 3 (control day), testing was done after not smoking for 48 hours and then the subjects were instructed to wear a transdermal nicotine patch (PROSTEP 22 mg/day) for 24 hours and replace it with another so that, on day 5, testing took place after the subjects had worn the patch for approximately 34 hours. At each testing session, digital artery pulse amplitude and a number of clinical and serum blood level parameters were measured. Relative digital blood flow after smoking (69.2 +/- 5.8%) and with the patch (80.4 +/- 7.6%) was lower than on the control day (100.0 +/- 0.0%). The nicotine patch, unlike smoking, had no effect on vasopressin or fibrinogen concentrations, hematocrit, or white cell or platelet counts; both smoking and the patch resulted in elevated norepinephrine levels.
Allelic frequencies of RFLPs at loci closely linked to the HD gene, D4S95, D4S91, D4S141, and D4S90, were determined in 13 Huntington's disease (HD) patients from nine Chinese families and 129 normal subjects. These were similar for non-HD and HD chromosomes and the HD gene in Chinese is associated with multiple haplotypes. Hence the HD gene probably arose independently in the background haplotypes of the Chinese population. The heterozygosity rates for the two most useful RFLP sites are 0.659 for D4S95-AccI VNTR and 0.494 for D4S141-HindIII. (CAG)n repeat numbers ranged from 12 to 27 in 174 normal chromosomes. In 52 meiotic recombinations, the (CAG)n repeats were stably inherited in normal families. In HD families, 12 of 13 HD patients had expanded (CAG)n repeats of 40 to 58. Additionally, 10 asymptomatic family members had expanded (CAG)n repeats and the inheritance of the expanded repeat was unstable in these families.
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Two multi-allelic microsatellite polymorphisms within the factor VIII gene were studied in 138 Chinese subjects. The allele sizes detected were higher than those found in Caucasian populations, whereas the heterozygosity rates were lower, being 0.5370 for intron 13 and 0.4444 for intron 22 repeats respectively. Their usefulness in diagnosis was compared to other intragenic and extragenic RFLPs, using previous data on the same 31 unrelated haemophilia A families. These intragenic microsatellite repeat polymorphisms were only informative for 18/31 families (58%); however, with the combined use of all existing RFLPs, the cumulative informativeness would be 100%.
Changes in the oral microbial flora, some of which are related to mucosal disease, have been detected in the elderly, but the causes are not fully understood. This study has examined the possible role of micronutrient depletions in the reduced colonisation resistance and oral infection exhibited by some elderly subjects. The oral health, oral microbiology and micronutrient status of 37 geriatric patients aged 65-91 years (mean 81 years) were examined. Ten of the patients had no oral mucosal disease. Mucosal pathology in the remainder included erythema (27%), denture stomatitis (24%), angular cheilitis (16%) and atrophic glossitis (41%). Those with mucosal pathology had significantly lower serum iron concentrations (P = 0.02). Serum or plasma concentrations of zinc, copper, selenium, C-reactive protein, transferrin, caeruloplasmin, albumin, vitamin A and vitamin E were not significantly different between those with oral disease and those with healthy mouths. Similarly, activity of the selenium-containing enzyme, red cell glutathione peroxidase, did not differ significantly between the two groups. In both groups, plasma selenium concentrations (82%), red cell glutathione peroxidase activity (47%), plasma zinc concentrations (58%) and albumin concentrations (44%) tended to be below the lower limit of the reference interval. The influence of subclinical infection on these values is discussed.
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Two independent studies were designed to investigate the separate and combined effects of acipimox and cholestyramine on plasma low density lipoprotein subfractions. In the first study, normolipidaemic subjects were given cholestyramine (16 g day-1, 4 weeks), followed, after an 8-week wash-out period, by acipimox (750mg day-1, 4 weeks). In the second study, moderately hypercholesterolaemic subjects were prescribed acipimox (1250mg day-1, 10 weeks), followed by acipimox in combination with low dose cholestyramine (12g day-1) for a further 10 weeks. In the normal subjects, cholestyramine decreased total LDL mass (density (d) = 1.019-1.063g ml-1) by selectively reducing the largest, least dense LDL-I (d 1.025-1.034 g ml-1, P less than 0.05) and LDL-II (d 1.034-1.044 g ml-1, P less than 0.005) subfractions. The small, dense LDL-III (d 1.044-1060 g ml-1) showed a variable response to the resin. In the same subjects acipimox produced no overall change in total LDL mass but showed a tendency to redistribute LDL towards LDL-I (+10%) and LDL-II (+10%) in a manner related to the changes in plasma triglyceride (TG) (TG vs. LDL-III r = 0.75, P less than 0.05). In the hypercholesterolaemic subjects acipimox induced a substantial redistribution of LDL subfractions (LDL-I +84% P less than 0.05; LDL-III -50%) without affecting total LDL mass. The addition of cholestyramine produced a significant decrease in total LDL mass which was again confined to the LDL-I (-28%) and LDL-II (-23%) subfractions.(ABSTRACT TRUNCATED AT 250 WORDS)