Biomedical subjects
Publications and source records attributed to S Lin.
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Hydroxychloroquine (HCQ), an antimalarial agent used to treat patients with autoimmune diseases, has been shown to suppress human immunodeficiency virus type 1 (HIV-1) replication in vitro in T cells and monocytes by inhibiting posttranscriptional modification of the virus. These in vitro observations have been expanded into an in vivo study of HCQ as a potential anti-HIV-1 agent in HIV-1-infected patients. A randomized, double-blind, placebo-controlled clinical trial was conducted in 40 asymptomatic HIV-1-infected patients who had CD4+ counts between 200 and 500 cells/mm3. Patients were randomly assigned to receive either HCQ 800 mg/d or placebo for 8 weeks. Virologic and immunologic parameters, including HIV-1 ribonucleic acid (RNA) via use of polymerase chain reaction, viral culture, antigen and mitogen responses, and proinflammatory cytokine levels were measured at the beginning and end of the study. The amount of recoverable HIV-1 RNA in plasma declined significantly in the HCQ group over the 8-week period (P = 0.022), while it increased in the placebo group. The percentage of CD4+ T cells remained stable in the HCQ-treated group (18.1 +/- 9.2% before treatment vs 18.6 +/- 10.5% after treatment) and fell significantly in the placebo group (21 +/- 7% before treatment vs 19.3 +/- 6.3% after treatment; P = 0.032). However, this was not reflected as a change in absolute CD4+ counts for either group (HCQ, 262.8 +/- 166 cells/mm3 vs 251 +/- 163 cells/mm3; placebo, 312 +/- 121 cells/mm3 vs 321 +/- 124 cells/mm3). Mitogen- and antigen-specific responses remained constant in the HCQ group while T cell proliferative responses to Candida decreased in the placebo group (4.8 +/- 3.6 x 10(3) SI [stimulation index] vs 3.0 +/- 3.0 x 10(3) SI; P = 0.032). Lastly, serum interleukin 6 levels declined in the HCQ group (14.3 +/- 13.5 U/mL vs 12.0 +/- 16.7 U/mL; P = 0.023) but not in the placebo group (11.3 +/- 8.8 U/mL vs 7.0 +/- 11.7 U/mL); this was coincident with a decrease in serum immunoglobulin (Ig)G (2563 +/- 1352 mg/mL vs 2307 +/- 1372 mg/dL; P = 0.032), compared with the placebo group (2733 +/- 1473 mg/dL vs 2709 +/- 1501 mg/dL). No other parameters, including serum p24 and beta-2 microglobulin levels, were altered by HCQ therapy. HCQ thus may be useful in the treatment of patients with HIV-1 infection.
The oropharyngeal swallow was modeled with computer based animation using data from biplane videofluorographic and dynamic CT images of 10 ml liquid swallows of a volunteer subject. Tracings of oropharyngeal structures from synchronized, magnification adjusted, images of the posterior-anterior, lateral, and cross-sectional planes were aligned in three dimensions with graphics animation software. Twenty oropharyngeal configurations were created at 1/15 second intervals to dynamically illustrate the swallow. These three-dimensional reconfigurations could be sequenced into an animation routine. Software analysis of the model permitted quantification of structural movement and intrapharyngeal volume across time. Such analyses can be used to detail both the efficacy of individual functional elements of the swallow as well as global pump function. It is hoped that modeling the oropharyngeal swallow will be useful to analyze mechanisms of dysphagia and the mechanics of compensatory therapeutic strategies.
Glucose is the main source or energy for the mammalian cells and its entry is mediated via various transporters. About 7 facilitative (GULT-1 to -7) and 2 concentrative glucose transporters (SGLT-1 and -2) have been identified. The facilitative glucose transporters allow the glucose entry into the cell interior due to the concentration gradient and the latter via the Na+-dependent electrochemical gradient. They have similar structural motifs with 12-14 putative transmembrane domains with a predicted protein size varying from 50 to 76kDa. Some of the facilitative glucose transporters (GLUT-1, -2, -4 and -5) and both the sodium glucose co-transporters (SGLT-1 and -2) are expressed in the kidney. The transporters that are involved in the major transport of glucose in the kidney include GLUT-2 and SGLT-2. They are of high capacity and low affinity type and are expressed in the S1 segment of the proximal tubule. All the transporters expressed in the kidney are developmentally regulated. The mRNA expression of renal GLUTs is variable during the fetal and postnatal periods. On the other hand the mRNA of SGLTs increases steadily from the fetal period to maturity along with the increase in their functional activity, i.e., glucose uptake. Recent studies indicate that the SGLTs are believed to selectively regulate tubulogenesis since they are expressed in the metanephric tubules very early in the embryonic life in mammals.
Aldo-keto reductases (AKRs) are a family of monomeric oxido-reductases with molecular weight ranging from 35-40 kDa and currently includes upwards of 60 members. They are expressed in a wide variety of tissues, where they catalyze the NADPH-dependent reduction of various aliphatic and aromatic aldehydes and ketones. The functions of most of the family members are not well defined. But two members, aldehyde reductase (AKRIA) and aldose reductase (AKRIB), have been extensively studied. The latter has received the most attention since being relevant to the complications of diabetes mellitus. It is up-regulated during hyperglycemia, and at the same time there is an increased activity of the sorbitol pathway and non-enzymatic glycation of proteins with ensuing damage in various tissues. It is developmentally regulated in the ocular lens, and is believed to modulate lens fiber morphogenesis during fetal life. Unlike the other AKR family members that are ubiquitously expressed, recently a renal-specific oxio-reductase has been described that is expressed exclusively in the proximal tubules. Although, it has no homology with other AKR members, it binds to NADPH with high affinity and is up-regulated in streptozotocin-induced diabetes in mice. It is also developmentally regulated and seems to selectively modulate renal tubulogenesis during embryonic life.
A male dwarf blue sheep was collected 60 km south of Batang east to the Jinsha Jiang river, and a male Subei blue sheep (Greater form) was collected from Gansu, China, representing two geographically separated blue sheep forms. Chromosome preparations were prepared from fibroblast cultures. The dwarf blue sheep has a 2n = 54 and a karyotype with three biarmed formations that resulted from acrocentric chromosome fusions (based on the 2n = 60 Capra autosomal equivalents) 14p/5q, 27p/1q, and 29p/2q from the largest to the smallest biarmed chromosome, respectively. The 14p/5q fusion is metacentric, whereas the 27p/1q and 29p/2q are submetacentric. The Subei blue sheep had a 2n = 56, with only the 27p/1q and 29p/2q biarmed chromosome fusions. The remainder of the chromosomes in both blue sheep are acrocentric; the X is the largest acrocentric chromosome and the Y is a minute biarmed chromosome. Our observation is one evidence showing that chromosome evolution within blue sheep has followed a series of centric fusions resulting in the reduction of chromosome number, which is typical of all extant genera within the tribe Caprini.
Crossover interference is now known to exist in humans but to date has been ignored in routine genetic mapping because of the computational burden involved. In a recent paper by Weeks et al. [Hum Hered 1993;43:86-97], interference was accounted for by the use of a variety of multilocus feasible map functions and a crossover model of Goldgar and Fain [Am J Hum Genet 1988;43:38-45]. In this paper, we present an alternative approach to incorporating crossover interference into multilocus likelihood computation, by modelling the underlying chiasma process directly using the chi 2 model, supplemented by an assumption of no chromatid interference. This procedure was applied to the same CEPH consortium chromosome 10 data set that was analyzed by Weeks et al. A fit to the data was achieved which was significantly better than that offered by the no-interference model, and comparable to the best of the alternatives considered by Weeks et al. We briefly discuss the relative merits of the different models for interference.
A colony of cats affected with hypertrophic feline muscular dystrophy was used to study the occurrence of cardiomyopathy associated with dystrophin deficiency. Affected male and female cats, obligate carrier females, and unaffected healthy littermates were followed from 12 weeks of age into adulthood. Thoracic radiography, 2-D echocardiography, and 2-D-derived M-mode echocardiography were performed at 3-month intervals until 12 months of age and regularly thereafter. From 9 months of age, all affected cats had larger hearts than normal and carrier animals. Left ventricular wall thickness in systole and in diastole and interventricular septal thickness in systole were greater in affected cats 12 months and older when compared with normal or heterozygous animals (P < .05). The myocardium of affected cats was diffusely hypoechoic and thickened. Multiple hyperechoic foci were in the myocardium and papillary musculature. Shortening fraction was normal in all cats. Changes seen in carrier females included enlargement and hyperechogenicity of the papillary musculature after the age of 2 years. Gross and light microscopic examination revealed left ventricular wall thickening with multiple foci of mineralization in 2 of 5 hearts from dystrophin-deficient cats. Although approximately 10% of the normal dystrophin amount was present in the skeletal muscle, dystrophin could not be detected in the myocardium. Early onset concentric myocardial hypertrophy was present in all adult cats. Lesions were mainly localized in the myocardium of the left ventricular free wall and interventricular septum, papillary musculature, and the endocardium. Clinical signs of heart failure developed only infrequently in cats with hypertrophic feline muscular dystrophy.
Drugs acting at G protein coupled receptors can be classified in biological assays as either agonists, partial agonists, neutral antagonists, or as inverse agonists. Very little is known about the actual molecular events and structural changes that occur in the receptor following ligand binding and during transmission of a signal across the membrane. Therefore, the structural basis for the biological classification of drug action remains unknown. To date, the conformational state of G protein coupled receptors has been inferred from the activity of the effector enzyme modulated by the G protein. We have used two different approaches to monitor conformational changes in beta 2 adrenergic receptor. Fluorescence spectroscopy can be used to directly monitor structural changes in purified beta 2 adrenergic receptor in real-time. The emission from many fluorescent molecules is strongly dependent on the polarity of the environment in which they are located. Thus, fluorescent probes covalently bound to proteins can be used as sensitive indicators of conformational changes and protein-protein interactions. In addition, we examined functional differences between agonists and partial agonists using fusion proteins between wild-type beta 2 receptor or a constitutively active beta 2 receptor mutant and Gs alpha. These receptor-G protein fusion proteins guarantee highly efficient coupling with a defined stoichiometry. The results of these experiments will be discussed in the context of current models of G protein coupled receptor activation.
OBJECTIVE: To examine the impact of participation in community-based support groups and human immunodeficiency virus (HIV) viral load on sexual behavior among gay men. METHODS: Using self-administered questionnaires, 46 seropositive support-group participants and 20 seropositive comparison subjects were asked about viral load and frequency of unprotected anal intercourse in 1996 and 1997 following the XI International Conference on AIDS. RESULTS: Support group participants reported less unprotected receptive anal sex at follow-up than did comparison subjects. Overall, study participants with undetectable viral loads reported more unprotected anal intercourse at follow-up than did participants with detectable viral loads. CONCLUSION: Among HIV-seropositive gay men, knowledge of an undetectable viral load may contribute to high-risk sexual-risk behavior.
To find whether green tea has anti-obesity effects in mice, female ICR mice were fed on diets containing 1, 2 and 4% green tea powder for 16 weeks and the body weight and food intake were weighed. After the administration of green tea, the ovaries, kidneys, adrenals, liver, spleen, brain, pituitary and intraperitoneal adipose tissues in the mice were weighed and lipid levels in the serum and in the liver and serum leptin levels were measured. It was found that body weight increase and intraperitoneal adipose tissues were remarkably suppressed by the administration of diets containing 2 and 4% green tea powder. Food intake was suppressed by feeding the 4% green tea diet. Concentrations of total cholesterol in the liver, triglycerides in serum and liver and nonestrified fatty acids in serum from mice which were administered green tea diet were lower than those in the controls. Leptin levels in serum showed a decrease with green tea treatments. These results indicated that lipid metabolism in mice was suppressed by the administration of green tea powder and thereby the fatty accumulation and body weight increase was suppressed.
In this research work, a low-temperature examination method for scanning electron microscopy (SEM) is introduced. A water-absorbable polymer material, the sulfonated polyethylene (SPE) ion-exchange hollow fiber membrane, was used for the experiments. With this low-temperature technique, the wet morphology of the water-absorbable sulfonated polyethylene hollow fiber membrane was revealed. The results obtained from this investigation offer some important information to explain the behavior of the SPE hollow fiber membranes when they are applied in pervaporation separation of water/organic solvent mixtures, such as water/ethylene glycol, water/ethanol, and so forth.
Health professionals' clinical breast examination accuracy and skills are not optimal. We conducted a randomized trial to evaluate changes in physicians' and nurses' lump detection accuracy and examination skills after a training program emphasizing development of tactile skills and using silicone breast models containing lumps of varying sizes, degrees of hardness, and depth of placement. Sensitivity, specificity, and examination technique were measured before and four months after training in 43 experimental group and 46 control group participants. Mean sensitivity increased from 57% to 63% in the experimental group but decreased from 57% to 56% in the control group (P less than or equal to .05). The experimental group's posttest sensitivity was better for each lump characteristic, with statistically significant improvement for the very small (0.3 cm) and medium hard lumps. Duration of examination independently predicted sensitivity. Specificity decreased from 56% to 41% in the experimental group while it increased from 56% to 68% in the control group (P less than or equal to .05). Physicians had significantly higher mean sensitivity than nurses overall, as well as for the larger (1.0 cm), very small (0.3 cm), and softer lumps, but significantly lower mean specificity (33% versus 57%, P = .03). The experimental group improved significantly in five of six technique components while the control group improved in only one. To determine the effect of training on specificity in the clinical setting, we examined medical records of women seen by a subset of experimental and control physicians during the six months following training. There were no significant differences in the proportion of abnormal breast examinations reported or the number of mammograms ordered by experimental and control physicians. Our results show health professionals can be taught successfully to improve their clinical breast examination accuracy and skills.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.