Biomedical subjects
Publications and source records attributed to R Fan.
The manufacturing methods and testing results of the pneumatic left ventricular assist pump(L-Y pump) are introduced in this paper. The results demonstrate that L-Y pump is reliable, biocompatible and in keeping with the clinical requirements.
A technique for preserving fluorescence in retrogradely labelled neurons embedded in resin was developed. Four retrograde tracers were tested, Fast Blue (FB); Diamidino Yellow (DY); tetramethylrhodamine dextran (fluoro-ruby) (TMRD) and fluorescein dextran (fluoro-emerald) (FD). These tracers were applied to the cut end of the sciatic nerves in rats either by: (a) direct application of tracer crystals, or (b) dipping the nerve into an aqueous solution containing the tracer. Each lumbar spinal cord was removed and dehydrated by one of two methods: (a) conventional alcohol dehydration, or (b) dehydration through a graded series of aqueous methacrylate infiltration solutions (inert dehydration). Specimens were embedded in methacrylate and horizontal sections cut. The location of labelled motoneurons was mapped using a fluorescence microscope. Direct application of tracer crystals labelled more motoneurons than dipping. Fast Blue labelled considerably more motoneurons than tetramethylrhodamine. Labelling by all tracers was retained following methacrylate embedding. Fast Blue and Diamidino Yellow required inert dehydration, while tetramethylrhodamine dextran and fluorescein dextran were preserved using conventional dehydration. These results indicate that tissue labelled with commonly used fluorescent tracers can be processed and embedded in methacrylate, thereby permitting quantitative analysis by modern stereological methods.
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The neuroendocrine response to stressors increases the concentration of several endogenous mediators, some of which are immunosuppressive. However, quantitative aspects of these effects have been overlooked. Although it should be possible to predict the degree of suppression of particular immunological functions by measuring the concentrations of stress-related mediators such as corticosterone, this cannot be done with data presently available. This study was designed to develop regression models to predict the relationship between the area under the corticosterone concentration vs. time curve (AUC) and two immunological parameters. Models were developed using mice treated with exogenous corticosterone and mice subjected to various periods of restraint stress. The latter treatment was included to determine if the effects of corticosterone were different from those of corticosterone in association with the other mediators induced in a restraint-stress response. Models relating corticosterone AUC to expression of MHC class II proteins on splenocytes were very similar, whether the corticosterone was exogenous or produced as part of a restraint-stress response. This was also true for splenic natural killer (NK) cell activity. However, MHC class II expression was more sensitive to the effects of corticosterone or restraint than was NK cell activity. The corticosterone and restraint models predicted the previously published effect of a chemical stressor (ethanol) on MHC class II expression, but neither model predicted the suppression of NK cell activity by ethanol. These results have mechanistic implications, which are discussed in the context of previous studies. The quantitative models described here should be useful in determining and predicting the stress-related portion of chemical-induced immunosuppression. In addition, these models provide quantitative data essential for a complete understanding of stress-induced immunosuppression.
CBS human colon carcinoma cells are poorly tumorigenic in athymic nude mice, whereas FET colon carcinoma cells are non-tumorigenic. Both cell lines have well differentiated properties in tissue culture. Transforming growth factor alpha (TGF-alpha) was ectopically expressed by stable transfection of a TGF-alpha cDNA under repressible tetracycline control. The TGF-alpha-transfected cells showed enhanced clonal initiation and shortened lag phase growth in tissue culture without an alteration in doubling time in exponential phase relative to untransfected cells. Furthermore, the TGF-alpha transfectants showed increased independence from exogenous growth factors in clonal growth assays and induction of DNA synthesis after release from quiescence. Growth factor independence was associated with sustained epidermal growth factor receptor activation in quiescent TGF-alpha-transfected cells and the requirement of exogenous insulin for stimulation of quiescent cells to re-enter the cell cycle. Higher cloning, reduced lag time in tissue, and the acquisition of growth factor independence for DNA synthesis without a change in doubling time of TGF-alpha-transfected cells indicate that autocrine TGF-alpha functions by facilitating re-entry into the cell cycle from sub-optimal growth states rather than promoting or controlling the proliferation of actively cycling cells. The modulation of growth regulation by autocrine TGF-alpha was associated with increased malignant properties as TGF-alpha transfectants showed increased tumorigenicity in athymic nude mice. The administration of tetracycline reversed the effects of TGF-alpha expression in these cells both in vivo and in vitro, indicating that the alterations of the biological properties were due to the expression of TGF-alpha. Since these cells are continuously grown in a completely chemically defined medium without serum supplementation, it was possible to assign the mechanism underlying the generation of growth factor independence to the replacement of a requirement for exogenous insulin in parental cells by autocrine TGF-alpha.
Heat-shock protein 90 (Hsp90) coordinates the trafficking and regulation of diverse signalling proteins, but its precise role in regulating specific cellular targets is not known. Here we show that Hsp90 associates with endothelial nitric oxide synthase (eNOS) and is rapidly recruited to the eNOS complex by agonists that stimulate production of nitric oxide, namely vascular endothelial growth factor, histamine and fluid shear stress. Moreover, the binding of Hsp90 to eNOS enhances the activation of eNOS. Inhibition of signalling through Hsp90 attenuates both agonist-stimulated production of nitric oxide and endothelium-dependent relaxation of isolated blood vessels. Our results indicate that Hsp90 facilitates signalling mediated by growth-factor, G-protein and mechanotransduction pathways that lead to the activation of eNOS. These observations indicate that in addition to its role as a molecular chaperone involved in protein folding and maturation, Hsp90 may also be recruited to cellular targets depending on the activation state of the cell.
Haplotype mapping has emerged in the past few years as a powerful tool for the fine mapping of disease genes. It is typically carried out on a sample of affected individuals from a population isolate. If the chromosome neighborhood of a disease gene is saturated with markers, then each new mutation in the population or existing mutation introduced by a population founder exhibits a unique haplotype signature at the time of its introduction. Partial disruption of these signatures by recombination can be visualized in affects and provide important clues to the location of the disease gene. The current paper models haplotype evolution with the intention of clarifying the most favorable circumstances for haplotype mapping. Comparisons with linkage mapping are stressed. For dominant diseases, both deterministic and stochastic models are suggested. Numerical examples based on Finnish population parameters illustrate the general theory in the presence of the complications of selection, mutation, and slow, exponential growth of the isolate.
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To study histologically the biological behaviour of the grafts and the reactions in the receipt area after reconstruction of temporomandibular joint (TMJ), we have reconstructed experimentally removed TMJs on purebred juvenile pigs by transplanting autogenous costo-chondral grafts. The findings of continuously survey of histologic changes in the receipt areas and the grafts showed that autogenous grafts healed well with the surrounding soft tissues, and induced the mesenchymal-like cells from the receipt region, rather than the periosteal cells which might be left, to differentiate and ossify both within and at the surface of them, and they themselves were gradually replaced by the new-formed bone; and that active osteogenesis could also be seen within the thick tissues far from the graft, which could not be the result of graft's induction. It may be concluded that the new bone, both from the induction of the graft which acts as a framework and somehow from the outside tissues, reconstructs the new condyle and determines the postsurgical growth of the mandible.
A population-based case-control study was conducted in Beijing, as part of Sino-Monica Project, to explore etiology of lung cancer in non-smoking women. Results showed that there was certain association between passive smoking and lung cancer in non-smoking women, with an OR of 2.52, P < 0.05, and its strength also increased with cigarette-years of smoking. A statistically significant risk of lung cancer was observed in non-smoking women, as their passive cigarette-years accumulated to more than 200. Adenocarcinoma of the lung was more possibly induced by environmental tobacco smoke (ETS) (OR = 2.32, P < 0.05), and it seemed to have little relation between ETS and squamous lung cancer (OR = 1.04, P < 0.05).
The regulation of endothelial nitric oxide synthase (eNOS) by phosphorylation is poorly understood. Here, we demonstrate that eNOS is tyrosine-phosphorylated in bovine aortic endothelial cells (BAEC) using 32P metabolic labeling followed by phosphoamino acid analysis and by phosphotyrosine specific Western blotting. Treatment of BAEC with hydrogen peroxide and the protein tyrosine phosphatase inhibitor, sodium orthovanadate, increases eNOS tyrosine phosphorylation. Utilizing a novel immunoNOS assay, the increase in tyrosine phosphorylation is associated with a 50% decrease in the specific activity of the enzyme. Because eNOS is localized in plasmalemma caveolae, we examined if tyrosine phosphorylated eNOS interacts with caveolin-1, the coat protein of caveolae. Immunoprecipitation of eNOS from bovine lung microvascular endothelial cells resulted in the co-precipitation of caveolin-1. Conversely, immunoprecipitation of caveolin-1 resulted in the co-precipitation of tyrosine-phosphorylated eNOS. Thus, tyrosine phosphorylation is a novel regulatory mechanism for eNOS and caveolin-1 is the first eNOS-associated protein. Collectively, these observations provide a novel regulatory mechanism for eNOS and suggest that tyrosine phosphorylation may influence its activity, subcellular trafficking, and interaction with other caveolin-interacting proteins in caveolae.
Forty-three cases of aplastic anemia were treated with fetal blood transfusion, Chinese medicinal herbs and Vit. C. The results showed that the effective rate of the treated group was 79.1%, among them, the chronic aplastic anemia (CAA) was 88.9%, acute aplastic anemia (AAA) was 62.5%, both rates were higher than that of the control group (with western medicine alone, n = 46). The difference of treatment results between two groups was highly significant. The mechanism was that the therapy could rebuild hematopoietic function, modulate immune function and improve microcosmic environment in bone marrow so that it promoted in all aspect the recovery of hematopoietic function in organism.
Diabetic retinopathy is a leading cause of blindness in adults in Singapore and it is increasing in incidence. The difficulties and problems of screening for diabetic retinopathy were discussed as well as strategies laid out for overcoming this disease of national importance. Cost considerations and savings in health costs were also discussed. The authors suggested ways of instituting a nation-wide Diabetic Screening and Education programme with hospital diabetic centre based clinic as well as a mobile screening service. A five-year screening plan as well as the costs and equipment necessary for such a programme were examined.
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We propose the maximal mydriasis test (MMT) as a simple and safe means to provide the cataract surgeon with objective and dependable preoperative information on the idiosyncratic mydriatic response of the pupil. The MMT results of a consecutive series of 165 eyes from 100 adults referred for cataract evaluation are presented to illustrate the test's practical applications and value. The results enable the surgeon to anticipate problem eyes preoperatively so he or she can plan an appropriate and effective surgical strategy. The MMT has also improved out cost-effectiveness by cutting down unnecessary delays in the operating room and enabling better utilization of restricted costly resources.
Laser iridotomies in dark coloured irides are associated with higher complication and failure rates. A prospective clinical study to evaluate the use of the argon and Nd:YAG laser in sequential combination for iridotomy was carried out on 20 eyes of 13 patients with dark irides. Patent iridotomies were achieved in single treatment sessions for all the eyes. Iridotomy closure was observed in one eye during a mean follow-up period of 14 months (range 6-20 months). Complications from the treatment occurred in five eyes and were minor. Total mean energy used for the argon and Nd:YAG stages respectively were a third of most studies on pure argon and Nd:YAG iridotomies. Sequential argon-YAG laser iridotomy combines most of the advantages of both laser types while avoiding some of their disadvantages. We find it a safe and effective tool for iridotomy in otherwise difficult dark irides.
Na(+)-H+ exchange in the rat proximal tubule luminal membrane increases approximately 30% within 15 min after the contralateral uninephrectomy. The present study was designed to test whether altered renal sympathetic nerve outflow to the remaining kidney is the underlying mechanism of increased antiport activity and whether suppression of Na(+)-H+ antiport activity by renal denervation inhibits renal hypertrophy in the remaining kidney after uninephrectomy. Sprague-Dawley rats were divided into four groups: 1) sham operated, 2) uninephrectomized, 3) uninephrectomized with prior denervation of the remaining kidney, and 4) contralateral renal denervation. Na(+)-H+ antiport activity (brush-border vesicles), Na(+)-K(+)-ATPase activity (basolateral vesicles), and kidney weight were measured days 1-7. On days 1 and 7, Na(+)-H+ antiport activity and Na(+)-K(+)-ATPase activities were significantly greater in uninephrectomized rats. Denervation of the remaining kidney before contralateral uninephrectomy prevented the stimulation of the antiporter and Na(+)-K(+)-ATPase activity, but failed to inhibit renal hypertrophy by day 7. In separate experiments, contralateral renal denervation alone without removal of the kidney stimulated the Na(+)-H+ antiporter and Na(+)-K(+)-ATPase activity. Kidney weight, however, remained unchanged. The results demonstrate a dissociation between the activation of the Na(+)-H+ antiporter and induction of renal hypertrophy in vivo.