Search PubMed⌕ Search

Biomedical subjects

S Wei

Publications and source records attributed to S Wei.

At least 109 records · Page 6Linked to original sources

An integrated genetic map of the rat with 562 markers from different sources.

Genetic maps are the primary resources for genetic study. Genetic map construction was quite difficult in the past decade for lack of polymorphic markers. This situation has been changed since the development of microsatellite markers or simple sequence length polymorphisms (SSLPs) because they are abundant and more polymorphic. Here we report the construction of an integrated genetic map of the rat derived from two F2 intercrosses. A map of 376 markers from 160 (OLETF x F344)F2 progenies and a map of 333 markers from 71 (F344 x LEC)F2 animals are integrated by use of common set of 120 anchor markers chosen to be spaced at an average of 15 cM in the genome. The resulting integrated map with 194 newly developed rat markers from WIBR/MIT CGR, 269 Mit/Mgh markers, 94 Wox markers, and 5 markers of various origins covers the majority of 21 chromosomes of the rat with a total genetic distance of 1797 cM and an average marker spacing of 3.2 cM. The current map provides detailed information for markers from different sources and, therefore, should be helpful to the research community.

Animals↗

The fragmented neuronal Golgi apparatus in amyotrophic lateral sclerosis includes the trans-Golgi-network: functional implications.

The Golgi apparatus (GA) of spinal cord motor neurons is fragmented in sporadic amyotrophic lateral sclerosis (ALS), and in asymptomatic and symptomatic transgenic mice expressing the G93A mutation of the gene of the human Cu,Zn superoxide dismutase, found in certain cases of familial ALS (FALS) [Gonatas NK (1994) Am J Pathol 145:751-761; Mourelatos Z, et al. (1996) Proc Natl Acad Sci USA 93:5472-5477]. A similar fragmentation of the GA has been described in cells treated with microtubule-depolymerizing drugs, where the organelle is functional and contains both Golgi stacks and trans-Golgi network (TGN), the compartment of exit and targeting of proteins processed by the GA. To gain a better definition of the structure of the fragmented neuronal GA in ALS, four cases of sporadic ALS with numerous Bunina bodies in spinal cord motor neurons were stained with antibodies against human TGN and against the lumenal and cytoplasmic domains of MG160, a protein of the medial cisternae of the GA. The fragmented GA was stained with the three antibodies, indicating the presence of both Golgi stacks and TGN. Furthermore, the staining of the fragmented GA by the antiserum against the cytoplasmic domain of MG160 indicates that the fragmentation of the GA is not the result of a terminal and global cytoplasmic lytic event. The Bunina bodies were not stained by the anti-MG160 antibodies, suggesting that they are not derived from the GA. The perikarya of neurons with fragmented GA showed normal immunoreactivity with antibodies against the heavy neurofilament subunit and alpha-tubulin. However, because of the lack of appropriate antibodies the localization of proteins such as spectrin, ankyrin, centractin and others which link the microtubules with the GA were not done. The findings support the hypothesis that, in ALS, the fragmented neuronal GA is functional. Additional work with animal models of ALS may establish whether the fragmentation of the GA is a sign of early degeneration or a compensatory reaction of the injured motor neuron.

Aged↗

Intact autocrine activation and cytokine production by PMNs from injured adults with elevated Candida antigen titres.

Injured patients with Candida antigen titres have increased mortality due to sepsis. Polymorphonuclear leucocytes (PMNs) from injured patients with elevated Candida antigen titres demonstrate impaired function against Candida albicans growth when compared with PMNs from injury matched controls. To determine if PMN dysfunction is global, PMNs from patients with positive Candida antigen titres were evaluated for their ability to activate the anticandidal function of normal PMNs (autocrine activation) and to produce tumour necrosis factor (TNF) and interleukin 8 (IL8), known activators of PMN anticandidal function, this study demonstrates that the PMN dysfunction is not global, as PMN cytokine production and autocrine activation remain intact.

Adult↗

Altered expression of sialylated carbohydrate antigens in HT29 colonic carcinoma cells.

To determine whether cell growth conditions impacted carbohydrate expression, HT29 cells were gradually transferred from a conventional glucose-containing media to a glucose-free galactose containing media. Indirect immunofluorescence on acetone fixed cells showed increased expression of sialyl Lewis A antigen (CA19-9), sialyl Lewis C (DUPAN2) and Tn/sialyl-Tn on the surface of HT29 cells grown in the glucose-free galactose containing media compared to those grown in the glucose containing media. Sialyltransferases responsible for the synthesis for these sialylated epitopes were Increased in the galactose-fed HT29 cells. Media overlying the cells was subjected to isopycnic ultracentrifugation in cesium chloride and the fractions derived from both glucose and galactose media with equivalent buoyant densities of 1.56 g/L, which are predicted to contain mucin glycoforms, were further separated by HPLC using a Mono-Q anion exchange column. The chromatograph of eluent from the sample derived from the cells growing in the galactose containing media showed an increased peak that reacted with the anti-sialyl Lewis A antibody, CA19-9. These results show that alteration of in vitro culture conditions may cause HT29 colonic carcinoma cells to alter the expression of sialylated carbohydrates.

Adenocarcinoma↗

Identification of a quantitative trait locus influencing plasma insulin levels after 70% pancreatectomy using the OLETF rat.

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model for obese-type non-insulin-dependent diabetes mellitus (NIDDM) in humans. The OLETF rat has poor capacity for proliferation of pancreatic beta-cells after partial pancreatectomy, which may be the critical pathogenetic event in NIDDM development. The poor pancreatic beta-cell proliferation in this model is characterized by reduction in beta-cell mass and decrease in insulin content in the remnant pancreas. Our investigation was designed to identify quantitative trait loci (QTLs) responsible for beta-cell mass and plasma insulin levels after partial pancreatectomy by performing a genome-wide scan in an F2 intercross obtained by mating the OLETF and the Fischer-344 (F344) rats. We have identified a suggestive QTL for the plasma insulin levels, near D20Mgh5 on rat chromosome 20, with a maximum lod score of 3.75 which accounts for 20% of the total variance, while no QTLs were detected for beta-cell mass. This chromosome 20 QTL, whose OLETF allele is associated with low plasma insulin levels through acting in an incompletely recessive manner, may affect insulin secretion itself rather than beta-cell proliferation.

Animals↗

X-linked locus is responsible for non-insulin-dependent diabetes mellitus in the OLETF rat.

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat has been recently established as the best model of non-insulin-dependent diabetes mellitus (NIDDM) with mild obesity. In this study, we found that the F1 progeny produced from the crosses of OLETF and F344 rats exhibit a reciprocal cross effect on NIDDM-relevant phenotypes, fasting and postprandial glucose levels and body weight, suggesting the existence of X-linked locus affecting susceptibility to NIDDM. We thus examined the linkage between 7 X-linked microsatellite markers and NIDDM-relevant phenotypes, using 160 (OLETF x F344)F2 progeny. Suggestive evidence for a X-linked locus affecting glucose levels at 120 min after glucose administration was found in a region near X-linked marker, DXMgh4. The identified locus also showed significant effects on fasting glucose levels and body weight.

Animals↗

Local action of exogenous growth hormone and insulin-like growth factor-I on dihydroxyvitamin D production in LLC-PK1 cells.

Previous in vivo studies have shown that growth hormone (GH) affects vitamin D and mineral metabolism. Insulin-like growth factor-I (IGF-I) was recently reported to be a regulator of renal 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) production, suggesting that it mediates the effects of GH on vitamin D metabolism. However, there is no direct evidence to support this. The present study was designed to investigate the in vitro effects of GH and IGF-I on the renal production of 1,25-(OH)2D3 and 24,25-dihydroxyvitamin D3 (24,25-(OH)2D3) in a pig kidney cell line, LLC-PK1. Confluent cells were preincubated in serum-free medium with hormone (GH or IGF-I) or vehicle, and then incubated with 25-[3H]OHD3. The levels of 1,25-[3H](OH)2D3 and 24,25-[3H](OH)2D3 produced were determined after lipid extraction and HPLC purification. Production of 1,25-(OH)2D3 and 24,25-(OH)2D3 was increased after both IGF-I and GH preincubation in a dose-dependent manner. Significant increases were found after preincubation with 13 nmol/l IGF-I (1,25-(OH)2D3, 1.8-fold: 24,25-(OH)2D3, 1.5-fold)or 0.9 or 9 nmol/lGH (1,25-(OH)2D3, 1.3-fold and 1.5-fold; 24.25-(OH)2D3, 1.4-fold and 1.5-fold respectively). Furthermore, the effect of 9 nmol/l GH on 1.25-(OH)2D3 and 24,25-(OH)2D3 production was blocked in the presence of IGF-I receptor monoclonal antibody. These results confirm that IGF-I acts on renal tubules, resulting in induction of 1,25-(OH)2D3 and 24,25-(OH)2D3 production, and the findings suggest that GH stimulates 1.25-(OH)2D3 and 24,2 5-(OH)2D3 production by increasing local IGF-I production in the kidney.

24,25-Dihydroxyvitamin D 3↗

Effects of combined radiation and thermal burn injury on the survival of skin allograft and immune function in rats.

OBJECTIVES: To investigate the effects of combined radiation and thermal burn injury on the survival of skin allografts and to analyze the relationship between the prolongation of allograft survival and the changes of immune functions of the thymocytes and splenocytes in rats. METHODS: Wistar rats were irradiated with 3, 4, 5, 6 and 8 Gy of gamma rays. Thirty minutes after radiation, 15% TBSA III-degree burn was inflicted to the rats. Twenty-four hours after the burn injury, allografts were used to cover the burn wounds. In the 8 Gy group, 1 hour before skin grafting, the bone marrow cells (4 x 10(8)) from the same donor were also transplanted. All rats were carefully observed after injury. The rats with single radiation injury of 5 Gy gamma rays, with single burn injury and with combined radiation-burn injury were killed 3, 7, 10, 15 and 30 days after skin grafting for immunological assay and pathological study. RESULTS: All the allografts in the single burn group were rejected in 10 days. In the combined injury groups, the survival rates of the allografts in rats undergoing 3 and 4 Gy radiation were 20% and 30%, respectively. In the combined injury groups undergoing 5, 6 and 8 Gy radiation, the 10-day survival rates of the allografts were 69%, 88% and 100% respectively, and the 30-day survival rates in the three groups were 36%, 42% and 100% separately. The grafted allogenic skin, with normal epithelial cells and good vascularity, healed well with the recipient's skin. Hairs grew well from the allografts 30 days after grafting. Three, 7 and 15 days after allografting, in the single burn group, the proliferative activities of the thymocytes were 90%, 185% and 130% of the preinjury level, and the antibody forming capacities of the splenocytes were 200%, 171% and 300% of the preinjury level, respectively; in the combined injury groups, the proliferative activities were 6%, 99% and 91% of the preinjury level, and the forming capacities were 2%, 36% and 90% of the preinjury level. CONCLUSIONS: The survival rate of allograft in rats undergoing combined radiation and thermal burn injury rises with the increase in radiation dosage. The allograft covering single bun injury is severely rejected by immune reaction. The prolongation of the survival of allograft in combined injury group mainly results from radiation that suppresses immune functions.

Animals↗

[Effects of neuroactive substances on intracellular free Ca2+ concentration in isolated outer hair cells of the guinea pig cochlea].

OBJECTIVE: To measure the effects of neuro-active substances on intracellular free Ca2+ concentration ([Ca2+]i) in isolated outer hair cells(OHCs) of the guinea pig cochlea. METHODS: The fura-2 microfluorimetry was used to measure changes of [Ca2+]i in OHCs of the guinea pig cochlea after application of acetylcholine, ATP and carbacholine. RESULTS: Acetylcholine, ATP and carbacholine increased [Ca2+]i (acetylcholine: 0.74 +/- 0.12 mumol/L, ATP: 0.65 +/- 0.11 mumol/L, carbacholine: 1.16 +/- 0.27 mumol/L) in OHCs in the presence of extracellular Ca2+. In the absence of extracellular Ca2+, however, only ATP induced a gradual and small [Ca2+]i elevation, whereas other substances did not. CONCLUSION: Acetylcholine and carbacholine, the cholinergic mascarinic agonists, increased [Ca2+]i in OHCs by acting at receptor-induced ion channel resulting in Ca2+ efflux. ATP-induced elevation of [Ca2+]i without Ca2+ in extracellular medium is due to a release of Ca2+ from an intracellular reservoir.

Acetylcholine↗

[Separation of human bladder cancer cells from bone marrow with a kind of immunomagnetic microspheres].

By binding a monoclonal antibody BDI-1 to polystyrene magnetic micospheres using physical and chemical methods together, a kind of immunomagnetic microspheres (IMMS), which can specifically bind target cells and give it magnetic response, was sucessfully constituted. The results of indirect immunofluorescence and cell binding suggest that IMMS can effectively bind target cells while do not have non-specific binding activity. The influence of antibody added and the ratio between IMMS and cells were also studied. After purging cancer cells from bone marrow of mice with IMMS, the cancer cells were effectively removed while most of the bone marrow cells were recovered.

Animals↗

[In vitro release kinetics and hypoglycemic effect on diabetic rats after oral administration of insulin loaded nanoparticles].

The insulin-loaded polyalkylcyanoacrylate nanoparticles (INS-NP) were made with Dextran 70 as the stabilizer. The mean diameter of INS-NP was 252.4 nm with a poly dispersity of 0.005. The associating ratio of insulin to the nanoparticles reached 70.1% +/- 2.3%, while the loading capacity was 0.14 u.mg-1. Studies on in vitro release kinetics showed that release profiles can be well modelled using a biexponential function. The burst effect was obvious, and a faster release was observed in acidic media. After various doses of INS-NP were intragastrically given to diabetic rats, significant decrease of glucose level was achieved in the 10 and 20 u.kg-1 groups, with no significant difference between these two doses. The relative bioavailability after p.o. administration of INS-NP 10 u.kg-1 over s.c. administration of insulin solution 1 u.kg-1 was 7.58% calculated by the area over the curve of glucose level (%) versus time profiles. The correlation was obvious between the % of insulin released at pH 7.0 and the % of glucose decreased within the first 7 hours. Hence, an oral insulin preparation with rather high bioavailability was provided in this study, and its shorter effective time will make it more convenient for the control of the glucose level in clinics.

Animals↗

[Multiple dose pharmacokinetic and bioavailability studies of oral sustained release and conventional formulations of isosorbide-5-mononitrate in healthy volunteers].

The pharmacokinetics of a new sustained release tablets (40 mg, qd) of isosorbide-5-mononitrate (IS-5-MN) was investigated together with a conventional preparation (20 mg, bid) after multiple oral administration in ten healthy human subjects using an open, randomized two-way crossover experimental design. Based on three statistical analyses of the area under the plasma concentration-time curve (AUC), the two tablet formulations are judged to be bioequivalent (P > 0.1), with a relative bioavailability of 108.95% for the IS-5-MN sustained release formulation. Pharmacokinetic data showed that the sustained release formulation reached mean peak plasma levels significantly later and lower minimum plasma concentration (Cmin), compared with the conventional preparation. But no statistically significant difference was found for other pharmacokinetic parameters including peak plasma levels (Cmax), AUC, elimination constant (Ke), elimination half-life (T1/2) and fluctuation index (FI) between the two preparations (P > 0.05).

Adult↗

[A method of morphological observation on the endothelialization of bioprosthetic heart valve materials in vitro].

In order to examine the endothelialization of yak pericardial materials in vitro, we used Wright staining and successfully observed the morphology, number and order of endothelial cells seeded on pericardial patches under light microscope. Compared with scanning electron microscopy, the method of light microscopy is simple, easy to do and may be carried out at any time. In laboratory, it brings much convenience in morphological observation on the endothelialization of biomaterials and therefore is worth recommendation.

Animals↗

Single and multiple dose pharmacokinetic studies of oral sustained release and non-sustained release formulations of isosorbide-5-mononitrate in healthy volunteers.

The pharmacokinetics of a new sustained release tablet (40 mg, "test") of isosorbide-5-mononitrate (CAS 16051-77-7, IS-5-MN) was investigated together with a reference preparation (20 mg, "reference") after single and multiple oral administration in ten healthy human subjects using an open, randomised two-way crossover experimental design. Based on the statistical evaluation of the area under the plasma concentration-time curve (AUC), the two tablet formulations are judged to be the same with regard to the amount absorbed. Pharmacokinetic data showed that with the test tablet significantly lower and delayed mean peak plasma levels (Cmax) were reached compared with the reference preparation in both single and multiple dose studies. The test formulation also produced lower minimum plasma concentration (Cmin). However, there was no statistically significant difference for other pharmacokinetic parameters, including the elimination rate constant (Kel), the elimination half-life (t1/2) and the peak-trough fluctuation constant (PTF) between the two treatments. It was demonstrated that the new sustained release formulation of isosorbide-5-mononitrate could be useful in clinical practice for the treatment of angina pectoris and congestive heart failure.

Adult↗

Retinyl ester hydrolysis and retinol efflux from BFC-1beta adipocytes.

Adipose tissue is an important storage depot for retinol, but there are no data regarding retinol mobilization from adipose stores. To address this, dibutyryl cAMP was provided to murine BFC-1beta adipocytes and its effects on retinol efflux assessed. High performance liquid chromatography analysis of retinol and retinyl esters in adipocytes and media indicated that cAMP stimulated, in a time- and dose-dependent manner, retinol accumulation in the culture media and decreased cellular retinyl ester concentrations. Study of adipocyte retinol-binding protein synthesis and secretion indicated that cAMP-stimulated retinol efflux into the media did not result from increased retinol-retinol-binding protein secretion but was dependent on the presence of fetal bovine serum in the culture media. Since our data suggested that retinyl esters can be hydrolyzed by a cAMP-dependent enzyme like hormone-sensitive lipase (HSL), in separate studies, we purified a HSL-containing fraction from BFC-1beta adipocytes and demonstrated that it catalyzed retinyl palmitate hydrolysis. Homogenates of Chinese hamster ovary cells overexpressing HSL catalyzed retinyl palmitate hydrolysis in a time-, protein-, and substrate-dependent manner, with an apparent Km for retinyl palmitate of 161 microM, whereas homogenates from control Chinese hamster ovary cells did not.

Adipocytes↗