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Biomedical subjects

Y Liang

Publications and source records attributed to Y Liang.

At least 217 records · Page 12Linked to original sources

Bromocriptine/SKF38393 ameliorates islet dysfunction in the diabetic (db/db) mouse.

Dysfunction of pancreatic islets plays a crucial role in the etiology of type II diabetes. Chronic hyperglycaemia or hyperlipidaemia may impair islet function. Previous studies by our laboratory have demonstrated that dopaminergic agonists ameliorated hyperglycaemia and hyperlipidaemia in obese and diabetic rodents. In the present study, we investigated the effect of a treatment with the dopamine D2/D1 receptor agonists (bromocriptine/SKF38393, BC/SKF) on islet dysfunction in db/db mice. Our results show that a 2-week BC/SKF treatment markedly reduced hyperglycaemia and hyperlipidaemia, and significantly improved islet dysfunction demonstrated by an increase of secretagogue-stimulated insulin release from islets of db/db mice to levels observed in islets from lean mice. There was also a fourfold increase of insulin content in the pancreas of BC/SKF-treated db/db mice compared with that in untreated controls. The effect of BC/SKF on islet function cannot be mimicked in pair-fed animals. BC/SKF had no direct stimulatory effect on islet insulin secretion, suggesting BC/SKF treatment improved islet function via an indirect mechanism. This treatment markedly improved the abnormally elevated daily levels of corticosterone, blood glucose and plasma lipids, supporting the view that BC/SKF may affect the neuroendocrine system that in turn regulates peripheral metabolism and thereby improves islet function.

Animals↗

Langerhans cells in prurigo nodularis investigated by HLA-DR and S-100 immunofluorescence double staining.

The Langerhans cell is one of the antigen-presenting cells in the immune system. To study the presence of cutaneous Langerhans cells in prurigo nodularis, age- and sex-matched prurigo nodularis patients and healthy volunteer skin biopsies were investigated by an HLA-DR and S-100 immunohistochemical double staining method. The results showed that the HLA-DR- and S-100-immunoreactive (IR) Langerhans cells were altered in prurigo nodularis epidermis and dermis. The number of epidermal Langerhans cells in the prurigo nodularis patients was decreased in five and increased in two cases. In the dermis, the HLA-DR- and S-100-IR cells were apparently more numerous than in the controls. In the involved skin there were also more S-100-IR coarse nerve fibres in the dermis as compared to controls. The results indicate that dermal Langerhans cells (HLA-DR and S-100 double-labeled) as well as other dermal HLA-DR- and S-100-IR dendritic cells, but most likely not epidermal Langerhans cells, may be critically involved in the development or persistence of prurigo nodularis.

Aged↗

Additive effect of mifepristone and tamoxifen on apoptotic pathways in MCF-7 human breast cancer cells.

MCF-7 cells growing in culture were used to study the mechanism of the antiproliferative activity of the antiprogestin mifepristone, as compared with the antiestrogen 4-hydroxytamoxifen or the combination of both. These steroid antagonists induced a significant time- and dose-dependent cell growth inhibition (cytotoxicity). This inhibition of cell survival was associated with a significant increase in DNA fragmentation (apoptosis), downregulation of bcl2, and induction of TGFbeta1 protein. Abrogation of the mifepristone- and/or 4-hydroxytamoxifen-induced cytotoxicity by TGFbeta1 neutralizing antibody confirms the correlation between induction of active TGFbeta1 and subsequent cell death. The effect of a combination of mifepristone and 4-hydroxytamoxifen on cell growth inhibition, on the increase in DNA fragmentation, bcl2 downregulation, and induction of TGFbeta1 protein was additive and significantly different (P < 0.05) from the effect of monotherapy. A translocation of protein kinase C (PKC) activity from the soluble to the particulate and/or nuclear fraction appeared to be also additive in cells treated with a combination of both 4-hydroxytamoxifen and mifepristone. These results suggest that the mechanism of the additive antiproliferative activity of mifepristone and tamoxifen could be explained at least in part by an additive induction of apoptosis in both estrogen and progesterone receptor positive MCF-7 breast cancer cells. A bcl2 downregulation, the PKC transduction pathway, and TGFbeta1 expression seem to be involved in this additive mechanism of action. Our data further suggest that a combination of an antiprogestin with tamoxifen may be more effective than tamoxifen monotherapy in the management of human breast cancer.

Apoptosis↗

Effect of antiprogestins and tamoxifen on growth inhibition of MCF-7 human breast cancer cells in nude mice.

This is the first report demonstrating an in vivo antitumor activity of antiprogestins (mifepristone, onapristone) alone and in combination with tamoxifen in the MCF-7 human breast cancer model. The MCF-7 cells produced progressive growing tumors in female nude mice supplemented with 17beta-estradiol. Tumor regression was observed following either estrogen ablation alone or estrogen ablation in combination with tamoxifen. Monotherapy with tamoxifen or antiprogestins caused a retardation of estrogen-induced tumor progression. Complete inhibition or prevention of tumor growth occurred as a result of simultaneous administration of mifepristone and tamoxifen. The addition of mifepristone in this combination treatment was also effective in delaying or preventing tumor escape (relapse) from the antiestrogenic (antitumor) effect of tamoxifen. These results suggest a potential clinical benefit of adding an antiprogestin to antiestrogen therapy of breast cancer patients.

Animals↗

Light and electron microscopic demonstration of the p75 nerve growth factor receptor in normal human cutaneous nerve fibers: new vistas.

The nerve growth factor and its receptor are important in nerve growth, differentiation, maturation, and maintenance. In order to explore the exact distribution of p75 low-affinity nerve growth factor receptor (p75 NGFr) expression in cutaneous nerve fibers, p75 NGFr and neuron-specific enolase double immunofluorescence and immunoelectron microscopic studies were conducted on normal human skin samples. After p75 NGFr and neuron-specific enolase immunofluorescence double staining, the dermal nerves were strongly p75 NGFr-immunoreactive (IR); however, very few p75 NGFr-IR nerve fibers were found in the epidermis. p75 NGFr immunoreactivity was found mainly in the peripheral part of cutaneous nerve trunks and fibers, whereas neuron-specific enolase immunoreactivity was mainly seen within the axons. After ultrastructural immunostaining, the Schwann cell membrane was strongly p75 NGFr-IR. The Schwann cell membrane facing the connective tissue was more strongly p75 NGFr-IR than the part of the membrane close to the axon; the Schwann cell cytoplasm nearest to the membrane sometimes also showed a high p75 NGFr immunoreactivity, whereas the rest of the cytoplasm was generally more weakly p75 NGFr-IR; however, the axon itself seldom showed any such immunoreactivity; actually, only a few parts of the axonal membrane revealed a weak staining, leaving most of the membrane unstained. The axoplasm was not p75 NGFr-IR. The results--that in human cutaneous nerves it is mainly the Schwann cells that express p75 NGFr immunoreactivity--further stress the active role of the glial ensheathment in the control and maintenance of a normal target innervation.

Fluorescent Antibody Technique↗

A serotonin-like immunoreactivity is present in human cutaneous melanocytes.

Immunohistochemistry was applied in the investigation of the possible existence of serotonin in human skin. It was found that epidermal melanocytes express a serotonin-like immunoreactivity. The immunoreactivity was associated with both the cytoplasm and the cellular membrane, though the latter was only found in certain cells. The serotonin anti-serum labeled the same cells as NKI-beteb, which is known as a reliable marker of melanocytes. Blocking experiments showed that both serotonin and NKI-beteb have different epitopes in the melanocytes. In in vitro studies, serotonin-like immunoreactivity appeared in approximately 90% of cultured human melanocytes, and was found both in the cytoplasm and also in the nuclei. Thus, we believe the melanocytes to be the origin of serotonin (or a serotonin-like molecule) in the skin.

Antibodies, Monoclonal↗

A novel frameshift mutation induced by an adenosine insertion in the polycystic kidney disease 2 (PKD2) gene.

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common Mendelian disorders and is genetically heterogeneous. Linkage studies have shown that the majority (approximately 85%) of ADPKD cases are due to mutations in PKD1 on chromosome 16p13.3, while mutations in PKD2 on chromosome 4q21-q23 are thought to account for most of the remaining cases. In this report, we describe the mutation in a large four-generation ADPKD family (TOR-PKD77) which we had mapped to the PKD2 locus by linkage analysis. In this family, we screened for mutations by directly sequencing two nested RT-PCR fragments (PKD2N1 and PKD2N2) that cover approximately 90% of the PKD2 open reading frame. In the affected members, we identified a novel single adenosine insertion (2160InsA) in the PKD2N2 fragment. This mutation occurred in the polyadenosine tract (nt2152-2159) of exon 11 and is predicted to result in a frameshift with premature translation termination of the PKD2 product, polycystin 22, immediately after codon 723. The truncated polycystin 2 is predicted to lack the calcium-binding EF-hand domain and two cytoplasmic domains required for the homodimerization of polycystin 2 with itself and for the heterodimerization of polycystin 2 with polycystin 1.

Adenosine↗

Genetic mapping refines DFNB3 to 17p11.2, suggests multiple alleles of DFNB3, and supports homology to the mouse model shaker-2.

The nonsyndromic congenital recessive deafness gene, DFNB3, first identified in Bengkala, Bali, was mapped to a approximately 12-cM interval on chromosome 17. New short tandem repeats (STRs) and additional DNA samples were used to identify recombinants that constrain the DFNB3 interval to less, similar6 cM on 17p11.2. Affected individuals from Bengkala and affected members of a family with hereditary deafness who were from Bila, a village neighboring Bengkala, were homozygous for the same alleles for six adjacent STRs in the DFNB3 region and were heterozygous for other distal markers, thus limiting DFNB3 to an approximately 3-cM interval. Nonsyndromic deafness segregating in two unrelated consanguineous Indian families, M21 and I-1924, were also linked to the DFNB3 region. Haplotype analysis indicates that the DFNB3 mutations in the three pedigrees most likely arose independently and suggests that DFNB3 makes a significant contribution to hereditary deafness worldwide. On the basis of conserved synteny, mouse deafness mutations shaker-2 (sh2) and sh2J are proposed as models of DFNB3. Genetic mapping has refined sh2 to a 0.6-cM interval of chromosome 11. Three homologous genes map within the sh2 and DFNB3 intervals, suggesting that sh2 is the homologue of DFNB3.

Alleles↗

Histamine-containing mast cells and their relationship to NGFr-immunoreactive nerves in prurigo nodularis: a reappraisal.

The mast cell, which is a histamine-containing cell, has been found to have far more functions in skin inflammation than hitherto understood. To investigate the appearance of mast cells in prurigo nodularis, histamine immunohistochemistry in combination with nerve growth factor receptor (NGFr) double-staining as well as electron microscopic studies were performed. The results revealed that the histamine-containing cell number was increased in the lesional dermis. The mast cell size was also increased and the shape had become more dendritic. They tended to contact the epidermis and even infiltrated into it. In the histamine and NGFr double-staining, both an increased histamine-containing mast cell number and an increased number of NGFr-immunoreactive nerve fiber profiles were revealed in the upper dermis of the prurigo nodularis lesional skin. Mast cells were seen in close vicinity to NGFr-positive nerves and sometimes even seemingly to contact single nerve fibers. At the ultrastructural level, it is obvious that the mast cell bodies become larger, having more abundant cytoplasm and organelles (e.g. mitochondria), but comparatively fewer characteristic granules. Mast cells were often observed to sprout long dendrites, with or without granules. The cells were also frequently seen to contact other cell types, and a mast cell infiltration into the epidermis was also found. The statistical results of mast cell numbers showed a significant increase in prurigo nodularis lesional skin compared to the normal controls. The present results further indicate that mast cells, together with cutaneous nerve fibers, are actively involved in the pathogenesis of the disease.

Aged↗

Effects of copper-aspirin complex on platelet aggregation and thrombosis in rabbits and mice.

The effects of intragastric and intraduodenal copper-aspirin complex on rabbit platelet aggregation were observed by Born's method. Myers's method was used to evaluate the antithrombotic effect of copper-aspirin complex in mice. In-vitro copper-aspirin complex selectively inhibited arachidonic acid-induced platelet aggregation with an IC50 value (concentration resulting in 50% inhibition) of 13.2 microM (95% confidence limits 9.1-16.8 microM). Copper-aspirin complex (10 mg kg(-1) given intragastrically or intraduodenally) was more potent than aspirin in inhibiting arachidonic acid-induced platelet aggregation. Copper-aspirin complex (10 mg kg(-1)) had a stronger inhibitory effect and a longer duration of action when given intragastrically than when given intraduodenally. It was shown by radioimmunoassay that copper-aspirin complex significantly reduced the level of thromboxane B2 in plasma while markedly increasing that of 6-ketoprostaglandin F1alpha (6keto-PGF1alpha). Copper-aspirin complex (10 mg kg(-1) given intragastrically for 7 days) significantly reduced mouse mortality caused by intravenous injection of arachidonic acid. The results suggest that both in-vitro and in-vivo copper-aspirin complex is more potent in selectively inhibiting arachidonic acid-induced platelet aggregation than aspirin. When given intragastrically the complex has a more potent antiplatelet effect and a longer duration of action than when given intraduodenally. The antithrombotic effect of the complex was more potent than that of aspirin.

6-Ketoprostaglandin F1 alpha↗

Objective measurement of motion in patients undergoing spiral CT examinations.

PURPOSE: To develop and evaluate an objective measurement of patient motion during spiral computed tomography (CT). MATERIALS AND METHODS: An acrylic rod was attached along the length of the torso in 109 patients (56 women, 53 men; age range, 21-79 years; mean age, 51 years) who underwent abdominal spiral CT examinations. Subjective evaluation of motion was graded on a five-point scale by two radiologists. Objective measurements of motion were determined by means of computer reconstruction of the rod in three dimensions and calculation of the deviation of the rod from its estimated position in the motionless state with time. RESULTS: Complete data were available in 98 patients. Subjective and objective measurements of patient motion showed a moderately high Spearman correlation coefficient of .49 (P < .001). The correlation between either observer and objective measurements was similar to the correlation between one observer and the other. CONCLUSION: This objective technique for assessing patient motion correlated well with subjective methods and may be useful in evaluating scanning parameters that may affect patient motion and hence scan quality.

Artifacts↗

Spiral CT with ionic and nonionic contrast material: evaluation of patient motion and scan quality.

PURPOSE: To assess the effect of rapidly injected ionic or nonionic contrast material on patient motion and scan quality in spiral computed tomography (CT). MATERIALS AND METHODS: One hundred nine patients were prospectively, randomly chosen to receive ionic or nonionic contrast material. An acrylic rod was attached to the anterior abdomen with tape, which allowed an objective measurement of motion. Abdominal spiral CT was performed after intravenous injection of contrast material at a rate of 0.9 g of iodine per second. Scans were evaluated subjectively and objectively for motion and subjectively for quality. Complete data were available in 98 patients (47 in the ionic and 51 in the nonionic group). RESULTS: The acrylic rod moved an average of 0.44 mm per section in the nonionic group and 0.71 mm per section in the ionic group. Both subjective and objective measurements showed a statistically significant difference in patient motion. Use of nonionic contrast material resulted in less patient motion. Scan quality was better with nonionic contrast material. CONCLUSION: Less patient motion occurs and scan quality improves when spiral CT is performed with nonionic contrast material.

Artifacts↗

Immunohistochemical localization of peroxisomal enzymes in developing rat kidney tissues.

We studied the developmental changes in the localization of peroxisome-specific enzymes in rat kidney tissues from embryonic Day 16 to postnatal Week 10 by immunoblot analysis and immunohistochemistry, using antibodies for the peroxisomal enzymes catalase, d-amino acid oxidase, l-alpha-hydroxyacid oxidase (isozyme B), and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase bifunctional protein. Peroxisomal enzymes were detected in the neonatal kidney by immunoblot analysis and their amount increased with kidney development. By light microscopic immunohistochemistry, they were first localized in a few proximal tubules in the juxtamedullary cortex of 18-day embryos. The distribution of proximal tubules positive for them expanded towards the superficial cortex with development. The full thickness of the cortex became positive for the staining by 14 days after birth. Peroxisomes could be detected by electron microscopy in structurally immature proximal tubules in 18-day embryos. Their size increased and the ultrastructure of subcompartments became clear with continuing development of proximal tubules. These results show that peroxisomal enzymes appear in the immature proximal tubules in the kidney of embryos and that the ultrastructure of the peroxisomes and localization of the peroxisomal enzymes develop along with the maturation of proximal tubules and kidney tissues.

3-Hydroxyacyl CoA Dehydrogenases↗

A spectrum of mutations in the polycystic kidney disease-2 (PKD2) gene from eight Canadian kindreds.

Autosomal dominant polycystic kidney disease (ADPKD) is a common Mendelian disorder that affects approximately 1 in 1000 live births. Linkage studies have shown that the majority (approximately 85%) of cases are due to mutations in PKD1 on chromosome 16p, while mutations in PKD2 on chromosome 4q account for most of the remaining cases. Locus heterogeneity in ADPKD is known to contribute to differences in disease severity, with PKD1-linked families having earlier onset of end-stage renal disease (ESRD) than PKD2-linked families (mean age at ESRD: 56 versus 70, respectively). In this study, 11 Canadian families with ADPKD were screened for PKD2 mutations. In four families, linkage to PKD2 was previously documented. In the remaining seven smaller families, one or more affected members had late-onset ESRD at age 70 or older. Using single-stranded conformational polymorphism analysis, one affected member from each family was screened for mutations in all 15 exons of PKD2, which were PCR-amplified from genomic templates. A spectrum of mutations was found in approximately 73% (8 of 11) of the families screened, with no difference in the detection rate between the PKD2-linked families and the families with late-onset ESRD. In three unrelated families, insertion or deletion of an adenosine in a polyadenosine tract (i.e., (A)8 at nt 2152-2159) was found on exon 11, suggesting that this mononucleotide repeat tract is prone to mutations from "slipped strand mispairing." All mutations, scattered between exons 1 and 11, are predicted to result in a truncated polycystin 2 that lacks both the calcium-binding EF-hand domain and the two cytoplasmic domains required for the interaction of polycystin 2 with polycystin 1 and with itself. Furthermore, no correlation was found between the location of the mutations in the PKD2 coding sequence and disease severity. Thus, these findings are consistent with other recently published reports and suggest that most PKD2 mutations are inactivating.

Adolescent↗

[Effects of carbon disulfide on neurotransmitter and its metabolites in rats].

OBJECTIVE: In order to study the mechanism of neurotoxic effects of carbon disulfide (CS2) on animal behavior. METHODS: Changes in monoamine transmitter, amino acid transmitter and their metabolites in brain tissues were observed in rats exposed to CS2 at levels of 0, 1,200 and 2,400 mg/m3 respectively, for two months, with high performance liquid chromatography. RESULTS: Indicated that exposure to CS2 could cause decrease in 3-methoxy-4-hydroxy mandelic acid (VMA), increase in 3,4-dioxybenzoic acid, a metabolite of dopamine, and high vanillic acid in rat straitum, decrease in excitatory amino acids and their metabolites (glutamine, aspartic acid and asparagine), with a certain relationship between contents of VMA, aspartic acid and asparagine and changes in neurobehavior. CONCLUSION: Disturbance of neurotransmitter metabolism plays an important role in neurotoxic effects of CS2.

Animals↗

[Effects of aluminum on neurobehavioral function and metabolism of monoamine neurotransmitter].

OBJECTIVE: To evaluate the effects of occupational exposure to aluminum on neurobahavioral function and metabolism of monoamine neurotransmitter. METHODS: Thirty-three workers exposed to aluminum and 40 controls were studied. Air aluminum concentrations in workplace environment were detected with an atomic absorption spectrophotometer, homovanillic acid (HVA) and vanilylmandellic acid (VMA) in urine and aluminum in serum and urine were detected with high perfolmance liquid chromatography. Neurobehavioral function was tested with Neurobehavioral Core Test Battery recommended by WHO. RESULTS: Geometric time-weighted average of aluminum in workplace environment was 0.95 mg/m3, ranging from 0.31 to 4.12 mg/m3, and urine aluminum levels in workers exposed to aluminum averaged 12.25 micrograms/L, significantly higher than that in controls (5.78 micrograms/L). There was no significant difference in serum aluminum between the exposed and controls. Both urine VMA and HVA levels were higher in the workers exposed to aluminum, and urine VMA level in the exposed was significantly higher than that in controls. There was significant difference in neurobehavioral test, including Santa Ana, digit symbol and Benton tests between the exposed and control workers. CONCLUSION: It suggests that occupational exposure to low level of aluminum can affect the neurobehavioral function and metabolism of monoamine neurotransmitter.

Adult↗

Study on the transmission threshold value of bancroftian filariasis.

OBJECTIVE: To elucidate the transmission dynamic and epidemic trend of bancroftian filariasis occurred under the condition with no control measure taken 5 years after elimination of filariasis. METHODS: A 10-year longitudinal observation (from 1984 to 1994) was made in Huayuan Village in Shengli Township of Tancheng County, which used to be a high bancroftian filariasis-endemic area in southern part of Shandong Province. RESULTS: The microfilarial rate decreased from 0.56% before the study to 0.12% after the study and 8 out of the 9 previous microfilaria-positive cases became negative gradually. During the study period, 6 new microfilaremia cases were detected, 5 of which became negative naturally within 3 to 4 years. Eighty-eight point eight nine per cent of the detected patients with microfilaremia converted into IgG4-negative after 10 years. The natural infective rate of vectors decreased year by year and became zero by the tenth year of the study, the annual transmission potency decreased also from 3.47 to zero by the tenth year. CONCLUSIONS: It showed that under the local natural environment the biting rate representing the vector density which was obtained by capture method was from 24.1 to 52.5 person/night among the residents who did not use mosquito nets, and 13.5 to 21 person/night among the residents who used mosquito nets. The microfilarial rate of 0.56% in population with the average microfilarial density of 6.6 to 20.7 capita/60 microliters ear blood of residual microfilaria-positive patients might be considered as the terminal threshold of transmission.

Animals↗

[Clinical applyeation of neural stump buried into muscle for the prevention and treatment of neuroma].

In order to verify the effectiveness of neural stump buried into the muscle in the prevention and treatment of neuroma, 17 cases were reported, in which 8 cases having 19 painful neuromas and 9 cases having 13 amputated meural stumps, buried into muscle. They wese followed up for 6 months to 40 months, It was shown that good and excellent results were obtained and no evidence of neuroma was observed in all cases except in one which had painful neuroma occurred from the failure of embedment of the neural stump into the muscle. The conclusion was that the neural stump buried into muscle was an effective method for the prevention and treatment of neuroma.

Adult↗