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Biomedical subjects

M Hu

Publications and source records attributed to M Hu.

At least 127 records · Page 7Linked to original sources
PubMed1998

Cytotoxic effects of sphingolipids as single or multi-modality agents on human melanoma and soft tissue sarcoma in vitro.

We evaluated the cytotoxic effects of a cell-permeable ceramide (Cer), N-hexanoyl-D-sphingosine (C6-Cer) and of two related sphingoid bases, sphingosine (So) and dihydrosphingosine (sphinganine; Sa) on human melanoma cell lines and on soft tissue sarcoma lines recently established from fresh surgical biopsy specimens. These cell lines ranged from high susceptibility (939 melanoma) to strong resistance (A2058 melanoma and all three sarcomas) to tumour necrosis factor (TNF), an inducer of elevated intracellular Cer levels. However, all the cell lines demonstrated a dose-dependent susceptibility to C6-Cer with protracted cytotoxic kinetics, with the C8161 melanoma being the most sensitive and A2058 the least. Protein kinase C (PKC) antagonizes Cer-dependent apoptosis, and chelerythrine chloride, So and Sa, which inhibit PKC, caused extremely rapid cytotoxicity of melanoma cell lines, irrespective of their relative sensitivity to C6-Cer. So-mediated cytotoxicity was extensive even after only 90 min of treatment, within the time frame of limb perfusion. So and Sa only slightly potentiated the cytotoxic responses to TNF, C6-Cer or melphalan. Sphingolipid-driven intracellular pathways may offer opportunities for therapy of these tumours.

Alkaloids↗
PubMed1998

Stress distribution in the mandible with unilateral condylar fracture.

OBJECTIVE: The purpose of this study was to investigate the influence of unilateral condylar neck fracture upon the stress distribution in the mandible and the temporomandibular joint (TMJ) to realize primarily the biomechanical mechanism of the temporomandibular joint disorders (TMD) caused by TMJ injury. METHODS: The character of stress distribution in the mandible of a normal human and a patient with TMD induced by unilateral condylar neck fracture followed by malpositioned healing was analyzed quantitatively and compared during centric occlusion by combining spiral computed tomography scanning technology with the three-dimensional finite element method. RESULTS: The patient with unilateral condylar neck fracture followed by malpositioned healing had unbalanced stress distribution in the mandible, such as differing nature and value of stress. The stress in the fractured side was higher than in the nonfractured side, in which the condyle was more evident. The maximum principal stress and minimum principal stress of each region in the fractured mandible were much higher than those in a normal mandible. Stress quality also differed. CONCLUSIONS: The abnormal stress changes after unilateral condylar neck fracture with malpositioned healing may be related to the effect of condylar shape change on masticatory muscle function and occlusion. TMJ injury not only damaged the condylar structure, but also compromised its biomechanic environment. It is preliminarily thought that unbalanced stress distribution, evidently increased stress, and varied stress character are biomechanic mechanisms of TMD. Condylar dislocated fracture should be treated promptly and properly to maintain the proper prognostic stress distribution.

Adult↗
PubMed1998

[Preoperative localized diagnosis of insulinoma by aterial stimulating and venous sampling methods].

OBJECTIVE: To establish a method for bocative diagnoses of insulinoma, METHOD: Five patients with insulinoma were given locative diagnoses by using ASVS methods which mean injecting calcium stimulatant into pancreatic supplying arteries and then taking blood specimens from henatic vein to gauge the insulin levels. Six samples, each 2 ml, were taken before and 30, 60, 90, 120, 180 seconds after the injection. RESULTS: If the peak of blood-insulin level was twice or higher than the basic level, the tumor was located in the domain. These results were confirmed operatively in all the five cases. CONCLUSION: ASVS is an accurate technique to localize insulinoma.

Adult↗
PubMed1998

[Purification of recombinant erythropoietin by reversed-phase high performance liquid chromatography (RP-HPLC)].

Recombinant erythropoietin is a glycoprotein which is strongly hydrophobic. We purified recombinant erythropoietin by RP-HPLC. The results showed that 30 nm Spherisorb C4 reversed-phase column and acetonitrile-TFA mobile phase with gradient elution, could readily isolate recombinant erythropoietin from crude samples with high speed and efficiency. Erythropoietin could be eluted at the concentration of about 50% acetonitrile with appropriate sample purity and elution gradient. When RP-HPLC is used as a final step of purification, the purity of sample should be at least 60%. The purity of the product tested by SDS-PAGE was nearly 100%. And the specific activity of the product was about 1.96 x 10(3) IU/g protein.

Chromatography, High Pressure Liquid↗
PubMed1998

[Biomechanical analysis of occlusal splint therapy].

OBJECTIVE: The changes of the location and force of the condyle influenced by occlusal splint were investigated in order to know the biomechanical mechanism of occlusal splint therapy. METHODS: Auto-CAD technology, CT scanning, computer imaging analysis measurement and finite element method were separately used to comparatively analyze condylar position and its stress distribution in patients with temporomandibular joint disorders (TMD) treated with or without occlusal splint. RESULTS: Occlusal splint could lessen anterior space, in crease posterior and upper space in the temporomandibular joint (TMJ), so the condylar position move anterioinferiorly; the stress on condylar surface was lowered, mainly in anterior oblique surface or lateral side of condylar loading position; and the stress symmetry was bilaterally improved. OCCLUSION: The study suggests that regulating condylar position and improving the stress distribution is considered one of biomechanical mechanism of occlusal splint treatment.

Adult↗
PubMed1998

[Mandibular compound organs allotransplantion in canines].

OBJECTIVE: To evaluate the feasibility of transplanting composite madibular allogratts to reconstruct large mandibular defects. METHODS: Three composite mandibular transplantation models were designed. The first consisted of hemimandible with the attached teeth, muscles and skin, and oral mucosa. The second was transplanted as the first excluding oral mucosa and some teeth, and the third excluding oral mucosa and all dental crowns. Fourteen transplanting operations were done in canines. Cyclosporine A and methylprednisone were given for immunosuppression. RESULTS: It was confirmed that the composite mandibular organs had an effective and closed return circuit. Transplantation of vascularized mandibular compound organs allografts was feasible. Two longest survivors. 67 and 76 days, were in the third model. Cyclosporine A was successful in suppressing rejection in composite allograft transplant and prolonging survival of transplant models. CONCLUSION: The compoite mandibular allografts had the availability of large bloc of living composite tissues and the good restoration of appearance and function for severe mandibular defects.

Animals↗
PubMed1998

Inhibition effect of cyclosporin A on human retinal pigment epithelial cells in vitro.

PURPOSE: To select effective drugs against cellular proliferation in the vitreous. METHODS: Cyclosporin A (0.125 mg/l-4.0 mg/l) was added to cultures of human retinal pigment epithelial (RPE) cells with or without macrophage-conditioned medium (MCM). Proliferation rate of the cells was measured with (3H)-thymidine incorporation and liquid scintillation techniques on days 3 and 5. RESULTS: Cyclosporin A at a dosages of 0.125 mg/l had a slight inhibition on human RPE cells proliferation (-3.8%-4.1%, P > 0.05). Cyclosporin A at a dose ranging from 0.25 mg/l to 4.0 mg/l inhibited cellular proliferation effectively and in a dose-dependent manner (8.7%-95.1%, P < 0.05 r = 0.94, P < 0.001) with its ID50 of 1.49 mg/l. In the culture of RPE with MCM, the inhibition on day 5 was more effective than that on day 3. CONCLUSION: Cyclosporin A had an effective inhibition on human RPE cell proliferation and it may be of potential use clinically.

Adult↗
PubMed1997

Peripheral but not hepatic insulin resistance in mice with one disrupted allele of the glucose transporter type 4 (GLUT4) gene.

Glucose transporter type 4 (GLUT4) is insulin responsive and is expressed in striated muscle and adipose tissue. To investigate the impact of a partial deficiency in the level of GLUT4 on in vivo insulin action, we examined glucose disposal and hepatic glucose production (HGP) during hyperinsulinemic clamp studies in 4-5-mo-old conscious mice with one disrupted GLUT4 allele [GLUT4 (+/-)], compared with wild-type control mice [WT (+/+)]. GLUT4 (+/-) mice were studied before the onset of hyperglycemia and had normal plasma glucose levels and a 50% increase in the fasting (6 h) plasma insulin concentrations. GLUT4 protein in muscle was approximately 45% less in GLUT4 (+/-) than in WT (+/+). Euglycemic hyperinsulinemic clamp studies were performed in combination with [3-3H]glucose to measure the rate of appearance of glucose and HGP, with [U-14C]-2-deoxyglucose to estimate muscle glucose transport in vivo, and with [U-14C]lactate to assess hepatic glucose fluxes. During the clamp studies, the rates of glucose infusion, glucose disappearance, glycolysis, glycogen synthesis, and muscle glucose uptake were approximately 55% decreased in GLUT4 (+/-), compared with WT (+/+) mice. The decreased rate of in vivo glycogen synthesis was due to decreased stimulation of glucose transport since insulin's activation of muscle glycogen synthase was similar in GLUT4 (+/-) and in WT (+/+) mice. By contrast, the ability of hyperinsulinemia to inhibit HGP was unaffected in GLUT4 (+/-). The normal regulation of hepatic glucose metabolism in GLUT4 (+/-) mice was further supported by the similar intrahepatic distribution of liver glucose fluxes through glucose cycling, gluconeogenesis, and glycogenolysis. We conclude that the disruption of one allele of the GLUT4 gene leads to severe peripheral but not hepatic insulin resistance. Thus, varying levels of GLUT4 protein in striated muscle and adipose tissue can markedly alter whole body glucose disposal. These differences most likely account for the interindividual variations in peripheral insulin action.

Adipose Tissue↗
PubMed1997

Purification and characterization of human lung fibroblast motility-stimulating factor for human soft tissue sarcoma cells: identification as an NH2-terminal fragment of human fibronectin.

Paracrine motogenic factors, including motility cytokines and extracellular matrix molecules secreted by normal cells, can stimulate metastatic cell invasion. Both intact extracellular matrix molecules and their degradative products may exhibit these activities. We have found that human lung fibroblasts produce paracrine motility-stimulating factors for recently established human sarcoma cell strains. We purified the major fibroblast motility-stimulating factor (FMSF) from human lung fibroblast-conditioned medium by sequential heparin affinity chromatography and DEAE anion exchange chromatography. Lysylendopeptidase C digestion of FMSF and sequencing of peptides purified by reverse-phase high-pressure liquid chromatography identified FMSF as an NH2-terminal fragment of human fibronectin. Using SYN-1 sarcoma cells, FMSF predominantly stimulated chemotaxis and some chemokinesis, and it was chemotactic for a variety of human sarcoma cells, including fibrosarcoma, leiomyosarcoma, liposarcoma, synovial sarcoma, and neurofibrosarcoma cells. The FMSF activity present in human lung fibroblast-conditioned medium was completely eliminated by either neutralization or immunodepletion with a rabbit antihuman-fibronectin antibody, thus further confirming that the NH2-terminal fibronectin fragment was the FMSF responsible for the motility stimulation of human soft tissue sarcoma cells. Because human soft tissue sarcomas have a distinctive hematogenous metastatic pattern (predominantly lung), and lung-derived fibroblasts secrete large amounts of FMSF, FMSF and fibronectin may play a role in stimulating sarcoma invasion into lung tissue.

Amino Acid Sequence↗
PubMed1997

Proviral insertions induce the expression of bone-specific isoforms of PEBP2alphaA (CBFA1): evidence for a new myc collaborating oncogene.

The til-1 locus was identified as a common retroviral integration site in virus-accelerated lymphomas of CD2-myc transgenic mice. We now show that viral insertions at til-1 lead to transcriptional activation of PEBP2alphaA (CBFA1), a transcription factor related to the Drosophila segmentation gene product, Runt. Insertions are upstream and in the opposite orientation to the gene and appear to activate a variant promoter that is normally silent in T cells. Activity of this promoter was detected in rodent osteogenic sarcoma cells and primary osteoblasts, implicating bone as the normal site of promoter activity. The isoforms encoded by the activated gene all encompass the conserved runt DNA-binding domain and share a novel N terminus different from the previously reported PEBP2alphaA products. Minor products include isoforms with internal deletions due to exon skipping and a novel C-terminal domain unrelated to known runt domain factors. The major isoform expressed from the activated til-1 locus (G1) was found to account for virtually all of the core binding factor activity in nuclear extracts from its corresponding lymphoma cell line. Another member of this gene family, AML1(CBFA2), is well known for its involvement in human hemopoietic tumors. These results provide evidence of a direct oncogenic role for PEBP2alphaA and indicate that the Myc and Runt family genes can cooperate in oncogenesis.

Amino Acid Sequence↗
PubMed1997

Role of the glucosamine pathway in fat-induced insulin resistance.

To examine whether the hexosamine biosynthetic pathway might play a role in fat-induced insulin resistance, we monitored the effects of prolonged elevations in FFA availability both on skeletal muscle levels of UDP-N-acetyl-hexosamines and on peripheral glucose disposal during 7-h euglycemic-hyperinsulinemic (approximately 500 microU/ml) clamp studies. When the insulin-induced decrease in the plasma FFA levels (to approximately 0.3 mM) was prevented by infusion of a lipid emulsion in 15 conscious rats (plasma FFA approximately 1.4 mM), glucose uptake (5-7 h = 32.5+/-1.7 vs 0-2 h = 45.2+/-2.8 mg/kg per min; P < 0.01) and glycogen synthesis (P < 0.01) were markedly decreased. During lipid infusion, muscle UDP-N-acetyl-glucosamine (UDP-GlcNAc) increased by twofold (to 53.4+/-1.1 at 3 h and to 55.5+/-1.1 nmol/gram at 7 h vs 20.4+/-1.7 at 0 h, P < 0.01) while glucose-6-phosphate (Glc-6-P) levels were increased at 3 h (475+/-49 nmol/gram) and decreased at 7 h (133+/-7 vs 337+/-28 nmol/gram at 0 h, P < 0.01). To discern whether such an increase in the skeletal muscle UDP-GlcNAc concentration could account for the development of insulin resistance, we generated similar increases in muscle UDP-GlcNAc using three alternate experimental approaches. Euglycemic clamps were performed after prolonged hyperglycemia (18 mM, n = 10), or increased availability of either glucosamine (3 micromol/kg per min; n = 10) or uridine (30 micromol/kg per min; n = 4). These conditions all resulted in very similar increases in the skeletal muscle UDP-GlcNAc (to approximately 55 nmol/gram) and markedly impaired glucose uptake and glycogen synthesis. Thus, fat-induced insulin resistance is associated with: (a) decreased skeletal muscle Glc-6-P levels indicating defective transport/phosphorylation of glucose; (b) marked accumulation of the endproducts of the hexosamine biosynthetic pathway preceding the onset of insulin resistance. Most important, the same degree of insulin resistance can be reproduced in the absence of increased FFA availability by a similar increase in skeletal muscle UDP-N-acetyl-hexosamines. In conclusion, our results support the hypothesis that increased FFA availability induces skeletal muscle insulin resistance by increasing the flux of fructose-6-phosphate into the hexosamine pathway.

Animals↗
PubMed1997

Multilineage gene expression precedes commitment in the hemopoietic system.

We have tested the hypothesis that multipotential hemopoietic stem and progenitor cells prime several different lineage-affiliated programs of gene activity prior to unilineage commitment and differentiation. Using single cell RT-PCR we show that erythroid (beta-globin) and myeloid (myeloperoxidase) gene expression programs can be initiated by the same cell prior to exclusive commitment to the erythroid or granulocytic lineages. Furthermore, the multipotential state is characterized by the coexpression of several lineage-affiliated cytokine receptors. These data support a model of hemopoietic lineage specification in which unilineage commitment is prefaced by a "promiscuous" phase of multilineage locus activation.

Animals↗
PubMed1997

Abnormal regulation of HGP by hyperglycemia in mice with a disrupted glucokinase allele.

Glucokinase (GK) catalyzes the phosphorylation of glucose in beta-cells and hepatocytes, and mutations in the GK gene have been implicated in a form of human diabetes. To investigate the relative role of partial deficiencies in the hepatic vs. pancreatic GK activity, we examined insulin secretion, glucose disposal, and hepatic glucose production (HGP) in response to hyperglycemia in transgenic mice 1) with one disrupted GK allele, which manifest decreased GK activity in both liver and beta-cells (GK+/-), and 2) with decreased GK activity selectively in beta-cells (RIP-GKRZ). Liver GK activity was decreased by 35-50% in the GK+/- but not in the RIP-GKRZ compared with wild type (WT) mice. Hyperglycemic clamp studies were performed in conscious mice with or without concomitant pancreatic clamp. In all studies [3-(3)H]glucose was infused to measure the rate of appearance of glucose and HGP during 80 min of euglycemia (Glc approximately 5 mM) followed by 90 min of hyperglycemia (Glc approximately 17 mM). During hyperglycemic clamp studies, steady-state plasma insulin concentration, rate of glucose infusion, and rate of glucose disappearance (Rd) were decreased in both GK+/- and RIP-GKRZ compared with WT mice. However, whereas the basal HGP (at euglycemia) averaged approximately 22 mg x kg(-1) x min(-1) in all groups, during hyperglycemia HGP was suppressed by only 48% in GK+/- compared with approximately 70 and 65% in the WT and RIP-GKRZ mice, respectively. During the pancreatic clamp studies, the ability of hyperglycemia per se to increase Rd was similar in all groups. However, hyperglycemia inhibited HGP by only 12% in GK+/-, vs. 42 and 45%, respectively, in the WT and RIP-GKRZ mice. We conclude that, although impaired glucose-induced insulin secretion is common to both models of decreased pancreatic GK activity, the marked impairment in the ability of hyperglycemia to inhibit HGP is due to the specific decrease in hepatic GK activity.

Alleles↗
PubMed1997

Fat accretion and the regulation of insulin-mediated glycogen synthesis after puberty in rats.

Peripheral insulin sensitivity decreases after puberty in both humans and rodents and can be explained mostly by a reduction in insulin-mediated glycogen synthesis. We tested the hypothesis that the increase in postpubertal fat mass (FM), reflecting an alternative energy store, regulates a decrease in the capacity to store muscle glycogen. We studied Sprague-Dawley rats (n = 21) before puberty (Pre) or after puberty (at 4 mo of age) in groups that were either ad libitum fed (Post) or moderately caloric restricted (CR). FM (by 3H2O isotope dilution technique) was decreased by >40% in CR compared with Post. Glucose uptake (Rd, by 18 mU x kg(-1) x min(-1) hyperinsulinemic clamp) was 63 +/- 8 mg x kg(-1) x min(-1) in Pre and decreased to 39 +/- 2 mg x kg(-1) x min(-1) in Post (P < 0.001). However, it increased in CR to 53 +/- 2 mg x kg(-1) x min(-1) (P < 0.001 vs. Post). This increase in Rd was mainly accounted for by an increase in glycogen synthesis (Rd glycolysis determined by the rate of conversion of 3H-labeled glucose to 3H2O) from 23 +/- 2 in Post to 33 +/- 2 mg x kg(-1) x min(-1) in CR (P < 0.001; 38 +/- 7 mg x kg(-1) x min(-1) in Pre). Correction of glycogen synthesis in CR to near-prepubertal levels was further supported by directly assayed muscle glycogen content after insulin stimulation that was 45% higher and by a 35% enhanced accumulation of [3H]glucose into glycogen. No changes in the enzyme kinetics of glycogen synthase or phosphorylase were observed. An additional group of 2-mo-old postpubertal ad libitum-fed rats was matched with CR for lean body mass but had more FM. This group demonstrated 25% lower rates of insulin-mediated glycogen synthesis compared with CR, further supporting the notion that a moderate reduction of FM prevents the decline in insulin responsiveness and glycogen synthesis occurring after puberty. These data suggest a cause-effect relationship between the increased deposition of fat and the reduced ability to store glucose in skeletal muscle after puberty.

Adipose Tissue↗
PubMed1997

Intracellular pathways of insulin-mediated glucose uptake before and after puberty in conscious rats.

Studies in humans and animals indicate that peripheral insulin sensitivity is decreased after puberty. Although glucose, after its uptake and phosphorylation, will be diverted to either the glycolytic or glycogen synthesis pathway, these pathways have not been characterized after the transition to puberty. Thus, we examined the changes in the pathways of glucose utilization in conscious (n = 22) prepuberty (81 +/- 3 g), and postpuberty (258 +/- 9 g) Sprague-Dawley rats. Insulin stimulated (by insulin clamp 18 mU/kg/min) glucose uptake [rate of glucose disappearance (Rd)] was decreased by approximately 30% postpuberty (from 339 +/- 22 to 239 +/- 28 mumol/kg/min; p < 0.001). Although glycolysis (estimated by the rate of conversion of [3H]glucose to 3H2O) decreased by approximately 15% (p < 0.05), glycogen synthesis decreased by approximately 40% (from 200 +/- 17 prepuberty to 122 +/- 22 mumol/kg/min postpuberty; p < 0.001), and accounted for approximately 80% of the decrease in Rd postpuberty. Decrease in the capacity to store glycogen in response to insulin was also confirmed by approximately 40% decrease in both glycogen levels, and in 3H accumulation into glycogen (from 3H-glucose) at the end of the clamp study. This occurred in the absence of any changes in either the K(m) or the Vmax of glycogen synthase nor in the activity of glycogen phosphorylase. We conclude that the postpubertal decrease in insulin responsiveness is characterized by decreased ability to store muscle glycogen. We propose that high capacity for muscle glycogen synthesis may be required to sustain the increased metabolic requirements during peripubertal growth.

Adipose Tissue↗
PubMed1997

[Human papillomavirus (HPV) and DNA test in inverted papillomas of the nasal cavities and paranasal sinuses].

To understand the relationship between inverted papillomas and human papilloma virus, 38 cases (44 specimens) of inverted papillomas of nasal cavities and paranasal sinuses were examined for the presence of human papilloma virus (HPV) DNA using polymerase chain reaction (PCR). The genetic studies were performed on the formalin fixed and parafin embeded specimens. The results showed that 30 cases were infected by HPV-DNA, in which HPV11 positive was noted for 30 times (68.2%), HPV16 positive for 18 times (40.9%), and HPV18 positive for 2 time (4.5%). 18 HPV11,16 (40.9%) and 2 were HPV11,18 (4.5%). The result suggests that HPV plays a role in the etiology of nasal and paranasal inverted papillomas.

Adult↗
PubMed1997

Effects of chronic ethanol exposure on GABA receptors and GABAB receptor modulation of 3H-GABA release in the hippocampus.

Chronic ethanol treatment (CET), sufficient for decreasing long-term potentiation (LTP) in rats, also enhances 3H-GABA release from hippocampal slices in these same animals. The mechanism for an increase in GABA release may involve changes in presynaptic receptors. Therefore, we characterized presynaptic autoreceptor modulation of 3H-GABA release in hippocampal slices from control and CET rats. The effects of a GABAB receptor agonist (baclofen) and antagonist [2-hydroxy (OH)-saclofen] were tested for their ability to modulate electrically stimulated 3H-GABA release from superfused hippocampal slices. Baclofen decreased stimulated release in a dose-dependent manner and 2-OH-saclofen increased release consistent with the existence of presynaptic GABAB autoreceptors in hippocampus. The GABAA antagonist bicuculline did not significantly modulate basal or stimulated release. When the effects of baclofen and 2-OH-saclofen were measured in animals 48 hr after withdrawal from CET, presynaptic modulation of release by baclofen and 2-OH-saclofen was decreased. In addition, we examined the density of 3H-baclofen and 3H-bicuculline binding in the hippocampal formation using quantitative autoradiographic techniques. We found that the density of 3H-baclofen binding sites was not affected by CET, whereas the density of 3H-bicuculline binding sites was increased by 28% in ethanol-treated rats. These data may explain how CET increases presynaptic regulation of GABA release from hippocampus that may contribute to the decrease in LTP seen in rats after CET.

Alcoholism↗