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Biomedical subjects

H Lin

Publications and source records attributed to H Lin.

At least 307 records · Page 17Linked to original sources
PubMed1997

[Role of endothelial-derived nitric oxide and its synthase in the development of hypoxic pulmonary hypertension in rat].

To clarify the role of endothelial-derived nitric oxide (EDNO) and its synthase (NOS) in the normal and hypertensive pulmonary vasculature, activity of endothelial NOS in the lungs, ENDO-dependent vasodilating response induced by bradykinin (BK), and cGMP content of lung tissue in normoxic and hypoxic rats were investigated. We also studied the effects of NOS inhibitor-L-NAME on the activity of NOS, cGMP content, mean pulmonary arterial pressure (mPAP) and carotid systolic arterial pressure (CAPs) in both rats. The results were as follows (1) In normoxic rats there was no NOS activity in the endothelium of small vessels (phi < or = 80 microns) and no relaxing response to BK. Long-term administration of L-NAME obviously inhibited the activity of ecNOS and cGMP content in the lungs of normoxic rats, therefore it led to the increment of CAPs but failed to elevate mPAP. (2) After hypoxic exposure for 10 days, NADPH-diaphorase (NADPH-d and ecNOS immunoreactivity turned to be positive in the endothelium of small vessels with diameter less than 80 microns. BK-induced EDNO-dependent vasodilation, the enzyme activity of cNOS and cGMP content in the lungs of hypoxic rats were significantly enhanced as compared with normoxic rats. Long-term administration of L-NAME in hypoxic rats markedly inhibited the enhancement of cNOS enzyme activity, the production of EDNO and cGMP content in rat lungs, consequently it significantly decreased mPAP but elevated CAPs obviously. These results suggest that the role of EDNO in maintaining the low basal tone of normal adult pulmonary circulation remain to be studied more precisely. The increased activity of ecNOS and the enhancement of EDNO synthesis might act to moderate the hypertension. The excess synthesis of EDNO might be toxic to the endothelium of pulmonary vessels, therefore potentiating the development of pulmonary hypertension.

Animals↗
PubMed1997

[Study on the relationship between PS2 protein expression and prognosis in invasive breast carcinoma].

OBJECTIVE: To study the relationship between the expression of PS2 protein and prognosis in the invasive breast cancer (IBC). METHOD: Using LSAB immunohistochemical method, PS2 protein expression in 86 cases of IBC was detected. RESULTS: The positive rate of PS2 protein was 66.27% (57/86) in 86 cases of IBC. Under the following 3 conditions, PS2 protein expression levels in the more-than-5-year-survival group (A) were higher than those in the less-than-5-year-survival group (B). (1) In 86 cases of IBC, the expression level was 80.55% (29/36) for Group A, Significantly different from the 56.00% (28/50) of Group B (P < 0.025). (2) In 62 cases of premenopausal patients, the corresponding data were 86.20% (25/29) and 54.54% (18/33) respectively, P < 0.005; whereas in 24 cases of postmenopausal patients, 4/7 and 58.82% (10/17) respectively, P > 0.5. (3) In 62 cases of axillary node positive patients, the expression levels for Groups A and B were 82.35% (14/17) and 55.55% (25/45) respectively, P < 0.05; while in 24 cases of axillary node negative patients, 78.94% (15/19) and (3/5) respectively, P > 0.5. CONCLUSIONS: These results suggest that the expression of PS2 protein was positively correlated with 5-year-survival in IBC, and could be considered as a prognostic predictor for breast cancer, PS2 protein expression was a useful indicator for endocrine therapy in premenopausal patients. In axillary node positive patients, the expression of PS2 protein was associated with a better prognosis.

Adult↗
PubMed1997

[Effect of L-arg and SNP on pulmonary arterial pressure and vascular structural changes of chronically hypoxic rats].

The effects of L-arginine (L-arg) and sodium nitroprusside (SNP) on pulmonary arterial pressure, the percentage of muscularization of intra-acinar vessels and ultrastructural changes of extra pulmonary artery and pulmonary arteriole of chronically hypoxic rats were studied. The results showed that: (1) Both L-arg and SNP decreased mean pulmonary arterial pressure of chronically hypoxic rats significantly. (2) Both L-arg and SNP reduced the percentage of muscularization of intra-acinar vessels of chronically hypoxic rats significantly. (3) Both L-arg and SNP protected pulmonary artery from the damages of endothelium and the changes in smooth muscle cell phenotype by hypoxia. These results suggested that exogenous nitric oxide might play a role in the protection of pulmonary arterial function and structure which alleviate the development of pulmonary hypertension induced by chronic hypoxia.

Animals↗
PubMed1997

[Effect of hypoxia on distribution and activity of nitric oxide synthase in rat lung].

Nitric oxide is an important cellular messenger molecule that has been implicated in a wide range of physiological and pathophysiological actions in cardiovascular, immune, and nervous systems. Nitric oxide synthase (NOS) is the sole and key enzyme responsible for the generation of nitric oxide. The effect of hypoxia-induced pulmonary hypertension on NOS in the lung is controversial. To clarify the effect of hypoxia on distribution and activity of NOS in rat lung, localization of NOS in the lungs of hypoxic and normoxic rats were studied using NADPH-diaphorase histochemical staining techniques, NOS enzyme activity in the lung homogenates was assessed by [3H] arginine to [3H] citrulline conversion. In the normoxic rat, NADPH-d was distributed in the endothelial cells of large pulmonary vessels (ID > 150 microns) and medium-sized (50 microns < ID < 150 microns) vessels but was not detected in the endothelium of small vessels (ID < 50 microns), and there was an absence of NADPH-d staining in the smooth muscle cells of small, medium, and large pulmonary vessels. However, after hypoxic exposure for two weeks, NADPH-d staining increased dramatically in the endothelial cells of large and medium-sized pulmonary vessels, and NADPH-d became markedly positive in the endothelial cells of small vessels. Hypoxia was also found to induce de novo NOS expression in the smooth muscle cells of small, medium-sized, and large pulmonary vessels. The enzyme activity of constitutive NOS(cNOS) was decreased obviously in the hypoxic rat lungs, but that of inducible NOS(iNOS) was increased significantly in the hypoxic rat lungs. These results suggested that the inhibited endothelium-derived relaxing factor (EDRF)/NO-dependent vasodilation after hypoxic exposure might be induced by decreased activity of cNOS in the endothelium of pulmonary vessels, and hypoxia-induced upregulation of iNOS expression and activity in the rat lung might play an important role in the adaptation of pulmonary circulation to hypoxia.

Animals↗
PubMed1997

[A three-year clinical evaluation of five light-cured composite resins in fillings of posterior teeth].

In order to study the clinical performance and the evaluation method of light-cured composite resin in filling for posterior teeth, two evaluation methods were used to evaluate 5 light-cured posterior composite resin fillings in 169 adult posterior class I cavity. Results showed that each evaluation method has its own advantages. The curative effect was declined with time in this study. Failures and defects were mainly occurred after 3 years. Secondary caries, loss of fillings and marginal stainings were the main reasons of failures. Compared with the effect of 1 year, the success rate after 3 years declined significantly, and further long-term clinical observation is needed.

Adolescent↗
PubMed1997

[Clinical evaluation for wear of composite resin in filling of molars].

To study the best evaluation method for wear of composite resins, 93 occlusal cavities of molars were restored with four kinds of light-cured composite resins, and three-year clinical research of wear analyses was performed using either direct evaluation method (USPHS) or indirect cast comparison (Leinfelder) method. The results suggested that the direct evaluation method for early wear of restorations would be less sensitive, but it remains the preferred system for the evaluation otherwise; the indirect method would be more reliable and sensitive, and numerical estimates of wear are more readily suitable for statistical analysis. The combination of direct and indirect methods will evaluate composite resin wear objectively and comprehensively.

Adolescent↗
PubMed1997

[An analysis of dynamic ECG of 36 pilots].

24h dynamic electrocardiogram (DCG) of 36 healthy male fighter pilots, aged 25-35 years were recorded and analysed, then the data were compared with DCG of 55 normal subjects. The results showed that supraventricular arrythmias were more than ventricularones; both supraventricular and ventricular arrythmias of pilots were more than that of the control; the appearing rate of ST setment depression of pilots was higher.

Adult↗
PubMed1997

[Aetiologic study on the outbreaks of influenza-like disease in Shenzhen].

During March to May in 1994, the outbreaks of influenza like disease occurred in Shenzhen city. The outbreaks were caused by influenza B virus demonstrated by aetiologic and serological studies. The antigenic analysis indicated that the isolates were antigenically similar to B/Shanghai/1/93 and B/Guangdong/8/93 strains (both are B/Victoria/2/87. like virus). The genetic analysis showed that the HA1 genes of the isolates were 1038 nucleotides in length coding for HA1 protein of 346 amino acids which were same as those of B/Shanghai/1/93 virus and that the homogeneity of amino acid sequence on HA1 protein between isolates and B/Shanghai/1/93 virus was as high as 95%. These results further demonstrated that the isolates were B/Victoria/2/87 like strains. Meanwhile, this paper also revealed that the two antigenically distinct genetic lineages of influenza B virus were cocirculating in human population.

Amino Acid Sequence↗
PubMed1997

[Cloning and expression of heavy- and light-chain variable region genes of monoclonal antibody specific for human fibrin].

OBJECTIVE: To obtain the minimum molecule having activity to bind human fibrin. METHODS: The immunoglobulin heavy- and light-chain variable region (VH and Vkappa) genes were isolated from 8E5 hybridoma cells, which secreted a monoclonal antibody against human fibrin, by RT-PCR. An expression vector pOPE51-8E5 was constructed for the recombinant VH-Vkappa expression. The transformed E. coli JM 109 cells were propagated and induced by IPTG. RESULTS AND CONCLUSION: Expression product was found in the periplasmic space and inclusion bodies by SDS-PAGE and immunobloting. It was a 30000 single chain fragment (scFv) with antigen-binding specificity. The yield of the scFv was 28.9% of the total bacterial proteins.

Animals↗
PubMed1997

Synthesis and antinociceptive activity of [D-Met2, Pro5] enkephalin [N1,5-beta-D-2,3,4,6-O-tetraacetylglycosyl]--amide and [D-Met2, Pro5] enkephalinamide.

Tetra-O-acetylgalactopyranosylamine and tetra-O-acetylglucopyranosylamine of D-Met2, Pro5 enkephalin were designed and synthesized to enhance their membrane penetration, biological activity and resistance to proteolytic hydrolysis. Three approaches to the synthesis were attempted, which lead to a new synthetic scheme with a higher yield and enhanced ease of purification. The improved procedure involved attaching the tetra-O-acetylglycopyranosylamine to a t-Boc-Gly-Phe-Pro-OH peptide, removing the t-Boc, and condensing it with t-Boc-Tyr-D-Met-OH. Biological evaluation in vivo showed that these acetylglycopyranosylamine derivatives bind to mu and delta opioid receptors in homogenate binding assays and possess analgesic activity. The analgesic potency was less than that of the parent compound D-Met2, Pro5 enkephalin. These acetylglycopyranosylamine derivatives showed enhanced lipophilicity compared to their parent compound by a partition coefficient study and they also showed greater membrane permeability, using the rabbit cornea as a model system. These derivatives also are resistant to hydrolytic enzymes as compared to the endogenous met-enkephalin when evaluated in homogenized iris-ciliary body and aqueous humor from rabbit eyes.

Analgesics↗
PubMed1997

Inhibition of bufalin on pituitary and testicular function in rats.

The effects of bufalin on the secretion of testosterone and luteinizing hormone (LH) and the accumulation of testicular adenosine 3':5'-cyclic monophosphate (cAMP) were studied. Male rats were injected with bufalin, human chorionic gonadotropin (hCG), gonadotropin releasing hormone (GnRH), hCG plus bufalin or GnRH plus bufalin via a jugular catheter. Blood samples were collected at several intervals subsequent to the challenge. In the in vitro study, rat testis blocks were incubated with bufalin, hCG or both for 1 h. The anterior pituitary gland was incubated with bufalin, GnRH or both for 30 min. The media were analyzed for testosterone or LH. For studying cAMP accumulation, testicular blocks were incubated for 1 h with the medium containing isobutyl-1-methylxanthine. After incubation, tissues were extracted by ethanol before measuring cAMP concentration. A single intravenous injection of bufalin decreased the basal and hCG-stimulated levels of plasma testosterone. Administration of bufalin in vitro resulted in an inhibition of both basal and hCG-stimulated release of testosterone. Bufalin diminished cAMP accumulation in rat testes. However, the basal levels of plasma and medium LH were not altered by bufalin administration. Likewise, the LH response to GnRH was diminished by bufalin administration, both in vivo and in vitro. These results suggest that the inhibition of testosterone production by bufalin is partly caused by a decrease of testicular cAMP accumulation and LH response to GnRH in rats.

1-Methyl-3-isobutylxanthine↗
PubMed1997

The use of personal protective measures in control of malaria in a defined community.

Malaria is one of the main health problems in the non-immune immigrant workers and army personnel of the malaria endemic areas in Myanmar. Due to changes in the vector bionomics and multiresistant strains of P. falciparum, chemoprophylaxis alone is not an effective means of control of malaria in them. So it is envisaged that the combined used of personal protective measures (deltamethrin impregnated bed-nets, scalves and hand-bands) and the chemoprophylaxis will be an effective means of control of malaria in the define group of people. The study also intended to find out the side effects of the deltamethrin and feasibility and acceptability of methods by the users. The study was conducted in Theini Township, Northern Shan State, from March to November 1993. The study population consisted of all ages of both sexes 554 and 440 persons in the test and control groups respectively. At the initial phase of the study, malaria infected persons from both the groups were treated. The experimental group received personal protective measures with impregnation of bed-nets using 25 mg ai/m2 of deltamethrin at 4 monthly intervals and the scarves and hand-bands at twice the concentration of the insecticides at monthly intervals. Chemoprophylaxis was given to both the groups at weekly intervals using age adjusted dosage of Pyrixine tablet (sulfadoxine-pyrimethamine). The parasitological, entomological, and epidemiological indices were collected at two month intervals in both the groups. The study clearly showed the impact of personal protective measures and chemoprophylaxis on malaria infection in the studied subjects. During the study period, the out patient malaria cases of the test group was 6% to 11.2% and that of the control group was 12% to 21.6% in Theini Hospital. The reinfection rate of the test group (0.9 to 4.7%) was also significantly lower than the control group (6.1 to 14.3%) from July to November. Acceptance of the treated bed-nets, scarves and hand-bands was high and good compliance was found in the follow up. The results of the study clearly showed that malaria can be controlled effectively in the defined group of persons for a malaria transmission season by using chemoprophylaxis and personal protective measures.

Adult↗
PubMed1997

Fusion expression of green fluorescent protein and HCV capsid antigene in Escherichia coli cells.

A chimeric gene of the green fluorescent protein (GFP) and hepatitis C virus (HCV) core antigene were constructed and expressed in E. coli cells. The expressed fusion protein was examined by Dot-ELISA and Western blot and the three antigenic determinants were detected. The GFP-Core fusion protein showed not only the striking green fluorescence under natural light but also the HCV antigenic activity. A new method of immunological diagnosis is greatly anticipated in the light of this fusion protein which can be seen as the HCV antigen tagged with the green fluorescent protein.

Animals↗
PubMed1996

A common mutant epidermal growth factor receptor confers enhanced tumorigenicity on human glioblastoma cells by increasing proliferation and reducing apoptosis.

Alterations of the EGFR gene occur frequently in human gliomas where the most common is an in-frame deletion of exons 2-7 from the extracellular domain, resulting in a truncated mutant receptor (deltaEGFR or de 2-7 EGFR). We previously demonstrated that introduction of deltaEGFR into human U87MG glioblastoma cells (U87MG.deltaEGFR) conferred remarkably enhanced tumorigenicity in vivo. Here, we show by cell-mixing experiments that the enhanced tumorigenicity conferred by deltaEGFR is attributable to a growth advantage intrinsic to cells expressing the mutant receptor. We analyzed the labeling index of the proliferation markers Ki-67 and bromodeoxyuridine and found that tumors derived from U87MG.deltaEGFR cells had significantly higher labeling indexes than those of tumors derived from U87MG cells that were either naive, expressed kinase-deficient mutants of deltaEGFR, or overexpressed exogenous wild-type EGFR. We also utilized terminal deoxynucleotidyl transferase-mediated nick end-labeling assays and showed that the apoptotic index of U87MG.deltaEGFR tumors was more than 4-fold lower than that of parental U87MG tumors. This decrease in cell death was inversely correlated with the expression level of Bcl-X(L), a negative regulator of apoptosis, which was more than 3-fold higher in U87MG.deltaEGFR-derived tumors than in those derived from parental cells. Similar observations were obtained in vitro in serum-free conditions. These results suggest that deltaEGFR exerts its pronounced enhancement of glioblastoma tumorigenicity by stimulating proliferation and inhibiting apoptosis and that the effects are directly attributable to its constitutively active signal.

Animals↗
PubMed1996

Enhanced tumorigenic behavior of glioblastoma cells expressing a truncated epidermal growth factor receptor is mediated through the Ras-Shc-Grb2 pathway.

A mutant epidermal growth factor receptor (DeltaEGFR) containing a deletion of 267 amino acids from the extracellular domain is common in human glioblastomas. We have previously shown that the mutant receptor fails to bind EGF, is constitutively phosphorylated, and confers upon U87MG glioblastoma cells expressing it (U87MG. DeltaEGFR), an increased ability to form tumors in mice. Here we demonstrate that the constitutively phosphorylated DeltaEGFR enhances growth of glioblastoma cells through increased activity of Ras: 1) there was an increase in the proportion of Ras present in the GTP-bound form, and 2) introduction of neutralizing anti-Ras 259 antibodies into U87MG and U87MG.DeltaEGFR cells by microinjection inhibited DNA synthesis to the same low level in both cell populations. We also show that the truncated EGF receptor constitutively associates with the adapter proteins Shc and Grb2 which are involved in the recruitment of Ras to activated receptors. Several derivatives of DeltaEGFR containing single, or multiple mutations at critical autophosphorylation sites were constructed and used to demonstrate that the major Shc binding site is Tyr-1148, and that Grb2 association occurs primarily through Tyr-1068. We conclude that the increased tumorigenic potential of glioblastoma cells expressing the truncated EGF receptor is due at least in part to Ras activation presumably involving the Shc and Grb2 adapter proteins.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Differential expression of lacZ in the liver and kidney of transgenic mice carrying chimeric lacZ-erythropoietin gene constructs with or without its 1.2 kb 3'-flanking sequence.

Erythropoietin (EPO) plays a key role in erythropoiesis and is expressed predominantly in the fetal liver and in the adult kidney. The EPO gene is up-regulated at the transcriptional level under hypoxic/anemic conditions. We studied the role of the 5'- and 3'-flanking sequences of the mouse EPO gene in its tissue-specific and hypoxia-induced expression by developing transgenic mouse lines carrying chimeric EPO-lacZ gene constructs. Transgenic mice carrying a 6.5 kb segment of the 5'-sequence and most of the EPO gene in which lacZ was substituted for exon 1 (5'-lacZ-EPO) demonstrated induction of lacZ expression following hypoxia/ anemia induction in both the liver and kidney of adult mice. However, transgenic mice carrying the above construct along with the 1.2 kb 3'-flanking sequence (5'-lacZ-EPO-3') showed a high level of lacZ expression following hypoxia/anemia induction in adult kidney but not in adult liver. With the aim of further understanding the role of the 3'-flanking sequence in tissue-specific expression of the EPO gene, we studied the interactions of protein factors with this 1.2 kb 3' region and demonstrated that multiple sets of protein factors interact tissue specifically with a 10 bp sequence, TCAAAGATGG, located downstream of the previously characterized 3' hypoxia-responsive enhancer element.

Animals↗
PubMed1996

A combinatorial library strategy for the rapid humanization of anticarcinoma BR96 Fab.

We have used a combinatorial mutagenesis strategy to humanize BR96, a monoclonal antibody that binds to the Lewis Y class of tumor antigens. This approach allows simultaneous assessment of hundreds of humanized variable regions to identify the molecules that best preserve affinity, thus overcoming the major drawback of current humanization procedures, the requirement to construct and analyze each humanized antibody separately. Murine residues of BR96 were mutated to human if they were solvent-exposed residues that did not participate in the formation of the antigen binding site and were not at the interface of the light and heavy chain. At positions that might be involved in binding to antigen, the choice between the murine and human residue was more difficult. Murine and human alternatives were incorporated into a combinatorial library at positions representing buried residues that might affect the structural integrity of the antigen binding site. By encoding this library of humanized BR96 Fabs in an M13 phage vector, we rapidly identified several candidates with nearly identical antigen binding, within 2-fold, of the chimeric Fab. Additional mutagenesis directed at sites suggested in the literature as potentially important for antigen binding in a similar anti-Lewis Y antibody yielded no further improvements.

Amino Acid Sequence↗