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Biomedical subjects

H Lu

Publications and source records attributed to H Lu.

At least 253 records · Page 14Linked to original sources
PubMed1998

Adenovirus-mediated delivery of a uPA/uPAR antagonist suppresses angiogenesis-dependent tumor growth and dissemination in mice.

AdmATF is a recombinant adenovirus encoding a secreted version of the amino-terminal fragment (ATF) of murine urokinase (uPA). This defective adenovirus was used in three murine models to assess the antitumoral effects associated with local or systemic delivery of ATF, a broad cell invasion inhibitor that antagonizes uPA binding to its cell surface receptor (uPAR). A single intratumoral injection of AdmATF into pre-established MDA-MB-231 human breast xenografts grown in athymic mice, or into pre-established C57/BL6 syngeneic Lewis lung carcinoma resulted in a specific arrest of tumor growth. Neovascularization within and at the vicinity of the injection site was also suppressed, suggesting that AdmATF inhibited primary tumor growth by targeting angiogenesis. AdmATF also interfered with tumor cell establishment at distant sites: (1) lung dissemination of Lewis lung carcinoma cells was significantly reduced following intratumoral injection at the primary site; and (2) systemic administration of AdmATF inhibited subsequent liver metastasis in a LS174T human colon carcinoma xenograft model. These data outline the potential of using a recombinant adenovirus directing the secretion of an antagonist of cell-associated uPA for cancer gene therapy.

Adenoviridae↗
PubMed1998

Quantum dynamics of the femtosecond photoisomerization of retinal in bacteriorhodopsin.

The membrane protein bacteriorhodopsin contains all-trans-retinal in a binding site lined by amino acid side groups and water molecules that guide the photodynamics of retinal. Upon absorption of light, retinal undergoes a subpicosecond all-trans-->13-cis phototransformation involving torsion around a double bond. The main reaction product triggers later events in the protein that induce pumping of a proton through bacteriorhodopsin. Quantum-chemical calculations suggest that three coupled electronic states, the ground state and two closely lying excited states, are involved in the motion along the torsional reaction coordinate phi. The evolution of the protein-retinal system on these three electronic surfaces has been modelled using the multiple spawning method for non-adiabatic dynamics. We find that, although most of the population transfer occurs on a timescale of 300 fs, some population transfer occurs on a longer timescale, occasionally extending well beyond 1 ps.

Bacterial Proteins↗
PubMed1998

Office and laboratory blood pressures as predictors of daily blood pressure level in normotensive subjects and borderline and mild hypertensive subjects.

A series of standardized laboratory tests [10 min sitting and supine, 9 min standing, dynamic; cycle ergometer (ERG) and isometric exercise; handgrip (HG)] were performed during intra-arterial blood pressure (BP) recording in 97 healthy unmedicated men, initially classified as normotensive (NT, n = 34), borderline hypertensive (BHT, n = 29) or mildly hypertensive (HT, n = 34) by repeated office blood pressure (OBP) measurements. After testing, a 24-h intra-arterial ambulatory BP (IABP) recording was obtained while subjects performed their normal activities. Day and night periods were analysed as well as 24-h averages for systolic BP (SBP) and diastolic BP (DBP) using Pearson correlations and multiple linear regressions. In normotensive subjects, the supine SBP predicted IABP measurements best (r range 0.39-0.69, P < 0.05-0.001). In multiple regression, supine SBP explained 49% of 24-h SBP variance (F = 12.4, P = 0.001). For BHT, supine SBP was also the best predictor (r range 0.09-0.64, P NS to P < 0.001), and it explained 37% of 24-h SBP variance (F = 15.6, P = 0.0005). In HT, ERG DBP correlated best with IABP (r range 0.52-0.75, P < 0.01-0.001). ERG SBP explained 49% of 24-h SBP (F = 31.0, P = 0.0000) and ERG DBP explained 56% of 24-h DBP (F = 35.4, P = 0.0000) variance. Laboratory BP correlations were generally better with day than with night measurements. OSBP correlated moderately well with IABP in NT, and weakly in BHT and HT; ODBP instead correlated with IABP in NT and HT but not significantly in BHT. In conclusion, OBP is less closely related to IABP than laboratory BP, but even laboratory BP generally explains less than 50% of IABP variance. Stressors such as exercise are useful only in HT. For BHT, the prediction of IABP with laboratory measures was even weaker than in other groups, and thus ambulatory measurements cannot be replaced by short-duration laboratory measurements and stress tests.

Adult↗
PubMed1998

The effects of oestrogen and progesterone on serotonin and its metabolite in the lateral septum, medial preoptic area and ventromedial hypothalamic nucleus of female rats.

The effects of sex steroid hormones on serotonin and its metabolite, 5-hydroxyindole-3-acetic acid (5-HIAA) in the lateral septal nucleus (LS), the medial preoptic area (MPA) and the ventromedial nucleus of the hypothalamus (VMH) of female rats were investigated, using immunohistochemistry and high-performance liquid chromatography (HPLC). Female rats were divided into three groups: ovariectomized rats (OVX group); OVX-rats treated with estradiol benzoate alone (E2 group); and OVX-rats treated with E2 plus progesterone (E2 + P group). We analysed the density of serotonin-immunoreactive fibres with a computer-assisted image analysis system, and measured the tissue concentrations of serotonin and 5-HIAA. Many serotonin-immunoreactive fibres were observed in the LS, MPA and VMH in all three groups. The density of serotonin-immunoreactive fibres in the MPA and VMH was significantly lower in the E2 and E2+P groups compared to the OVX group, whereas the LS showed no detectable differences among the three groups. In the HPLC study, the concentrations of serotonin in the MPA and VMH of the E2 and E2+P groups were significantly lower than that in the OVX group. There was no significant difference in the concentration of serotonin in the LS. The concentration of 5-HIAA and the ratio of 5-HIAA/serotonin in the LS, MPA and VMH showed no significant differences among the OVX, E2 and E2+P groups. The present results suggest that E2 priming for sexual behaviour can affect the serotonergic system by decreasing serotonin content, but not the turnover rate, in the MPA and VMH of female rats.

Animals↗
PubMed1998

Differential in vitro hepatic and intestinal metabolism of ifosfamide in the rat.

1. Metabolism of ifosfamide (IF) in intestinal and hepatic microsomes has been investigated in the rat. The generation of three primary metabolites, 4-hydroxyifosfamide (HOIF), N2-dechloroethylifosfamide (N2D) and N3-dechloroethylifosfamide (N3D), was followed. 2. Microflora in rat small intestine showed no metabolic activity towards IF. The overall metabolic activity was higher in the hepatic microsomes than in the intestinal microsomes, and the hydroxylation pathway accounted for 53.6% of total IF metabolism in the hepatic microsomes. In contrast, hydroxylation of IF in intestinal microsomes was only 9.8% of the total monitored metabolic activity and N3-dechloroethylation of IF was a major pathway, constituting 73.0% of the monitored activity. 3. In summary, the intestinal metabolism of IF was demonstrated for the first time and these in vitro data indicate that the intestinal metabolism of IF could contribute significantly to the overall first-pass metabolism.

Animals↗
PubMed1998

The effects of sevoflurane on cerebral blood flow autoregulation in rats.

UNLABELLED: In this study, we investigated the effect of sevoflurane on cerebral blood flow (CBF) autoregulation in rats. Twenty-four male Sprague-Dawley rats were randomly assigned to receive one of the following anesthetic treatments. In Group 1 (n = 8, control) anesthesia was maintained using fentanyl (25 microg x kg(-1) x h(-1)) and N2O/O2 (fraction of inspired oxygen 0.33). In Group 2 (n = 8) and Group 3 (n = 8), anesthesia was maintained using 2% sevoflurane (1 minimum alveolar anesthetic concentration [MAC]) and 2 MAC sevoflurane (4 vol%) in O2/air (fraction of inspired oxygen 0.33), respectively. Cortical CBF autoregulation was measured during graded hemorrhage within the mean arterial pressure (MAP) range of 100-30 mm Hg using laser Doppler flowmetry. CBF was constant with fentanyl/ N2O (Group 1) and 1 MAC sevoflurane (Group 2) within the MAP range of 100-40 mm Hg. In Group 3 (2 MAC sevoflurane), CBF decreased as a linear function of hemorrhagic hypotension. These results indicate that CBF autoregulation was intact during 1 MAC sevoflurane. In contrast, CBF autoregulation was impaired with 2 MAC sevoflurane. This is probably related to a reduction of baseline cerebrovascular tone with higher concentrations of sevoflurane, which results in a decreased capacity of autoregulatory cerebrovascular dilation during hemorrhage. IMPLICATIONS: The purpose of the present study was to investigate the effect of sevoflurane on cerebral blood flow autoregulation in rats. Cerebral blood flow autoregulation was intact with 1 minimum alveolar anesthetic concentration sevoflurane but was impaired with 2 minimum alveolar anesthetic concentration sevoflurane.

Anesthetics, Inhalation↗
PubMed1998

Skeletal muscle ventricles: full versus half aortic ligation.

BACKGROUND: Skeletal muscle ventricles have been shown to provide effective aortic diastolic counterpulsation in an experimental model. Construction has included full ligation of the thoracic aorta. The authors sought to determine if these muscle pumps could function effectively without fully ligating the aorta. METHODS: Skeletal muscle ventricles were constructed in two groups of dogs. Group 1 had their aortas fully ligated (n = 10) while group 2 had their aortas narrowed by 50% (n = 10). The animals were followed for 10 weeks. RESULTS: There was no significant difference in femoral diastolic augmentation at implant or at 10 weeks (19.1% +/- 9.9% in group 1 [full ligation] versus 16.3% +/- 10.2% in group 2 [half ligation] p = 0.502). Survival to 10 weeks was significantly better in group 1 (full ligation). Nine of 10 animals in this group survived versus 4 of 10 in group 2 (p = 0.019). Two animals survived in the half ligation group with effective augmentation and without thrombus formation. CONCLUSION: Both models produce effective diastolic counterpulsation. Survival was decreased in this model using half ligation, and survival without complication was observed in 2 of 10 animals. Currently the overall results are better with the full aortic ligation model. However, design modifications will probably result in an effective model of diastolic counterpulsation without full aortic ligation.

Animals↗
PubMed1998

Interactions among Drosophila nuclear envelope proteins lamin, otefin, and YA.

The nuclear envelope plays many roles, including organizing nuclear structure and regulating nuclear events. Molecular associations of nuclear envelope proteins may contribute to the implementation of these functions. Lamin, otefin, and YA are the three Drosophila nuclear envelope proteins known in early embryos. We used the yeast two-hybrid system to explore the interactions between pairs of these proteins. The ubiquitous major lamina protein, lamin Dm, interacts with both otefin, a peripheral protein of the inner nuclear membrane, and YA, an essential, developmentally regulated protein of the nuclear lamina. In agreement with this interaction, lamin and otefin can be coimmunoprecipitated from the vesicle fraction of Drosophila embryos and colocalize in nuclear envelopes of Drosophila larval salivary gland nuclei. The two-hybrid system was further used to map the domains of interaction among lamin, otefin, and YA. Lamin's rod domain interacts with the complete otefin protein, with otefin's hydrophilic NH2-terminal domain, and with two different fragments derived from this domain. Analogous probing of the interaction between lamin and YA showed that the lamin rod and tail plus part of its head domain are needed for interaction with full-length YA in the two-hybrid system. YA's COOH-terminal region is necessary and sufficient for interaction with lamin. Our results suggest that interactions with lamin might mediate or stabilize the localization of otefin and YA in the nuclear lamina. They also suggest that the need for both otefin and lamin in mediating association of vesicles with chromatin might reflect the function of a protein complex that includes these two proteins.

Animals↗
PubMed1998

Release of dopamine and norepinephrine by hypoxia from PC-12 cells.

We examined the effects of hypoxia on the release of dopamine (DA) and norepinephrine (NE) from rat pheochromocytoma 12 (PC-12) cells and assessed the involvement of Ca2+ and protein kinases in stimulus-secretion coupling. Catecholamine release was monitored by microvoltammetry using a carbon fiber electrode as well as by HPLC coupled with electrochemical detection (ECD). Microvoltammetric analysis showed that hypoxia-induced catecholamine secretion (PO2 of medium approximately 40 mmHg) occurred within 1 min after the onset of the stimulus and reached a plateau between 10 and 15 min. HPLC-ECD analysis revealed that, at any level of PO2, the release of NE was greater than the release of DA. In contrast, in response to K+ (80 mM), DA release was approximately 11-fold greater than NE release. The magnitude of hypoxia-induced NE and DA releases depended on the passage, source, and culture conditions of the PC-12 cells. Omission of extracellular Ca2+ or addition of voltage-gated Ca2+ channel blockers attenuated hypoxia-induced release of both DA and NE to a similar extent. Protein kinase inhibitors, staurosporine (200 nM) and bisindolylmaleimide I (2 microM), on the other hand, attenuated hypoxia-induced NE release more than DA release. However, protein kinase inhibitors had no significant effect on K+-induced NE and DA releases. These results demonstrate that hypoxia releases catecholamines from PC-12 cells and that, for a given change in PO2, NE release is greater than DA release. It is suggested that protein kinases are involved in the enhanced release of NE during hypoxia.

Animals↗
PubMed1998

Isolation and partial characterization of a receptor to surfactant protein A expressed by rat type II pneumocytes.

Surfactant protein A (SP-A), the most abundant protein component in pulmonary surfactant, has been shown to enhance surfactant phospholipid uptake by the type II alveolar epithelial cell. Recent evidence has shown that this process may be receptor-mediated. We undertook this study to isolate the putative receptor from type II cell membranes. We isolated two specific SP-A binding proteins from type II cells with apparent molecular weights (Mr) of 86 and > 200 kD under nonreducing conditions. Under reducing conditions, the higher-Mr protein was not present, but three proteins with apparent Mr of 65, 55, and 50 kD were visible, in addition to the 86-kD protein, indicating that the higher-Mr protein was composed of the smaller peptides which form disulfide bonds. The 86-kD protein is a glycoprotein with approximately 30% of its mass as carbohydrate. The 50-kD protein is also a glycoprotein (approximately 30% of its mass as carbohydrate), and SP-A binds to the protein core. Polyclonal and monoclonal antibodies to these peptides saturably bind to the surface of type II cells but not other lung cells, as shown by immunohistochemistry. SP-A competitively inhibits binding of one monoclonal antibody to type II cells, and the monoclonal antibody was able to block the effect of SP-A on phospholipid uptake by type II cells, indicating that this complex is a receptor to SP-A which is expressed on type II cells. This novel receptor is fundamental to the biology of surfactant metabolism in the lung.

Animals↗
PubMed1998

The co-existence of insulin-mediated decreased mean arterial pressure and increased sympathetic nerve activity is not mediated by the baroreceptor reflex and differentially by hypoglycemia.

In this study we measured simultaneously and sequentially the lumbar sympathetic nerve activity (LSNA) or renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP), and heart rate (HR) in response to insulin with co-existing hypoglycemia or with glucose replacement in normal rats. Sinoaortic denervation (SAD) was used to evaluate the influence of the baroreflex. LSNA, RSNA, MAP and HR were determined using an acquisition processor and computer software. Bolus insulin infusion where the blood glucose was allowed to decrease resulted in an immediate decrease in MAP. The HR decreased for approximately 15 min and subsequently increased. The LSNA increased immediately after insulin infusion peaking at 25 minutes and then recovered toward baseline. Insulin infusion with glucose replacement resulted in a decrease in MAP and HR. The LSNA progressively increased and was maintained throughout the experimental period. Insulin infusion with hypoglycemia increased RSNA and when hypoglycemia was prevented the RSNA decreased. SAD attenuated the decrease in MAP and LSNA response to insulin. Thus, insulin acts to decrease MAP while simultaneously increasing HR, LSNA and RSNA when hypoglycemia is allowed to occur. However, insulin acts to decrease HR and RSNA when euglycemia is maintained. The insulin-induced increase in LSNA is modulated by the baroreflex mechanism. We conclude that insulin has independent direct and indirect effects on LSNA, RSNA, MAP and HR that are modulated by glycemia and the baroreflex.

Animals↗
PubMed1998

[A community-based survey on hypertension in the medium-aged-elderly in Jiuxianqiao area Beijing].

UNLABELLED: To investigate the epidemiologic features of hypertension and major risk factors in the middle-elderly in Jiuxianqiao area and to develop reasonable preventive strategies, from June to December 1996, nine communities of Jiuxianqiao area were selected for the study. Two thousand and fifty-five middle-elderly (age > or = 50 years old) were investigated including measurement of blood pressure and identifying risk factors of hypertension. Two hundred and thirty-nine hypertensive patients and two hundreds sixty-seven person with normal blood pressure from the study population were examined through oral 75 grams glucose tolerance and electrocardiogram. The prevalence rates of definite and borderline hypertension were 31.6% and 10.9% respectively with a total rate of 42.5%. The prevalence rate of definite hypertension in males was significantly higher than that in females (P < 0.05). The prevalence rate of systolic hypertension was 7.5% but increased paralelly with age (P < 0.05). The prevalence rate of systolic hypertension in females was not significantly higher than that in males. 25.6% of patients with hypertension under investigation denied or were ignorant about having hypertension. The prevalence rates of diabetes, impaired glucose tolerance (IGT) and coronary heart disease in hypertensive group were significantly higher than that in people with normal blood pressure (P < 0.01). CONCLUSION: Hypertension is a disease that seriously endangers the health of the middle-elderly in the community on which calls for more care and education in the community.

Aged↗
PubMed1998

[Analysis of the causes of vascular crisis following anastomosis of small vessel and its prophylaxis and treatment].

In order to find out the causes, diagnosis, and the prevention and treatment of vascular crisis following anastomosis of small vessels, 314 cases vascular crisis from 1985 to 1997, were analyzed, in which 152 cases, suffered from tissue necrosis either total or partial, making up 48.4%. One hundred and forty-four cases underwent conservative treatment occupying 45.8% and 104 cases had tissue necrosis, occupying 68.4%. Operative exploration was done on 170 cases, occupying 54.1% and 48 cases of them suffered from necrosis, which made up 31.6% of all necrotic cases. Eighty-six cases were followed up by regular visits, ranging from 40 days to 7 years, with the finding that those who had regained normal circulation after vascular crisis recovered as well as those without crisis, and among those who did not regain normal circulation but survived with the help of collateral circulation after vascular crisis, they were usually cases of bad union, healing of wound, persistent swelling, different degree of tissue atrophy, poor recovery of sensation. It was concluded that proper use of vascular anastomosis technique and prophylactic measures preventing postoperative vascular spasm were extremely important, in the prevention of development of vascular crisis following anastomosis of small vessels. If vascular crisis did not respond well to conservative treatment, prompt surgical exploration should be undertaken.

Adolescent↗
PubMed1998

[Expectant treatment of placenta previa with ritodrine].

OBJECTIVE: To investigate the effectiveness of the expectant treatment in placenta previa with adrenergic agonist ritodrine. METHODS: 50 women with placenta previa of preterm labor were randomly assigned into two groups. 26 patients treated with magnesium sulfate were served as control group. 24 patients were enrolled in the study group, receiving ritodrine 100 mg in 5% glucose 500 ml intravenous. The drip speed was started at 8 drips per minute routinely, then adjusted according to the treatment response, and oral ritodrine was used after vaginal bleeding and uterine contraction disappeared 12 hours. If contraction reappeared, the i.v. infusion would be restarted. RESULTS: The study group prolonged the gestational period to an average of 28.24 days and increased the birth weight of newborn to an average of 2,913.68 g (P < 0.05). CONCLUSION: Ritodrine is highly effective and safe for expectant treatment of placenta previa.

Adrenergic beta-Agonists↗
PubMed1998

[Time selection for RA synovectomy].

OBJECTIVE: To discuss the time selection for RA synovectomy. METHOD: Eighty-six knees in 64 RA patients underwent synovectomy in 7 years. 8 of the 64 patients were in RA stage I, 26 in II, 24 in III, 8 in IV. The mean age was 43.9 years and the average follow-up period lasted 38.2 months. RESULTS: Pain relief and swelling reduction were significant clinical features after synovectomy. The overall assessment of the effect of synovectomy showed satisfactory results (72.9%) including all RA-I, and RA-II (87.2%). CONCLUSION: If the patients have sustained or intractable joint swollening with exuberant synovium after strict drug therapy over half a year, synovectomy is an appropriate consideration, it is very important to select the time for synovectomy.

Adolescent↗
PubMed1998

[Cloning and expressing of HCV NS5 partial gene and dynamic changes of anti-NS5].

OBJECTIVE: To study antigenicity of HCV NS5 protein and dynamic changes of anti-NS5 in post-transfusion hepatitis C (PT-HC). METHODS: Epitopes of HCV NS5 protein were analyzed by Goldkey Program. NS5 gene fragment was amplified by reverse transcription and polymerize chain reaction (RT-PCR) from sera of PT-HC patients. Sequence analysis was performed, and recombinant strain was constructed. Series sera from PT-HC were detected for anti-NS5, ALT and HCV RNA. RESULTS: The homology of nucleotide and amino acid with genotype II in the same region was 91.8% and 92.4%, respectively. SDS-PAGE analysis showed an expressing band around 50 kD, the fusion protein represented about 21.4% of total bacterial protein. Western blot result proved the expressing band could specifically react with sera from hepatitis C patients. Detection results of series blood samples from PT-HC showed that the antibody against NS5 appeared relatively late, the positive conversion time was 182.9 +/- 168.5 day. Dynamic changes of anti-NS5 were correlated with serum ALT in most cases. The types of dynamic change of anti-NS5 were passing positive; intermittent positive; persistent positive, and persistent negative in two years. CONCLUSION: Antibody against NS5 may reflect the disease activity to some extent. It appears relatively late, and is of no value in early stage diagnosis.

Cloning, Molecular↗
PubMed1998

[The impact of the missense mutation-ser20gly in islet amyloid polypeptide gene on NIDDM in Chinese].

OBJECTIVES: To ascertain the presence of the Ser 20Gly mutation of islet amyloid polypeptide (IAPP) gene and its impact on NIDDM in Chinese. METHODS: In 896 Chinese, 825 were unrelated subjects (NIDDM in 609 and non-diabetics, 216) and 71 were family members of the pedigrees with IAPP gene-Ser 20Gly carrier probands detected from population screening. The mutation was examined by PCR-RFLP MspI digestion in population screening and the results was randomly checked by direct DNA sequencing. Data were analyzed through association as well as linkage approaches. RESULTS: The Ser20Gly mutation of the IAPP gene was observed in Chinese. It was more prevalent in NIDDM (17 cases, 2.8%) than in non-diabetics (1 cases, 0.5%) (Fisher two-tailed exact P = 0.05). The mutation carrier detected by PCR-RFLP was confirmed to be the A to G point mutation in nucleotide 582 of IAPP gene cDNA encoding the amino acid codon 20. All the mutation carriers detected in population screening were heterozygotes. Analysis of the family members of the 12 NIDDM pedigrees with the IAPP gene Ser20Gly mutation showed that in two families, the mutation was not cosegregated with the affection status. The older was the age of Ser20Gly mutant carrier, the more prevalent was the diabetes in families (P = 0.0001). The highest total lod score of this 12 pedigree was 0.021(theta = 0) in parametric linkage analysis with the model of autosomal dominance with incomplete penetrance. CONCLUSION: The Ser20Gly mutation of IAPP gene was present in Chinese. This mutation does not cause monogenic inheritance diabetes, but may be a pathogenetic factor for the development of NIDDM, the complex genetic disease.

Adult↗