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Biomedical subjects

H Wu

Publications and source records attributed to H Wu.

At least 595 records · Page 33Linked to original sources
PubMed1996

Targeted in vivo expression of the cyclin-dependent kinase inhibitor p21 halts hepatocyte cell-cycle progression, postnatal liver development and regeneration.

The CDK inhibitor p21 (WAF-1/CIP-1/SDI-1) has been implicated in DNA damage-induced p53-mediated G1 arrest, as well as in physiological processes, such as cell differentiation and senescence, that do not involve p53 function. To determine the impact of p21 on normal development and cell-cycle regulation in vivo, we have generated transgenic mice that abundantly express p21 specifically in hepatocytes. During postnatal liver development, when transgenic p-21 protein becomes detectable, hepatocyte proliferation is inhibited dramatically. This disturbance causes a reduction in the overall number of adult hepatocytes, resulting in aberrant tissue organization, runted liver and body growth, and increased mortality. The transgenic p21 protein is associated with most, if not all, of the cyclin D1-CDK4 in liver but not significantly with other cyclin/CDK proteins, indicating the importance of cyclin D1-CDK4 function in normal liver development. The appearance of large polyploid nuclei in some hepatocytes indicates that p21 may also cause arrest during the G2 phase of the cell cycle. Significantly, partial hepatectomy failed to stimulate hepatocytes to proliferate in p21 transgenic animals. These results provide the first in vivo evidence that appropriate p21 levels are critical in normal development and further implicate p21 in the control of multiple cell-cycle phases.

Animals↗
PubMed1996

Type I collagen-deficient Mov-13 mice do not retain SPARC in the extracellular matrix: implications for fibroblast function.

The Mov-13 strain of mice was created by the insertion of the murine Moloney leukemia virus into the first intron of the alpha 1 (I) collagen gene. Consequently, Mov-13 embryos do not transcribe alpha 1 (I) collagen mRNA and lack type I collagen protein in the extracellular matrix (ECM). Homozygotes die within 12-14 days of embryonic development, in part from the rupture of large blood vessels, and also exhibit deficiencies in hematopoesis and assembly of the ECM (Lohler et al. [1984] Cell 38:597-607). Several matricellular proteins, proteoglycans, and growth factors bind to type I collagen, e.g., fibronectin, secreted protein acidic and rich in cysteine (SPARC), decorin, and transforming growth factor-beta. Here we investigate the expression and function of SPARC in the absence of type I collagen. We show that fibroblasts isolated from Mov-13 homozygous, heterozygous, and wild-type embryos transcribed and translated SPARC mRNA in vitro. However, accumulation of extracellular SPARC was severely affected in the tissues of Mov-13 homozygotes, whereas extracellular deposition of the secreted glycoproteins fibronectin and type III collagen was not altered. Since SPARC has been shown to be a regulator of cell shape, the functional consequences of the absence of extracellular SPARC were evaluated in collagen gel contraction assays. Fibroblasts isolated from homozygous Mov-13 mice did not contract native type I collagen gels as efficiently as fibroblasts from heterozygous littermates; however, addition of exogenous SPARC enhanced the contraction of collagen by homozygous Mov-13 fibroblasts. The stimulatory effect of SPARC was blocked by antibodies specific for the amino terminus of the protein. These results provide evidence that type I collagen is one of the major extracellular proteins that binds SPARC in vivo. Furthermore, the capacity of fibroblasts to contract ECM in vitro is enhanced by extracellular SPARC. We therefore propose that the remodeling of ECM by cells in vivo is regulated in part by a specific interaction between SPARC and type I collagen.

Animals↗
PubMed1996

Neuroprotective effects of the pyrrolopyrimidine U-104067F in 3-acetylpyridine-treated rats.

The neuroprotective effects of U-104067F[(9-(2-morpholinyl)ethyl) 2,4-di-l-pyrrolidinyl-9H-pyrimidino (4,5-b)(4,5indole monohydrochloride hydrate], a pyrrolopyrimidine antioxidant, were investigated in 3-acetylpyridine (3-AP)-treated Wistar rats. A significant (P < 0.01) reduction in cerebellar cGMP and ATP was observed at 96 h after treatment with 3-AP (500 micromol/kg ip). Oral administration of U-104067F significantly attenuated 3-AP-induced reductions in cGMP and ATP, and this effect was dose related. Consistent with the neurochemical effect, U-104067F prevented 3-AP-induced loss of motor coordination. 3-Acetylpyridine produced a significant (P < 0.01) loss of neurons in the inferior olivary nucleus. Treatment with U-104067F partially, but significantly (P < 0.01), prevented the loss of inferior olivary neurons. The physiological and neurochemical parameters were maintained within normal limits by U-104067F in 3-AP-treated rats despite only partial preservation of inferior olivary neurons.

Adenosine Triphosphate↗
PubMed1996

Unilateral neonatal hippocampal lesion alters septal innervation and trophism of the entorhinal cortex.

It is generally assumed that central nervous system injury sustained during development produces less severe behavioral deficits than damage in the adult, due to increased plasticity of the immature brain. However, developmental plasticity may also exacerbate deficits, presumably through formation of anomalous connections. Previous studies showed that after unilateral neonatal, but not adult, electrolytic hippocampal lesion spatial memory is severely impaired. To determine whether the memory deficit is correlated with anatomical changes in a major hippocampal afferent system, the septal input, the anterograde tracer Phaeseolus vulgaris leucoagglutinin was injected into the medial septum 2 months after unilateral neonatal hippocampal lesion. The density of septal fiber projections into the entorhinal cortex (EC) was found to be increased. Choline-acetyltransferase activity increased significantly in the EC 2 months postlesion, suggesting that septal cholinergic fibers are sprouting. Finally, nerve growth factor (NGF), which can mediate sprouting, was measured in the EC, NGF protein increased transiently 7 to 12 days postlesion in the ipsilateral EC, suggesting that increased trophic support is associated with growth of septal afferents into the EC. Thus, neonatal hippocampal lesion causes a reorganization of axonal connections associated with elevated NGF in the target region of the increased septal input. Moreover, since previous studies showed that the neonatal lesion is accompanied by a spatial memory deficit, this plasticity may compromise function of the remaining circuitry.

Animals↗
PubMed1996

Effect of huoxuequyu recipe on erythrocyte ultrastructure and membrane ATPase activity in rats with passive smoking.

The effect of "Huoxuequyu" recipe on erythrocyte membrane Ca(2+)-ATPase activity, Na(+)-K(+)-ATPase activity and erythrocyte ultrastructure in rats exposed to passive smoking were observed. The erythrocyte membrane Ca(2+)-ATPase activity and Na(+)-K(+)-ATPase activity were found to be decreased in the model group as compared with the control group (P < 0.01, P < 0.01), while no significant difference existed between the treated group and the control group (P > 0.05). Our results also showed that there were more deformed red blood cells in model group than in control group under TCM and SEM (P < 0.0001). No significant difference was found between control group and treated group (P > 0.05). Furthermore, these findings indicated that "Huoxuequyu" recipe, a prepared natural herbal medicine, may be involved in modulation of the activity of erythrocyte membrane enzymes, thereby protecting erythrocyte membrane, so as to improve the erythrocyte function.

Adult↗
PubMed1996

A scintigraphic study on gastric emptying in patients with non-ulcer dyspepsia.

Solid gastric emptying rates (GER) were determined with scintigraphic techniques in 20 patients with non-ulcer dyspepsia (NUD) and 9 healthy volunteers. GER were significantly decreased in NUD patients compared with controls, especially 45 min (P < 0.05), 60 and 90 min (P < 0.01) and 120 min (P < 0.05) after ingestion. In 13 out of 20 NUD patients who demonstrated lower GER, only 4 cases gave a lower GER at all stages throughout the determination, the other 9 showed their abnormal GER only after 60 min. In 3 cases who received repeated GER studies after cisapride therapy, 2 patients showed symptomatic relief accompanied by GER improvement. It is concluded that gastric emptying delay may be present with a high percentage in patients with non-ulcer dyspepsia. Scintigraphic gastric emptying test is a safe and reliable technique with good reproducibility. It may be helpful in quantitative study about gastric motion disorders.

Adolescent↗
PubMed1996

Comparative dopaminergic and muscarinic antagonist activity of clozapine and haloperidol.

Clozapine is an atypical antipsychotic drug, and its dopamine and muscarinic antagonist activity has been compared with haloperidol in rodents. Elevation in rat striatal acetylcholine (ACh) and mice cerebellar cGMP has been used as an agonist response for oxotremorine and quinpirole. Pretreatment with clozapine significantly blocked oxotremorine-induced elevation in striatal ACh (p<0.01) and cerebellar cGMP(p<0.05). At the same doses, clozapine had no significant effect on quinpirole-induced increases in ACh and cGMP levels. Pretreatment with haloperidol significantly antagonized quinpirole-induced elevation in striatal ACh (p<0.01) and cerebellar cGMP(p<0.05), and haloperidol had no significant effect on oxotremorine-induced agonist responses. Thus, clozapine is antimuscarinic at a dose level that lacks dopamine antagonist properties, whereas haloperidol is a dopamine antagonist and lacks antimuscarinic activity. The atypical neuroleptic profile of clozapine may be due to its high antimuscarinic and low antidopaminergic activity.

Acetylcholine↗
PubMed1996

Saponins from Mussaenda pubescens.

From the hydrophilic fractions of aerial parts of Mussaenda pubescens, three new saponins named mussaendosides D, E and H, along with a known saponin, mussaendoside S, were isolated. Their structures were elucidated on the basis of chemical and spectral evidence.

Carbohydrate Sequence↗
PubMed1996

Saponins from Clematis chinensis.

From ethanol extracts of the roots of Clematis chinensis, a new saponin, named clematichinenoside C, was isolated and its structure was established as 3-O-beta-D-glucopyranosyl-(1-4)-beta-D-ribopyranosyl-(1-3)-alpha-L - rhamnopyranosyl-(1-2)-alpha-L-arabinopyranosyl oleanolic acid 28-O-alpha-L-rhamnopyranosyl-(1-4)-beta-D-glucopyranosyl- (1-6)-beta-D-glucopyranosyl ester by spectroscopic and chemical means. In addition, one known saponin, huzhongoside B, was identified in the plant.

Carbohydrate Sequence↗
PubMed1996

Steroidal glycosides from Tribulus terrestris.

In addition to hecogenin 3-O-beta-D-glucopyranosyl(1--> 4)-beta-D-galactopyranoside, two new steroidal saponins were isolated from the aerial parts of Tribulus terrestris L. On the basis of chemical and spectroscopic evidence, especially 2D NMR spectroscopic techniques, the structures of the new saponins were established as 26-O-beta-D-glucopyranosyl-3-O-[-beta-D-xylopyranosyl(1--> 3)--beta-D-galactopyranosyl(1-->2)--beta-D-glucopyranosyl (1--> 4)-beta-D-glucopyranosyl]-5 alpha-furost-20(22)-en-12-one-3 beta,26-diol and 26-O-beta-D-glucopyranosyl-3-O-[{beta-D-xylopyranosyl (1-->3)--beta-D-galactopyranosyl(1-->2)--beta-D-glucopyranosyl(1 -->4)-beta-D-glucopyranosyl]-5 alpha-furostan-12-one-3 beta,22,26-triol.

Carbohydrate Conformation↗
PubMed1996

Lepidic intrapulmonary growth of malignant mesothelioma presenting as recurrent hydropneumothorax.

We report a case of malignant mesothelioma with unusual clinical and histological findings. The patient presented with recurrent hydropneumothorax and minimal pleural thickening on chest computed tomography (CT). Histologically, the pleura was involved by the malignant mesothelioma, albeit to a limited degree. Unexpectedly, the lung parenchyma from two different lobes showed focal nests of mesothelioma cells filling the alveolar spaces and growing on the luminal surface of the alveolar septa, closely resembling the multicentric growth pattern of bronchioloalveolar adenocarcinoma. Immunohistochemical and ultrastructural studies confirmed that the pulmonary lesions were an extension of the malignant mesothelioma. This case illustrates clinically, the importance of a high index of suspicion for malignancy in older patients with unexplained recurrent hydropneumothorax; and histologically the potential of malignant mesothelioma to invade the lung at an early stage of growth.

Aged↗
PubMed1996

Prediction of high-frequency electron paramagnetic resonance spectra of spin S = 3/2, 5/2 systems.

By the use of the universal EPR simulation program created by the author, spin S = 3/2 and S = 5/2 systems are studied and their simulated EPR spectra at high frequencies (Q-band for 35 GHz and W-band for 95 GHz) are presented here. The mononuclear Fe3+ in rubredoxin, isolated from Pseudomonas oleovorans (which is an S = 5/2 system with D = 1.76 cm-1 and E/D = 0.28), is extensively studied by EPR spectrum simulation at the Q-band, W-band, and "Z"-band. The molybdenum- and iron-containing protein (MoFe protein), which has g values at g = 4.32, 3.65, and 2.01 (S = 3/2, D = 6.0 cm-1, and E/D = 0.055) at the X-band, is also studied by EPR spectrum simulation at high frequencies.

Computer Graphics↗
PubMed1996

Affecting the activity of soybean lipoxygenase-1.

The iron content in soybean lipoxygenase-1 is important for enzyme activity. If the iron is removed by a chelating agent, the activity of the enzyme will decrease. The active center includes the iron ligands and the surrounding environment, and any conformational change in the active center may affect the activity of the enzyme. It is shown that the activity of soybean lipoxygenase-1 is enhanced by chloride anion, phosphate, formate, borate, etc., especially at a lower concentration of substrate. It is also shown that one of four thiols in soybean lipoxygenase-1 is accessible to DTNB at 0.1% SDS without losing great activity, and that all four thiols are accessible to DTNB at 1% SDS and lose all activity. Two or three of the four thiols are accessible to mercuric cyanide without losing great activity. These results support the hypothesis that only one, or possibly two cysteines are responsible for the loss of activity. Two-substrate and two-product binding site models are proposed here and discussed in view of high-resolution X-ray crystal structure.

Binding Sites↗
PubMed1996

Why spin = 1, 2 species have no electron paramagnetic resonance signal under normal conditions: possible detection by electron paramagnetic resonance at frequency close to D value?

A universal EPR simulation program has been created by the author, which is based on the following spin Hamiltonian equation: [equation: see text] where D and E are the axial and rhombic zero-field splitting parameters, respectively. The program can be used for simulation of EPR spectra with half-integer electronic spin (S = n/2, n = 3, 5, 7, 9) systems. In this article, the integer spin (S = n/2, n = 2, 4) systems are also considered. The EPR simulation results show that when D > frequency, no EPR signal can be seen from EPR simulation; when D approximately frequency, whichever X/Q/W-band is used, the EPR signal can be seen on the basis of the simulated EPR results presented.

Computer Graphics↗
PubMed1996

Ascaris, people and pigs in a rural community of Jiangxi Province, China.

A longitudinal investigation on natural populations of Ascaris in humans and pigs and an investigation of soil contamination with Ascaris eggs were carried out from June 1993 to June 1994 in 2 villages, Manhu area, Xinjian County, Jiangxi Province, China. Results from these studies indicate that although human ascariasis is endemic there is significant fluctuation in both prevalence and the mean number of eggs/g faeces (epg) of the communities. Fluctuation of age-stratified prevalence and mean epg was detected in children but not in most adult groups. Most cases of human ascariasis were judged to involve low intensities of infection and a typical overdispersion distribution pattern was observed through the year. It was estimated that during the year, nearly half of the eggs discharged in the environment came from infections in children aged between 2 and 15 years which accounted for about 30% of the total population. Soil in and around houses and in vegetable gardens was found to be contaminated by Ascaris eggs and this situation remained relatively stable throughout the year. Monthly developmental rate of Ascaris eggs in soil was detected and the results suggest that the fluctuation in prevalence observed during the year should be directly attributed to the effect of seasonality of egg development. Features of Ascaris infection in pigs were found to be similar to those in humans except for a lower mean intensity of infection. The possibility of cross-infection of Ascaris between human and pig hosts is discussed.

Adolescent↗
PubMed1996

Distribution and nucleotide biases of the somatic hypermutations in the functional kappa light chain gene of a human follicular lymphoma line.

The immunoglobulin kappa chain gene of human lymphoma cell line HF-1.3.4 was partially sequenced from the 3' end of the leader exon 2.0 kb downstream. The sequenced stretch of DNA included 1.5 kb of the non-coding JK region 3' to the JK2 element of the mature gene. Among the known VK germline genes the closet relative was KV328, which was 91% homologous to HF-1.3.4. In the 1.5 kb JK region homology with JK allele of Whitehurst et al. (allele 2) was 89%, with the allele of Hieter et al. (allele 1) 87%. The vast majority of the differences located in the leader intron, the VJ exon or 0.6 kb 3' to the exon, a localization characteristic of somatic hypermutations of immunoglobulin genes. Another indication that most of the differences observed were due to somatic hypermutations is that the 153 bp stretch of the kappa constant gene (CK) sequenced from the mRNA was 100% homologous with the published CK sequence. The most differences between the JK region sequence and that of Whitehurst et al. probably represent somatic mutations: 43% were transversions, 55% transitions and 2% deletions. In the non-coding JK region transversions of C.G to G.C rather than to A.T were heavily over-represented. This is possibly a feature of B-cell hypermutations in humans and mice.

Amino Acid Sequence↗
PubMed1996

High-level expression of active human plasminogen activator inhibitor type 1 (PAI-1) in E. coli.

Plasminogen activator inhibitor 1 (PAI-1) is an important regulator of plasminogen activation, which inhibits both tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA). The DNA sequence encoding mature PAI-1 protein was inserted into an inducible expression vector. This gene was highly expressed to produce a soluble active protein in E. coli cells. The amount of the recombinant protein was up to 20% of total cellular protein. By efficient purification with a yield of about 15-20%, the recombinant protein could be purified to homogeneity with its specific activity up to 6.1 x 10(4) (uPA) IU/mg. Its inhibitory activity declined during incubation at 37 degrees C with a half life of about 2 hr.

Escherichia coli↗