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Biomedical subjects

H Wang

Publications and source records attributed to H Wang.

At least 1,369 records · Page 76Linked to original sources
PubMed1998

Functions of the perikaryon and dendrites in magnocellular vasopressin-secreting neurons: new insights from ultrastructural studies.

Magnocellular hypothalamic neurosecretory neurons secreting vasopressin or oxytocin provide a robust model system for the investigation and understanding of many aspects of peptidergic neuronal function. Many of their functions and the cellular organelles involved are well understood. However, recent ultrastructural studies have thrown new light on various aspects of magnocellular neurosecretory function which have not previously received much attention. This review concerns two of these: the effects of mutations in the vasopressin gene on the handling of the translated peptide by the rough endoplasmic reticulum; and the role of the magnocellular dendrites in the production, secretion and localisation of peptides. Investigation of the synthesis of proteins derived from vasopressin genes which have undergone various mutations has at the moment provided more answers than questions: Why do some abnormal products accumulate as masses of peptide in the rough endoplasmic reticulum while others do not? Why do accumulations in humans appear to be damaging to the neurons while those in the rat do not? Investigations of the role of dendrites in the production and release of peptides show that the dendrites have all the machinery needed for protein translation and appear to synthesize locally proteins required for dendritic function. Of particular interest is the possibility that various transmitter receptor proteins could be synthesized in the dendrites close to the synapses in which they become localized. Precisely how such membrane proteins are inserted into the synaptic complex is, however, unclear, because the most part of the dendrites lack any form of the Golgi packaging organelle that can be recognised as such either by immunocytochemistry or electron microscopy. Better established is the ability of magnocellular dendrites to secrete either vasopressin or oxytocin in response to a variety of stimuli including sex steroids. This local release of peptide into the magnocellular nuclei has important but as yet incompletely defined effects on the functioning of the neurons.

Animals↗
PubMed1998

Disseminated histoplasmosis in an infant with acquired immunodeficiency syndrome.

Disseminated histoplasmosis has been recognized as a serious opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS). However, cases reported in the literature have been predominantly in adult patients. Here we report an infant with AIDS who presented with fever, cough, rhinorrhea, hepatosplenomegaly, pancytopenia and coagulopathy, and died of respiratory failure. Autopsy revealed disseminated histoplasmosis involving multiple organs including lungs, intestines, liver, spleen, bone marrow, lymph nodes, kidneys, and meninges. The diagnosis was established based on histomorphology and confirmed by blood culture.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Controlled release microparticles as a single dose diphtheria toxoid vaccine: immunogenicity in small animal models.

Diphtheria toxoid (DT) was encapsulated in microparticles prepared from polylactide-co-glycolide (PLG) polymers using a solvent evaporation technique. Combinations of small and large sized microparticles with controlled release characteristics were used to immunize Sprague Dawley rats and the antibody responses were monitored for one year. For comparison, control groups of rats were immunized at 0, 1 and 2 months with DT adsorbed to alum. The antibody responses generated by the microparticles were comparable to the alum immunized control groups from 32 weeks. Microparticles with a single entrapped antigen (DT) induced better antibody responses than microparticles with two antigens entrapped simultaneously (DT + TT). Microparticles prepared from a single polymer were less effective for long term antibody induction than a combination of microparticles prepared from three different polymers. A combination vaccine consisting of antigen absorbed to alum and also entrapped in microparticles gave the best response. In an inhibition assay designed to determine the relative binding of antisera to the antigen, the sera from the microparticle and the alum immunized animals showed comparable binding. An intradermal challenge study was performed in rabbits, which showed similar levels for the alum and the microparticle immunized animals at 4, 12 and 32 weeks after immunization.

Animals↗
PubMed1998

Ozone levels in Chongqing: a potential threat to crop plants commonly grown in the region?

Chongqing, a city with a population of >2.5 million, constitutes the biggest industrial and commercial centre in southwest China. Recent industrialization has led to an increasing air pollutant problem which is exacerbated by the topography and prevailing climate of the region. To date, interest has remained firmly focused on the levels of traditional air pollutants (sulphur dioxide [SO2], oxides of nitrogen [NOx], smoke and suspended particulate matter [SPM]), with little attention paid to photochemical oxidants such as ozone (O3). This paper reports the first assessment of ambient O3 levels in southwest China. Measurements were made in and around Chongqing using a combination of UV-absorption (at a site located in the northern sector of the city) and passive samplers (at 20 sites located in and around the city) between 1993 and 1996. The 7-h daily mean O3 concentrations ranged between 2 and 16 ppb (x10(9)) during the winter months, increasing to 18-41 ppb during the summer (June-August), when peak hourly mean O3 concentrations of 93 ppb were attained. Ozone exposures across the region commonly approached (or exceeded) UN-ECE and WHO short-term guidelines for the protection of crops. In addition, controlled chamber studies, in which 11 cultivars of Chinese crops commonly grown in the Chongqing region were screened for relative O3 sensitivity, indicated the potential for subtle effects on the growth of a number of crop plants, if ambient O3 levels continue to rise in the region. Employing ozone exposures somewhat higher than those experienced in the field, several cultivars of commonly grown Chinese cereal, vegetable and salad crops were found to be sensitive to O3 in terms of growth, but this was not always associated with the appearance of visible symptoms of injury and, in contrast to what was generally expected, only three species showed significant O3-induced reductions in root:shoot partitioning. There is a clear and urgent need for a comprehensive study of ambient air quality and its impact on crops and natural vegetation in this, as in other, rapidly developing regions of China.

Journal Article↗
PubMed1998

Deletion of the K(V)1.1 potassium channel causes epilepsy in mice.

Mice lacking the voltage-gated potassium channel alpha subunit, K(V)1.1, display frequent spontaneous seizures throughout adult life. In hippocampal slices from homozygous K(V)1.1 null animals, intrinsic passive properties of CA3 pyramidal cells are normal. However, antidromic action potentials are recruited at lower thresholds in K(V)1.1 null slices. Furthermore, in a subset of slices, mossy fiber stimulation triggers synaptically mediated long-latency epileptiform burst discharges. These data indicate that loss of K(V)1.1 from its normal localization in axons and terminals of the CA3 region results in increased excitability in the CA3 recurrent axon collateral system, perhaps contributing to the limbic and tonic-clonic components of the observed epileptic phenotype. Axonal action potential conduction was altered as well in the sciatic nerve--a deficit potentially related to the pathophysiology of episodic ataxia/myokymia, a disease associated with missense mutations of the human K(V)1.1 gene.

Action Potentials↗
PubMed1998

Differential expression of MAM-subfamily protein tyrosine phosphatases during mouse development.

The MAM-subfamily of type II transmembrane protein tyrosine phosphatases (PTPases) currently comprises the enzymes PTPkappa, PTPmu and PCP2. In an effort to elucidate the individual physiological roles of these closely related proteins we performed a detailed analysis of their mRNA transcript distributions at different stages of mouse embryogenesis and postnatal brain development. Our in situ hybridization studies revealed distinct and complementary expression patterns of PTPkappa, PTPmu and PCP2 transcripts. Based on our results and previous reports we discuss MAM-PTPases as a new class of morphoregulatory molecules.

Amino Acid Sequence↗
PubMed1998

Design and selection of DMP 850 and DMP 851: the next generation of cyclic urea HIV protease inhibitors.

BACKGROUND: Recent clinical trials have demonstrated that HIV protease inhibitors are useful in the treatment of AIDS. It is necessary, however, to use HIV protease inhibitors in combination with other antiviral agents to inhibit the development of resistance. The daunting ability of the virus to rapidly generate resistant mutants suggests that there is an ongoing need for new HIV protease inhibitors with superior pharmacokinetic and efficacy profiles. In our attempts to design and select improved cyclic urea HIV protease inhibitors, we have simultaneously optimized potency, resistance profile, protein binding and oral bioavailability. RESULTS: We have discovered that nonsymmetrical cyclic ureas containing a 3-aminoindazole P2 group are potent inhibitors of HIV protease with excellent oral bioavailability. Furthermore, the 3-aminoindazole group forms four hydrogen bonds with the enzyme and imparts a good resistance profile. The nonsymmetrical 3-aminoindazoles DMP 850 and DMP 851 were selected as our next generation of cyclic urea HIV protease inhibitors because they achieve 8 h trough blood levels in dog, with a 10 mg/kg dose, at or above the protein-binding-adjusted IC90 value for the worst single mutant--that containing the Ile84-->Val mutation. CONCLUSIONS: In selecting our next generation of cyclic urea HIV protease inhibitors, we established a rigorous set of criteria designed to maximize chances for a sustained antiviral effect in HIV-infected individuals. As DMP 850 and DMP 851 provide plasma levels of free drug that are sufficient to inhibit wild-type HIV and several mutant forms of HIV, they could show improved ability to decrease viral load for clinically significant time periods. The ultimate success of DMP 850 and DMP 851 in clinical trials might depend on achieving or exceeding the oral bioavailability seen in dog.

Animals↗
PubMed1998

Antimicrobial effects of metal ions (Ag+, Cu2+, Zn2+) in hydroxyapatite.

The antimicrobial ceramics (AC) based on hydroxyapatite (HA) were made in a wet chemical process with additions of AgNO3, Cu(NO3)2. 3H2O and Zn(NO3)2. 6H2O. The ACs were composed of metal-ion substituted hydroxyapatite and nitrate-apatite, which was identified by X-ray diffraction. The viable count and turbidity measurement was adopted to observe the antimicrobial effects of the various ACs. The aerobic Escherichia coli was used in the study. An obvious antimicrobial effect against E. coli was observed in Ag+ AC. In contrast to Ag+ AC, it was difficult to ascertain any bactericidal effect in the case of Cu2+ and Zn2+ AC. The bactericidal effect of Ag+ was observed using a dialysis tube experiment. This suggests that Ag+ dissolved out and reacted with E. coli, thus inhibiting its growth.

Journal Article↗
PubMed1998

A zebrafish model for hepatoerythropoietic porphyria.

Defects in the enzymes involved in the haem biosynthetic pathway can lead to a group of human diseases known as the porphyrias. yquem (yqe(tp61)) is a zebrafish mutant with a photosensitive porphyria syndrome. Here we show that the porphyric phenotype is due to an inherited homozygous mutation in the gene encoding uroporphyrinogen decarboxylase (UROD); a homozygous deficiency of this enzyme causes hepatoerythropoietic porphyria (HEP) in humans. The zebrafish mutant represents the first genetically 'accurate' animal model of HEP, and should be useful for studying the pathogenesis of UROD deficiency and evaluating gene therapy vectors. We rescued the mutant phenotype by transient and germline expression of the wild-type allele.

Amino Acid Sequence↗
PubMed1998

Breast cancer in Norway 1970-1993: a population-based study on incidence, mortality and survival.

The incidence, mortality and survival of breast cancer patients from 1970 to 1993 were studied using data from the Cancer Registry of Norway. The age-adjusted incidence rate increased from 62.0 to 76.9 per 100,000 person-years during the period, and more than 2000 cases are now registered annually. The increase tends to be highest in the age group below 40 years. The increase is mainly found in cases with localized tumours at the time of diagnosis. The mortality rate has been almost unchanged in the period; the age adjusted mortality rate is 27.0 per 100,000 person-years at the end of the study period. The 5-year overall survival has increased among cases with axillary lymph node metastases at the time of diagnosis; the other stages show only little improvement.

Adolescent↗
PubMed1998

Physiological degradation converts the soluble syndecan-1 ectodomain from an inhibitor to a potent activator of FGF-2.

The activity of fibroblast growth factor 2 (FGF-2) is stringently controlled. Inactive in undisturbed tissues, it is activated during injury and is critical for tissue repair. We find that this control can be imposed by the soluble syndecan-1 ectodomain, a heparan sulfate proteoglycan shed from cell surfaces into wound fluids. The ectodomain potently inhibits heparin-mediated FGF-2 mitogenicity because of the poorly sulfated domains in its heparin sulfate chains. Degradation of these regions by platelet heparanase produces heparin-like heparin sulfate fragments that markedly activate FGF-2 mitogenicity and are found in wound fluids. These results establish a novel physiological control for FGF-2 and suggest new ways to modulate FGF activity.

Binding Sites↗
PubMed1998

Successful treatment of Epstein-Barr virus-associated natural killer cell large granular lymphocytic leukaemia using allogeneic peripheral blood stem cell transplantation.

We report a case of natural killer cell large granular lymphocytic (NK-LGL) leukaemia successfully treated with allogeneic peripheral blood stem cell transplantation (allo-PBSCT). The peripheral blood (PB) revealed an abnormal expansion of LGL that were CD3-, CD16- and CD56+, and had natural killer activity. In situ EBER-1 hybridization of the PB mononuclear cells showed the presence of Epstein-Barr virus (EBV) in the LGL as well as in lymphocytes infiltrating the tonsils and colon. Southern blotting with an EBV-terminal repetitive sequence probe demonstrated clonal proliferation of EBV+ cells. The patient received allo-PBSCT from his HLA-matched sister with a conditioning regimen involving the use of cyclophosphamide and fractionated total body irradiation. The patient promptly recovered trilineage haematopoiesis without graft-versus-host disease, and has been in complete remission without therapy for 10 months since allo-PBSCT, suggesting that allo-PBSCT could eradicate the NK-LGL leukaemic cells.

Adolescent↗
PubMed1998

A novel monoclonal antibody 107-1A4 with high prostate specificity: generation, characterization of antigen expression, and targeting of human prostate cancer xenografts.

Monoclonal antibodies with high specificity for prostate tissue are of interest for prostate cancer research and treatment. Reactivity and specificity of a new murine monoclonal antibody, 107-1A4, was assessed by immunohistochemistry, ELISA and indirect immunofluorescence (IDIF). 107-1A4 stained all normal and malignant prostate tissue specimens while reactivity to non-prostate tissue was limited to the tubules of the normal kidney and renal cell carcinoma. Twenty two human cell lines were included in the reactivity survey; only the immunogen prostate cancer line LNCaP reacted with 107-1A4. Seminal plasma proteins PSA, PAP, PSMA, and PSP-94 were determined not to be the 107-1A4 antigen.

Journal Article↗
PubMed1998

Collagen biosynthesis by neointimal smooth muscle cells cultured from rabbit aortic explants 15 weeks after de-endothelialization.

Extracellular matrix (ECM) accumulation in arterial neointima, developed in response to de-endothelialization, is a prolonged process. In this study, we examined the relationship between increased collagen accumulation and synthetic activity of neointimal smooth muscle cells (SMCs) derived from aortic explants fifteen weeks after balloon catheter injury. Freshly confluent SMCs, derived either from normal aorta or from aortic neointima, were used in this study. The newly synthesized collagen was analysed by measuring [3H]-proline incorporation; and the mRNA expression for two major types of collagen, collagen type I and type III, was studied by Northern blot analysis. Our results indicated a three fold increase in protein (collagen) synthesis by neointimal SMCs. At the same time, the steady-state mRNA for procollagen I and procollagen III was elevated five and three times, respectively. These data indicate that persistent synthesis contributes to collagen accumulation in the arterial neointima and both transcriptional and post-transcriptional regulation take part in this process.

Animals↗
PubMed1998

HREM and STEM of intergranular films at zinc oxide varistor grain boundaries.

Grain boundaries in model ZnO-Bi2O3 and ZnO-Bi2O3-CoO varistors and a commercial multicomponent varistor have been characterized by high-resolution electron microscopy (HREM) and scanning transmission electron microscopy (STEM), in order to determine the relationship between Bi grain boundary segregation and formation of thin intergranular films. By controlling Bi2O3 content, applied pressure and temperature, the grain boundary Bi excess has been systematically varied from nearly zero to GammaBi = 1 x 1015 cm-2 ( approximately 1 monolayer), as measured by HB 603 STEM using an area-scan method. HREM shows that intergranular amorphous films are clearly distinguishable in samples with GammaBi > 8 x 1014 cm-2. These films range in thickness, depending on the Bi excess, from 0.6 to 1.5 nm. Similar films of approximately 1 nm thickness are widely observed in the commercial varistor. The composition of the films is a ZnO-Bi2O3 solid solution, which is in all cases more enriched in ZnO than the bulk eutectic liquid. The Bi-doped grain boundaries in ZnO varistors therefore contain an intergranular amorphous film which has not only an equilibrium thickness, but also a distinct equilibrium composition.

Journal Article↗