Search PubMed⌕ Search

Biomedical subjects

F Wang

Publications and source records attributed to F Wang.

At least 523 records · Page 29Linked to original sources
PubMed1995

Alternately spliced NH2-terminal immunoglobulin-like Loop I in the ectodomain of the fibroblast growth factor (FGF) receptor 1 lowers affinity for both heparin and FGF-1.

Alternate splicing of a single exon encoding an NH2-terminal immunoglobulin (Ig) disulfide loop in the ectodomain of the fibroblast growth factor receptor (FGFR) types 1 and 2 results in alpha and beta isoforms that exhibit 3- and 2-Ig loops, respectively. Previously we demonstrated that alternately spliced Loop I has no independent ligand binding activity but is sufficiently interactive with the ligand- and heparin-binding site formed by Loops II and III to lower affinity for the same fibroblast growth factor (FGF) ligand. Here we show that a lower affinity of FGFR1 alpha for heparin parallels the lower affinity for FGF-1. A mutant of FGFR1 alpha in which the sequence between Loops I and II was deleted exhibits high affinity for both FGF-1 and heparin and other properties of the FGFR1 beta isoform, which include resistance to degradation by trypsin and display of specific antibody epitopes. This suggests that the interloop sequence facilitates the interaction of Loop I with Loops II and III. Lack of expression of both exons coding for Loop I and the sequence between Loops I and II in the FGFR2 gene characterizes rat prostate tumor cells, which exhibit a loss of the low affinity class of FGF receptors. Although the exon coding for the sequence between Loops I and II is alternately spliced in the FGFR2 beta isoform, coordinate expression with the exon coding for Loop I results in the functional differences between the FGFR alpha and FGFR beta variants.

Alternative Splicing↗
PubMed1995

Massive cell death of immature hematopoietic cells and neurons in Bcl-x-deficient mice.

bcl-x is a member of the bcl-2 gene family, which may regulate programmed cell death. Mice were generated that lacked Bcl-x. The Bcl-x-deficient mice died around embryonic day 13. Extensive apoptotic cell death was evident in postmitotic immature neurons of the developing brain, spinal cord, and dorsal root ganglia. Hematopoietic cells in the liver were also apoptotic. Analyses of bcl-x double-knockout chimeric mice showed that the maturation of Bcl-x-deficient lymphocytes was diminished. The life-span of immature lymphocytes, but not mature lymphocytes, was shortened. Thus, Bcl-x functions to support the viability of immature cells during the development of the nervous and hematopoietic systems.

Animals↗
PubMed1995

Incidence proportion of and risk factors for AIDS patients diagnosed with HIV dementia, central nervous system toxoplasmosis, and cryptococcal meningitis.

We undertook this study to determine the incidence proportion of and risk factors for AIDS patients diagnosed with human immunodeficiency virus (HIV) dementia, central nervous system (CNS) toxoplasmosis, and cryptococcal meningitis. A historical cohort of 487 consecutive inpatients with AIDS treated by San Francisco General Hospital inpatient and outpatient services entered the study. We abstracted all available records for demographic information, diagnoses, and dates of death and estimated the incidence proportion of AIDS patients diagnosed with major CNS complications using the Kaplan-Meier method. We used the Cox proportional hazards model to analyze the effect of demographic factors on the hazard (risk per unit time) of diagnosis with these CNS conditions. The estimated incidence proportion of patients diagnosed with HIV dementia within 1 and 2 years of AIDS diagnosis increased from 0.10 to 0.18. Corresponding proportions were 0.10 and 0.19 for CNS toxoplasmosis and 0.10 and 0.14 for cryptococcal meningitis. Only HIV dementia was independently associated with increasing age at AIDS diagnosis (relative hazard [RH] of 2.75 for ages 41-50 [95% confidence interval, 1.08-6.98]; RH of 4.73 for ages > 50 [95% confidence interval, 1.41-15.87]) and with injection drug use (RH of 2.03; 95% confidence interval, 1.19-3.47). HIV dementia, CNS toxoplasmosis, and cryptococcal meningitis are about equally common complications in patients with AIDS, but only HIV dementia is associated with increasing age at AIDS diagnosis and injection drug use.

AIDS Dementia Complex↗
PubMed1995

Perfused Kupffer cell mass. Correlation with histology and severity of chronic liver disease.

The perfused Kupffer cell mass determines sulfur colloid distribution by liver spleen scan (LSS) and is proportional to the perfused hepatocyte mass. This accounts for the correlation of sulfur colloid distribution with tests of hepatic function and raises the question of whether the LSS can be used as a quantitative test of hepatic function. The recent ability to precisely measure sulfur colloid distribution by single-photon-emission computerized tomography (SPECT) prompted us to evaluate the clinical value in 329 consecutive patients with adequate LSS and clinical information, of which 27 apparent normals and 220 patients with chronic liver disease (CLD) were included in this study. The liver-bone marrow index (LBI) indicated the distribution of counts between the liver and bone marrow. The liver-spleen index (LSI) indicated the distribution between liver and spleen adjusted for spleen size. The LBI and LSI correlated with each other (r = 0.753; P < 0.001). The arithmetic mean of LBI and LSI was defined as the severity score. Detailed clinical evaluation was available in these patients and included 109 who had liver biopsy. A severity score in 27 normals was 102 +/- 5 (mean +/- SD) with all values > 85. The severity score correlated with hepatic fibrosis (r = -0.694; P < 0.001) in 109 patients with benign liver disease who had recent biopsies and with the Child-Pugh classification (r = 0.78; P < 0.001) in 220 patients with CLD.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗
PubMed1995

Bone marrow purging with dibutyl phthalate--experimental basis and a preliminary clinical application.

It has been found recently that di-n-butyl phthalate (DBP) possesses a new pharmacological activity in the selective elimination of tumor cells from marrow. In combination with long-term liquid culture of marrow cells in vitro, DBP purged autologous bone marrow transplantation has first been applied to a case of acute myeloid leukemia at the first complete remission with successful reconstitution of hematopoiesis.

Adult↗
PubMed1995

The liver-spleen scan as a quantitative liver function test: correlation with liver severity at peritoneoscopy.

Sulfur colloid distribution on liver-spleen scan is determined by the perfused Kupffer cell mass. The perfused Kupffer cell mass is proportional to the perfused hepatocyte mass, but is less affected by acute changes in hepatocyte function. Thus, sulfur colloid distribution parameters (precisely measured by quantitative liver-spleen scan [QLSS]) may be an excellent test of the perfused hepatic mass. Although no gold standard exists for confirmation, a close correlation should exist between liver disease severity assessed at peritoneoscopy and sulfur colloid distribution. Peritoneoscopy severity (scored as total peritoneoscopy score [PS]; range, 0-5) was assessed in 76 patients who also had QLSS. Multivariate equation were generated to estimate liver disease severity from the QLSS. These were then applied prospectively in 20 consecutive patients to validate these equations. In 76 patients, 62 were evaluated because of chronic liver disease (CLD) and included those with micronodular (20) and macronodular (20) cirrhosis with various degrees of severity (Child's A, 16; B, 29; C, 17). Multivariate analysis yielded a number of combinations of QLSS parameters that correlated with peritoneoscopic severity. These equations were used to estimate liver disease severity. Estimates of liver disease severity (estimated PS [EPS]) correlated well with the PS in these 76 patients (r = .9064; r2 = .8216; P < .0001). Adding histological fibrosis to the QLSS parameters yields an equation for estimating PS that was even more effective (r = .9462; r2 = .8953; P < .001). However, validation of multivariate equations requires confirmation of their value in a second population.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Continuous detection of CMV DNA in plasma of patients with advanced HIV infection implies the poorest prognosis.

BACKGROUND: The contribution of cytomegalovirus (CMV) to progressive HIV infection is still controversial. OBJECTIVE: The occurrence of CMV DNA in the plasma of patients with advanced HIV infection was studied in relation to the development of clinical disease. STUDY DESIGN: Plasma samples were collected every 2 weeks for 6 months. The patients have thereafter been followed clinically at least every 3 months. CMV DNA was extracted and analysed by a nested PCR. RESULTS: CMV DNA was repeatedly detected in the plasma of five patients for more than 45 days (group 1). These patients also had very low CD4+ cell counts 51+/-41 x 10(6) /l). Three patients in group 1 developed CMV complications and CMV was the cause of death in two cases. Two patients with anti-CMV IgM responses did not develop CMV complications. All five patients died at a mean of 17 months after CMV DNA became continuously detectable by PCR. In another six patients, CMV DNA was not or only sporadically detected (group 2). In these six patients, four are still alive after more than 3.5 years and only one patient developed CMV retinitis 3 years later. CONCLUSIONS: The presence of CMV DNA in plasma was frequent in 11 patients with advanced HIV infection. The continued presence of CMV DNA in plasma of the patients with low CD4+ cell counts was related to the development of clinical CMV disease and carried the poorest prognosis.

Journal Article↗
PubMed1995

Hydrophobic contribution constants of amino acid residues to the hydrophobicities of oligopeptides.

PURPOSE: The main purpose of this study is to explore the additive-constitutive nature of common amino acids in their contribution to the partition coefficients of small peptides. METHODS: The Log P values and other physico-chemical parameters of the peptides studied are taken from the literature. The frequency of appearance (ni) of each individual amino acid is calculated as the number of the amino acids in a given peptide. RESULTS: The partition coefficients (Log P(oct./buff.) at pH 7) of 87 N-acetyl-peptide-amides have been correlated with the frequency of appearance of amino acids. From the correlation obtained, the de novo hydrophobic contribution constants of 19 amino acid residues are derived for the first time. The contribution constants are extended to 59 unmodified regular peptides with the inclusion of the pka values of both N-terminal and C-terminal amino acids. The models thus obtained have been validated with additional 27 peptides (both N-acetyl-peptide-amides and unmodified). CONCLUSIONS: The Log P of oligopeptides is very well correlated with the de novo hydrophobic contribution constants of amino acids. The models we have derived are reasonably accurate in predicting the hydrophobicities of new oligopeptides (< or = tetrapeptides) at a fixed pH (e.g., 7).

Amino Acid Sequence↗
PubMed1995

Tap-1 and Tap-2 gene therapy selectively restores conformationally dependent HLA Class I expression in type I diabetic cells.

Genetic susceptibility to many autoimmune diseases, including insulin-dependent diabetes mellitus (IDDM) is statistically linked to the HLA class II region of chromosome 6. However, a distinguishing feature of patients with HLA class II-linked autoimmune disease is an abnormally low density of conformationally correct, self-peptide filled HLA class I molecules on the lymphocyte cell surface. The transporters associated with antigen processing (Tap-1 and Tap-2) are essential for normal class I expression and presentation of intracellular peptides, and these genes are located within the HLA class II region. The aims of this project were to determine if Tap genes could be implicated in the defective class I expression associated with IDDM by using a novel Epstein-Barr virus (EBV)-mediated gene transfer system to introduce a cloned, normal Tap-2 or Tap-1 gene into B cell lines from normal and IDDM patients and analyzing the effect on conformationally dependent class I expression. The results show that Tap-2 gene transfer in B cells from 40% of randomly selected IDDM patients increased expression of conformationally correct, cell-surface class I molecules to levels comparable with similarly treated B cells from normal control individuals. B cells from another 40% of IDDM patients responded to Tap-1 gene transfer. These effects were specific because B cells from normal individuals did not respond to Tap-1 or Tap-2 gene transfer with increased class I expression, and B cells from IDDM patients responding to Tap-2 gene transfer did not respond to Tap-1 gene transfer and vice versa. Thus, these complementation studies identify distinct, non-overlapping subsets of IDDM patients whose class I defect in B cells can be reversed by Tap-1 or Tap-2 gene transfer. The increase in class I expression induced by Tap gene transfer is associated with a reduction in the number of peptide-empty class I molecules as demonstrated by the response to exogenous peptide loading. Furthermore, the increase in self-peptide filled class I molecules induced by Tap gene transfer into B cells from IDDM patients is associated with restored antigen presentation to autologous T cells. These studies conclude that Tap gene dysfunctions may contribute to the defect in class I phenotype and antigen presentation demonstrated by IDDM patients. Defective presentation of self-peptides by antigen presenting cells can lead to the failed T cell education and tolerance to self antigens evident in IDDM. These studies functionally identify HLA class II region genes that contribute to an immunologic defect in IDDM.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Human and viral interleukin-10 in acute Epstein-Barr virus-induced infectious mononucleosis.

Human interleukin 10 (hIL-10), a product of monocytes, T cells, and B cells, shares extensive structural and functional similarity with viral IL-10 (vIL-10), a product of Epstein-Barr virus (EBV) replication. With two ELISAs, one that recognizes both hIL-10 and vIL-10 and the other specific for vIL-10, IL-10 was measured in serum or plasma and in saliva from 50 patients with acute EBV-induced infectious mononucleosis and from 19 normal subjects. In serum or plasma, 60% of the patients had measurable hIL-10 and/or vIL-10 and 18% had measurable vIL-10. In saliva, 20% of the patients had detectable hIL-10 and/or vIL-10 and none had detectable vIL-10. In contrast, hIL-10 and/or vIL-10 was undetectable in all 19 normal serum or plasma samples (P < .001 vs. patient samples). Among normal saliva samples, 21% had detectable hIL-10 and/or vIL-10 but none had detectable vIL-10. Thus, most patients with acute EBV-induced infectious mononucleosis transiently have abnormally high levels of circulating IL-10.

Acute Disease↗
PubMed1995

Counting total cell numbers microscopically on stained films.

Two main sources of error in the conventional stained film cell count method, i.e. errors from imperfect spreading of the suspension and uneven distribution of cells in the film, have been eliminated by counting all the cells in the film. Staining solution and sodium alginate were added to the suspension before spreading over the slide. With a microsyringe, 20-microliters suspension was spread in two bands of ca 1.7 mm x 60 mm each. Then total cells could be counted easily in the x 100 magnification field by moving the slide in one direction. Results were satisfactory. Coefficients of variation were 2.6 and 1.1% in two separate yeast determinations each with five replicates. For counting higher magnifications, a suitable image analyser for automating the method is believed worthy of study.

Colony Count, Microbial↗
PubMed1995

The Epstein-Barr virus nuclear protein 2 acidic domain can interact with TFIIB, TAF40, and RPA70 but not with TATA-binding protein.

The Epstein-Barr virus nuclear antigen 2 (EBNA-2) acidic domain is essential for B-lymphocyte growth transformation and can activate transcription when brought to a promoter by a sequence-specific DNA-binding domain. We now show that the EBNA-2 acidic domain has slightly less activity than the proteotypic acidic transactivator VP16 in depleting nuclear extracts of basal transcription activity. Like VP16, EBNA-2 associates with TFIIB, TAF40, and RPA70. However, EBNA-2 has much less avidity for TATA-binding protein. A Trp-to-Thr mutation within the acidic domain abolishes EBNA-2 transactivating activity and greatly compromises the association with TFIIB, TAF40, and RPA70, establishing a genetic linkage between transactivating activity and these associations.

Antigens, Viral↗
PubMed1995

A Tat-induced auto-up-regulatory loop for superactivation of the human immunodeficiency virus type 1 promoter.

The virus-encoded Tat protein strongly activates transcription of human immunodeficiency virus (HIV). A well-recognized mechanism involves interaction of Tat with the nascent RNA transcript of the viral tar gene; mutation of tar greatly decreases activation by Tat. However, Tat still provides a low level of activation, demonstrating that it also has a tar-independent mode of action. We propose that this tar-independent mode of Tat action is through activation of gene transcription to produce tumor necrosis factor alpha. This cytokine and other compounds that activate NF-kappa B up-regulate the HIV promoter at a low level, similarly to the second Tat action. Through this mechanism, they also activate promoters of tumor necrosis factor alpha and other cytokines and thereby establish an auto-up-regulatory loop. Activated NF-kappa B motifs in the HIV promoter synergize with Tat/tar. Mutations of these motifs decrease activation by Tat to a few percent of the wild-type value. In cooperation, the two modes of activation by Tat (tar dependent and cytokine based) set up positive up-regulatory loops which greatly superactivate transcription of HIV. Agents that block these synergistic pathways at three different steps and are more inhibitory in combination than is any one alone have been found. Thereby, multidrug modalities for transcription of HIV are proposed for virus suppression.

Base Sequence↗
PubMed1995

5' Coding and regulatory region sequence divergence with conserved function of the Epstein-Barr virus LMP2A homolog in herpesvirus papio.

B-lymphotropic herpesviruses naturally infecting Old World primates share biologic, epidemiologic, pathogenic, and molecular features with the human pathogen Epstein-Barr virus (EBV). These related gammaherpesviruses have colinear genomes with considerable nucleotide homology. The replicative cycle genes share a high degree of homology across species, whereas the transformation-associated EBV latent genes appear to be much more divergent. For example, the EBV BamHI Nhet fragment, which encodes all or part of the EBV latent infection membrane proteins, cross-hybridizes poorly to DNA from nonhuman primate B-lymphotropic herpesviruses. A viral DNA fragment corresponding to this region of the EBV genome was isolated from the baboon B-lymphotropic herpesvirus, herpesvirus papio, and used to clone a herpesvirus papio cDNA corresponding to EBV LMP2A. At least three tyrosine kinase interaction motifs are conserved despite significant amino acid divergence of the herpesvirus papio LMP2A first exon from the EBV homolog. Functionally, the herpesvirus papio LMP2A is tyrosine phosphorylated and induces tyrosine phosphorylation of cell proteins similar to EBV LMP2A. The 12 hydrophobic LMP2 transmembrane domains are well conserved. Two CBP (Jk) binding sites important for EBNA-2-induced transactivation of the LMP2A promoter are also present in the herpesvirus papio LMP2A promoter, and the simian LMP2A promoter is also responsive to EBV EBNA-2-induced transactivation in human B cells. Thus, transcriptional regulation, splicing, kinase interaction sites, and tyrosine phosphorylation of the LMP2A homologs have been conserved despite significant sequences heterogeneity in the preterminal repeat regions of these human and nonhuman primate EBVs. The conservation of the LMP2 gene, despite its apparent nonessential role for in vitro EBV infection, suggests an important role for LMP2A in vivo. The similarities between these human and simian B-lymphotropic herpesviruses, and the LMP2 genes in particular, suggest that the function of LMP2 in vivo could be addressed by using recombinant LMP2A-mutant simian viruses and experimental infection of Old World primates.

Amino Acid Sequence↗
PubMed1995

Ovarian failure in oral cyclophosphamide treatment for systemic lupus erythematosus.

Ninety-two women with systemic lupus erythematosus treated with oral cyclophosphamide were studied to ascertain the prevalence and the factors associated with ovarian dysfunction. Menstrual disturbance during treatment occurred in 55% of patients: 36% had amenorrhoea and 19% had oligomenorrhoea. Sustained oligomenorrhoea occurred in 12% patients. Permanent amenorrhoea (> 12 months) after cessation of oral cyclophosphamide occurred in 27% of patients. Hormonal studies in these patients were consistent with ovarian failure. Older age at initiation of treatment and high cumulative dose of cyclophosphamide were found to be associated with this outcome. There was a trend towards linear relationship between the age of initiation of cyclophosphamide therapy and frequency of amenorrhoea. A statistically significant association between amenorrhoea and cumulative dose of cyclophosphamide after adjustment for age was found whereas no such association was linked to the duration of treatment. Fourteen of the 23 women who wished to become pregnant after cessation of treatment conceived resulting in 20 live births and two abortions.

Abortion, Spontaneous↗