Biomedical subjects

C Wang

Publications and source records attributed to C Wang.

At least 703 records · Page 39Linked to original sources

PubMed1997

Identical genetic changes in different histologic components of Wilms' tumors.

BACKGROUND: In young children and infants, Wilms' tumor is the most common cancer of the kidney. Wilms' tumor exhibits heterogeneous histopathologic features, consisting of rapidly proliferating blastemal and epithelial cells and a stromal component that has heterologous elements (e.g., cartilage, bone, and striated muscle). It is unclear whether the stromal and heterologous components of sporadic Wilms' tumor are neoplastic or should be considered non-neoplastic. PURPOSE: Our purpose was twofold: 1) to selectively analyze the different histologic tissue components of sporadic Wilms' tumors, including blastemal, epithelial, stromal, and heterologous elements, for loss of heterozygosity (LOH) of the WT1 gene and for expression of the WT1 gene and 2) to determine the role of WT1 gene expression in the development of these tissues. METHODS: By use of tissue microdissection techniques, various histologic elements (blastema, stroma, epithelium, and striated muscle) of sporadic Wilms' tumor were obtained from specimens taken from 18 patients. DNA was extracted from the dissected tissue fragments, and DNA solutions were amplified by use of the polymerase chain reaction and the polymorphic genomic markers D11S1392 and D11S904 to detect LOH at the WT1 gene locus (11p13). Three selected specimens with heterologous elements and LOH at 11p13 were analyzed for expression of the WT1 gene by means of the in situ reverse transcription-polymerase chain reaction. RESULTS: Nine (50%) of the 18 specimens showed LOH at the WT1 locus. Although identical WT1 gene deletion was consistently observed in all of the various histologic components of these nine specimens, WT1 gene expression was high in the blastemal and epithelial elements and low in the stromal and heterologous elements. CONCLUSIONS AND IMPLICATIONS: Identical allelic deletion at 11p13 in all components of the sporadic Wilms' tumors examined suggests that the stromal tissue components are neoplastic rather than non-neoplastic. In conjunction with variable WT1 gene expression in the different histologic components, the results raise the possibility that undifferentiated blastemal cells are the precursors of the stromal and heterologous elements. Morphologically benign stromal and heterologous elements may therefore be derived from neoplastic cells. The developmental state of the various tissue components of Wilms' tumor may be attributed to an altered residual WT1 gene that is required for the maturation of blastemal and epithelial cells but that is not required for the maturation of stromal and heterologous elements.

Alleles↗

PubMed1997

Normal junctional diversification of immune receptors in p53-deficient mice.

One of the strategies that the immune system utilizes to generate Ab and TCR diversity is programmed imprecision of coding joint formation. This is accomplished by both nucleotide loss and random nucleotide addition (N segments) to the termini of immune receptor coding segments before resolution. Although it has been known for more than a decade that terminal deoxynucleotidyl transferase is the enzyme responsible for N segment addition, the enzymes responsible for nucleotide loss have not been identified. Recently, the p53 tumor suppressor protein was shown to have an intrinsic exonuclease activity; we reasoned that p53 as an exonuclease might be responsible for coding end processing during V(D)J recombination. Thus, we examined nucleotide loss from Ig and TCR-beta coding joints in mice lacking p53. We find no significant difference in the degree of nucleotide loss in coding joints isolated from these animals as compared with littermate controls. Thus, we conclude that p53 does not play a role in removal of nucleotides from coding termini during V(D)J recombination. Additionally, recent evidence has surfaced suggesting that p53 may play an important checkpoint role in early thymocyte differentiation. More specifically, it has been suggested that p53 is required to prevent thymocytes from maturing to the double-positive stage in the absence of a functionally rearranged TCR-beta allele. Our data suggest that TCR-beta selection is not affected in p53-deficient, V(D)J rearrangement-proficient mice.

Animals↗

PubMed1997

A point mutation of human nucleoside diphosphate kinase A found in aggressive neuroblastoma affects protein folding.

The point mutation serine 120 to glycine in the human nucleoside diphosphate kinase A has been identified in several aggressive neuroblastomas (Chang, C. L., Zhu, X. X., Thoraval, D. H., Ungar, D., Rawwas, J., Hora, N., Strahler, J. R., Hanash, S. M. & Radany, E. (1994) Nature 370, 335-336). We expressed in bacteria and purified wild-type and S120G mutant nucleoside diphosphate kinase A. The mutant enzyme had enzymatic and structural properties similar to the wild-type enzyme, whereas its stability to denaturation by heat and urea was markedly reduced. More importantly, upon renaturation of the urea-denatured mutant protein, a folding intermediate accumulated, having the characteristics of a molten globule. It had no tertiary structure, as shown by near UV circular dichroism, whereas the secondary structure was substantially recovered. The hydrophobic probe 8-anilino-1-naphthalene sulfonate bound to the intermediate species with an increase in fluorescence intensity and a blue shift. The hydrodynamic size was between that expected for a folded and an unfolded monomer. Finally, electrophoresis in a transverse urea gradient displayed no renaturation curve, and the protein showed the tendency to aggregate at the lowest urea concentrations. The existence of a molten globule folding intermediates resulting from an altered folding in the mutated protein might be related to the aggressiveness of neuroblastomas.

Antigens, Neoplasm↗

PubMed1997

A case-control study of diet and lung cancer in northeast China.

A case-control study involving interviews with 227 lung-cancer cases and 227 matched hospital controls was conducted in Heilongjiang Province in northeast China to examine the influence of dietary factors on the risk of developing lung cancer. Lung-cancer cases were all incident cases judged to be suitable candidates for tumor removal by surgery. Controls were selected among hospitalized patients with non-neoplastic and non-lung disease. The overall male lung-cancer risks associated with cigarette smoking were similar to those reported in other Chinese studies but quite low compared to risks in Western countries. However, the subjects in this study were relatively young (average age 53.2), had started to smoke on average at a relatively old age (21.3 years), and only smoked an average of 18.7 cigarettes per day. Lung-cancer risk was not strongly associated with any of the nutrients examined, when all cases were compared to all controls. However, the data were suggestive of differences in the relationship of diet to risk among smokers and non-smokers. Cautious interpretation is required because of the wide confidence intervals due to limited sample size. Among the smokers, only higher beta-carotene was associated with estimates suggesting a lowered risk. Among non-smokers, the evidence suggested that increased vegetable consumption might reduce risk, consumption of any fruit might reduce risk but beta-carotene was unrelated to risk. The differences observed in the relationship of diet to lung-cancer risk between Chinese smokers and non-smokers warrant further study.

Case-Control Studies↗

PubMed1997

Characterization of the pathogenic KU-SHIV model of acquired immunodeficiency syndrome in macaques.

By animal-to-animal passage in macaques we derived a pathogenic chimeric simian-human immunodeficiency virus (SHIV) that caused CD4+ T cell loss and AIDS in pigtail macaques and used it to inoculate 20 rhesus and pigtail macaques by the intravaginal and intravenous routes. On the basis of the outcome of infection and patterns of CD4+ T cell loss and viral load, disease was classified into four patterns: acute, subacute, chronic, and nonprogressive infection. During the study period, 15 of the 20 animals developed fatal disease, including AIDS, encephalitis, pneumonia, and severe anemia. Opportunistic pathogens identified in these animals included Pneumocystis, cytomegalovirus, Cryptosporidium, Toxoplasma, and Candida. No single parameter by itself predicted outcome, although a combination of low CD4+ T cell counts in blood, high plasma virus levels, and presence of autoantibodies to red blood cells reliably predicted a fatal outcome. Five animals (25%) died within 3 months of inoculation and constituted the group with acute disease, whereas the nine animals (45%) with subacute disease died between 3 and 8 months postinoculation. This 70% mortality within 8 months is significantly shorter than in HIV-1-infected human beings, of whom 70% develop fatal disease a decade after infection. SHIV infection in macaques provides a useful model with which to evaluate antiviral strategies, combining all the advantages of the SIVmac system, yet using a virus bearing the envelope gene of HIV-1.

AIDS-Related Opportunistic Infections↗

PubMed1997

Serum amyloid P component forms a stable complex with human C5b6.

A 30,000 m.w. protein bound tightly to C5b6, which was formed by activating C7-depleted human serum with zymosan. The protein remained bound to the C5b6 complex during the isolation procedure for C5b6, including chromatography on lysine-Sepharose and an anion exchange resin. Following electrophoresis and electroblotting of the C5b6 complex to a polyvinylidene difluoride transfer membrane, the 30,000 m.w. protein was microsequenced. The 24 N-terminal amino acid sequence was determined and showed identity of the 30,000 m.w. protein with the serum amyloid P (SAP) component. The C5b6-SAP complex did not dissociate in the presence of 10 mM EDTA, which distinguishes SAP-C5b6 binding from SAP's usual Ca2+-dependent binding to other molecules. SAP, which was isolated from serum by chromatography, was able to bind to preformed C5b6, which had been assembled and isolated from purified components. Functionally, the C5b6-SAP could bind C7, and the resulting C5b67-SAP complex had only moderately lower specific hemolytic activity than that of C5b67. In addition, hemolytically inactive C5b67-SAP, such as hemolytically inactive C5b67, was chemotactically active for neutrophils, while isolated SAP had no effect on cell mobility. Because SAP reacts with other serum proteins and with cells, it is likely that the addition of SAP to terminal complement complexes may affect the fate of these complexes.

Calcium↗

PubMed1997

Genistein inhibits Na+/Ca2+ exchange activity in primary rat cortical neuron culture.

We have examined the possible regulatory effect of tyrosine kinase activity on Ca2+ transport observed in the cultured rat cortical neurons. Na+/Ca2+ exchange was studied using cells cultured for various time periods. A nearly two fold increase in Ca2+ uptake was seen when comparing 3 day and 9 day cultures. Western blot analysis also showed a two fold increase in Na+/Ca2+ exchanger (NCX1) protein levels as cells matured in culture. To study the effect of genistein (a specific tyrosine kinase inhibitor) cells were incubated with 100 microM genistein (in 1% DMSO) for 1 hour before the assay of Na+/Ca2+ exchange activity. There was a significant decrease of Ca2+ uptake in genistein treated neurons (control: 4.596+/-0.205 nmol/mg protein/15 min, n=12; genistein: 1.420+/-0.131 nmol/mg protein/15 min, n=12, mean+/-S.E. P<0.001). Daidzein, an inactive analog of genistein and phorbol myristate acetate (PMA), a PKC activator were without effect. The results suggest that as cells mature in culture, Na+/Ca2+ exchange capacity increases, as a result of greater protein expression. Exposure to genistein inhibited Ca2+ uptake suggesting that the exchanger may be modulated by tyrosine phosphorylation.

Animals↗

PubMed1997

The carboxyl terminus of mouse delta-opioid receptor is not required for agonist-dependent activation.

The pharmacological effects caused by use of opiate are exerted through the opioid receptors (ORs). ORs couple to the inhibitory G protein (Gi) and result in decreased cAMP levels upon activation by specific agonists. To initiate study of the structure-function relationship during this process, we first ectopically expressed the wild-type delta OR and a C-terminally truncated mutant in CHO cells to investigate the necessity of its C-terminus. The binding potency of both the wild-type and truncated delta ORs to ligands including DPDPE, DSLET, DAGO, and U-50488 was compared. Their membrane localization and ability to mediate signal transduction were also studied. We conclude that the C-terminus of delta OR is not essential for plasma membrane targeting, ligand specificity, and agonist-dependent activation.

Amino Acid Sequence↗

PubMed1997

Both the isomerase and chaperone activities of protein disulfide isomerase are required for the reactivation of reduced and denatured acidic phospholipase A2.

The spontaneous reactivation yield of acidic phospholipase A2 (APLA2), a protein containing seven disulfide bonds, after reduction and denaturation in guanidine hydrochloride is very low. Protein disulfide isomerase (PDI) markedly increases the reactivation yield and prevents the aggregation of APLA2 during refolding in a redox buffer containing GSH and GSSG. S-methylated PDI (mPDI), with no isomerase but as nearly full chaperone activity as native PDI, has no effect on either the reactivation or aggregation of APLA2. However, the simultaneous presence of PDI and mPDI in molar ratios to APLA2 of 0.1 and 0.9 respectively fully reactivates the denatured enzyme, as does PDI alone at a ratio of 1. At ratios of 0.1 and 0.15 respectively, they completely suppress APLA2 aggregation, as does PDI alone at a ratio of 0.25. Moreover, delayed addition of PDI to the refolding buffer greatly diminished the reactivation yield of APLA2, but this deteriorating effect can be alleviated markedly by the presence of mPDI in the refolding buffer. Without GSSG, mPDI prevents the aggregation of APLA2 during refolding. It is proposed that the in vitro action of PDI as a foldase consists of both isomerase and chaperone activities, and the latter activity can be fully replaced by mPDI.

Agkistrodon↗

PubMed1997

Association of U2 snRNP with the spliceosomal complex E.

In metazoans, the E complex is operationally defined as an ATP-independent spliceosomal complex that elutes as a single peak on a gel filtration column and can be chased into spliced products in the presence of an excess of competitor pre-mRNA. The A complex is the first ATP-dependent functional spliceosomal complex. U1 snRNP first binds tightly to the 5'splice site in the E complex and U2 snRNP first binds tightly to the branch site in the A complex. In this study, we have generated and characterized a monoclonal antibody (mAb 4G8) directed against SAP 62, a component of U2 snRNP and a subunit of the essential mammalian splicing factor SF3a. We show that this antibody is highly specific for SAP 62, detecting only SAP 62 on Western blots and immunoprecipitating only SAP 62 from nuclear extracts. The anti-SAP 62 antibody also immunoprecipitates U2 snRNP and the A complex. Significantly, however, we find that the E complex is also efficiently immunoprecipitated by the anti-SAP 62 antibody. This antibody does not cross-react with any E complex-specific components, indicating that SAP 62 itself is associated with the E complex. To determine whether other U2 snRNP components are associated with the E complex, we used antibodies to the U2 snRNP proteins B"and SAP 155. These antibodies also specifically immunoprecipitate the E complex. These observations indicate that U2 snRNP is associated with the E complex. However, we find that U2 snRNP is not as tightly bound in the E complex as it is in the A complex. The possible significance of the weak association of U2 snRNP with the E complex is discussed.

Animals↗

PubMed1997

Determination of deoxymyoglobin changes during graded myocardial ischemia: an in vivo 1H NMR spectroscopy study.

1H NMR spectroscopy was used to detect the proximal histidyl Ndelta proton signal of deoxymyoglobin from canine hearts in vivo during graded myocardial ischemia. The NMR signal intensity provided an indicator of intracellular oxygenation in myocardium. The relationship between the myocardial blood flow and the deoxymyoglobin concentration was successfully measured during resting, partial, and complete coronary artery occlusion conditions. The results demonstrate the feasibility to detect deoxymyoglobin using a 1H NMR spectroscopy technique in living hearts for the first time and the possibility to use this technique for investigating myocardial oxidative metabolism nondestructively and repetitively.

Animals↗

PubMed1997

The development of neurobehavioral toxicology in China: the 1994 Hänninen Lecture.

With the rapid growth of industrialization in China, occupational and environmental exposure to chemicals has increased in frequency and in types of chemical exposures. A growing number of Chinese researchers are showing a special interest in exploring the effects of chemicals on the central nervous system. This paper presents a comprehensive review of neurobehavioral toxicology in China. It describes research into the "reference values" of the Neurobehavioral Core Test Battery (NCTB) tests, the development and improvement of the computer-administered Chinese version of the Neurobehavioral Evaluation System (NES-C), and exploration of related biomarkers. On the basis of this research, baseline data for the reference values for six subtests of the NCTB were preliminarily recommended. The upgraded NES-C2 has proven to possess higher stability and validity compared with the previous version, NES-C. Biomarkers derived from the changes in levels of neurotransmitter metabolites might be used as supplementary biomarkers of Pb-induced neurotoxicity.

Adolescent↗

PubMed1997

Androgen-behavior correlations in hypogonadal men and eugonadal men. I. Mood and response to auditory sexual stimuli.

Mood and response to auditory sexual stimuli were assessed in 33 hypogonadal men receiving testosterone (T) replacement therapy, 10 eugonadal men receiving T in a male contraceptive clinical trial, and 19 eugonadal men not administered T. Prior to and after 6 weeks of hormone administration, men completed a mood questionnaire, rated sexual arousal to and sexual enjoyment of auditory sexual stimuli, and performed a dichotic listening task measuring selective attention for sexual stimuli. Mood questionnaire results suggest that T has positive effects on mood in hypogonadal men when hormone levels are well below the normal male range of values, but does not have any effects on mood when hormone levels are within or above the normal range. However, increased sexual arousal and sexual enjoyment were associated with T administration regardless of gonadal status. Eugonadal men administered T also increased in the bias to attend to sexual stimuli. In contrast, the comparison group of eugonadal men not administered T showed no mood or sexual behavior changes across the two test sessions. These data support a positive relationship between T and sexual interest, sexual arousal, and sexual enjoyment in men.

Administration, Sublingual↗

PubMed1997

The use of augmented-pressure colostography in imperforate anus.

Colostomy is recommended in most newborns with imperforate anus (IA), except those with low-type anorectal malformations (ARM). Accurate demonstration of the anatomy of any associated fistula between the rectum and the urogenital tract is essential for optimal surgical management. Augmented-pressure distal colostography is recommended to fulfill this requirement prior to definitive surgical repair of IA. We examined 12 cases of high or intermediate-type ARM using this technique, which clearly demonstrated the distal perineal anatomy. All were confirmed at posterior sagittal anorectoplasty.

Anal Canal↗

PubMed1997

Oligozoospermia induced by exogenous testosterone is associated with normal functioning residual spermatozoa.

OBJECTIVE: To determine the functional capacity of residual spermatozoa in semen samples from normal men with T enanthate-induced oligozoospermia. DESIGN: Prospective clinical study. SETTING: Academic research center. PATIENT(S): Twelve healthy men were studied while participating in a multicenter T enanthate contraceptive efficacy study. Data were analyzed from only eight subjects, whose sperm concentrations were between 1.3 and 10 x 10(6)/mL at the suppression phase. INTERVENTION(S): Testosterone enanthate (200 mg) was administered IM weekly during the suppression and treatment (efficacy) phases (total 15 months). MAIN OUTCOME MEASURE(S): Sperm function tests (stimulated acrosome reaction, sperm hyperactivation [HA], and zona-free hamster oocyte penetration tests) were performed during the pretreatment, suppression (usually after 6 to 10 weeks of treatment, when sperm concentration was anticipated to decrease to < 10 x 10(6)/mL), and recovery phases. Studies were not done during the contraceptive efficacy phase because only one of the subjects was not azoospermic. RESULT(S): Mean sperm concentration was reduced but sperm motility, motility characteristics, and morphology were not affected by T enanthate treatment. The residual spermatozoa in the ejaculate could acrosome react, exhibited normal HA, and maintained the capacity to penetrate and fuse with the oocyte. CONCLUSION(S): Suppression of spermatogenesis to moderate oligozoospermia (< 10 x 10(6)/mL) with exogenous T enanthate administration was not associated with impaired sperm function of the residual spermatozoa. The study did not exclude the possibility that disorders of sperm function might occur when spermatogenesis is suppressed further to very severe oligozoospermia (< 1 x 10(6)/mL), commonly observed in hormonal male contraceptive clinical trials.

Adult↗

PubMed1997

Effect of increased scrotal temperature on sperm production in normal men.

OBJECTIVE: To determine whether application of polyester-lined athletic supports to bring the testes closer to the abdomen increases scrotal temperature and decreases sperm production. DESIGN: Prospective clinical study. SETTING: University academic medical center. PATIENT(S): Twenty-one healthy male volunteers. INTERVENTION(S): The study consisted of a pretreatment period of 6 weeks, a treatment phase of 52 weeks, and a recovery phase until return to normal sperm production. During the treatment phase, the men wore polyester-lined athletic supports (single layer, double layer, or double layer impregnated with aluminum) throughout the day. MAIN OUTCOME MEASURE(S): Semen parameters and sperm function tests. RESULT(S): In all three groups of subjects, scrotal temperature was consistently increased by 0.8 to 1 degree C while the subjects were wearing the athletic supports. Mean sperm concentration; sperm motility, morphology, and viability; sperm hyperactivation; and ability of spermatozoa to penetrate zone-free hamster oocytes were not affected by the increase in scrotal temperature. CONCLUSION(S): The increase in scrotal temperature induced by polyester-lined athletic supports was insufficient to cause significant suppression of spermatogenesis or alteration of sperm function.

Adult↗

PubMed1997

Loss of heterozygosity on the short arm of chromosomes 1 and 3 in sporadic pheochromocytoma and extra-adrenal paraganglioma.

Pheochromocytomas and extra-adrenal paragangliomas are tumors of the paraganglia with similar histological characteristics. We examined 12 sporadic pheochromocytomas and 5 extra-adrenal paragangliomas for loss of heterozygosity (LOH) in chromosomes 1p and 3p using a microdissection technique. Chromosomes 1p34-36, 3p21 and the von Hippel-Lindau (VHL) gene locus (3p25) were analyzed. LOH of a selected region on chromosome 1p was detected in 5 of 11 (45%) informative pheochromocytoma cases and in 0 of 5 (0%) informative extra-adrenal paraganglioma cases. LOH of the chromosome 3p25 VHL gene locus was detected in 5 of 9 (45%) informative pheochromocytoma cases and in 0 of 3 (0%) informative extra-adrenal paraganglioma cases. LOH of 3p21 was detected in 2 of 4 (50%) informative extra-adrenal paraganglioma cases. The allelic deletions in chromosomes 1p and 3p appear to be separate events. In conclusion, significant deletions were found at 1p34-36 and 3p25 in sporadic pheochromocytomas but not in extra-adrenal paragangliomas. These findings suggest (1) that multiple genetic factors may be involved in pheochromocytoma tumorigenesis, and (2) extra-adrenal paragangliomas may have a different genetic mechanism of tumorigenesis compared with pheochromocytomas.

Adolescent↗

PubMed1997

Expression of human tissue kallikrein in rat salivary glands and its secretion into circulation following adenovirus-mediated gene transfer.

Replication-deficient adenovirus Ad.CMV-cHK, expressing human tissue kallikrein under the control of the cytomegalovirus enhancer/promoter, was introduced into rat salivary glands via a direct intracapsular injection. A single injection of Ad.CMV-cHK at a dose of 4 x 10(9) pfu resulted in a sustained expression of human tissue kallikrein in rat salivary glands. The level of immunoreactive human tissue kallikrein in rat sera was the highest at 1 day post gene delivery when both salivary glands were injected and decreased in a time-dependent manner after gene delivery. Human tissue kallikrein levels in sera increased concomitantly with the amount of adenovirus used in direct salivary injection. The detection of human tissue kallikrein in sera after gene delivery into salivary glands provided direct evidence indicating that rat salivary glands secrete locally synthesized human tissue kallikrein to the systemic circulation. The direct injection of salivary glands with replication-deficient adenovirus could provide a systemic route for gene delivery for studying salivary gland function and development. Targeted gene delivery to the salivary gland may provide the means to express therapeutic proteins in saliva and the systemic circulation.

Adenoviridae↗