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A Huang

Publications and source records attributed to A Huang.

At least 145 records · Page 8Linked to original sources

CTLA-4-B7 interaction is sufficient to costimulate T cell clonal expansion.

T cell costimulation, particularly by the B7 family members B7-1 and B7-2, plays a critical role in regulating T cell-mediated immunity. Two molecules on T cells, CD28 and CTLA-4, are known to bind to B7. It has been suggested that CD28-B7 interaction promotes T cell response, whereas B7-CTLA-4 interaction downregulates T cell clonal expansion. However, the proposed responses of individual receptors to B7 have not been verified directly. Here, we report that B7-1 promotes clonal expansion of CD28-deficient T cells, and that the CD28-independent costimulatory activity is mediated by CTLA-4, as it is completely blocked by intact and Fab of anti-CTLA-4 mAb. In addition, a mutant B7-1 molecule, B7W88 >A, which has lost binding to CD28 but retained significant CTLA-4 binding activity, promotes T cell clonal expansion. Furthermore, while presence of CD28 enhances T cell response to B7-1, such response is also completely blocked by anti-CTLA-4 mAb. Taken together, our results demonstrate that B7-CTLA-4 interaction promotes T cell clonal expansion, and that optimal T cell response to B7 is achieved when both CD28 and CTLA-4 interact with B7. These results establish an important function of CTLA-4 in promoting T cell activation, and suggest an alternative interpretation of the function of CTLA-4 in T cell activation.

Abatacept↗

Tuboovarian abscess in the adolescent.

Tuboovarian abscess is a serious consequence of pelvic inflammatory disease, especially in the adolescent population. Early diagnosis and treatment are essential to prevent further sequelae including infertility, ectopic pregnancy, and chronic pelvic pain. Not all patients, however, present with pelvic pain, pelvic mass, fever, and leukocytosis. We present the case of a sexually active 15-year-old black girl who presented with mild abdominal pain and excessive vaginal bleeding without pelvic mass, fever, or leukocytosis. Erythrocyte sedimentation rate was 66 mm/h. Pelvic ultrasound revealed bilateral complex ovarian masses. At laparoscopy, the patient had bilateral tuboovarian abscesses with extensive adhesions to the pelvic side walls. This case illustrates the need for a high index of suspicion of tuboovarian abscess in sexually active adolescents.

Abscess↗

Secular rates of twinning in Asia: recent observations and review of literature.

OBJECTIVE: To study the rates of twinning in Asian countries using the most recent data available. METHOD: A Medline search was performed and all primary and secondary references obtained. RESULTS: Data was obtained from 5 Asian countries from reports published between 1983 and 1993. Total twinning rates varied. CONCLUSION: Twinning among Asians is much more variable than had been reported previously. Further documentation in this area is indicated.

Asia↗

Gender difference in myogenic tone of rat arterioles is due to estrogen-induced, enhanced release of NO.

The characteristics of arteriolar myogenic responses of female rats have not been investigated. Thus experiments were conducted on isolated gracilis muscle arterioles (approximately 55 microm diameter) of four groups of 12-wk-old rats: male rats, female rats, ovariectomized female rats with no estrogen replacement (OV), and ovariectomized female rats with estrogen replacement (OV + E2, 50 microg/kg s.c. injection of 17beta-estradiol benzoate every 48 h). Diameter changes in response to increases in perfusion pressure from 20 to 140 mmHg and to various concentrations of substance P (SP, 10(-9)-5 x 10(-8) M) and sodium nitroprusside (SNP, 10(-8)-10(-6) M) were measured before and after administration of N(omega)-nitro-L-arginine (L-NNA, 10(-4) M), an inhibitor of NO synthase. Arteriolar diameters of male and OV female rats were significantly less at 60-140 mmHg pressure than those of normal female and OV + E2 female rats (at 80 mmHg, 45.4 +/- 1.8 and 43.1 +/- 2.2 vs. 58.4 +/- 1.6 and 57.3 +/- 1.3%). L-NNA elicited a significantly greater downward shift of pressure-diameter curves in arterioles of normal female and OV + E2 female rats than in arterioles of male and OV female rats (28.6 +/- 4.6 and 30.6 +/- 4.7 vs. 13.2 +/- 0.9 and 10.4 +/- 2.6%). Dilations of arterioles from normal female and OV +/- E2 female rats to SP were significantly greater (by 50-60%) than those from male and OV female rats (20.8 +/- 1.8 and 22.3 +/- 1.9 vs. 13.8 +/- 1.4 and 13.8 +/- 0.6% at 10(-8) M). L-NNA did not affect dilations to SNP but significantly reduced the dilation of arterioles in all groups to SP, more so in arterioles of male and OV female rats than in arterioles of the other two groups. We conclude that pressure-induced myogenic constriction of arterioles of female rats is less pronounced than that of male rats; this is, most likely, due to the enhanced release and/or activity of NO related to the presence of estrogen.

Animals↗

Estrogen maintains nitric oxide synthesis in arterioles of female hypertensive rats.

We hypothesized that in female spontaneously hypertensive rats (SHR), estrogen moderates the dysfunction of arterioles by preserving nitric oxide synthesis. To this end, we conducted experiments on isolated gracilis muscle arterioles (approximately 55 microns in diameter) of 12-week-old (SHR divided into four groups: females (fSHR), ovariectomized females (fSHR-OV), ovariectomized females with estrogen replacement (fSHR-OV+ES, 50 micrograms/kg SC 17 beta-estradiol benzoate every 48 hours), and males (mSHR). Arteriolar diameter in the presence of perfusion pressures of 60, 80, 100, and 120 mm Hg were obtained, and diameter changes were measured (at 80 mm Hg) in response to various concentrations of substance P (10(-9) to 5 x 10(-8) mol/L), sodium nitroprusside (10(-8) to 10(-6) mol/L), and A23187 (5 x 10(-8) to 10(-6) mol/L). The pressure-induced diameter of mSHR and fSHR-OV arterioles was significantly less (by approximately 10%) than that of fSHR and fSHR-OV+ES arterioles. N omega-nitro-L-arginine (10(-4) mol/L), a nitric oxide synthase inhibitor, elicited a significant decrease in basal arteriolar diameter of fSHR (by approximately 19%) and fSHR-OV+ES (by approximately 17%), thereby eliminating the differences in tone among the various groups. Dilations of fSHR and fSHR-OV+ES arterioles to substance P were significantly greater (by 140% at a concentration of 5 x 10(-8) mol/L) than those of mSHR and fSHR-OV arterioles, whereas dilations to sodium nitroprusside were not different among the groups. A23187 (a nitric oxide releaser) elicited dilations in arterioles of fSHR (5.9 +/- 1.5%, 13.0 +/- 1.8%, and 19.2 +/- 2.1%) and fSHR-OV+ES (4.3 +/- 1.0%, 10.3 +/- 2.4%, and 15.0 +/- 4.0%) but constrictions in those of mSHR (-7.5 +/- 1.6%, -25.3 +/- 39%, and -36.9 +/- 4.1%) and fSHR-OV (-2.6 +/- 1.7%, 7.4 +/- 3.3%, and -11.5 +/- 6.1%). We conclude that estrogen in fSHR is responsible for the preservation of nitric oxide synthesis in skeletal muscle arterioles, resulting in a greater modulation of pressure-induced myogenic tone than in mSHR and maintenance of nitric oxide-mediated dilations.

Animals↗

Endothelin and prostaglandin H2 enhance arteriolar myogenic tone in hypertension.

We hypothesized that endothelin in addition to prostaglandin (PG)H2 may also contribute to the enhanced myogenic tone of skeletal muscle arterioles of spontaneously hypertensive (SH) rats. Changes in the diameter of isolated, cannulated arterioles (approximately 60 microm) from cremaster muscles of 30-week-old normotensive Wistar Kyoto (WKY) and SH rats were measured as a function of perfusion pressure (20 to 140 mm Hg). Pressure-induced constrictions were significantly enhanced between 60 to 140 mm Hg in arterioles of SH rats compared with those of WKY rats; at 80 and 140 mm Hg the normalized diameter of arterioles (expressed as a percentage of corresponding passive diameter) of SH rats was 11.0% and 15.4% less (P<.05) than that of WKY rats. After inhibition of thromboxane A2-PGH2 receptors by SQ 29,548 (10[-6] mol/L), the still enhanced myogenic response of SH arterioles was eliminated by the removal of endothelium or the administration of BQ-123 (10[-7] mol/L), an endothelin A (ET-A) receptor blocker, which also inhibited constrictions to exogenous ET-1 (10[-11] to 5x10[-10] mol/L). ET-1 elicited comparable responses in arterioles of SH and WKY rats. Thus, in SH rats the enhanced arteriolar constriction to increases in intravascular pressure seems to be due to the production of endothelium-derived constrictor factors PGH2 and endothelin.

Animals↗

[Analysis of the vol atiles from pigeon's excrement with capillary gas chromatography].

The volatiles from pigeon's excrement were obtained with a simultaneous distillation and extraction (SDE) equipment. The chemical composition of the volatiles was examined by means of capillary gas chromatography and combined gas chromatography-mass spectrometry. Forty seven constitutents of the volatiles were identified by gas chromatography-mass spectrometry. Of these compounds, thirty nine were further identified by measuring their temperature-programmed retention indexes or retention times on OV-1 and PEG-20M columns and making comparison with those of the corresponding authentic samples. The total compounds identified make 57% of the total peak areas. The compound classes consist of alcohols (4), aldehydes (11), ketones(4), acids (8), esters (5), and phenols (2), amounting to 43.68% of the total peak areas. The ten compounds with highest contents are, hexadecanoic acid (9.03%), ethyl acetate (6.85%), ethanol (4.03%), 1-ethoxy-2-methylpropane (3.87%), acetic acid (3.23%), heptadecane-(8)-carbonic acid (3.20%), (Z,Z)-9,12-octadecadienoic acid (3.18%), nonanal (2.85%), 1,2-benzenedicarboxylic, dibutyl ester (2.65%), and acetaldehyde (2.32%). Pigeon's excrement has long been used as a Chinese traditional medicine for the therapeutic treatment of haemorrhoid. Some of the constituents identified in the work have been reported to have antibacterial activities.

Animals↗

Expression of estrogen receptor variant messenger RNAs and determination of estrogen receptor status in human breast cancer.

Estrogen receptor (ER) status of breast cancer can be assessed by immunohistochemical assay (IHA), although we have previously observed that ER-IHA levels can be inconsistent between amino-terminal and carboxyl-terminal-targeted antibodies. To address the hypothesis that this discrepancy is attributable to expression of ER variant mRNAs encoding truncated ER-like proteins, we have studied 39 IHA-consistent and 24 IHA-inconsistent breast tumors by reverse transcription polymerase chain reaction to examine the expression of multiple exon-deleted (D-ER) variant mRNAs and the truncated ER clone 4 variant mRNA. ER variants D7-ER, D-3-4-ER, and D4-7-ER were detected at similar frequencies in both groups. However, ER variants D2-3/7-ER, D2-3-4-ER (P < 0.05), and D-3-7-ER (P < 0.01), which encode putative short ER-like proteins that might be recognized only by an amino-terminal-targeted antibody, were preferentially detected in inconsistent cases. ER clone 4 mRNA expression was also higher in inconsistent tumors (P < 0.001). Further analysis showed that, whereas overall prevalence of ER variant mRNAs was similar in both tumor groups, occurrence of the subset of variant mRNAs encoding putative truncated proteins was also higher in IHA-inconsistent tumors (P < 0.05). These data suggest that ER variant mRNAs encoding truncated ER proteins may contribute to discrepancies in ER-IHA levels determined using amino- or carboxyl-terminal-targeted antibodies.

Breast Neoplasms↗

Prevalence of estrogen receptor variant messenger RNAs in human breast cancer.

A new approach, based on the competitive amplification of wild-type and exon-deleted estrogen receptor (ER) variant cDNAs, was used to screen 100 human breast tumors for the presence of ER variants. Already described exon 4-deleted ER mRNA was preferentially detected in tumors with lower grades (P < 0.05) or higher progesterone receptor levels (P < 0.01), whereas new ER variants, deleted in exons 2-4 or in regions within exons 3-7 were associated with higher grades (P < 0.025) and higher ERs (P < 0.001). This approach allows investigation of the expression of multiple ER variant mRNAs and may implicate them as new prognostic markers and as possible contributors to tumor progression.

Breast Neoplasms↗

Suppression of malignancy by the 3' untranslated regions of ribonucleotide reductase R1 and R2 messenger RNAs.

Mammalian ribonucleotide reductase is rate limiting for the synthesis of DNA. The active enzyme is composed of two dissimilar components called R1 and R2, encoded by different genes. The 3' untranslated regions (3' UTRs) of R1 and R2 messages contain sequences that are important in regulating gene expression through changes in message stability. We have constructed expression plasmids containing the R1 or R2 mRNA 3' UTRs, and we show that transfection of these plasmids into highly malignant mouse 10 T1/2 cells significantly suppresses the tumorigenic properties of these cells in syngeneic mice when compared with cells transfected with the same plasmid lacking R1 or R2 3' UTR sequences or when compared with cells transfected with the same plasmid expressing a heterologous sequence as a control. Furthermore, cells expressing the R2 3' UTR exhibit significantly reduced potential to disseminate to the lungs of syngeneic animals in experimental metastasis assays. The tumor-suppressive effects of the mouse R1 and R2 3' UTRs were not confined to mouse cells, because human HeLa cells transfected with expression plasmids containing either RI or R2 3' UTRs were also significantly less tumorigenic in assays using BALB/c nu/nu mice. These studies demonstrate that the untranslated regions of ribonucleotide reductase mRNAs can function as modifiers of tumor cell development and for the more complex process of tumor dissemination. We propose that these malignancy-suppressive effects are mediated through RNA interactions with cellular components involved in growth regulation through mechanisms of posttranscriptional control of gene expression. In addition, these observations emphasize the enormous potential of untranslated RNA to act directly as modifiers of biological characteristics relevant to mechanisms of malignancy.

Animals↗

Crystallization and preliminary X-ray analysis of chicken-liver glutathione S-transferase CL 3-3.

Five different crystal forms of recombinant chicken-liver glutathione S-transferase CL 3-3 have been obtained by the vapor-diffusion method. The form A crystals are monoclinic C2, a = 125.56, b = 85.81, c = 52.71 A and beta = 114.64 degrees, and diffract to 4 A resolution. The form B crystals are monoclinic P2(1), a = 105.13, b = 118.54, c = 62.62 A and beta = 124.74 degrees, and diffract to 2.8 A resolution. The form C crystals are orthorhombic C222(l), a = 101.69, b = 115.46, c = 95.40 A, and diffract to 2.8 A resolution. The form D crystals are tetragonal, P4(1)2(1)2 or P4(3)2(1)2, a = b = 115.31, c = 171.20 A and diffract to 3.5 A resolution. The form E crystals are hexagonal, P6(1) or P6(5), a = b = 104.23, c = 114.35 A, diffract to 3.5 A resolution. Forms A, C and E have one dimer of molecular weight 50 kDa, while forms B and D have two dimers per asymmetric unit, respectively.

Journal Article↗

Basic fibroblast growth factor selectively regulates ornithine decarboxylase gene expression in malignant H-ras transformed cells.

Cell growth regulation by fibroblast growth factors (FGFs) is highly complex. The present study demonstrates a novel link between alterations in bFGF regulation during malignant conversion and the expression of ornithine decarboxylase, a key rate-limiting and regulatory activity in the biosynthesis of polyamines. H-ras transformed mouse 10T 1/2 cell lines exhibiting increasing malignant potential were investigated for possible bFGF-mediated changes in ornithine decarboxylase gene expression. Selective induction of ornithine decarboxylase gene expression was observed, since, in contrast to nontransformed 10T 1/2 cells and cells capable of only benign tumor formation, H-ras transformed metastatic cells exhibited marked elevations in ornithine decarboxylase message levels. Evidence for regulation of ornithine decarboxylase gene expression by bFGF at both transcription and posttranscription was found. Actinomycin D pretreatment of malignant cells prior to bFGF exposure inhibited the increase in ornithine decarboxylase message. Furthermore, striking differences in the rates of ornithine decarboxylase message decay were observed when cells treated with bFGF were compared to untreated control cells, with the half-life of ornithine decarboxylase mRNA increasing from 2.4 h in untreated cells to 12.5 h in cells exposed to bFGF. Evidence was also obtained for a cycloheximide-sensitive regulator of ornithine decarboxylase gene expression whose effect, in combination with bFGF, resulted in a further augmentation of ornithine decarboxylase gene expression. Furthermore, evidence is presented to suggest a possible role for G-protein-coupled events in the bFGF-mediated regulation of ornithine decarboxylase gene expression. The bFGF regulation of ornithine decarboxylase expression in H-ras transformed malignant cells appeared to occur independent of protein kinase C-mediated events. These results show that bFGF can modulate ornithine decarboxylase gene expression in malignant H-ras transformed cells and further suggests a mechanism of growth factor stimulation of malignant cells wherein early alterations in the regulatory control of ornithine decarboxylase gene expression are critical.

Animals↗

Immunohistochemical assay for oestrogen receptors in paraffin wax sections of breast carcinoma using a new monoclonal antibody.

The aim of this study was to evaluate the utility of a new monoclonal antibody (AER311) that targets the oestrogen receptor (ER) in an immunohistochemical assay (IHA) applied to breast cancers. Ninety-seven cases of invasive ductal carcinoma were studied by AER311-IHA using a pressure-cooking antigen retrieval technique applied to formaldehyde-fixed, paraffin-embedded tissue sections; immunostaining was assessed by semi-quantitative scoring (H score). There was 80 per cent concordance between the ER status measured by dextran-coated charcoal (DCC) assay and AER311-IHA, with 63/97 (65 per cent) tumours positive and 15/97 (15 per cent) tumours negative by both assays. Of the 12 DCC-positive cases that were negative by AER311-IHA, 11 were borderline positive (3-8 fmol/mg). Similarly, six of seven DCC-negative cases that scored positive by AER311-IHA had only borderline positive H scores (< 50). When AER311-IHA was compared with ID5-IHA, there was good concordance in ER status (77 per cent) and a significant correlation (r = 0.7, P < 0.001) between H scores. Nevertheless, the correlation between ER level determined by AER311-IHA and that measured by DCC (r = 0.53, P < 0.001) was higher than that for 1D5-IHA (r = 0.32, P = 0.002). AER311-IHA can therefore provide reliable information about the ER status of breast carcinoma on paraffin sections and is an acceptable alternative to other commercially available monoclonal antibodies.

Breast Neoplasms↗

A program for eradication of hepatitis B from Taiwan by a 10-year, four-dose vaccination program.

Approximately 15 percent of the Taiwanese population are chronic carriers of hepatitis B virus (HBV), among the highest rates in Asia. In July 1984, the Taiwanese government initiated a nationwide HBV-vaccination program. The program began with educational efforts and voluntary prenatal screening for HBsAg. Infants of HBsAg-carrier mothers received a four-dose regimen of hepatitis B vaccine. Those born to highly infectious mothers also received a dose of hepatitis-B immune globulin within 24 hours after birth. Seroepidemiologic studies were conducted using a random sample of infants. Serum samples were collected at 18, 24, 36, and 48 months and analyzed via radioimmunoassay for HBsAg, anti-HBs, and anti-HBc. Infants of highly infectious mothers had HBsAg positivity rates of 14.2 percent (vaccine plus HBIG) and 19.7 percent (vaccine only) when on schedule, and 17.0 percent when off schedule. Infants of moderately infectious mothers had an HBsAg positivity rate of 3.0 percent when on schedule and 6.4 percent when off schedule. These low positivity rates persisted throughout the 48-month follow-up period. This represents a dramatic improvement upon the 40 to 96 percent vertical transmission rate seen before the program implementation. This program demonstrates that mass immunoprophylaxis for HBV is feasible, and provides practical strategies for other Asian countries.

Adolescent↗

Both nitric oxide and prostaglandin-mediated responses are impaired in skeletal muscle arterioles of hypertensive rats.

OBJECTIVE: To investigate the role played by endothelium-derived dilator factors in the regulation of peripheral vascular resistance by determining whether the dysfunction of the endothelium contributes to the reduced dilator responsiveness of skeletal muscle arterioles in hypertension. METHODS: The endothelial function of isolated, cannulated, pressurized (at 80 mmHg) gracilis muscle arterioles (45-50 microns diameter) of normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) was compared by utilizing vasoactive agents of known action. RESULTS: Acetylcholine (ACh, 10(-9), 10(-8) and 5 x 10(-8) mol/l) and sodium nitroprusside (SNP, 10(-8), 10(-7) and 10(-6) mol/l) elicited similar dilations in arterioles of WKY rats and SHR. Substance P (10(-9), 10(-8) and 5 x 10(-8) mol/l) caused significantly less dilation (by approximately 70%) of SHR arterioles compared with WKY rat arterioles. The calcium ionophore A23187 (5 x 10(-8), 5 x 10(-7) and 10(-6) mol/l) elicited dilations in WKY rat arterioles (9.1 +/- 1.1, 24.0 +/- 1.5, and 39.0 +/- 3.4%, respectively), whereas it evoked constrictions (6.5 +/- 1.1, 14.9 +/- 1.5, and 25.5 +/- 1.6%, respectively) in SHR arterioles. Removal of endothelium, inhibition of prostaglandin synthesis (indomethacin) or blockade of prostaglandin H2 (PGH2) receptors (by SQ 29548) eliminated A23187-induced constrictions of SHR arterioles. The nitric oxide synthase blocker, NG-nitro-L-arginine elicited a significantly greater inhibition of substance P-induced dilations and a greater reduction in basal diameter of WKY rat arterioles than it did in those from SHR. CONCLUSIONS: These data suggest that, in SHR arterioles, the synthesis and/or action of nitric oxide is, or are, impaired and the metabolism of arachidonic acid is altered, resulting in an enhanced production of PGH2. The simultaneous dysfunction of these two dilator pathways of arteriolar endothelium could contribute significantly to the enhanced peripheral resistance observed in hypertension.

Acetylcholine↗

A case of Munchausen syndrome with claims of trauma and haemophilia.

A case of Munchausen syndrome presented with both factitious trauma and factitious haemophilia. He was treated inappropriately with factor VIII concentrate before the history of the presenting complaint could be validated. Clinical suspicion remains the most important aid to diagnosis.

Accidents, Traffic↗

Transforming growth factor beta-1 and beta-2 in human tear fluid.

PURPOSE: To evaluate human tear fluid for transforming growth factor beta isoforms 1 and 2 (TGF-beta1 and TGF-beta2). METHODS: To accomplish this, human tears were evaluated for TGF-betas by quantitative antibody sandwich ELISA (sELISA), mink lung epithelial cell (MLEC) growth inhibition bioassay and western blotting. Various physical and chemical treatments were used to activate TGF-beta in these assays. RESULTS: TGF-betas could not be detected in untreated or heated tears by sELISA; however, mean TGF-beta1 concentrations of 2.32 ng/ml were detected in acid-activated tears by sELISA. Furthermore, 10.54 ng/ml of TGF-beta1 and 2.98 ng/ml of TGF-beta2 were detected in tears treated with the mucolytic agent, acetylcysteine. Total TGF-beta bioactivity in human tears measured by the MLEC assay was found to be 13.04 ng/ml in untreated tears and 24.85 ng/ml in acid-activated tears. Approximately one-half TGF-beta in tear specimens was biologically active (mean = 52%, range 39-71%). Total tear TGF-beta bioactivity could be completely neutralized by recombinant human TGF-beta1 latency associated peptide (rh TGF-beta1 LAP). Mean neutralization of tear TF-beta bioactivity was 83% by TGF-beta1-specific antisera, and was 13% by TBF-beta2-specific antisera. Immunoreactive TBF-beta bands at approximately 12.5 and 95 kD were observed in immunoblots of reduced acidified tears. A high molecular weight (MW) TGF-beta band (>203 dD) was noted in untreated tears; however, this band disappeared following treatment with acetylcysteine. CONCLUSIONS: The results of these studies indicate that TGF-beta1 and TGF-beta2 are present in human tear fluid, and TGF-beta1 is the predominant isoform. There appear to be factors in human tears capable of binding TGF-beta.

Acetylcysteine↗