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Biomedical subjects

A Huang

Publications and source records attributed to A Huang.

At least 19 recordsLinked to original sources
PubMed2002

Serum tryptophan decrease correlates with immune activation and impaired quality of life in colorectal cancer.

Cancer-related indoleamine (2,3)-dioxygenase up-regulation by interferon-gamma might influence quality of life by depleting serum tryptophan. We correlated serum tryptophan levels with immune activation and quality of life in patients with colorectal liver metastases. Venous blood was sampled from patients with primary colorectal cancer and from patients with metachronous colorectal liver metastases who completed quality of life and psychological questionnaires. Serum tryptophan, kynurenine, neopterin, interleukin 2 soluble receptor alpha (IL-2 sRalpha), soluble tumour necrosis factor receptor I (sTNF RI), interleukin 6, and C-reactive protein were measured. Liver metastasis volume was estimated by computerised tomography, and survival from blood sampling was noted. Sixty-six patients with colorectal cancer were studied (39 males; median age 66 years) of whom 25 had colorectal liver metastases only (17 males; median age 62 years; median liver metastasis volume 208 ml; median survival 234 days). Reduced serum tryptophan was significantly associated with Rotterdam Symptom Checklist physical symptom (r=-0.51, P=0.01) and Sickness Impact Profile (r=-0.42, P=0.04) scores, and correlated with increased serum neopterin (r=-0.36, P=0.003), IL-2 sRalpha (r=-0.51, P=0.01) and sTNF RI (r=-0.45, P=0.02) levels. Stepwise regression analyses suggested that serum tryptophan was an independent predictor of Rotterdam Symptom Checklist physical symptom (regression coefficient -20.78, P=0.01) and Sickness Impact Profile (regression coefficient -109.09, P=0.04) scores. The results supported a role for interferon-gamma-mediated serum tryptophan decrease in cancer-induced quality of life deterioration.

Adenocarcinoma↗
PubMed2002

Flow cytometry correlates with RT-PCR for detection of spiked but not circulating colorectal cancer cells.

The aim of this study was to determine whether flow cytometry (FACS) could detect spiked or circulating colorectal cancer cells. A flow cytometric assay was developed and its sensitivity compared with the reverse transcription polymerase-chain reaction (RT-PCR), using carcinoembryonic antigen (CEA) and cytokeratin (CK) 20 mRNA as target markers. Sensitivity limits for RT-PCR and flow cytometry (FACS) were established using spiked blood, and pre-operative blood samples from 20 colorectal cancer patients and 16 healthy no-cancer controls were analysed for circulating tumour cells (CTC) using both methods. Blood samples for FACS analysis were immuno-magnetically enriched using ferrofluid particles. CTC were defined as positive for pan-cytokeratin and negative for CD45 pan-leucocyte antigen (CK+/CD45- events). There was a significant (P < 0.0001) correlation between the number of spiked cancer cells and their recovery using FACS. The lowest detectable concentration was 20 spiked cancer cells in 14 ml blood for both RT-PCR and FACS. A positive FACS result significantly (P < 0.05) concurred with a positive RT-PCR result in spiked blood. The number of CK+/CD45- events detected in the blood of colorectal cancer patients was not significantly greater (P = 0.07) than in blood taken from 'no cancer' controls and furthermore there was no concordance (P = 1) between RT-PCR and FACS positivity in cancer patients' blood. FACS detection of tumour cells was feasible in vitro, and correlated with RT-PCR. However, its sensitivity in vivo was poor and did not correlate with RT-PCR detection of CTC. Uncertainties about antigen expression on normal circulating cells and about CTC phenotype need to be resolved, before FACS can be developed for detection of tumour cells within the circulation.

Adult↗
PubMed2002

Description of fourteen new DRB alleles found in a stem cell donor registry.

Fourteen DRB alleles, DRB1*0705, DRB1*11014, DRB1*1134, DRB1*1136, DRB1*1141, DRB1*1335, DRB1*1337, DRB1*1338, DRB1*1342, DRB1*1343, DRB1*1349, DRB1*1510, DRB3*0105, and DRB5*0103, are described. Among them, eleven are variants which differ by only one nucleotide from previously described alleles, including one silent variant (DRB1*11014). Alleles, DRB1*0705, DRB1*1335 and DRB3*0105, display unique sequence motifs that have never been observed in DRB alleles.

Alleles↗
PubMed2002

Phase I study of percutaneous cryotherapy for colorectal liver metastasis.

BACKGROUND: The aim was to determine the safety and feasibility of percutaneous cryotherapy for treating irresectable colorectal liver metastases. METHODS: Liquid nitrogen cryoprobes were inserted percutaneously into metastases using the Seldinger technique under computed tomographic guidance. Single-probe treatments were performed with either 3.6- or 6.3-mm cryoprobes (ice-ball volumes 18 and 59 cm3 respectively), or dual-probe treatments with two adjacent 6.3-mm probes (ice-ball volume 205 cm3). Treatment involved a single freeze--thaw cycle. RESULTS: Fifteen patients received 25 single-probe treatments and seven patients received 14 dual-probe treatments. The treatment-related mortality rate was zero and complications occurred after six of 39 treatments. Liver metastasis growth was significantly delayed for 2 months after dual-probe but not single-probe treatment. Metastasis cryotherapy stimulated an immediate rise, followed by a fall, in serum carcinoembryonic antigen (CEA) level, associated with immune upregulation that was significantly greater after dual-probe treatments. CONCLUSION: Ablation zones that were approximately four times larger than those produced by previously described percutaneous techniques delayed the growth of metastases, reduced serum CEA concentration, and induced detectable inflammatory and T-lymphocyte responses. Percutaneous cryotherapy for treatment of colorectal liver metastases is feasible and may have a place in conjunction with chemotherapy.

Aged↗
PubMed2002

Transferrin regulates transcription of the MBP gene and its action synergizes with IGF-1 to enhance myelinogenesis in the md rat.

Myelin-deficient (md) rats and their unaffected littermates were injected at postnatal day 4 either with a single dose of transferrin (Tf) or insulin-like growth factor one (IGF-1) singly or combined. Two weeks later, their brains were perfused and coronal sections were analyzed for MBP by in situ hybridization and for transferrin and myelin basic protein (Tf and MBP) by double immunofluorescence. Each of the factors separately had an effect on mutant animals as seen by both increased OL maturation, and MBP mRNA and protein synthesis. The combination of factors resulted in a profound enhancement of the myelinogenic properties of oligodendrocytes (OL) with a consequent increase in the number of MBP-labeled fibers. The brains of unaffected littermates also responded to growth factor(s) injection either by increasing myelination in some brain areas or by regulating the synthesis of MBP in OL. Using rat OL cultures we studied the site of transferrin action for the expression of MBP gene. We found by run off transcription that the MBP mRNA was significantly increased at the nuclear level but the PLP message was unaffected. Thus, transferrin selectively regulates MBP at the transcriptional level and together with IGF-1 synergizes to increase both the maturation and myelinogenic properties of md and normal OL.

Animals↗
PubMed2001

[Gene cloning and expression of outer membrane protein of Helicobacter pylori].

OBJECTIVE: To construct a recombinant vector which expresses the 18 kDa outer membrane protein (OMP) from Helicobacter pylori (Hp), and exploit the possibility of obtaining Hp vaccine and diagnostic reagent kit for rapid diagnosis of Hp infection. METHODS: The gene encoding the structural 18 kDa outer membrane protein of Hp was amplified from Hp chromosomal DNA by PCR. The purified PCR product and identified plasmid pQE30 underwent restriction enzyme (Hind III, BamHI, BgLI) digestion and purified by PCR purification reagent kit, and then linked in the proportion of 4:1 (molar weight). The recombinant vector was sequenced with T7 as seqiencing primer. Homology of the determined DNA sequence was analyzed by DNA analysis software. The recombinant vector was selected and identified by restriction enzyme digestion, and then transformed into DH5 a (PREP4) Escherichia coli strain which was cultured and induced by isopropylthio-beta-D-galactosideso as to determine its expressed products. RESULTS: The gene segment inserted into the recombinant vector was identified as the gene experssing the OMP of HP with a molecular mass of 18 fDa. As compared with previously reports, 2% of the gene was mutated, 1.68% of the amino acid residues was changed, and the homogeneity was about 98%. The level of soluble expression products was about 18% of total cellular protein. ELISA results showed that this objective protein could be recognized by anti-serum against Hp. CONCLUSION: The product expressed by Hp OMP gene clone has good antigenicity. The recombinant vector expressing 18 kDa OMP may be a potential source for effective protein vaccine against Hp infection and reagent kit of Hp infection diagnosis.

Bacterial Outer Membrane Proteins↗
PubMed2001

The outbreak of West Nile virus infection in the New York City area in 1999.

BACKGROUND: In late August 1999, an unusual cluster of cases of meningoencephalitis associated with muscle weakness was reported to the New York City Department of Health. The initial epidemiologic and environmental investigations suggested an arboviral cause. METHODS: Active surveillance was implemented to identify patients hospitalized with viral encephalitis and meningitis. Cerebrospinal fluid, serum, and tissue specimens from patients with suspected cases underwent serologic and viral testing for evidence of arboviral infection. RESULTS: Outbreak surveillance identified 59 patients who were hospitalized with West Nile virus infection in the New York City area during August and September of 1999. The median age of these patients was 71 years (range, 5 to 95). The overall attack rate of clinical West Nile virus infection was at least 6.5 cases per million population, and it increased sharply with age. Most of the patients (63 percent) had clinical signs of encephalitis; seven patients died (12 percent). Muscle weakness was documented in 27 percent of the patients and flaccid paralysis in 10 percent; in all of the latter, nerve conduction studies indicated an axonal polyneuropathy in 14 percent. An age of 75 years or older was an independent risk factor for death (relative risk adjusted for the presence or absence of diabetes mellitus, 8.5; 95 percent confidence interval, 1.2 to 59.1), as was the presence of diabetes mellitus (age-adjusted relative risk, 5.1; 95 percent confidence interval, 1.5 to 17.3). CONCLUSIONS: This outbreak of West Nile meningoencephalitis in the New York City metropolitan area represents the first time this virus has been detected in the Western Hemisphere. Given the subsequent rapid spread of the virus, physicians along the eastern seaboard of the United States should consider West Nile virus infection in the differential diagnosis of encephalitis and viral meningitis during the summer months, especially in older patients and in those with muscle weakness.

Adolescent↗
PubMed2001

FKBP12, the 12-kDa FK506-binding protein, is a physiologic regulator of the cell cycle.

FKBP12, the 12-kDa FK506-binding protein, is a ubiquitous abundant protein that acts as a receptor for the immunosuppressant drug FK506, binds tightly to intracellular calcium release channels and to the transforming growth factor beta (TGF-beta) type I receptor. We now demonstrate that cells from FKBP12-deficient (FKBP12(-/-)) mice manifest cell cycle arrest in G(1) phase and that these cells can be rescued by FKBP12 transfection. This arrest is mediated by marked augmentation of p21(WAF1/CIP1) levels, which cannot be further augmented by TGF-beta1. The p21 up-regulation and cell cycle arrest derive from the overactivity of TGF-beta receptor signaling, which is normally inhibited by FKBP12. Cell cycle arrest is prevented by transfection with a dominant-negative TGF-beta receptor construct. TGF-beta receptor signaling to gene expression can be mediated by SMAD, p38, and ERK/MAP kinase (extracellular signal-regulated kinase/mitogen-activated protein kinase) pathways. SMAD signaling is down-regulated in FKBP12(-/-) cells. Inhibition of ERK/MAP kinase fails to affect p21 up-regulation. By contrast, activated phosphorylated p38 is markedly augmented in FKBP12(-/-) cells and the p21 up-regulation is prevented by an inhibitor of p38. Thus, FKBP12 is a physiologic regulator of cell cycle acting by normally down-regulating TGF-beta receptor signaling.

Animals↗
PubMed2001

Solution structure of the second extracellular loop of human thromboxane A2 receptor.

Thromboxane A(2) receptor (TP receptor), a prostanoid receptor, belongs to the G protein-coupled receptor family, composed of three intracellular loops and three extracellular loops connecting seven transmembrane helices. The highly conserved extracellular domains of the prostanoid receptors were found in the second extracellular loop (eLP(2)), which was proposed to be involved in ligand recognition. The 3D structure of the eLP(2) would help to further explain the ligand binding mechanism. Analysis of the human TP receptor model generated from molecular modeling based on bacteriorhodopsin crystallographic structure indicated that about 12-14 A separates the N- and C-termini of the extra- and intracellular loops. Synthetic loop peptides whose termini are constrained to this separation are presumably more likely to mimic the native loop structure than the corresponding loop region peptide with unrestricted ends. To test this new concept, a peptide corresponding to the eLP(2) (residues 173-193) of the TP receptor has been made with the N- and C-termini connected by a homocysteine disulfide bond. Through 2D nuclear magnetic resonance (NMR) experiments, complete (1)H NMR assignments, and structural construction, the overall 3D structure of the peptide was determined. The structure shows two beta-turns at residues 180 and 185. The distance between the N- and C-termini of the peptide shown in the NMR structure is 14.2 A, which matched the distance (14.5 A) between the two transmembrane helices connecting the eLP(2) in the TP receptor model. This suggests that the approach using the constrained loop peptides greatly increases the likelihood of solving the whole 3D structures of the extra- and the intracellular domains of the TP receptor. This approach may also be useful in structural studies of the extramembrane loops of other G protein-coupled receptors.

Circular Dichroism↗
PubMed2001

Endothelial K(ca) channels mediate flow-dependent dilation of arterioles of skeletal muscle and mesentery.

The role of Ca(2+)-activated potassium channels (K(Ca)) in flow-initiated intracellular events in microvessels is not known. We hypothesized that K(Ca) channels in the arteriolar endothelium are responsible for the mechanotransduction of flow/shear stress-induced arteriolar dilation in skeletal muscle and mesentery of rats. The active diameter of arterioles isolated from gracilis (80 mm Hg) and cremaster (60 mm Hg) muscles and mesentery (80 mm Hg) at a constant intraluminal pressure was 53 +/- 3, 77 +/- 5, and 72 +/- 6 microm, respectively. Their passive diameter (in Ca(2+)-free solution) was 113 +/- 3, 152 +/- 12, and 121 +/- 7 microm, respectively. At a constant intraluminal pressure stepwise increases in perfusate flow (25, 40, and 14 microL/min in 5, 10, and 2 microL/min steps) elicited a gradual increase in diameter of all three groups of arterioles up to 93 +/- 5, 137 +/- 11, and 102 +/- 7 microm, respectively. Flow-induced dilations of arterioles were eliminated by intraluminal administration of iberiotoxin (ibTX 10(-9) M), an inhibitor of high conductance K(Ca) channels (BK(Ca)). In contrast, arteriolar dilations to acetylcholine and sodium nitroprusside were not altered by this agent, indicating that BK(Ca) channels are not involved in the receptor-mediated endothelial synthesis of nitric oxide (NO) and that the inhibitor did not affect the action of NO on smooth muscle. Abluminal application of ibTX (10(-8) M) did not affect flow-dependent dilation. We conclude that in arterioles of several tissues activation of endothelial BK(Ca) channels is an obligatory step in the transduction of the signal initiated by changes in intraluminal flow/shear stress, leading to the release of endothelial factors evoking dilation.

Animals↗
PubMed2001

Location-probability profiles for the mouth region of human primary motor-sensory cortex: model and validation.

The mouth representation of the human, primary motor cortex (M1) is not reliably identified by surface anatomy but may be reliably localized by means of spatial coordinates. For this report, three quantitative metanalyses were performed which jointly described the mean location, location variability and location-probability profiles of the human M1-mouth representation. First, a literature metanalysis of intersubject functional-area variability was performed using eleven, per-subject studies, each of which reported a coordinate-referenced measure of intersubject variability for one or more brain areas. From these data, a weighted-mean value for intersubject variability was computed, which proved to be small (5.6 mm, standard deviation), consistent across coordinate axes (x, y, z), and consistent across brain areas. Second, a literature metanalysis of the location of M1-mouth was performed using seven, coordinate-referenced, group-mean studies (71 subjects in all), each of which reported a grand-average location for M1-mouth. From this, a weighted-mean location and weighted values for total variability (interlaboratory plus interindividual) were determined. Using these two literature metanalyses as input data, location-probability profiles were computed for the cardinal axes (x, y, and z) of the reference space, using the functional volumes modeling (FVM) statistical model. Third, an original-data metanalysis was performed on in-house PET data from 30 normal subjects performing overt-speech tasks. M1-mouth's mean location, location variability, and location-probability profiles were consistent with those conjointly modeled by FVM from the two literature metanalyses. Collectively, these observations provide a detailed, consensus probabilistic description of the location of the human M1-mouth representation in standardized coordinates.

Adult↗
PubMed2001

Labor and vaginal delivery with maternal aortic aneurysm.

BACKGROUND: Maternal aortic aneurysm can be an unsettling finding for the practicing obstetrician. However, thoracic surgeons generally do not treat asymptomatic aortic aneurysms that are less than 6 cm in diameter in otherwise healthy adults. CASE: A young nullipara was incidentally found to have a 4.5-cm thoracic aortic aneurysm during prenatal care. After extensive counseling and discussions with thoracic surgeons, anesthesiologists, and perinatologists, the patient requested a trial of labor and underwent an uncomplicated assisted vaginal delivery of a healthy female infant. CONCLUSION: A vaginal delivery occurred safely in a woman with an asymptomatic aortic aneurysm that was less than 6 cm in diameter and not associated with Marfan's syndrome.

Adult↗
PubMed2001

Structural and functional homology between duck and chicken interferon-gamma.

The Duck interferon gamma (DuIFN-gamma) cDNA was cloned from a phytohaemaglutinin-stimulated duck spleen cDNA library screened using a chicken IFN-gamma (ChIFN-gamma) cDNA probe. The DuIFN-gamma cDNA is 1392 nt long and shows 99% and 80% sequence identity with another cloned DuIFN-gamma cDNA, and with ChIFN-gamma cDNA, respectively. The cDNA contains a 495 bp ORF that encodes a putative 164 amino acid (AA) protein that shares 67% identity with ChIFN-gamma, but only 30-35% identity with mammalian IFN-gamma. The predicted three-dimensional (3D) structures of DuIFN-gamma and ChIFN-gamma are similar when analysed by comparative protein modelling. Culture supernatant collected from COS cells transfected with DuIFN-gamma cDNA was able to activate nitrite secretion from a chicken macrophage cell line (HD11) in a dose-dependent fashion. This activity could not be neutralised by an anti-ChIFN-gamma monoclonal antibody (Mab 85) that was able to neutralise the activity of ChIFN-gamma. Recombinant DuIFN-gamma (rDuIFN-gamma) protein was expressed in E. coli as an N-terminally His-tagged protein and was purified on a nickel affinity column. The eluted protein, which was detected as a approximately 18 kDa band with a purity of >90%, was also detected by Western blot using the anti-ChIFN-gamma monoclonal antibody (Mab 9.1). The rDuIFN-gamma was shown to activate nitrite secretion by HD11 cells in a dose-dependent fashion with a specific activity that was approximately 16-fold lower than a rChIFN-gamma control. Two rabbit antisera raised against rDuIFN-gamma were able to neutralise COS cell-expressed DuIFN-gamma activity; one of these also neutralised ChIFN-gamma activity. These findings indicate that DuIFN-gamma shares structural and functional identity with ChIFN-gamma, which is consistent with our previous results which demonstrated cross reactivity with other lymphokines from the two species.

Amino Acid Sequence↗
PubMed2001

Quantitative (stereological) study of placental structures in women with pregnancy iron-deficiency anemia.

OBJECTIVE: To determine the compensatory morphometric changes of placental structures in cases of maternal iron-deficiency anemia. METHODS: Placentas were obtained from a random sample of 26 full-term pregnant women, and methacrylate-embedded vertical sections were utilized to estimate parameters of placental structures with stereological methods. Materials were divided into three groups based on maternal hemoglobin levels: anemic (hemoglobin<100g/l), intermediate and non-anemic (hemoglobin>or=110g/l). RESULTS: Placental volume and absolute volume of the intervillous space or the chorionic villi per placenta significantly increased in the anemic group. There was a significant negative correlation between maternal hemoglobin level and absolute volume or surface area of the intervillous space or the villi. No significant difference, however, was found between the groups in the volume fraction or surface density of placental structures. CONCLUSION: Placental hypertrophy was associated with mild and moderate degree of maternal iron-deficiency anemia and the enlargement of placenta appeared to be a uniform (proportional) physiological compensatory growth.

Adult↗
PubMed2001

Glial cell line-derived neurotrophic factor promotes survival and induces differentiation through the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathway respectively in PC12 cells.

PC12-GFRalpha1 cells, a clonal cell line engineered to express glial cell line-derived neurotrophic factor receptor alpha1 were constructed. Given glial cell line-derived neurotrophic factor could induce the differentiation and promote the survival of PC12-GFRalpha1 cells at low concentrations, the cells provide an unlimited source of monoclonal cells for studies on the signal transduction pathway of glial cell line-derived neurotrophic factor. To characterize the involvement of the mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways in the biological effect of glial cell line-derived neurotrophic factor, we used the mitogen-activated protein kinase kinase inhibitor PD98059 and the phosphatidylinositol 3-kinase inhibitor LY294002. PD98059 blocked glial cell line-derived neurotrophic factor-induced PC12-GFRalpha1 cells neurite formation in a dose-dependent manner, without significantly altering cell viability. LY294002 reversed the survival-promoting effect of glial cell line-derived neurotrophic factor on the PC12-GFRalpha1 cells in serum-deprived medium. The present study demonstrates that phosphatidylinositol 3-kinase pathway seems to mediate the survival-promoting effect of glial cell line-derived neurotrophic factor on PC12-GFRalpha1 cells, while the activation of mitogen-activated protein kinase pathway could be an important step in mediating PC12-GFRalpha1 cells differentiation induced by glial cell line-derived neurotrophic factor. Therefore, it is inferred that similar intracellular signaling components are used by distinct growth factors toward a common biological effect.

Animals↗
PubMed2001

Treatment and outcome of Taiwanese patients with 6-pyruvoyltetrahydropterin synthase gene mutations.

Ten cases of tetrahydrobiopterin (BH4) deficiency were identified in 1,337,490 newborns screened in a Chinese population in Taiwan. The high incidence of BH4 deficiency in the Taiwanese population may be explained by a founder effect, since all of the patients revealed 6-pyruvoyltetrahydropterin synthase gene mutations, and grouping N52S and P87S mutations together constituted 88.9% of the disease alleles. BH4 supplementation with restriction of high-protein foods gave control of plasma phenylalanine within normal range, and levodopa itself prevented seizure. However, the average intelligence quotient (IQ) score of these patients was only 76 +/- 14 (56-98). Statistically, the age of starting medication, including 5-hydroxytryptophan (5-HTP), was inversely correlated to IQ scores of these patients. We suggest the combination of BH4, levodopa and 5-HTP as the standard protocol to commence the treatment of BH4 deficiency as early as possible, although prenatal brain damage could have existed.

5-Hydroxytryptophan↗