Biomedical subjects
Publications and source records attributed to S Gao.
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Syk has been demonstrated to play a crucial role in oxidative stress signaling in B cells. Here we report that Syk is required for the activation of the phosphatidylinositol (PI) 3-kinase-Akt survival pathway in B cells exposed to oxidative stress. Phosphorylation and activation of the serine-threonine kinase Akt were markedly increased in B cells treated with H(2)O(2). In Syk-deficient DT40 cells treated with low doses of H(2)O(2) (10-100 microm), Akt activation was considerably reduced. Pretreatment with wortmannin, a PI 3-kinase-specific inhibitor, completely blocked the Syk-dependent Akt activation. Following stimulation by low doses of H(2)O(2), a significant increase in PI 3-kinase activity was found in wild-type but not in Syk-deficient cells. These findings suggest that PI 3-kinase mediates Syk-dependent Akt activation pathway. Furthermore, viability of Syk-deficient cells, after exposure to H(2)O(2), was dramatically decreased and caspase-9 activity was greatly increased compared with that of the wild-type cells. These results suggest that Syk is essential for the Akt survival pathway in B cells and enhances cellular resistance to oxidative stress-induced apoptosis.
PURPOSE: Kaposi's sarcoma-associated herpesvirus (KSHV, or human herpesvirus 8) is etiologically associated with Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL). Although previous studies have assessed the geographic distribution of KSHV genotypes, the molecular epidemiology of KSHV remains largely unknown. The purpose of the present study was to examine the genotypes of KSHV isolates from KS patients in South Texas.METHODS: Eighteen KSHV isolates from 16 KS and 1 PEL patients in South Texas were collected between 1996 and 1998 and analyzed for KSHV subtypes by PCR sequencing of ORFK1 gene and KS330 fragment, and by PCR of ORFK15 gene. DNA sequences were aligned with known sequences and KSHV subtypes were assigned based on sequence variations.RESULTS: Of 18 KSHV isolates, 13 exhibited C subtype, and 5 exhibited A subtype in ORF K1 gene. ORF K15 genotyping showed that 10 of the isolates exhibited M form, of which 9 had C3 subtype. A unique C subtype isolate was found and classified as C6 clade. All of the M form KSHV isolates were found among KS patients over 50 years of age. Conversely, all KS patients under 40 years of age had only the P form KSHV isolates.CONCLUSIONS: In South Texas there is a distinct distribution of C3/M KSHV isolates, which are rarely found in other US regions (1 of 29). The C3/M KSHV genotype is more prevalent in HIV-negative elderly KS patients while the P-form of KSHV is more common among many young AIDS-KS patients.
Platelet-type von Willebrand disease is a bleeding disorder resulting from gain-of-function mutations of glycoprotein (GP) Ibalpha that increase its affinity for von Willebrand factor (vWf). The two known naturally occurring mutations, G233V and M239V, both enrich the valine content of an already valine-rich region within the Cys(209)-Cys(248) disulfide loop. We tested the effect of converting other non-valine residues in this region to valine. Of 10 mutants expressed in CHO cells as components of GP Ib-IX complexes, four displayed a gain-of-function phenotype (G233V, D235V, K237V, and M239V) based on (125)I-vWf binding and adhesion to immobilized vWf. The remainder displayed loss-of-function phenotypes. The gain-of-function mutants bound vWf spontaneously and had a heightened response to low concentrations of ristocetin or botrocetin, whereas the loss-of-function mutants bound vWf more poorly than wild-type GP Ibalpha. No distinct gain- or loss-of-function conformations were identified with conformation-sensitive antibodies. Compared with cells expressing wild-type GP Ibalpha, cells expressing the gain-of-function mutants rolled significantly more slowly over immobilized vWf under flow than wild-type cells and were able to adhere to vWf coated at lower densities. In aggregate, these data indicate that the region of GP Ibalpha bounded by Asn(226) and Ala(244) regulates the affinity for vWf.
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In this paper we compare several methods for estimating population disease prevalence from data collected by two-phase sampling when there is non-response at the second phase. The traditional weighting type estimator requires the missing completely at random assumption and may yield biased estimates if the assumption does not hold. We review two approaches and propose one new approach to adjust for non-response assuming that the non-response depends on a set of covariates collected at the first phase: an adjusted weighting type estimator using estimated response probability from a response model; a modelling type estimator using predicted disease probability from a disease model; and a regression type estimator combining the adjusted weighting type estimator and the modelling type estimator. These estimators are illustrated using data from an Alzheimer's disease study in two populations.
Five short tandem repeat (STR) systems of TH01, vWA, LPL, F13B and FES/FPS were investigated in five ethnic groups living in China (Tujia, Miao, Bai, Chaoxian and Han). All five loci did not deviate from the Hardy-Weinberg equilibrium (P>0.05). At the five loci of each ethnic group, the observed heterozygosity, the mean exclusion chance (MEC), and the power of discrimination (PD) ranged from 0.42 to 0.86, from 0.20 to 0.66 and from 0.61 to 0.95, respectively. For the five ethnic groups, the combined MEC and combined PD were >0. 9360 and >0.9998, respectively, suggesting that combinations of these five systems are feasible for DNA typing in forensic investigations such as personal identification or paternity testing. Furthermore, the allelic frequencies at the five loci suggested that these five ethnic groups were distinctly different communities. Judging from the phylogenetic tree constructed based on the genetic distance among the five ethnic groups, Han, Chaoxian and Tujia were involved in an identical cluster, and Miao and Bai in another. These findings indicate that each of the five groups examined is not only a distinct community, but also has a relationship with each of the others.
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The new heteronuclear iminodiacetic acid (H2L) complexes [LnCu6(mu 3-OH)3(HL)2(L)4](ClO4)(2).25H2O with Ln = La (1) and Tb (2) have been prepared in aqueous solution and characterized by single-crystal X-ray diffraction to be isomorphous (crystallographic data for 1 and 2: hexagonal, P63/m; a = b = 12.6425(14) A, c = 24.541(5) A, Z = 2 (1); a = b = 12.5802(9) A, c = 24.285(4) A, Z = 2 (2)). Ln3+ was found to be located in the center of the trigonal prismatic cage formed by six Cu2+ ions, with a tricapped trigonal prismatic coordination environment of nine O atoms. The magnetic properties of complexes 1 and 2 have been studied. The results indicate the presence of ferromagnetic couplings between Tb3+ and Cu2+ in compound 2.
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The relation between trace element levels in drinking water and cognitive function was investigated in a population-based study of elderly residents (n = 1,016) in rural China in 1996-1997. Cognitive function was measured using a Chinese translation of the Community Screening Interview for Dementia. A mixed effects model was used to evaluate the effect of each of the elements on cognitive function while adjusting for age, sex, and educational level. Several of the elements examined had a significant effect on cognitive function when they were assessed in a univariate context. However, after adjustment for other elements, many of these results were not significant. There was a significant quadratic effect for calcium and a significant zinc-cadmium interaction. Cognitive function increased with calcium level up to a certain point and then decreased as calcium continued to increase. Zinc showed a positive relation with cognitive function at low cadmium levels but a negative relation at high levels.
A method for the screening and analysis of biologically active compounds in traditional Chinese medicine is proposed. Affinity chromatography using a human serum albumin (HSA) stationary phase was applied to separate and analyze the bioactive compounds from Artemisia capillaris Thunb. Five major peaks and several minor peaks were resolved based on their affinity to HSA, two of them were identified as scoparone (SCO, 6,7-dimethoxycoumarin) and capillarisin (CAP). CAP shows a much higher affinity to HSA than SCO. The effects of acetonitrile concentration, eluent pH, phosphate concentration and temperature on the retention behaviors of several major active components were also investigated, and it was found that hydrophobicity and eluent pH play major roles in changing retention values. The results demonstrate that the affinity chromatography with a HSA stationary phase is an effective way for analyzing and screening biologically active compounds in traditional Chinese medicine.
A significant interaction among total serum cholesterol (TC), APOE genotype, and AD risk was found in a population-based study of elderly African Americans. Increasing TC was associated with increased AD risk in the group with no epsilon4 alleles, whereas TC was not associated with increased AD risk in the group with one or more epsilon4 alleles. Further study of the relationship between cholesterol and APOE genotype is needed to confirm this association, but the results suggest that cholesterol may be a potentially modifiable environmental risk factor for AD.
OBJECTIVE: To examine the relationship between level of education and childhood rural residence as possible risk factors for AD in African Americans in Indianapolis. BACKGROUND: Low level of education has been a risk factor for AD in some studies, but childhood rural residence has not been addressed in most of these studies. METHODS: A two-stage community-based prevalence study of AD was conducted in a random sample of 2,212 African Americans > or =65 years of age. A subsample of clinically assessed normal individuals (180) and individuals diagnosed with AD (43) were compared on the variables of rural/urban residence in childhood and low (< or =6 years) or high (> or =7 years) education. A logistic regression model was used with interaction between rural residence and low education to estimate odds ratios for the two risk factors combined, adjusting for age and gender. RESULTS: Odds ratios for AD: 6.5 (95% CI: 2.6 to 16.7) low education/rural residence; 0.5 (95% CI: 0.1 to 2.9) low education/urban residence; 1.5 (95% CI: 0.4 to 5.2) high education/rural residence, comparing with the group of high education/urban residence. CONCLUSION: Childhood rural residence, combined with < or =6 years of school, was associated with an increased risk of AD in this sample. It is possible that low education by itself is not a major risk factor for AD, but, rather, is a marker for other accompanying deleterious socioeconomic or environmental influences in childhood.
Numerous approaches have been described for creating relatively small folded biomolecular structures. "Peptide-amphiphiles," whereby monoalkyl or dialkyl hydrocarbon chains are covalently linked to peptide sequences, have been shown previously to form specific molecular architecture of enhanced stability. The present study has examined the use of monoalkyl hydrocarbon chains as a more general method for inducing protein-like structures. Peptide and peptide-amphiphiles have been characterized by CD and one- and two-dimensional nmr spectroscopic techniques. We have examined two structural elements: alpha-helices and collagen-like triple helices. The alpha-helical propensity of a 16-residue peptide either unmodified or acylated with a C(6) or C(16) monoalkyl hydrocarbon chain has been examined initially. The 16-residue peptide alone does not form a distinct structure in solution, whereas the 16-residue peptide adopts predominantly an alpha-helical structure in solution when a C(6) or C(16) monoalkyl hydrocarbon chain is N-terminally acylated. The thermal stability of the alpha-helix is greater upon addition of the C(16) compared with the C(6) chain, which correlates to the extent of aggregation induced by the respective hydrocarbon chains. Very similar results are seen using a 39-residue triple-helical model peptide, in that structural thermal stability (a) is increasingly enhanced as alkyl chain length is increased and (b) correlates to the extent of peptide-amphiphile aggregation. Overall, structures as diverse as alpha-helices, triple helices, and turns/loops have been shown to be induced and/or stabilized by alkyl chains. Increasing alkyl chain length enhances stability of the structural element and induces aggregates of defined sizes. Hydrocarbon chains may be useful as general tools for protein-like structure initiation and stabilization as well as biomaterial modification.
The Community Screening Interview for Dementia (CSI 'D') was developed as a screening instrument for dementia for use in cross-cultural studies. It consists of two components, a cognitive test for non-literate and literate populations and an informant interview regarding performance in everyday living. The development of the CSI 'D', involving harmonization, translation, back translation and pilot testing, for use in five sites is described. The results demonstrate the adaptability and utility of the CSI 'D' in populations from very different socioeconomic backgrounds. The inclusion of informant data adds significantly to the performance of the CSI 'D' as a dementia screen. The combination of informant and cognitive scores in a discriminant score produces better sensitivity and specificity for dementia than cognitive scores alone. The informant score has a significant independent effect in predicting dementia.
In the anatomy of the colon vasculature, the ascending branch of the left colic artery is the primary supplying vessel (96.91%). Isoperistaltic transposition of the transverse colon is preferred (83.58%). Riolan's vascular arcade is not a major vessel of the colon. It can only be found in less than 10% of patients, and whether or not this arcade is complete cannot be used as criterion to judge colon blood supply. Animal experiments and clinical studies have confirmed the superiority of one-layer over two-layer anastomosis. The former is simpler, safer, and more reliable, with a lower incidence of anastomotic leak or stricture. Based on a comprehensive evaluation of the disease type, patient age, heart and lung functions, nutritional status, and accompanying diseases, three colon transposition routes are available (anterosternal subcutaneous tunnel, retrosternal tunnel, and esophageal bed passage). The advantages and disadvantages of each route are analyzed, and the left-middle-left retrosternal route is described. The indications for esophageal reconstruction with colon operation (ERC) were collected and verified, increasing the number of indications to seven categories of diseases. The main complications of ERC, i.e., colon segment necrosis, anastomotic leak, recurrent laryngeal nerve injury, and intestinal obstruction were systematically studied, and their causes and prevention are detailed. The number of patients is the highest in a single unit among all the published reports. The incidence of complications and deaths are the lowest.