Biomedical subjects

M S Chen

Publications and source records attributed to M S Chen.

At least 91 records · Page 5Linked to original sources

PubMed1995

K65R mutation of human immunodeficiency virus type 1 reverse transcriptase encodes cross-resistance to 9-(2-phosphonylmethoxyethyl)adenine.

Cloned variants of human immunodeficiency virus type 1 that contain the K65R mutation in reverse transcriptase have previously been shown to display approximately 10- to 30-fold resistance against 2',3'-dideoxycytidine, 2',3'-dideoxyinosine, and 2',3'-dideoxy-3'-thiacytidine. On the basis of tissue culture studies with both primary T cells and established cell lines, we now report that the K65R mutation confers approximately 12- to 15-fold resistance to 9-(2-phosphonylmethoxyethyl)adenine (PMEA). Likewise, a chain termination system revealed that mutated recombinant K65R reverse transcriptase displays resistance to PMEA diphosphate, the active metabolite of PMEA, in cell-free enzyme assays. Parallel studies have shown that the M184V mutation in reverse transcriptase, associated with high-level resistance against the (-) enantiomer of 2',3'-dideoxy-3'-thiacytidine, does not confer resistance to PMEA in tissue culture. Viruses and enzymes that included both the K65R and M184V mutations were resistant to PMEA and PMEa diphosphate, respectively, but only to the extent conferred by the K65R mutation alone.

Adenine↗

PubMed1995

Biochemical basis for increased susceptibility to Cidofovir of herpes simplex viruses with altered or deficient thymidine kinase activity.

It has been observed that herpes simplex virus mutants with deficient or altered thymidine kinase activity are more susceptible to Cidofovir (CDV; 1-[(S)-3-hydroxy-2-(phosphonomethoxy)propyl]cytosine dihydrate) in tissue culture than are the parental strains. During infection of cells, the elevation of the dCTP pool by thymidine kinase mutant viruses is less than that induced by the wild-type virus. The competition between CDV diphosphate and dCTP at the viral polymerase is therefore changed in favor of CDV diphosphate, enhancing its activity.

Acyclovir↗

PubMed1995

Early change of vascular permeability in hypercholesterolemic rabbits.

To study the effect of hyperlipidemia on vascular permeability, serial anterior chamber fluorophotometric examinations were carried out on 33 control rabbits (group 1) and 32 diet-induced hypercholesterolemic (group 2) rabbits. Changes in the blood-aqueous barrier function associated with total serum cholesterol (CHO) and triglyceride (TG) levels were studied at the beginning of the study and every 2 weeks thereafter for up to 16 weeks following 0.5% cholesterol-enriched diet feeding. Concurrently, a slit-lamp biomicroscope was used to examine the iris for evidence of atheromatous plaque. In group 1, the CHO level decreased slightly during the first 6 weeks and remained rather steady thereafter. The status of the blood-aqueous barrier correlated significantly with serum CHO and TG levels (r = .46, P < .001; r = .23, P = .01, respectively). In group 2, CHO and TG levels increased significantly after 2 and 8 weeks of cholesterol-enriched diet feeding, respectively. The blood-aqueous barrier also became more permeable than that in group 1 after 2 weeks' and increased above its baseline level after 6 weeks' feeding. Both CHO and TG levels correlated well with the degree of blood-aqueous barrier breakdown (r = .51, P < .001; r = .25, P < .001, respectively). The first evidence of iridic lipid-streak deposition was noted at 7.6 +/- 0.7 weeks, while definite iridic atheromatous plaque appeared 11.2 +/- 0.7 weeks after feeding. The change in the blood-aqueous barrier also correlated well with the semiquantitative score of iridic plaque (r = .58, P < .001) and usually preceded visual evidence of plaque formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Misclassification of smoking status among Southeast Asian adult immigrants.

A total of 1,403 Southeast Asian adult immigrant males (n = 783) and females (n = 620) from Cambodia, Laos, and Vietnam who currently resided in Central Ohio were interviewed to determine the self-reported smoking prevalence among them, and underwent biochemical confirmation of their smoking status. Variables having to do with the subjects' sociodemography, acculturation, and smoking history that were related to the misclassification of smoking status were also investigated. Self-reported current smoking rates were 40.9% and 5.6% for males and females, respectively. After verification of the subjects' smoking status by saliva cotinine assay (smoker status > or = 14 ng/ml), the rates of smoking were found to be greater, at 43.7% for males and 14.8% for females. Years of education, self-reported smoking status, country of origin, and method of healthcare payment were significant predictors of misclassification. These findings suggest that the prevalence of smoking is higher among Southeast Asian adult females than has been previously reported. Variables that predict misclassification with regard to smoking status are presented, and their implications for clinicians and researchers are discussed.

Acculturation↗

PubMed1994

Kinetic analysis of the interaction between the diphosphate of (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine, ddCTP, AZTTP, and FIAUTP with human DNA polymerases beta and gamma.

The inhibitory effects of the diphosphate of (S)-1-(3-hydroxy-2-phosphonylmethoxy-propyl)cytosine (HPMPCpp) toward human DNA polymerases beta and gamma were studied. The Ki values of HPMPCpp were compared with the Ki values of the triphosphates of 3'-azidothymidine (AZTTP), 2',3'-dideoxycytidine (ddCTP) and 5-iodo-2'-fluoroarabinosyluridine (FIAUTP). The Ki values toward DNA polymerase beta in increasing order were 1.32, 1.43, 140, and 520 microM for ddCTP, FIAUTP, AZTTP and HPMPCpp, respectively. The Ki values toward DNA polymerase gamma in increasing order were 0.034, 0.031, 18.3 and 299 microM for ddCTP, FIAUTP, AZTTP and HPMPCpp, respectively. Therefore, HPMPC would be expected to have less inhibitory effects on DNA repair (DNA polymerase beta) and mitochondrial DNA synthesis (DNA polymerase gamma) than ddC, FIAU or AZT.

Antiviral Agents↗

PubMed1994

Expression of multiple neuregulin transcripts in postnatal rat brains.

The distribution of neuregulin transcripts in rat brains was studied by both RNA blotting and in situ hybridization. Our data demonstrate that multiple neuregulin transcripts are expressed in neurons of the basal forebrain, the hippocampus, the diencephalon, the cerebellum, the brainstem, and the spinal cord. Developmental changes in the distribution of neuregulin transcripts were observed only in the cerebellum and the hippocampus. The intense neuregulin hybridization signals in the brainstem motor and sensory nuclei and the spinal motor neurons are suggestive of a functional involvement of neuregulins in motor and sensory systems. The expression of neuregulins in other parts of the brain also indicates that these factors are involved in a variety of central nervous system functions.

Animals↗

PubMed1994

Behavioral and psychosocial cancer research in the underserved. An agenda for the future.

BACKGROUND: This research was undertaken to review the status of behavioral and psychosocial cancer research in the underserved. METHODS: The author extensively reviewed the literature related to behavioral and psychosocial cancer research in the underserved for this article. The author's experience as the Principal Investigator for the only National Institutes of Health smoking cessation study targeting Asian-Americans also was used in analyzing the literature and developing an agenda for the future. RESULTS: Two questions and accompanying agenda items were addressed. The underserved were defined, and the effect of being underserved was illustrated through their disproportionate and earlier (younger) presence in morbidity and mortality statistics. Initiating behavioral and psychosocial cancer research in the underserved begins with a proper attitude and making accommodations to culture. The agenda for research should be practical and assessed on the basis of prevalence and preventability of cancer related behaviors. Examples from underserved Asian-American populations were cited. CONCLUSIONS: Behavioral and psychosocial cancer research needs to be done.

Forecasting↗

PubMed1994

Potential therapeutic recombinant proteins comprised of peptides containing recombined T cell epitopes.

The complete primary structure of Fel d I2 has been determined and shown to be comprised of two separate polypeptide chains (designated chain 1 and 2). Overlapping peptides covering the entire sequence of both chains of Fel d I have been used to map the major areas of human T cell reactivity. The present study describes three non-contiguous T cell reactive regions of < 30 aa in length that were assembled in all six possible configurations using PCR and recombinant DNA methods. These six recombinant proteins comprised of defined non-contiguous T cell epitope regions artificially combined into single polypeptide chains have been expressed in E. coli, highly purified, and examined for their ability to bind to human cat-allergic IgE and for human T cell reactivity. Several of these recombined T cell epitope-containing polypeptides exhibit markedly reduced IgE binding as compared to the native Fel d I. Importantly, the human T cell reactivity to individual T cell epitope-containing regions is maintained even though each was placed in an unnatural position as compared to the native molecule. In addition, T cell responses to potential junctional epitopes were not detected. It was also demonstrated in mice that s.c. injection of T cell epitope-containing polypeptides inhibits the T cell response to the individual peptides upon subsequent challenge in vitro. Thus, these recombined T cell epitope-containing polypeptides, which harbor multiple T cell reactive regions but have significantly reduced reactivity with allergic human IgE, constitute a novel potential approach for desensitization to important allergens.

Allergens↗

PubMed1994

Comparison of the levels of the major allergens Der p I and Der p II in standardized extracts of the house dust mite, Dermatophagoides pteronyssinus.

Allergy to the house dust mite Dermatophagoides pteronyssinus is mediated by IgE to the major allergens Der p I and Der p II in the majority of mite-allergic patients. In recent years, standardized preparations of D. pteronyssinus, commercially available from several sources, have become widely used for the diagnosis and immunotherapy of mite allergy. As standardization implies uniformity of allergen composition and potency, we directly compared the absolute and relative quantities of Der p I and Der p II in six different commercial standardized extracts of D. pteronyssinus. Our findings reveal variability in levels of both Der p I and Der p II, producing ratios of Der p I/Der p II ranging from 1.1/1 to 6/1. Although the content of minor allergens in the extracts was not evaluated here, their contribution to the overall reactivity of mite-allergic patients to the commercial extracts was judged to be minimal. This was demonstrated by showing that plasma depleted of reactivity to both Der p I and Der p II had virtually no residual IgE directed against extract components. The variation in the proportion of Der p I and Der p II among different D. pteronyssinus extracts is likely to influence their biological effectiveness. Patients with reactivity against only Der p I or Der p II, who were found to comprise approximately one-third of the mite-allergic population, may not respond optimally to extracts containing relatively low levels of the allergen to which they are sensitive.

Allergens↗

PubMed1994

Experimental myopia in chickens induced by corneal astigmatism.

Astigmatism has been suggested to be an important factor in the production and/or progression of myopia. Chickens have been used as a myopic animal model for several years. In the present investigation our aim was to evaluate the importance of surgically induced corneal astigmatism by peripheral corneal incision with compression suture in one eye, the right, of 3-day-old chicks. Vertical incision (2 mm) with compression suture (nylon 9-0, one stitch) induces against-the-rule astigmatism, horizontal incision with compression induces with-the-rule astigmatism. Four groups were studied 1) with one vertical cut, 2) one horizontal cut, 3) two vertical cuts, 4) two horizontal cuts. The eyes were measured by caliper after 8 weeks. Eye enlargements were induced in all groups, however, less by one cut (astigmatism around 5 diopters) than by two cuts (astigmatism 10 diopters, or more). In the latter groups the pattern of equatorial eye enlargement depended on the axis of the induced astigmatism, the greater elongation being associated with the strongest refracting corneal meridian. All considered, the results suggest that significant corneal astigmatism could be another factor in the production of myopia, possibly acting by way of optical degradation of retinal image quality.

Animals↗

PubMed1994

1-[((S)-2-hydroxy-2-oxo-1,4,2-dioxaphosphorinan-5-yl)methyl] cytosine, an intracellular prodrug for (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine with improved therapeutic index in vivo.

1-[((S)-2-hydroxy-2-oxo-1,4,2-dioxaphosphorinan-5-yl)methyl]cytosi ne (cyclic [cHPMPC]) was evaluated as a novel antiviral agent in comparison with (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC). Evaluation for in vitro activity against herpes simplex virus type 2 in MA-104 and MRC-5 cells showed that both cHPMPC and HPMPC have comparable activities and cytotoxicities. cHPMPC was found to be stable on incubation in human plasma and human liver homogenates. Intracellular metabolism studies revealed that cHPMPC was converted inside of the cells to HPMPC and then to the monophosphate, the diphosphate, and the monophosphate choline metabolites. In a mouse herpes simplex virus type 2 encephalitis model, both cHPMPC and HPMPC exhibited similar potencies in vivo. Nephrotoxicity, which is the dose-limiting toxicity of HPMPC, was assessed in a 14-day repeated-dose toxicity study in rats; cHPMPC has an improved safety margin of > or = 13-fold over that of HPMPC.

Animals↗

PubMed1994

Surgical management of substernal goiter.

Seventeen cases of large substernal goiter are reviewed. The commonest clinical features were frequent upper respiratory tract infections, dyspnea and a cervical mass. Five of the patients had previous thyroidectomy. The substernal goiter was located in the right chest in 11 cases, the left chest in five and bilaterally in one case. On computed tomograms it was pretracheal or prevascular in ten cases and retrovascular in seven. Tracheal deviation was present in 15 cases, causing tracheal compression or stenosis in 14. Thyroidectomy was performed on all 17 patients (8 subtotal, 9 total) through a low transverse collar incision. The recommended technique for substernal goiter extending from the neck to a level below the subcarinal region includes concomitant finger dissection and upward traction of the cervical thyroid through the subcapsular plane, with obliteration of the postresection substernal dead space by sutures. Follow-up radiography showed that all the deviated tracheas had resumed near normal position 2-3 months postoperatively and the average diameter of the compressed tracheas had increased significantly.

Adult↗

PubMed1994

Vitreous fluorophotometry in patients with crystalline retinopathy.

Patients with various stages of crystalline retinopathy were examined with vitreous fluorophotometry and the results were compared with those of normal subjects. Two patients with glistening crystals without pigment clumps, together with atrophy of the retinal pigment epithelium in the posterior pole, showed a normal inward permeability of fluorescein. Three patients with a large area of choriocapillaris atrophy in the posterior pole, in addition to atrophy of retinal pigment epithelium, demonstrated an increase in the rate of inward fluorescein penetration. Three patients with extensive areas of choriocapillaris atrophy throughout the fundus also revealed an increased posterior vitreous penetration ratio.

Adult↗

PubMed1994

[Clinical factors affecting prognosis of small hepatocellular carcinoma after hepatectomy].

One hundred and two patients with histologically diagnosed small hepatocellular carcinoma (< or = 5cm HCC) underwent curative irregular hepatectomy in our hospital from Nov 1972 to Nov 1992. The postoperative survival rates at 1,3,5 and 10 years were 93.9%, 75.3%, 52.8% and 44.6%, respectively. We analysed the clinical factors using a Cox model and found that the clinical staging of HCC, gamma-GT, satellite tumor nodules, tumour capsule and postoperative recurrence have significant effect on the survival rate of patients. We conclude that early diagnosis of sub--clinical HCC, transarterial embolism after hepatectomy to reduce postoperative recurrence, and active treatment with operation and/or TAE after recurrence are effective methods to improve survival of HCC patients.

Adult↗

PubMed1993

Selective action of 4'-azidothymidine triphosphate on reverse transcriptase of human immunodeficiency virus type 1 and human DNA polymerases alpha and beta.

4'-Azidothymidine (ADRT) is a novel nucleoside analogue that exhibits potent inhibitory activity against the replication of human immunodeficiency virus (HIV) in lymphocytes. The mechanisms by which ADRT inhibits HIV reverse transcriptase (HIV-RT) as ADRT 5'-triphosphate (ADRT-TP), the active intracellular metabolite of ADRT, and as the ADRT-MP molecule incorporated into DNA were examined and compared to their effects on human DNA polymerases alpha and beta. Inhibition of HIV-RT by ADRT-TP is competitive against TTP and is more potent against RNA to DNA synthesis (Ki = 0.009 microM versus Km = 3.3 microM for TTP) than it is against DNA to DNA synthesis (Ki = 0.95 microM versus Km = 16.3 microM for TTP). ADRT-TP is also a more potent inhibitor for primer elongation on RNA template than on DNA template. ADRT-TP is a poor inhibitor of human DNA polymerases alpha (Ki = 62.5 microM) and beta (Ki = 150 microM) (Chen et al., 1992). The consequences of ADRT incorporation into DNA are strikingly different for the HIV-RT and for human DNA polymerases alpha and beta. DNA polymerases alpha and beta incorporate a single ADRT-MP molecule into nascent DNA at a very slow rate and continue to elongate. They are unable to incorporate a second consecutive ADRT-MP. However, HIV-RT is able to efficiently incorporate two consecutive ADRT molecules. Incorporation of two consecutive ADRT-MP molecules by HIV-RT prevents further DNA chain elongation. Incorporation of two ADRT-MP molecules separated by one deoxyribonucleoside monophosphate (dAMP, dCMP, or dGMP) also abolishes DNA chain elongation by HIV-RT.

Antiviral Agents↗

PubMed1993

Glial growth factors are alternatively spliced erbB2 ligands expressed in the nervous system.

Glial growth factors, proteins that are mitogenic for Schwann cells, and several ligands for the p185erbB2 receptor, are products of the same gene. Alternative splicing of the messenger RNA generates an array of putative membrane-attached, intracellular and secreted signalling proteins, at least some of which are expressed in the developing spinal cord and brain. These factors are probably important in the development and regeneration of the nervous system.

Alternative Splicing↗

PubMed1993

An acculturation scale for Southeast Asians.

This article reports the development of an acculturation scale for Southeast Asian immigrants. From factor analyses of responses on 13 items obtained from samples of three different Southeast Asian ethnic groups, i.e., Cambodians, Laotians, and Vietnamese, two subscales were derived: (1) proficiency in languages (land of origin versus English), and (2) language, social and food (LSF) preferences. Inter-item reliability of the scales was demonstrated for each of the three ethnic groups, with Cronbach alpha coefficients of 0.76 or above. Construct validity was also established within each of the three ethnic groups by demonstrating expected associations of the subscales with current age, years in the USA, total years of education, percentage of lifetime in the USA, and age on entering the USA. Multivariate analyses within each of the ethnic groups revealed that, once controlling for years of education, percentage of lifetime in the USA, and type of health care coverage, although not significant for the Cambodians (P = 0.08) males tended to show higher scores for the proficiency in language subscale in comparison to females. Similar multivariate analyses for the LSF preference subscale showed that although slightly higher for the males, the differences between the genders was not significant for the Cambodians (P = 0.78); both the Laotian (P = 0.23) and Vietnamese (P = 0.01) females showed higher scores in comparison to males although only just reaching significance for the Vietnamese.

Acculturation↗

PubMed1993

Development of macrovascular diseases in NIDDM patients in northern Taiwan. A 4-yr follow-up study.

OBJECTIVE: To assess the development of macrovascular diseases and explore major associative factors in NIDDM. RESEARCH DESIGN AND METHODS: A total of 479 NIDDM patients > or = 40 yr of age were recruited from four community primary care health centers of northern Taiwan in July 1986 for a cohort study with a 4-yr follow-up. No patient required insulin therapy within 1 yr of diagnosis nor had a history of diabetic ketoacidosis. All were able to participate independently in the activities of daily living. BP and ECG were measured, and a structured questionnaire was asked of each patient. Venous blood after overnight fasting was collected every year to measure cholesterol, HDL cholesterol, plasma glucose, and HbA1c. RESULTS: The duration of diabetes was associated with the development of stroke with a relative risk of 1.063 for every 1-yr increment (P = 0.07). As for HVDs, the significant risk factors were serum cholesterol and HbA1c. For every 1-mg/dl increase in mean total cholesterol level, the relative risk of developing HVD increased 1.016-fold (P = 0.04). For every 1% increase in HbA1c, the relative risk of developing HVD increased 1.170-fold (P = 0.01). With regard to leg VDs, sex and cigarette smoking were significant risk factors. Women diabetic subjects had a higher relative risk than men. Cigarette smoking was significantly associated with leg VD with a relative risk of 6.9 for smokers compared with nonsmokers. The most significant risk factor for LVD was the total cholesterol level. For every 1-mg/dl increase in mean serum cholesterol level, the relative risk of LVD increased 1.013-fold. CONCLUSIONS: In the prevention of macrovascular diseases, effective intervention of the nondiabetic cardiovascular risk factors may be as important as or even more important than the good control of diabetes.

Adult↗