Biomedical subjects

M Tang

Publications and source records attributed to M Tang.

At least 91 records · Page 5Linked to original sources

PubMed1997

Mapping and retinal phenotype of the hugger mutation in the mouse.

Hugger, hug, is a recessively expressed mutation in mice that features mildly abnormal locomotion, not yet explained, and a unique combination of developmental and degenerative retinal abnormalities. Analysis with the efficient MEV linkage testing stock established that hug is on mouse Chr 19 about 14 cM from th centromere, between the microsatellite markers D19Mit28 and D19Mit14. An abnormal retinal phenotype was recognized on the day of birth, when some retinal ganglion cells already lie in abnormal positions in the inner plexiform layer. By postnatal day 18 the number of neurons is reduced in all three cellular layers of the retina. Rod photoreceptor cells develop only rudimentory outer segments, and by 9 months of age, about 75% of the photoreceptor cells have completely disappeared. Similar photoreceptor cell abnormalities are seen in prph2 (formerly rds) homozygotes, which lack the peripherin/rds protein of the rod outer segments, but a mating of the respective homozygotes yielded normal progeny. Rom1, which codes for an outer segment protein similar to peripherin/rds, maps to a more proximal position on Chr 19.

Animals↗

PubMed1997

Association of estrogens with human plasma lipoproteins: studies using estradiol-17beta and its hydrophobic derivative.

Estrogen replacement therapy is widely used to combat symptoms of menopause, but factors influencing the transport of estrogen in plasma and its cellular uptake have been explored only to a limited extent. In this study, labeled estradiol-17beta (E2) was compared with its hydrophobic derivative (estradiol-3,17-diacetate, E2AA) in terms of (1) distribution within various lipoproteins and lipoprotein-free fractions of human plasma by ultracentrifugation and (2) uptake by human endothelial cells. Although added E2 was predominantly bound to HDL and lipoprotein-free fractions, E2AA was associated to some degree with VLDL and LDL but was still present in significant amounts in HDL and lipoprotein-free fractions. Significant associations of E2 with lipoproteins were also confirmed by polyacrylamide gel electrophoretic separation of E2-labeled plasma. In normal plasma, however, <10% of E2 was associated with lipoproteins when measured by radioimmunoassay. Incubation of E2AA and E2 with human dermal capillary endothelial cells showed similar uptake by 24 hours. A significant portion of E2AA was hydrolyzed to estradiol-17-monoacetate both in plasma and in cells. The addition of HDL and LDL to medium containing lipoprotein-deficient serum significantly reduced labeled E2 and E2AA uptake, respectively, by endothelial cells. These studies suggest that (1) although the association of E2 with HDL under normal conditions may be small, it increases significantly with higher estrogen concentrations of E2; (2) the hydrophobic ester of E2 shows increased binding to VLDL and LDL; and (3) this approach may be useful in manipulating the delivery of selected E2 derivatives to cells.

Endothelium, Vascular↗

PubMed1997

Use of the intestinal bile acid transporter for the uptake of cholic acid conjugates with HIV-1 protease inhibitory activity.

PURPOSE: To investigate the ability of the human intestinal bile acid transporter to transport cholic acid conjugates with potential HIV-1 protease inhibitory activity. METHODS: Cholic acid was conjugated at the 24 position of the sterol nucleus with various amino acids and amino acid analogs. The CaCo-2 cell line was used as a model to investigate the interaction of these bile acid conjugates with the human intestinal bile acid transporter. Interaction between the carrier and the conjugates was quantified by inhibition of taurocholic acid transport and confirmed by transport of radiolabelled conjugates in this cell line. RESULTS: The highest interaction with the transporter, as quantified by inhibition of taurocholic acid transport, occurred when a single negative charge was present around the 24 to 29 region of the sterol nucleus. A second negative charge or a positive charge significantly reduced the interaction. Transport of radiolabelled cholyl-L-Lys-epsilon-tBOC ester and cholyl-D-Asp-beta-benzyl ester was inhibited by taurocholic acid. Of all tested compounds, only cholyl-D-Asp-beta-benzyl ester showed modest HIV-1 protease inhibitory activity with an IC50 of 125 microM. CONCLUSIONS: Cholic acid-amino acid conjugates with appropriate stereochemistry are recognized and transported by the human bile acid transporter and show modest HIV-1 protease inhibitory activity. Transport of these conjugates by the bile acid carrier is influenced by charge and hydrophobicity around the 24 position of the sterol nucleus.

Amino Acids↗

PubMed1997

Molecular defects in Hb H hydrops fetalis.

The molecular defect in two unique cases of Hb H hydrops fetalis has been characterized. Both cases are due to co-inheritance of a 'non-deletion' defect affecting the alpha2 gene: at codon 30 delta GAG, Glu) and codon 59 (G --> A, Gly --> Asp) respectively, and a zeta-alpha thalassaemia (thal) 1 or alpha thal 1 genotype. These two non-deletion defects, unlike previously described cases, resulted in severe anaemia of the fetuses and emphasize the importance of performing prenatal diagnosis for these families.

Gene Deletion↗

PubMed1997

New-onset bronchospasm or recrudescence of asthma associated with cocaine abuse.

OBJECTIVE: To determine whether the occurrence of new-onset bronchospasm or the recrudescence of asthma is associated with the use of cocaine. METHODS: A consecutive sample of patients presenting to an inner-city adult ED with new-onset bronchospasm or recrudescence of bronchospasm after > 5 years were prospectively enrolled in a case-control prevalence study. The bronchospasm patients were queried as to their exposure to illicit drugs, and urine was obtained to screen for cocaine and its metabolite, benzoylecgonine. An age- and sex-matched control group was composed of randomly chosen subjects without respiratory complaints or a history of asthma. The control group was also screened by urine toxicology for cocaine and its metabolite, benzoylecgonine. RESULTS: In the asthma group, 21/59 (36%) had a urine toxicologic screen positive for cocaine metabolite (benzoylecgonine). Of the 21 with a positive screen for cocaine, 8 denied illicit drug abuse. Among the 13 patients reporting drug use, 10 said that they smoked crack and 3 snorted cocaine. In the control group, 8/53 (15%) were positive. Multivariate logistic regression analysis, with adjustment for age and sex, indicated that the use of cocaine was associated with a 3-fold higher prevalence of new-onset bronchospasm or recrudescence of asthma (OR = 3.28, 95% CI: 1.26 to 8.50). CONCLUSIONS: There appears to be an association between cocaine use and new-onset bronchospasm or recrudescence of asthma in this inner-city ED population. Further study is necessary to determine the basis for this association.

Adult↗

PubMed1997

Alzheimer's disease after remote head injury: an incidence study.

OBJECTIVE: To evaluate a history of remote head injury as a risk factor for subsequent dementia due to Alzheimer's disease. METHODS: 271 participants of a community based longitudinal study of aging in north Manhattan without evidence of significant cognitive impairment were interrogated for a history of head injury on two occasions at entry into the study. The examining physician sought a history of head injury with loss of conciousness. Independently, a risk factor interviewer inquired about a history of head injury with loss of consiousness or amnesia, the duration of any loss of consiousness, and the date of the head injury. Patients were followed up with standardised annual evaluations for up to five years to determine the first occurrence of dementia. RESULTS: Over the course of the study incident dementia due to probable or possible Alzheimer's disease was diagnosed in 39 patients. Cox proportional hazards modelling showed that a history of head injury with loss of consiousness reported to the physician was associated with earlier onset of dementia due to Alzheimer's disease (relative risk (RR) = 4.1, 95% confidence interval (95% CI) 1.3-12.7). head injury with loss of consiousness or amnesia reported to the risk factor interviewer was not significantly associated with earlier onset of Alzheimer's disease overall (RR 2.0, 95% CI 0.7-6.2), but those who reported loss of consiousness exceeding five minutes were at significantly increased risk (RR 11.2, 95% CI 2.3-59.8). Incident Alzheimer's disease was significantly associated with head injury which occurred within the preceding 30 years (RR 5.4, 95% CI 1.5-19.5). CONCLUSION: The results of this cohort study are consistent with the findings of several case-control studies suggesting that head injury may be a risk factor for Alzheimer's disease.

Age of Onset↗

PubMed1997

[The genetical effects of degUS gene in Bacillus subtilis Ki-2-132].

Using the methods of recombination and gene disruption, the effects of degUS gene in Bacillus subtilis Ki-2-132 were studied. The results showed that the gene could affect all protease-producing, competence formation, cell mobility and repression effects of glucose on protease-production. This implies that it is a pleitropic gene in Bacillus subtilis Ki-2-132. The disruption of the gene caused morphological changes and repressed the expression of aprE in vectors.

Bacillus subtilis↗

PubMed1997

[Inhibition of gastric motility by microinjection of CCK-8 into rat amygdala].

Intranulear microinjection and electrical stimulation technique were employed to evaluate the effect of ventromedial hypothalamus (VMH) on the gastric inhibition elicited by basomedial amygdala nucleus (BMA) excitation. The results were as follows: (1) Microinjections of CCk-8 (50 ng/microliter) into bilateral BAM resulted in significant decrease in intragastric pressure (IGP) and gastric motility frequency (GMF) (P < 0.01). (2) Neither CCK-A receptor antagonist [L364, 718] nor CCK-8 receptor antagonist [L365, 260] induced effects on IGP or GMF when given alone. (3) If bilateral BMA were pretreated with [L364, 718], CCK-8 could no longer induce any inhibitory effects, whlie [L365, 260] had no similar suppressive effect. (4) The inhibitory effects were not found in other nuclei in the amygdaloid body, such as bed nucleus of the stria terminalis intramygdaloid (BSTIA) and amygdaloid nucleus medial (Me). (5) Electrical stimulation of unilateral VMH or BMA would result in the inhibition of IGP and GMF. (6) After electric coagulation of VMH unilateraly injection of CCK-8 to or stimulation of homolateral VMH could no longer inhibite IGP or GMF. The above results suggest that in BMA CCK-8 exerts inhibitory effect on both motility and intragastric pressure through CCK-A receptors.

Amygdala↗

PubMed1997

[Bioimpedance measurement theory and technology].

Bioimpedance is an electrical character of living tissue, organ, cell or living body. When direct or alternating current of effective value below the exitation threshold passes through the living tissue, bioimpedance can be measured indirectly by voltage. It has been studied both theoretically and experimentally by many researchers. In this paper, the bioimpedance measurement theory and technologies are reviewed.

Body Composition↗

PubMed1996

Preferential formation of benzo[a]pyrene adducts at lung cancer mutational hotspots in P53.

Cigarette smoke carcinogens such as benzo[a]pyrene are implicated in the development of lung cancer. The distribution of benzo[a]pyrene diol epoxide (BPDE) adducts along exons of the P53 gene in BPDE-treated HeLa cells and bronchial epithelial cells was mapped at nucleotide resolution. Strong and selective adduct formation occurred at guanine positions in codons 157, 248, and 273. These same positions are the major mutational hotspots in human lung cancers. Thus, targeted adduct formation rather than phenotypic selection appears to shape the P53 mutational spectrum in lung cancer. These results provide a direct etiological link between a defined chemical carcinogen and human cancer.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

PubMed1996

[Psychological theories in relation to the development of schizophrenia].

A description of schizophrenia is given from a psychodynamic perspective. The illness is subsequently illuminated by means of different psychological theories, as the characteristic symptomatology is explained through five basic branches of psychology: The psychology of perception, motivation, cognition, personality formation and developmental psychology. Finally, current treatment-strategies are discussed.

Humans↗

PubMed1996

The multidomain protein Trio binds the LAR transmembrane tyrosine phosphatase, contains a protein kinase domain, and has separate rac-specific and rho-specific guanine nucleotide exchange factor domains.

rho-like GTP binding proteins play an essential role in regulating cell growth and actin polymerization. These molecular switches are positively regulated by guanine nucleotide exchange factors (GEFs) that promote the exchange of GDP for GTP. Using the interaction-trap assay to identify candidate proteins that bind the cytoplasmic region of the LAR transmembrane protein tyrosine phosphatase (PT-Pase), we isolated a cDNA encoding a 2861-amino acid protein termed Trio that contains three enzyme domains: two functional GEF domains and a protein serine/threonine kinase (PSK) domain. One of the Trio GEF domains (Trio GEF-D1) has rac-specific GEF activity, while the other Trio GEF domain (Trio GEF-D2) has rho-specific activity. The C-terminal PSK domain is adjacent to an Ig-like domain and is most similar to calcium/calmodulin-dependent kinases, such as smooth muscle myosin light chain kinase which similarly contains associated Ig-like domains. Near the N terminus, Trio has four spectrin-like repeats that may play a role in intracellular targeting. Northern blot analysis indicates that Trio has a broad tissue distribution. Trio appears to be phosphorylated only on serine residues, suggesting that Trio is not a LAR substrate, but rather that it forms a complex with LAR. As the LAR PTPase localizes to the ends of focal adhesions, we propose that LAR and the Trio GEF/PSK may orchestrate cell-matrix and cytoskeletal rearrangements necessary for cell migration.

Amino Acid Sequence↗

PubMed1996

Estrogens protect against hydrogen peroxide and arachidonic acid induced DNA damage.

The ability of estrogens to protect against DNA damage induced by either hydrogen peroxide or arachidonic acid alone or in combination with Cu2+ was investigated. DNA strand breaks were determined by conversion of double stranded supercoiled OX-174 RFI DNA to double stranded open circular DNA and linear single stranded DNA. Estradiol-17 beta significantly decreased the formation of single and double strand breaks in DNA induced by H2O2 alone or with Cu2+. Equilin (an equine estrogen) was more effective than estradiol-17 beta at the doses tested. Arachidonic acid in the presence of Cu2+ caused the formation of high levels of linear DNA which was protected by estrogen with equilen being more effective. These studies suggest that estrogens through this protective effect on DNA damage might contribute to cardioprotection.

Arachidonic Acid↗

PubMed1996

Estradiol-17beta as an antioxidant: some distinct features when compared with common fat-soluble antioxidants.

Estrogens are potent antioxidants both in vitro and in vivo. In this study the antioxidant affect of estradiol-17beta (estradiol) was compared with those of fat-soluble antioxidants (alpha-tocopherol and beta-carotene) in terms of both fatty acid (thiobarbituric acid-reactive substances and diene conjugation) and cholesterol oxidation (oxysterols). The addition of alpha-tocopherol (54 micromol/L) inhibited low-density lipoprotein (LDL) oxidation by 92.6% and high-density lipoprotein (HDL) oxidation by 76.5%. In similar experiments, estradiol (54 micromol/L) inhibited LDL oxidation by 77.5% but inhibited HDL oxidation by only 55.4%. Beta-carotene had no antioxidant effect. Lag times (diene conjugation method) for alpha-tocopherol and beta-carotene increased by 175% and 125%, respectively. Estradiol markedly reduced the maximum formation of diene conjugates as compared with results with alpha-tocopherol and beta-carotene, and it exhibited a linear curve (no change in lag time). In terms of cholesterol oxidation, estradiol was far more effective than alpha-tocopherol or beta-carotene in inhibiting oxysterol formation (microg/ml plasma) (control = 24.56 +/- 2.31, beta-carotene = 20.59 +/- 3.32, alpha-tocopherol = 20.19 +/- 1.58, estradiol = 14.38 +/- 0.70). This study shows that estradiol is as effective an antioxidant as alpha-tocopherol in terms of fatty acid peroxidation but is far more effective than alpha-tocopherol in terms of cholesterol peroxidation.

Adipocytes↗

PubMed1996

Superior and distinct antioxidant effects of selected estrogen metabolites on lipid peroxidation.

The effect of the estrogen metabolites, 4-hydroxyestrone and 17alpha-dihydroequilin (metabolites of estradiol-17beta and equilin, respectively), were examined for antioxidant effects on plasma and lipoprotein lipid peroxidation . Lipid peroxidation was evaluated by products of both fatty acid (thiobarbituric acid-reactive substances [TBARS]) and cholesterol (oxysterols) oxidation from lipoproteins or whole plasma. Although all estrogens significantly reduced lipid peroxidation, 4-hydroxyestrone was far more potent than either equilin or 17alpha-dihydroequilin in inhibiting TBARS formation in lipoproteins induced by Cu2+. Similar effects were also noted on TBARS formation in THP-l macrophages in culture. However, 17alpha-dihydroequilin (along with equilin) strongly inhibited oxysterol formation, whereas 4-hydroxyestrone was ineffective. These studies suggest that different estrogens might act preferentially on distinct lipid substrates in exhibiting antioxidant effects.

Antioxidants↗

PubMed1996

College research associates: a program to increase emergency medicine clinical research productivity.

STUDY OBJECTIVE: To evaluate a program using health care preprofessional college students as research associates (RAs) to facilitate research in emergency medicine. METHODS: We developed a program using health care preprofessional college students as RAs in an urban ED with an emergency medicine residency program. RAs were recruited from four local colleges. Potential RAs were instructed during four 2-hour sessions on clinical research in emergency medicine, the ethical issues of confidentiality and informed consent, personal safety, and specifics on data collection for the individual studies. For the 13 weeks of the 1995 spring semester, each RA served one 4-hour shift in the ED each week. They identified patients who were eligible for the studies, began the informed-consent process, obtained nonclinical and historical information, and assisted the physicians in the study protocols. The RAs were evaluated on every shift by two faculty members from New York Medical College. The RAs were surveyed at the completion of the semester about their experiences with the program. RESULTS: Forty-one students completed the orientation course and served at least one shift in the ED. Thirty-three completed more than 7 of 13 possible shifts and received credit for the semester. The average number of shifts served for all RAs was 9 (average numbers of shifts served by RAs receiving credit for the semester and RAs not receiving credit were 10.3 and 4, respectively). Two studies were completed during the semester, each with a significant increase in patient enrollment after the RAs' arrival. Three studies were ongoing at the end of the semester and had patient entries well above projected expectations. The principal investigators for the studies expressed their satisfaction with the RAs' productivity. The faculty evaluations were overwhelmingly positive, as were the results of the RA survey at the end of the semester. The cost of the program was minimal. CONCLUSION: College students serving as research associates can be an economical and successful tool for clinical studies in the emergency department.

Emergency Medicine↗

PubMed1996

Using UvrABC nuclease to detect 7,12-dimethylbenz[a]anthracene anti-diol epoxide-DNA binding specificity in the mouse H-ras gene.

DNA fragments modified with chemically synthesized 7,12-dimethylbenz[a]anthracene anti-diol epoxide (anti-DMBADE) are sensitive to UvrABC nuclease incision. The incisions occur mainly 7 bases 5' and 4 bases 3' of an anti-DMBADE-modified adenine or guanine residue, and the kinetics of incision at different sequences in a DNA fragment are the same. These results indicate that UvrABC incision on anti-DMBADE-DNA adducts is independent of DNA sequences and is quantitative, the same as on syn-DMBADE-DNA adducts. This method was used to analyze the anti-DMBADE-DNA binding spectrum in the exon 2 region of the mouse H-ras gene, and it was found that anti-DMBADE binds to the two adenine residues at codon 61 of the H-ras gene with an average affinity. Previously, we have demonstrated that syn-DMBADE binds strongly to the adenines at codon 61 of H-ras; these results together suggest that the oncogenic mutation in H-ras may be induced by anti- and syn-DMBADE-DNA adducts.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1996

A preliminary study of apolipoprotein E genotype and psychiatric manifestations of Alzheimer's disease.

We evaluated the frequency of depression and psychosis in 46 patients with AD and 135 control subjects with the apolipoprotein (APO) E3/3 or E3/4 genotype. Patients with AD and the APOE3/4 genotype had a more than threefold increase in the signs of depression and psychosis when compared with either patients with the APOE3/3 genotype or to control subjects. Our preliminary study suggests that the phenotype of AD associated with the epsilon 4 allele is more likely to include psychiatric manifestations.

Aged↗