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Biomedical subjects

K Chen

Publications and source records attributed to K Chen.

At least 487 records · Page 27Linked to original sources

Molecular biology of serotonin (5-HT) receptors.

The recent cloning of three types of 5-hydroxytryptamine (5-HT, serotonin) receptors substantiates radioligand-based definitions of 5-HT receptors, and provides a framework in which to understand the function and evolution of the receptors. The primary sequences determined by molecular cloning of the 5-HT1c, 5-HT1a and 5-HT2 receptors place each of these 5-HT receptor subtypes into the class of G protein-coupled receptors. These receptors all share similar functional and structural features. Each receptor is positioned in the lipid bilayer with seven membrane-spanning domains and corresponding intracellular and extracellular domains. By analogy to the known functional structures of the beta-adrenergic receptor, the binding site of 5-HT is proposed to be in the membrane domains and the intracellular domain is important for G protein interaction. The primary sequences and the second messenger systems of the receptors indicate the 5-HT2 and 5-HT1c receptors are closely related, whereas the 5-HT1a receptor is more distantly related to the 5-HT2 and 5-HT1c receptors.

Amino Acid Sequence↗

NGF improves spatial memory in aged rodents as a function of age.

Aged rats were tested for place navigation in a circular water maze for spatial memory ability at 18 and 30 months of age; 45% of the 18-month-old rats displayed impaired place navigation performance relative to young control rats, while essentially all of the 30-month-old rats were impaired. The aged impaired rats were retested twice during NGF or vehicle infusion in the right lateral ventricle. In the 18-month-old group, NGF-infused rats showed improved retention of previously acquired place navigation performance and improved spatial acuity over the former platform site when the invisible platform was removed. NGF infusion also had a significant effect in the much more severely impaired 30-month-old rats: while the vehicle-infused aged rats showed a progressive decline in the performance between the first and second test weeks, the performance of the NGF-infused rats remained stable throughout the infusion period. The interpretation of these effects in the oldest animals, however, was confounded by a progressive decline in swim speed seen in the vehicle-infused animals. The 30-month-old vehicle-infused control rats showed a significant cell loss and cell shrinkage relative to the young control rats in the septal/diagonal band area, the striatum, and the nucleus basalis as assessed by NGF-receptor (NGFr) and ChAT double-label immunocytochemistry. A significant increase in the size but not in the number of cells was observed on the side of the NGF infusion in the 30-month-old NGF-infused rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

[Comparison of Spatholobus suberectus Dum, Euonymus alatus (Thunb.) Sieb. and Eupolyphaga sinensis Walker on regulation of plasma lipid].

The Spatholobus suberectus (SS) of hexue type, the Euonymus alatus (EA) of huoxue type and the Eupolyphaga sinensis (ES) of poxue type were selected and their influence on plasma lipid in the experimental hyperlipidemia quails was observed. The ES could raise plasma HDL-C/TC ratio and increase LCAT activity. The SS could raise plasma HDL2-C/HDL3-C ratio. The effect of EA on plasma HDL-C/TC, HDL2-C/HDL3-C and LCAT levels was between SS and ES. All the three huoxue huayu Chinese drugs could lower plasma HDL3-C level and slow down the progress of atherosclerosis to a certain degree. The above-mentioned results show that certain orders exist between the action range of huoxue huayu drugs and their effect on regulating plasma lipid.

Animals↗

Inhibition of platelet GPIIb/IIIa binding to fibrinogen by serum factors: studies of circulating immune complexes and platelet antibodies in patients with hemophilia, immune thrombocytopenic purpura, human immunodeficiency virus-related immune thrombocytopenic purpura, and systemic lupus erythematosus.

We have studied the conditions of in vitro binding of platelet glycoprotein IIb/IIIa (GPIIb/IIIa) to fibrinogen and applied the results to identify and measure the serum inhibitors to the binding. For the enzyme-linked immunosorbent assay, platelet extract was delivered to a fibrinogen-coated microtiter plate that was incubated for 2 hours, followed by incubation with anti-GPIIb/IIIa monoclonal antibody for another 2 hours. The plate was then incubated with peroxidase-conjugated anti-mouse IgG for color development. The binding was shown to be calcium-dependent. The binding was partially blocked by treating the coated fibrinogen with anti-fibrinogen antibody. Reduction or dissociation of GPIIb/IIIa resulted in the total loss of its ability to bind to fibrinogen. Platelet extracts of patients with hemophilia showed decreased binding (25% and 14%, compared with control platelet extract), and an extract from a patient with Glanzmann's thrombasthenia showed no binding. With the enzyme-linked immunosorbent assay we have measured serum inhibitors to GPIIb/IIIa binding to fibrinogen in 35 hemophilia A, 17 immune thrombocytopenic purpura, 22 human immunodeficiency virus-related immune thrombocytopenic purpura, and 29 systemic lupus erythematosus serum samples. In those patients with inhibition by serum, polyethylene glycol precipitation of circulating immune complexes (CICs) decreased the inhibition by the supernatants, and all the resolubilized CIC precipitates demonstrated inhibition, which indicates that CICs play a major role in the inhibition of GPIIb/IIIa binding to fibrinogen. This, then, provides evidence of CIC-mediated impaired GPIIb/IIIa binding to fibrinogen in hemophilia A, HIV-ITP, and SLE.

Antibodies↗

Frameshift suppression at tandem AGA and AGG codons by cloned tRNA genes: assigning a codon to argU tRNA and T4 tRNA(Arg).

Arginine is coded for by CGN (N = G, A, U, C), AGA and AGG. In Escherichia coli there is little tRNA for AGA and AGG and the use of these codons is strongly avoided in virtually all genes. Recently, we demonstrated that the presence of tandem AGA or AGG codons in mRNA causes frameshifts with high frequency. Here, we show that phaseshifts can be suppressed when cells are transformed with the gene for tRNA(T4Arg) or E. coli tRNA(argU,Arg) demonstrating that such errors are the result of tRNA depletion. Bacteriophage T4 encoded tRNA(Arg) (anticodon UCU) corrects shifts at AGA-AGA but not at AGG-AGG, suggesting that this tRNA can only read AGA. Similarly, comparison of the translational efficiencies in an argU (Ts) mutant and in its isogenic wild type parent indicates that argU tRNA (anticodon UCU) reads AGA but not AGG. An argU (Ts) mutant barely reads through AGA-AGA at 42 degrees C but translation of AGG-AGG is hardly, if at all, affected. Overexpression of argU+ relaxes the codon specificity. The thermosensitive mutant in argU, previously called dnaY because it is defective in DNA replication, can be complemented for growth by the gene for tRNA(T4Arg). This implies that the sole function of the argU gene product is to sustain protein synthesis and that its role in replication is probably indirect.

Base Sequence↗

Diet, physical activity, and colorectal cancer among Chinese in North America and China.

In a population-based case-control study of colorectal cancer among Chinese men and women in western North America and the People's Republic of China, a common protocol was used to assess past life-style characteristics of 905 cases diagnosed during 1981-1986 and 2,488 controls. Risks for cancers of both the colon and rectum increased with increased food energy from fat, protein, carbohydrate, and all energy sources combined, for both sexes and on both continents. Yet, in multivariate analysis, colorectal cancer risk was significantly associated only with saturated fat; no relationships were seen with other dietary sources of energy. Colon cancer risk was elevated among men employed in sedentary occupations. On both continents and in both sexes, risks for cancers of both the colon and rectum increased with increasing time spent sitting. Further, the association between colorectal cancer risk and saturated fat was stronger among the sedentary than among the active. Risk among sedentary Chinese Americans of either sex increased more than fourfold from the lowest to the highest category of saturated fat intake. Among migrants to North America, risk increased with increasing years lived in North America. These observations suggest (a) that colorectal cancer risk increases with duration of exposure to a sedentary life-style and a diet rich in saturated fat; (b) that higher incidence among Chinese-American men relative to women is due to longer duration of these habits among men, who have lived longer in North America; and (c) that higher risk among Chinese Americans of both sexes relative to risk among the general population in China is due to differences in such habits. Attributable risk calculations suggest that, if these associations are causal, saturated fat intakes exceeding 10 g/day, particularly in combination with physical inactivity, could account for 60% of colorectal cancer incidence among Chinese-American men and 40% among Chinese-American women.

Adult↗

Nucleotide sequence of the sacS locus of Bacillus subtilis reveals the presence of two regulatory genes.

The nucleotide sequence of 3 kb of Bacillus subtilis chromosomal DNA, including sacS, reveals that the regulatory locus for levansucrase synthesis consists of two genes, sacX and sacY. The sacX gene product is remarkably similar to sucrose-specific enzyme II of the B. subtilis phosphoenolpyruvate-dependent phosphotransferase system. The product of sacY is similar, both in amino acid sequence and most probably in its function, to BglG, an Escherichia coli transcriptional antitermination factor.

Amino Acid Sequence↗

The expression of human MAO-A and B genes.

Northern analysis using 32P-labeled subfragments of human liver MAO-A and B cDNA clones detected 5Kb and 3Kb transcripts, respectively in fetal tissues and adult brains. The tissue distribution of these transcripts was determined. Small intestine and placenta express, in addition to the MAO-A 5Kb transcript, a 2Kb transcript determined to lack a 3' flanking region. MAO-A appeared prior to MAO-B in the fetal brain, whereas both MAO-A and B were found in adult brain.

Blotting, Northern↗

The cytotoxic principles of Pseudolarix kaempferi: pseudolaric acid-A and -B and related derivatives.

Pseudolaric acid-A and -B, the novel diterpene acids isolated from Pseudolarix kaempferi, and their related derivatives have been tested for cytotoxicity against KB, A-549, HCT-8, P-388, and L-1210 tumor cells. The results showed that pseudolaric acid-A and -B demonstrated potent cytotoxicity. The selectivity of pseudolaric acid-A and -B which inhibit the growth of particular cell types within the disease-oriented human cancer cell line panels is discussed.

Animals↗

The effect of recombinant interferon-alpha on lymphocyte subpopulations and HLA-DR expression on liver tissue of HBV-positive individuals.

Interferon-alpha (IFN-alpha) has been reported to be beneficial in the treatment of chronic active hepatitis occurring as a result of hepatitis B virus (HBV) infection. Treatment with IFN-alpha has been proposed as a means of reducing the high rate of allograft infection in clinical liver transplantation in patients transplanted for HBV-related chronic active hepatitis and cirrhosis who are positive for hepatitis B surface antigen (HBsAg). We obtained resected whole livers from two groups of patients who received liver transplants. Group A consisted of 11 patients who were HBsAg+ but were not treated with IFN-alpha, and group B consisted of 10 patients who were also HBsAg+ but received IFN-alpha therapy for 29.4 +/- 5.6 days prior to orthotopic liver transplantation. No differences between the two groups existed in terms of a variety of demographic and clinical characteristics. The liver tissue was stained with monoclonal antibodies to cell surface antigens unique to different mononuclear cell populations by the avidin-biotin-immunoperoxidase technique to determine the effect of IFN-alpha on the lymphocyte subsets as well as HLA antigen expression on liver-infiltrating mononuclear cells. The number of HLA-DR+ lymphocytes in the liver was significantly increased (P less than 0.005) within the portal areas in group B compared with that found in group A (84 +/- 14 versus 33 +/- 5 per one high-power field). Moreover, the intensity of the HLA-DR antigen expression on lymphocytes in the portal areas (P less than 0.02) and in the hepatic lobule (P less than 0.05) was greater in group B than in group A. The number of natural killer (NK) cells was increased in the portal areas (P less than 0.05) of group B compared with group A. These alterations in the lymphocyte and NK cell populations present in the liver in response to IFN-alpha therapy presumably reflect an IFN-alpha-induced enhancement of the immune response to virus-infected cells.

Adult↗

Tissue distribution of human monoamine oxidase A and B mRNA.

Monoamine oxidase (MAO) A and B play important roles in the metabolism of biogenic amines. Northern analysis using 32P-labeled subfragments of human liver MAO A and B cDNA clones detected a 5- and a 3-kb transcript, respectively, in most human tissues examined. However, fetal heart and thymus express minute amounts of MAO A transcript, whereas fetal brain, muscle, thymus, spleen, meninges, and placenta express minute amounts of MAO B transcript. Small intestine and placenta express, in addition to the MAO A 5-kb transcript, a 2-kb transcript, which may arise from an alternative polyadenylation site. MAO A and B transcripts are expressed in similar regions of adult human brain. The highest concentrations of these transcripts were located in frontal cortex and locus coeruleus. This study demonstrates the tissue-specific distribution of the MAO genes and will provide insight into the physiological functions of MAO A and B.

Brain↗

Characterization of factors that direct transcription of rat ribosomal DNA.

The protein components that direct and activate accurate transcription by rat RNA polymerase I were studied in extracts of Novikoff hepatoma ascites cells. A minimum of at least two components, besides RNA polymerase I, that are necessary for efficient utilization of templates were identified. The first factor, rat SL-1, is required for species-specific recognition of the rat RNA polymerase I promoter and may be sufficient to direct transcription by pure RNA polymerase I. Rat SL-1 directed the transcription of templates deleted to -31, the 5' boundary of the core promoter element (+1 being the transcription initiation site). The second factor, rUBF, increased the efficiency of template utilization. Transcription of deletion mutants indicated that the 5' boundary of the domain required for rUBF lay between -137 and -127. Experiments using block substitution mutants confirmed and extended these observations. Transcription experiments using those mutants demonstrated that two regions within the upstream promoter element were required for optimal levels of transcription in vitro. The first region was centered on nucleotides -129 and -124. The 5' boundary of the second domain mapped to between nucleotides -106 and -101. DNase footprint experiments using highly purified rUBF indicated that rUBF bound between -130 and -50. However, mutation of nucleotides -129 and -124 did not affect the rUBF footprint. These results indicate that basal levels of transcription by RNA polymerase I may require only SL-1 and the core promoter element. However, higher transcription levels are mediated by additional interactions of rUBF, and possibly SL-1, bound to distal promoter elements.

Animals↗

Nifedipine pharmacodynamics and pharmacokinetics in treatment of congestive heart failure.

In 22 of 27 cases of congestive heart failure (CHF) treated with nifedipine (NIF), significant improvements in resting hemodynamics were noticed. The higher the basal systemic vascular resistance (SVR) and pulmonary artery end diastolic pressure (PAEDP), the greater the magnitude of reduction was achieved (r = 0.84 and 0.77, P less than 0.01, respectively). Exercise hemodynamic investigation showed that NIF lowered SVR, PAEDP and pulmonary vascular resistance (PVR), with an increase in stroke volume (SV) at the serum concentration of 5-10 ng/ml. Maximum effect was observed at the concentration of 20 ng/ml. No further vasodilation was attainable with serum concentrations above 20 ng/ml. No remarkable deviation of NIF pharmacokinetic parameters from the normal ranges was found in CHF patients. The plasma norepinephrine level decreased markedly 2 and 7 hours after the use of NIF. It is concluded that oral NIF is beneficial to severe CHF patients with low cardiac output and high SVR.

Adolescent↗