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Biomedical subjects

R Chen

Publications and source records attributed to R Chen.

At least 505 records · Page 28Linked to original sources

Mortality from lung cancer among copper miners.

A cohort mortality study of lung cancer in 7088 copper miners was made from 1 January 1969 to 31 December 1988. There was an excess of deaths from lung cancer in the copper miners. The standardised mortality ratio (SMR) was 147 (p < 0.01). The SMR increased with calendar period. There was a higher risk of deaths from lung cancer in the miners employed in the 1950s. Age at the start of exposure had no effect on the risk of lung cancer. The risk of death from lung cancer increased with the duration of exposure and the time since first exposure. The SMR for lung cancer was 173 in underground miners and 193 for drilling miners (both p < 0.01). These data show that exposure to dust is associated with an excess of deaths from lung cancer in copper miners whereas exposure to radiation does not seem to carry such risk.

Adolescent↗

Sodium restriction increases aldosterone biosynthesis by increasing late pathway, but not early pathway, messenger ribonucleic acid levels and enzyme activity in normotensive rats.

To determine whether changes in dietary sodium intake modify the early and/or late pathways of aldosterone biosynthesis, we studied in Sprague-Dawley rats the effect of sodium restriction on early (conversion of cholesterol to pregnenolone) and late (conversion of corticosterone to aldosterone) pathway activity and on the mRNA levels for the enzymes regulating these steps. Sodium restriction increased basal and angiotensin-II-stimulated aldosterone output from isolated zona glomerulosa cells by 5- to 9-fold. This increase in aldosterone output did not appear to be due to changes in the conversion of cholesterol to pregnenolone or in the mRNA levels of the early pathway enzyme, cholesterol side-chain cleavage cytochrome P-450. In contrast, sodium restriction increased the conversion of corticosterone to aldosterone 10-fold and increased by over 10-fold the mRNA levels of the late pathway enzyme aldosterone synthase. Sodium restriction had no effect on zona glomerulosa levels of 11 beta-hydroxylase mRNA. In two other normotensive rats, Dahl salt-resistant and Wistar Kyoto, sodium restriction again specifically increased aldosterone synthase mRNA without altering 11 beta-hydroxylase or cholesterol side-chain cleavage cytochrome P-450 mRNA levels. Thus, it appears that sodium restriction specifically increases late pathway aldosterone synthase mRNA levels, resulting in an increase in enzyme levels, followed by an increase in late pathway activity and an increase in aldosterone output.

Aldosterone↗

Cloning and functional expression of a rat brain corticotropin releasing factor (CRF) receptor.

Corticotropin releasing factor (CRF), a key neuroregulator of the hypothalamic-pituitary-adrenal cortical axis, also displays a broad range of effects on the endocrine, central nervous and immune systems. Having recently characterized the human pituitary CRF receptor by expression cloning of cDNA from a human Cushing's corticotropic adenoma, we report here the structure of the cDNA for a rat brain CRF receptor (rCRF-R) which was cloned by hybridization from a rat brain cDNA library. The sequence of the rCRF-R encodes a 415 amino acid protein comprising seven membrane spanning domains. The rCRF-R is 97% identical at the amino acid level to the human pituitary tumor CRF receptor, differing by only 12 amino acids. When expressed in COSM6 cells, the rCRF-R binds CRF with high affinity (Kd = 1.7 (0.8-3.8)nM). The receptor transduces a CRF stimulated accumulation of intracellular cAMP which is inhibited by the CRF antagonist, alpha helCRF(9-41). These results suggest that the brain expresses a CRF receptor similar to that in the pituitary.

Amino Acid Sequence↗

Tektin B1 from ciliary microtubules: primary structure as deduced from the cDNA sequence and comparison with tektin A1.

Tektins are a class of proteins that form filamentous polymers in the walls of ciliary and flagellar microtubules, and they may also be present in centrioles, centrosomes and mitotic spindles. We report here the cloning and sequencing of a cDNA for ciliary tektin B1. Comparison of the predicted amino acid sequence of tektin B1 with the previously published sequence for tektin A1 reveals several features that better define this class of proteins. Like tektin A1, the central region of the tektin B1 polypeptide chain is predicted to form a coiled-coil rod, consisting of four major alpha-helical regions that are separated by non-helical linkers. Between the central rod domains of tektins A and B there is a 34%/20% amino acid sequence identity/similarity, including equivalent 50-residue segments containing 36 identities, and a high probability of long-range structural homology. The tektin polypeptide chains are divided into two major segments that have significant sequence homology to each other, both within a given tektin chain and between tektins A and B, indicative of gene duplication events. The tektins have a secondary structure and molecular design similar to, but a low primary sequence homology with, intermediate filament proteins. Unlike tektin A1, tektin B1 lacks any part of the C-terminal IFP consensus sequence.

Amino Acid Sequence↗

Large granular lymphoproliferative disease associated with nephrotic syndrome, renal failure and leukoencephalopathy.

A 23-year-old black female presented with general malaise, headache, high white cell count (136 x 10(9)/L), thrombocytopenia and nephrotic syndrome. She proved to have large granular lymphoproliferative disease with a natural killer cell phenotype and without a clonal rearrangement of the T-cell receptor genes. Renal biopsy demonstrated focal segmental glomerulosclerosis (FSGS). She developed a monophasic neurological illness, and rapidly became comatose six days after the initiation of high dose prednisone therapy. Computerized tomography of the brain showed marked hypodensity of the subcortical white matter. She regained consciousness subsequently, but died six months after her initial presentation with uncontrolled lymphocytosis and renal failure. Autopsy revealed FSGS with glomerular collapse and microcystic dilatation of the renal tubules, and there was perivascular demyelination in the subcortical white matter of the brain. We speculate that lymphokines released by the natural killer cells may have played an important role in the pathogenesis of both the nephrotic syndrome and leukoencephalopathy.

Acute Disease↗

[The genotyping of HLA-D region and specific RFLP patterns for Chinese Han population].

The HLA class II antigens play very an important role in presenting foreign antigens. The class II gene typing at the DNA level possesses higher capability to recognize polymorphism so that it can disclose new specificities. According to the RFLP patterns of DRB and DQA genes for Caucasian HTC and some Chinese homozygous cells, we typed 90 randomly sampled healthy Chinese Hans in Shanghai area, and compared the results obtained with those from serological typing. In addition to being reliable and superior to serological typing, we found some unique RFLP patterns of the HLA-D region in Chinese Han population based on comparison with Caucasian patterns.

Blood Grouping and Crossmatching↗

[Revelations of the origin of Chinese nation from clustering analysis and frequency distribution of HLA polymorphism in major minority nationalities in mainland China].

This paper is a joint report on the analysis of polymorphism of HLA class I, II and III antigens in Chinese major minority nationalities (Miao, Buyi, Mongol of Inner Mongolia, Man, Hui, Tibetan and Uygur), and southern and northern Han samples as a part of the workshop organized by the 11th International Histocompatibility Workshop and Conference (IHWC) held on 6-13 November 1991 in Yokohama. Clustering analysis showed that Miao and Buyi cluster with the southern Han and Mongol, Man, Hui and Tibetan cluster around the northern Han, suggesting that the Chinese nation comprises northern and southern two major populations. Uygur clusters with a large group of Caucasoid samples from very far point. Frequencies of HLA alleles of Caucasoid origin (A3, B8 and others) decrease eastwards and southwards, and those of HLA alleles of Southeast Asia Mongoloid origin (B46 and others) decrease northwards. The gradient distribution of HLA allele frequencies suggests the unceasing migration and mutual amalgamation of our ancestors since the remote pre-historic times. From the fact that Chinese nation comprises northern and southern two major populations, this paper discussed the possible revelations of the origin of Chinese nation.

Asian People↗

Growth hormone and vitamin A induce P4502C7 mRNA expression in primary rat hepatocytes.

The effects of growth hormone (GH) and retinoids on P4502C7 mRNA levels were investigated in cultured primary hepatocytes from normal female rats. Northern blot analysis of total nucleic acids from hepatocytes maintained in culture for 90 hr showed low basal levels of P4502C7 mRNA, which were marginally increased after continuous treatment with GH. Retinal treatment gave a slightly higher induction than GH, whereas treatment with all-trans retinoic acid alone or with GH in combination with retinol induced P4502C7 mRNA to levels about one-third of those in normal female rat liver. The effects of retinoids on P4502C7 mRNA were dependent on both the dose and type of retinoid used. All-trans retinoic acid produced a saturable dose-response curve with a 50% maximal induction of P4502C7 mRNA at 1.5 microM. The isomer 9-cis retinoic acid showed a dose-dependent activation of P4502C7 mRNA similar to that of all-trans retinoic acid. Retinol gave a 50% maximal response at approximately 5 microM. In the presence of GH, the induction of P4502C7 mRNA appeared additive to the effect of retinol at all concentrations used and to all-trans retinoic acid at concentrations up to 1 microM. As determined by a quantitative solution hybridization assay, P4502C7 mRNA levels were induced 3-fold by GH, 5-fold by retinol, and 19-fold by all-trans retinoic acid. In the presence of GH, P4502C7 was induced 8-fold by retinol, whereas the induction by saturating concentration of all-trans retinoic acid showed no significant additional effect of GH. The importance of vitamin A for the expression of P4502C7 in vivo was confirmed by the low abundance of P4502C7 mRNA in vitamin A-deficient animals as compared with vitamin A-adequate control rats. Nuclear run-on experiments performed in cultured primary hepatocytes showed that both GH and retinoic acid exert their effects at the transcriptional level. We conclude that both GH and retinoids can induce P4502C7 mRNA in rat liver hepatocytes, retinoic acid being the dominant inducer.

Animals↗

The ATP4- receptor-operated ion channel of human lymphocytes: inhibition of ion fluxes by amiloride analogs and by extracellular sodium ions.

Extracellular ATP is known to increase the membrane permeability of a variety of cells. Addition of ATP to human leukemic lymphocytes loaded with the Ca2+ indicator, fura-2, induced a rise in cytosolic Ca2+ concentration which was attenuated or absent in NaCl media compared with KCl, choline Cl, or NMG Cl media. In contrast, anti-immunoglobulin antibody gave similar Ca2+ transients in NaCl and KCl media. A half-maximal inhibition of peak ATP-induced Ca2+ response was observed at 10-16 mM extracellular Na+. Basal 45Ca2+ influx into lymphocytes was stimulated 9.6-fold by ATP added to cells in KCl media, but the effect of ATP was greatly reduced for cells in NaCl media. Hexamethylene amiloride blocked 74% of the ATP-stimulated Ca45 uptake of cells in KCl media. Flow cytometry measurements of fluo-3-loaded cells confirmed that the ATP-induced rise in cytosolic Ca2+ was inhibited either by extracellular Na+ or by addition of hexamethylene amiloride. Extracellular ATP stimulated 86Rb efflux from lymphocytes 10-fold and this increment was inhibited by the amiloride analogs in a rank order of potency 5-(N-methyl-N-isobutyl)amiloride greater than 5-(N,N-hexamethylene)amiloride greater than 5-(N-ethyl-N-isopropyl)amiloride greater than amiloride. ATP-induced 86Rb efflux showed a sigmoid dependence on the concentration of ATP and Hill analysis gave K1/2 of 90 and 130 microM and n values of 2.5 and 2.5 for KCl and NaCl media, respectively. However, the maximal ATP-induced 86Rb efflux was 3-fold greater in KCl than in NaCl media. Raising extracellular Na+ from 10 to 100 mM increased ATP-induced Na+ influx from a mean of 2.0 to 3.7 nEq/10(7) cells/min, suggesting either saturability or self-inhibition by Na+ of its own influx. These data suggest that ATP opens a receptor-operated ion channel which allows increased Ca2+ and Na+ influx and Rb+ efflux and these fluxes are inhibited by extracellular Na+ ions as well as by the amiloride analogs.

Adenosine↗

The effect of cobrotoxin on cholinergic neurons in the mouse.

By using multiple time-point constant-rate infusions of deuterium-labeled phosphorylcholine, appropriate kinetic parameters were obtained for use in the calculation of the turnover rate of acetylcholine (TRACh) in selected mouse brain regions. After obtaining these data, the relationship between the analgesic agent cobrotoxin (CT) and the activity of central cholinergic neurons was investigated by determination of TRACh in selected mouse brain regions 3 hours following intracerebroventricular (i.c.v.) injection of CT. There were no obvious changes in the concentrations of ACh and choline (Ch) in the cortex, hippocampus, hypothalamus, midbrain, striatum, or thalamus of the mouse after injection of an analgesic dose of CT (2 micrograms, i.c.v.). TRACh in the thalamus and the striatum were significantly increased, as compared to controls. On the other hand, i.c.v. injection of CT was found to significantly reduce TRACh in the hippocampus and midbrain. These results suggest that the activity of hippocampal and midbrain cholinergic neurons is suppressed by CT, whereas the activity of striatal and thalamic cholinergic neurons is increased by CT at a time when a maximum analgesic response to CT is expressed.

Acetylcholine↗

Orally self-administered cocaine: reinforcing efficacy by the place preference method.

In three separate place preference conditioning (PPC) experiments, groups of rats were exposed to different modes of receiving cocaine: IP cocaine doses (7.5 mg/kg), PO cocaine self-administered bolus doses (15 mg/kg), and 1-h schedule-induced cocaine-solution drinking sessions (19.1 mg/kg). Oral cocaine self-administration of PO bolus and schedule induction took place in situations that preceded transfer into an apparatus for PPC sessions. Thus, the reinforcing efficacies of the pharmacological consequences of both oral cocaine self-administration methods were evaluated by a procedure separate from the self-administration behavior itself. The IP cocaine dose imposition and the two oral cocaine self-administration arrangements all resulted in dose-exposure conditions sufficient for the production of PPC. The serum and brain cocaine pharmacokinetics sufficient for the production of reinforcing efficacy were measured and related to previous data.

Administration, Oral↗

Predicting childlessness for recent cohorts of American women.

Over 50% of the American women now in the midst of the childbearing years have never borne a child. These levels of childlessness for women in their 20s are the highest ones in a time series that spans most of the twentieth century. Will postponed parenthood be translated into very high levels of permanent childlessness? Or will these cohorts "catch-up" with a late fertility flurry in their 30s and 40s? The authors examine 3 projection strategies: one using women's stated fertility expectations, a second relying on the patterns of previous cohorts, and a third which posits that current rates will persist into the future. The predictive validity of these different projection strategies are tested with data for the 1980-87 period. They show that the projection based on current period rates performs well. Further, the authors argue that it better captures the first birth process than other models. They forecast levels of 20% childless for cohorts of white women born in the early 1960s. Recent trends for nonwhites are very different from those for whites: levels of 4% are forecast for nonwhite women.

Age Distribution↗

Advanced Chinese NiTi alloy wire and clinical observations.

Chinese NiTi wire was studied on the bench with six other nickel-titanium-alloy wires. Bending and torsional tests were conducted and temperatures of phase transformation compared. The Chinese NiTi wire was found to have a low stiffness, high springback and constant bending and torsional moments on unloading, in a very large deformation region. It can produce a gentle, nearly constant force. These factors make it desirable for clinical application. Included in this paper are clinical observations of case selected from over 100 patients in current treatment with Chinese NiTi wires. Chinese NiTi wire reduced the leveling and alignment phase of treatment without discomfort to the patient. Chinese NiTi wire can be used in both children and adults.

China↗