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Biomedical subjects

X M Jiang

Publications and source records attributed to X M Jiang.

33 records · Page 2Linked to original sources

Pretranslational down regulation of cytochrome P450 2C11 in vitamin A-deficient male rat liver: prevention by dietary inclusion of retinoic acid.

Manipulation of vitamin A intake has been associated with altered rates of cytochrome P450 (P450)-mediated microsomal drug oxidation. Dietary vitamin A deficiency reportedly results in decreased rates of P450-dependent substrate oxidation, but the mechanisms underlying these changes remain unclear. In this study, the effects of dietary vitamin A modulation, as well as dietary inclusion of all-trans-retinoic acid (ATRA), on major constitutive P450s were defined. Total microsomal P450 in deficient male rats was decreased to 72% of control (0.63 +/- 0.07 vs. 0.88 +/- 0.08 nmol/mg of protein; P < .05); this was prevented by inclusion of ATRA (12 micrograms/g) in the deficient diet. Dietary vitamin A deficiency decreased rates of P450 2C11-mediated testosterone 2 alpha- and 16 alpha-hydroxylation in rat liver to 44 and 47% of respective adequate control, whereas rates of 6 beta- and 7 alpha-hydroxylation of the steroid were unaltered; inclusion of ATRA into the deficient diet prevented the loss of 2C11 activities. Immunoblot and RNA analysis revealed decreases in P450 2C11 apoprotein and its corresponding mRNA in liver from deficient rats that was prevented by inclusion of ATRA in the deficient diet. Serum testosterone concentrations were reduced in deficient rats and this also was prevented by dietary ATRA. To discern whether this was a direct effect of vitamin A on P450 2C11 regulation, further experiments evaluated the effect of ATRA administration to male rats maintained on standard rat chow (vitamin A-adequate). Dose- and time-dependent decreases in P450 2C11 activity were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Timing of vulnerability of the brain to iodine deficiency in endemic cretinism.

BACKGROUND: Endemic cretinism, caused by severe iodine deficiency during pregnancy, is the world's most common preventable cause of mental retardation. It can be prevented by iodine treatment before conception, but whether it can be prevented or ameliorated by treatment during pregnancy or after delivery is not known. METHODS: In a severely iodine-deficient area of the Xinjiang region of China, we systematically administered iodine to groups of children from birth to three years of age (n = 689) and women at each trimester of pregnancy (n = 295); we then followed the treated children and the babies born to the treated women for two years. We used three independent measures of neural development: the results of the neurologic examination, the head circumference (which correlates with brain weight in the first postnatal year), and indexes of cognitive and motor development. Untreated children one to three years of age, who were studied when first seen, served as control subjects. RESULTS: The prevalence of moderate or severe neurologic abnormalities among the 120 infants whose mothers received iodine in the first or second trimester was 2 percent, as compared with 9 percent among the 752 infants who received iodine during the third trimester (through the treatment of their mothers) or after birth (P = 0.008). The prevalence of microcephaly (defined as a head circumference more than 3 SD below U.S. norms) decreased from 27 percent in the untreated children to 11 percent in the treated children (P = 0.006), and the mean (+/- SD) developmental quotient at two years of age increased (90 +/- 14, vs. 75 +/- 18 in the untreated children; P < 0.001). Treatment in the third trimester of pregnancy or after delivery did not improve neurologic status, but head growth and developmental quotients improved slightly. Treatment during the first trimester, which was technically problematic, improved the neurologic outcome. CONCLUSIONS: Up to the end of the second trimester, iodine treatment protects the fetal brain from the effects of iodine deficiency. Treatment later in pregnancy or after delivery may improve brain growth and developmental achievement slightly, but it does not improve neurologic status.

Brain↗

Pretranslational down-regulation of male specific hepatic P450s after portal bypass.

Diversion of portal blood away from the liver in the portal vein ligated (PVL) male rat results in dysfunction of the hypothalamo-pituitary-gonadal axis, as reflected by an increase in circulating oestradiol, a decrease in serum testosterone and decreased expression of the male-specific cytochrome P450 2C11 in hepatic microsomes. The present study assessed whether there was a decline in the hepatic concentrations of mRNA species corresponding to male-specific P450s and whether female-specific hepatic enzymes may be upregulated after PVL. In microsomes from PVL male rat liver the activities of P450s 2C11 and 3A2 (androstenedione 16 alpha- and 6 beta-hydroxylation, respectively) were decreased to 45% (P < 0.001) and 43% (P < 0.002) of control. Slot blotting revealed a decline in the mRNAs for P450 2C11 and 3A2 to 46 +/- 7 and 27 +/- 4% of respective control (relative to beta-actin mRNA). In contrast, mRNAs for the female specific P450 2C12 and delta 4-ketosteroid-5 alpha-oxidoreductase were unchanged from control (100 +/- 13% and 122 +/- 28%, respectively). P450 2C12 protein was not detected in either control or PVL male rat liver but a slight increase in the rate of 5 alpha-dihydrotestosterone formation was noted after PVL (2.95 +/- 0.40 vs 1.00 +/- 0.22 nmol/min/mg protein, P < 0.05; corresponding, respectively, to 30 and 10% of the activity in female liver microsomes). These studies indicate that the male-specific P450 2C11 and 3A2 are down-regulated at a pretranslational level whereas upregulation of the female-specific enzymes P450 2C12 and delta 4-ketosteroid-5 alpha-oxidoreductase does not occur after PVL. Thus, the endocrine effects of portal bypass result in biochemical demasculinization, but not feminization, of hepatic enzymes involved in steroid biotransformation. Because male-specific P450s are effective steroid hydroxylating enzymes, their down regulation after PVL would significantly decrease hepatic androgen extraction.

Androstenedione↗

Iodination of irrigation water as a method of supplying iodine to a severely iodine-deficient population in Xinjiang, China.

Severe iodine deficiency still occurs in many countries, and causes cretinism and mental impairment. In southern Xinjiang province, China, after usual methods of iodine supplementation had failed, we iodinated irrigation water to increase iodine in soil, crops, animals, and human beings. 5% potassium iodate solution, dripped into an irrigation canal for 12 or 24 days, increased soil iodine 3-fold, and crop and animal iodine 2-fold. Median urinary iodine excretion in children increased from 18 to 49 micrograms/L (two groups of similar age). The cost for iodine was US $0.05 per person per year. Soil iodine remained stable over one winter, and dripping of iodine during the second year (US $0.12 per person per year) resulted in a further 4-fold increase in soil iodine and a 1.8-fold increase in iodine in crops. We conclude that iodination of irrigation water is an advantageous and cost-effective method of supplying iodine in southern Xinjiang, and may be useful in other areas dependent on irrigation.

Agriculture↗

Detection of human papillomavirus type 16 E6/E7 transcripts in histologically cancer-free pelvic lymph nodes of patients with cervical carcinoma.

Human papillomavirus (HPV) 16 E6/E7 mRNAs have been detected in paraffin-embedded sections of histologically cancer-free pelvic lymph nodes from four of six patients with HPV 16-associated cervical cancer. The cDNA obtained from the viral mRNA by reverse transcription was amplified by the polymerase chain reaction (PCR). Transcripts were present in a small but significant proportion (6/42, 14%) of the histologically negative/HPV 16 DNA-positive lymph node blocks; but neither HPV 16 DNA nor transcripts were found in 12 lymph node blocks from two patients whose cervical cancers were not HPV-related. Both of the HPV 16 mRNAs detectable by the PCR primers used in the assay (the E6*I and the full-length E6 transcript) were found in the primary tumors, but the transcription patterns in the lymph nodes were variable. The presence of HPV E6/E7 mRNAs in lymph nodes of patients with HPV-related cancer may be a more sensitive indicator of metastasis than conventional histology. In addition, their detections is likely to be more significant than that of HPV DNA sequences alone. The practical significance of the findings, however, awaits correlation with the ultimate clinical outcome.

Adult↗

Characterization of binding sites of a memory-enhancing peptide AVP(4-8) in rat cortical synaptosomal membranes.

The pentapeptide pGlu-Asn-Cyt-Pro-Arg [AVP(4-8), termed ZNC(C)PR in this article] has been found as a metabolite of arginine-vasopressin (AVP) in rat brain and has been shown to have potent memory-enhancing activity and to yield a series of biochemical events in brain tissues. [35S]ZNC(C)PR was chemically synthesized with high specific activity (232 Ci/mmol), and specific binding sites for ZNC(C)PR were located in synaptosomal membrane preparations of rat brain. We identified a specific binding site for ZNC(C)PR with a Kd of 3.12 nM and Bmax of 31 fmol/mg protein in anterior cortical synaptosomal membranes in the presence of 5 mM Ni2+. A comparison of synthetic analogues of ZNC(C)PR competing with [35S]ZNC(C)PR for binding to anterior cortical receptor are presented. ZDC(C)PR, a 2-aspartyl substitute of the 2-asparaginyl residue in ZNC(C)PR, had the most potent competition, but AVP did not show significant ability to compete for the receptor with ZNC(C)PR.

Amino Acid Sequence↗

Clinical and pathological studies on peripheral neuropathy of six Chinese patients with lung cancer: morphometric evaluation of the sural nerve on biopsy.

We attempted to elucidate the nature of the nerve fiber degeneration and clinical features of six Chinese patients with lung cancer preceded by sensory disturbances, with special emphasis put on the morphometric analysis of the nerve fibers of the sural nerve obtained on biopsy. The patients were all male and ranged from thirty-nine to sixty-seven years of age on admission. They all complained of paresthesia as the initial symptom in the distal portion of both extremities, two to seventy-two months prior to the diagnosis of the cancer. The paresthesia was slowly progressive and mild to moderate in severity without obvious subjective sensory loss. Four patients showed diminished Achilles reflex and decreased vibration sensation at the lateral malleolus. Morphometric evaluation of the sural nerve revealed that the loss of myelinated and unmyelinated fibers was not frequent and the increase in the density of the small myelinated fibers was prominent, suggesting the presence of axonal atrophy. Therefore, it was concluded that the histologic findings of our patients are different from those found in subacute carcinomatous sensory neuropathy associated with lung cancer that is well established clinically and histologically, and are compatible with those of axonal atrophy, partly related to unknown remote effects of cancer.

Adult↗

Detection of human papillomavirus type 16 E6/E7 transcripts in fixed paraffin-embedded cervical cancers by the polymerase chain reaction.

A simple, and sensitive method for the detection of human papillomavirus (HPV) 16 E6/E7 transcripts in RNA purified from formalin acetic alcohol (FAA)-fixed, paraffin embedded cervical cancer (CaCx) tissue is described. The entire procedure, including polymerase chain reaction (PCR) amplification of cDNA obtained from mRNA by reverse transcription, can be completed within a day. The results obtained compare favourably with those using total nucleic acids extracted from the same fixed material, and are consistent with results using RNA purified from corresponding fresh tumour tissue. Although developed for investigating the expression of HPV in tumours, this method should find general application in studies of gene expression and viral detection.

DNA, Single-Stranded↗

Structure and sequence of the rfb (O antigen) gene cluster of Salmonella serovar typhimurium (strain LT2).

The rfb gene cluster of Salmonella LT2 has been cloned and sequenced. The genes rfbA, rfbB, rfbD, rfbF, rfbG, rfbK, rfbM and rfbP were located individually and the gene rfbL was located outside the cluster. Approximately 16 open reading frames were found in the region which is essential for the expression of O antigen. The gene products of rfbB and rfbG were found to have homology with the group of dehydrogenase and related enzymes described previously. Analysis of the G + C ratio of the rfb cluster extended the area of low-G + C composition previously found in the sequence of rfbJ to the whole rfb gene cluster. Three to five segments with discrete G + C contents and codon adaptation indices are present in the rfb region, indicating a heterogeneous origin of these segments. Potential promoters were found near the start of the rfb region, supporting the possibility that the rfb gene cluster is an operon.

Amino Acid Sequence↗

The use of a drug resistance cartridge for in vitro insertion and deletion mutagenesis of a cosmid clone.

A drug-resistant cartridge was employed in the construction of families of insertion mutants of a cosmid clone. The cartridge contains a cml gene and has identical restriction enzyme sites, EcoRI, BamHI, SalI, and PstI, on both ends. The families of mutants were made by ligation of the cartridge to the cosmid, which was linearized or partially digested, followed by in vitro packaging and transduction. From these families we selected cosmid derivatives which either have a unique BamHI site at a predetermined site in the cosmid or have deletions covering different portions of the original clone. The extent of a large gene cluster cloned into the original cosmid was identified by confirming the gene function in some of the deletion mutants. The possibility for further and various uses of this cartridge is discussed.

Chromosome Deletion↗

[A clinical, histochemical and ultrastructural study of mitochondrial myopathy].

Among 189 consecutive cases with neuromyopathies, abnormalities of mitochondria in the muscles were seen in 5 cases. Ragged rad fibers (Rrf) were found with muscle biopsy with the use of staining of Gomory Trichrome. The ultrastructural abnormalities as revealed under the electron microscope in the mitochondria were as follows: 1. the mitochondria contained a lot of paracrystalline inclusion; 2. they were composed of lamellae; and 3., the mitochondria also showed dense spherical inclusions with abundant glycogen-rich sarcoplasm. The clinical manifestations of these patients consisted of: 1. muscular atrophy of various degrees. 2. muscular weakness of the proximal parts of the limbs, and 3. ptosis and ophthalmoplegia (in three cases). Three of the patients were treated with coenzyme Q10 with improvement of some of the symptoms and signs.

Adult↗

A low copy number cosmid.

A low copy number cosmid was constructed by subcloning the pair of cos sites and the kanamycin resistance gene of pcos2EMBL into pGB2. The resulting cosmid, pPR691, has the pSC101 replicon and specifies resistance to kanamycin, spectinomycin, and streptomycin. pPR691 also carries restriction sites suitable for cloning partial Sau3A digests using the strategy of Bates and Swift (P. F. Bates and R. A. Swift, 1983, Gene 26, 137-146). A library of Salmonella typhimurium chromosomal DNA was made using this cosmid and the rfb gene cluster (map position 42) was isolated from this library.

Cloning, Molecular↗

Dynamics of environmental supplementation of iodine: four years' experience of iodination of irrigation water in Hotien, Xinjiang, China.

Hotien prefecture, Xinjiang Province, China, in the Taklamakan Desert, is an area of severe iodine deficiency. Because usual methods of iodine supplementation failed here, we began supplementation in 1992 with potassium iodate, which was added to irrigation water (Lancet 1994; 334:107-110). We report 4 y experience with this method in 3 townships that contained a total treated population of 37,000. Potassium iodate was dripped into irrigation water (to a concentration 10-80 microg/l) during a 2- to 4-wk period. During the 3 y that followed, no further supplementation was made, and iodine concentrations increased several fold in crops and plants, sheep and chicken thyroid glands, and meat and in urine of children 2-6 y of age and of women who were of childbearing age. Infant mortality decreased 50%, and sheep production increased 43%. Iodine repletion of soil through irrigation water is an effective and cost-efficient way of providing iodine in appropriate situations.

Adolescent↗