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Biomedical subjects

J Zhou

Publications and source records attributed to J Zhou.

At least 433 records · Page 24Linked to original sources
PubMed1999

Papillomavirus capsid protein expression level depends on the match between codon usage and tRNA availability.

Translation of mRNA encoding the L1 and L2 capsid proteins of papillomavirus (PV) is restricted in vivo to differentiated epithelial cells, although transcription of the L1 and L2 late genes occurs more widely. The codon composition of PV late genes is quite different from that of most mammalian genes. To test the possibility that PV late gene codon composition determines the efficiency of PV late gene expression in some cell types, synthetic bovine papillomavirus type 1 (BPV1) late genes were constructed with codon composition modified to resemble the typical mammalian gene. Expression of these genes from a strong promoter in Cos-1 cells was compared with expression of wild-type BPV1 late genes from the same promoter. Both unmodified and modified PV late genes were transcribed in Cos-1 cells, but only the codon-modified genes were translated. In vitro translation of wild-type but not synthetic BPV1 L1 mRNA was markedly enhanced by addition of aminoacyl-tRNAs. Codon composition thus limits BPV1 late gene translation in Cos-1 cells, and this limitation can be overcome by modification of the codon composition of the genes or by provision of excess tRNA. Replacement of codons in the green fluorescent protein (gfp) gene with those frequently used in PV late genes did not alter gfp transcription in Cos-1 cells but almost abolished translation, supporting the hypothesis that the observed differences in efficiency of translation of modified and unmodified PV capsid genes were related to codon usage rather than mRNA structure. As tRNA populations vary within and between tissues in the same eukaryotic organism, we speculate that matching of tRNA availability to codon usage may be one determinant of the restriction of expression of PV late genes to differentiated epithelium.

Amino Acid Sequence↗
PubMed1999

Inhibition of tumor necrosis factor alpha by an adenovirus-encoded soluble fusion protein extends transgene expression in the liver and lung.

The cellular and humoral immune responses to adenovirus (Ad) remain a major barrier to Ad-mediated gene therapy. We recently reported that mice deficient in tumor necrosis factor alpha (TNF-alpha) or Fas (APO-1, CD95) have prolonged expression of an Ad transgene expressing a foreign protein in the liver. To determine whether blockade of TNF-alpha or Fas would have the same effect in normal mice, we created transgenes that expressed soluble murine CD8 or CD8 fused to the extracellular regions of TNF receptor 1 (TNFR) or Fas and inserted into the left-end region of first-generation (E1/E3-) Ad vectors. Consistent with the results observed in TNF-deficient mice, expression of the TNFR-CD8 fusion protein was prolonged in vivo compared to that of control proteins. Not only did expression of TNFR-CD8 persist in the liver and the lung, but when coadministered with another first-generation vector, the protein provided "transprotection" for the companion vector and transgene. In addition, TNFR-CD8 attenuated the humoral immune response to the Ad. Together, these findings demonstrate that blockade of TNF-alpha is likely to be useful in extending the expression of an Ad-encoded transgene in a gene therapy application.

Adenoviridae↗
PubMed1999

Sustained effects of repeated restraint stress on muscle and adipocyte metabolism in high-fat-fed rats.

Repeated restraint stress 3 h/day for 3 days in rats causes a temporary hypophagia but a sustained weight loss. We investigated whether poststress changes in peripheral tissue metabolism contributed to these responses. One day after the last restraint, insulin sensitivity, measured by oral glucose tolerance test, was improved in restrained rats. Restraint and pair-fed rats weighed less than controls, but body fat content was the same in all groups. Muscle glucose uptake, measured in vitro, was not changed by treatment, whereas in vitro adipocyte glucose uptake was substantially inhibited only in restrained rats. Adipocytes from restrained rats had elevated rates of fatty acid oxidation but not fatty acid esterification, indicating a shift in energy supply from glucose to fatty acids. Five days after the last restraint, the reduced weight of restrained and pair-fed rats resulted from loss of both lean and fat tissue. These results demonstrate that restraint caused sustained, tissue-specific changes in metabolism that may contribute to changes in body composition and body weight of the rats.

Adipose Tissue↗
PubMed1999

Does beta(3)-adrenoreceptor blockade attenuate acute exercise-induced reductions in leptin mRNA?

We investigated the effect of a single bout of exercise on leptin mRNA levels in rat white adipose tissue. Male Sprague-Dawley rats were randomly assigned to an exercise or control group. Acute exercise was performed on a rodent treadmill and was carried out to exhaustion, lasting an average of 85.5 +/- 1.5 min. At the end of exercise, soleus muscle and liver glycogen were reduced by 88% (P < 0.001). Acutely exercised animals had lower (P < 0.05) leptin mRNA levels in retroperitoneal but not epididymal fat, and this was independent of fat pad weight. To test the hypothesis that beta(3)-adrenergic-receptor stimulation was involved in the downregulation of leptin mRNA in retroperitoneal fat, a second experiment was performed in which rats were randomized into one of four groups: control, control + beta(3)-antagonist, exercise, and exercise + beta(3)-antagonist. A highly selective beta(3)-antagonist (SR-59230A) or vehicle was given by gavage 30 min before exercise or control experiment. Exercise consisted of 55 min of treadmill running, sufficient to reduce liver and muscle glycogen by 70 and 80%, respectively (both P < 0.0001). Again, acute exercise reduced leptin mRNA in retroperitoneal fat (exercise vs. control; P < 0.05), but beta(3)-antagonism blocked this effect (exercise + beta(3)-antagonist vs. control + beta(3)-antagonist; P = 0.42). Unexpectedly, exercise increased serum leptin. This would be consistent with the idea that there are releasable, preformed pools of leptin within adipocytes. We conclude that beta(3)-receptor stimulation is a mechanism by which acute exercise downregulates retroperitoneal adipose tissue leptin mRNA in vivo.

Adipose Tissue↗
PubMed1999

Evidence for genetic heterogeneity in benign familial hematuria.

Benign familial hematuria (BFH: MIM141200) is an autosomal-dominant disease accounting for one-fifth of all hematuria of unknown cause in children. Previous observations suggest that BFH may be allelic to recessive Alport syndrome (AS: MIM 203780) with a mutation in the COL4A3/COL4A4 locus. However, it is not clear whether all cases of BFH are due to heterozygous mutation of COL4A3/COL4A4 genes. We report here the exclusion of linkage between BFH and COL4A3/COL4A4 loci at 2q35-37 in a restricted population from Sicily (Italy). Total lod score is -9.6 at theta 0. Furthermore, in some cases exclusion of linkage is evident even considering single families. We conclude that BFH is genetically heterogeneous.

Adult↗
PubMed1999

Role of C/A polymorphism at -20 on the expression of human angiotensinogen gene.

-Angiotensinogen is the glycoprotein precursor of 1 of the most potent vasoactive hormones, angiotensin II. Human angiotensinogen gene contains a C/A polymorphism at -20 located between the TATA box and transcriptional initiation site. We show here that when nucleoside A is present at -20, this sequence binds to the estrogen receptor. We also show that transcriptional activity of reporter constructs containing human angiotensinogen gene promoter with nucleoside A at -20 is increased on cotransfection of an expression vector containing human estrogen receptor-alpha coding sequence in human hepatoma cells (HepG2) followed by estrogen treatment. On the other hand, adenoviral major late transcription factor binds preferentially to this region of the promoter when nucleoside C is present at -20. We also show that reporter constructs containing human angiotensinogen gene promoter with nucleoside C at -20 have increased basal promoter activity on transient transfection in HepG2 cells as compared with reporter constructs with nucleoside A at -20. Our data suggest that C/A polymorphism at -20 may modulate the expression of human angiotensinogen gene in a sex-specific manner.

Adenoviridae↗
PubMed1999

Spectrum of activity of lamotrigine in treatment-refractory bipolar disorder.

OBJECTIVE: New mood stabilizers are needed that possess efficacy for all phases of bipolar disorder. This study was designed to provide preliminary evidence for the safety and efficacy of a new anticonvulsant, lamotrigine, in adult patients with bipolar disorder who had been inadequately responsive to or intolerant of prior pharmacotherapy. METHOD: A 48-week, open-label, prospective trial was conducted in 75 patients with bipolar I or bipolar II disorder. Lamotrigine was used as adjunctive therapy (N = 60) or monotherapy (N = 15) in patients presenting in depressed, hypomanic, manic, or mixed states. RESULTS: Of the 40 depressed patients included in the efficacy analysis, 48% exhibited a marked response and 20% a moderate response as measured by reductions in 17-item Hamilton Depression Rating Scale scores. Of the 31 with a hypomanic, manic, or mixed state, 81% displayed a marked response and 3% a moderate response on the Mania Rating Scale. From baseline to endpoint, the depressed patients exhibited a 42% decrease in Hamilton depression scale scores, and the patients presenting with hypomania, mania, or a mixed state exhibited a 74% decrease in Mania Rating Scale scores. The most common drug-related adverse events were dizziness, tremor, somnolence, headache, nausea, and rash. Rash was the most common adverse event resulting in drug discontinuation (9% of patients); one patient developed a serious rash and required hospitalization. CONCLUSIONS: These open-label data provide preliminary evidence that lamotrigine may be an effective treatment option for patients with refractory bipolar disorder; however, potential benefits must be weighed against potential side effects, including rash.

Adult↗
PubMed1999

Glucagon-like peptide-1 regulates the beta cell transcription factor, PDX-1, in insulinoma cells.

Glucagon-like peptide-1 (GLP-1) enhances insulin biosynthesis and secretion as well as transcription of the insulin, GLUT2 and glucokinase genes. The latter are also regulated by the PDX-1 homeoprotein. We investigated the possibility that GLP-1 may be having its long-term pleiotropic effects through a hitherto unknown regulation of PDX-1. We found that PDX-1 mRNA level was significantly increased (p<0.01) after 2 hours and insulin mRNA level was subsequently increased (p<0.01) after 3 hours of treatment with GLP-1 (10 nM) in RIN 1046-38 insulinoma cells. Under these experimental conditions, there was also a 1.6-fold increase in the expression of PDX-1 protein in whole cell and nuclear extracts. Overexpression of PDX-1 in these cells confirmed the finding of the wild type cells such that GLP-1 induced a 2-fold increase in whole cell extracts and a 3-fold increase in nuclear extracts of PDX-1 protein levels. The results of electrophoretic mobility shift experiments showed that PDX-1 protein binding to the Al element of the rat insulin II promoter was also increased 2 h post treatment with GLP-1. In summary, we have uncovered a previously unknown aspect to the regulation of PDX-1 in beta cells. This has important implications in the physiology of adult beta cells and the treatment of type 2 diabetes mellitus with GLP-1 or its analogs.

Animals↗
PubMed1999

Effects of Igf1 gene deletion on postnatal growth patterns.

This study documents the temporal and organ-specific effects of Igf1 gene deletion on postnatal growth patterns. Igf1-/- mice are 63+/-4% the size of wildtype (wt) littermates at birth and this ratio persists through postnatal day 20 (P20). After P20, Igf1-/- mice virtually stop growing, while wt littermates double in size from P20 to P40, after which their growth markedly decelerates. As a result, 'full-grown' Igf1-/- mice are less than one third the size of wt littermates. Igf1 gene deletion has disproportionate effects on organ growth. For example, at P10 and P40, Igf1-/- body weights are 63% and 31% of wt, respectively, while Igf1-/- lungs weigh only 34% and 22% of wt at these ages. In contrast, the Igf1-/- heart is disproportionately enlarged, representing approximately 85% of wt at P10 and approximately 56% at P40. Igf1-/- kidney, spleen and liver are slightly but significantly increased in size relative to the degree of reduction in Igf1-/- body weight. These data demonstrate that Igf1 has two major phases or modes of growth promotion. There is an early, growth hormone (GH)-independent Igf1 growth augmentation during perinatal development, responsible for about 35% of growth prior to P20. Then there are later effects due to GH-induced Igf1, which are responsible for increasing animal size by approximately 100% between P20 and 40. The fact that there is virtually no GH-induced growth in the Igf1-/- mice supports the view that Igf1 mediates GH's major effects on somatic growth. Finally, this study shows that Igf1 has discordant effects on pulmonary and cardiac growth parameters, with relative hypoplasia of Igf1-/- lungs and hypertrophy of Igf1-/- hearts.

Aging↗
PubMed1999

Androgen and follicle-stimulating hormone interactions in primate ovarian follicle development.

We have previously shown that androgens stimulate early stages of follicular development and that granulosal androgen receptor (AR) gene expression is positively correlated with follicular growth. The present study was aimed at elucidating potential interactions between FSH and androgens in follicular development. Study groups included eight normal cycling rhesus monkeys (five follicular and three luteal-phase), eight testosterone (T)-treated, and four FSH-treated animals. Examination of sequential ovary sections revealed selective colocalization of AR and FSH receptor (FSHR) messenger RNAs (mRNAs) in healthy, growing follicles. Moreover, individual follicles demonstrate a highly significant (P < 0.001) positive correlation between FSHR and AR mRNA levels in all study groups. Androgen treatment significantly increased granulosa cell FSHR mRNA abundance (by approximately 50-100%, depending on follicle size). FSH treatment increased granulosa AR mRNA levels only in primary follicles. The finding that T augments follicular FSHR expression suggests that androgens promote follicular growth and estrogen biosynthesis indirectly, by amplifying FSH effect, and may partially explain the enhanced responsiveness to gonadotropin stimulation noted in women with polycystic ovary syndrome.

Androgens↗
PubMed1999

Characterization of the transvection mediating region of the abdominal-B locus in Drosophila.

Genetic studies have identified an unusual transvection process in the Abdominal-B (Abd-B) locus of Drosophila. In some cases distal infraabdominal (iab) regulatory domains continue to activate the Abd-B promoter even when translocated onto different chromosomes. Transvection depends on an approx. 10 kb genomic DNA sequence, termed the transvection mediating region (tmr), located immediately downstream of the Abd-B transcription unit. Here we report a detailed analysis of this region. Different DNA fragments from the tmr were inserted into a variety of P-transformation vectors. Analyses of reporter gene expression in transgenic embryos and adults identify at least three cis-regulatory elements, including two enhancers (IAB7 and IAB8) and a new insulator DNA (Frontabdominal-8, Fab-8). Evidence is also presented for a Polycomb Response Element (PRE) linked to the IAB8 enhancer, and an internal promoter in the iab-8 domain, which transcribes the iab-7 and iab-8 cis-regulatory DNA, including the Fab-8 insulator. We discuss the significance of these findings with regard to Abd-B transvection and long-range enhancer-promoter interactions in mammalian globin loci.

ATP-Binding Cassette Transporters↗
PubMed1999

Glucagon-like peptide 1 and exendin-4 convert pancreatic AR42J cells into glucagon- and insulin-producing cells.

In this article, we show that glucagon-like peptide 1 (GLP-1) can induce AR42J cells to differentiate into insulin, pancreatic polypeptide, and glucagon-positive cells. In their natural state, these cells, which are derived from a chemically induced pancreatic tumor, possess exocrine and neuroendocrine properties but are negative for islet hormones and their mRNAs. We found that when these cells were exposed to GLP-1 (1 or 10 nmol), a peptide normally released from the gut in response to food and a modulator of insulin release, intracellular cAMP levels were increased, and proliferation of cells was increased for the first 24 h, followed by inhibition. Up to 50% of the cells became positive for islet hormones. The mRNAs for glucose transporter 2 and glucokinase were detected in the GLP-1-treated cells. Insulin was detected by radioimmunoassay (RIA) in the medium of GLP-1-treated cells, and the cells were capable of releasing insulin in a glucose-mediated fashion. Exendin-4, an analog of GLP-1, in some critical experiments performed in a similar manner to GLP-1, with the exception of it being 10-fold more potent. We therefore propose that GLP-1 and exendin-4 are capable of causing pancreatic precursor cells to differentiate into islet cells.

Adenylyl Cyclases↗
PubMed1999

BHRF1 antisense oligonucleotide inhibits anti-apoptosis of nasopharyngeal carcinoma cells.

Epstein-Barr virus gene BHRF1 has homology with proto-oncogene bcl-2, which can protect cells from apoptosis, thus, it may play important roles in oncogenesis and affect treatment of EBV-related cancers. We used BHRF1 antisense oligonucleotide to block its expression in nasopharyngeal carcinoma cell line, CNE2. The results showed that after blocking by BHRF1 antisense oligonucleotide, CNE2 cells had higher S-phase cell percentage, more susceptibility to radiation with weaker ability of proliferation, colony forming efficiency and tumor development in nude mice after radiation. Our results suggest that BHRF1 antisense oligonucleotide could inhibit BHRF1 anti-apoptotic ability, and may contribute to the treatment of EBV-related cancers.

Animals↗
PubMed1999

Plaque pathology and coronary thrombosis in the pathogenesis of acute coronary syndromes.

Coronary atherosclerosis is by far the most frequent cause of ischemic heart disease and plaque disruption with superimposed thrombosis is the main cause of the acute coronary syndromes of unstable angina, myocardial infarction, and sudden coronary death. Therefore, for event-free survival, the vital question is not why atherosclerosis develops but rather why, after years of indolent growth, it suddenly becomes complicated by life-threatening thrombosis. Therefore, we have to focus on plaque composition and vulnerability to rupture and plaque thrombogenicity rather than on plaque size and stenosis severity. The risk for plaque disruption depends more on plaque vulnerability (plaque type) than on degree of stenosis (plaque size). Lipid-rich and soft plaques are more vulnerable and prone to rupture than collagen-rich and hard plaques. They are also highly thrombogenic after disruption because of high content of tissue factor. There seems to be three major determinants of a plaque's vulnerability to rupture: 1) the size and consistency of the lipid-rich atheromatous core, 2) the thickness of the fibrous cap covering the core, and 3) ongoing inflammation and repair processes within the fibrous cap. Lipid accumulation, cap thinning, lack of smooth muscle cells (smc), and macrophage-related inflammation destabilize plaques, making them vulnerable to rupture. In contrast, smc-related healing and repair processes stabilize plaques, protecting them against disruption. Plaque size or stenosis severity tell nothing about a plaque's vulnerability. Many vulnerable plaques are invisible angiographically due to their small size and compensatory vascular remodeling.

Acute Disease↗
PubMed1999

[Identification of mutations in the human EXT1 and EXT2 genes].

OBJECTIVE: To investigate further the genetic basis of hereditary multiple exostoses (EXT) and provide useful information for gene diagnosis of the disease. METHODS: Polymerase chain reaction-single strand conformation polymorphism was used to examine the entire coding regions of EXT(1) gene on chromosome 8 and EXT(2) gene on chromosome 11 for mutation in thirty EXT families. Mutations were further identified by sequencing. RESULTS: Two frameshift mutations were identified in two unrelated EXT families. One was the deletion of one base(T) in exon 6 of the EXT(1) gene, and the other was the deletion of four bases (tgtt) in exon 2 of the EXT(2) gene. Both of the mutations resulted in a frameshift and premature termination of translation. CONCLUSION: EXT is a genetically heterogeneous bone disorder caused by the mutation of EXT tumor suppressor gene. These results could be directly applied in the genetic counseling and prenatal genetic diagnosis of EXT.

Chromosome Deletion↗