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Biomedical subjects

W Hu

Publications and source records attributed to W Hu.

At least 181 records · Page 10Linked to original sources

The human glutamate receptor delta 2 gene (GRID2) maps to chromosome 4q22.

We isolated the human glutamate receptor delta 2 (GRID2) gene, which has 97.0% identity in amino acid sequence to the mouse glutamate receptor delta 2 (Grid2) gene. We subsequently mapped this gene to human chromosome 4q22 by radiation hybrid mapping and by hybridization to two overlapping human yeast artificial chromosomes that are located in 4q22. The Grid2 gene, which is mutated in lurcher (Lc) mice, maps to mouse chromosome 6. Thus, the mapping of the GRID2 gene to human chromosome 4q22 confirms and refines a region of synteny between mouse and human genomes.

Amino Acid Sequence↗

Experimental mucosal induction of uveitis with the 60-kDa heat shock protein-derived peptide 336-351.

Subcutaneous (s.c.) immunization of rats with the human 60-kDa heat shock protein (HSP)-derived peptide 336-351 induced clinical and/or histological uveitis in 80 % of rats. Subsequent experiments to prevent the development of uveitis by oral or nasal administration of the peptide have failed. Instead, uveitis was induced in 74.6 % of rats given the peptide orally (5 times), in 75 % given the peptide nasally (5 times) or 91.7 % of those administered the peptide by both routes (10 times). Histological examination showed that any one route of administration of the peptide elicited iridocyclitis in 42.2 % but loss of photoreceptors only in 4.9 % of rats. In contrast, sequential administrations of the peptide by a combined mucosal-s.c. route resulted in iridocyclitis in only 25 % but loss of photoreceptors in 40 % of animals. Examination of mRNA from CD4-enriched splenic cells by reverse transcription-PCR failed to yield significant differences in Th1 or Th2 cytokines. Treatment with monoclonal antibody (mAb) to CD4 yielded a dose-dependent decrease in uveitis from 82 % to 25 %. Similarly, treatment with IL-4 significantly decreased the development of uveitis from 68 % to 30.4 %. Conversely, treatment of the rats with mAb to CD8 greatly enhanced the onset of uveitis (from about 22 days in the controls to 11 days) and all the rats developed uveitis by day 24. Thus, CD4+ cells mediate, whereas CD8+ cells suppress the development of uveitis. We suggest that this novel experimental mucosal model of induction of uveitis by the human 60-kDa HSP-derived peptide 336-351, which is specific in stimulating T cell responses in Behcet's disease, is consistent with the oro-genital onset of this disease and the development of uveitis.

Administration, Intranasal↗

Determination of the peptide torsion angle phi by 15N chemical shift and 13Calpha-1Halpha dipolar tensor correlation in solid-state MAS NMR.

We demonstrate a dipolar-chemical shift correlation technique for sign-sensitive determination of the torsion angle phi in solid peptides and proteins under magic-angle spinning. The indirect dimension of the experiment is obtained by separate but synchronous evolution of the magnetization under the 15N chemical shift and the C-H dipolar coupling. The resulting sum and difference spectrum of the two frequencies, with more than ten independent sidebands, depends strongly on the relative orientation of the 15N chemical shift tensor and the Calpha-Halpha bond. This relative orientation reflects the C(O)i-1-N-Calpha-C(O)i torsion angle. The technique can distinguish phi angles over the full range of 360 degrees when the amide 15N chemical shift tensor does not possess reflection symmetry with respect to the peptide plane. Thus it complements our previous HNCH experiment, in which two mirror-symmetric conformers of the HN-N bond relative to the Calpha-Halpha bond around the N-Calpha axis cannot be distinguished.

Magnetic Resonance Spectroscopy↗

Hormone secretion by cell culture of human GH-PRL secreting pituitary adenomas: effects of bromocriptine.

Dopamine agonists effectively reduce the secretion of prolactin (PRL) in the great majority of prolactinomas and reduce the bulk of the adenomas, as well as have partial therapeutic effect on some patients with acromegaly. The inhibitory effect of bromocriptine (BC), a dopamine agonist, on growth hormone (GH) and PRL secretion of dispersed cells from the pituitary adenomas of 16 cases of acromegaly, which secret GH and PRL simultaneously, were evaluated in vitro. The significant inhibitory effects of BC on PRL secretion were found in 12 cases. It was also found that PRL secretion was strongly inhibited when GH was suppressed; on the contrary, when GH secretion was not suppressed, the production of PRL was not or weakly inhibited. The exact mechanism of the effects is unclear so far. It is necessary to investigate, at molecular level, the etiology of GH-PRL adenomas and its response to therapeutic agents.

Adenoma↗

Randomized, double-blind, placebo-controlled trial of oral enalapril in patients with neurally mediated syncope.

BACKGROUND: The purpose of this study was to study the effect of enalapril on neurally mediated syncope (NMS). Several agents (except for angiotensin-converting enzyme [ACE] inhibitors) have been used to treat patients with NMS. It is unknown whether ACE inhibitors have beneficial effects on NMS. METHODS AND RESULTS: Thirty subjects who had reproducible NMS induced with head-up tilt table test (HUT) were randomly assigned and divided in double-blind fashion into placebo and enalapril (an ACE inhibitor) groups. Hemodynamics and plasma catecholamine concentrations were studied. Before administration of enalapril, syncope induced by HUT was associated with vigorous hypotension and bradycardia. Plasma catecholamine concentrations were significantly elevated during NMS compared with the supine position before tilt. Oral enalapril rather than placebo produced a marked reduction in diastolic blood pressure during supine positioning before tilt. Administration of enalapril prevented HUT-induced NMS and increase of plasma catecholamine concentrations in all patients examined. Conversely, placebo had no effect in the majority of patients with NMS (12 of 15 subjects). Follow-up data showed that NMS disappeared in 14 (93%) of 15 patients treated with enalapril. CONCLUSIONS: This study demonstrates that ACE inhibitors may efficiently prevent NMS, presumably through inhibition of sympathetic system activation and peripheral hypotensive effect.

Administration, Oral↗

3D HCCH-COSY-TOCSY experiment for the assignment of ribose and amino acid side chains in 13C labeled RNA and protein.

A new 3D HCCH-COSY-TOCSY experiment is presented for the assignment of RNA sugar and protein side chains. The experiment, which combines COSY and TOCSY units, is more powerful than the sum of individual HCCH-COSY and HCCH-TOCSY pulse sequences. The experiment was applied to a 13C, 15N-labeled 26 mer RNA complexed with the antibiotic tobramycin, and a 12 kDa 13C, 15N-labeled FKBP12 protein sample. The power of HCCH-COSY-TOCSY is demonstrated through complete spin system assignments of sugars in the 26 mer RNA sample, which could not be assigned using a combination of HCCH-COSY, HCCH-TOCSY and 13C-edited NOESY experiments.

Amino Acids↗

Genetic diversity of Yunnan local pig breeds inferred from blood protein electrophoresis.

Protein electrophoresis was used to examine the blood protein polymorphism in Yunnan local pig breeds, i.e., the Saba pig, Dahe pig, and Diannan small-ear pig breeds. Of 38 genetic loci surveyed, 9 were found to be polymorphic. The percentage of polymorphic loci (P) varies from 0.1875 to 0.2121, and the mean individual heterozygosity (H) varies from 0.0712 to 0.1027 in three pig breeds. The results indicate that blood protein polymorphism in Yunnan pig breeds is high. Yunnan local pig breeds have a wealth of genetic diversity at the level of blood proteins.

Animals↗

Solution structure of P22 transcriptional antitermination N peptide-boxB RNA complex.

We have determined the solution structure of a 15-mer boxB RNA hairpin complexed with a 20-mer basic peptide of the N protein involved in bacteriophage P22 transcriptional antitermination. Complex formation involves adaptive binding with the N peptide adopting a bent alpha-helical conformation that packs tightly through hydrophobic and electrostatic interactions against the major groove face of the boxB RNA hairpin, orienting the open opposite face for potential interactions with host factors and/or RNA polymerase. Four nucleotides in the boxB RNA hairpin pentaloop form a stable GNRA like tetraloop structural scaffold on complex formation, allowing the looped out fifth nucleotide to make extensive hydrophobic contacts with the bound peptide. The guanidinium group of a key arginine is hydrogen-bonded to the guanine in a loop-closing sheared G.A mismatch and to adjacent backbone phosphates. The identified intermolecular contacts account for the consequences of N peptide and boxB RNA mutations on bacteriophage transcriptional antitermination.

Amino Acid Sequence↗

Mutual exclusivity of DNA binding and nuclear localization signal recognition by the yeast transcription factor GAL4: implications for nonviral DNA delivery.

A novel approach to nonviral DNA delivery is the use of combinations of DNA-binding proteins such as the yeast transcriptional activator GAL4 and plasmid DNA containing the specific binding sequence of the DNA-binding protein inserted within it, in addition to the gene of interest to be transferred into target cells. The amino terminal 147 amino acids of GAL4 contain a DNA-binding domain that has been shown to bind specifically to a 17 bp nucleotide recognition sequence, while the amino terminal 74 amino acids have been shown to be sufficient to target large heterologous proteins to the nucleus. Although it has been previously exploited as a gene transfer vehicle, the exact relationship between GAL4's DNA binding and nuclear targeting activities has not been investigated. Using gel mobility shift assays and ELISA-based binding assays, this study examines this issue directly, establishing the mutual exclusivity of the DNA-binding and nuclear targeting activities of GAL4. We demonstrate that GAL4(1-147) can specifically enhance transfection of plasmids containing the 17 bp recognition sequence. Interestingly, we found that the nuclear localization signal (NLS) of GAL4 is distinct from conventional NLSs, such as those of the SV40 large tumor antigen and bipartite NLSs, in that it is recognized exclusively by the nuclear pore targeting beta-subunit of the NLS-receptor importin complex, rather than the alpha-subunit. Specific binding to DNA was blocked by beta-subunit binding, while the converse was also true, making the GAL4-NLS novel in being regulated by DNA binding; this may play an important role in effecting release of GAL4 from the beta-subunit following transport through the nuclear pore. This study encompasses the first direct analysis of NLS recognition/accessibility in vehicles for nonviral DNA transfer, with the results having relevance to the use of GAL4 and comparable DNA-binding proteins in such vehicles.

Animals↗

IkappaB is a substrate for a selective pathway of lysosomal proteolysis.

In lysosomes isolated from rat liver and spleen, a percentage of the intracellular inhibitor of the nuclear factor kappa B (IkappaB) can be detected in the lysosomal matrix where it is rapidly degraded. Levels of IkappaB are significantly higher in a lysosomal subpopulation that is active in the direct uptake of specific cytosolic proteins. IkappaB is directly transported into isolated lysosomes in a process that requires binding of IkappaB to the heat shock protein of 73 kDa (hsc73), the cytosolic molecular chaperone involved in this pathway, and to the lysosomal glycoprotein of 96 kDa (lgp96), the receptor protein in the lysosomal membrane. Other substrates for this degradation pathway competitively inhibit IkappaB uptake by lysosomes. Ubiquitination and phosphorylation of IkappaB are not required for its targeting to lysosomes. The lysosomal degradation of IkappaB is activated under conditions of nutrient deprivation. Thus, the half-life of a long-lived pool of IkappaB is 4.4 d in serum-supplemented Chinese hamster ovary cells but only 0.9 d in serum-deprived Chinese hamster ovary cells. This increase in IkappaB degradation can be completely blocked by lysosomal inhibitors. In Chinese hamster ovary cells exhibiting an increased activity of the hsc73-mediated lysosomal degradation pathway due to overexpression of lamp2, the human form of lgp96, the degradation of IkappaB is increased. There are both short- and long-lived pools of IkappaB, and it is the long-lived pool that is subjected to the selective lysosomal degradation pathway. In the presence of antioxidants, the half-life of the long-lived pool of IkappaB is significantly increased. Thus, the production of intracellular reactive oxygen species during serum starvation may be one of the mechanisms mediating IkappaB degradation in lysosomes. This selective pathway of lysosomal degradation of IkappaB is physiologically important since prolonged serum deprivation results in an increase in the nuclear activity of nuclear factor kappa B. In addition, the response of nuclear factor kappa B to several stimuli increases when this lysosomal pathway of proteolysis is activated.

Animals↗

Interchromosomal recombination in Zea mays.

A new allele of the 27-kD zein locus in maize has been generated by interchromosomal recombination between chromosomes of two different inbred lines. A continuous patch of at least 11,817 bp of inbred W64A, containing the previously characterized Ra allele of the 27-kD zein gene, has been inserted into the genome of A188 by a single crossover. While both junction sequences are conserved, sequences of the two homologs between these junctions differ considerably. W64A contains the 7313-bp-long retrotransposon, Zeon-1. A188 contains a second copy of the 27-kD zein gene and a 2-kb repetitive element. Therefore, recombination results in a 7.3-kb insertion and a 14-kb deletion compared to the original S+A188 allele. If nonpairing sequences are looped out, 206 single base changes, frequently clustered, are present. The structure of this allele may explain how a recently discovered example of somatic recombination occurred in an A188/W64A hybrid. This would indicate that despite these sequence differences, pairing between these alleles could occur early during plant development. Therefore, such a somatically derived chimeric chromosome can also be heritable and give rise to new alleles.

Alleles↗

Early captopril treatment prevents hypertrophydependent gene expression in hearts of SHR.

Treatment of spontaneously hypertensive rats (SHR) with captopril (100 mg . kg-1 . day-1) throughout development and during the first 16 wk of life leads to a reduction in blood pressure and left ventricular hypertrophy. Blood pressures and hypertrophy are reduced in these animals (vs. untreated SHR) for up to 24 wk after discontinuation of the drug. We used conventional blot hybridization and Western analysis to examine hypertrophy-dependent gene expression during this period. Ventricular expression of the atrial natriuretic peptide gene was reduced by >90% at 16 wk of age in the captopril-treated SHR. Expression increased in the 24 wk after discontinuation of treatment, but remained well below that of the untreated SHR. A similar reduction in ventricular c-myc gene expression was seen with captopril treatment. Neither renal expression of the atrial natriuretic peptide gene nor ventricular expression of the c-fos gene was affected by captopril. This study demonstrates that captopril treatment during a critical period of development in the SHR leads to a sustained reduction in hypertrophy-dependent myocardial gene expression, which does not revert to levels seen in the untreated SHR after discontinuation of the drug.

Animals↗

[Neurolysis of the median nerve at the wrist with 2-portal endoscopic technique. Analysis of 102 consecutive cases].

Based on a retrospective clinical series, the authors evaluated the results of endoscopic nerve release according to Chow's technique, particularly in terms of the complications. The population consisted of 96 patients, corresponding to 102 hands, operated between January 1993 and January 1996. Paraesthesiae had completely resolved at 3 months in 87.2% of cases, while 29.7% of patients complained of discomfort in the hypothenar region. At last review, with a mean follow-up of 13.5 months, paraesthesiae had completely resolved in the same proportion of patients. 93.3% of patients with discomfort in the hypothenar region reported complete cure and 94 patients (92.2%) declared to be satisfied. Eighteen patients were operated on both sides. None of them preferred the conventional technique either in the short-term or in the long-term. One case of section of the superficial palmar arch, one case of severe reflex sympathetic dystrophy, one neurological complication (1%) in the form of dysaesthesia in the middle finger, persisting at last follow-up, one incomplete opening of the extensor retinaculum subsequently repaired via an open approach. Chow's technique presents certain advantages in terms of postoperative comfort, but the safety of this technique must be ensured by prevention of neurovascular complications, based on respect of 3 golden rules: thorough training in the technique, preferably in the anatomy laboratory, open conversion at the slightest doubt concerning visibility of the extensor retinaculum and compliance with the absolute contraindications of the technique.

Adult↗

[Association between ACE gene polymorphism and therapeutic responsiveness of ACEI in diabetic nephropathy].

OBJECTIVE: [corrected] To clarify the association between ACE gene polymorphism and therapeutic responsiveness of ACEI in diabetic nephropathy. METHOD: With the polymerase chain reaction technique, the angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism was studied in 31 NIDDM patients, 58 NIDDM patients with nephropathy, and 50 normal controls. RESULTS: There was no significant difference in the frequency of ACE genotypes among those NIDDM patients, NIDDM patients with nephropathy and nomal controls. Among 40 patients of DN group treated with ACE inhibitor(ACE-I), there was significant difference in genotype distribution between 19 efficacious cases and 21 nonefficacious cases: 8/2/9 vs 1/3/17 had DD/DI/II genotypes responsively (P < 0.01), DD genotype was best and II genotype was worst in therapeutic efficacy of ACE-I in NIDDM patients with nephropathy. CONCLUSION: The examination of ACE gene polymorphism is helpful for the diagnosis of the therapeutic efficacy of ACE-I in NIDDM with nephropathy.

Angiotensin-Converting Enzyme Inhibitors↗

[The application of frequency-domain harmonics-to-noise ratio in the acoustic analysis of the normal voice and the abnormal voice].

The frequency-domain relative harmonics-to-noise ratios were analysed in 36 normal women and 30 patients who had suffered from abnormal voice. The result indicated: the frequency-domain relative harmonics-to-noise ratios of the normal voice were distributed stably and the relative harmonics-to-noise ratios of the diseased voice differed obviously from that of the normal one above 1,700 Hz (P < 0.01). The frequency-domain relative harmonics-to-noise ratio was considered as a valuable parameter in distinguishing normal voice and diseased voice.

Adult↗

[Study on therapeutical effect of treating hepatolenticular degeneration by the HLD-Tablet I].

OBJECTIVE: To investigate the efficacy of HLD-Tablet I in treating hepatolenticular degeneration (HLD) and its effect on urinary trace element in 24 hours. METHODS: After 4 weeks of treatment on 34 cases of HLD by oral taken HLD-Tablet I, the clinical practice was closely observed on the patients' change of symptoms, signs and daily life pattern, and measured the level of urinary trace element in 24 hours before the therapy and after that every week. RESULTS: The total effective rate reached 70.59%, marked effective rate was 8.82%. The effect of treatment was better in the infantile and mild patient. After treatment, the daily output of urinary copper was obviously increased every week than that before (P < 0.01). It was highly negative linear correlated with the duration of treatment (r = -0.96, P < 0.05). But it was insignificantly different between any two weekly excretion of urinary copper per 24 hours after treatment by the HLD-Tablet I (P > 0.05), so its effect on urinary copper excretion was not decreased. CONCLUSION: The HLD-Tablet I could increase the output of urinary copper, hence it was effective in treating HLD without apparent toxic or side reaction.

Adolescent↗

[Effect of noise on human mental rotation performance].

To investigate the effect of moderate level low frequency noise on human mental rotation performance, letter rotation and compass orientation tests were performed in 24 healthy young male subjects during 2 h exposure to 85-95dB (A), it was found that during 120 min exposure to noise of 85dB (A), the mean reaction time increased (P<0.05), performance of reaction time and total performance decreased (P<0.01) significantly as compared with control in letter rotation test, meanwhile, performance of reaction time and total performance at 120 min exposure were significantly higher than that at 30 min (P<0.05). During 120 min exposure to noise of 95dB (A), the mean reaction time increased (P<0.01), the performance of reaction time and total performance decreased (P<0.01) significantly as compared with control in compass orientation test, meanwhile, performance of reaction time at 120 min were significantly higher than that at 30 min(P<0.05). The results show that exposures to 85 dB(A) and 95 dB(A) noise for 2 h have certain effect on the performance of human mental rotation and may affect performance of complex tasks with a higher workload.

Adolescent↗