Biomedical subjects

W Wu

Publications and source records attributed to W Wu.

At least 235 records · Page 13Linked to original sources

PubMed1998

X-linked retinitis pigmentosa in two families with a missense mutation in the RPGR gene and putative change of glycine to valine at codon 60.

OBJECTIVE: This study describes the ophthalmic findings in two unrelated white families with X-linked retinitis pigmentosa (XLRP) caused by a missense mutation in the retinitis pigmentosa GTPase regulator (RPGR) gene. DESIGN: Genetic screening and clinical correlation. PARTICIPANTS: Thirty-six families with XLRP seen by the authors were screened for a possible mutation in the RPGR gene to identify three affected hemizygotes with retinitis pigmentosa and four heterozygote carriers in one family and one hemizygote and one carrier in a second family. INTERVENTION: All nine patients underwent a routine ocular examination, including slit-lamp biomicroscopy and a dilated fundus examination. Goldmann visual field kinetic perimetry, static threshold perimetry, and electroretinography also were obtained. The DNA screening was performed on the three affected male patients and four obligate carriers examined from one family and the two examined patients, plus an additional male and obligate carrier, from the second family to determine the presence of any causative mutation in the RPGR gene. MAIN OUTCOME MEASURES: Findings on fundus examination, static threshold and kinetic perimetry, and electroretinography testing were the main outcome measures. RESULTS: A G-->T nucleotide change at position 238 in exon 3 of the RPGR gene resulting in a putative substitute of Gly-->Val at codon 60 was shown to segregate with RP in affected males and the carrier state in female heterozygotes in these two families. The ophthalmologic findings in hemizygotes as well as the carriers in this family were within the spectrum of findings characteristically noted in XLRP families. A tapetal-like reflex was not observed in any of the five female carriers. Psychophysical and electrophysiologic testing on the carriers indicated that cone and rod functions were impaired equivalently. When present in the carriers, visual field restriction was most apparent in, or limited to, the superotemporal quadrant, which corresponded to the retinal pigmentary changes that tended to occur in the inferonasal retina. CONCLUSIONS: A mutation in exon 3 of the RPGR gene, which would result in a putative glycine to valine substitution at codon 60, is associated with a severe clinical phenotype in male patients and a patchy retinopathy without a tapetal-like reflex in carrier females. In these families, heterozygote carriers showed equivalent impairment of their cone and rod function.

Adolescent↗

PubMed1998

Antigenic characterization of HIV-1 gp41 binding proteins.

The envelope protein HIV-1 gp41 has been shown to exert various effects on human T-cells, B-cells and monocytes like inhibition of cell proliferation, modulation of MHC expression and cytokine production. In contrast to gpl20, where several receptor molecules have been identified, the receptor for gp41 is still unknown. Using a sepharose column, coupled with recombinant soluble gp41, (rsgp41; Env amino acids 539-684), five gp41-binding proteins of 37, 45, 50, 62 and 100 kDa had been isolated from lysates of the B-cell line Raji. Two mouse antiserums were generated against the proteins P45 and P62 and were tested against the binding specificity of both antiserums. In Western blot analysis the antiserums recognized two protein bands of 45 and 62 kDa in complete Raji cell lysates, as well as the purified proteins P45 and P62, respectively, but did not show any cross-reaction, indicating that the two proteins do not share any immunological epitopes. Besides, the polyclonal antiserums did not recognize the other gp41-binding proteins P37, P50 and P100. Using the P62 antiserum proteins of the same size as in Raji cell lysates were stained in the lysates of the monocytic cell line U937 and the T-cell line H9, demonstrating distribution of P62 in different blood cells. P45 seems not to be identical to HLA-C which had been shown to bind to gp41. These results indicate, that P45 and P62 are two separate gp41-binding proteins without homology to each other or to the other gp41-binding proteins.

Animals↗

PubMed1998

Comparison of classification approaches applied to NIR-spectra of clinical study lots.

NIR-spectroscopy combined with pattern recognition approaches is applied to classify samples of clinical study lots in the pharmaceutical industry. The performance of linear discriminant analysis (LDA), quadratic discriminant analysis (QDA) and K-nearest neighbour (KNN) method is evaluated on a tablet data set and a capsule data set. To establish a classification model a strategy is followed, which is described in this work. Frequently, in the pharmaceutical industry, several batches of the same clinical study lot are produced. We tested whether it is possible to merge several batches in one class for modelling or, instead, whether it is necessary to model each batch individually.

Capsules↗

PubMed1998

The cultural context of caregiving: a comparison of Alzheimer's caregivers in Shanghai, China and San Diego, California.

BACKGROUND: Systematic comparisons of the psychological and physical responses of caregivers of Alzheimer's disease (AD) patients in the US and China have not been previously reported. METHODS: Informal caregivers of community dwelling AD patients in Shanghai, China and demographically-matched non-caregiving Chinese controls were compared with a sample of American caregivers residing in San Diego, California and demographically-matched American controls. RESULTS: Despite some demographic discrepancies, caregivers from both China and the US were similar. Caregivers from both cultures reported more depressive symptoms and more physical symptoms when compared with non-caregivers. Both groups of caregivers reported that patients required similar amounts of care and help with activities of daily living (ADLs). However, Shanghai caregivers reported less access to emotional support when compared with the San Diego sample. A conceptual model, guided by the stress process model of Pearlin et al. (1990), was used to explore multivariate relationships between caregiver characteristics and the physical and psychological health of our sample of AD caregivers in Shanghai, China. Results from a path analytical procedure revealed that the relationships among these variables and health outcome did not differ significantly from those observed in the US sample. CONCLUSIONS: Although elderly family members are venerated in the stereotypical Chinese family unit, and informal caregiving of disabled family members is socially mandated, the negative health consequences of caregiving appear to be similar to those observed among caregivers in the US.

Aged↗

PubMed1998

Mutations in PROP1 cause familial combined pituitary hormone deficiency.

Combined pituitary hormone deficiency (CPHD) in man denotes impaired production of growth hormone (GH) and one or more of the other five anterior pituitary hormones. Mutations of the pituitary transcription factor gene POU1F1 (the human homologue of mouse Pit1) are responsible for deficiencies of GH, prolactin and thyroid stimulating hormone (TSH) in Snell and Jackson dwarf mice and in man, while the production of adrenocorticotrophic hormone (ACTH), luteinizing hormone (LH) and follicle stimulating hormone (FSH) is preserved. The Ames dwarf (df) mouse displays a similar phenotype, and appears to be epistatic to Snell and Jackson dwarfism. We have recently positionally cloned the putative Ames dwarf gene Prop1, which encodes a paired-like homeodomain protein that is expressed specifically in embryonic pituitary and is necessary for Pit1 expression. In this report, we have identified four CPHD families with homozygosity or compound heterozygosity for inactivating mutations of PROP1. These mutations in the human PROP1 gene result in a gene product with reduced DNA-binding and transcriptional activation ability in comparison to the product of the murine df mutation. In contrast to individuals with POU1F1 mutations, those with PROP1 mutations cannot produce LH and FSH at a sufficient level and do not enter puberty spontaneously. Our results identify a major cause of CPHD in humans and suggest a direct or indirect role for PROP1 in the ontogenesis of pituitary gonadotropes, as well as somatotropes, lactotropes and caudomedial thyrotropes.

Adolescent↗

PubMed1998

Correlation of moniliformin, but not fumonisin B1 levels, in culture materials of Fusarium isolates to acute death in ducklings.

Five isolates of Fusarium moniliforme and two isolates Fusarium proliferatum of the Section Liseola were each fermented on rice for 21 d at 25 C. Each Fusarium-fermented rice, when dried and mixed into a poultry diet (10% by weight), caused a varied degree of acute mortality in baby Pekin ducklings. The acute (death in less than 48 h) mortality correlated significantly only to the amount of moniliformin in fermented rice, thus in the diet, but not to the amount of fumonisin B1 in fermented rice. This correlation of moniliformin concentration and noncorrelation of fumonisin B1 concentrations to acute toxicity were confirmed by duckling assay using diets containing these purified mycotoxins.

Animal Feed↗

PubMed1998

Activation of MAPKs in human bronchial epithelial cells exposed to metals.

We have previously shown that in vitro exposure to metallic compounds enhances expression of interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha in human bronchial epithelial cells. To characterize signaling pathways involved in metal-induced expression of inflammatory mediators and to identify metals that activate them, we studied the effects of As, Cr, Cu, Fe, Ni, V, and Zn on the mitogen-activated protein kinases (MAPK) extracellular receptor kinase (ERK), c-Jun NH2-terminal kinase (JNK), and P38 in BEAS cells. Noncytotoxic concentrations of As, V, and Zn induced a rapid phosphorylation of MAPK in BEAS cells. Activity assays confirmed marked activation of ERK, JNK, and P38 in BEAS cells exposed to As, V, and Zn. Cr and Cu exposure resulted in a relatively small activation of MAPK, whereas Fe and Ni did not activate MAPK under these conditions. Similarly, the transcription factors c-Jun and ATF-2, substrates of JNK and P38, respectively, were markedly phosphorylated in BEAS cells treated with As, Cr, Cu, V, and Zn. The same acute exposure to As, V, or Zn that activated MAPK was sufficient to induce a subsequent increase in IL-8 protein expression in BEAS cells. These data suggest that MAPK may mediate metal-induced expression of inflammatory proteins in human bronchial epithelial cells.

Activating Transcription Factor 2↗

PubMed1998

Phenotypic variability in familial combined pituitary hormone deficiency caused by a PROP1 gene mutation resulting in the substitution of Arg-->Cys at codon 120 (R120C).

As pituitary function depends on the integrity of the hypothalamic-pituitary axis, any defect in the development and organogenesis of this gland may account for a form of combined pituitary hormone deficiency (CPHD). A mutation in a novel, tissue-specific, paired-like homeodomain transcription factor, termed Prophet of Pit-1 (PROP1), has been identified as causing the Ames dwarf (df) mouse phenotype, and thereafter, different PROP1 gene alterations have been found in humans with CPHD. We report on the follow-up of two consanguineous families (n = 12), with five subjects affected with CPHD (three males and two females) caused by the same nucleotide C to T transition, resulting in the substitution of Arg-->Cys in PROP1 at codon 120. Importantly, there is a variability of phenotype, even among patients with the same mutation. The age at diagnosis was dependent on the severity of symptoms, ranging from 9 months to 8 yr. Although in one patient TSH deficiency was the first symptom of the disorder, all patients became symptomatic by exhibiting severe growth retardation and failure to thrive, which was mainly caused by GH deficiency (n = 4). The secretion of the pituitary-derived hormones (GH, PRL, TSH, LH, and FSH) declined gradually with age, following a different pattern in each individual; therefore, the deficiencies developed over a variable period of time. All of the subjects entered puberty spontaneously, and the two females also experienced menarche and periods before a replacement therapy was necessary.

Adrenocorticotropic Hormone↗

PubMed1998

The PROP1 2-base pair deletion is a common cause of combined pituitary hormone deficiency.

Combined pituitary hormone deficiency (CPHD) has an incidence of approximately 1 in 8000 births. Although the proportion of familial CPHD cases is unknown, about 10% have an affected first degree relative. We have recently reported three mutations in the PROP1 gene that cause CPHD in human subjects. We report here the frequency of one of these mutations, a 301-302delAG deletion in exon 2 of PROP1, in 10 independently ascertained CPHD kindreds and 21 sporadic cases of CPHD from 8 different countries. Our results show that 55% (11 of 20) of PROP1 alleles have the 301-302delAG deletion in familial CPHD cases. Interestingly, although only 12% (5 of 42) of the PROP1 alleles of our 21 sporadic cases were 301-302delAG, the frequency of this allele (in 20 of 21 of the sporadic subjects given TRH stimulation tests) was 50% (3 of 6) and 0% (0 of 34) in the CPHD cases with pituitary and hypothalamic defects, respectively. Using whole genome radiation hybrid analysis, we localized the PROP1 gene to the distal end of chromosome 5q and identified a tightly linked polymorphic marker, D5S408, which can be used in segregation studies. Analysis of this marker in affected subjects with the 301-302delAG deletion suggests that rather than being inherited from a common founder, the 301-302delAG may be a recurring mutation.

Alleles↗

PubMed1998

Comparisons of pleurodesis induced by talc with or without thymol iodide in rabbits.

STUDY OBJECTIVE: At the present time, talc administered either as a slurry or an aerosol is a popular agent for producing pleurodesis. Some investigators use iodized talc while others use plain talc. The purpose of the present study was to determine if iodized talc slurry produced a better pleurodesis in animals than did plain talc. DESIGN: New Zealand white male rabbits were randomly assigned to receive talc slurry, 200 mg/kg, with or without the addition of 50 mg iodide intrapleurally. Approximately 10 rabbits in each group were killed 1, 2, 4, 7, 14, and 28 days after the injection. The amount and character of pleural fluid, the degree of pleural adhesions, and the microscopic changes were compared in the two different groups. RESULTS: The pleural fluid findings, the gross adhesion score for the pleura, and the microscopic changes in the visceral pleura were essentially identical for the rabbits that received iodized talc and those that received plain talc. The injection of both plain talc and iodized talc produced a normoglycemic exudative pleural effusion that had, for the most part, disappeared by the fourth day postinjection. The amount of pleural fluid at 48 h was 3.3+/-0.6 mL in the plain talc and 2.2+/-0.5 mL in the iodized talc group. At 28 days, the mean degree of gross pleurodesis in the talc group was 2.6+/-0.2 compared with 2.3+/-0.2 in the iodized group, while the mean degree of microscopic fibrosis was 1.4+/-0.3 in the plain talc group compared with 2.0+/-0.3 in the iodized talc group. CONCLUSION: From this study, we conclude that the addition of 50 mg of iodide does not improve the results with talc slurry pleurodesis in rabbits.

Animals↗

PubMed1998

Doxycycline pleurodesis in rabbits: comparison of results with and without chest tube.

We have reported previously that there is a high incidence of hemothorax and substantial mortality in rabbits that are given tetracycline derivatives intrapleurally. However, such complications have not been reported in humans when pleurodesis is attempted with tetracycline derivatives. One primary difference in the two situations is that a chest tube is placed only in humans. The objective of this study was to evaluate the hypothesis that chest tube placement would prevent the development of hemothoraces and lead to better pleurodesis in rabbits given doxycycline intrapleurally. Eighty New Zealand White male rabbits received doxycycline, 20 mg/kg, in a total volume of 2 mL. One half of the rabbits were randomized to receive a chest tube at the time of the injection and were subjected to pleural fluid aspiration twice daily. The remaining rabbits (control group) received no chest tube and no aspiration. Ten rabbits from each group were killed on days 4, 7, 14, and 28. The intrapleural injection of doxycycline induced the production of large exudative effusions. The insertion of chest tubes prevented the development of hemothorax (0/20 in chest tube group, 15/20 in control group, p<0.001). The insertion of chest tubes was also associated with a significant reduction in mortality and a significant improvement in pleurodesis. When pleurodesis is attempted in rabbits with intrapleural doxycycline, the insertion of a chest tube will prevent hemothorax and lead to a better pleurodesis.

Animals↗

PubMed1998

Construction of phosphorylatable chimeric monoclonal antibody CC49.

Phosphorylation sites were introduced into chimeric monoclonal antibody CC49 (MAb-chCC49) by inserting synthetic fragments encoding two and six phosphorylation sites into an expression vector, pdHL7. The phosphorylation sites were created by using the predicted consensus sequences for phosphorylation by the cAMP-dependent protein kinase to the carboxyl terminus of the heavy chain constant region of the MAb-chCC49. The resultant modified antibodies (MAb-chCC49K1 and MAb-chCC49-6P) were expressed in NS0 cells and purified. The MAb-chCC49K1 protein contains two phosphorylation sites per heavy chain whereas the MAb-chCC49-6P protein contains six sites per heavy chain. Both MAb-chCC49K1 and MAb-chCC49-6P proteins can be phosphorylated by the catalytic subunit of cAMP-dependent protein kinase with [gamma-32P]ATP to high specific activity. The 32P-labeled MAb-chCC49K1 and MAb-chCC49-6P proteins bind to cells expressing TAG-72 antigens. The introduction of phosphorylation sites into a monoclonal antibody provides a reagent for the diagnosis and treatment of cancer. The use of multiple phosphorylation sites provides antibodies with very high specific radioactivity and demonstrates that cassettes of phosphorylation sites can be introduced into proteins without altering their functional activity.

Amino Acid Sequence↗

PubMed1998

[Early changes in rat lungs caused by lower-dose quartz dust].

OBJECTIVE: To study the features of damages in the lungs caused by lower dose quartz. METHODS: Cell count, contents of protein and total lipid and activity of lactate dehydrogenase (LDH) in bronchoalveolar lavage, changes in content of collagen in the whole lungs of the rats were determined after their exposure to lower dose quartz and asbestosdust (10 mg per rat), and pathological changes in the lungs were also observed. RESULTS: Cell count, contents of protein and total lipid and activity of lactate dehydrogenase in bronchoalveolar lavage, and content of total collagen in the whole lungs increased persistently in the rats exposed to quartz; and, only cell count and activity of lactate dehydrogenase increased transiently in rats 10 days after exposure to asbestos, and content of collagen also increased gradually, but not so obviously as caused by quartz. CONCLUSION: Lower dose quartz has very strong toxicity to the lungs leading to pulmonary fibrosis.

Animals↗

PubMed1998

Preventive effect of artemether on schistosome infection.

OBJECTIVE: To study the preventive effect of artemether (Art) in protecting the people from schistosome infection during flood fighting in schistosomiasis endemic area of Poyang Lake, Jiangxi Province. METHODS: From mid July to mid August in 1996, the water level in Poyang Lake rose due to torrential rains and 2 embankments, Zhedi and Jiangtongdi, which appeared in dangerous situation and were selected as the pilot spots. After those who went to fight against flood arrived at the pilots their sera were collected within 48 hours and were examined with indirect hemagglutination test (IHA), enzyme-linked immunosorbent assay (ELISA) and McAb-ELISA. Individuals with negative outcome in the 3 tests were then selected as the study subjects and were allocated randomly to the Art or the control group. The first dose of Art given to the individuals contacted with the infested water within 11-15 days was 6 mg/kg. If the individual continually contacted the infested water, the same dose of Art was given once every 15 days. After the individuals withdrew from the pilot, one more dose of Art was administered 7-15 days later. Placebo (starch) was given to individuals in the control group at the same period as in artemether group. Stool examinations were made in both groups 40-50 days after the last medication for evaluation of the preventive effect of artemether. Double blind method was used in the administration of both artemether and placebo. RESULTS: In Zhedi pilot, the individuals fought against flood for about 1 month. In Art group, 99 individuals receiving 3 doses of the drug completed the stool examination with egg-positive rate of 4% and no acute schistosomiasis was seen. In the control group, among 110 people who completed the observation, 44 were egg-positive with an infection rate of 40%, and 29 were identified as having acute schistosomiasis. In Jiangtondi, the studied individuals contacted the infested water for only about 4 hours. But in the control group 4 out of 102 individuals were egg-positive, while none of the 103 individuals in Art group receiving 2 doses of the drug showed schistosome infection. No apparent side effect was seen in the people treated with artemether. CONCLUSION: After oral Art was given to the people fighting against flood in schistosomiasis endemic area of Poyang Lake, it was shown that the oral Art has a promising effect on controlling acute schistosomiasis and reducing the infection rate.

Adolescent↗

PubMed1998

[Studies on cytotoxicity of man-made mineral fiber to alveolar macrophage].

OBJECTIVE: To compare the difference in cytotoxicity to human alveolar macrophage caused by ten kinds of man-made mineral fiber. METHODS: Ten kinds of man-made mineral fiber prepared by Japan Fibrous Materials Research Association (JFM) were used with alveolar macrophage extracted from guinea pigs in vitro as the target cells. Changes in the production of O2- and H2O2, levels of glutathione and cellular free calcium ion (Ca2+) in alveolar macrophage were determined. RESULTS: Most of the 10 kinds of JFM fiber could cause increased production of O2- and H2O2, reduction of levels of glutathione and increase of cellular free calcium ion (Ca2+) in alveolar macrophage, to a extent less than that caused by chrysotile. CONCLUSION: In general, the cytotoxicity of JFM fiber was less than that of chrysotile. Although these mineral fiber could be used as substitutes for asbestos, they still could cause certain harm to human bodies.

Animals↗

PubMed1998

Effects of amiodarone on cardiac electrophysiology in right ventricular rapid pacing-induced heart failure dogs.

AIM: To study the effects of amiodarone (Ami) on cardiac electrophysiologic properties and ventricular fibrillation threshold (VFT) in right ventricular rapid pacing-induced congestive heart failure (CHF) dogs. METHODS: Dogs (n = 25) were randomly allocated into 3 groups: A) control group; B) CHF group induced by right ventricular rapid pacing (4 pulses.s-1) for 4-5 wk; C) CHF models p Ami 300 mg.d-1 for 4-5 wk. The electrophysiologic parameters and VFT were evaluated by electric stimulation and monophasic action potential (MAP) recording. RESULTS: In CHF models, ventricular MAP duration (MAPD90), ventricular late repolarization duration (VLRD), and intra-ventricular conduction time (IVCT) were prolonged by 43%, 318%, and 19%, respectively; the ratio of ventricular effective refractory period (VERP) to MAPD90 (VERP/ MAPD90) and VFT were decreased by 13% and 48% respectively; the dispersion of ventricular recovery time (RT-D) was increased by 185%. In CHF models, Ami had no effects on ventricular MAPD90, but increased VERP/ MAPD90, IVCT, and VFT by 15%, 10%, and 67%, respectively, shortened VLRD by 87%; and decreased RT-D by 87%. Ami had no significant influences on the hemodynamic parameters of the CHF dogs. CONCLUSION: Ami normalizes the cardiac electrophysiologic properties in CHF dogs.

Action Potentials↗

PubMed1998

Effect of radix Salviae miltiorrhizae on the gene expression of nitric oxide synthase in ischemic rat brains.

The effect of Radix Salviae Miltiorrhizae (RSM) on the gene expression of nitric oxide synthase (NOS) in rat brains during ischemia was studied with in situ hybridization and the results were analyzed with IBAS 2000 Image Analysis System. It was found that NOS gene expression of cerebral cortex and caudate-putamen was markedly increased in 24 hours in ischemia group (P < 0.01). In RSM-treated rats, although the NOS gene expression of ischemic side was also increased as compared with contralateral cortex and caudate-putamen, it was significantly lower in RSM-treated rats than those of the controls (P < 0.05, P < 0.01). The present study indicates that RSM can partly inhibit NOS gene expression of cerebral cortex and caudate-putamen during ischemia. This may be one of the protective mechanisms of RSM on cerebral ischemia.

Animals↗

PubMed1998

Radix Salviae miltiorrhizae protects rat hippocampal neuron in culture from anoxic damage.

Radix Salviae Miltiorrhizae (RSM), a well-known traditional Chinese medicinal herb, has been used to improve blood circulation and resolve blood stasis. We have previously found that RSM has neuroprotective effect on ischemia and/or ischemia-reperfusion rats. The purpose of this study was to obtain further information on the mechanism of the RSM-induced neuroprotection and to examine the neuroprotective effect on neurons exposed to anoxia. The effect of RSM on anoxic damage in cultured hippocampal neurons of neonatal rat was investigated by using morphological changes and heat shock protein 70 kD (HSP70) expression as indicators. RSM given 0.5 h before 2 h-anoxia followed by 48 hours reoxygenation could significantly increase survival rate of hippocampal neurons and number of HSP70 positive cells. The results suggest that RSM has a direct neuroprotective effects on anoxic damage in hippocampal neurons.

Animals↗