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Biomedical subjects

K Wu

Publications and source records attributed to K Wu.

At least 235 records · Page 13Linked to original sources
PubMed1994

Tissue and tumor expression of a cell surface glycoprotein complex containing an integral membrane glycoprotein activator of p185neu.

Ascites 13762 rat mammary adenocarcinoma cells contain an abundant heterodimeric cell surface glycoprotein complex. It is composed of a transmembrane subunit and a sialomucin subunit and is the product of a single gene. The transmembrane subunit has two EGF-like domains and activates the proto-oncogene receptor kinase p185neu. Southern blot comparisons of the ascites tumor and rat liver demonstrated the presence of the gene encoding the complex in normal tissues and showed an amplification of about fivefold in the ascites tumor. Polymerase chain reaction assays showed the presence of mRNA for the complex in rat brain and lung, but not in liver, pancreas, placenta, intestine, kidney, ovary and uterus. Northern blot analyses showed that the 9 kb transcript for the complex is expressed at an approximately 500-fold higher level in the ascites cells than in rat brain. Immunocytochemical studies using antiserum directed against the transmembrane subunit showed its presence in bronchial epithelium, brain ependymal and neurons of four day old animals and in the endoderm and neuronal cells of embryos. Similar immunocytochemical studies showed the presence of the transmembrane subunit in some human breast tumors. These results suggest that the gene encoding this complex is regulated in a tissue-specific manner, is overexpressed in some tumors and may play a role in tumor progression.

Animals↗
PubMed1994

Biochemical and morphological changes in the lenses of selenium and/or vitamin E deficient rats.

The activities of glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R), superoxide dismutase (SOD) and the contents of malondialdehyde (MDA) and free radicals were measured, and the morphological changes were observed in the lens of control rats, selenium-deficient (SeD) and/or vitamin E deficient (VED) rats. The activities of GSH-Px in the lens of SeD rats decreased significantly. The GSH-Px activities of lens were positively related to erythrocytes selenium level. There was a free radical at g = 2.0015 in the rat lens of all groups, but the content of free radicals in the lens of SeD group was significantly higher than that of the control group. The free radical content of lens was negatively related to erythrocytes selenium level, as well as the GSH-Px activities in the lens. In vitro, ultraviolet radiation caused the generation of another kind of free radical (g = 2.0097) in the lens of all groups, but the amount of the free radical in the lens of the SeD group was also significantly higher than that of the control group. The activities of SOD and GSSG-R in VED rat lens were significantly decreased. The amount of MDA in the lens of SeD and/or VED rats were significantly increased. The results showed that the decrease of antioxidative capability in the lenses of SeD and/or VED rats accelerated the lipid peroxidation and generation of free radicals. Although only early morphological changes in SeD and/or VED rat lens were observed, it is considered that selenium and vitamin E deficiency may be involved in the occurrence of cataract.

Animals↗
PubMed1994

[The prognostic characteristics of hypertensive left ventricular hypertrophy in a rural population].

One hundred and twenty-six rural hypertensive patients with ECG left ventricular hypertrophy (HT-LVH) were followed up for 10 years to investigate the prognostic characteristics in a population with low prevalence of hypertension (2.93%) and low plasma cholesterol (4.59 +/- 1.00mmol/L). A cohort of age, sex, region and occupation matched hypertensives without LVH (HT, n = 163) and normotensives (NT, n = 275) served as controls. The major cause of death in rural hypertensives with ECG LVH in this study was stroke (56.8%). After stratification of BP, no significant difference of stroke risk was found between patients with LVH and hypertensives without LVH, while cardiovascular risk in the patients with LVH plus ST segment depression persisted. LVH per se seems not to be an independent factor for stroke. The high stroke rate in patients with LVH may be ascribed to the coexisting higher level of BP. After adjustment of coexisting hypertension, ECG LVH based on voltage only was not an independent risk factor of stroke and cardiovascular events, while LVH plus ST segment depression was closely related to cardiovascular events. In this low level, plasma cholesterol did not affect the mortality rate of stroke.

Adult↗
PubMed1993

Anti-HIV-1 activity and cellular pharmacology of various analogs of gossypol.

We previously reported that the racemic mixture and both enantiomers of gossypol inhibit the replication of human immunodeficiency virus-type 1 (HIV-1) (Lin et al., Antimicrob Agents Chemother 33: 2149-2151, 1989). The present study evaluates the activities of a variety of analogs of gossypol as well as a few non-gossypol analogs. Compounds 2, 3, 10, and 13 were slightly more inhibitory than (-)-gossypol to the replication of HIV-1 in cell culture. Compounds 4 and 8 were cytotoxic to human peripheral blood monocyte (PBM) cells, and compounds 2 and 3 were cytotoxic to Vero cells but not PBM cells. The effects of the two enantiomers of gossypol on the cell volume and migration of H9 cells through the cell cycle were evaluated during 72 hr of incubation. The (-)-enantiomer of gossypol was more toxic to H9 cells than the (+)-enantiomer of gossypol as evidenced by cell destruction. Prior to cell destruction, there appeared to be no significant effect on cell cycle distribution with either enantiomer.

Animals↗
PubMed1993

Randomized trial of high-dose chemotherapy with autologous bone marrow support as adjuvant therapy for high-risk, multi-node-positive malignant melanoma.

BACKGROUND: Chemotherapy adjuvant to surgery in metastatic melanoma has been evaluated in only a few prospective randomized trials. In the treatment of metastatic melanoma, dacarbazine has response rates of 15%-25% and in several studies, when combined with other alkylating agents, has yielded even higher response rates. Among the highest response rates are those achieved by using high-dose chemotherapy regimens combined with autologous bone marrow support (transplantation). PURPOSE: We conducted a prospective randomized clinical trial to test the efficacy of high-dose alkylating agents in combination with autologous bone marrow support given as adjuvant therapy for high-risk stage II (World Health Organization) melanoma. METHODS: Thirty-nine patients with metastases involving five or more lymph nodes were randomly assigned to one of two treatment arms within 8 weeks of lymphadenectomy: immediate treatment or observation only. The immediate-treatment arm consisted of 19 patients who, immediately after random assignment, received high-dose chemotherapy with alkylating agents, followed 3 days later by reinfusion of autologous bone marrow. The observation arm consisted of 20 patients who were observed until relapse (confirmed by biopsy) and were then treated with the identical high-dose alkylating agent chemotherapy followed by reinfusion of autologous bone marrow. Bone marrow was harvested from the patients under general anesthesia 1-2 weeks prior to chemotherapy and was cryopreserved. Chemotherapy consisted of intravenous administration of cyclophosphamide (1875 mg/m2 as a 1-hour infusion daily for 3 days), cisplatin (55 mg/m2 per day by continuous infusion over the same 72-hour period), and carmustine (BCNU) (600 mg/m2) given immediately after cisplatin on the 4th day as a 2-hour infusion. The total doses of the three drugs were 5625, 165, and 600 mg/m2, respectively. All patients received medical evaluations every 6-12 weeks over the study period. Kaplan-Meier estimates were used to determine the time to disease progression on the basis of intent to treat. RESULTS: There was no statistically significant difference in overall survival or in time to disease progression between the two treatment arms. However, the median time to progression was 16 weeks in the observation arm and 35 weeks in the immediate-treatment arm. CONCLUSIONS: Immediate adjuvant high-dose chemotherapy with alkylating agents followed by autologous bone marrow support more than doubled the time to disease progression compared with observation alone, though the difference was not statistically significant. No differences in overall survival were noted.

Adult↗
PubMed1993

Protein product of the somatic-type transcript of the Hoxa-4 (Hox-1.4) gene binds to homeobox consensus binding sites in its promoter and intron.

The murine Hoxa-4 gene encodes a protein with a homeodomain closely related to those produced by the Antennapedia-like class of Drosophila genes. Drosophila homeodomain proteins can function as transcription factors, binding to several specific DNA sequences. One sequence that is frequently encountered contains a core ATTA motif within a larger consensus sequence, such as CAATTAA. The in vitro synthesized protein product of Hoxa-4 was shown to bind to a subset of restriction fragments of the Hoxa-4 gene itself as determined by gel retardation experiments. Direct examination of the sequences of the fragments bound by Hoxa-4 protein revealed the presence of four regions containing the core ATTA motif. Two regions contained sequences of the CAATTAA class and were located approximately 1 kb upstream from the putative somatic Hoxa-4 promoter and within the intron. Two additional binding sites containing the consensus target sequence involved in autoregulation of Drosophila Deformed gene were identified: one immediately downstream of the putative embryonic transcription start site and one within the intron, respectively. Specific binding of the in vitro produced Hoxa-4 protein to oligonucleotides corresponding to these sequences was observed in gel retardation assays. The same results were obtained with Hoxa-4 protein produced in a Baculovirus expression system. Experiments using oligonucleotides containing base substitutions in positions 1, 3, 4, and 5 in the sequence CAATTAA showed severely reduced binding. The use of truncated mutant Hoxa-4 proteins in gel retardation assays and in transient co-transfection experiments revealed that the intact homeodomain was required for the binding. These results also suggested that the Hoxa-4 gene has the potential to auto-regulate its expression by interacting with the homeodomain binding sites present in the promoter as well as in the intron.

Amino Acid Sequence↗
PubMed1993

Effect of neuropeptide Y on natural killer activity of normal human lymphocytes.

The in vitro effect of neuropeptide Y (NPY) on natural killer (NK) cell activities of normal lymphocytes was investigated. NPY at 10(-9) to 10(-12) M concentrations produced significant suppression of NK activity against K 562 target cells. NPY at 10(-9) to 10(-12) M concentrations also produced significant inhibitory effects on NK activities of NK-enriched large granular lymphocytes against LAV-infected 8E5/LAV target cells. The suppression was dose dependent against both targets. NPY-induced suppression of NK activity of lymphocytes against K 562 target cells was specifically reversed by rabbit anti-NPY antisera at 1:800 and 1:1600 dilutions, showing the specificity of reactions. Pretreatment of target cells with NPY concentrations capable of inhibiting NK activity did not affect the sensitivity of K 562 target cells for lysis by effector cells. Inhibition of cytotoxicity was not due to direct toxicity of effector cells, because lymphocytes treated with NPY showed normal levels of 51Cr release and their viability was comparable to that of untreated control cells. These studies demonstrated that NPY, a product of sympathetic nervous system activation, may have a significant immunoregulatory effect on NK cell activities of normal lymphocytes that may be of clinical significance.

Adult↗
PubMed1993

Measurement of endogenous synthesis of plasma cholesterol in rats and humans using MIDA.

We used the mass isotopomer distribution analysis (MIDA) technique to measure endogenous synthesis of plasma cholesterol in vivo in rats and normal human subjects. Sodium [1-13C]- or [2-13C]acetate was infused, and plasma free cholesterol was analyzed by gas chromatography-mass spectrometry. Frequencies of mass isotopomers M0-M4 (mass-to-charge ratio 368-372) were quantified. The enrichment of the true precursor for cholesterol synthesis (acetyl-coenzyme A in contributing tissues) was determined using the MIDA method. This technique remains mathematically valid even if more than one tissue contributes to circulating free cholesterol. The fractional contribution (f) from endogenous synthesis to free cholesterol in normal women (n = 5) was 2.48 +/- 0.39% after 7 h in the postabsorptive state and 1.27 +/- 0.41% after 8 h of refeeding. In ad libitum-fed rats (n = 12), f was 2.89 +/- 0.44% after 12 h, whereas administration of recombinant tumor necrosis factor increased this value fourfold. Next, the rate constant (k) for removal of labeled free cholesterol from plasma was calculated. Higher masses (M2-M4) were followed to avoid the problem of persistent label incorporation. During the 60 h after cessation of [13C]acetate infusions, k was 0.02490 +/- 0.00298/h in humans. Using these values of k and f, absolute cholesterogenesis was 568 +/- 55 mg/day in normal women (follicular menstrual phase), similar to prior estimates based on whole body sterol balances. Women also exhibited a diurnal variation for endogenous cholesterol synthesis (34.6 +/- 5.4 mg/h nighttime vs. 15.9 +/- 5.2 mg/h daytime) consistent with current knowledge about rhythms in cholesterogenesis. Checks on the model were internally consistent (e.g., comparisons among different isotopomers for calculating precursor enrichment). We conclude that fractional and absolute endogenous cholesterol synthesis can be measured using stable isotopes in vivo by the MIDA technique.

Adult↗
PubMed1993

Lipoprotein[a] as a risk factor for preclinical atherosclerosis.

Elevated mean levels of lipoprotein[a] (Lp[a]) have been associated with symptomatic cardiovascular diseases such as clinically manifest myocardial infarction (MI), coronary artery disease, restenosis of coronary artery vein grafts after bypass, and a family history of MI. Associations of Lp[a] with arterial wall thickening in asymptomatic individuals previously have not been addressed and are evaluated in this report among participants of the Atherosclerosis Risk in Communities (ARIC) Study. Intima-media wall thickening in the extracranial carotid arteries was assessed noninvasively with B-mode ultrasonography; Lp[a] was measured as its total protein component. Individuals with wall thickening > or = 90th percentile of the population maximum far-wall thickness were pair matched to participants < 75th percentile of wall thickness by race, gender, center, 10-year age group, and time of examination. These selection criteria yielded 492 matched pairs, with 395 white pairs and 97 black pairs. The mean Lp[a] protein level for all black participants was 174.6 micrograms/mL compared with 77.8 micrograms/mL for whites. Conditional logistic regression analysis for the association of Lp[a] with case-control status yielded a statistically significant prevalence odds ratio (OR) estimate of 1.49, based on a 1-SD difference in Lp[a] protein, after adjusting for age, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fibrinogen, hypertension, and cigarette smoking. None of these risk factors significantly altered the OR, in agreement with reports that Lp[a] is unaffected by environmental influences. In addition, no differential effect of Lp[a] protein on case-control status (effect modification) was observed by race, gender, low-density lipoprotein cholesterol, or fibrinogen in this population.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriosclerosis↗
PubMed1993

Increased de novo hepatic lipogenesis in human immunodeficiency virus infection.

We measured de novo lipogenesis in human immunodeficiency virus (HIV) infected men using a newly developed stable isotope method. HIV-infected subjects with a history of weight loss (n = 17, mean weight loss 14.9 +/- 3.2 kg), asymptomatic HIV-seropositive subjects with normal CD4 T-cell counts (n = 7) and healthy HIV seronegative controls (n = 11) were studied. Hepatic lipogenesis was determined by infusion of [2-13C]-acetate, using the recently described xenobiotic probe technique with mass isotopomer analysis. Hepatic acetyl-coenzyme A enrichment was measured by high performance liquid chromatography/mass spectrometry of secreted sulfamethoxazole-acetate, with measurement of incorporation into very low density lipoprotein-fatty acids by gas chromatography-mass spectrometry. Circulating tumor necrosis factor (TNF), interleukin-1 (IL-1), interferon alpha (IFN alpha), insulin, and triglycerides were measured concurrently, and 7-day weighed food records were performed. De novo hepatic lipogenesis was increased 3- to 4-fold in HIV-infected subjects with weight loss compared to normal controls (P < 0.05 for palmitate and stearate in both overnight-fasted and fed states), and was also significantly increased in asymptomatic HIV seropositive subjects. Circulating TNF and IL-1 were not measurable in any subject (detection limit 2 pg/ml for IL-1 and 20 pg/ml for TNF). Serum IFN alpha was measurable in 11 out of 17 subjects with wasting and correlated significantly with de novo lipogenesis in overnight-fasted but not fed states. Serum IFN alpha was unmeasurable in asymptomatic HIV-infected subjects despite elevated lipogenic rates. Serum triglyceride concentrations were elevated in subjects with weight loss (2.09 +/- 0.28 mmol/L) and asymptomatic HIV-positives (1.34 +/- 0.34 mmol/L) in comparison to controls (0.67 +/- 0.08 mmol/L), and correlated with lipogenesis. Food intake correlated inversely with lipogenesis in the overnight-fasted state. We conclude that HIV infection is characterized by abnormal fat anabolism. This applies to subjects with reduced lean body mass and to asymptomatic HIV-positive subjects with normal T-cell counts. The former observation may have implications for the pathophysiology and treatment of the wasting syndrome. The latter observation is consistent with activation of the immune response and a state of viral nonlatency in early HIV disease.

Adult↗
PubMed1993

[Relations between opacification of lens protein and pH].

Some of the acidic reagents or medicines (i.e. HCl, GSH & GSSG, Vit. C, Vit. B6) and basic reagents (Tris) were used to regulate the pH of water soluble protein and urea soluble protein solution of human lenses. At a certain pH, the lens protein solution appears opalescence, the pH of opacity solution which is measured by pH meter is around 5.6-6.3. The opalescence of water soluble and urea soluble lens protein solution of human fetal, adult and cataractous lenses were also determined by gradient acidic and basic solution. The result show that the opacity is more obvious in soluble protein solution of cataractous lenses and clear lenses than in that of fetal lenses, and the lens urea soluble protein has a marked opalescence in comparison with the water soluble protein. So we assume that cataractogenesis might be associated with the change of pH within lens.

Adult↗
PubMed1993

The prognostic characteristics of hypertensive left ventricular hypertrophy in a population with low prevalence of hypertension and low plasma cholesterol.

One hundred and twenty-six hypertensive patients with ECG left ventricular hypertrophy (HT-LVH) were followed for 10 years to investigate the prognostic characteristics in a population with low prevalence of hypertension (2.93%) and low plasma cholesterol (4.26 +/- 0.91 mmol/L). A cohort of age-, sex-, region- and occupation-matched, randomized hypertensives without ECG-LVH (n = 163) and normotensives (n = 275) served as controls. HT-LVH was found to be associated with an increased risk of overall death, stroke mortality and cardiovascular mortality. The major cause of death in rural hypertensives with ECG-LVH was stroke (56.8%). After adjusting BP and BP stratification, no significant difference of stroke risk was found between patients with and without LVH, while cardiovascular risk persisted in patients with LVH plus ST segment depression. LVH per se did not appear to be an independent factor for stroke death. Higher stroke mortality in patients with LVH may be ascribed to the coexisting higher level of BP. Furthermore, after adjusting for the coexisting hypertension, ECG-LVH in terms of voltage only was not related to the prognosis of stroke and cardiovascular death. The mortality rate of stroke was not affected by plasma cholesterol levels, as the levels seen were in a low range.

Adult↗
PubMed1993

Virus DNA detection of herpes simplex keratitis by PCR.

HSV-DNA of seven corneal lesions suspected with herpes simplex keratitis (HSK) and nine normal human donor corneas were detected by PCR. Five out of seven diseased corneas showed positive results, and the other two diseased corneas and nine normal corneas negative. The results suggest the PCR may be useful as a rapid and sensitive method for diagnosing HSK.

Adult↗
PubMed1993

[Synthesis and bio-activity of coumarin derivatives and studies on its relationships between activity and lipophilicity].

4-Methyl-7-hydroxy-6 or 8-allylcoumarin, a new type of radioprotectors, has poor solubility in water and in oil, which influences markedly its absorption in body and effectiveness of peroral administration. For improving its solubility, 14 coumarin derivatives were synthesized on the basis of increasing its hydro- or lipophilicity, and studied preliminarily on their toxicities, radioprotective activities, and relations between their hydro- or lipophilicity and activities. It is found that both compounds (5a, 6a), can be dissolved in ethyl oleate and the latter in water partially as well, retain the radioprotective activities basically, and improve the survival of 65% (P < 0.01) of mice exposed to 9.0 Gy 60Co gamma-ray when administered before irradiation. In synthesis, von Pechmann reaction was improved; 6-allyl intermediate was synthesized by the method of blocking the 8-position by iodine, and the process was studied. Mannich base was synthesized under high pressure by using CH2Cl2 as C1 synthon.

Animals↗
PubMed1993

Election spin resonance studies of free radical formation and oxygen consumption of lens epithelium during ultraviolet exposure.

A long life election spin resonance (ESR) signal at g = 2.0006 was observed in the normal lens epithelium and cortical fibers. During ultraviolet (UV) exposure, a new ESR signal at g = 2.0060 was found in the lens epithelium. But this specific signal was not detected in the lens cortical fibers. This suggested that lens epithelial cells were more susceptible to the free radical formation which was induced by UV light. By means of ESR spin probe oximetry, the oxygen uptake of lens epithelial cells was measured. The more the oxygen uptake, the higher the K value was. The K value of the oxygen consumption of epithelial cell linearly correlated with time of consumption (20-60 min) and increased as a function of UV exposure time (1-5 min). The oxygen consumption rate of lens epithelial cell was approximately 1.38 x 10(6) and increased to 7.1 x 10(6) O2 molecules per cell per sec. The oxygen consumption rate increased more than 5 times. These results indicates that UV light can accelerate the respiratory function of lens epithelial cells. The necessity of excess oxygen of lens epithelial cells may play a role in the cataract formation induced by UV light.

Animals↗
PubMed1993

[Study on human gamma-crystallins: IV. Photooxidation of fetal gamma 2-crystallin by ultra-violet irradiation].

Human fetal gamma 2-crystallin solution was irradiated by ultra-violet (UV) (lambda 365 nm) at varying time, and analysed by light scattering, SDS-PAGE with DACM, which could specifically combine to free sulphydryl, as well as tryptophan fluorescence and its quenching with acrylamide. The results showed that light scattering of gamma 2-crystallin solution increased after 24 hour irradiation; SDS-PAGE reveled formation of dimer which did not have free sulphydryl and low molecular weight peptide of gamma 2-crystallin. The tryptophan fluorescence of gamma 2-crystallin decreased, and acrylamide fluorescence quenching effect did not show significant change. It suggested that human fetal gamma 2-crystallin photooxidized by UV could aggreate by disulfide and degrated to low molecular weight peptide, and its tryptophan were also oxidized in some degree.

Crystallins↗
PubMed1992

Detection of dystrophin in the postsynaptic density of rat brain and deficiency in a mouse model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a common, lethal, chromosome X-linked inherited disease. Moderate cognitive impairment is a feature of DMD, but the underlying mechanisms are unknown. DMD is characterized by a defect in a protein, dystrophin, that is located predominantly in muscle but has been detected in brain. We sought to directly localize dystrophin within the complex synaptic structure of the cerebral cortex by focusing on the postsynaptic density (PSD), which appears to be central to synaptic function. We report that a specific anti-dystrophin antibody (anti 6-10) recognizes three distinct proteins in the purified PSD: the 400-kDa dystrophin and two previously unidentified dystrophin-related proteins of 120 and 110 kDa. These proteins exhibited differential regional expression in PSDs from cerebral cortex, cerebellum, and olfactory bulb. In the cortical PSD, the 400-kDa dystrophin was predominant, whereas the 120-kDa protein was the major species in cerebellum and olfactory bulb PSDs. The three proteins were differentially expressed in the PSD during cortical development: the 400-kDa protein exhibited a selective 9-fold increase during postnatal days 7 to 10, suggesting a normal physiological role in synaptic maturation. The PSD from the mdx mouse, a model of human DMD, contained no detectable 400-kDa dystrophin but expressed the two dystrophin-related proteins. Our results indicate that brain dystrophins are localized to the PSD, potentially as three isoforms, and raise the possibility that cognitive abnormalities in DMD are attributable to synaptic dysfunction associated with deficits in brain dystrophin molecules.

Animals↗