Biomedical subjects

K Zhu

Publications and source records attributed to K Zhu.

At least 55 records · Page 3Linked to original sources

PubMed2000

[Development of a system for Polymyxa graminis infection and transmission of wheat yellow mosaic virus].

In growth chambers, a system was developed for infection of Polymyxa graminis to wheat(Triticum aestivum L.), which is an obligate parasite. By the system, the fungus could be propagated in large quantity rapidly and the life cycle of P. graminis in wheat was observed in a period of 13 to 15 days. The methods for separating P. graminis as single cystosori from cultured wheat roots or dried roots were simplified. By tests for the factors affecting on P. graminis infection, including inocula types, seedling age of host plants, temperatures, pH value and nutrient contents etc., the system was modified to more perfection. With an integration of optimal temperature and other elements in the system, which affect on infection and development of P. graminis, wheat yellow mosaic virus (WYMV) was transmitted constantly and efficiently by the fungal vector. In average, 70% of wheat plants inoculated by the viruliferous fungi could infected by WYMV and the typical symptom of wheat mosaic disease would appear at 30 days post-inoculation mechanically.

Ascomycota↗

PubMed1999

Adriamycin inhibits human RH II/Gu RNA helicase activity by binding to its substrate.

RNA helicases are enzymes important in RNA synthesis, processing, transport, and turnover. Human nucleolar RNA helicase II/Gu protein (RH II/Gu) was expressed in a baculovirus system. The purified recombinant RH II/Gu protein has RNA helicase activity on a 5' tailed ds RNA substrate in vitro. We found that Adriamycin, a widely used anticancer drug, inhibited RH II/Gu helicase activity in a dose-dependent manner with an IC(50) of 40 microM. Adriamycin bound to the RNA substrate, and the binding was disrupted by boiling or treatment with 1% SDS, suggesting that the binding of Adriamycin to RNA is reversible. Adriamycin was also found by gel electrophoresis to bind to yeast tRNA to form slow-migrating complexes. These results suggest that Adriamycin can inhibit RNA synthesis or processing by binding to RNA substrates.

Antineoplastic Agents↗

PubMed1999

p53 induces TAP1 and enhances the transport of MHC class I peptides.

The transporter associated with antigen processing (TAP) 1 is required for the major histocompatibility complex (MHC) class I antigen presentation pathway, which plays a key role in host tumor surveillance. Since more than 50% of tumors have a dysfunctional p53, evasion of tumor surveillance by tumor cells may be linked to loss of p53 function. Here we found that TAP1 is strongly induced by p53 and DNA-damaging agents through a p53-responsive element. We also found that p73, which is homologous to p53, is capable of inducing TAP1 and cooperates with p53 to activate TAP1. Furthermore, we found that by inducing TAP1, p53 enhances the transport of MHC class I peptides and expression of surface MHC-peptide complexes, and cooperates with interferon gamma to activate the MHC class I pathway. These results suggest that tumor surveillance may be a mechanism by which p53 and/or p73 function as tumor suppressors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1999

Differential regulation of cellular target genes by p53 devoid of the PXXP motifs with impaired apoptotic activity.

Activation of the p53 tumor suppressor protein can lead to either cell cycle arrest or apoptosis. Several functional domains necessary for mediating cell cycle arrest and apoptosis in p53 have been mapped, e.g., the proline-rich domain. The proline-rich domain is located within residues 60-90, which comprise five PXXP motifs (where P represents proline and X any amino acid). To further delineate the function of the proline-rich domain and its potential role in transactivation, we generated several groups of cell lines that inducibly express various p53 mutants using a tetracycline-regulated expression system. We found that p53(delta62-91), which lacks all five PXXP motifs in human p53, is capable of inducing cell cycle arrest but not apoptosis, while p53(gln22-ser23/delta62-91), which contains a double point mutation in the activation domain as well as deletion of the proline-rich domain, completely loses its activity. However, p53(delta74-91), which contains only one PXXP motif at its N-terminus, is not only capable of inducing cell cycle arrest but also retains a partial apoptotic activity. Furthermore, we found that deletion of the proline-rich region has no or very mild effects on activation of several transiently transfected p53 target gene promoters, i.e., the p21, MDM2, BAX, and GADD45 promoters. However, such deletion differentially affects p53 induction of endogenous target genes, i.e., induction of p21, MDM2, BTG2, p85, PIG3, PIG6 and PIG11 was reduced or abrogated but induction of BAX, KILLER/DR5, PIG2, PIG7 and PIG8 was not substantially affected. Interestingly, induction of GADD45 was enhanced. These results suggest that the proline-rich region may play a role in chromatin remodeling, which counteracts chromatin-mediated repression for some of the endogenous p53 target genes.

Apoptosis↗

PubMed1999

Preventive practicum training in healthcare organizations. The Meharry model.

BACKGROUND: Practicum training for preventive medicine residents often occurs in agencies whose community is geographically defined and whose governance is closely linked to public election. We were unsure about the financial ability of such departments to support training and are concerned that over-reliance on traditional health departments might not be best for either medically indigent populations or preventive medicine. We, therefore, sought to apply a public health model--based on a strategic partnership between nursing and preventive medicine--to a large health care organization. The result was formation of a mini-health department, suitable for fully accredited preventive medicine practicum training, within the Alvin C. York Veterans Affairs Medical Center, Murfreesboro, TN. This Center serves a defined population of 21,594 patients and about 1600 employees. The theoretical framework for the new department was based on demonstration of a close fit between the competencies expected of preventive medicine physicians by the American College of Preventive Medicine (ACPM) and activities required by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO). Because of JCAHO requirements, many healthcare organizations already pay for preventive medicine services. CONCLUSIONS: By placing preventive medicine training faculty into existing budget slots at our institution, systemwide personnel costs for prevention decreased by about $36,000 per year, even as personnel funding for preventive medicine physicians increased from about $24,000 to $376,000 per year. Moreover, there was dramatic, sustained improvement in 17 indicators of preventive care quality as determined by an external peer review organization. In addition to providing a new venue for training, this model may also improve the quality and reach of preventive services, decreased fixed costs for service delivery, and yield new employment opportunities for preventive medicine physicians.

Delivery of Health Care↗

PubMed1999

Comparison of self-report data and medical records data: results from a case-control study on prostate cancer.

BACKGROUND: Self-report and review of medical records are the most common methods for the assessment of past exposures. However, information obtained from self-reports and medical records may not be consistent. This study compared information provided in a self-administered questionnaire with medical records data. METHODS: Self-report and medical records data came from a case-control study on prostate cancer. Cases were 181 patients with primary prostate cancer and controls were 297 men without the disease, enrolled in Group Health Cooperative (GHC) in Seattle. The consistencies between the two data sources were examined. RESULTS: In general, agreement between the two data sources was almost perfect for demographic and anthropometric variables, substantial for the history of inguinal hernia and kidney stones, and moderate for vasectomy, family history of prostate cancer, smoking and alcohol consumption. However, the two data sources generally were poorly concordant for prior genitourinary diseases that have less explicit diagnostic criteria such as benign prostatic hyperplasia and prostatitis. Analyses of discordant data showed that men were more likely to report an exposure or medical condition that could not be verified from medical records. No discernible patterns in the difference of agreement were found according to age, GHC membership length or case-control status. CONCLUSIONS: This study suggests that agreement between self-reported data and medical records data varies depending upon the study variables. While both data sources are subject to some problems, self-report may provide more complete and comparable information, at least for variables unrelated to diagnosis.

Adult↗

PubMed1999

The multiple roles of conserved arginine 286 of 1-aminocyclopropane-1-carboxylate synthase. Coenzyme binding, substrate binding, and beyond.

A pyridoxal 5'-phosphate (PLP)-dependent enzyme, 1-aminocyclopropane-1-carboxylic acid (ACC) synthase (S-adenosyl-L-Met methylthioadenosine-lyase, EC 4.4.1.14), catalyzes the conversion of S-adenosyl-L-methionine (AdoMet) to ACC. A tomato ACC synthase isozyme (LE-ACS2) with a deletion of 46 amino acids at the C terminus was chosen as the control enzyme for the study of the function of R286 in ACC synthase. R286 of the tomato ACC synthase was mutated to a leucine via site-directed mutagenesis. The ACC synthase mutant R286L was purified using a simplified two-step purification protocol. Circular dichroism (CD) analysis indicated that the overall three-dimensional structure of the mutant was indistinguishable from that of the control enzyme. Fluorescence spectroscopy revealed that the binding affinity of R286L ACC synthase for its cofactor PLP was reduced 20- to 25-fold compared with control. Kinetic analysis of R286L showed that this mutant ACC synthase had a significantly reduced turnover number (k(cat)) of 8.2 x 10(-3) s(-1) and an increased K(m) of 730 microM for AdoMet, leading to an 8,000-fold decrease in overall catalytic efficiency compared with the control enzyme. Thus, R286 of tomato ACC synthase is involved in binding both PLP and AdoMet.

Amino Acid Sequence↗

PubMed1999

Irreversible inhibition of human immunodeficiency virus type 1 integrase by dicaffeoylquinic acids.

Human immunodeficiency virus type 1 (HIV-1) and other retroviruses require integration of a double-stranded DNA copy of the RNA genome into the host cell chromosome for productive infection. The viral enzyme, integrase, catalyzes the integration of retroviral DNA and represents an attractive target for developing antiretroviral agents. We identified several derivatives of dicaffeoylquinic acids (DCQAs) that inhibit HIV-1 replication in tissue culture and catalytic activities of HIV-1 integrase in vitro. The specific step at which DCQAs inhibit the integration in vitro and the mechanism of inhibition were examined in the present study. Titration experiments with different concentrations of HIV-1 integrase or DNA substrate found that the effect of DCQAs was exerted on the enzyme and not the DNA. In addition to HIV-1, DCQAs also inhibited the in vitro activities of MLV integrase and truncated variants of feline immunodeficiency virus integrase, suggesting that these compounds interacted with the central core domain of integrase. The inhibition on retroviral integrases was relatively specific, and DCQAs had no effect on several other DNA-modifying enzymes and phosphoryltransferases. Kinetic analysis and dialysis experiments showed that the inhibition of integrase by DCQAs was irreversible. The inhibition did not require the presence of a divalent cation and was unaffected by preassembling integrase onto viral DNA. The results suggest that the irreversible inhibition by DCQAs on integrase is directed toward conserved amino acid residues in the central core domain during catalysis.

Animals↗

PubMed1999

[Angiotensin 1-converting enzyme gene insertion/deletion polymorphism in patients with coronary artery disease and essential hypertension and its nucleotide sequence].

OBJECTIVE: To determine angiotensin 1-coverting enzyme(ACE) gene insertion/deletion(I/D) polymorphism distributions in patients with coronary artery disease(CAD) and essential hypertension(EH),and to detect its nucleotide sequence. METHODS: ACE genotypes of 137 patients with CDA, 42 patients with EH and 63 healthy people were detected by PCR methods. At the same time, nucleotide sequences of D and I allele were determined by fluorescein labeling automatic sequencing method. RESULTS: the frequency of DD genotype in CAD group was significantly higher than that in control group (0.45 and 0.21,P < 0.01), but there was no significant difference of ACE geneI/D polymorphism distribution between EH and control group. The lengths of D and I alleles are 191bp and 479bp separately and their nucleotide sequences are somewhat different with the results of foreign countries. CONCLUSION: ACE gene I/D polymorphism is an independent risk factor of CAD, but it has no relationship with EH. A 288bp insertion segment results in the I/D polymorphism of ACE gene.

Adult↗

PubMed1999

[Influence of nitric oxide upon cerebral infarction in 15 cases].

To study the role of the nitric oxide(NO) in patients with cerebral infarction, NO in cerebrospinal fluid was determined in cerebral infarction group(15 cases) and control group(10 cases). Infarct volume was determined by CT between the second and the 7th day after the onset of symptoms. The severity of neurological deficits was assessed with the stroke scale of Ministry of Public Healthy(China). The results showed that NO was higher in cerebral infarction group (3.12 +/- 1.60) than that in control group(1.19 +/- 1.01) (P < 0.01). The concentration of NO was positively correlated with infarction volume(r = 0.57, P < 0.05) and severity of neurological of deficits(r = 0.54, P < 0.05), respectively. The results support the conclusion that NO produced in large amounts in the postischemic tissue contributes to the progression of the brain damage, which was demonstrated in animal models of focal cerebral ischemia.

Adult↗

PubMed1999

[Progress in studies on cavitation of mechanical heart valve].

This paper reviews the researches on cavitation of mechanical heart valve in recent years and presents a discussion on the research methods. The achievements are summarized and the prospects of further research on cavitation in mechanical heart valve are brought forth.

Heart Valve Prosthesis↗

PubMed1999

[Cloning of DNA fragment related to salt tolerance in Sinorhizobium meliloti 042B].

Total DNA partially digested by EcoR I was prepared for S. meliloti 042B, in which 15-25 kb DNA fragments were collected. Vector pLAFR I was purified and digested by EcoR I, and then the various DNA fragments of 042B were ligated with pLAFR I by T4DNA ligase. Gene library of S. meliloti 042B was constructed with pLAFR I using E. coli S17-1 as recipient. The number of bacterial recombinants obtained was about 8,000 and 95% of them contained foreign DNA fragments. Using NTG, 042B was mutated on FY plates and 12 sensitive strains were screened at 0.5 mol/L NaCl from 2,000 colonies. One of them was named GZ17 and selected as a recipient strain. By biparental mating the foreign DNA fragments were introduced from gene library of strain 042B into recipient strain GZ17 which is sensitive to 0.5 mol/L NaCl. Then the transconjugants were grown on FY plates containing tetracycline (20 micrograms/mL) and 0.5 mol/L NaCl. A 7 kb inserted DNA fragment related to salt tolerance was obtained. In subcloning experiment, a 4 kb DNA fragment related to salt tolerance was obtained.

Cloning, Molecular↗

PubMed1999

Prostate cancer in relation to the use of electric blanket or heated water bed.

Using data from a case-control study conducted in Group Health Cooperative (GHC) of Puget Sound, we examined the relation between the use of electric blankets or heated water beds and the risk of prostate cancer. Cases were 175 prostate cancer patients ages 40-69 years. Controls were 258 male GHC members frequency matched to cases. The odds ratio (OR) for prostate cancer associated with the use of an electric blanket or heated water bed was 1.4 (95% confidence interval (CI) 0.9-2.2). The risk, however, did not tend to be higher with increasing months per year or years of use. This study did not provide clear evidence on the hypothesized association.

Adult↗

PubMed1998

Methyl-deficient diets, methylated ER genes and breast cancer: an hypothesized association.

Recent molecular studies show that ER-negative breast cancer results from the lack of ER gene transcription due to the methylation of the CpG island 5' to the gene. Because CpG island methylation is an early event in carcinogenesis and because methyl-deficient diets could result in CpG island methylation, it is relevant to postulate that methyl-deficient diets may be a risk factor for breast cancer with methylated ER genes (as opposed to the disease with unmethylated ER genes). This molecular-based etiologic hypothesis may facilitate epidemiological research on the relationship between breast cancer and diet that has been unclear until now.

Breast Neoplasms↗

PubMed1998

Non-Hodgkin's lymphoma and family history of malignant tumors in a case-control study (United States).

Using data from a case-control study in the United States (the Selected Cancers Study), we examined the relationship between non-Hodgkin's lymphoma (NHL) and family history of different cancers. Cases were 1,511 men aged 31 to 59 years and diagnosed pathologically with non-Hodgkin's lymphoma during 1984-88. Controls were men, frequency-matched to cases by age range and cancer registry (n = 1,910). All study subjects with acquired immunodeficiency syndrome were excluded from analyses. Our results showed that the risk of NHL is associated with a history of lymphoma (odds ratio [OR] = 3.0, 95 percent confidence interval [CI] = 1.7-5.2) and hematologic cancer (OR = 2.0, CI = 1.2-3.4) in first-degree relatives after adjustment for age, ethnic background, and educational level. Further analyses were performed for the subgroups defined by age at diagnosis (younger than 45 years cf 45 years or older). The association of NHL with a family history of lymphoma and hematologic cancer was found primarily among men aged 45 and older (OR = 4.1, CI = 1.9-8.8 for lymphoma and OR = 2.3, CI = 1.3-4.0 for hematologic cancer). The association among men aged 45 and older did not vary by whether or not there were any familial patients diagnosed at the age of 45 or older. No significant associations could be found for a family history of lung cancer, breast cancer, prostate cancer, colon cancer, skin cancer, liver cancer, stomach cancer, brain cancer, thyroid cancer, or myeloma. This study suggests that the familial risk of NHL is influenced primarily by hematolymphoproliferative malignancies rather than other cancers. The familial effects of hematolymphoproliferative malignancies may be stronger for men aged 45 to 59, compared with those aged 31 to 44.

Adult↗

PubMed1998

Structure and mutagenesis of the Dbl homology domain.

Guanine nucleotide exchange factors in the Dbl family activate Rho GTPases by accelerating dissociation of bound GDP, promoting acquisition of the GTP-bound state. Dbl proteins possess a approximately 200 residue catalytic Dbl-homology (DH) domain, that is arranged in tandem with a C-terminal pleckstrin homology (PH) domain in nearly all cases. Here we report the solution structure of the DH domain of human PAK-interacting exchange protein (betaPIX). The domain is composed of 11 alpha-helices that form a flattened, elongated bundle. The structure explains a large body of mutagenesis data, which, along with sequence comparisons, identify the GTPase interaction site as a surface formed by three conserved helices near the center of one face of the domain. Proximity of the site to the DH C-terminus suggests a means by which PH-ligand interactions may be coupled to DH-GTPase interactions to regulate signaling through the Dbl proteins in vivo.

Amino Acid Sequence↗

PubMed1998

Self-reported infectious mononucleosis and 6 cancers: a population-based, case-control study.

A study was undertaken to estimate the magnitude of association between self-reported infectious mononucleosis (IM) and 6 types of cancer, including Hodgkin's disease, non-Hodgkin's lymphoma, nasopharyngeal cancer, nasal cancer, primary liver cancer, and sarcoma. Cases were male, aged 15-39 y in 1968, who lived in 8 cancer registry areas. Controls were men selected by random-digit telephone dialing. Cases included 1511 persons with non-Hodgkin's lymphoma, 343 with Hodgkin's disease, 386 with sarcoma and 168, 113 and 70 with primary liver, nasopharyngeal and nasal cancers, respectively. There were 1910 controls. For the 6 cancers combined, the overall odds ratio for IM occurring < 5 and > or = 5 y of the reference date were 5.40 [95% (Confidence Interval (CI) = 1.61, 18.09] and 1.08 (0.84, 1.40), respectively. Analogous values were 4.59 (1.25, 16.85) and 1.07 (0.78, 1.48) for non-Hodgkin's lymphoma and 7.49 (1.52, 36.92) and 1.35 (0.87, 2.09) for Hodgkin's disease. There was the suggestion of a protective association with IM occurring > or = 5 y before cancer onset for the 4 non-lymphomatous cancers. Strongly positive associations between self-reported IM and 6 types of cancer were observed for IM occurring < 5 y before the onset of cancer. There was a suggestion, which is noted with extreme caution, that IM earlier in life might have had a protective association with the 4 non-lymphomatous cancers.

Adolescent↗

PubMed1998

Phospholipase A2 activity in salivary glands and saliva of the lone star tick (Acari: Ixodidae) during tick feeding.

Phospholipase A2 (PLA2) activity levels in tick [Amblyomma americanum (L.)] salivary glands and saliva were examined during tick feeding by using 14C-phosphatidylcholine as the substrate. Saliva produced by stimulating female ticks to salivate with dopamine contains PLA2 (ts-PLA2) activity. The ts-PLA2 activity level in saliva did not change significantly during tick feeding except for a decrease in the last rapid feeding phase (> 200 mg) and in replete ticks. Phospholipase A2 activity was higher in salivary glands of fed than unfed ticks, both in males and females; activity increased during tick feeding correlating with salivary secretory rates during tick feeding suggesting that much of the PLA2 activity measured in whole salivary glands is synthesized for subsequent secretion. During the time course of in vitro salivation, the first 10 microliters of saliva contained higher ts-PLA2 activity than saliva secreted thereafter. Phospolipase A2 was identified in the saliva of artificially fed ticks indicating that ts-PLA2 is a physiological component of tick saliva.

Animals↗