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Biomedical subjects

K Wu

Publications and source records attributed to K Wu.

At least 217 records · Page 12Linked to original sources

[A study on behavioural characteristics of staying on the mountain and its relationship with malaria infection in Li and Miao minorities in Hainan Province].

A study of sociology combined with epidemiology was conducted in Li Minority's two villages and Miao Minority's two villages nearby the foot of mountain in a historically malaria hyperendemic area, Nanqiao Township of Wanning County in August, 1993. The results showed that malaria infection was closely correlated to the behaviour of staying overnight on the mountain of Li and Miao Minorities during farming seasons. Most of Li people stayed overnight on the mountain for planting areca were adults, accounting for 21.6% of the whole population, the duration of stay was about half a year; Miao people stayed overnight on the mountain planting and harvesting upland rice, always with their family member, so the percentage of people who had stayed on the mountain was as high as 82.1%, the duration of stay was about one and half a month. Blood smear examination showed that the malaria parasite rates in both Li and Miao villages were 11.1% and 24.1%, respectively, the positive rate of P. falciparum was 1.0% and 9.1%, respectively, the positive rate of IFA (titer >or= 1 : 40) was 31.2% and 46.5%, respectively. It is indicated that both the rate of parasitaemia and the P. falciparum infection were much higher in Miao Minority than those in Li Minority (P < 0.001). A cohort analysis showed that the malaria parasite rate of population who having not stayed, having ever stayed and being stayed on the mountain was 6.5%, 27.4% and 42.1%, respectively, of them the rate of P. falciparum infection was 0.5%, 8.8% and 18.4%, respectively. The results suggest that malaria acquired from mountainous forest referring to "up-mountain infection" is a major source of malaria infection and a significant risk factor in determining the prevalence of malaria (especially falciparum malaria) in Hainan Province. This behavioural risk factor has become the main obstacle for malaria control in Hainan Province. Therefore, controlling "up-mountain infection" and adopting appropriate anti-malaria measures to protect the risk population who have to work and stay on the mountain should be strengthened in the malaria control program.

China↗

Detection of tumor cells in the bone marrow of stage IV breast cancer patients receiving high-dose chemotherapy: the role of induction chemotherapy.

High-dose chemotherapy and hematopoietic support can produce long-term, disease-free remissions in selected patients with metastatic breast cancer. Occult bone marrow involvement may contribute to late relapse. We used five anti-breast cancer monoclonal antibodies and flow cytometry with cytological analysis of sorted immunostained cells to detect tumor cells in the bone marrow in two cohorts of patients. The first (Upfront) cohort was treated with a single course of high-dose chemotherapy and autologous bone marrow support (ABMS) without induction chemotherapy. The second (AFM) cohort received induction chemotherapy with doxorubicin, 5-fluorouracil and methotrexate prior to high-dose chemotherapy and ABMS. Of the 15 Upfront patients, seven (47%) had immunostained cells in the harvested bone marrow by flow cytometry and 8/15 (53%) had positive cytologies. Of the 49 AFM patients studied, nine (18%) had immunostained cells in the bone marrow, and only 1/49 (2%) had positive cytologies. Induction chemotherapy significantly decreased bone marrow contamination as detected by flow cytometry and cytology in patients with breast cancer. The detection of immunostained cells in the bone marrow did not predict for relapse or overall survival.

Antineoplastic Combined Chemotherapy Protocols↗

[Study on human gamma-crystallins: V. Non-enzymatic glycation of fetal lens gamma 1- and gamma 3-crystallins in vitro].

PURPOSE: To compare the non-enzymatic glycation of different human fetal gamma-crystallins induced by glucose and fructose. METHODS: gamma 1- and gamma 2-crystallin were separated by the Sephadex gel chromatography from human fetal lenses. The non-enzymatic glycations of these gamma-crystallins were conducted by incubating with glucose or fructose at 37 degrees C for 20 days. The opacity and pellet formation as well as changes on SDS-polyacrymide gel electrophoresis (SDS-PAGE) pattern and blue fluorescence production were observed. RESULTS: Although the two gamma-crystallins displayed similar alterations, gamma 1-crystallin was easier to produce aggregation and insolublization in early stage (i.e. 3 days). SDS-PAGE showed that there were aggregates, formed through disulfide and non-disulfide cross-links, and degraded peptides produced. The blue fluorescence increased in glycated gamma 3-crystalline solution. Fructose had more significant effects (i.e. aggregation, degradation, producing blue fluorescence) on gamma-crystallins as compared with glucose. CONCLUSION: Human fetal gamma 1- and gamma 3-crystallins are sensitive, at different extent (gamma 1 > gamma 3), to response to non-enzymatic glycation, and fructose has stronger effect than glucose on the glycation.

Crystallins↗

Amonafide: An active agent in the treatment of previously untreated advanced breast cancer--a cancer and leukemia group B study (CALGB 8642).

Amonafide is a new imide derivative of naphthalic acid. The drug had demonstrated significant activity in preclinical studies and some activity in Phase I trials. The drug is extensively metabolized and detected in plasma and urine. Its toxicity has previously been correlated to the formation of an active metabolite, N-acetyl-amonafide. Amonafide was chosen for inclusion in the Cancer and Leukemia Group B (CALGB) master metastatic breast cancer protocol. CALGB 8642 randomizes previously untreated metastatic breast cancer patients either to one of several Phase II agents given for up to four cycles and then followed by standard cyclophosphamide-doxorubicin-5-fluorouracil, or to immediate treatment with standard cyclophosphamide-doxorubicin-5-fluorouracil. The end point of CALGB 8642 is to assess the difference in survival, toxicity, and overall response when limited exposure to Phase II agents precedes standard chemotherapy. This report deals only with amonafide as a Phase II agent. Comparisons with the cyclophosphamide-doxorubicin-5-fluorouracil arm will not be addressed. Patients had to have histologically documented measurable breast cancer and a performance status of 0-1. Patients could not have had prior chemotherapy for metastatic disease. Prior adjuvant chemotherapy was permitted. Patients could not have visceral crisis. Amonafide was given at 300 mg/m2/day i.v. for 5 days, and repeated at 21-day intervals for a maximum of four cycles. Escalation and reduction in dose was mandated dependent on hematotoxicity or lack thereof. Toxicity was primarily hematological and bimodal: 32% had grade 3 or 4 leukopenia and 24% had grade 3 or 4 thrombocytopenia; 22% had no leukopenia and 44% had no thrombocytopenia. The response rate was 18%, including one complete response. When response was analyzed by hematological toxicity, there was a 35.7% response if patients had leukopenia grade 3/4 (versus 8.3%, P = 0.08). There was a 50% response if patients had thrombocytopenia grade 3/4 (versus 7.1%, P = <0.01). We conclude that amonafide is somewhat active in previously untreated breast cancer patients. There may be a steep dose-response curve, based on the significant correlation between myelosuppression and response. Rates of responses in patients adequately dosed (i.e., with significant hematotoxicity) with amonafide ranged from 35 to 50%. Further studies will incorporate individualized dosing based on pretreatment acetylator phenotyping.

Adenine↗

Homeotic transformation of cervical vertebrae in Hoxa-4 mutant mice.

Hoxa-4 (previously known as Hox-1.4) is a mouse homeobox-containing gene that is expressed in the presumptive hindbrain and spinal cord, prevertebrae, and other tissues during embryogenesis. To understand the role of Hoxa-4 during development, we generated Hoxa-4 mutant mice. Homozygous mutants were viable and fertile. Analysis of neonatal skeletons revealed the development of ribs on the seventh cervical vertebra at variable penetrance and expressivity. A low frequency of alterations in sternal morphogenesis was also observed. In addition, we analyzed the skeletons of transgenic mice that overexpress Hoxa-4 and found that the formation of the small rib anlagen that often develop on the seventh cervical vertebra was suppressed. Analysis of adult homozygous mutant skeletons revealed that the dorsal process normally associated with the second cervical vertebra was also found on the third cervical vertebra. These results demonstrate that Hoxa-4 plays a role in conferring positional information along the anteroposterior axis to specify the identity of the third and the seventh cervical vertebrae.

Animals↗

Molecular cloning and sequencing of the mucin subunit of a heterodimeric, bifunctional cell surface glycoprotein complex of ascites rat mammary adenocarcinoma cells.

Ascites sublines of the highly metastatic 13762 rat mammary adenocarcinoma contain abundant amounts of a heterodimeric cell surface glycoprotein complex composed of a mucin subunit ASGP-1 (ascites sialoglycoprotein-1) and a transmembrane subunit (ASGP-2). Previous studies showed that the complex is synthesized from a single polypeptide encoded by a 9 kb transcript. The sequence of the transmembrane subunit was obtained from a 5-kilobase (kb) cDNA isolated from a plasmid library (Sheng, Z., Wu, K., Carraway, K. L., and Fregien, N. (1992) J. Biol. Chem. 267, 16341-16346). Completion of the sequence of this cDNA revealed the C-terminal domain of ASGP-1, which is rich in serine and threonine but contains no typical mucin-type repeats. The remainder of the sequence of ASGP-1 and the 9-kb transcript was obtained by two 5'-RACE (rapid amplification of cDNA ends) steps and primer extension analysis. These results revealed that the 5' half of the 9-kb transcript contains a short 5'-noncoding region and encodes a signal sequence, a short nonrepeat region, and a repeat domain containing 11 repeats. Nine of these repeats are found in tandem, but the two end repeats are separated from the others by short unique sequences. The repeats vary from 117-124 amino acids and are 70-90% identical to a consensus sequence. Overall, the sequence predicts that ASGP-1 contains 2172 amino acids (M(r) 224,190), 43% of which are serine and threonine. We propose that the complex of this mucin and its transmembrane subunit, which contains growth factor-modulating activity, may play an important role in tumor progression.

Adenocarcinoma↗

Variation in breast cancer surgery in Ontario.

OBJECTIVES: To analyse the extent of variation by county and hospital in the use of breast-conserving surgery in the initial management of breast cancer and to assess some factors that might explain the observed variation. DESIGN: Population-based retrospective cohort study. SETTING: Ontario. PATIENTS: All women with breast cancer newly diagnosed from Jan. 1, 1989, to Dec. 31, 1991. MAIN OUTCOME MEASURE: Proportion of women undergoing unilateral breast cancer surgery who had breast-conserving surgery in each hospital and county. RESULTS: Of the 14,570 women with newly diagnosed breast cancer 12,815 (88.0%) underwent unilateral breast cancer surgery. The mean proportion of breast-conserving procedures by county was 52% and ranged from 11% to 84%. The proportion of breast-conserving procedures in individual hospitals with one or more cases of breast cancer per month ranged from 6% to 84%. The variations in the rates between hospitals was greater than that expected by chance alone (p < 0.0001). CONCLUSIONS: There was marked variation at the hospital and county level in the use of breast-conserving surgery in the initial management of breast cancer. This variation was strongly associated with the hospital where the surgery was performed.

Analysis of Variance↗

Lung cancer among tin miners in southeast China: silica exposure, silicosis, and cigarette smoking.

The Dachang Tin Mine is an industrial facility with high rates of lung cancer compared to the resident population in Guangxi province in southern China. Historically, exposure to silica dust was very high in the 1950s, falling in recent years to levels in keeping with international standards. Radon levels in the mine are low. We report the findings of a case-control study nested into a cohort study on miners working in Dachang. Cases of lung cancer among miners incident from 1973-1989 were obtained from local comprehensive medical records covering workers employed at the mine. These were matched approximately 3 to 1 with miners randomly chosen from the district surrounding the mine within the same birth decade. Matched odds ratios of 2.42 (95% confidence limit [CL] 1.3, 4.4) for underground employment, 3.52 (95% CL 1.7, 7.5) for smoking, and 2.04 (95%) CL 1.2, 3.7) for silicosis as determined on chest film were noted. Multifactor analysis of unconditional logistic regression showed that among the risk factors for excess mortality from lung cancer only the years spent drilling underground and the cumulative smoking index (product of daily cigarette consumption and number of years smoking) were independent contributors to risk and there was no interaction observed. The presence of silicosis did not contribute to predicting risk independently of the years spent underground.

Case-Control Studies↗

Saturated molecular map of the rice genome based on an interspecific backcross population.

A molecular map has been constructed for the rice genome comprised of 726 markers (mainly restriction fragment length polymorphisms; RFLPs). The mapping population was derived from a backcross between cultivated rice, Oryza sativa, and its wild African relative, Oryza longistaminata. The very high level of polymorphism between these species, combined with the use of polymerase chain reaction-amplified cDNA libraries, contributed to mapping efficiency. A subset of the probes used in this study was previously used to construct an RFLP map derived from an inter subspecific cross, providing a basis for comparison of the two maps and of the relative mapping efficiencies in the two crosses. In addition to the previously described PstI genomic rice library, three cDNA libraries from rice (Oryza), oat (Avena) and barley (Hordeum) were used in this mapping project. Levels of polymorphism detected by each and the frequency of identifying heterologous sequences for use in rice mapping are discussed. Though strong reproductive barriers isolate O. sativa from O. longistaminata, the percentage of markers showing distorted segregation in this backcross population was not significantly different than that observed in an intraspecific F2 population previously used for mapping. The map contains 1491 cM with an average interval size of 4.0 cM on the framework map, and 2.0 cM overall. A total of 238 markers from the previously described PstI genomic rice library, 250 markers from a cDNA library of rice (Oryza), 112 cDNA markers from oat (Avena), and 20 cDNA markers from a barley (Hordeum) library, two genomic clones from maize (Zea), 11 microsatellite markers, three telomere markers, eleven isozymes, 26 cloned genes, six RAPD, and 47 mutant phenotypes were used in this mapping project. Applications of a molecular map for plant improvement are discussed.

Avena↗

Overexpression of p53 and HER-2/neu proteins as prognostic markers in early stage breast cancer.

OBJECTIVE: Overexpression of the p53 and HER-2/neu oncogenes are the two most common genetic abnormalities associated with breast cancer. Shorter survival time has been reported in patients with tumors with p53 or HER-2/neu. This report analyzes a retrospective cohort of early stage breast cancers for both oncogenes and relates overexpression to clinicopathologic parameters and survival. METHODS: Immunostaining for p53 and HER-2/neu was performed on 230 paraffin-embedded specimens of stage I and II breast cancers diagnosed and treated at Duke University Medical Center between 1984 and 1987. Positive staining for both p53 and HER-2/neu in paraffin-embedded tissues indicates an underlying genetic abnormality: point mutations in the p53 gene and amplification of the HER-2/neu gene. RESULTS: In this cohort of patients, 24% were positive for p53 and 17% for HER-2/neu. Four per cent were positive for both oncogenes. Significant correlations were found between p53 immunostaining and increasing tumor size, stage, and low estrogen and progesterone receptor contents. Univariate analysis showed that p53 and HER-2/neu were indicators of overall and failure-free survival. An additive effect on survival was observed in patients with both oncogene abnormalities. Nodal status, HER-2/neu, and p53 all attained independent prognostic value in a multivariate analysis. CONCLUSIONS: The p53 and HER-2/neu oncogenes have proven but limited prognostic value. An approach that combines several molecular genetic markers with established pathologic criteria may help physicians to make more accurate predictions of prognosis in patients with early stage breast cancer.

Biomarkers, Tumor↗

[Study on soluble proteins in human fetal lens].

Soluble proteins from corter of human fetal clear lenses were separated by column chromatography with Sepharyl S-300 (superfine) and determined by disc-PAGE and SDS-PAGE. The results documented from 18W, 21W (2 cases) and 24W fetal lenses suggested that a negative correlation tended to be presented between the age of fetus and fraction of alpha, beta 1 crystallins (r = -0.9542; r = -0.9674) and a positive correlation between the age of fetus and fraction of beta 2, gamma crystallins (r = 0.9666; r = 0.9970). There was no change in the alpha, beta 1, beta 2 crystallins on disc-PAGE. Among the fetuses of different ages, the blurred band of gamma crystallin seen in 18W and 21W fetal lenses was thickened in the 24W fetal lens. The SDS-PAGE showed that there was no significant difference among the polypeptides in each of alpha, beta 1, beta 2, gamma crystallins in the studied fetal lenses of different age groups. It is presumed that the normal lens is proportionally composed of four fractions of crystallin. This is hypothetically contributed to the maintenance of normal structure of the lens, why the proper proportion of four fractions of crystallins is depended either on proteins synthesis or on protein molecular assembly is not yet clear.

Chromatography, Gel↗