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Biomedical subjects

H Lai

Publications and source records attributed to H Lai.

At least 37 records · Page 2Linked to original sources

The lymphocytic choriomeningitis virus RING protein Z associates with eukaryotic initiation factor 4E and selectively represses translation in a RING-dependent manner.

Only a few host cell proteins that associate with arenaviruses have been identified. To date, the arenavirus Z protein associates with the promyelocytic leukemia protein PML and the ribosomal P proteins. The majority of PML is present in nuclear bodies which are translocated to the cytoplasm by infection with the arenavirus, lymphocytic choriomeningitis virus (LCMV). The Z protein is a small zinc-binding RING protein with an unknown function which is required for the viral life cycle. Here, we demonstrate an association between Z and the host cell translation factor, eukaryotic initiation factor 4E (eIF-4E) in infected and transfected cells. Z's association with both ribosomal proteins and this translation factor led us to investigate whether Z could modulate host cell translation. In cell culture, Z selectively represses protein production in an eIF-4E-dependent manner. Specifically, we see reduction in cyclin D1 protein production with no effect on glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in cells transfected with Z. Previous reports indicate that cyclin D1 is sensitive to eIF-4E levels, whereas GAPDH is not. Consistent with this, we observe preferential downregulation of cyclin D1 during infection and no effect on GAPDH. Further, no changes in RNA levels were observed for cyclin D1 or GAPDH transcripts. The interaction between eIF-4E and Z may provide a mechanism for slower growth observed in infected cells and a viral strategy for establishing chronic infection.

3T3 Cells↗

HIV-related high risk sexual behaviors and practices among women in Bogotá, Colombia.

Determinants associated with high-risk sexual behaviors were investigated in 1,133 sexually active women in Bogotá, Colombia. A self-administered questionnaire was completed by two groups of women: 721 representing the general population (GP), and 412 commercial sex workers (CSWs). High-risk sexual behaviors for HIV/AIDS were evident in both groups. Nevertheless, consistent condom use was reported by only 6% of the GP group, as compared to 67% of the CSWs. Failure to recognize high-risk routes for HIV infection was indicated in 69% of the GP women for anal sex, and by the majority of both groups for intercourse during menses (56% GP women and 54% CSWs). Multivariate analysis revealed that education level, actual age, and age of first sex experience were significant predictors of high-risk sexual practices. The necessity for educational programs regarding high-risk sexual practices and risk of HIV/ AIDS is evident for HIV/AIDS prevention.

Adolescent↗

The association between cigarette smoking and drug abuse in the United States.

Cigarette smoking has been identified as an independent risk factor for many human diseases. However, the association between cigarette smoking and illegal drug use has not been thoroughly investigated. We have analyzed the 1994 National Household Survey on Drug Abuse to clarify whether cigarette smoking has any effect on the initiation of illegal drug use. Data from 17,809 respondents completing the 1994 "new" (1994-B) questionnaire were analyzed. Logistic regression analyses were performed with the use of statistical package SUDAAN, taking into consideration the multistage sampling design. The results show that those who had smoked cigarettes were far more likely to use cocaine (OR = 7.5; 95% CI: 5.7-9.9), heroin (OR = 16.0; 95% CI: 6.8-37.9), crack (OR = 13.9; 95% CI: 7.9-24.5) and marijuana (OR = 7.3; 95% CI: 6.2-8.7). The associations are consistent across age-strata and remain after adjusting for race and gender. This study suggests that cigarette smoking may be a gateway drug to illegal drug use.

Adolescent↗

Acute exposure to pulsed 2450-MHz microwaves affects water-maze performance of rats.

Rats were trained in six sessions to locate a submerged platform in a circular water maze. They were exposed to pulsed 2450-MHz microwaves (pulse width 2 micros, 500 128;pulses/s, average power density 2 mW/cm(2), average whole body specific absorption rate 1.2 W/kg) for 1 h in a circular waveguide system immediately before each training session. One hour after the last training session, they were tested in a probe trial during which the platform was removed and the time spent in the quadrant of the maze in which the platform had been located during the 1-min trial was scored. Three groups of animals, microwave-exposed, sham-exposed, and cage control, were studied. Microwave-exposed rats were slower than sham-exposed and cage control rats in learning to locate the platform. However, there was no significant difference in swim speed among the three groups of animals, indicating that the difference in learning was not due to a change in motor functions or motivation. During the probe trial, microwave-exposed animals spent significantly less time in the quadrant that had contained the platform, and their swim patterns were different from those of the sham-exposed and cage control animals. The latter observation indicates that microwave-exposed rats used a different strategy in learning the location of the platform. These results show that acute exposure to pulsed microwaves caused a deficit in spatial "reference" memory in the rat.

Animals↗

[The relationship between ECochG and glycerol test in vertigo patients (report of 112 cases)].

OBJECTIVE: For further investigating the diagnostic value of the ECochG in Meniere's disease. METHOD: 112 vertigo patients including Meniere's disease, sudden deafness, cervical vertigo and other vertigo disease, had been done ECochG, glycerol test, audiometry and caloric test. The results were compared with those of normal group. RESULT: In Meniere's disease, the positive rate of abnormal-SP/AP in ECochG was 54.69% and the positive rate of glycerol test was 53.12%. There are no statistics difference (P > 0.05) between this two tests with X analysis. CONCLUSION: We think that the glycerol test and other relative examination are necessary for the diagnosis of Meniere's disease while the-SP/AP > 0.4 ms in the examination of ECochG.

Adolescent↗

Direct activation of the fission yeast PAK Shk1 by the novel SH3 domain protein, Skb5.

The p21-activated kinase (PAK) homolog Shk1 is essential for cell viability in the fission yeast Schizosaccharomyces pombe. Roles have been established for Shk1 in the regulation of cell morphology, sexual differentiation, and mitosis in S. pombe. In this report, we describe the genetic and molecular characterization of a novel SH3 domain protein, Skb5, identified as a result of a two-hybrid screen for Shk1 interacting proteins. S. pombe cells carrying a deletion of the skb5 gene exhibit no discernible phenotypic defects under normal growth conditions, but when subjected to hypertonic stress, become spheroidal in shape and growth impaired. Both of these defects can be suppressed by overexpression of the Shk1 modulator, Skb1. The growth inhibition that results from overexpression of Shk1 in S. pombe cells is markedly suppressed by a null mutation in the skb5 gene, suggesting that Skb5 contributes positively to the function of Shk1 in vivo. Consistent with this notion, we show that Skb5 stimulates Shk1 catalytic function in S. pombe cells. Furthermore, and perhaps most significantly, we show that bacterially expressed recombinant Skb5 protein directly stimulates the catalytic activity of recombinant Shk1 kinase in vitro. These and additional data described herein demonstrate that Skb5 is a direct activator of Shk1 in fission yeast.

Amino Acid Sequence↗

Visual quantification of DNA double-strand breaks in bacteria.

In this paper, we describe a method for the visualization of double-strand breaks in a single electrostretched Escherichia coli DNA molecule. We also provide evidence that electrostretched or migrated DNA under neutral microgel electrophoresis conditions is made up of individual chromosomes. Using the neutral microgel electrophoresis technique, DNA migration (stretching) was measured and the number of DNA double-strand breaks were counted following exposure of E. coli cells to 0, 12.5, 25, 50, or 100 rad of X-rays. The use of an intense fluorescent dye, YOYO and custom-made slides have helped us in visualizing individual bacterial DNA molecules. Bacterial DNA appears similar in structure compared to electrostretched DNA from human lymphocytes. We were able to detect changes in DNA migration (stretching) induced by an X-ray dose as low as 12.5 rad and an increase in the number of DNA breaks induced by a dose as low as 25 rad. The extent of DNA migration and number of breaks were directly correlated to X-ray dosage.

Benzoxazoles↗

Mortality risk in selenium-deficient HIV-positive children.

OBJECTIVE: To determine the independent contribution of specific nutritional factors on disease progression and survival in HIV-1-infected children. POPULATION: HIV-infected children (N = 24), who were perinatally exposed to the virus and symptomatic, were recruited between October and December of 1990 from the Jackson Memorial Pediatric Immunology Clinic, Miami, Florida, and observed for 5 years. METHODS: Immune status was measured by CD4 cell count; nutritional status was determined using serum albumin and plasma trace elements including iron, zinc, and selenium. Cox proportional hazards regression models were used to evaluate the relationship of these parameters to survival. Use of antiretroviral treatment was considered in the statistical model, and age at death was considered a parameter of disease progression. RESULTS: Over the course of the study, 12 children died of HIV-related causes. The final Cox multivariate analysis indicated that, of the variables evaluated, only CD4 cell count below 200 (risk ratio [RR] = 7.05; 95% confidence interval [CI], 1.87-26.5); p = .004], and low levels of plasma selenium (RR = 5.96; 95% CI, 1.32-26.81; p = .02) were significantly and independently related to mortality. Among the children who died, those with low selenium levels (< or =85 microg/L), died at a younger age, suggesting more rapid disease progression. CONCLUSIONS: In pediatric HIV-infection, low plasma level of selenium is an independent predictor of mortality, and appears to be associated with faster disease progression.

Child↗

Granulocyte colony-stimulating factor-mobilized peripheral blood stem cells in beta-thalassemia patients: kinetics of mobilization and composition of apheresis product.

beta-Thalassemias are often associated with bone marrow expansion and immunomodulation in terms of lymphocyte subsets and cytokine levels in the peripheral blood. The mobilization of peripheral blood stem cells (PBSC) by cytokines in such a background has not been reported. If achieved, the apheresis product could be used as a stem cell back-up for beta-thalassemia patients prior to bone marrow transplant. PBSC collection may also become a means for providing stem and progenitor cells for gene manipulation and therapy of this disorder. The aim of the study was to assess the administration of G-CSF in mobilizing stem and progenitor cells in these patients and to compare the kinetics of CD34+ cells and lymphocyte subsets with those of healthy PBSC donors. Results showed that the CD34+ cells were effectively mobilized by G-CSF (10-16 micrograms/day per kg) in 20 thalassemia patients and 11 healthy donors. Although no significant difference was observed in levels of daily stem cell counts between the two groups of subjects, a 1 day delay in achieving peak levels of CD34+ cells was observed in the majority of thalassemia patients. The peak increase of CD34+ cells was 21.5 +/- 6.1-fold and 30.8 +/- 7.6-fold of the basal steady-state levels in thalassemia patients and healthy donors, respectively. Similar to the situation of healthy donors, G-CSF stimulated essentially the CD34+ cells and the myeloid lineage (granulocytes, monocytes) in thalassemia patients and had a slight effect on lymphocyte subsets (T-helper, T-suppressor, NK, and B cells) and activation (CD25, HLA-DR, and CD45RO). Compositions of the apheresis products, including CD34+CD38-, CD34+CD33+ and CD34+HLA-DR- cells, were similar in the two groups of subjects. Correlation studies showed that the level of CD34+ cells in the PB is a good indicator of that in the apheresis product (r = 0.88, p < 0.001). The study has demonstrated that under close monitoring of CD34+ cell levels in PB, the mobilization by G-CSF and collection of PBSC in beta-thalassemia patients are feasible.

Adolescent↗

Total immunoglobulin E levels and dengue infection on San Andrés Island, Colombia.

An evaluation of total immunoglobulin E (IgE) and dengue serostatus in 168 subjects from San Andrés Island, Colombia, revealed altered levels of IgE in 89% of the population. IgE levels were higher in patients with a history of dengue or with a current secondary or current primary infection than in subjects with no exposure (P = 0. 01). Dengue infection accounted for 23% of the variation in IgE levels.

Antibodies, Viral↗

Direct binding and In vivo regulation of the fission yeast p21-activated kinase shk1 by the SH3 domain protein scd2.

The Ste20/p21-activated kinase homolog Shk1 is essential for viability and required for normal morphology, mating, and cell cycle control in the fission yeast Schizosaccharomyces pombe. Shk1 is regulated by the p21 G protein Cdc42, which has been shown to form a complex with the SH3 domain protein Scd2 (also called Ral3). In this study, we investigated whether Scd2 plays a role in regulating Shk1 function. We found that recombinant Scd2 and Shk1 interact directly in vitro and that they interact in vivo, as determined by the two-hybrid assay and genetic analyses in fission yeast. The second of two N-terminal SH3 domains of Scd2 is both necessary and sufficient for interaction with Shk1. While full-length Scd2 interacted with only the R1 N-terminal regulatory subdomain of Shk1, a C-terminal deletion mutant of Scd2 interacted with both the R1 and R3 subdomains of Shk1, suggesting that the non-SH3 C-terminal domain of Scd2 may be involved in defining specificity in SH3 binding domain recognition. Overexpression of Scd2 stimulated the autophosphorylation activity of wild-type Shk1 in fission yeast but, consistent with results of genetic analyses, did not stimulate the activity of a Shk1 protein lacking the R1 subdomain. Results of additional two-hybrid experiments suggest that Scd2 may stimulate Shk1 catalytic function, at least in part, by positively modulating protein-protein interaction between Cdc42 and Shk1. We propose that Scd2 functions as an organizing center, or scaffold, for the Cdc42 complex in fission yeast and that it acts in concert with Cdc42 to positively regulate Shk1 function.

Binding Sites↗

The effect of marital status on survival in late-stage cancer patients: an analysis based on surveillance, epidemiology, and end results (SEER) data, in the United States.

Recently findings that marital status is associated with survival in patients with late-stage prostate cancer led to an examination of the generalizability of this association for all cancers. We restricted the investigation to patients with late-stage cancer using population-based data collected from 261,070 patients with late-stage cancer at multiple sites in the United States to determine relations between marital status and survival. After controlling for age, race, and treatment, married patients with cancers of all major primary sites had significantly better survival than single, separated, divorced, or widowed patients. Although single and widowed patients had the poorest prognosis in general, single patients appeared to show the most consistently poor survival across the different types of cancers. Survival differences by marital status were more pronounced in men than in women. This observation raises the possibility that some characteristics associated with being married delay death from cancer. These findings require investigators to ask new questions about the effect of being married and its possible correlates, such as general health status, access to health care, and socioeconomic status. Known correlates of marital status, such as available social support and social isolation also merit attention in relation to these findings.

Journal Article↗

60 Hz magnetic fields and central cholinergic activity: effects of exposure intensity and duration.

In previous research, we have found that acute exposure to a 60 Hz magnetic field caused a decrease in cholinergic activity in the frontal cortex and hippocampus of the rat. In the present study, the effects of exposure to different intensities of the magnetic field and durations of exposure were investigated. Rats were exposed to a 60 Hz magnetic field for 60 min at a flux density of either 0.5, 1.0, 1.5, or 2.0 mT. A significant decrease in cholinergic activity was observed in the frontal cortex and hippocampus immediately after exposure to the 2.0 mT field. No significant effect was observed at lower intensities. In another experiment, effect of exposure to a 1.0 mT magnetic field for 30, 45, 60, and 90 min was investigated. A decrease in cholinergic activity was found in both brain areas after 90 min of exposure. No significant effect was observed after shorter durations of exposure. In a further experiment, the exposure duration was extended to 3 h at flux densities of 0.5, 0.1, and 0.05 mT. A significant decrease in cholinergic activity was observed in the frontal cortex and hippocampus of the rat immediately after exposure to all the intensities. It is concluded that the intensity and duration of exposure interact. By increasing the duration of exposure, effects can be observed at lower intensities.

Animals↗

[Determination of active components in caoyiguang wettable powder by reversed-phase high performance liquid chromatography].

The Caoyiguang wettable powder is composed of two active components, synergists and other additives. The active components, bensulfuron methyl (Londax) and metolachlor (Dual), in 15.5% Caoyiguang wettable powder were determined by reversed phase high performance liquid chromatographic method simultaneously. The ZORBAX SB-C18 column (4.6 mm i.d. x 250 mm, 5 microns) and acidic mixture of methanol and water as mobile phase were used. The results showed that the recoveries were 98.1%-102.6%, and the coefficients of variation were 0.4%-0.8%. The method has been used to determine samples with satisfactory results.

English Abstract↗

60 Hz magnetic field exposure induces DNA crosslinks in rat brain cells.

In previous research, we found an increase in DNA strand breaks in brain cells of rats acutely exposed to a 60 Hz magnetic field (for 2 h at an intensity of 0.5 mT). DNA strand breaks were measured with a microgel electrophoresis assay using the length of DNA migration as an index. In the present experiment, we found that most of the magnetic field-induced increase in DNA migration was observed only after proteinase-K treatment, suggesting that the field caused DNA-protein crosslinks. In addition, when brain cells from control rats were exposed to X-rays, an increase in DNA migration was observed, the extent of which was independent of proteinase-K treatment. However, the X-ray-induced increase in DNA migration was retarded in cells from animals exposed to magnetic fields even after proteinase-K treatment, suggesting that DNA-DNA crosslinks were also induced by the magnetic field. The effects of magnetic fields were also compared with those of a known DNA crosslink-inducing agent mitomycin C. The pattern of effects is similar between the two agents. These data suggest that both DNA-protein and DNA-DNA crosslinks are formed in brain cells of rats after acute exposure to a 60 Hz magnetic field.

Animals↗

Allogeneic peripheral blood stem cell transplant in children.

Allogeneic peripheral blood stem cell (PBSC) transplant has recently been introduced for the treatment of hematological malignancies. As the data were limited mainly to adult patients, this study aimed to assess the feasibility and safety of this procedure in pediatric patients and donors. Eleven children aged 2-16 years received allogeneic PBSC transplant for acute lymphoblastic leukemia (n = 4), acute myeloid leukemia (n = 1), myelodysplastic syndrome (n = 1), severe aplastic anemia (n = 3), and thalassemia (n = 2). Nine donors were human leukocyte antigen (HLA)-identical siblings and the other two were one antigen mismatched family members. Eight donors were younger than 18 years old (10 months to 17 years). Donors were primed with granulocyte colony-stimulating factor (G-CSF) at 10-16 micrograms/kg for 4-5 days. Aphereses were performed on 1 or 2 consecutive days, and the patients received a mean of 14.4 x 10(8)/kg nucleated cells, 6.9 x 10(6)/kg CD34 cells, and 6.9 x 10(8)/kg T cells. All patients achieved neutrophil counts of > 0.5 x 10(9)/l at a median of 16 days. Nine patients achieved platelet counts of > 20 x 10(9)/l at a median of 13 days. Grade II acute graft vs. host disease (GVHD) occurred in only one patient. Chronic GVHD was not observed in the seven patients with follow-up of more than 3 months. Eight patients remained in continuous complete remission after transplant ranged from 2 to 26 months. Allogeneic PBSC transplant appears safe in pediatric patients and donors, and it seems not to be associated with increase of acute GVHD or chronic GVHD.

Adolescent↗

Dimensions of quality of life in prostate cancer.

PURPOSE: Quality of life research in prostate cancer involves the use of many questionnaires and specific items that may be partly redundant. We examine dimensions of quality of life in prostate cancer in the hope of somewhat simplifying communication of basic information. MATERIALS AND METHODS: We analyzed cross-sectional survey data on quality of life in patients with prostate cancer belonging to a Southern California HMO. Quality of life was assessed with the University of California, Los Angeles prostate cancer index. Scree plot and parallel analysis were used to identify factors for extraction and orthogonal (varimax) rotation to examine scale loadings. RESULTS: Four extracted factors explained a cumulative variance of 86%. The 8 physical and emotional scales loaded on 1 general factor explained 41% of the cumulative variance. Urinary function and bother, sexual function and bother, and bowel function and bother scales loaded on factors explained 16, 15 and 14% of the cumulative variance, respectively. CONCLUSIONS: The observation of only 1 general quality of life factor diverges from consistent previous observations of distinct physical and emotional factors in other types of patients, and the tight interaction of emotional and physical scales supports the vulnerability hypothesis, "with age the increasing interactions across dimensions of health leave a patient vulnerable in all when any is affected." The tight interaction of physical and emotional scales in these but not other patients opens the door theoretically to better evaluation of and targeting of health services for patients with prostate cancer.

Aged↗

The correlation of telomerase and IL-10 with leukemia transformation in a mouse model of chronic lymphocytic leukemia (CLL).

Telomerase activity is upregulated in activated and malignant lymphocytes. We studied the correlation of telomerase and IL-10 to leukemia transformation in the NZB mouse model of human chronic lymphocytic leukemia (CLL). Telomerase levels increased from early to late leukemic stages, likewise IL-10 gene expression levels increased with the leukemic progression. The inverse relationship of telomerase and IL-10 levels to the survival of NZB mice was also established. Our data suggested that telomerase and IL-10 were involved in transformation in the murine model of CLL and the detection of telomerase activities might be of value in the prediction of CLL progression.

Age Factors↗