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Biomedical subjects

L Wei

Publications and source records attributed to L Wei.

At least 289 records · Page 16Linked to original sources
PubMed1980

Unscheduled DNA synthesis and chromosome aberrations induced by inorganic and organic selenium compounds in the presence of glutathione.

Glutathione strongly enhanced the induction of unscheduled DNA synthesis (UDS) in cultured human cells by inorganic selenium compounds: sodium selenate, sodium selenite and sodium selenide. In the presence of 10(-3) M glutathione, high levels of UDS (74-114 grains per nucleus) were observed in cells treated with (i) selenate at 10(-3) M, (ii) selenite at 10(-5)-3 X 10(-4) 7, and (iii) selenide at 10(-5)-10(-3) M. Glutathione at 10(-3) M also enhanced the clastogenic and cytotoxic effects of selenite and selenate in Chinese hamster ovary (CHO) cells. Glutathione at 10(-4) M or 10(-2) M caused less enhancement of DNA damage and toxicity in both the UDS and chromosome aberration assays. In the absence of glutathione, these inorganic selenium compounds induced low levels of UDS (up to 13 grains per nucleus) and moderate frequencies of chromosome aberrations (up to 11%). 3 organic selenium compounds (selenocystine, selenocystamine and selenomethionine) were also examined for the induction of UDS. No unscheduled DNA synthesis was detected in cells treated with selenocystamine or selenomethione, with or without added glutathione. However, selenocystine alone at 10(-4)-10(-3) M induced a low level of UDS; glutathione enhanced the DNA-damaging effect of selenocystine. The maximum amount of UDS (22 grains/nucleus) occurred in the presence of 10(-2) M glutathione. This was about one-fifth of that detected in cells treated with inorganic selenium compounds and 10-fold lower concentrations of glutathione (10(-3) M). The results suggest that recution is involved in the conversion of selenium compounds to mutagenic forms. The active mutagens may be selenols, GS-Se- from inorganic selenium and R-Se- from organic selenium compounds.

Animals↗
PubMed1979

Enhancement by transition metals of unscheduled DNA synthesis induced by isoniazid and related hydrazines in cultured normal and xeroderma pigmentosum human cells.

In combination with transition metals (Mn(II), Cu(II), and Fe(III)), isoniazid and related hydrazine compounds induced unscheduled DNA synthesis (DNA repair) in cultured human fibroblasts. Manganese at 10(-5) and 10(-4) M strongly enhanced DNA repair induced by isoniazid, iproniazid, nialamide and hydrazine. Peak levels of DNA repair occurred at 5 x 10(-4)--10(-3) M of the 4 hydrazine compounds. Copper caused less enhancement of DNA repair while iron had no detectable effect. Without added metal, unscheduled DNA synthesis was not observed in cells treated with any of the 4 freshly-prepared hydrazine compounds. However, following preincubation in medium for 6--12 h, isoniazid alone at high concentrations (10(-2) M--10(-1) M) induced DNA repair. With isoniazid/manganese mixtures, preincubation did not further enhance DNA repair except at low concentrations of isoniazid (2--5 x 10(-4) M). Catalase reduced the DNA damage caused by preincubated isoniazid and by the isoniazid/metal mixtures. Exposure of repair-deficient xeroderma pigmentosum cells to isoniazid plus manganese resulted in a DNA-repair profile similar to that of normal cells. The results are consistent with hydrogen peroxide being a critical intermediate for the production of free radicals which cause the observed DNA damage.

Cells, Cultured↗
PubMed1979

Enhancement of the chromosome-damaging action of ascorbate by transition metals.

Freshly prepared ascorbate inhibited mitosis and induced chromosome aberrations in cultured Chinese hamster ovary cells. Cu(II) and Mn(II) (10(-4) or 10(-5) M) enhanced both actions. Fe(II) and Fe(III) (10(-4) or 10(-5) M) reduced or abolished the mitosis-inhibiting action of ascorbate. At 10(-4) M, Fe(II) and Fe(III) strongly enhanced the chromosome-damaging capacity of ascorbate. Up to 100% of all examined metaphase plates had multiple chromosome exchanges or breaks. Since the cytostatic and clastogenic effect of ascorbate of H2O2 to induce chromosome aberrations was examined. H2O2 and a H2O2: Fe(II) mixture (Fenton reagent) induced chromosome breaks and exchanges but to a lesser degree than did ascorbate: Cu(II), Mn(II), Fe(II), or Fe(III) mixtures. Whether the strong chromosome damaging capacity of ascorbate plus transition metals as seen in the in vitro test system poses a health hazard only properly designed in vivo studies can reveal.

Animals↗
PubMed1978

The need for a mammalian test system for mutagens: action of some reducing agents.

Reducing agents and cysteine, cysteamine, glutathione, ascorbic acid and H2O2 with and without the addition of Cu2+ did not increase significantly the frequency of mutations in the Salmonella test at non-toxic concentrations but triggered a marked DNA repair synthesis and induced a relatively high frequency of chromosome aberrations in cultured mammalian cells. Both latter effects were reduced by the addition of catalase to solutions of the reducing agents plus Cu2+. To avoid 'False Negatives' in mutagenicity screening the use of several test subjects including mammalian cells seems to be required.

Animals↗
PubMedDate not supplied

Review of guidelines and literature for handling missing data in longitudinal clinical trials with a case study.

Missing data in clinical trials are inevitable. We highlight the ICH guidelines and CPMP points to consider on missing data. Specifically, we outline how we should consider missing data issues when designing, planning and conducting studies to minimize missing data impact. We also go beyond the coverage of the above two documents, provide a more detailed review of the basic concepts of missing data and frequently used terminologies, and examples of the typical missing data mechanism, and discuss technical details and literature for several frequently used statistical methods and associated software. Finally, we provide a case study where the principles outlined in this paper are applied to one clinical program at protocol design, data analysis plan and other stages of a clinical trial.

Clinical Trials as Topic↗
PubMedDate not supplied

Crystal structure of the tyrosine kinase domain of the human insulin receptor.

The X-ray crystal structure of the tyrosine kinase domain of the human insulin receptor has been determined by multiwavelength anomalous diffraction phasing and refined to 2.1 A resolution. The structure reveals the determinants of substrate preference for tyrosine rather than serine or threonine and a novel autoinhibition mechanism whereby one of the tyrosines that is autophosphorylated in response to insulin, Tyr 1,162, is bound in the active site.

Amino Acid Sequence↗
PubMedDate not supplied

Neuronal units linked to microvascular modules in cerebral cortex: response elements for imaging the brain.

How neuronal activity changes cerebral blood flow is of biological and practical importance. The rodent whisker-barrel system has special merits as a model for studies of changes in local cerebral blood flow (LCBF). Stimulus-evoked changes in neural firing and 'intrinsic signals' recorded through a cranial window were used to define regions of interest for repeated flow measurements. Whisker-activated changes in flow were measured with intravascular markers at the pia. LCBF changes were always prompt and localized over the appropriate barrel. Stimulus-related changes in parenchymal flow monitored continuously with H2 electrodes recorded short latency flow changes initiated in middle cortical layers. Activation that increased flow to particular barrels often led to reduced flow to adjacent cortex. Dye was injected into single penetrating arterioles from the pia of the fixed brain and injected into arterioles in slices of cortex where barrels were evident without stains. Arteriolar and venular domains at the surface were not directly related to underlying barrels. Capillary tufts in layer IV were mainly coincident with barrels. The matching between a capillary plexus (a vascular module) and a barrel (a functional neuronal unit) is a spatial organization of neurons and blood vessels that optimizes local interactions between the two. The paths of communication probably include: neurons to neurons, neurons to glia, neurons to vessels, glia to vessels, vessels to vessels and vessels to brain. Matching a functional grouping of neurons with a vascular module is an elegant means of reducing the risk of embarrassment for energy-expensive neuronal activity (ion pumping) while minimizing energy spent for delivery of the energy (cardiac output). For imaging studies this organization sets biological limits to spatial, temporal and magnitude resolution. Reduced flow to nearby inactive cortex enhances local differences.

Animals↗
PubMedDate not supplied

A new computer-assisted method for the quantification of enhancing lesions in multiple sclerosis.

PURPOSE: Our goal is to describe a new computerized method for the detection and quantification of enhanced multiple sclerosis (MS) lesions. METHOD: Gd-DTPA-enhanced, thin section, T1-weighted images of seven patients (involving 336 slice images) with definite MS were analyzed using a new method based on the theory of "fuzzy connected components," developed and implemented on the 3DVIEWNIX software system. Four neuroradiologists selected "true" lesions from the computer-detected potential lesions with a yes/no response to the program query on 2 different days. The enhanced lesion volume and number of enhancing lesions for each image and each observer were subsequently computed. Additional studies involving 720 slices were conducted to determine lesions that were missed by the system. RESULTS: The intra- and interobserver variability in the system was 0%. It took approximately 1 min of operator time per 3D study. The system output has no false positives and a mean false-negative volume of 1.3%. CONCLUSION: The novel system calculates enhancing lesion volume and the number of enhancing lesions with very little operator time, inter- and intraoperator variability, or false-positive and false-negative volumes. Computer-based quantification of enhancing lesion volume is an important objective measure of the activity of MS. The system is now in routine use in clinical investigations that study the role of enhancing lesions in the MS disease.

Brain↗
PubMedDate not supplied

Extended effects of human papillomavirus 16 E6-specific short hairpin RNA on cervical carcinoma cells.

Most cervical carcinomas express high-risk human papillomavirus (HPV) E6 and E7 oncogenes. Small interfering RNA can mediate sequence-specific inhibition of gene expression in mammalian cells. To find a most effective short hairpin RNA (shRNA) for HPV16 E6 messenger RNA (mRNA) and investigate the extended effects of the HPV16 E6 shRNA on cervical carcinoma cells, we stably transfected SiHa cells with four shRNA expression vectors (E6A-D). HPV16 E6A shRNA was found to be the most efficient in our study, which caused the reduction of HPV16 E6 mRNA to 10% in SiHa cells but did not reduce HPV18 E6 mRNA expression in HeLa cells. We subsequently demonstrated that E6A could stably express shRNA and effectively reduce HPV16 E6 and E7 viral genes expression in SiHa cells for more than 4 months. After E6 and E7 repression, there was a dramatic accumulation of p53, p21, and hypophosphorylated pRb proteins in cells. Furthermore, cell proliferation, colony formation ability, tumorigenicity, and in vitro cell invasive capability were suppressed substantially in E6A-transfected cells. These results suggest that the use of shRNA expression vector may be a potential approach for the treatment of persistent HPV infection and HPV-positive cervical carcinoma.

Animals↗
PubMedDate not supplied

Expression of estrogen receptor-related receptor isoforms and clinical significance in endometrial adenocarcinoma.

Estrogen receptor-related receptors (ERRs) are members of orphan nuclear receptors closely related to the estrogen receptors (ERs). Researches showed that the ERRs bound to estrogen response elements and interfered in the ER signal pathway. Therefore, it might be associated with estrogen-dependent diseases. The purpose of this study was to explore whether ERRs were involved in the tumorigenesis of endometrial adenocarcinoma. We examined the expression of ERRs in endometrial adenocarcinoma and normal endometrium using semiquantitative reverse transcription-polymerase chain reaction and immunohistochemistry. Clinicopathologic features including FIGO stage, histologic grade, myometrial invasion, and nodal metastasis were reviewed. Results showed that messenger RNA (mRNA) levels of ERRalpha, ERRbeta, and ERRgamma were positively associated with the immunoreactivities (P= 0.009, P= 0.014, and P= 0.001, respectively). The expression rate and relative level of ERRalpha mRNA in ERalpha-positive endometrial adenocarcinomas were lower than in normal endometriums (P= 0.049 and P= 0.023), whereas the relative level of ERRgamma mRNA in ERalpha-positive endometrial adenocarcinomas was higher than in normal endometriums (P= 0.014). Expression of ERRalpha mRNA was positively correlated with FIGO stage (P= 0.019) and myometrial invasion (P= 0.043). A negative correlation was observed between expression of ERRgamma mRNA and nodal metastasis (P= 0.021). Results suggested that ERRalpha and ERRgamma might participate in the tumorigenesis of endometrial adenocarcinoma. ERRalpha and ERRgamma are promising to be new prognostic factors in endometrial adenocarcinoma.

Adenocarcinoma↗
PubMedDate not supplied

Optimizing ACTH-stimulated steroid secretion by cultured adrenocortical tumor cells.

If 1 mM supplemental Ca++, or 1.6 mg hemoglobin (Hb)/ml medium (23.5 uM, a concentration comparable to that in 1 ml mouse blood), was added to Eagle's minimum essential medium (MEM) (which contains 1 mM Ca++), basal and maximally stimulated 20-dihydroprogesterone (20-DHP) secretion by cultured Y-1 mouse adrenal tumor cells [49-65th passages] could be measured by radioimmunoassay after a 0.5 hr incubation. ACTH-stimulated, but not basal, 20-DHP secretion increased after 1 mM Ca++ treatment. 5 mM EGTA significantly reduced basal and stimulated 20-DHP secretion, although significant ACTH stimulation still remained. Basal and stimulated secretion significantly increased when Hb was present. Although O2 involvement in the Hb effect was tested by bubbling medium with 100% O2 for 10 minutes, basal and stimulated secretion was unaffected. Since proteins, such as Hb, non-specifically bind free steroids, enhancing secretion, albumin (Al) was compared to Hb. Al enhanced unstimulated, but not ACTH-stimulated, 20-DHP secretion. The Hb effect may not be due to non-specific protein-steroid binding. Ca++ supplementation and chelation studies suggest the necessity to optimize co-factors in steroidogenic tissue incubation media to maximize basal and stimulated steroid synthesis and secretion. Since physiologically relevant Hb levels enhanced basal and stimulated Y-1 cell steroid secretion by mechanisms other than protein-steroid binding and soluble O2 had little effect, Hb may more efficiently transport O2 to cultured cells than soluble O2 diffusion through medium does.

20-alpha-Dihydroprogesterone↗
PubMedDate not supplied

Serial analysis of magnetization-transfer histograms and Expanded Disability Status Scale scores in patients with relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: Magnetization transfer ratio histogram peak height (MTR-HPH) has been shown to correlate with macroscopic and microscopic brain disease in patients with multiple sclerosis (MS). We studied the changes in MTR-HPH and in Kurtzke's Expanded Disability Status Scale (EDSS) scores over time in a group of patients with relapsing-remitting MS. METHODS: Twenty adult patients with relapsing-remitting MS (four men and 16 women) were followed up for a period of 334 to 1313 days. In all, 86 MR imaging studies of the brain were obtained, and MTR-HPH was calculated for each MR examination by using a semiautomated technique. Changes in MTR-HPH were compared between patients over the study's duration. A neurologist specialized in the care of MS patients assessed the EDSS score for each patient as a measure of clinical disability. RESULTS: Serial MR data showed a subtle but significant decline in MTR-HPH with time. No significant changes in EDSS scores were noted over the same period. CONCLUSION: Patients with relapsing-remitting MS have a significant progressive decline in normalized MTR-HPH, which is independent of EDSS score. MTR-HPH measurements can be used to monitor subclinical disease in patients with relapsing-remitting MS over a short time frame of 1 to 4 years. This parameter might be applied in future therapeutic trials to assess its usefulness.

Adult↗
PubMedDate not supplied

MR lesion load and cognitive function in patients with relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) is a demyelinating disease most often associated with progressive physical impairment; however, its effects are noted to extend beyond physical disability. Our purpose was to determine the relationship between T2 lesion volume and neurocognitive and physical disability in relapsing-remitting multiple sclerosis. METHODS: We studied a cohort of 19 patients with relapsing-remitting MS. Of this group, there were 15 women and four men from varying socioeconomic backgrounds. This volunteer sample was selected from a larger group of 53 patients with MS in our longitudinal MS study because they had been untreated with any beta-interferon medications, had been followed for at least 12 months, and had a clinical status of relapsing-remitting MS. RESULTS: Of 12 neurocognitive parameters tested, two correlated significantly with lesion loads. The correlation of the Symbol-Digit Modalities test, which analyzes information-processing speed, was significant (P = .0204). The correlation of the fifth trial of the Rey Auditory Verbal Learning test, which tests verbal long-term memory, was also significant (P = .0348). None of the other 10 neurocognitive examinations, however, showed a significant correlation with total lesion volume (Paced Auditory Serial Addition test-1.6, P = .7381; Paced Auditory Serial Addition test-2.0, P = .4180; Controlled Oral Word Association test, P = .8906; Category Fluency test, P = .4423; Bells test, P = .9097; Rey Auditory Verbal Learning test-delay, P = .9843, Rey Auditory Verbal Learning test-recognition, P = .7467; Word Span test, P = .4939; Road Map test, P = 0.4939). The lesion load also did not correlate with the physical disability scales as rated according to the Expanded Disability Status Scale (P = .68) or Ambulation Index (P = .95). CONCLUSION: Our results indicate that T2 lesion volume does not seem to be a robust surrogate marker of neuropsychological impairment in patients with MS. We think that global measurements of parameters that are more specific to the disease process may offer more precise correlation with cognitive dysfunction and other disability parameters.

Adult↗
PubMedDate not supplied

Isolation and identification of chicken infectious anemia virus in China.

A chicken infectious anemia virus (CIAV) isolate was obtained from broiler flocks aged 25-40 days with anemia and poor performance and was designated SR43. The CIAV isolate was resistant to treatment with chloroform and induced thymus atrophy, bone marrow aplasia, and low hematocrit values when inoculated into 1-day-old, susceptible, specific-pathogen-free chicks. CIAV-specific antigens could be demonstrated in SR43-infected MDCC-MSB-1 cells, a cell line derived from a Marek's disease lymphoma, with the use of a monoclonal antibody specific for CIAV. CIAV DNA in infected MDCC-MSB-1 cell cultures was detected by using a polymerase chain reaction assay. These findings demonstrate that CIAV is present in China.

Animals↗