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Biomedical subjects

M Ma

Publications and source records attributed to M Ma.

At least 55 records · Page 3Linked to original sources
PubMed2000

Methodological issues in the use of guidelines and audit to improve clinical effectiveness in breast cancer in one United Kingdom health region.

AIMS: To develop a system to improve and monitor clinical performance in the management of breast cancer patients in one United Kingdom health region. DESIGN: An observational study of the changes brought about by the introduction of new structures to influence clinical practice and monitor change. SETTING: North Thames (East) Health region, comprising seven purchasing health authorities and 21 acute hospitals treating breast cancer. SUBJECTS: The multi-disciplinary breast teams in 21 hospitals and an audit sample of 419 (28%) of the breast cancer patients diagnosed in 1992 in the region. INTERVENTIONS: Evidence-based interventions for changing clinical practice: regional guidelines, senior clinicians acting as < >, audit of quality rather than cost of services, ownership of data by clinicians, confidential feed-back to participants and education. OUTCOME MEASURES: Qualitative measures of organizational and behavioural change. Quantitative measures of clinical outcomes compared to guideline targets and to results from previous studies within this population. RESULTS: Organizational changes included the involvement, participation of and feedback to 16 specialist surgeons and their multidisciplinary teams in 21 hospitals. Regional clinical guidelines were developed in 6 months and the dataset piloted within 9 months. The audit cycle was completed within 2 years. The pilot study led to prospective audit at the end of 2 years for all breast cancers in the region and a 15-fold increase in high quality clinical information for these patients. Changes in clinical practice between 1990 and 1992 were observed in the use of chemotherapy (up from 17-23%) and axillary surgery (up from 46-76%). CONCLUSIONS: The approach used facilitated rapid change and found a balance between local involvement (essential for sustainability within a hospital setting) and regional standardization (essential for comparability across hospitals). The principles of the approach are generalized to other cancers and to other parts of the UK and abroad.

Breast Neoplasms↗
PubMed2000

Carvedilol enhances atrial and brain natriuretic peptide mRNA expression and release in rat heart.

To clarify the role of the natriuretic peptide (NP) system in the myocardial protective effects of carvedilol, a beta-blocking agent, we investigated the effects of carvedilol on the NP system in the rat heart. After oral administration of carvedilol (low-dose group: 2 mg/kg/day, group C2; high-dose group: 20 mg/kg/day, group C20) for 1 week, plasma rat atrial NP (r-ANP), atrial mRNA levels of ANP, left ventricular mRNA of brain NP (BNP), NP receptor-A and NP receptor-C (NPR-C) (as a clearance receptor) were measured. Values were compared with those in vehicle-treatment rats (group V). The concentration of r-ANP was significantly higher in group C2 (135 +/- 9 pg/ml) and group C20 (161 +/- 11 pg/ml) than group V (75 +/- 6 pg/ml; both p < 0.01). ANP and BNP mRNA levels were significantly increased and NPR-C was significantly down regulated in group C2 (151 +/- 7, 120 +/- 8 and 78 +/- 7%, respectively, vs. group V) and group C20 (164 +/- 8. 133 +/- 7 and 72 +/- 8%, respectively, vs. group V) compared with group V (all p < 0.01). These results suggest that not only a high dose, but a low dose of carvedilol has the effect of increasing plasma ANP and BNP levels. This effect was closely related to the upregulation of ANP and BNP mRNA expression, and the down regulation of NPR-C mRNA expression in the heart. These mechanisms seem to account for a sizable portion of the protective effect of carvedilol for heart diseases.

Adrenergic beta-Antagonists↗
PubMed2000

Determination of monomethylarsonous acid, a key arsenic methylation intermediate, in human urine.

In this study we report on the finding of monomethylarsonous acid [MMA(III)] in human urine. This newly identified arsenic species is a key intermediate in the metabolic pathway of arsenic biomethylation, which involves stepwise reduction of pentavalent to trivalent arsenic species followed by oxidative addition of a methyl group. Arsenic speciation was carried out using ion-pair chromatographic separation of arsenic compounds with hydride generation atomic fluorescence spectrometry detection. Speciation of the inorganic arsenite [As(III)], inorganic arsenate [As(V)], monomethylarsonic acid [MMA(V)], dimethylarsinic acid [DMA(V)], and MMA(III) in a urine sample was complete in 5 min. Urine samples collected from humans before and after a single oral administration of 300 mg sodium 2,3-dimercapto-1-propane sulfonate (DMPS) were analyzed for arsenic species. MMA(III) was found in 51 out of 123 urine samples collected from 41 people in inner Mongolia 0-6 hr after the administration of DMPS. MMA(III )in urine samples did not arise from the reduction of MMA(V) by DMPS. DMPS probably assisted the release of MMA(III) that was formed in the body. Along with the presence of MMA(III), there was an increase in the relative concentration of MMA(V) and a decrease in DMA(V) in the urine samples collected after the DMPS ingestion.

Arsenic↗
PubMed2000

Adenoviral-mediated gene transfer of ICP47 inhibits major histocompatibility complex class I expression on vascular cells in vitro.

PURPOSE: Many viruses have evolved mechanisms to evade detection by the host immune system. The herpes simplex gene ICP47 encodes a protein that binds to the host antigen-processing transporter, inhibiting the formation of major histocompatibility complex class I (MHC-I) antigens in infected cells. MHC-I antigen expression is also important in acute allograft rejection. This study was designed to quantitate the effect of adenoviral-mediated gene transfer of ICP47 on MHC-I cell surface expression of human vascular cells. We hypothesized that the transduction of vascular cells with a replication-incompetent adenoviral vector that was expressing ICP47 (AdICP47) would inhibit constitutive and inducible MHC-I expression and thereby reduce the rate of cytolysis of ICP47-transduced vascular cells by sensitized cytotoxic T lymphocytes (CTL). METHODS: A replication-incompetent adenoviral vector, AdICP47, was created to express ICP47 driven by the cytomegalovirus immediate early promoter. Cultured human vascular endothelial and smooth muscle cells and human dermal fibroblasts were transduced with either AdICP47 or the control empty vector AddlE1. Cell surface constitutive and gamma-interferon-induced MHC-I expression were quantitated by flow cytometry. A standard 4-hour chromium release cytotoxicity assay was used to determine the percent cytolysis of transduced and nontransduced endothelial cells by sensitized CTL. Finally, to quantitate the specificity of the effect of ICP47 on MHC-I expression, adhesion molecule expression was quantitated in both transduced and nontransduced cells. RESULTS: Constitutive MHC-I expression in AdICP47-transduced endothelial cells was inhibited by a mean of 84% +/- 5% (SEM) in five experiments. After 48 hours of exposure to gamma-interferon, AdICP47-transduced cells exhibited a mean of 66% +/- 8% lower MHC-I expression than nontransduced cells. Similar inhibition in MHC-I expression was achieved in AdICP47-transduced vascular smooth muscle cells and dermal fibroblasts. Percent cytolysis of AdICP47-transduced endothelial cells by CTL was reduced by 72%. Finally, the specificity of the effect of transduction of ICP47 on vascular cell MHC-I expression was confirmed by a lack of significant change in either constitutive or tumor necrosis factor-induced vascular cell adhesion molecule/intercellular adhesion molecule expression. CONCLUSION: Transduction of vascular cells with AdICP47 strongly inhibits both constitutive and inducible MHC-I expression in human vascular cells. AdICP47-transduced cells exhibited a substantial reduction in cytolysis by CTL. Thus AdICP47 transduction holds promise as a technique to characterize the role of MHC-I expression in acute vascular allograft rejection in vivo and as a potential therapeutic intervention.

Adenoviridae↗
PubMed2000

[Construction of B. thuringiensis shuttle vector and expression of the cry1C gene].

We have constructed the E. coli-Bt shuttle vector pHV-1 by cloning the replicon (approximately 1.6 kb) of Bt ken-Ag and the aphI gene of pUC4K into pUC19. The rate of plasmid maintenance is more than 80% after 100 generations in E. coli, whereas 80% after 40 generations in Bti 4Q8. We have also constructed pHV-cry1C through cloning the alpha-amylase promoter from B. licheniformis and the cry1C gene from Bt 9510 into pHV-1 and introduced it into Bti 4Q8 by means of electroporation. Under the microscope, we can see that there is no crystal in Bti 4Q8, however, there are many rhomboid crystals in Bti 4Q8 (pHV-cry1C), which are smaller than those of Bt 9510. The bioassay result of Bti 4Q8 (pHV-cry1C) demonstrates that the expressed crystal protein is insecticidally active against Spodoptera exigue.

Animals↗
PubMed2000

[Analysis of lymphocytic clone formation after stem cell transplantation and immunological reconstitution by gene fingerprinting].

OBJECTIVE: To analyze T lymphocytic clone formation in patients with malignant disease after bone marrow or peripheral blood stem cell transplantation and to understand the relationship between immunological reconstitution and clinic remission. METHODS: Due to the different TCRgamma gene rearrangements in different gamma/delta T cell clones, a gene fingerprinting was set up by PCR and denatured gel electrophoresis. The gene fingerprinting was used to analyze the gamma-delta T cell clone variations in 8 patients who received stem transplantation. In order to identify the source of the regenerated lymphocytes, the polymorphism of microsatellite was used at mean time. RESULTS: After PCR amplification and electrophoresis of each TCRgammaV region gene on a 60 cm sequence gel, a gene fingerprinting composed of about a hundred bands was set up. It showed the basic distribution of the dominant gamma/delta T cell clones in the body. Usually, a new band presenting after transplantation represented an expansive lymphocytic clone. Successful immunological reconstitution led to a good prognosis; and unsuccessful immunological reconstitution led to bad prognosis. After transplantation, some T cell clones expanded. Comparing the sequences of a expansive T cell clone in a multiple myeloma patient after auto-stem cell transplantation with 230 000 genes of immunoglobulin and T cell receptor in GeneBank, we found that two T cell line had homogenous sequences. Both T cell clones recognized homogeneous antigen. CONCLUSION: A new method to observe the distribution of gamma/delta T cells called gene fingerprinting was set up. Gene fingerprinting is useful in the analysis of immunological reconstitution after stem cells transplantation. The effect of transplantation is correlated to immunological reconstitution. Transplantation patients may appear some expansive T cell clones; probably they have anti - tumor effect.

Adult↗
PubMed2000

[An ultrastructural observation on rat retina after photoreceptor cell implantation].

OBJECTIVE: To further study the retinal neuronal signal. METHODS: The Wistar/RCS (RCS rats are rats with hereditary photoreceptor degeneration) rats were respectively as donors/acceptors, and the retinal pathway was reconstructed with the technique of pure photoreceptor transplantation. The photoreceptor layer of the retina was obtained with the technique of retinal whittle by manual method or excimer laser. The specimens were got separately at 2 weeks and 1 month after the transplantation and studied under the light and transmission electron microscopes. RESULTS: Most transplanted photoreceptors with physical poles were lined up regularly between the retinal pigment epithelium (RPE) and inner nuclear layer. It was shown that in the new outer plexiform layer the relatively integral synapse and its interconnection were seen. CONCLUSION: The retinal neuronal pathway can be reconstructed by retinal transplantation.

Animals↗
PubMed2000

[Expression of ET of early ischemic myocardium in rats].

To study the expression of ET of early ischemic myocardium, we designed a model of early myocardial ischemia (EMI) in rats. The study was conducted with SABC method and HE staining. Cardiac myocytes of ischemia showed a little ET-positive at 60-min. Cardiac myocytes, endothelium and smooth muscle of vessel showed ET-positive staining in the area of EMI after 120-min. Staining was negative for Ischemia myocardium at 30-min and for the control group. No change was seen with HE staining in all groups. The data indicates that ET-SABC method may reveal the injury of myocardial ischemia 60-min and longer and may provide a new marker to diagnose EMI in forensic pathology.

Animals↗
PubMed1999

Humoral response to herpes simplex virus is complement-dependent.

The complement system represents a cascade of serum proteins, which provide a major effector function in innate immunity. Recent studies have revealed that complement links innate and adaptive immunity via complement receptors CD21/CD35 in that it enhances the B cell memory response to noninfectious protein antigens introduced i.v. To examine the importance of complement for immune responses to virus infection in a peripheral tissue, we compared the B cell memory response of mice deficient in complement C3, C4, or CD21/CD35 with wild-type controls. We found that the deficient mice failed to generate a normal memory response, which is characterized by a reduction in IgG antibody and germinal centers. Thus, complement is important not only in the effector function of innate immunity but also in the stimulation of memory B cell responses to viral-infected cell antigens in both blood and peripheral tissues.

Animals↗
PubMed1999

Electrophysiological characterization of rat and mouse olfactory receptor neurons from an intact epithelial preparation.

To understand the coding mechanisms underlying olfactory discrimination, it is necessary to characterize odor response properties of olfactory receptor neurons (ORNs). In contrast with rapid progress in molecular biology, there is little physiological data from ORNs in rodent. To facilitate acquisition of such data, we have developed an intact olfactory epithelial preparation from both rat and mouse. We have carried out initial studies of this preparation by monitoring odor responses by patch-clamping directly on the ORN dendritic knobs, a subcellular site very close to the locus of olfactory signal transduction. Our results show that rat and mouse ORNs have similar intrinsic membrane properties. Most cells fired spontaneously at a low frequency (f) and about one half fired repetitively in response to current (I) injection with a linear f/I relation. About one third of rat and mouse ORNs responded to a mixture of four odors in a dose-dependent manner and about 60% of them responded to IBMX, a potent inhibitor of phosphodiesterase. The results suggest that this intact preparation offers the advantage of approximating in vivo physiological conditions, while furnishing an opportunity to map single neuron responses in the epithelium in a spatially-defined manner, using electrophysiological or cell imaging methods.

1-Methyl-3-isobutylxanthine↗
PubMed1999

Impaired odor adaptation in olfactory receptor neurons after inhibition of Ca2+/calmodulin kinase II.

Odor adaptation in vertebrate olfactory receptor neurons (ORNs) is commonly attributed to feedback modulation caused by Ca(2+) entry through the transduction channels, but it remains unclear and controversial whether this Ca(2+)-mediated adaptation resides in the cAMP-gated channel alone or whether other molecules of the transduction cascade are modulated as well. Attenuation of adenylyl cyclase activity by Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) has also been proposed as a mechanism for adaptation. To test this in intact ORNs, we have compared the properties of adaptation induced by a sustained (8 sec) or brief (100 msec) odor stimulus. Although adaptation induced by both types of stimuli occurs downstream from the odor receptors and is Ca(2+)-dependent, only adaptation induced by a sustained pulse involves alterations in the odor response kinetics, consistent with a reduction in the rate of adenylyl cyclase activation. By disrupting CaMKII to block adenylyl cyclase attenuation using a specific peptide inhibitor of CaMKII, autocamtide-2-related inhibitory peptide (AIP), we show that this reaction is necessary for odor adaptation in vivo. With CaMKII disrupted, adaptation induced by a sustained stimulus is significantly impaired: the onset rate of adaptation is decreased by threefold, and the recovery rate from adaptation is increased by up to sixfold. In contrast, adaptation induced by a brief odor pulse is unaffected, demonstrating that the effect of AIP must be highly specific. The results indicate that CaMKII controls the temporal response properties of ORNs during odor adaptation. We propose that CaMKII plays a prominent role in odor perception.

Adaptation, Physiological↗
PubMed1999

[Pathogenic gene linkage analysis and hemopoietic characteristics in a kindred with sideroblastic anemia].

OBJECTIVE: Analysis of pathogenic gene linkage and hemopoietic characteristics in a kindred with sideroblastic anemia. METHODS: PCR amplification of the microsatellites DXS991,DXS1199 in chromosome Xp11.22 linked gene ALAS2 and of the microsatellite DXS1226 in Xp22. 13 linked another irrelevant gene and analysis of gene linkage in a kindred with 2 patients and 7 normal persons. The bone marrow hemopoietic cells from 2 patients were cultured in condition culture matrix with various cytokines added in and the CFU-E, CFU-GM and CFU-Meg formations were observed at different times. RESULTS: The kindred study revealed that pathogenic gene linked with DXS991 and DXS1199 but did not link with DXS1226.Hemopoietic cell culture showed that erythroid colonies of the two patients grew more vigorously than controls and they could grew in the absence of Epo except in common condition matrix. The erythroid colonies withered after a week and were smaller than the controls after 13 days. CONCLUSION: The kindred is subject to an X-linked sideroblastic anemia(XLSA) with the pathogenic gene ALAS2 involved. In XLSA,the function of stem cells is primarily normal before erythropoiesis, then the erythroid progenitors become dysplasia.

Adult↗
PubMed1999

Murine leukemia virus pseudotypes of La Crosse and Hantaan Bunyaviruses: a system for analysis of cell tropism.

We have developed a system for the preparation of La Crosse virus (LAC) and Hantaan virus (HTN) pseudotypes using a murine leukemia virus vector. After concentration, the pseudotypes were present in quantities sufficient to analyze cell tropism and neutralization. Cells resistant to LAC could not be infected with the MLV (LAC) pseudotypes, and the pseudotypes were sensitive to neutralizing monoclonal antibodies prepared against LAC glycoproteins, as well as to inhibition by a soluble form of the virus cell-attachment protein, G1. Perhaps because of lower expression of the HTN glycoproteins at the cell surface, MLV (HTN) pseudotypes were present at lower titers. However, they were also sensitive to appropriate neutralizing antibodies. This pseudotype system will be useful for analysis of the entry process of the Bunyaviridae, and for neutralization studies with some Bunyaviruses whose high virulence normally requires specialized containment facilities.

Animals↗
PubMed1999

Sequence polymorphism in the mtDNA HV1 region in Japanese and Chinese.

We investigated the nucleotide substitution and insertion/deletion polymorphism of the HV1 region in mtDNA by sequencing blood samples from 150 unrelated Japanese and 120 unrelated Chinese and revealed 108 sequence types from the Japanese group and 87 sequence types from the Chinese. Some substitutions were characteristic of East Asian populations as compared with data reported on Caucasian populations, and some were area-specific among East Asians. The level of genetic diversity and genetic identity revealed by this system was superior to that obtained by VNTR systems for nuclear DNA. These results show the usefulness of mtDNA sequencing in forensic examination for individual identification. We also found some sequence variations in the homopolymeric tract of cytosine (np16180-16194 in the Anderson's reference sequence) that might suggest some hints regarding the mechanisms for and the development of heteroplasmic length variations in this tract.

Journal Article↗
PubMed1999

Serotonin N-acetyltransferase mRNA levels in photoreceptor-enriched chicken retinal cell cultures: elevation by cyclic AMP.

Serotonin N-acetyltransferase (AA-NAT; arylalkylamine N-acetyltransferase; EC 2.3.1.87) is a key regulatory enzyme in the biosynthesis of melatonin. Previous studies have shown that the activity of this enzyme in the chicken retina is regulated by a cyclic AMP-dependent mechanism. In the present report, we investigated whether cyclic AMP can regulate the levels of AA-NAT mRNA in photoreceptor-enriched chick retinal cell cultures. AA-NAT mRNA levels were elevated by acute treatment with cyclic AMP protagonists, including forskolin; this response was blocked by H-89, a selective inhibitor of cyclic AMP-dependent protein kinase. Forskolin did not alter the rate of disappearance of AA-NAT mRNA in actinomycin D-treated cells, suggesting that cyclic AMP enhances transcription of the AA-NAT gene. Forskolin-induced elevation of AA-NAT mRNA levels was enhanced by cycloheximide, which decreased the degradation of the transcript in cells treated with actinomycin D. These studies indicate that the abundance of AA-NAT mRNA is regulated in part through a cyclic AMP-dependent mechanism.

Animals↗
PubMed1999

Sample preparation and storage can change arsenic speciation in human urine.

BACKGROUND: Stability of chemical speciation during sample handling and storage is a prerequisite to obtaining reliable results of trace element speciation analysis. There is no comprehensive information on the stability of common arsenic species, such as inorganic arsenite [As(III)], arsenate [As(V)], monomethylarsonic acid, dimethylarsinic acid, and arsenobetaine, in human urine. METHODS: We compared the effects of the following storage conditions on the stability of these arsenic species: temperature (25, 4, and -20 degrees C), storage time (1, 2, 4, and 8 months), and the use of additives (HCl, sodium azide, benzoic acid, benzyltrimethylammonium chloride, and cetylpyridinium chloride). HPLC with both inductively coupled plasma mass spectrometry and hydride generation atomic fluorescence detection techniques were used for the speciation of arsenic. RESULTS: We found that all five of the arsenic species were stable for up to 2 months when urine samples were stored at 4 and -20 degrees C without any additives. For longer period of storage (4 and 8 months), the stability of arsenic species was dependent on urine matrices. Whereas the arsenic speciation in some urine samples was stable for the entire 8 months at both 4 and -20 degrees C, other urine samples stored under identical conditions showed substantial changes in the concentration of As(III), As(V), monomethylarsonic acid, and dimethylarsinic acid. The use of additives did not improve the stability of arsenic speciation in urine. The addition of 0.1 mol/L HCl (final concentration) to urine samples produced relative changes in inorganic As(III) and As(V) concentrations. CONCLUSIONS: Low temperature (4 and -20 degrees C) conditions are suitable for the storage of urine samples for up to 2 months. Untreated samples maintain their concentration of arsenic species, and additives have no particular benefit. Strong acidification is not appropriate for speciation analysis.

Arsenicals↗
PubMed1999

Synergy of topotecan in combination with vincristine for treatment of pediatric solid tumor xenografts.

Topotecan and vincristine were evaluated alone or in combination against 13 independent xenografts and 1 vincristine-resistant derivative, representing childhood neuroblastoma (n = 6), rhabdomyosarcoma (n = 5), or brain tumors (n = 3). Topotecan was given by i.v. bolus on a schedule found previously to be optimal. Drug was administered daily for 5 days on 2 consecutive weeks with cycles repeated every 21 days over a period of 8 weeks. Doses of topotecan ranged from 0.16 to 1.5 mg/kg to simulate clinically achievable topotecan lactone plasma systemic exposures. Vincristine was administered i.v. every 7 days at a fixed dose of 1 mg/kg. Given as a single agent, vincristine induced complete responses (CRs) in all mice bearing two rhabdomyosarcomas (Rh28 and Rh30) and some CRs in Rh12-bearing mice (57%) but relatively few CRs (<29%) in other tumors. As a single agent, topotecan induced CR in a low proportion of tumor lines. A dose-response model with a logit link function was used to investigate whether the combination of topotecan and vincristine resulted in greater than expected responses compared with the activity of the agents when administered alone. Only CR was used to evaluate tumor responses. The combination resulted in significantly greater than expected CRs than individual agents in nine tumor lines (four neuroblastoma, three brain tumors, and two rhabdomyosarcomas). Similar event-free (failure) distributions were shown in SJ-GBM2 glioblastoma xenografts, whether vincristine was administered on day 1 or day 5 of each topotecan course. To determine whether the increased antitumor activity with the combination was attributable to a change in drug disposition, extensive pharmacokinetic studies were performed. However, little or no interaction between these two agents was determined. Toxicity of the combination was marked by prolonged thrombocytopenia and decreased hemoglobin. However, approximately 75 and 80% of the maximum tolerated dose of each single agent, topotecan (1.5 mg/kg) or vincristine (1 mg/kg), could be given in combination, resulting in a combination toxicity index of approximately 1.5. These results show that the therapeutic effect of combining topotecan with vincristine was greater than additive in most tumor models of childhood solid tumors, and toxicity data suggest that this can be administered to mice with only moderate reduction in the dose levels for each agent.

Animals↗