Biomedical subjects

Y Ma

Publications and source records attributed to Y Ma.

At least 127 records · Page 7Linked to original sources

PubMed2001

Overexpression of gamma-aminobutyric acid transporter subtype I leads to susceptibility to kainic acid-induced seizure in transgenic mice.

Gamma-aminobutyric acid (GABA) is the principal inhibitory neurotransmitter, and the GABAergic synaptic transmission is normally terminated by the rapid uptake through GABA transporters. With transgenic mice ubiquitously overexpressing GABA transporter subtype I (GAT1), the present study explored the pathophysiological role of GAT1 in epileptogenesis. Though displaying no spontaneous seizure activity, these mice exhibit altered electroencephalographic patterns and increased susceptibility to seizure induced by kainic acid. In addition, the GABA(A) receptor and glutamate transporters are up-regulated in transgenic mice, which perhaps reflects a compensatory or corrective change to the elevated level of GAT1. These preliminary findings support the hypothesis that excitatory and inhibitory neurotransmission, and seizure susceptibility can be altered by neurotransmitter transporters.

ATP-Binding Cassette Transporters↗

PubMed2001

Genetic control of susceptibility to experimental Lyme arthritis is polygenic and exhibits consistent linkage to multiple loci on chromosome 5 in four independent mouse crosses.

C3H/He mice infected with Borrelia burgdorferi develop severe arthritis and are high antibody responders, while infected C57BL/6 and BALB/c mice develop mild arthritis and less robust humoral responses. Genetic analysis using composite interval mapping (CIM) on reciprocal backcross populations derived from C3H/HeN and C57BL/6N or C3H/HeJ and BALB/cAnN mice identified 12 new quantitative trait loci (QTL) linked to 10 murine Lyme disease phenotypes. These QTL reside on chromosomes 1, 2, 4, 6, 7, 9, 10, 12, 14, 15, 16, and 17. A reanalysis of an F(2) intercross between C57BL/6N and C3H/HeN mice using CIM identified two new QTL on chromosomes 4 and 15 and confirmed the location of seven previously identified loci. Two or more experimental crosses independently verified six QTL controlling phenotypes after B. burgdorferi infection. Additionally, Bb2 on chromosome 5 was reproduced in four experimental populations and was linked to the candidate locus Cora1. Evidence of four distinct QTL residing within the 30-cM region of chromosome 5 encompassing the previously mapped Bb2 and Bb3 loci was shown by CIM. Interestingly, some alleles contributing to susceptibility to Lyme arthritis were derived from C57BL/6N and BALB/cAnN mice, showing that disease-resistant strains harbor susceptibility alleles.

Animals↗

PubMed2001

Autoantibodies to human cytosol: a marker of sporadic porphyria cutanea tarda.

The enzymes potentially involved in the pathogenesis of sporadic porphyria cutanea tarda (PCT) reside in liver cytosoles and microsomes. PCT is frequently associated with hepatitis C virus (HCV) infection, which is in turn associated with autoimmune manifestations. To investigate whether autoimmune reactions, possibly triggered by HCV, are involved in the pathogenesis of PCT, we measured by immunoblot autoantibodies to human cytosolic and microsomal liver fractions in 82 patients with PCT (77% with HCV infection), 105 with other liver disorders and 40 healthy subjects. Anti-liver cytosolic antibodies were more frequent in PCT patients (38/82, 46%) than in pathological controls (P < 0.05-P < 0.001) or in healthy subjects (3/40, 8%, P < 0.001). Among PCT patients, anticytosolic antibodies were more frequent in HCV positive (36/63, 57%) than in HCV negative (2/19, 11%, P < 0.05) cases. Reactivity to a 40-kDa cytosolic polypeptide was present in 20 PCT patients (19 HCV positive), being more frequent than in all pathological controls (P < 0.01-P < 0.0001). Histological activity index (P = 0.04) and antibodies to HCV (P = 0.027) - but not HCV RNA - were associated independently with anticytosolic antibodies as assessed by multivariate analysis. In contrast, frequency of antiliver microsomal antibodies was similar in PCT patients (24/82, 29%) and pathological controls (8-26%), being higher in the autoimmune hepatitis control group (23/23, 100%, P < 0.0001). In conclusion, anticytosolic antibodies, particularly to a 40-kDa polypeptide, are frequent in PCT and associated with HCV infection and severity of liver damage.

Adult↗

PubMed2001

Intrinsic inhibition of aldose reductase.

The development of aldose reductase inhibitors for the treatment of diabetic complications, such as cataract and retinopathy, has been of intense interest in the pharmaceutical community for the last 20 years. To date, aldose reductase inhibitors have been synthetically developed from leads obtained from in vitro screening studies. Recently, we have observed that mammalian tissues contain intrinsic inhibitors of aldose reductase, which may be used as potential drugs for treating diabetic complications with potentially less side effects than synthetic aldose reductase inhibitors. Intrinsic inhibitor(s) of aldose reductase have been observed in the methanolic extracts from rat and human kidneys and bovine lenses that were subjected to a number of chromatographic techniques, including counter current chromatography, flash chromatography, gel filtration and high pressure liquid chromatography. This inhibition results from a direct interaction between the inhibitor and enzyme. The intrinsic inhibitor, present in the lipophilic fraction of human kidney and bovine lens extracts, can easily penetrate into the lens to inhibit sugar alcohol formation. Intraperitoneal injection of partially purified bovine lens extract inhibited lens polyol formation in young rats fed 50% galactose diet.

Aldehyde Reductase↗

PubMed2001

Networks mediating the clinical effects of pallidal brain stimulation for Parkinson's disease: a PET study of resting-state glucose metabolism.

Employing [(18)F]fluorodeoxyglucose (FDG) and PET, we have found previously that stereotaxic ablation of the internal globus pallidus (GPi) for Parkinson's disease causes resting metabolic changes in brain regions remote from the lesion site. In this study we determined whether similar metabolic changes occur in Parkinson's disease patients treated with deep brain stimulation (DBS) of the GPi. We studied seven Parkinson's disease patients with FDG-PET to measure resting regional cerebral glucose utilization on and off GPi stimulation. We used statistical parametric mapping to identify significant changes in regional brain metabolism that occurred with this intervention. We also quantified stimulation-related changes in the expression of a specific abnormal Parkinson's disease-related pattern of metabolic covariation (PDRP) that had been identified in earlier FDG-PET studies. Metabolic changes with DBS were correlated with clinical improvement as measured by changes in Unified Parkinson's Disease Rating Scale (UPDRS) motor ratings off medication. GPi DBS improved UPDRS motor ratings (36%, P < 0.001) and significantly increased regional glucose metabolism in the premotor cortex ipsilateral to stimulation and in the cerebellum bilaterally. GPi DBS also resulted in a significant (P < 0.01) decline in PDRP activity ipsilateral to stimulation, which correlated significantly with clinical improvement in UPDRS motor ratings (P < 0.03). Clinical improvement with GPi DBS is associated with reduced expression of an abnormal Parkinson's disease-related metabolic network involving elements of the cortico-striato-pallido-thalamocortical and the cerebello-cortical motor loops.

Adult↗

PubMed2001

Distribution and significance of epithelial types in columnar-lined esophagus.

An abnormal columnar-lined esophagus (CLE) is characterized by the presence of cardiac mucosa (CM) oxynto-cardiac mucosa (OCM), and intestinal metaplastic epithelium (IM) between gastric oxyntic mucosa and esophageal squamous epithelium. Thirty-two patients with CLE measuring 2-16 cm long had 5-37 biopsies per patient that showed CM, OCM, or IM for a total of 424 biopsies. Detailed mapping of the distribution of epithelial types within the CLE showed a distinct zonation of epithelial types; CM was present throughout the CLE, whereas OCM and IM tended to occur in the distal and proximal part of the CLE, respectively. All 32 patients (64 of 68 biopsies) showed IM at the most proximal level, compared with 22 of 32 patients (40 of 102 biopsies) in the most distal level biopsies. The density of goblet cells was highest in the most proximal level. The differences in prevalence and density of goblet cells between most proximal and most distal level biopsies were highly significant. These data suggest that for a given number of biopsies within the CLE, the likelihood of finding IM is greatest when the biopsies are concentrated in the most proximal area of the CLE. We suggest that glandular transformation of squamous epithelium results in CM. which evolves into OCM and IM by development of specialized parietal cells and goblet cells, respectively. The severity and nature of reflux cause these epithelial transformations in a constant and predictable manner. Recognition of these changes permits the development of morphologic definitions of reflux disease and the characterization of the sequence of epithelial changes that represent the reflux-adenocarcinoma sequence.

Barrett Esophagus↗

PubMed2001

Idiopathic pulmonary fibrosis and malignancy.

The reported frequency of lung cancer in the setting of diffuse pulmonary fibrosis varies greatly, depending on the country of origin and the type of study. Most recent reports regarding diffuse pulmonary fibrosis in general and idiopathic pulmonary fibrosis in particular and lung cancers come from Japan; only a few clinical studies of this issue are available from other countries of the world, including the United States. The reported frequency ranges from 4.8% in the United States to 48.2% in Japan. The most frequent type of cancer is adenocarcinoma. Risk factors may include cigarette smoking, exposure to metal dusts, onset of idiopathic pulmonary fibrosis at an older age, and male predominance. Possible pathologic mechanisms are summarized. Given the very poor prognosis of idiopathic pulmonary fibrosis itself, with a mean survival of only 2.8 years, and that different diagnostic criteria were used in each study, it is likely that many of these studies are flawed because they evaluate lesions other than idiopathic pulmonary fibrosis. Thus, the frequency of lung cancer in idiopathic pulmonary fibrosis is still uncertain, and clearly requires follow-up of cohorts of clinically well-characterized patients, using standard diagnostic criteria for idiopathic pulmonary fibrosis. Finally, if the association between idiopathic pulmonary fibrosis and lung cancer is reconfirmed in these studies, the molecular and genetic mechanisms governing the development of lung cancer in this setting require additional study.

Biopsy↗

PubMed2001

Thermoanaerobacter tengcongensis sp. nov., a novel anaerobic, saccharolytic, thermophilic bacterium isolated from a hot spring in Tengcong, China.

A new, extremely thermophilic bacterium, designated strain MB4T, was isolated from a Chinese hot spring. The new isolate was an obligately anaerobic, rod-shaped, gram-negative, saccharolytic bacterium. Spore formation was not observed. Growth occurred at temperatures between 50 and 80 degrees C, with an optimum of around 75 degrees C; at pH values between 5.5 and 9.0, with an optimum of 7.0-7.5; and at salinities between 0 and 2.5% NaCl, with an optimum of around 0.2% NaCl. The organism utilized glucose, galactose, maltose, cellobiose, mannose, fructose, lactose, mannitol and starch. Acetate was the main end product from glucose fermentation. Thiosulfate and sulfur were reduced to hydrogen sulfide. Sulfate, sulfite and nitrate were not reduced. Growth was inhibited by hydrogen. The G+C content of the DNA was 33 mol%. Phylogenetic analyses based on the 16S rDNA sequence indicated that the isolate was a new member of the genus Thermoanaerobacter and formed a monophyletic unit within the Thermoanaerobacter cluster. Based on its phenotypic and phylogenetic characteristics, the isolate was proposed as a new species, Thermoanaerobacter tengcongensis. The type strain is MB4T (= Chinese Collection of Microorganisms AS 1.2430T = JCM 11007T).

Anaerobiosis↗

PubMed2001

Natrialba hulunbeirensis sp. nov. and Natrialba chahannaoensis sp. nov., novel haloalkaliphilic archaea from soda lakes in Inner Mongolia Autonomous Region, China.

Two haloalkaliphilic archaeal strains, X21T and C112T, were isolated from soda lakes in Inner Mongolia Autonomous Region, China. Their morphology, physiology, biochemical features, polar lipid composition and 16S rRNA genes were characterized in order to elucidate their taxonomy. According to these data, strains X21T and C112T belong to the genus Natrialba, although there are clear differences with respect to their physiology and polar lipid composition between the two strains and the type species, Natrialba asiatica. On the basis of low DNA-DNA hybridizations, these two strains should be considered as new species of genus Natrialba. The names Natrialba hulunbeirensis sp. nov. (type strain X21T = AS 1.1986T = JCM 10989T) and Natrialba chahannaoensis sp. nov. (type strain C112T = AS 1.1977T = JCM 10990T) are proposed.

Base Composition↗

PubMed2001

Drug targeting Mycobacterium tuberculosis cell wall synthesis: genetics of dTDP-rhamnose synthetic enzymes and development of a microtiter plate-based screen for inhibitors of conversion of dTDP-glucose to dTDP-rhamnose.

An L-rhamnosyl residue plays an essential structural role in the cell wall of Mycobacterium tuberculosis. Therefore, the four enzymes (RmlA to RmlD) that form dTDP-rhamnose from dTTP and glucose-1-phosphate are important targets for the development of new tuberculosis therapeutics. M. tuberculosis genes encoding RmlA, RmlC, and RmlD have been identified and expressed in Escherichia coli. It is shown here that genes for only one isotype each of RmlA to RmlD are present in the M. tuberculosis genome. The gene for RmlB is Rv3464. Rv3264c was shown to encode ManB, not a second isotype of RmlA. Using recombinant RmlB, -C, and -D enzymes, a microtiter plate assay was developed to screen for inhibitors of the formation of dTDP-rhamnose. The three enzymes were incubated with dTDP-glucose and NADPH to form dTDP-rhamnose and NADP(+) with a concomitant decrease in optical density at 340 nm (OD(340)). Inhibitor candidates were monitored for their ability to lower the rate of OD(340) change. To test the robustness and practicality of the assay, a chemical library of 8,000 compounds was screened. Eleven inhibitors active at 10 microM were identified; four of these showed activities against whole M. tuberculosis cells, with MICs from 128 to 16 microg/ml. A rhodanine structural motif was present in three of the enzyme inhibitors, and two of these showed activity against whole M. tuberculosis cells. The enzyme assay was used to screen 60 Peruvian plant extracts known to inhibit the growth of M. tuberculosis in culture; two extracts were active inhibitors in the enzyme assay at concentrations of less than 2 microg/ml.

Carbohydrate Dehydrogenases↗

PubMed2001

Role of the dinitrogenase reductase arginine 101 residue in dinitrogenase reductase ADP-ribosyltransferase binding, NAD binding, and cleavage.

Dinitrogenase reductase is posttranslationally regulated by dinitrogenase reductase ADP-ribosyltransferase (DRAT) via ADP-ribosylation of the arginine 101 residue in some bacteria. Rhodospirillum rubrum strains in which the arginine 101 of dinitrogenase reductase was replaced by tyrosine, phenylalanine, or leucine were constructed by site-directed mutagenesis of the nifH gene. The strain containing the R101F form of dinitrogenase reductase retains 91%, the strain containing the R101Y form retains 72%, and the strain containing the R101L form retains only 28% of in vivo nitrogenase activity of the strain containing the dinitrogenase reductase with arginine at position 101. In vivo acetylene reduction assays, immunoblotting with anti-dinitrogenase reductase antibody, and [adenylate-(32)P]NAD labeling experiments showed that no switch-off of nitrogenase activity occurred in any of the three mutants and no ADP-ribosylation of altered dinitrogenase reductases occurred either in vivo or in vitro. Altered dinitrogenase reductases from strains UR629 (R101Y) and UR630 (R101F) were purified to homogeneity. The R101F and R101Y forms of dinitrogenase reductase were able to form a complex with DRAT that could be chemically cross-linked by 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide. The R101F form of dinitrogenase reductase and DRAT together were not able to cleave NAD. This suggests that arginine 101 is not critical for the binding of DRAT to dinitrogenase reductase but that the availability of arginine 101 is important for NAD cleavage. Both DRAT and dinitrogenase reductase can be labeled by [carbonyl-(14)C]NAD individually upon UV irradiation, but most (14)C label is incorporated into DRAT when both proteins are present. The ability of R101F dinitrogenase reductase to be labeled by [carbonyl-(14)C]NAD suggested that Arg 101 is not absolutely required for NAD binding.

ADP Ribose Transferases↗

PubMed2001

Cell wall core galactofuran synthesis is essential for growth of mycobacteria.

The mycobacterial cell wall core consists of an outer lipid (mycolic acid) layer attached to peptidoglycan via a galactofuranosyl-containing polysaccharide, arabinogalactan. This structural arrangement strongly suggests that galactofuranosyl residues are essential for the growth and viability of mycobacteria. Galactofuranosyl residues are formed in nature by a ring contraction of UDP-galactopyranose to UDP-galactofuranose catalyzed by the enzyme UDP-galactopyranose mutase (Glf). In Mycobacterium tuberculosis the glf gene overlaps, by 1 nucleotide, a gene, Rv3808c, that has been shown to encode a galactofuranosyl transferase. We demonstrate here that glf can be knocked out in Mycobacterium smegmatis by allelic replacement only in the presence of two rescue plasmids carrying functional copies of glf and Rv3808c. The glf rescue plasmid was designed with a temperature-sensitive origin of replication and the M. smegmatis glf knockout mutant is unable to grow at the higher temperature at which the glf-containing rescue plasmid is lost. In a separate experiment, the Rv3808c rescue plasmid was designed with a temperature-sensitive origin of replication and the glf-bearing plasmid was designed with a normal original of replication; this strain was also unable to grow at the nonpermissive temperature. Thus, both glf and Rv3808c are essential for growth. These findings and the fact that galactofuranosyl residues are not found in humans supports the development of UDP-galactopyranose mutase and galactofuranosyl transferase as important targets for the development of new antituberculosis drugs.

Bacterial Proteins↗

PubMed2001

Evidence for retroviral intramolecular recombinations.

As a consequence of being diploid, retroviruses have a high recombination rate. Naturally occurring retroviruses contain two repeat sequences (R regions) flanking either end of their RNA genomes, and recombination between these two R regions occurs at a high rate. We deduced that recombination may occur between two sequences within the same RNA molecule (intramolecular) as well as between sequences present within two separate RNA molecules (intermolecular). Intramolecular recombination would usually result in a deletion within the progeny provirus. In this report, we demonstrate that intramolecular recombination between two identical sequences occurred within a chimeric RNA vector. In addition, high rates of recombination between two identical sequences within the same RNA molecule resulted mostly from intramolecular recombination.

Blotting, Southern↗

PubMed2001

Molecular cloning and characterization of a novel human gene (HSPBAP1) from human fetal brain.

Rat PASS1 is a novel protein binding specifically to hsp27 and thus plays a role in regulating stress response in the living cell. Here we report on a human homologue of PASS1, encoded by the gene HSPBAP1. The gene was cloned and identified during a large-scale sequencing analysis of a human fetal brain cDNA library. The human protein shared 80% amino acid identity with rat PASS1. According to bioinformatics analysis, the HSPBAP1 gene is located on chromosome 3q21. RT-PCR analysis indicated that HSPBAP1 was abundant in thymus and pancreas but had a ubiquitously low expression pattern in other human adult tissues except for brain where it was absent.

Amino Acid Sequence↗

PubMed2001

Jacobson's nerve schwannoma: a rare middle ear mass.

The case of a 55-year-old woman with a middle ear mass is presented. The preoperative diagnostic workup, including an audiogram and imaging studies, and the histopathologic findings of the tumor are reviewed. The tumor, a schwannoma, arose from Jacobson's nerve in the middle ear. The surgical anatomy of Jacobson's nerve and the surgical approach to this tumor and to other tumors of the middle ear space are discussed. Tumors of the tympanic cavity are rare, with the exception of cholesteatoma; otherwise, the most common among them are paraganglioma and facial nerve neuroma. This report represents the first documented case of a schannoma arising from Jacobson's nerve in the tympanic cavity.

Cranial Nerve Neoplasms↗

PubMed2001

Bone anabolic effects of sonic/indian hedgehog are mediated by bmp-2/4-dependent pathways in the neonatal rat metatarsal model.

A neonatal rat metatarsal organ culture model has been employed to study the anabolic effects of Sonic/Indian hedgehog and BMP-4. In this culture system, a significant increase in endochondral ossification is measured by an increase in length of mineralized bone, after daily treatment for 7 days with Sonic hedgehog protein (Shh-N). Previous evidence indicated that PTH related protein (PTHrP) is a critical target of hedgehog function in endochondral ossification. Using a PTHrP blocking antibody, it is shown that hedgehog mediates this activity via pathways other than through PTHrP. A dose-related increase in endochondral ossification is observed when metatarsals are treated with 25 ng/ml recombinant human bone morphogenetic protein 4 (BMP-4). However, this activity is not evident at higher doses of BMP-4 (200 ng/ml). High doses of BMP-4 resulted in increased expression of noggin messenger RNA and cotreatment of noggin and Shh-N resulted in reversal of the anabolic action of Shh-N. This observation suggests that BMP-4 signaling can influence the Shh-N mediated increase in endochondral ossification. Finally, we show that the Shh-N and BMP-4 mediated increase in endochondral ossification is reversed by treatment with antisense oligonucleotides targeted against Cbfa1. Thus, this report identifies Shh-N as an inducer of endochondral ossification that mediates its effect via BMP-4 and Cbfa1-dependent pathways.

Animals↗

PubMed2001

Solid-state fermentation of phytase from cassava dregs.

Phytases produced by numerous microorganisms and plants degrade phytic acid that has chelated with metal ions in food and feed. It is important to study phytase for the role of metal ions in nutrition of animals and humans as well as in the reduction of organic phosphate content of aqueous environment. This article reports on solid-state fermentation of phytase from a new substrate of cassava dregs. Large quantities of cassava dregs are produced in tropical areas as a byproduct of cassava starch processing. Protein and inorganic salts were found to be low in cassava dregs. Cassava dregs could be employed for phytase synthesis after the addition of a nitrogen source and mineral salts. Ammonium nitrate was the best nitrogen source among the nitrogen sources investigated, including beef extract, yeast extract, urea, ammonium nitrate, sodium nitrate, and ammonium sulfate. Sodium dodecyl sulfate promoted phytase production from cassava dregs. A maximum phytase yield of 6.73 U/g of dry mass was obtained. The obtained phytase was stable at feed-processing temperature, since 70% of initial enzyme activity was maintained after 30 min of treatment at 75 degrees C.

6-Phytase↗

PubMed2001

Pediatric autoimmune liver diseases: the molecular basis of humoral and cellular immunity.

Pediatric autoimmune liver disease is mainly represented by two similar liver disorders: autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (ASC), both characterized by hypergammalobulinemia, interface hepatitis and the presence of a wide range of circulating autoantibodies. Although similar features are seen in AIH and inflammatory bowel disease, histological biliary changes are more common in ASC. In addition to their role as diagnostic markers, autoantibodies, such as anti-extractable nuclear antigen (ENA) antibodies and liver kidney microsomal antibody type 1 (LKM1) may be involved directly in inducing aggressive liver diseases. Although the cellular immune response in pediatric autoimmune liver disease has been less intensively investigated than humoral immunity, the importance of antigen specific T cells has been explored. Both alphabeta and gammadelta T cells derived from either peripheral blood and liver biopsies have highly heterogeneous TCR gene usage and cytolytic activity has been demonstrated. There have been attempts to seek triggers of liver autoimmunity and several sequences shared in common between autoantigens and hepatotropic viruses, namely hepatitis B, C and cytomegalovirus have been identified. The presence of cross-reactivity between homologous sequences, especially between HCV and cytochromes, supports the possibility that molecular mimicry plays a role in the induction of autoantibodies and autoreactive cytotoxic T cells.

Amino Acid Sequence↗