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Biomedical subjects

L Lin

Publications and source records attributed to L Lin.

At least 73 records · Page 4Linked to original sources

The validity of screening for post-traumatic stress disorder and major depression among Vietnamese former political prisoners.

The aim of this study was to investigate the validity of the Harvard Trauma Questionnaire (HTQ) and the depression sub-scale of the Hopkins Symptom Checklist-25 (HSCL-25) in screening for post-traumatic stress disorder (PTSD) and major depressive disorder (MDD) among Vietnamese former political prisoners (POWs). The study population included Vietnamese POWs (n = 51) who migrated to the Boston metropolitan area between January 1990 and July 1992 under the Special Released Re-education Center Detainees Resettlement Program. The criterion validity of the HTQ in assessing PTSD and of the depression sub-scale of the HSCL-25 in assessing MDD is supported by the results. Consideration of an appropriate cut-off score should include examination of the utility of a given screening instrument for PTSD or MDD within different settings, such as refugee camps vs. countries of third asylum.

Adult

Mechanism of the acceleration of CO2 production from pyruvate in liver mitochondria by HCO3-.

To investigate the mechanism by which HCO3- accelerates pyruvate metabolism in guinea pig liver mitochondria, we measured continuously, at pH 7.4 and 37 degrees C, 13C16O2 production from [1-13C]pyruvate by mass spectrometry and NADH concentration by fluorescence and analyzed total malate, citrate, and beta-hydroxybutyrate produced by standard biochemical methods. When [1-13C]pyruvate is added to the mitochondrial suspension, 13C16O2 concentration rises steeply in the first seconds and then slows to a steady lower rate. Carbonic anhydrase (CA) eliminates this initial phase, which shows that decarboxylation of pyruvate produces CO2, not HCO3-, and it does this more rapidly than it can equilibrate without CA. HCO3- (25 mM) increased 13C16O2 production, O2 consumption and total malate and citrate production and decreased NADH concentration and total beta-hydroxybutyrate production. After obtaining the total amount of 13C16O2, malate, citrate, and beta-hydroxybutyrate produced, we calculated that the addition of 25 mM HCO3- to the suspension medium increased the amount of pyruvate decarboxylated by pyruvate dehydrogenase (PDH) 16% and increased the amount carboxylated by pyruvate carboxylase 300%. This supports our initial proposal that HCO3- accelerates the pyruvate carboxylation, which in turn consumes ATP directly and NADH and acetyl CoA secondarily, all of which increase PDH activity. However, we found no acceleration of pyruvate decarboxylation by 0.5 and 1 microM free Ca2+ concentration, unless the mitochondria were uncoupled and ATP was added.

3-Hydroxybutyric Acid

[Antagonistic effect of calcitonin gene related peptide on arrhythmia in rats].

Premature ventricular contraction (PVC), ventricular tachycardia (VT) and ventricular fibrillation (VF) were developed by endothelin-1 (ET-1) injected into the coronary ostia at the dose of 900 pmol/kg in anesthetized rats. No arrhythmia was elicited but blood pressure fell temporarily by calcitonin gene related peptide (CGRP), the injection into the coronary ostia. After pretreatment with CGRP incidence and severity of arrhythmia decreased at the same ET-1 dose. Arrhythmia score in CGRP 1200 pmol/kg + ET-1 group was lower than that in ET-1 group (P < 0.01). The results revealed that antiarrhythmic effect of CGRP may be partially brought about by its antagonistic effect against ET-1 induced arrhythmia.

Animals

Dynamic and conventional spin-echo MR of pituitary microlesions.

PURPOSE: To determine whether dynamic traditional spin-echo MR imaging, with the use of routine T1 parameters during contrast infusion, is superior to standard MR imaging after contrast administration for detecting microlesions of the pituitary gland. METHODS: Sixty-four patients with pituitary microlesions 3 to 10 mm in diameter were examined with a dynamic traditional spin-echo technique; that is, a typical T1 spin-echo sequence of 500-600/20-25/2 (repetition time/echo time/excitations), 3-mm-thick sections, 16-cm field of view, 256 x 128 matrix, and a scan time ranging from 2 minutes to 2 minutes 40 seconds during contrast infusion. In addition, standard imaging with unenhanced and contrast-enhanced spin-echo sequences were obtained. The three sequences were evaluated retrospectively and graded for gland-lesion contrast conspicuity, lesion homogeneity, and delineation of lesion margin. RESULTS: The dynamic sequence was judged to be better than the standard enhanced sequence for depicting microlesions in 42% to 47% of patients. Lesions were identified only on the dynamic study in an additional 1% to 14% of patients. Lesions were seen equally well on the standard and dynamic sequences only in 16% to 23% of cases. The standard postcontrast sequence was judged better in 12.5% to 17% of cases, with lesions identified only on the standard sequence in an additional 8% to 9%. CONCLUSION: Dynamic traditional spin-echo MR imaging improved lesion detection and provided increased clarity over standard sequences after contrast infusion. Both sequences are important, since lesions were detected only on the dynamic sequence in 11% to 14% of patients and only on the standard sequence in 8% to 9% of patients.

Adenoma

Hepatitis G viral RNA in serum and in peripheral blood mononuclear cells and its relation to HCV-RNA in patients with clotting disorders.

The hepatitis G virus (HGV) has recently been identified as a new member of the Flaviviridae family. Infection by this virus is thought to be associated with blood borne hepatitis. In this study, the presence of HCV- and HGV-RNAs in serum or plasma (175 patients) and in peripheral blood mononuclear cells (PBMC) (133 patients) was investigated in patients with clotting disorders using a sensitive reverse transcriptase polymerase chain reaction (RT-PCR). HGV-RNA was detected in serum of 26 patients (14.8%). In apparently healthy blood donors, serum HGV-RNA was detected in 4 of 358 individuals investigated (1.12%). Ninety two percent of the 26 serum HGV-RNA positive patients had coinfection with the hepatitis C virus (HCV), especially with HCV genotype 1b, the most common genotype in Belgium. Of these coinfected patients, 15 (62.5%) showed elevated serum ALT levels. Two patients who were solely infected with HGV had normal serum ALT.HGV-RNA in PBMC was found in 18 patients, of whom 3 were negative for serum HGV-RNA. As in case of HCV, HGV-RNA in PBMC is preferentially sensitive to interferon treatment. Nevertheless, rapid reappearance of HGV-RNA in PBMC was observed after cessation of treatment. In one patient, persistent serum ALT elevation seems to be associated with continued HGV viremia, despite the disappearance of serum HCV-RNA.

Adolescent

Muscle characteristics in effort angina before and after CABG.

Seven males with effort angina undertook graded ergometer tests and had muscle biopsies taken from their vastus lateralis muscle before, and three and six months after coronary bypass surgery. Muscle fibre composition (percentage of slow twitch fibres), ubiquinone (vitamin Q), and oxidative and fermentative enzyme activities were determined. After six months, muscle ubiquinone and oxidative enzymes were still depressed, indicating sustained muscle trauma. The only peripheral changes were that muscle lactate dehydrogenase and its skeletal muscle-specific subunits and isozymes were increased 35% to 40% (P < 0.001) three to six months postsurgery. Onset of blood lactate accumulation (2.0 mmol/L), symptom-limited ('maximal') exercise and peak blood lactate increased linearly over time (r = 0.52, P < 0.05; r = 0.63, P < 0.01; and r = 0.76, P < 0.001, respectively). It is suggested that the initial physical performance increase was due to improved circulatory capacity, oxygen delivery and lactate efflux, whereas the increased fermentative capacity ('anaerobic power') first contributed after a lag of three or more months. Whether the muscle histochemical changes reflected a healing process (recovery) is speculative.

Angina Pectoris

Global regulatory considerations for unified assay specifications.

When developing a biotechnology product for global registration, there are several aspects to evaluate in an effort to unify specifications. These include differences between the United States, Europe and Japan, and Rest-of-World (ROW) countries with regard to the respective regulatory guidelines and pharmacopoeias in force, the state-of-the-art of product testing analytical methods, and the interval between submitting a registration dossier to different countries. In terms of regulatory guidelines, one country may have a monograph or required specifications for particular tests, for example the potency that a product has to meet before clinical trials can be initiated. For pharmacopoeias, different assay methods are required for sterility, general safety, and pyrogen testing, so that one may have to test a specific lot of a product at two or three different times to evaluate the same parameter, because of specific testing differences required for each country's pharmacopoeia. In addition, the state of analytical methods is always evolving and better analytical techniques become available. Sometimes, from starting with one set of tests, and based on the time in development, new tests may be added to the existing list of release specifications, because new analytical techniques have become available. Examining the global registration approval process for Betaseron, (interferon beta-1b) illustrates when specifications were able to be unified and when they were not.

Animals

Detection of differentially expressed genes in methylnitrosourea-induced rat mammary adenocarcinomas.

In this study, altered gene expression in five methylnitrosourea (MNU)-induced rat mammary adenocarcinomas was investigated using a newly developed competitive cDNA library screening assay. In order to detect the differentially expressed cDNA transcripts, three cDNA libraries (rat mammary, rat liver, and rat kidney) with over 18,000 clones were differentially screened with competing normal and neoplastic mammary cDNA probes. Ninety-eight clones indicated by competitive hybridization to be differentially expressed in tumors were verified by dot-blot hybridization analysis. Of these clones, 45 were found to be overexpressed while 53 were underexpressed in tumors. Forty-five of the confirmed clones were further analyzed by single-pass cDNA sequence determination. Four clones showed homology with cytochrome oxidase subunit I, polyoma virus PTA noncoding region, cytoplasmic beta-actin, and mouse secretory protein containing thrombospondin motifs. Further investigation into the potential roles of these identified genes should contribute significantly to our understanding of the molecular mechanism(s) of rat mammary tumorigenesis.

Adenocarcinoma

[Mean corpuscular volume and red blood cell volume distribution width in the diagnosis of iron deficiency anemia in pregnancy].

OBJECTIVE: To evaluate the value of combined measurement of mean corpuscular volume (MCV) and red blood cell volume distribution width (RDW) in the diagnosis of iron deficiency anemia in pregnancy. METHODS: Hemoglobin concentration (HGB), MCV, RDW, serum iron concentration (Fe), total iron binding capacity (TIBC) and transferrin saturation percentage (TS%) were simultaneously assayed in 605 pregnant women at prenatal examination. The results in different groups were analysed. RESULTS: There were 68 cases in iron deficiency anemia group, 57 cases in non-iron deficiency anemia group and 480 pregnant women in normal group. RDW was significantly increased and MCV greatly decreased in iron deficiency anemia group as compared with that in normal group and non-iron deficiency anemia group. There were no differences in both MCV and RDW between normal group and non-iron deficiency anemia group. CONCLUSIONS: Low MCV and high RDW were the characteristic changes of iron deficiency anemia in pregnancy. We recommend the use of RDW and MCV in the initial classification of anemia in pregnancy.

Adult

Identification of a (CUG)n triplet repeat RNA-binding protein and its expression in myotonic dystrophy.

Myotonic dystrophy (DM) is an autosomal dominant neuromuscular disease that is associated with a (CTG)n repeat expansion in the 3'-untranslated region of the myotonin protein kinase (Mt-PK) gene. This study reports the isolation and characterization of a (CUG)n triplet repeat pre-mRNA/mRNA binding protein that may play an important role in DM pathogenesis. Two HeLa cell proteins, CUG-BP1 and CUG-BP2, have been purified based upon their ability to bind specifically to (CUG)8 oligonucleotides in vitro. While CUG-BP1 is the major (CUG)8-binding activity in normal cells, nuclear CUG-BP2 binding activity increases in DM cells. Both CUG-BP1 and CUG-BP2 have been identified as isoforms of a novel heterogeneous nuclear ribonucleoprotein (hnRNP), hNab50. The CUG-BP/hNab50 protein is localized predominantly in the nucleus and is associated with polyadenylated RNAs in vivo. In vitro RNA-binding/photocrosslinking studies demonstrate that CUG-BP/hNab50 binds to RNAs containing the Mt-PK 3'-UTR. We propose that the (CUG)n repeat region in Mt-PK mRNA is a binding site for CUG-BP/hNab50 in vivo, and triplet repeat expansion leads to sequestration of this hnRNP on mutant Mt-PK transcripts.

Amino Acid Sequence

Construction of phosphorylatable monoclonal antibody to a tumor-associated antigen.

A phosphorylation site was introduced into chimeric monoclonal antibody B72.3 (MAb-chB72.3) by site-specific mutation of the coding sequence. The phosphorylation site for the cAMP-dependent protein kinase was positioned at the carboxyl terminus of the heavy-chain constant region of MAb-chB72.3. The resultant modified MAb-chB72.3-P was expressed in 293 cells and purified. The MAb-chB72.3-P protein was phosphorylated by the catalytic subunit of cAMP-dependent protein kinase with [gamma-32P]ATP to high radiospecific activity. The 32P-labeled MAb-chB72.3-P protein bound to cells expressing the tumor-associated glycoprotein 72 antigen. The introduction of phosphorylation sites into MAbs provides a new type of MAb for the diagnosis and treatment of cancers.

Amino Acid Sequence

Functional expression of thyrotropin receptor in differentiated 3T3-L1 cells: a possible model cell line of extrathyroidal expression of thyrotropin receptor.

Thyrotropin receptor (TSHR) in extrathyroidal tissue, especially fat tissue, is supposed to have important roles in the development of extrathyroidal manifestations of Graves' disease. However, the molecular mechanism of TSHR expression is not known. Expression of TSHR mRNA and TSH-dependent cAMP production were observed in differentiated but not in undifferentiated 3T3-L1 cells. Maximal expression was obtained when the cells were differentiated in the presence of insulin, dexamethasone, and isobutylmethylxanthine (IBMX). Dexamethasone and IBMX were indispensable for the first three days. On the other hand, after day 4, insulin was indispensable for the expression of TSHR. 3T3-L1 cell is the first non-thyroidal cell line reported that expresses TSHR and whose expression can be induced. 3T3-L1 cell can be a good model to investigate the mechanism of expression of TSHR and extrathyroidal manifestations of Graves' disease.

1-Methyl-3-isobutylxanthine

Mutational analysis suggests the same design for editing activities of two tRNA synthetases.

Although the structural basis for amino acid activation by class I tRNA synthetases is known, that for their editing activities has remained elusive. Two class I tRNA synthetases discriminate closely similar amino acids by RNA-independent and RNA-dependent mechanisms. In the absence of tRNA, isoleucyl-tRNA synthetase misactivates valine, while valyl-tRNA synthetase misactivates threonine. Both enzymes improve amino acid discrimination by tRNA-dependent hydrolytic editing reactions. Recent mutational analysis of an isoleucyl-tRNA synthetase showed that discrimination of valine from isoleucine by amino acid activation was functionally independent of discrimination by editing. In this work, we used mutational analysis to test whether the two types of amino acid discrimination were functionally independent in valyl-tRNA synthetase. We obtained four mutations in the valine enzyme which severely affected amino acid activation. The two most defective enzymes reduced kcat/Km for activation of valine by more than 4 orders of magnitude and were essentially inactive for aminoacylation. These two defective enzymes were tested and found to be unaltered in catalysis of rapid and selective removal of threonine misacylated onto valine tRNA. On the basis of these data, and in spite of there being few residues conserved between the two proteins in a region believed important for editing, we propose that the valine and isoleucine enzymes share a global design which functionally separates amino acid editing from amino acid activation.

Amino Acid Sequence

Muscle ubiquinone in healthy physically active males.

Thirty-five (35) healthy physically active males had muscle biopsies taken from their vastus lateralis muscle to analyze for ubiquinone (vitamin Q, UQ), oxidative (muscle fiber types expressed as %ST and citrate synthase activity, CS) and fermentative (lactate dehydrogenase, LD) profiles. Graded cycle ergometer exercise to determine the intensities corresponding to onset of blood lactate accumulation set to 4.0 mmol x l-1 (WOBLA) and symptom limited exercise ('maximal', WSL) were also undertaken. Eleven (11) subjects had also recently participated in a marathon race. UQ was positively related to CS (r = 0.67, p < 0.001) and %ST (r = 0.60, p < 0.001) but not to LD. UQ was also positively related to exercise capacity and/or marathon performance (e.g. WOBLA x kg-1 BW, r = 0.70, p < 0.001). It was suggested that muscle UQ allocation in man was related to variables describing molecular oxygen availability, respiratory activity and oxidative energy releasing processes but not to fermentation activity. UQ allocation to ST fibers/CS activity was suggested to be due to the double role of UQ: 1) as a mitochondrial coenzyme (CoQ10) and 2) as a nonspecific antioxidant.

Adult