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Biomedical subjects

T H Lin

Publications and source records attributed to T H Lin.

At least 91 records · Page 5Linked to original sources

Toxicity to alveolar macrophages in rats following parenteral injection of mercuric chloride.

Alveolar macrophages collected by pulmonary lavage from male Fisher-344 rats at intervals (24-72 h) after HgCl2 injection (1-5 mg/kg, s.c.) were analyzed by several techniques. Within 24-72 h, the macrophages showed morphological signs of activation (hypertrophy and ruffled plasma membrane). Lipid peroxidation (increased malondialdehyde concentration) was not detected until 48 h. Dose- and time-related effects of HgCl2 on malondialdehyde concentration and mercury content of alveolar macrophages were observed 24-72 h postinjection. Diminished cell viability occurred only at 72 h after the highest dosage of HgCl2. This study demonstrates that the alveolar macrophage was a cellular target for mercury toxicity following parenteral exposure to HgCl2.

Animals↗

Lipid peroxidation in liver of rats administrated with methyl mercuric chloride.

Parenteral administration of methyl mercuric chloride (MMC, CH3HgCl) to rats enhanced lipid peroxidation in liver of rats, as measured by the thiobarbituric acid reaction for malondialdehyde (MDA) in fresh tissue homogenates. After sc injection of CH3HgCl (5 mg/kg body wt), MDA concentration in liver became significantly increased at 24 h and further increased at 48 h. Dose-response studies were carried out with male albino rats of the Fisher-344 strain (body wt 170-280 g) injected with 3 or 5 mg Hg/kg as CH3HgCl and sacrificed after 24 h. In time-response studies, animals were administered 5 mg Hg/kg as CH3HgCl and sacrificed after 24 and 48 h. Studies in the authors' laboratory have shown that (1) mercury is accumulated in liver; (2) concentration of MDA is increased in liver of CH3HgCl-treated rats; (3) severity of hepatotoxicity is generally proportional to the elevation of MDA concentration, based upon the dose-effect relationships observed after administration of CH3HgCl to rats. The results of this study implicate that the lipid peroxidation is one of the molecular mechanisms for cell injury in acute CH3HgCl poisoning.

Alanine Transaminase↗

Lipid peroxidation in rats administrated with mercuric chloride.

Parenteral administration of mercuric chloride (HgCl2) to rats enhanced lipid peroxidation in liver, kidney, lung, testis, and serum (but not in heart, spleen, or muscle), as measured by the thiobarbituric acid reaction for malondialdehyde (MDA) in fresh tissue homogenates and body fluids. After sc injection of HgCl2 (5 mg/kg body wt), MDA concentrations in liver and kidney became significantly increased by 9 h and reached peak values at 24 h. Dose-response studies were carried out with male albino rats of the Fisher-344 strain (body wt 170-280 g) injected with 1, 3, 5 mg Hg/kg as HgCl2 and sacrificed after 24 h. In time-response studies, animals were administered 5 mg Hg/kg as HgCl2 and sacrificed after 3, 9, 18, 24, and 48 h. Studies in the authors' laboratory have shown that (1) concentrations of MDA are increased in targets (liver, kidney, lung, and testis) of HgCl2-treated rats; (2) severity of hepatotoxicity and nephrotoxicity is generally consistent with the elevation of Hg and MDA concentrations, based upon the time-course and dose-effect relationships observed after administration of HgCl2 to rats; and (3) concentrations of MDA are reduced in target tissues after pre-treatment with antioxidants and chelators to HgCl2-treated rats. The results of this study implicate that the lipid peroxidation is one of the molecular mechanisms for cell injury in acute HgCl2 poisoning.

Animals↗

Dynamics of trimethoprim bound to dihydrofolate reductase--a deuterium NMR study.

We have employed deuterium NMR techniques to determine the dynamics of trimethoprim (TMP) in a binary complex with dihydrofolate reductase (DHFR) or in a ternary complex with DHFR and cofactor NADP+ in the fully hydrated state. TMP was deuterated at the following positions: (2',6'-D2)TMP, (3'-Ome-D3)TMP and (3',4'-Ome-D6)TMP. Dynamics of TMP were deduced from lineshape simulation and relaxation measurements of the deuterium NMR powder spectra of the three samples obtained at various temperatures. The results showed that in the polycrystalline state the TMP molecule is very rigid. The only detectable motion is the methyl group rotation at a rate of 10(10) s-1 at 25 degrees C, as determined from simulation of the partially relaxed powder patterns. When bound to DHFR a residual deuterium quadrupole splitting of 140 kHz was observed for (2',6'-D2)TMP at temperatures up to 30 degrees C, suggesting that the benzyl ring in the bound state is also very rigid. In contrast, in the binary complex with DHFR the methoxyl groups of TMP undergo librational motion of 10(7) s-1 about the C3-O bond at an amplitude of 54 degrees for the meta methoxyl group and about the C4-O bond at an amplitude of 70 degrees and similar rate for the para methoxyl group at 30 degrees C. The presence of the cofactor, NADP+, appears to tighten up the binding pocket such that the motion freedom of TMP is more restricted. The rigidity of TMP in a protein complex as revealed by our deuterium NMR results is in accord with the tight binding of TMP to DHFR.

Deuterium↗

Characterization of the structure and melting behavior of the loop I fragment of ColE1 RNA I.

We have synthesized two RNA fragments: a 42-mer corresponding to the full loop I sequence of the loop I region of ColE1 antisense RNA (RNA I), plus three additional Gs at the 5'-end, and a 31-mer which has 11 5'-end nucleotides (G(-2)-U9) deleted. The secondary structure of the 42-mer, deduced from one- and two-dimensional NMR spectra, consists of a stem of 11 base-pairs which contains a U-U base-pair and a bulged C base, a 7 nucleotide loop, and a single-stranded 5' end of 12 nucleotides. The UV-melting study of the 42-mer further revealed a multi-step melting behavior with transition temperatures 32 degrees C and 71 degrees C clearly discernible. In conjunction with NMR melting study the major transition at 71 degrees C is assigned to the overall melting of the stem region and the 32 degrees C transition is assigned to the opening of the loop region. The deduced secondary structure agrees with that proposed for the intact RNA I and provides structural bases for understanding the specificity of RNase E.

Base Composition↗

Lipid peroxidation in workers exposed to manganese.

OBJECTIVES: The following hypothesis was tested: plasma manganese concentration is associated positively with the product of lipid peroxidation, and lipid peroxidation is associated negatively with the activities of antioxidants in workers exposed to manganese. METHODS: The plasma manganese concentration of 22 manganese-exposed workers and 45 referents was determined by graphite furnace atomic absorption spectrophotometry. Malondialdehyde, the product of lipid peroxidation, was determined by high-performance liquid chromatography, and the activities of protective enzymes were measured by ultraviolet-visible spectrophotometry. RESULTS: The activities of superoxide dismutase, glutathione peroxidase, and catalase spread widely among the referents. The activity of superoxide dismutase and the concentrations of malondialdehyde and manganese were significantly higher in the manganese workers than in the referents. The concentration of malondialdehyde in the exposed workers was correlated strongly with the manganese level of plasma. CONCLUSIONS: Malondialdehyde can be used as an index of lipid peroxidation induced by manganese exposure.

Antioxidants↗

Kinetics of acetyl coenzyme A:arylamine N-acetyltransferase from rapid and slow acetylator frog tissues.

N-acetyltransferase (NAT) activity was determined in 100 frog (Rana tigrina) livers using 2-aminofluorene and p-aminobenzoic acid as substrates. Overall, the liver NAT activity of the 50 females was higher than the liver NAT activity of the 50 males. The activities (mean +/- SD) of NAT from the bladder, blood, colon, and liver of males was 0.30 +/- 0.11, 0.05 +/- 0.03, 0.09 +/- 0.05, and 0.93 +/- 0.56 nmol/min/mg protein for the acetylation of aminofluorene and 0.29 +/- 0.06, 0.36 +/- 0.04, 0.26 +/- 0.02, and 0.32 +/- 0.14 nmol/min/mg protein for the acetylation of p-aminobenzoic acid. In the bladder, blood, colon, and liver from female frogs, the activities obtained were 1.00 +/- 0.41, 0.52 +/- 0.07, 0.08 +/- 0.05, and 1.27 +/- 0.49 nmol/min/mg protein for aminofluorene and 0.34 +/- 0.12, 0.36 +/- 0.04, 0.34 +/- 0.07, and 0.48 +/- 0.21 nmol/min/mg protein for p-aminobenzoic acid. Kinetic constants for arylamine NAT activity in the blood, liver, bladder, and colon from frogs with rapid, intermediate, and slow acetylator activities were determined. KM and Vmax values for aminofluorene were 2- to 6-fold higher for liver than for the other tissues. KM and Vmax values for p-aminobenzoic acid showed a smaller variation among the tissues examined, with values obtained for the liver and bladder being somewhat higher than the values for the blood and colon. An apparent KM difference for aminofluorene was found in the liver from frogs with high and low acetylator activity. Based on the aminofluorene NAT activity of liver, there seems to be a polymorphism in NAT activity with 4 rapid, 21 intermediate, and 75 slow acetylators among the 100 frogs assayed. Distribution of acetylator phenotypes was similar among the 50 males and 50 females in this study. This is the first demonstration of acetyl coenzyme A:arylamine NAT activity in an amphibian and could lead to the development of a frog model for monitoring the effect of pollution of wetland environments on native species.

Acetyl Coenzyme A↗

Transcatheter embolization of a coronary arteriovenous fistula with a complex, helical-fibered platinum coil.

Transcatheter embolization was successfully performed on a 51-year-old man with a coronary arteriovenous fistula arising from the left circumflex coronary artery and draining into the superior vena cava. The patient presented with typical manifestations of angina pectoris that were first noticed during childhood but had worsened over the past 5 years. A 2 x 20 mm complex, helical-fibered platinum coil was placed in the mid-portion of the fistula and successfully occluded the fistula within 30 minutes. The patient has been free from angina pectoris since the procedure.

Arteriovenous Fistula↗

Integrin-mediated tyrosine phosphorylation and cytokine message induction in monocytic cells. A possible signaling role for the Syk tyrosine kinase.

Activation of cytoplasmic tyrosine kinases is an important aspect of signal transduction mediated by integrins. In the human monocytic cell line THP-1, either integrin-dependent cell adhesion to fibronectin or ligation of beta 1 integrins with antibodies causes a rapid and intense tyrosine phosphorylation of two sets of proteins of about 65-75 and 120-125 kDa. In addition, integrin ligation leads to nuclear translocation of the p50 and p65 subunits of the NF-kappa B transcription factor, to activation of a reporter gene driven by a promoter containing NF-kappa B sites, and to increased levels of mRNAs for immediate-early genes, including the cytokine interleukin (IL)-1 beta. The tyrosine kinase inhibitors genistein and herbimycin A block both integrin-mediated tyrosine phosphorylation and increases in IL-1 beta message levels, indicating a causal relationship between the two events. The components tyrosine phosphorylated subsequent to cell adhesion include paxillin, pp125FAK, and the SH2 domain containing tyrosine kinase Syk. In contrast, integrin ligation with antibodies induces tyrosine phosphorylation of Syk but not of FAK or paxillin. In adhering cells, pre-treatment with cytochalasin D suppresses tyrosine phosphorylation of FAK and paxillin but not of Syk, while IL-1 beta message induction is unaffected. These observations indicate that the Syk tyrosine kinase may be an important component of an integrin signaling pathway in monocytic cells, leading to activation of NF-kappa B and to increased levels of cytokine messages.

Benzoquinones↗

Chemical speciation of arsenic in urine of patients with blackfoot disease.

Blackfoot disease is a peripheral vascular disease resulting in gangrene of the lower extremities. Although extensive epidemiological study has implicated high arsenic content in artesian well water of the endemic area bears some important connection with the disease, the etiology of the disease is still not clarified. In this study, attention is paid to chemical speciation of arsenic in order to find out whether the concentrations of arsenic species in urine of Blackfoot disease patients are different from those of controls. Experimental results indicate that the total arsenic, inorganic arsenic, monomethylarsonic acid, and other forms of arsenic in the urine of patients are significantly higher than those of the controls. The possible connection of those arsenic species with the etiology of the disease is discussed.

Arsenic↗

Trace element concentration and arsenic speciation in the well water of a Taiwan area with endemic blackfoot disease.

Blackfoot disease is a peripheral vascular disease resulting in gangrene of the lower extremities. Although extensive epidemiological study has implicated high arsenic content in artesian well water in the endemic area, there is more to learn about the etiology of the disease. In this study, effort is paid on multielement determination and arsenic speciation in order to find out whether the trace element concentration pattern in well water in the Blackfoot disease endemic area is different from those of two control areas. Experimental results indicate that the concentrations of Fe, P, Na, and Ba in well water in the Blackfoot disease endemic area are found to be significantly higher than those of the controls, but they are still below the drinking water standard. The total arsenic in well water in the endemic area (671 +/- 149 ppb) is much higher than that of one normal control area of Hsin-Chu (< 0.7 ppb), but is a similar level as that of other control areas of I-Lan (653 +/- 71 ppb) where no Blackfoot disease has ever been found. It was also found that the insoluble arsenic in the endemic area (21.9 ppb) is much higher than that in two control areas (< or = 1.8 ppb), and the concentration ratio between As(III) and As(V) species in the endemic area (2.6) is much lower than that in one of the control areas, where the total arsenic is also high (14.7). The possible connection of Blackfoot disease with trace elements, arsenic species, and possibly other as yet undefined environmental factors in the artesian well water, is discussed.

Arsenic↗

Lead-catalyzed peroxidation of essential unsaturated fatty acid.

In the present study, the reaction mixtures (lead compounds with essential unsaturated fatty acids) were preincubated at 37 degrees C for 24 h prior to the measurement of malondialdehyde (MDA) by HPLC. The metal-catalyzed reactions were also compared in the presence of butylated hydroxytoluene (BHT), a free radical scavenger. Our results showed that according to the difference in the number of double bonds of essential unsaturated fatty acids, the kinds of lead compounds, and the concentrations of lead compounds, the extent of lipid peroxidation was different. The addition of BHT to the reaction mixtures significantly reduced the production of MDA (P < 0.01). These in vitro studies support prior in vivo reports that the important mechanism of the acute toxic effects of the lead compounds is owing at least in part, to metal-catalyzed peroxidation of polyunsaturated fatty acids.

Arachidonic Acid↗

Acute heroin intoxication with complications of acute pulmonary edema, acute renal failure, rhabdomyolysis and lumbosacral plexitis: a case report.

After intravenous injection of heroin, a 27-year-old male with altered mental status and hypotension was seen at the Emergency Service where acute pulmonary edema was noted. The problem was resolved three days later after oxygen therapy had been administered by face mask. Acute renal failure, rhabdomyolysis and monoplegia of the patient's left leg were exhibited during his stay at the Intensive Care Unit. Neurological examination and electro-diagnostic studies (electromyography and nerve conduction velocity) showed left lumbosacral plexitis. Hemodialysis was given. Though the patient's hospital course was uneventful, satisfactory recovery from his left leg weakness, which persisted for one year after hospital discharge, was finally achieved.

Acute Disease↗

Existence of a well-defined pulmonary lesion on plain chest film predicts poor response of chemotherapy in small cell lung cancer.

BACKGROUND: Plain chest film is the most convenient and common tool used to evaluate the response of lung cancer to chemotherapy. Many authors tried to evaluate the use of plain chest films to predict chemotherapy response. This study investigated a new factor which could be used to predict the chemotherapy response of small cell lung cancer (SCLC). METHODS: Sixty-two patients with cytopathologically proven small cell lung cancer receiving at least two courses of chemotherapy were included in this study. Among these patients, thirty-nine patients received six courses of chemotherapy. The regimens of chemotherapy are Etoposide (100 mg/m2) and Cisplatin (25 mg/m2). We divided these patients into two groups according to whether a well-defined pulmonary lesion excluding hilar and mediastinal lymphoadenopathy, could be identified on plain chest X-ray (CXR). Group I consisted of 31 patients with identified lesions on the CXR; group II consisted of 31 patients with unidentifiable lung lesions. CXRs were taken each time before chemotherapy and were collected and compared to evaluate the chemotherapy response. The 39 patients receiving six course of chemotherapy, were further divided into group I (n = 19) and group II (n = 20) to evaluate the chemotherapy response. RESULTS: After two courses of chemotherapy, we found 23 patients [74.2% (23/31)] in group I had partial response(PR) as compared to 12 patients [38.7% (12/31)] in group II (P < 0.05). For the 39 patients receiving six courses of chemotherapy, we could find only five patients [16.1% (5/19)] in group I who had a complete response (CR) as compared to 17 patients [85% (17/20)] in group II (P < 0.001). CONCLUSION: For patients with SCLC, a well-defined lung lesion on a CXR could be an important new factor to predict the chemotherapy response. It could predict less responsiveness to chemotherapy.

Adult↗

Thrombophilia associated with obesity in ethnic Chinese.

OBJECTIVE: To investigate a possible interrelationship between obesity and the coagulation and fibrinolytic systems of ethnic Chinese. DESIGN: The Cardiovascular Disease Risk Factor Two-Township Study, a longitudinal, prospective study in Taiwan, which focuses on the evolution of cardiovascular disease risk factors. MEASUREMENTS: Haemostatic parameters measured in this study included prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, factor VIIc, factor VIIIc, antithrombin III and plasminogen. RESULTS: Present data demonstrated that all haemostatic parameters show a dose-dependent change with body weight. PT and APTT shortened with increased body mass index (BMI). Fibrinogen, factor VIIc, factor VIIIc, plasminogen and antithrombin III increased with higher BMI. CONCLUSION: The present result shows that haemorrheological abnormalities do exist in obese subjects and this thrombophilic phenomenon sheds further light on the study of higher cardiovascular and cerebrovascular mortality and morbidity in the obese.

Adult↗

Integrin-mediated cell adhesion activates mitogen-activated protein kinases.

Integrins can function as signal-transducing receptors capable of modulating cell growth and gene expression (Juliano, R. L., and Haskill, S. (1993) J. Cell Biol. 120, 577-585; Hynes, R. O. (1992) Cell 69, 11-25). An early event in integrin signaling in fibroblasts and other cells involves activation of pp125FAK, a cytoplasmic tyrosine kinase (Hanks, S. K., Calalb, M. B., Harper, M. C., and Patel, S. K. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 8487-8491; Schaller, M. D., Borgman, C. A., Cobb, B. S., Vines, R. R., Reynolds, A. B., and Parsons, J. T. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 5192-5196). Here we report a novel aspect of integrin-mediated signal transduction. We demonstrate that adhesion of cells to substrata coated with extracellular matrix proteins, or with a synthetic peptide containing the RGD sequence, can cause activation of mitogen-activated protein (MAP) kinases in 3T3 or REF52 fibroblasts. Activation of MAP kinases seems to depend on integrin engagement rather than simply on cell attachment. Thus, MAP kinases are activated when cells adhere to substrata coated with the integrin ligands fibronectin or laminin, but not when cells adhere to poly-D-lysine, a nonspecific adhesion-promoting polypeptide. Treatment of cells with cytochalasin D, an inhibitor of actin microfilament assembly, almost completely blocks adhesion-induced MAP kinase activation, indicating a critical role for the cytoskeleton. In REF52 cells, we have observed that activation of MAP kinases is accompanied by redistribution of the protein to the nucleus, suggesting that the activated kinases may impinge on factors regulating gene expression. Thus, integrin-mediated cell adhesion seems a sufficient stimulus to cause activation and nuclear translocation of MAP kinases. This may have important implications for the regulation of cell growth and differentiation by the extracellular matrix.

3T3 Cells↗

Detection of soluble P-glycoprotein in culture media and extracellular fluids.

Multidrug resistance (MDR) is a unique phenomenon in cancer patients and is commonly associated with an overexpression of the human MDR gene mdr1, which encodes an energy-dependent Mr 180 kDa membrane bound protein, known as P-glycoprotein. P-glycoprotein serves as a membrane efflux to pump the drugs out of the cancer cells. Western blot analysis, using a newly generated monoclonal antibody F4 which recognizes specifically an extracellular epitope of human MDR1 P-glycoprotein, reveals that soluble P-glycoprotein is detected in the cultured media of viable adriamycin-resistant human ovarian carcinoma 2780AD cells, whereas those of the drug-sensitive parent A2780 cells contain no detectable level of soluble P-glycoprotein. Soluble P-glycoprotein also is detected in extracellular fluids of cancer patients, such as malignant ascites and serum, and is not detectable in serum samples of normal healthy individuals. The Mr of soluble P-glycoprotein is the same as that of membrane bound P-glycoprotein. The presence of soluble P-glycoprotein in extracellular fluids may provide the basis for its use as a quantitative parameter of MDR and as a means to lessen or reverse MDR.

ATP Binding Cassette Transporter, Subfamily B, Mem↗