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Biomedical subjects

T H Lin

Publications and source records attributed to T H Lin.

At least 37 records · Page 2Linked to original sources

Reduced acute rejection and superior 1-year renal allograft survival with basiliximab in patients with diabetes mellitus. The Global Simulect Study Group.

BACKGROUND: Renal allograft recipients with diabetes mellitus often demonstrate poorer clinical outcomes than nondiabetic patients. Basiliximab (Simulect), a chimeric anti-interleukin-2 receptor monoclonal antibody, reduced the incidence of acute rejection in renal allograft recipients in 2 multicenter, placebo-controlled, phase III trials. METHODS: An analysis of pooled results from the 2 trials was conducted to compare the efficacy and safety of basiliximab with placebo in renal transplant recipients with and without prior diabetes. Patients received either basiliximab (20 mg on day 0 and day 4 posttransplantation) or placebo in combination with cyclosporine for microemulsion (Neoral) and steroids. RESULTS: A total of 722 patients (150 diabetic, 572 nondiabetic) were eligible for intent-to-treat analysis. At 12 months, basiliximab as compared with placebo reduced the proportion of patients experiencing first acute rejection by 41% in diabetics (P<0.01) and by 29% in nondiabetics (P<0.001). Biopsy-confirmed rejection was reduced by 44% in diabetics (P<0.01) and by 26% in nondiabetics (P<0.01). The first acute rejection episode requiring augmented immunosuppression other than steroids was reduced by 49% in diabetics (P<0.01) and by 41% in nondiabetics (P<0.001); death, graft loss, or first rejection episode was reduced by 43% in diabetics (P=0.001) and by 22% in nondiabetics (P<0.01). Superior graft survival was maintained in diabetic recipients treated with basiliximab versus placebo (96% vs. 86%; P=0.022). There were no significant differences in safety between basiliximab and placebo in both diabetic and nondiabetic patients. CONCLUSIONS: Basiliximab is associated with a significant reduction in acute rejection and an excellent safety profile in renal transplant recipients with and without diabetes mellitus. Superior graft survival was evident in diabetic patients.

Acute Disease↗

Effects of selenium dioxide on blood and femoral bone marrow of rats.

This study was undertaken to investigate the effects of selenium dioxide (SeO2) on rat blood and femoral bone-marrow oxidant mechanisms. Treatment with SeO2, 67 microg Se/kg i.p. daily for 14 d, significantly decreased lipid peroxidation and the concentrations of Fe in serum and bone marrow. The concentrations of Se in serum and bone-marrow cells were significantly increased after SeO2 treatment. The activities of glutathione peroxidase (GPx) in blood and bone-marrow cells were markedly increased. The levels of oxyhemoglobin in blood were significantly increased, while the concentrations of methemoglobin were decreased after SeO2 administration. The fragility of erythrocytes membranes was significantly decreased in SeO2-treated rats compared to controls. Data suggest that treatment with a low dose of SeO2 may provide antioxidant nutrients to blood and bone marrow.

Animals↗

Dengue NS1-specific antibody responses: isotype distribution and serotyping in patients with Dengue fever and Dengue hemorrhagic fever.

To understand the antibody responses to dengue (DEN) nonstructural 1 (NS1) glycoprotein and their roles in protective immunity or pathogenesis of dengue fever (DF) and dengue hemorrhagic fever (DHF), we have analyzed the NS1-speccific IgM, IgA and IgG antibodies from patients with DF and DHF. An isotype-specific, indirect enzyme-linked immunosorbent assay (ELISA) was established by coating a NS1-specific monoclonal antibody (MAb), D2/8-1, to capture soluble NS1 antigens secreted in the culture supernatants of Vero cells infected with DEN virus. We observed strong anti-NS1 antibody responses in all of the convalescent sera of patients with DF and DHF. Similar NS1-specific isotypic and serotypic antibody responses were found in the sera from DF and DHF patients. The results showed that all DEN infections induced significant NS1-specific IgG, whereas 75% and 60% of primary DF patients vs. 40% and 90% of secondary DF patients produced IgM and IgA antibodies, respectively. Specificity analysis showed that DEN NS1-specific IgG and IgA antibodies cross-react strongly to Japanese encephalitis (JE) virus NS1 glycoprotein, whereas DEN NS1-specific IgM antibodies do not cross-react to JE virus NS1 glycoprotein at all. The serotype specificity of NS1-specific IgM, IgA and IgG were found to be 80%, 67% and 75% for primary infections, and 50%, 22% and 30% for secondary infections in positive samples of DF patients. Similar pattern was found in DHF patients. The results showed that all of the DF and DHF patients produced significant NS1-specific antibodies. We did not observe direct correlation between the anti-NS1 antibody responses and DHF because sera from patients with DF and DHF showed similar anti-NS1 antibody responses.

Antibodies, Monoclonal↗

Adaptive local contrast enhancement method for medical images displayed on a video monitor.

It is known that light-box luminance is an important factor in the detection of objects on radiographs. Existing methods for image contrast enhancement do not consider the luminance effect so that the enhancement may be inappropriate for the processed image displayed on a video monitor. Based on the properties of human visual system (HVS), an adaptive local contrast enhancement (ALCE) method was developed to enhance the medical image displayed on the video monitor by investigating the influence on human eyes of display luminance difference between a conventional light-box and a video monitor. The HVS model indicated parts of a radiograph unclear to human eyes at a given display luminance. By calculating the contrast of the image pixel by pixel, we found the parts of an image that are needed to be amplified at low display luminance and provided these parts with adequate enhancement. The processed image displayed on a video monitor was visually equivalent to the raw radiograph displayed on a light-box. A quantitative evaluation method of image quality assessment was used to compare the ALCE-processed image with others.

Biophysical Phenomena↗

Trace elements and lipid peroxidation in human seminal plasma.

In the present study, the concentrations of copper, iron, zinc, and malondialdehyde in human seminal plasma were measured and correlated with the sperm count and motility in human semen. Copper, iron, and zinc were analyzed by atomic absorption spectrometry, whereas malondialdehyde was measured by high-performance liquid chromatography. The malondialdehyde concentrations in asthenospermia and oligoasthenospermia were significantly higher than in normospermia. Copper and iron levels were higher in asthenospermia, whereas the zinc concentrations in both oligospermia and asthenospermia were lower than in normal controls. A negative correlation (r = -0.28, p < 0.05) between the malondialdehyde concentration and sperm motility was observed in the abnormal groups. There was no association among copper, iron, zinc, and malondialdehyde in seminal plasma. We concluded that changes in trace elements may be related to sperm quality and that lipid peroxidation, although it is not promoted in the seminal plasma by copper or iron or ameliorated by zinc, may be involved in the loss of sperm motility.

Humans↗

Determination of trace elements in some natural drugs by atomic absorption spectrometry.

Fifteen kinds of common plants, animals, and minerals used as traditional medicines by the Chinese people have been subjected to analysis by atomic absorption spectrometry for its content of seven metals: lead, cadmium, arsenic, mercury, copper, cobalt, and manganese. The concentrations of these elements are significantly different according to their vegetal, animal, or mineral origin. The average values found for lead, cadmium, arsenic, cobalt, and manganese in drugs of mineral origin are higher than those derived from plants and animals, except for copper, which was higher in drugs of animal origin. Our results suggest that the user of traditional Chinese crude drugs should be warned of the potential danger of heavy-metal poisoning because their concentrations seem to be higher than the maximum values allowed by health agencies in several countries.

Drugs, Chinese Herbal↗

Cadmium-induced liver, heart, and spleen lipid peroxidation in rats and protection by selenium.

The purpose of this study was to evaluate the effects of cadmium-induced peroxidative damage to rat liver, heart, and spleen. Sprague-Dawley rats were injected subcutaneously with a single dose of 25, 125, 500, or 1250 microg Cd/kg and evaluated 6, 12, 24, or 72 h later. Liver, heart, and spleen were analyzed for lipid peroxidation and Fe, Cu, Zn, Se, and Cd concentrations. Data showed that Cd produced enhanced lipid peroxidation in the liver, heart, and spleen. These Cd-induced changes were accompanied by a significant rise in liver, heart, and spleen Fe and Cu, and a fall in spleen Zn and liver, heart, and spleen Se. Concurrent treatment with Se and Cd reduced the Cd-induced alterations in liver, heart, and spleen peroxidation and essential metal levels. Data suggest that lipid peroxidation is associated with cadmium toxicity and that Se was found effective in preventing lipid peroxidation.

Animals↗

Diagnosis and follow-up of acute promyelocytic leukemia by detection of PML-RAR alpha gene rearrangement.

BACKGROUND: Rapid and accurate diagnosis of acute promyelocytic leukemia (APL) is essential for management of the disease, as all-trans retinoic acid (ATRA) therapy only induces complete remission in patients whose leukemic cells harbor a t(15;17) translocation, resulting in promyelocytic-retinoic acid receptor alpha (PML-RAR alpha) fusion transcripts. Moreover, a positive reverse transcriptase-polymerase chain reaction (RT-PCR) of PML-RAR alpha is reported to be a sensitive predictor of relapse in APL. This prompted us to use RT-PCR for rapid diagnosis and monitoring of minimal residual disease in APL patients. METHODS: A nested RT-PCR technique was applied to detect the unique PML-RAR alpha fusion transcript in 13 APL patients. The test was applied to help clarify the diagnosis and monitor minimal residual disease after treatment. RESULTS: All 13 APL patients had a positive test result: five patients with the S-form, seven patients with the L-form and one patient with the V-form of mRNA fusion transcripts. Minimal residual disease was prospectively monitored using this technique in six patients. Although in clinical remission, all four patients treated with ATRA alone were persistently PCR positive. Of the six patients receiving various forms of consolidation chemotherapy, one was persistently PCR positive while in remission and relapsed four months after the positive PCR test. Five patients were PCR negative. One of the five negative patients relapsed six months after a negative PCR test. The other four patients remained in remission, with a follow-up period of 25 to 46 months after the negative test. PCR was performed in two patients who had been in continuous remission for 3.5 and seven years, respectively. They both had negative PCR tests. CONCLUSIONS: Nested RT-PCR is valuable for confirming the diagnosis of APL and in monitoring minimal residual disease. However, we found that negative test cannot absolutely exclude the possibility of future relapse.

Adolescent↗

The effect of fluvastatin on fibrinolytic factors in patients with hypercholesterolemia.

Several studies have shown cardiovascular benefit in treating hypercholesterolemia with HMG-CoA reductase inhibitor. However, in addition to the lowering of cholesterol, the beneficial effects of this inhibitor reflect other pharmacological activities. Whether these beneficial effects are partly mediated by changes in fibrinolytic factors remains to be proven, since clinical studies on the effects of HMG-CoA reductase inhibitors on fibrinolytic factors have not yielded consistent results. The purpose of this study was to evaluate the effects of fluvastatin on fibrinolytic factors in hypercholesterolemic patients. After 6 weeks on a low-fat, low-cholesterol diet, 23 outpatients known to have primary hypercholesterolemia with low density lipoprotein cholesterol (LDL-C) > or = 130 mg/dl with at least 2 risk factors or fasting LDL-C > or = 160 mg/dl were selected for the study. Venous blood samples were collected at baseline and at 8 weeks after fluvastatin therapy (40 mg/day) to measure of tissue plasminogen activator (t-PA), plasminogen activators inhibitor-1 (PAI-1), fibrinogen, D-dimer and lipid profile. After 8 weeks of therapy, fluvastatin reduced serum cholesterol by 11% (261.9 mg/dl vs 233.2 mg/dl, P < 0.01) and LDL-C by 22% (191.9 mg/dl vs 149.3 mg/dl, P < 0.01). D-dimer was significantly decreased (0.38 ng/L vs 0.28 ng/L, P = 0.02) and tPA, PAI-1 and fibrinogen tended to decrease after therapy. Fluvastatin therapy improved fibrinolytic profile; the result of this study may in part explain the benefit of HMG-CoA reductase inhibitor on cardiovascular system other than lipid lowering.

Aged↗

Oxidative effects of nickel on bone marrow and blood of rats.

This study was undertaken to examine the oxidative effects of nickel (Ni) on rat blood and bone marrow. Treatment with either 100, 250, or 500 micromol/kg Ni i.p. significantly enhanced lipid peroxidation in serum and bone marrow after 24 h. The concentrations of Ni and Fe in serum and bone marrow cells were also significantly increased after NiCl2 administration. After treatment with NiCl2, the activities of glutathione peroxidase (GPx) and levels of alpha-tocopherol in bone marrow cells were markedly reduced. There was an inverse association thiobarbituric acid elevated (TBA)-chromogen product with decreased GPx activity and alpha-tocopherol levels in bone marrow cells of NiCl2-treated rats. The concentrations of alpha-tocopherol in blood significant reduced with 100 and 250 micromol/kg Ni but returned to control at the 500-micromol/kg dose. Data suggest that lipid peroxidation may be a contributing factor in Ni-induced tissue oxidative stress.

Analysis of Variance↗

Cadmium-induced renal lipid peroxidation in rats and protection by selenium.

Cadmium has been recognized as one of the most toxic environmental and industrial pollutants. The kidney is a critical target organ following Cd exposure. The aim of this study was to investigate the effects of cadmium-induced peroxidative damage to rat kidney. Treatment of rats with Cd resulted in a time- and dose-related accumulation of metal in kidney. Cd produced enhanced lipid peroxidation in plasma and kidney. These Cd-induced changes were accompanied by a significant rise in renal Fe and Cu, and a fall in tissue Zn and Se. Concurrent treatment with Se and Cd reduced the Cd-induced alterations in renal peroxidation and essential metal levels. Data suggest that lipid peroxidation is associated with Cd toxicity and that Se was found effective in attenuation of these renal effects.

Animals↗

Lipid peroxidation in workers exposed to hexavalent chromium.

The aim of this study was to investigate whether exposure to hexavalent chromium induces lipid peroxidation in human. This study involved 25 chrome-plating factory workers and a reference group of 28 control subjects. The whole-blood and urinary chromium concentrations were determined by graphite furnace atomic absorption spectrophotometry. Malondialdehyde (MDA), the product of lipid peroxidation, was determined by high-performance liquid chromatography, and the activities of protective enzymes were measured by ultraviolet-visible spectrophotometry. In the chrome-plating workers, the mean concentrations of chromium in blood and urine were 5.98 microg/L and 5.25 microg/g creatinine, respectively; the mean concentrations of MDA in blood and urine were 1.7 micromol/L and 2.24 micromol/g creatinine. The concentrations of both chromium and MDA in blood and urine were significantly higher in the chromium-exposed workers. The activities of superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) were not markedly different between control and exposed workers. Data suggest that MDA may be used as a biomarker for occupational chromium exposure. Antioxidant enzymic activities are not a suitable marker for chromium exposure.

Adult↗

A comparative molecular field analysis study on several bioactive peptides using the alignment rules derived from identification of commonly exposed groups.

A 3D convex hull computation algorithm designed by us previously is used as a tool to align a series of structures randomly generated for eleven bioactive tachykinin peptides. There are 10 random structures generated for each peptide. A random structure is selected for each peptide to form a structural set of eleven structures. The total number of structural sets generated is 100. The convex hull computation algorithm is applied to each peptide structure generated. We count the frequency of atoms lying on the vertices of each hull computed. Vertices of the same atom type are gathered together as a set of commonly exposed atoms for a structural set generated. Structures are then aligned by treating the set of commonly exposed atoms as a set of correspondences using the FIT option of the SYBYL 6.4 program. All the structure sets are also aligned by using the coordinates of the backbone C alpha atoms as a set of correspondences through the same program. It is found that while a smaller degree of structural similarity for structures aligned by the convex hull alignment rule is detected, the overall SYBYL comparative molecular field analysis (CoMFA) statistics computed for the aligned structures using the alignment rule is better than that computed for the aligned structures using the C alpha atoms alignment rule. A similar conclusion is drawn for a subset of structures selected and probed by a different type of atoms using the SYBYL CoMFA program. These results indicate that computation of 3D convex hulls is a feasible way that one can use to align structures generated for highly flexible molecules of this kind.

Algorithms↗

Association between oxidative stress and changes of trace elements in patients with breast cancer.

OBJECTIVES: To investigate the association between oxidative stress and certain trace elements in the blood of breast cancer patients. DESIGN AND METHODS: Malondialdehyde (MDA) was measured in serum of patients with breast cancer (n = 35) and controls (n = 35) by high performance liquid chromatography. Trace elements were determined by atomic absorption spectrophotometry. RESULTS: In the present study, significantly increased lipid peroxidation, measured as MDA, was demonstrated in the serum of breast cancer patients (p < 0.01). The concentrations of zinc and iron remained unaltered. However, the mean serum copper level in patients with breast cancer was significantly higher than the control group (p < 0.01). In addition, the mean serum selenium level in patients with stage III was significantly lower than the control group (p < 0.05). Moreover, a positive correlation was also observed between copper and MDA levels in the patient group but not in the control group. CONCLUSION: In the present study, the presence of an association between oxidative stress and trace elements was observed in patients with breast cancer. We suggest that increased oxidative stress in patients with breast cancer may result from changes in the levels of certain trace elements.

Adult↗

Cadmium induced lipid peroxidation in rat testes and protection by selenium.

The main goal of this study was to investigate the role of cadmium in the promotion of lipid peroxidation in the homogenates of rat testes and the effect of selenium on lipid peroxidation in testes of rats after cadmium injection. Treatment of rats with cadmium resulted in a time- and dose-related accumulation of the metal ions in testes. The concentrations of cadmium, copper, zinc, selenium and iron in the tissues were determined by an atomic absorption spectrophotometer and lipid peroxidation in testes was measured by a spectrophotometer. Cadmium produced enhanced lipid peroxidation in testes. These cadmium-induced changes were accompanied by a significant increase of iron and copper, and a decrease of zinc in testes. Concurrent treatment with selenium and cadmium reduced the cadmium-induced alterations in lipid peroxidation and essential metal levels. Data suggest that lipid peroxidation was associated with cadmium toxicity in testes and that the addition of selenium was found to be effective in attenuation of this effect.

Animals↗

Mosquito fauna in water-holding containers with emphasis on dengue vectors (Diptera: Culicidae) in Chungho, Taipei County, Taiwan.

A survey was conducted to characterize the mosquito fauna in water-holding containers in residential and open areas with emphasis on Aedes albopictus Skuse, and to determine the prevalence of mosquito-positive containers to obtain background information for a source reduction program. Seven container-inhabiting mosquito species were collected in residential areas, including Ae. albopictus, Culex quinquefasciatus Say, C. pallidothorax Theobald, C. neomimulus Lien, C. bicornutus Theobald, C. fuscanus Wiedemann, and Tripteroides aranoides Theobald. Ae. albopictus was the most abundant species and was collected in 18.49% of the containers examined. Other mosquito species were found in 0.02-0.16% of the total numbers of water containers checked. Of the positive water containers, 97.33% contained Ae. albopictus larvae. Sixteen species were collected in open areas away from residential sites. Ae. albopictus was most abundant and was present in 24.50% of the total number of containers examined. C. bicornutus, C. quinquefasciatus, and C. pallidothorax were present in 2.17, 1.48, and 1.08%, respectively. Ae. albopictus larvae were found in 74.78% of the mosquito-positive water containers. The mean Breteau index (+/- SE) in 1997 (17.22 +/- 1.59 mosquito-positive containers per 100 premises) per village in residential areas was not significantly higher than the index in 1996 (16.86 +/- 1.33). The frequency of occurrence of Ae. albopictus in different containers is presented. A greater preference for containers in outdoor habitats was found. The ratio of the total number of containers indoors and outdoors per premises was 1.15:1.00, whereas the ratio of mosquito-positive containers indoors and outdoors was 1.00:1.83. Most indoor breeding containers (86.11%) in residential areas were used for planting purposes and for recreation (12.50%). The number of breeding containers in residential areas that were classified as trash increased from 0.35% indoor to 39.03% outdoor, whereas the number used for planting reduced to 34.95%. Most breeding containers (63.02%) in open areas were trash; natural containers (11.86%) were the 2nd most common breeding site followed by temporarily unused (8.84%), watering (6.98%), and planting containers (5.81%).

Aedes↗

The N terminus domain of type VI adenylyl cyclase mediates its inhibition by protein kinase C.

Previous results from our laboratory have shown that phosphorylation of type VI adenylyl cyclase (ACVI) by protein kinase C (PKC) caused suppression of adenylyl cyclase activity. In the present study, we investigated the role of the N terminus cytosolic domain of ACVI in this PKC-mediated inhibition of ACVI. Removal of amino acids 1 to 86 of ACVI or mutation of Ser(10) (a potential PKC phosphorylation site) into alanine significantly relieved the PKC-mediated inhibition and markedly reduced the PKC-evoked protein phosphorylation. PKC also effectively phosphorylated a recombinant N terminus cytosolic domain (amino acids 1-160) protein of ACVI and a synthetic peptide representing Ser(10). In addition, the amino acids 1 to 86 truncated mutant exhibited kinetic properties similar to those of the wild type. Taken together, these data demonstrate that the highly variable N terminus cytoplasmic domain of ACVI is a regulatory domain with a critical role in PKC-mediated suppression, which is a hallmark of this adenylyl cyclase isozyme. In addition, Ser(10) was found to serve as an acceptor for the PKC-mediated phosphorylating transfer of ACVI.

Adenylyl Cyclase Inhibitors↗