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Biomedical subjects

M T Lin

Publications and source records attributed to M T Lin.

At least 19 recordsLinked to original sources
PubMed2006

Heat shock protein 72 overexpression protects against hyperthermia, circulatory shock, and cerebral ischemia during heatstroke.

This study extends our earlier studies in rats by applying our heatstroke model to a new species. Additionally, transgenic mice are used to examine the role of heat shock protein (HSP) 72 in experimental heatstroke. Transgenic mice that were heterozygous for a porcine HSP70i gene ([+]HSP72), transgene-negative littermate controls ([-]HSP72), and normal Institute of Cancer Research strain mice (ICR) under pentobarbital sodium anesthesia were subjected to heat stress (40 degrees C) to induce heatstroke. In [-]HSP72 or ICR, the values for mean arterial pressure, the striatal blood flow, and the striatal PO2 after the onset of heatstroke were significantly lower than those in preheat controls. The core and brain temperatures, the extracellular concentrations of ischemic and injury markers in the striatum, and the striatal neuronal damage scores were significantly greater than those in the preheat controls. In [-]HSP72 or ICR, the body temperatures, cell ischemia content, and injury marker in the striatum were significantly higher, and the mean arterial pressure, striatal blood flow, and striatal PO2 concentration were significantly lower during heatstroke than in [+]HSP72. Accordingly, the latency and the survival times for [+]HSP72 significantly exceeded those of [-]HSP72 or ICR. These results demonstrate that the overexpression of HSP72 in multiple organs improves survival during heatstroke by reducing hyperthermia, circulatory shock, and cerebral ischemia and damage in mice.

Animals↗
PubMed2006

Infusion of human umbilical cord blood cells protect against cerebral ischemia and damage during heatstroke in the rat.

Intravenously delivered human umbilical cord blood cells (HUCBC) have been previously shown to improve both morphologic and functional recovery of heat-stroked rats. To extend these findings, we examined both the morphologic and functional alterations in the presence of HUCBC or human peripheral mononuclear cells (PBMC) 24 h before initiation of heatstroke. Anesthetized rats, 1 day before the initiation of heatstroke, were divided into three major groups and given the following: (a) serum-free lymphocyte medium (0.3 ml) intravenously; (b) PBMC (5 x 10(6) in 0.3 ml serum-free lymphocyte medium); or (c) HUCBC (5 x 10(6) in 0.3 ml serum-free lymphocyte medium). Another group of rats were exposed to room temperature (26 degrees C) and used as normothermic controls. In vehicle-treated heatstroke rats, their mean arterial pressure, cerebral blood flow, and brain PO(2) were all lower than in normothermic controls after the onset of heatstroke. However, their body temperatures and striatal levels of inducible nitric oxide synthase (iNOS)-dependent NO, ischemia and damage markers (e.g., glycerol, glutamate, and lactate/pyruvate ratio), and neuronal damage in the striatum were all greater. The heatstroke-induced arterial hypotension, cerebral ischemia and hypoxia, and increased levels of iNOS-dependent NO in the striatum were all significantly reduced by pretreatment with HUCBC, but not with PBMC. Moreover, HUCBC were localized by immunohistochemistry and PCR analysis in the injured brain structures and spleen. These findings indicate that HUCBC transplantation, in addition to having therapeutic values, can be a good choice for preventing heatstroke occurrence.

Analysis of Variance↗
PubMed2006

Improved treatment results for childhood acute myeloid leukemia in Taiwan.

To improve treatment results for children with de novo acute myeloid leukemia (AML), we introduced a novel protocol, Taiwan Pediatric Oncology Group-AML-97A, for AML other than acute promyelocytic leukemia (APL), for which modified conventional protocols were used. From January 1, 1997, to December 31, 2002, 141 children younger than 17 years old with de novo AML were enrolled. In total, 117 patients with non-APL AML were treated with induction therapy of idarubicin and cytarabine (Ara-C), postremission therapy with high-dose Ara-C - containing regimens for four monthly courses, and moderate-dose therapy with idarubicin and Ara-C for four monthly courses. The first 19 patients with APL were treated with all-trans retinoic acid, idarubicin and Ara-C, with the remaining five patients receiving all-trans retinoic acid and idarubicin, followed by maintenance therapy for 2 years. Stem cell transplantation was performed in 29 patients in first remission with a similar outcome as chemotherapy alone. The remission rate in the AML-97A study was 90%, the 5-year survival 51 +/- 5.3% (s.e.) and the 5-year event-free survival 50 +/- 4.8%; for APL, these were 100%, 86 +/- 7.0, and 75 +/- 9.8%. For the whole group, the 5-year survival was 57 +/- 4.7% and the 5-year event-free survival 54 +/- 4.4%. The AML-97A regimen was well tolerated.

Adolescent↗
PubMed2005

Transcultural issues.

Pharmacogenetics as a field of research is increasing the basis of knowledge on the use of psychotropics in different ethnic patient populations. This chapter summarizes current knowledge on the metabolism of anxiolytic agents with emphasis on pharmacogenetics and ethnic variations in drug responses.

Anti-Anxiety Agents↗
PubMed2005

Calreticulin expression in neuroblastoma--a novel independent prognostic factor.

BACKGROUND: Calreticulin (CRT), an endoplasmic reticulum protein, has been reported to be essential for the differentiation of neuroblastoma (NB) cells, suggesting that CRT may affect the tumor behavior of neuroblastoma. The aim of this study was to evaluate the association of clinicopathologic factors and patient survival with the expression of CRT in patients with NB. PATIENTS AND METHODS: Sixty-eight NBs were investigated by immunohistochemical staining against CRT, and were divided into positive and negative immunostaining groups. Correlations between calreticulin expression, various clinicopathologic and biologic factors, and patient survival were studied. In seven tumor samples, CRT mRNAs and proteins were evaluated with real-time PCR and western blot, respectively, and correlated with immunohistochemical findings. RESULTS: Among 68 NBs, 32 (47.1%) showed positive CRT expression. Positive CRT immunostaining strongly correlated with differentiated histologies, as well as known favorable prognostic factors such as detected from mass screening, younger age (< or =1 year) at diagnosis and early clinical stages, but inversely correlated with MYCN amplification. Kaplan-Meier analysis revealed that NB patients with CRT expression did have better survival. Multivariate analysis demonstrated CRT expression to be an independent prognostic factor. Moreover, CRT expression also predicted better survival in patients with advanced-stage NBs, and its absence predicted poorer survival in patients whose tumor had no MYCN amplification. The amount of CRT mRNAs and proteins in NB tumor samples tested correlated well with the immunohistochemical expressions. CONCLUSIONS: CRT expression correlates with the differentiation of NB and predicts favorable survival, thereby suggesting CRT to be a useful indicator for planning treatment of NB.

Biomarkers, Tumor↗
PubMed2005

Sheng mai san, a Chinese herbal medicine, protects against renal ischaemic injury during heat stroke in the rat.

1. There is evidence that the induction of inducible nitric oxide synthase (iNOS) and peroxynitrite by ischaemia/reperfusion may lead to renal cell injury. Herein, we investigated whether Sheng mai san (SMS), a Chinese herbal medicine, protects against renal ischaemic injury during heat stroke by reducing iNOS-dependent nitric oxide (NO) and peroxynitrite formation. 2. Urethane-anaesthetized rats were exposed to heat stress (ambient temperature 43 degrees C) to induce heat stroke. Control rats were exposed to 24 degrees C. Mean arterial pressure and renal blood flow after the onset of heat stroke were significantly lower in heat stroke rats than in control rats. However, both colonic temperature and renal damage score were greater in heat stroke rats compared with control rats. Similarly, plasma NO, creatinine and blood urea nitrogen (BUN), as well as the renal immunoreactivity of iNOS and peroxynitrite, were significantly higher in heat stroke rats compared with their normothermic controls. 3. Pretreatment with SMS (1.2 g/day per rat for 7 consecutive days before the initiation of heat stress) significantly attenuated the heat stroke-induced arterial hypotension, hyperthermia, renal ischaemia and damage, the increased renal immunoreactivity of iNOS and peroxynitrite and the increased plasma levels of NO, creatinine and BUN. Pretreatment with SMS resulted in a prolongation of survival time in heat stroke. 4. The results of the present study suggest that SMS protects against renal ischaemic damage by reducing iNOS-dependent NO and peroxynitrite production during heat stroke.

Animals↗
PubMed2004

Dopamine overload visualized in the basal ganglia of rabbit brain during heatstroke can be suppressed by hypothermia.

The present study assesses the changes of dopamine levels in the basal ganglia (BG) of rabbit brain during heatstroke with or without hypothermia therapy. The dopamine levels were determined by using 6(F18) fluoro-L-dopa (FDOPA) positron emission tomography (PET) scan. Heatstroke was induced by exposing the anesthetized rabbits to a high blanket temperature (T(blanket)) of 45 degrees C. Hypothermia therapy was accomplished by decreasing T(blanket) from 45 to 16 degrees C. Regions-of-interest were carefully selected on the BG and cerebellum (C). The uptake ratio of FDOPA was defined as the mean counts per pixel from BG divided by the mean counts from C. BG/C ratios represent the dopamine levels of BG. The results showed that the values of mean arterial pressure (MAP) in heatstroke rabbits without hypothermia therapy were significantly lower than those in normothermic controls. However, BG/C FDOPA ratios were greater. Both the arterial hypotension and the increased BG/C FDOPA ratios observed during heatstroke were all reduced after hypothermia therapy. Our data demonstrate that the dopamine overload visualized in the BG of rabbit brain during heatstroke can be suppressed by hypothermia therapy.

Animals↗
PubMed2004

The roles of vascular endothelial growth factor and angiopoietin-2 in the regression of pregnancy pyogenic granuloma.

OBJECTIVES: The molecular mechanism for the regression of pregnancy pyogenic granuloma after parturition remains unclear. It has been proposed that, in the absence of vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2) causes blood vessels to regress. Therefore, we investigated the roles of Ang-2 and VEGF in the regression of pregnancy pyogenic granuloma. MATERIALS AND METHODS: The effects of tumor necrosis factor-alpha (TNF-alpha) on the transcription of Ang-2 were tested in endothelial cells by reverse transcriptase-polymerase chain reaction. A total of 15 specimens, including granulomas taken from five gravidas during pregnancy, five after parturition, and five from normal gingiva were compared by immunoblot assays for their relative expressions of Ang-1, Ang-2, Tie-2, VEGF, and beta-actin. Double staining, immunohistochemistry for Ang-2, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling for apoptotic cells, were used to evaluate their regression. Finally, a fibrin gel culture system was used to investigate whether the withdrawal of VEGF and addition of Ang-2 could cause newly grown microvessels to regress. RESULTS: TNF-alpha upregulated the expression of Ang-2 in all endothelial cell types tested. The protein levels of Ang-2 and Tie-2 were highest in the granulomas in pregnancy, followed by those after parturition and normal gingiva, while Ang-1 and beta-actin exhibited no significant differences. The amount of VEGF was high in the granulomas in pregnancy and almost undetectable after parturition. Double staining on granulomas after parturition revealed more apoptotic cells and less Ang-2 than did those in pregnancy. In the fibrin gel assay, VEGF alone or in combination with Ang-2 could protect microvessels from apoptosis, while Ang-2 alone had no effect. CONCLUSIONS: Our findings suggest that a lack of VEGF is associated with apoptosis of endothelial cells and regression of granuloma. The roles of Ang-2 require additional study.

Actins↗
PubMed2003

Protective effects of alpha-tocopherol and mannitol in both circulatory shock and cerebral ischaemia injury in rat heatstroke.

1. There is evidence that hydroxyl radicals are accumulated and oxidative stress is produced in multiple organs, including the brain, of rats with heat stroke. Herein, we investigated the effect on heat stroke-induced circulatory shock and cerebral ischaemic injury of two free radical scavengers, namely mannitol and alpha-tocopherol. 2. Urethane-anaesthetized rats were exposed to heat stress (ambient temperature 42 degrees C) to induce heat stroke. Control rats were exposed to 24 degrees C. Mean arterial pressure and cerebral blood flow after the onset of heat stroke were significantly lower in heat stroke rats than in control rats. However, cerebral free radicals, lipid peroxidation and the neuronal damage score were greater in heat stroke rats compared with control rats. Similarly, plasma cytokines, including tumour necrosis factor-alpha, interleukin (IL)-1beta and IL-6, were significantly higher in heat stroke rats compared with their normothermic controls. 3. Pretreatment with alpha-tocopherol (20 mg/kg, i.v.) or mannitol (10%, i.v.) 30 min before the onset of heat exposure significantly attenuated heat stroke-induced arterial hypotension, cerebral ischaemia and neuronal damage, the increased free radical formation and lipid peroxidation in the brain and the increased plasma levels of cytokines. Pretreatment with alpha-tocopherol or mannitol resulted in a prolongation of survival time in heat stroke. 4. These results demonstrate that although pretreatment with alpha-tocopherol and mannitol does not prevent the heat stroke syndrome entirely, an attenuation of the syndrome is observed.

Animals↗
PubMed2001

The hypothermic effects of dl-tetrahydropalmatine in rats.

Systemic administration of dl-tetrahydropalmatine (THP; 10-50 mg x kg(-1) intraperitoneally) produced a proportional decrease in both colonic temperature and release of hypothalamic serotonin (5-hydroxytryptamine (5-HT)) in rats at room temperature. The hypothermia was brought about by cutaneous vasodilation and decreased metabolism. The THP- induced hypothermia was significantly attenuated in rats with brain 5-HT depletion produced by control injection of 5,7-dihydroxytryptamine or in rats with 5-HT2A receptor activation produced by 1-(2,5-dimethoxy-4-iodophenyl) -2-aminopropane, or in rats with 5-HT1A receptor antagonist produced by (-)-pindolol. The results suggest involvement of serotoninergic antagonism in the THP-induced hypothermia in rats

Animals↗
PubMed2001

Improving efficacy of antifungal therapy by polymerase chain reaction-based strategy among febrile patients with neutropenia and cancer.

Early detection of fungal infections in and corresponding early treatment of febrile patients with neutropenia and cancer have been important issues and continue to be major challenges for clinicians. The use of nested PCR to make therapeutic decisions was studied. Sequential blood samples obtained from 42 patients with neutropenia and cancer were tested by nested PCR and culture. Instead of the empirical antifungal therapy strategy, amphotericin B treatment was initiated only for patients who had 2 consecutive positive results by nested PCR. A reduced mortality rate was observed for febrile patients with neutropenia and cancer who had fungal infections. Thus, this strategy, combined with the nested PCR for early detection of fungal infection in febrile patients with neutropenia, may be used as a guideline for antifungal therapy.

Adolescent↗
PubMed2001

Stimulatory effect of phenylephrine on the secretion of beta-endorphin from rat adrenal medulla in vitro.

In an attempt to investigate the role of alpha1-adrenoceptors in the regulation of opioid secretion from adrenal gland, phenylephrine was employed to investigate the effect on secretion of beta-endorphin-like immunoreactivity (BER) from adrenal medulla of rat in vitro. Phenylephrine enhanced the BER from isolated adrenal medulla in a concentration-dependent manner and this action was abolished by the antagonists of alpha1-adrenoceptors, prazosin and tamsulosin. Investigations of signal pathway further support that an activation of alpha1-adrenoceptors is responsible for the stimulatory effect of phenylephrine on BER secretion from adrenal medulla. In the presence of U73312, the specific inhibitor of phospholipase C (PLC), phenylephrine-induced change of BER was reduced in a concentration-dependent manner but it was not affected by U73343, the negative control of U73312. Moreover, chelerythrine and GF 109203X diminished the action of phenylephrine at concentration sufficient to inhibit protein kinase C (PKC). In conclusion, our results suggest that an activation of alpha1-adrenoceptors in adrenal medulla by phenylephrine may enhance the secretion of opioids from adrenal gland of rat via signals of PLC-PKC pathway.

Adrenal Medulla↗
PubMed2001

Cyclooxygenase-2 inducing Mcl-1-dependent survival mechanism in human lung adenocarcinoma CL1.0 cells. Involvement of phosphatidylinositol 3-kinase/Akt pathway.

Cyclooxygenase 2 (COX-2) has been reported to be commonly expressed in advanced stages of human lung adenocarcinoma. In this study, the COX-2 constitutive expression vector was transfected into a human lung adenocarcinoma cell line CL1.0 and several clones were obtained which stably expressed COX-2. These COX-2-overexpressed clones demonstrated remarkable resistance to apoptosis induced by Ultraviolet B (UVB) irradiation, vinblastine B (VBL) cell lymphoma-2 (Bcl-2), or other anti-cancer drugs. To understand how COX-2 prevents apoptosis, the investigators examined the expression level of Bcl-2 family members. Mcl-1, but not other Bcl-2 members, was significantly up-regulated by COX-2 transfection or prostaglandin E(2) (PGE(2)) treatment. Treatment of COX-2-overexpressed cells (cox-2/cl.4) with two specific COX-2 inhibitors, NS-398 and celecoxib, caused an effective reduction of the increased level of Mcl-1. These data suggest that the expression level of Mcl-1 is tightly regulated by COX-2. Moreover, transfection of cox-2/cl.4 cells with antisense Mcl-1 enhanced apoptosis induced by UVB irradiation, revealing that Mcl-1 plays a crucial role in cell survival activity mediated by COX-2. Furthermore, COX-2 transfection or PGE(2) treatment evidently activated the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Inhibition of the PI3K pathway by LY294002 or wortmannin effectively attenuated the increased level of Mcl-1 induced by COX-2 or PGE(2). Blocking the PI3K activity with a dominant-negative vector, DN-p85, also greatly diminished the level of Mcl-1 and enhanced UVB-elicited cell death in cells transfected by COX-2. In a similar way, LY294002 inhibited cell survival and Mcl-1 level in PGE(2)-treated CL1.0 cells. These findings suggest that COX-2 promotes cell survival by up-regulating the level of Mcl-1 by activating the PI3K/Akt-dependent pathway.

Adenocarcinoma↗
PubMed2001

DL-Tetrahydropalmatine may act through inhibition of amygdaloid release of dopamine to inhibit an epileptic attack in rats.

DL-Tetrahydropalmatine (THP), an active component isolated from corydalis (a Chinese herbal medicine), possesses analgesic effects. Systemic administration of picrotoxin (3-4 mg/kg) produced increases of locomotion (including horizontal motion, vertical motion, and total distance traveled), elevations of turnings (including both clockwise and anticlockwise), and inhibition of postural freezing in freely moving rats, and increases of amygdaloidal release of dopamine in anesthetizes rats. All the afore-mentioned activity measures induced by picrotoxin were suppressed following THP pretreatment. The results indicate that THP may act through inhibition of amygdaloid dopamine release to inhibit an epileptic attack.

Amygdala↗
PubMed2001

Loss of plasma glucose lowering response to cold stress in opioid mu-receptor knock-out diabetic mice.

Opioid mu-receptor plays an important role in the regulation of glucose homeostasis in diabetic rats lacking insulin. Opioid mu-receptor knockout mice were employed to identify the essential role of this receptor in the present study. Western blotting analysis characterized the deletion of opioid mu-receptor in liver of knockout mice as compared to that of normal (wild-type) mice. We found that the plasma glucose concentration of diabetic mice induced by intraperitoneal injection of streptozotocin was markedly decreased after exposure to cold-stress in a cold room for 1 h. However, this plasma glucose lowering response to cold-stress was disappeared in diabetic mice lacking opioid mu-receptor. The important role of opioid mu-receptor in the plasma glucose lowering response to cold stress can thus be considered. Moreover, bilateral adrenalectomy abolished this plasma glucose lowering response to cold stress in diabetic mice with opioid mu-receptor, as compared to the shamed-operated animals. Therefore, activation of opioid mu-receptor by opioid from adrenal gland appears to be responsible for the plasma glucose lowering response to cold-stress in diabetic mice with insulin deficiency.

Adrenal Glands↗
PubMed2001

Low mutational burden of individual acquired mitochondrial DNA mutations in brain.

Neurons may be particularly susceptible to oxidative damage, which has been proposed to induce somatic mutations, particularly in mitochondrial DNA (mtDNA). Therefore, acquired mtDNA mutations might preferentially accumulate in the brain and could play a role in aging and neurodegenerative disorders. Recently, a somatic T to G mtDNA mutation at noncoding nucleotide position 414 was reported in fibroblasts specifically from elderly subjects, with mutational burdens of up to 50%. We screened for this mutation in brain-derived mtDNA from 8 Alzheimer's disease patients, 27 Parkinson's disease patients, 4 multiple system atrophy patients, and 44 controls using up to three RFLP analyses. A total of 73 of these subjects were over the age of 65. The 414 mutation was absent in all cases. Next, individual mtDNA fragments from 6 elderly subjects were cloned, and a total of 70 clones were sequenced. The 414 mutation was absent in all clones, though occasional sequence variations were identified at other sites in single clones. The 414 mutation also was absent in blood (n = 6) and fibroblasts (n = 11) from elderly subjects. Our data suggest that it is rare for any one particular acquired mtDNA mutation to reach levels in the brain that are functionally significant. This does not exclude the possibility that the cumulative burden of multiple, individually rare, acquired mutations impairs mitochondrial function.

Aged↗