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Biomedical subjects

M T Lin

Publications and source records attributed to M T Lin.

At least 127 records · Page 7Linked to original sources

Inhibition of nitric oxide synthase or cyclo-oxygenase pathways in organum vasculosum laminae terminalis attenuates interleukin-1 beta fever in rabbits.

Fever was induced in rabbits by i.v. administration of lipopolysaccharide (LPS) or administration of interleukin-1 beta (IL-1 beta) into the organum vasculosum laminae terminalis (OVLT). Intra-OVLT injection of IL-1 receptor antagonist (IL-lra), 1 h before LPS or IL-1 beta injection, inhibited the LPS- or IL-1 beta-induced fever. Dexamethasone (a potent inhibitor of the transcription of inducible nitric oxide synthase, iNOS), L-N5-(1-iminoethyl)ornithine (an irreversible NOS inhibitor), aminoguanidine (a specific iNOS inhibitor), or indomethacin (an inhibitor of cyclo-oxygenase, COX) also inhibited IL-1 beta-induced fever when injected into the OVLT 1 h before IL-1 beta injection. These results suggest that iNOS or COX pathways in the OVLT mediate the IL-1 beta-induced fever in rabbits.

Animals↗

Regulation of plasminogen activator inhibitor activity by plasmin in endothelial cells.

The fibrinolytic activity in endothelial cells was regulated by balance of plasminogen activators and plasminogen activator inhibitors. Plasmin can specifically inhibit the biosynthesis of tissue-type plasminogen activator (t-PA), but not plasminogen activator inhibitor, type 1 (PAI-1) in endothelial cells. The PAI activity in the conditioned medium of endothelial cells was low and remained constant in 24 hours. However, the PAI activity in the conditioned medium of the plasmin-pretreated cells increased linearly in 24 hours. Pretreatment with protein kinase C inhibitors, H-7 or staurosporine, partially suppressed the PAI activity induced by plasmin. Pretreatment of endothelial cells with a G-protein inhibitor pertussis toxin resulted in an inhibition of the plasmin-induced PAI activity. The phospholipase A2 inhibitor mepacrine specifically eliminated the effect of plasmin stimulation on PAI activity. Cyclooxygenase and lipoxygenase inhibitors also partially inhibited the plasmin-stimulated PAI activity in endothelial cells. All these inhibitors did not affect the biosynthesis of the PAI-1 antigen in the presence or absence of plasmin. The results indicate that plasmin increased the PAI activity of endothelial cells via pathways in which protein kinase C, G protein, and phospholipase A2 may be involved.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Envelope gene sequences of human T-lymphotropic virus type 1 in Taiwan.

Three major types of HTLV-1 had been proposed, the Melanesian type, the Zairian type, and the cosmopolitan type, which was further divided into subtypes A, B and C, according to the phylogenetic tree constructed from LTR sequences of current HTLV-isolates. In this study, the envelope gene sequences of HTLV-1 from 9 Taiwanese were analyzed. Based on the phylogenetic tree constructed by unweighted pair group method and the sequence homology analysis by GCG computer programs, the envelope gene sequences of HTLV-1 proviruses from these 9 Taiwanese belonged to subtype A or subtype B of the cosmopolitan type and were closely related to HTLV-1 from Japan. Twelve subtype-specific nucleotide variations were deduced from the comparison of complete or partial envelope gene sequences of 16 HTLV-1 isolates of known subtypes as well as those of 9 Taiwanese. These data provided the basis for subtyping the cosmopolitan type of HTLV-1 by amplification of envelope gene sequences and restriction fragment length polymorphism studies. A more extensive survey based upon this proposal was warranted.

Base Sequence↗

Effects of three inhibitors of nitric oxide synthase on host resistance to bacterial infection.

OBJECTIVE: To examine the effects of three nitric oxide synthase inhibitors on survival in a murine sepsis model. DESIGN: Prospective randomized experimental trials. SETTING: Laboratory. SUBJECTS: Female Balb/c mice. INTERVENTIONS: Escherichia coli (10(8) colony-forming-units/body) were injected into the peritoneal cavities of Balb/c mice. NG-nitro-L-arginine-methyl-ester, NG-monomethyl-L-arginine, or N-iminoethyl-L-ornithine was given at various concentrations, intraperitoneally, one hour before bacterial challenge. MEASUREMENTS: One hundred and fifteen animals were observed for survival. RESULTS: These inhibitors provided the mice no protection from the bacterial challenge. Notably, pretreatment with NG-nitro-L-arginine-methyl-ester (100 mg/kg i.p.) actually reduced survival time after E. coli challenge. CONCLUSIONS: Inhibition of nitric oxide production improved neither the survival time nor rate in this murine sepsis model.

Animals↗

Subtyping of human T-lymphotropic virus type I by amplification of long terminal repeat sequences and restriction fragment length polymorphism analysis in carriers with multiple transfusions.

Five major subtypes of human T-lymphotropic virus type I (HTLV-I) have been proposed: cosmopolitan, Japanese, West African, Central African, and Melanesian. Based on nucleotide variations specific to particular subtypes, it was possible to genotype HTLV-I rapidly by restriction fragment length polymorphism (RFLP) studies following polymerase chain reaction (PCR). In this study, the restriction patterns of two LTR fragments were analyzed using eight restriction endonucleases (AvaI, Eco57I, BsoFI, NdeI, SacI, DraI, MaeII, and MaeIII). Genotyping of HTLV-I was done in nine patients with adult T-cell leukemia or HTLV-I-associated myelopathy/tropical spastic paraparesis, in three prostitutes, and in 19 carriers with multiple transfusion in Taiwan. The subtyping results of RFLP studies using these eight restriction endonucleases were in accordance with those of phylogenetic analysis. A substitution of G by A at nucleotide position 503, which creates the DraI site but suppresses the SacI site, was found not only in the Japanese subtype but also in a minority of the cosmopolitan subtype. A mutation near the position of subtype-specific nucleotide variations might suppress the restriction site and lead to unexpected restriction patterns. Amplification of more than one proviral fragment and RFLP studies with a group of appropriate restriction endonucleases may provide rapid and accurate genotyping of HTLV-I. More carriers are required to evaluate the possibility of mixed infection with different HTLV-I subtypes.

Base Sequence↗

Increased survival in experimental rat heatstroke by continuous perfusion of interleukin-1 receptor antagonist.

In order to assess the possible therapeutical value of interleukin-1 receptor antagonist (IL-1 ra) in the treatment of heatstroke, we evaluated the effects of heatstroke on survival time (interval between onset of heatstroke and death), systemic and striatal hemodynamic changes, and extent of striatal neuronal damage in rats treated with saline or IL-1 ra. The survival time of the heatstroke rats which received normal saline (single injection or continuous perfusion) was about 17 min. The heatstroke-induced ischemic damage to striatal neurons was due to systemic arterial hypotension, intracranial hypertension, decreased cerebral perfusion, and striatal dopamine (DA) accumulation (275%). Rats treated with a single injection of IL-1 ra (200 mu g/kg, i.v.) immediately after the onset of heatstroke survived much longer (91 min) than the controls. The prolongation of survival induced by IL-1 ra was brought about by attenuation of the arterial hypotension, intracranial hypertension, decreased cerebral perfusion, ischemic damage to striatal neurons, and striatal DA release value (204%). Furthermore, after continuous perfusion of IL-1 ra (200 mu g/kg per h, i.v.) immediately after the onset of heatstroke, the striatal DA release value of the rats was further reduced to 140% while the survival time of the rats was prolonged to up to 10 h from the onset of heatstroke. Thus, it appears that continuous i.v. perfusion of IL-1 ra is a good choice for heatstroke therapy.

Animals↗

Hypothalamic serotonin release and raised blood pressure after raphe nuclei stimulation in rats.

Electrical stimulation of dorsal raphe (DR) nuclei, in addition to enhancing serotonin (5-HT) release in the hypothalamus, elicited proportional hypertension and tachycardia in anesthetized rats. This could be mimicked by microinjection of two excitatory amino acids, kainic acid and glutamate, into the DR of rat brain. Intrahypothalamic administration of DOI (a 5-HT2 agonist), but not 8-OH DPAT (a 5-HT1 agonist) or 2-methyl-serotonin (a 5-HT3 agonist), also produced both hypertension and tachycardia in rats. The DR stimulation-induced hypertension, tachycardia, or increased hypothalamic 5-HT release were attenuated by prior destruction of the ascending serotonergic system produced by ICV injection of 5,7-dihydroxytryptamine and by prior blockade of postsynaptic serotonergic receptors produced by intrahypothalamic injection of 5-HT2 antagonists, cyproheptadine and ketanserin. The DOI-induced hypertension and tachycardia were also reduced by prior blockade of 5-HT2 receptors with cyproheptadine or ketanserin. Thus, it appears that DR stimulation activates the 5-HT release in the hypothalamus, then activates the hypothalamic 5-HT2 receptors and results in both hypertension and tachycardia in rats.

5,7-Dihydroxytryptamine↗

A new ultrasonic method for measuring minute motion activities of rats.

A new ultrasonic method is presented for measuring the minute motion activities of rats. A pair of low-cost 40 kHz ultrasonic transducers are used to transmit ultrasound toward a rat and receive the ultrasound reflected from the rat. The relative motion of the rat modulates the phase difference between the transmitted and received ultrasound signals. An 8-bit digital phase meter was designed to record the phase difference signal which was used to reconstruct the relative motion waveform of the rat in an 8751 single-chip microcomputer. The reconstructed data are then sent to a PC-AT microcomputer for further processing. This method employs a spectrum analysis for the reconstructed data and can measure three minute motion activities including locomotor activity (LMA), tremor and myoclonia. Finally, the method has been tested with real animal experiments. The main advantages of this new method are that it is non-invasive, non-contact, low cost and high precision. This new method could also be profitably employed for other behavioral studies and offer potential for research in basic medicine.

Animals↗

Effects of growth hormone and insulin-like growth factor 1 (IGF-1 ) on hepatic IGF-1-mRNA, plasma IGF-1 and nitrogen excretion in gastrectomized rats with liver cirrhosis.

The growth hormone (GH)-insulin-like growth factor 1 (IGF-1) axis is impaired in liver cirrhosis. We determined the effects of GH and IGF-1 treatments in gastrectomized rats with thioacetamide-induced cirrhosis. GH did not increase hepatic IGF-1-mRNA, plasma IGF-1 or the tissue, i.e. gastrocnemius muscle IGF-1 level. IGF-1 administration increased plasma IGF-1 without increasing hepatic IGF-1-mRNA. GH and IGF-1 independently decreased postoperative urinary nitrogen excretion. We conclude that both GH and IGF-1 improve postoperative nitrogen metabolism. Furthermore, GH may exert its anabolic effects directly and/or via actions mediated by IGF-1 production, other than in the liver and in the skeletal muscle, in the setting of cirrhosis.

Journal Article↗

Acute pancreatitis masquerading as testicular torsion.

A 40-year-old man presented with fat necrosis of scrotum as the complication of acute pancreatitis. Excessive fluid accumulation in the pancreas and the extrapancreatic spaces, including around the spermatic cord, was seen on computed tomography. Surgical specimen showed typical fat necrosis of tunica vaginalis and the spermatic cord. After the surgery, pain of the testicle subsided completely, without recurrence. From the clinical presentation alone, it had been difficult to differentiate this patient's condition from torsion of the spermatic cord.

Acute Disease↗

Six lignans from Phyllanthus myrtifolius.

Six lignans comprising phyllamyricins D (1), E (2), and F (3) and phyllamyricosides A (4), B (5), and C (6) were isolated in a continuing study of Phyllanthus myrtifolius. Compounds 1 and 2 are 2a-methoxy-4-aryl-2,3-naphthalides. Compounds 3-6 belong to the 4-arylnaphthalene class, with compounds 4-6 being O-beta-glucosides. Their structures were elucidated on the basis of spectral analysis. Compound 4 increased the activity of HIV-1 reverse transcriptase by 65% at a concentration of 1.89 microM.

HIV Reverse Transcriptase↗

Route of nutritional supply influences local, systemic, and remote organ responses to intraperitoneal bacterial challenge.

OBJECTIVE: The authors' aim was to investigate whether antecedent nutritional routes influence immune responses after surgical insult. SUMMARY BACKGROUND DATA: Total parenteral nutrition (TPN) may influence host responses to infection. To the best of the authors' knowledge, however, no study has focused on the mechanisms underlying the influence of nutritional route on local, systemic, and remote organ (lung) responses after surgical insult. METHODS: Sixty-eight rats were divided into TPN and total enteral nutrition (TEN) groups. The two groups received identical nutrients for 7 days and were then challenged intraperitoneally with 3 x 10(8) Escherichia coli. In the first experiment, the rats were observed for survival. In the second experiment, the rats were killed before (0 hours) challenge or 2 or 6 hours after challenge. Peritoneal exudative cells (PEC) and bronchoalveolar cells (BALC) were harvested and cultured in vitro. Colony-forming units of bacteria in the peritoneal lavage fluid (PLF) were determined. Tumor necrosis factor (TNF), interleukin-1 alpha (IL-1 alpha), interferon-gamma (IFN-gamma) levels in serum, PLF, bronchoalveolar lavage fluid (BALF), and cell culture supernatants were measured. RESULTS: The 48-hour survival rate was higher in TEN than in TPN rats. Local immunity was depressed in the TPN group. Bacterial colony counts in PLF were significantly higher in the TPN group than in the TEN group after challenge. The number of PECs was significantly lower, and at 2 hours, local cytokine (TNF and IL-1 alpha) responses were diminished in the TPN group compared with the TEN group at 2 hours. The number of PECs showed a significant positive correlation with levels of local cytokines in the TEN group but not in the TPN group. Elevation of local IFN-gamma was significant from 0 to 6 hours in the TEN group but not in the TPN group. In vitro production of TNF by PEC was impaired in the TPN rats before challenge. Remote organ (lung) responses were suppressed in the TPN group. The number of BALCs and the TNF levels in BALF declined significantly between 0 and 2 hours in the TEN group but not in the TPN group. Interferon-gamma levels in BALF were higher in the TEN group than in the TPN group at 2 hours. Systemic cytokine responses were disturbed in the TPN group. Production of systemic TNF was greater, but the IFN-gamma response was diminished in the TPN group compared with the TEN group after intraperitoneal bacterial challenge. CONCLUSION: Local, systemic, and remote organ (lung) immune responses to intraperitoneal bacterial challenge are suppressed in TPN-treated animals, leading to poor survival after challenge. Enteral nutrition before surgical insult may enhance host immune responses after the insult as compared to parenteral nutrition.

Animals↗

Growth hormone and insulin-like growth factor I augment Escherichia coli-killing activity of murine peritoneal exudative cells.

Effects of growth hormone (GH) and insulin-like growth factor (IGF)-I on Escherichia coli-killing activity of murine peritoneal exudative cells (PECs) were investigated. Plasma from the mice, injected subcutaneously with saline, GH (4.8 mg/kg/day), or IGF-I(24 mg/kg/day) for 6 days, was mixed with E. coli and pooled murine PECs. Plasma from GH- and IGF-I-treated mice modestly but significantly augmented the E. coli-killing activity of PECs, as compared with that from saline controls. Plasma from IGF-I-treated mice also enhanced PEC interleukin 1 production. In the next experiment, PECs preincubated with medium, GH (10-1000 ng/mL), or IGF-I (50-5000 ng/mL) for 3 h were investigated for E. coli-killing activity. Preincubation of PECs with all concentrations of GH and IGF-I significantly enhanced the E. coli-killing activity of PECs, as compared with the medium control. These results indicate that GH and IGF-I enhance phagocytosis and the E. coli-killing activity of PECs, via a modestly increased plasma capacity to support these activities, as well as by a strong direct action.

Animals↗

Antihypertensive effects of DL-tetrahydropalmatine: an active principle isolated from Corydalis.

1. The effects of DL-tetrahydropalmatine (DL-THP) on cardio-vascular function and hypothalamic release of monoamines were assessed in rats under urethane anaesthesia. 2. Intravenous administration of DL-THP (1-10 mg/kg) produced hypotension, bradycardia, a decrease in hypothalamic serotonin and noradrenaline release and an increase in hypothalamic dopamine release in rats. 3. Intrahypothalamic administration of DOI (a serotonergic 5-HT2 receptor antagonist) or apomorphine (a dopamine D2-receptor agonist) produced the opposite effects and reversed DL-THP-induced hypotension and bradycardia. 4. The data suggest that DL-THP acts through the 5-HT2 and/or D2-receptor antagonism in the hypothalamus to induce hypotension and bradycardia in rats.

Amphetamines↗

Nitric oxide synthase-cyclo-oxygenase pathways in organum vasculosum laminae terminalis: possible role in pyrogenic fever in rabbits.

1. Fever was induced in rabbits by administration of Escherichia coli endotoxin (lipopolysaccharide; LPS; 0.001-10 micrograms) into the organum vasculosum laminae terminalis (OVLT). Deep body temperature was evaluated over a period of 7 h. 2. The LPS-induced febrile response was mimicked by intra-OVLT injection of the nitric oxide (NO) donors, S-nitroso-acetylpenicillamine (SNAP, 1-10 micrograms), sodium nitroprusside (SNP, 50 micrograms), or hydroxylamine (10 micrograms), the cyclic GMP analogue 8-bromo-cyclic GMP (8-Br-cyclic GMP, 10-100 micrograms), or prostaglandin E2 (PGE2, 0.2 micrograms). 3. Dexamethasone (Dex, a potent inhibitor of the transcription of inducible NO synthase, iNOS, 10 micrograms), anisomycin (a protein synthesis inhibitor, 100 micrograms), L-N5-(1-iminoethyl)ornithine (L-NIO; an irreversible NOS inhibitor, 10-200 micrograms), aminoguanidine (a specific iNOS inhibitor, 1000 micrograms), or NG-methyl-L-arginine acetate (L-NMMA, a NOS inhibitor, 100 micrograms) inhibited fever induced by LPS when injected into the OVLT 1 h before LPS injection. An intra-OVLT dose of 1000 micrograms of NG-nitro-L-arginine methyl ester (L-NAME, a potent inhibitor of constitutive NOS) did not exhibit antipyretic effects. 4. Methylene blue (an inhibitor of NOS and soluble guanylate cyclase, 1-10 micrograms), 6-(phenylamino)-5,8-quinolinedione (LY-83583; an inhibitor of soluble guanylate cyclase and NO release, 20 micrograms), or indomethacin (an inhibitor of cyclo-oxygenase, COX, 400 micrograms) inhibited fever induced by LPS when injected into the OVLT 1 h before LPS injection. Pretreatment with methylene blue or haemoglobin (a NO scavenger, 100 micrograms) attenuated the fever induced by intra-OVLT injection of SNAP. 5. The PGE2-induced fever was potentiated, rather then attenuated, by pretreatment with an intra-OVLT dose of animoguanidine (1000 micrograms), L-NMMA (100 micrograms) or L-NIO (200 micrograms). 6. These results suggest that iNOS-COX pathways in the OVLT represent an important mechanism for modulation of pyrogenic fever in rabbits.

Animals↗

Brain serotonin depletion attenuates heatstroke-induced cerebral ischemia and cell death in rats.

To explore the importance of brain serotonin (5-hydroxytryptamine) in the heatstroke-induced cerebral ischemia and neuronal injury, we evaluated the effects of heatstroke on brain serotonin release, survival time, cerebral hemodynamic changes, and neuronal cell damage in rats with or without brain serotonin depletion produced by 5,7-dihydroxytryptamine. In vivo voltammetry was used to measure changes in extracellular concentrations of serotonin in the anterior hypothalamus, striatum, and frontal cortex. After the onset of heatstroke, rats without brain serotonin depletion displayed hyperthermia, decreased mean arterial pressure, increased intracranial pressure, decreased cerebral perfusion pressure, decreased cerebral blood flow, increased cerebral serotonin release, and increased cerebral neuronal damage compared with those of normothermic control rats. However, when the cerebral serotonin system was destroyed by 5,7-dihydroxytryptamine, the heatstroke-induced arterial hypotension, intracranial hypertension, ischemic damage to the brain, and elevated cerebral serotonin release were reduced. In addition, the survival time of the heatstroke rats was prolonged after the depletion of brain serotonin. The data indicate that brain serotonin depletion attenuates heatstroke-induced cerebral ischemia and cell death in rats.

5,7-Dihydroxytryptamine↗

Clinical and hematological characteristics of hepatosplenic T gamma/delta lymphoma with isochromosome for long arm of chromosome 7.

Hepatosplenic T gamma/delta lymphoma is a rare entity of peripheral T cell lymphoma. Three of 386 patients with non-Hodgkin's lymphoma in our institute were found to have this subtype of lymphoma. All had chromosomal abnormalities of isochromosome 7q and trisomy 8. The clinical and hematological features of these three patients are reported. All were males with ages ranging from 23 to 29 years. Initial presentation comprised purpura and variable degree of hepatosplenomegaly. None had superficial lymphadenopathy. Hematologically, they showed pictures resembling immune related thrombocytopenia and/or hemolytic anemia. Examination of the bone marrows revealed hypercellularity with increased number of megakaryocytes and erythroid cells and various degrees of abnormal lymphoid cell infiltration. The histopathologic section of the spleen from one patient who underwent splenectomy revealed abnormal cell infiltration in the sinusoids of the red pulp. Lymphoma cells showed T gamma/delta lymphoid immunophenotype (CD3+ CD2+ CD4- CD8-, TCR delta-1+, and beta F1-). The platelet counts were elevated transiently after initial treatment with corticosteroids, but the condition soon deteriorated. All died of refractory lymphoma five to nine months after diagnosis. Review of the literature, showed that only four other cases have been reported until now and although no cytogenetic data were available for these patients, they had very similar clinical pictures as those in this series. It is suggested that hepatosplenic T gamma/delta lymphoma represents a rare, but distinct, clinicopathological and cytogenetic entity.

Adolescent↗

Platelet adhesion following the administration of tissue-type plasminogen activator and its reversal by vitamin E in rats.

Thrombolytic therapy is known to induce platelet-related side effects. We used a parallel-plate flow chamber, which was connected to the femoral artery of the rat, to measure platelet adhesion ex vivo. A collagen-coated arterioarterial shunt between two carotid arteries was used to measure shunt patency duration as an index of antithrombotic efficacy. Tissue-type plasminogen activator (t-PA), vitamin E, and the combination of these two were intravenously administered for 60 min. Measurements were performed before drug administration, and at 30, 60, 120 min after the initiation of drug infusion. Our results indicated that (1) treatments with t-PA or t-PA/vitamin E prolonged the time to shunt occlusion at 30 and 60 min; (2) t-PA enhanced platelet adhesion at 60 and 120 min; (3) vitamin E tended to reduce platelet adhesion; (4) t-PA/vitamin E reduced the t-PA-enhanced platelet adhesion; (5) at the high-density area of platelet adhesion under t-PA treatment, the adherent platelets demonstrated severe morphological changes which could be blocked by vitamin E. These data suggest that t-PA may enhance platelet adhesion in rats and that this adverse effect can be suppressed by co-administration of vitamin E.

Analysis of Variance↗