Chronic ulcerations in the upper and lower extremities. Thromboangiitis obliterans (Buerger disease)
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Adult↗
Biomedical subjects
M T Lin
Publications and source records attributed to M T Lin.
Prenatal diagnosis for keratin mutations to exclude transmission of epidermolytic hyperkeratosis.
Epidermolytic hyperkeratosis (bullous congenital ichthyosiform erythroderma) is an autosomal dominant skin disorder caused by mutations in keratins 1 and 10. We have used direct gene sequencing to ascertain the status of a 15 week fetus of parents whose first child was affected with this disorder. The parents show no clinical signs of epidermolytic hyperkeratosis but were concerned about the possibility of transmitting the disorder due to germline mosaicism. Molecular analysis of the affected son revealed a G to A mutation in codon 156 of keratin 10, resulting in an arginine to histidine substitution within the highly conserved 1A region. Codon 156 has been previously identified as a mutational hot spot and substitutions of this arginine residue are very common in epidermolytic hyperkeratosis patients. Analysis of genomic DNA isolated from amniotic cells showed that the fetus did not harbour this mutation and a healthy infant was eventually born that was unaffected by this disorder.
Amniotic Fluid↗
Apoptosis of JHMV-specific CTL in the CNS in the absence of CD4+ T cells.
The role of CD4+ T cells in altering the activity of cytotoxic T lymphocytes (CTL) during infection of the central nervous system (CNS) by the neuroptropic JHMV strain of mouse hepatitis virus was examined. Adoptive transfer of in vitro activated CTL into CD4-depleted and control recipients showed that CTL were not effective in reducing JHMV replication within the CNS. The distribution of CD4+ and CD8+ T cells within the CNS during JHMV infection showed that the CD4+ T cells remained in perivascular and subarachnoid spaces and few entered the parenchyma. By contrast approximately half of the CD8+ T cells entered the parenchyma. In CD4-depleted mice the trafficking of CD8+ T cells was not inhibited; however, the majority of the cells were found to be apoptotic. These data suggested that CD4+ T cells were not required for CTL induction but were required for the maintenance of CTL viability. The limited role of CD4+ T cells in CTL induction was confirmed by comparison of CTL activity from CD4-depleted and control mice.
Adoptive Transfer↗
Mechanisms of viral clearance in perforin-deficient mice.
The roles of CD4+ T cells, IFN-gamma and TNF-alpha in viral clearance from the central nervous system (CNS) were examined in perforin gene deficient (PKO) mice. Depletion of CD4+ T cells from the PKO mice resulted in a significant 1 log10 PFU/gm increase in viral titer over control-treated PKO mice. PKO mice treated with anti-IFN-gamma mAb also had a significant 1 log10 increase in infectious virus whereas inhibition of TNF-alpha did not alter viral clearance or clinical disease in the PKO mice. These data suggest, in addition to perforin-mediated cytolysis, CD4+ T cells and IFN-gamma, but not TNF-alpha could contribute to JHMV clearance from the CNS.
Animals↗
MCT/LCT emulsion ameliorate liver fat deposition in insulin-treated diabetic rats receiving total parenteral nutrition.
This study was designed to investigate the effects of high energy infusion and insulin treatment on plasma and liver lipids in diabetic rats receiving total parenteral nutrition (TPN). Diabetes was induced in rats by streptozotocin. The diabetic rats were assigned to two TPN groups to receive either long chain triglyceride (LCT) or medium chain triglyceride (MCT)/LCT (1:1) as a fat source. The TPN solutions were isonitrogenous, isocaloric and identical in nutrient composition except for the fat emulsion. All rats received the TPN solution at an energy level of 35|kcal/100|g of body weight. The LCT and MCT/LCT groups were further divided into two subgroups, depending on whether they were treated with insulin. The results demonstrated that, between the MCT/LCT and LCT groups, no differences were observed in body weight and nitrogen retention, as well as the concentrations of plasma glucose, nonesterified fatty acids, beta-hydroxybutyrate, and total cholesterol. Diabetic TPN rats without insulin treatment had weight loss and negative nitrogen balance during the experiment. Diabetic TPN rats treated with insulin, however, demonstrated less weight loss and positive nitrogen retention. Insulin treated groups had significantly higher liver fat content than did those without insulin treatment. Furthermore, liver fat content was significantly higher in the LCT group than in the MCT/LCT group among insulin treated TPN rats. These results suggest that compared with the LCT emulsion, infusion of the MCT/LCT emulsion ameliorated liver fat deposition in insulin-treated diabetic rats receiving TPN.
3-Hydroxybutyric Acid↗
High-dose therapy with peripheral blood stem cell (PBSC) support using an innovative mobilization regimen in patients with high-risk primary or chemoresponsive metastatic breast cancers.
High-dose therapy followed by peripheral blood stem cell (PBSC) support was performed in 29 patients with primary high-risk (Group I) or chemoresponsive metastatic (Group II) breast cancer patients. Group I patients had received PBSC mobilization within 4 weeks of modified radical mastectomy. Group II patients had to achieve minimal residual disease (MRD) by induction chemotherapy before being considered eligible for PBSC mobilization and high-dose therapy. An innovative FE120C regimen (5-FU 600 mg/m2, i.v., day 1; epirubicin 120 mg/m2, i.v., day 1; cyclophosphamide 600 mg/m2, i.v., day 1) plus G-CSF (300 microg/day, subcutaneous injection for 9 days, from day 4 post-FE120C) was used to mobilize PBSCs. After high-dose CTCb (cyclophosphamide 6,000 mg/m2, thiothepa 500 mg/m2, carboplatin 800 mg/m2, in 4 days), patients received PBSC infusion and daily C-CSF 300 microg subcutaneous injection. There were 19 and 16 patients enrolled into Group I and Group II, respectively. Ten of the Group II patients had achieved minimal residual disease (MRD) after induction chemotherapy. The median numbers of mobilized total CD34 + cells for Group I and Group II patients were 27.3 (9.2 to 114.1) x 10(6)/kg and 17.1 (5.9 to 69.1) x 10(6)/kg respectively. The median time to neutrophil recovery (ANC > or = 500/microL) was 8 and 9 days in Group I and II, respectively. The median time to platelet recovery (> or = 50,000/microL) was 10 and 15 days in Group I and II, respectively. No major treatment-related toxicities were noted. In Group I, 13 out of 19 patients (68.4%; 43-87%, 95% C.I.) remained recurrence-free with a median follow-up of 31 months (6 + to 55 + months). In Group II, 3 out of 10 patients (30%; 7-65%, 95% C.I.) remained progression-free at 33 +, 35 +, 39 + months from induction therapy. We suggest that the FE120C plus G-CSF is an effective and innovative regimen for PBSC mobilization in breast cancer patients, and high-dose CTCb therapy with PBSC support is a safe and well-tolerated treatment modality.
Adult↗
Long QT syndrome manifested as fetal ventricular tachycardia and intermittent AV block.
A case of long QT syndrome diagnosed in the early neonatal period is described. This full-term female baby had intermittent atrioventricular (AV) block and ventricular tachycardia detected antenatally at the gestational age of 26 weeks. Sinus rhythm with prolonged QT interval (QTc = 0.636 sec) was found soon after birth. She developed variable degree of AV block with alternating left and right bundle branch block, which suggested the presence of multilevel AV block. Her mother had no lupus autoantibodies. Auditory brain stem evoked potential was normal. Family study revealed QT prolongation in her grandmother. Her condition improved after pacemaker implantation and oral beta-blocker usage.
Electrocardiography↗
Effects of growth hormone and insulin-like growth factor I on opsonin receptor expression on local and systemic phagocytes in a lethal peritonitis model.
OBJECTIVE: To investigate the effects of pretreatment with growth hormone (GH) and insulin-like growth factor I (IGF-I) on phagocyte exudation and bacterial clearance, focusing on CD11b and CD32/CD16 expression on local and systemic phagocytes, in a lethal peritonitis model. DESIGN: Prospective randomized experimental study. SETTING: Research laboratory in a university hospital. SUBJECTS: Balb/c mice (n = 21). INTERVENTIONS: Mice were challenged intraperitoneally with 1 x 10(8) Escherichia coli, after 6 days of pretreatment with saline (control), GH (4.8 mg/kg/day), or IGF-I (24 mg/kg/day). Samples were harvested at 4 hrs after the challenge. MEASUREMENTS AND MAIN RESULTS: Viable bacterial counts in peritoneal lavage fluid (PLF) and blood were determined. Peritoneal exudative cells and peripheral blood leukocytes were counted and analyzed for receptor expressions by flow cytometry. GH reduced viable bacterial counts in PLF, as compared with the saline control. GH (three-fold) and IGF-I (two-fold) increased the number of peritoneal exudative neutrophils (PENs), as compared with the saline control. The number of PENs showed an inverse correlation with PLF viable bacterial counts. By contrast, there were no differences in peripheral blood neutrophil (PN) counts among the three groups, nor was there a correlation between PN and PEN counts. CD11b expression was greater on PENs than on PNs in all three groups. CD11b expression on PNs did not differ among the three groups. However, GH increased CD11b expression on PENs, as compared with saline and IGF-I, and this expression showed a positive correlation with PEN numbers and an inverse correlation with PLF viable bacterial counts. CD11b expression on peritoneal macrophages and peripheral blood monocytes did not differ among the three groups. There were no differences in phagocyte CD32/CD16 expression among the three groups. CONCLUSIONS: GH pretreatment enhanced CD11b expression on PENs, but not PNs, possibly in association with enhanced neutrophil recruitment, phagocytosis, and bacterial elimination by PENs, without activation of PNs. GH prophylaxis may be useful for reducing the frequency rate and severity of septic complications, via modulation of CD11b expression on local and systemic neutrophils.
Animals↗
Definition of the gene encoding the minor histocompatibility antigen HA-1 and typing for HA-1 from genomic DNA.
Recipient mismatching for the minor histocompatibility antigen HA-1 has been associated with acute graft-versus-host disease after allogeneic marrow transplantation. Two polymorphic nucleotides near an exon-intron junction of the gene encoding this minor histocompatibility antigen have been identified. In this study, we determined the genomic DNA sequence of the intron downstream from this polymorphic exon. Based on this sequence, primers were designed to amplify the genomic HA-1 gene sequence, and analysis of restriction fragment length polymorphisms was used to assign the HA-1 genotypes of 160 unrelated probands and a paired sibling for each proband. Among probands, the HA-1H allele frequency was 0.441, and the HA-1R allele frequency was 0.559. The distribution of HA-1 genotypes showed close fit with Hardy-Weinberg equilibrium. Likewise, the number of sibling pairs with disparity for HA-1 alleles showed close fit with predictions based on Hardy-Weinberg equilibrium. These results provide a simple and well validated method for future studies correlating HA-1 disparity with clinical outcome after allogeneic marrow transplantation.
Alleles↗
Magnolol decreases body temperature by reducing 5-hydroxytryptamine release in the rat hypothalamus.
1. The effects of magnolol, isolated and purified from the cortex of Magnolia officinalis Rehd. et Wils, on thermoregulation and hypothalamic release of 5-hydroxytryptamine (5-HT) by in vivo microdialysis were assessed in normothermic rats and in febrile rats treated with interleukin-1 beta. 2. Intraperitoneal administration of magnolol (25-100 mg/kg) produced a decrease in colon temperature, an increase in foot skin temperature, a decrease in metabolic rate and a decrease in the endogenous release of 5-HT in the rat hypothalamus. 3. Depletion of rat brain 5-HT, produced by intracerebroventricular pretreatment with 5,7-dihydroxytryptamine, attenuated the magnolol-induced hypothermia, cutaneous vasodilation and decreased metabolism. 4. Intracerebroventricular administration of (+/-)-2,5-dimethoxy-4-iodoamphetamine (a 5-HT2 receptor agonist; 5-10 micrograms/5 microL) increased basal colon temperature and reversed the magnolol-induced hypothermia. 5. The increases in both colon temperature and hypothalamic 5-HT release produced by interleukin-1 beta injection were attenuated by treatment with magnolol. 6. The data suggest that magnolol decreases body temperature (due to increased heat loss and decreased heat production) by reducing 5-HT release in rat hypothalamus.
Animals↗
Changes in extracellular serotonin in rat hypothalamus affect thermoregulatory function.
Experiments were carried out to determine the effects of altering the serotonin (5-HT) levels in the hypothalamus on thermoregulatory function in unanesthetized restrained rats. Local perfusion of the hypothalamus with dialysis solution containing 5-hydroxytryptophan (a 5-HT precursor), fluoxetine (a 5-HT reuptake inhibitor), or high potassium significantly increased both colonic temperature (Tco) and the extracellular concentrations of 5-HT in the hypothalamus. Reciprocally, both extracellular concentration of 5-HT in the hypothalamus and Tco were decreased with a dialysis solution containing tetrodotoxin (which blocks the voltage-dependent sodium channel), zero calcium concentration, or systemic administration of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT,5-HT1A agonist). Intrahypothalamic administration of 8-OH-DPAT and (2,5-dimethoxy-4-iodophenyl)-2-aminopropane (a 5-HT2 agonist) produced hypothermic and hyperthermic effects, respectively. The results indicate that elevating the 5-HT levels in the hypothalamus activates postsynaptic 5-HT2 receptors and results in hyperthermic effects, whereas stimulation of presynaptic 5-HT1A receptors in the hypothalamus reduces the endogenous 5-HT release and results in hypothermic effects.
Animals↗
Catecholaminergic mechanisms-mediated hypothermia induced by magnolol in rats.
Intraperitoneal administration of magnolol (25-100 mg/kg) produced a dose-related fall in rats' colonic temperature. The magnolol-induced hypothermia was attenuated by pretreatment with intracerebroventricular 6-hydroxydopamine (200 microg/rat). The L-DOPA (200 mg/kg, i.p.) plus benserazide (50 mg/kg, i.p.)-induced hyperthermia was attenuated by magnolol. On the other hand, the alpha-methyltyrosine (100 mg/kg, i.p.)-induced hypothermia was potentiated by magnolol. Furthermore, magnolol (50 mg/kg, i.p.) decreased the dopamine and norepinephrine release in the hypothalamus, but did not change the concentrations for their metabolites (3,4-dihydroxyphenylacetic acid and homovanillic acid). The data suggest that magnolol decreases colonic temperature by reducing catecholaminergic activity in rat hypothalamus.
3,4-Dihydroxyphenylacetic Acid↗
Familial transmission of human T-lymphotropic virus type 1 (HTLV-1) in patients with adult T-cell leukemia/lymphoma or HTLV-1-associated myelopathy.
The seroprevalence of human T-lymphotropic virus type 1 (HTLV-1) in Taiwan is 0.48%. In this study, we investigated the patterns of intrafamilial transmission of HTLV-1 in Taiwanese patients with adult T-cell leukemia/lymphoma (ATL/L) or tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM). Fifteen index patients (9 men, 6 women, aged 31-71 yr), 13 with ATL/L, and two with TSP/HAM, and 98 relatives were included. Of the 98 relatives, 23 were seropositive for HTLV-1. Spouses of 11 patients were studied. Seven of eight wives of male patients but none of the three husbands of female patients were HTLV-1 carriers. Mother-to-child transmission was found in seven of 13 families and in 15 of 75 children tested. The correlation of breast-feeding with seropositivity in two families with seropositive mothers indicates its important role in vertical transmission of HTLV-1. Our findings suggest that husband-to-wife and mother-to-child transmission are the main forms of intrafamilial transmission of HTLV-1 in Taiwan, a nonendemic area. Screening for HTLV-1 in family members of patients with ATL/L or TSP/HAM, and seropositive blood donors, may be warranted. Seropositive individuals should be educated to prevent the spread of the virus through sexual contact and breast feeding.
Adult↗
Effects of insulin on protein phosphorylation and protein kinase C activity in human malignant gliomas.
Modulation of protein phosphorylation activities by insulin was investigated in glioma and normal glial cells. Insulin suppressed the in vitro protein phosphorylation of glioma cells in a dose-dependent manner while it stimulated that of meningiomas, neurilemmomas and glial cells. Although gliomas and glial cells contained different species of tyrosyl phosphoproteins before treatment, they expressed similar kinds of tyrosyl phosphoproteins in response to insulin. Insulin increased the activities of casein kinase II and total protein kinase C (PKC) in glioma and normal glial cells. The membrane-bound PKC activity in U373-MG cells was elevated by insulin. The PKC isozymes, including subtypes alpha, beta, delta, epsilon and gamma, were detected in gliomas, but few were found in glial cells. Insulin down regulated the cytosolic PKC-gamma and the membrane-bound PKC-epsilon proteins in gliomas. These results indicate that an altered insulin signaling pathway exists in human gliomas, which might involve differential regulation of PKC isozymes.
Casein Kinase II↗
Localization of protein kinase C alpha and zeta during the decidualization in pseudopregnant rats.
Our previous data showed that at least five PKC isoforms (alpha, delta, zeta, lambda and tau) were present in the decidualization. In this study, we then localized the PKC alpha and zeta by immunohistochemistry in the decidualized uterine tissues. The decidualized uterine tissues were induced by trauma-stimulation and fixed in formalin. The immunofluorescence were photographed by confocal microscope. The data revealed that the fluorescence of PKC alpha was present in the deciduomata and myometrium. In the deciduomata, PKC alpha was mainly located in the surrounding nuclear. This phenomenon of localization was especially performed on day 2 and 3 of the decidualization, just on the time of higher frequence of cell mitosis. Since the myometrium with hypertrophy did not display the phenomenon of perinuclear localization, these suggested that the expression and localization of PKC alpha may be associated with the cell proliferation. On the other hand, the PKC zeta was also present and distributed broadly in the deciduomata and myometrium. This expression was increased and similar to the previous Western blot studies. Thus, the data confirmed that the various expression and localization of PKC isoforms may be correlated with the development of deciduomata.
Animals↗
Mechanisms and sites of pyrogenic action exerted by staphylococcal enterotoxin A in rabbits.
The febrile responses induced by i.v. administrations of staphylococcal enterotoxin A (SEA) was mimicked by direct injection of SEA into the organum vasculosum laminae terminalis (OVLT) in unanesthetized rabbits. Compared with the febrile responses induced by i.v. injection of SEA, the OVLT route of injection required a much lower dose of SEA to produce a similar fever. Furthermore, the fever induced by intra-OVLT or i.v. injection of SEA was significantly attenuated by pretreatment with intra-OVLT injection of anisomycin (a protein synthesis inhibitor), indomethacin or diclofenac (inhibitors of cyclo-oxygenase (COX)), and aminoguanidine or dexamethasone (inhibitors of inducible nitric oxide synthase (iNOS)). These results suggest that COX or iNOS pathway in the OVLT mediate the SEA-induced fever in rabbits.
Animals↗
Tax of the human T-lymphotropic virus type I transactivates promoter of the MDR-1 gene.
The mdr-1 gene has been shown to confer resistance to chemotherapy of multiple drugs which share no obvious structural similarities. We and others have previously reported that some virus-associated malignant cells express high levels of MDR-1 (1,2), probably regulated by some viral proteins. In this study we have examined the role of Tax, the key protein of HTLV-1. An excellent correlation was found between the existence of HTLV-1 and the expression of MDR-1 among seven human T-cell lines. In the second part of the study, a 1. 76-kb DNA fragment representing the upstream regulatory elements of human mdr-1 gene was cloned into the CAT reporter plasmid. When the Tax expression plasmid was co-transfected with the MDR-1 reporter plasmid, a significant induction of CAT activity was observed. We conclude that Tax protein may up-regulate the expression of the mdr-1 gene.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Dexamethasone administered into organum vasculosum laminae terminalis of rabbits induced antipyresis via inhibiting nitric oxide pathway in situ.
Direct administration of lipopolysaccharide (LPS) into the organum vasculosum laminae terminalis (OVLT) increased the amount of nitric oxide (NO) release and inducible NO synthase expression. These increases paralleled the increase in deep body temperature in unanesthetized rabbits. Pretreatment with dexamethasone, a synthetic glucocorticoid, not only reduced the fever but also attenuated the NO release and the inducible NO synthase expression in the OVLT following an intra-OVLT dose of LPS. The data suggest that steroids such as dexamethasone exert their antipyresis by inhibiting the NO pathway in the OVLT of rabbit brain.
Analgesics, Non-Narcotic↗