Biomedical subjects

T Hayashi

Publications and source records attributed to T Hayashi.

At least 307 records · Page 17Linked to original sources

PubMed2001

Two cases of Japanese CADASIL with corpus callosum lesion.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a rare hereditary stroke disease. In the present study, a Japanese CADASIL family was first reported with missense mutation of Arg141Cys of Notch3 and a unique lesion of corpus callosum. Upon neuropsychological examination, our case 1 showed only right-handed constructional apraxia associated with corpus callosum lesion. No other callosal disconnection signs were present. Sagittal T2 weighted image of case 1 showed multiple small lesions along with the pericallosal branches from the truncus to the posterior part of the splenium in the corpus callosum. Although detailed mapping of the corpus callosum for functional fractionation in humans remains incomplete, the constructional apraxia on the right may be related to callosal dysfunction from the truncus to the posterior part of the splenium in the corpus callosum.

Corpus Callosum↗

PubMed2001

T-cell responses to mitogens in atomic bomb survivors: a decreased capacity to produce interleukin 2 characterizes the T cells of heavily irradiated individuals.

Significant decreases in the fraction of lymphocytes that are CD4(+) and increases in serum levels of some classes of immunoglobulin have been reported to occur in atomic bomb (A-bomb) survivors and in victims of the Chernobyl nuclear plant accident. To investigate the long-term effects of nuclear radiation on cellular immunity in more detail, we used limiting dilution assays with peripheral blood mononuclear cell preparations to analyze the T-cell responses of 251 A-bomb survivors exposed to less than 0.005 Gy and 159 survivors exposed to more than 1.5 Gy. The percentages of CD2-positive cells that were capable of proliferating in response to phytohemagglutinin (PHA) in the presence of exogenous interleukin 2 (IL2) did not differ substantially between distally exposed and more heavily exposed survivors. The heavily exposed survivors appeared to possess fewer T cells that were capable of proliferating in response to concanavalin A (Con A) or of producing interleukin 2. Assuming that CD4 T cells were the ones primarily responsible for producing IL2 in response to Con A, we were able to estimate how many cells in any given CD4 T-cell population were actually producing IL2. The results indicated that peripheral blood samples from heavily exposed survivors contained significantly fewer IL2-producing CD4 T cells than did similar samples from distally exposed survivors, indicating that significant exposure to A-bomb radiation may have a long-lasting negative effect on the capacity of CD4 T-cell populations to produce IL2.

Adult↗

PubMed2001

Comparisons of LET distributions measured in low-earth orbit using tissue-equivalent proportional counters and the position-sensitive silicon-detector telescope (RRMD-III).

Determinations of the LET distribution, phi(L), of charged particles within a spacecraft in low-Earth orbit have been made. One method used a cylindrical tissue-equivalent proportional counter (TEPC), with the assumption that for each measured event, lineal energy, y, is equal to LET and thus phi(L) = phi(y). The other was based on the direct measurement of LETs for individual particles using a charged-particle telescope consisting of position-sensitive silicon detectors called RRMD-III. There were differences of up to a factor of 10 between estimates of phi(L) using the two methods on the same mission. This caused estimates of quality factor to vary by a factor of two between the two methods.

Cosmic Radiation↗

PubMed2001

Reduction of ischemic damage by application of insulin-like growth factor-1 in rat brain after transient ischemia.

In order to investigate a possible effect of insulin-like growth factor-1 (IGF-1) on ischemic brain injury, IGF-1 was applied topically on the brain surface of reperfused rat brain after 60 min of transient middle cerebral artery occlusion. In contrast to the cases treated with vehicle, the infarct volume was greatly reduced at 24 h of reperfusion by the treatment with IGF-1. Immunohistochemical analysis in the middle cerebral artery territory showed that Caspase-3 staining was markedly reduced in the cases with IGF-1 treatment, but 72-kDa heat shock protein staining remained almost unchanged. The present results suggest that treatment with IGF-1 exerts a significant effect on ameliorating brain injury after transient focal brain ischemia. Moreover, this effect is greatly associated with the reduction of Caspase-3 staining, but is only minimally associated with a decreasd stress response at the cellular level.

Animals↗

PubMed2001

Two Japanese CADASIL families with a R141C mutation in the Notch3 gene.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary disease characterized by recurrent transient ischemic attacks (TIA) and strokes, and vascular dementia with Notch3 gene mutations as the cause of the disease. To date, there are only a few Japanese families ever reported with a mutation in the gene. Here, we report two more Japanese CADASIL families carrying a missense mutation in the Notch3 gene (R141C) with a unique lesion in the corpus callosum. This is the first report of two unrelated Japanese CADASIL families with a R141C mutation in the Notch3 gene. Although the disease is very rare among the Japanese population, our result suggests a possible relationship of this particular mutation (R141C) with the lesions of the corpus callosum.

Agenesis of Corpus Callosum↗

PubMed2001

Simultaneous onset of type 1 diabetes mellitus and painless thyroiditis following acute pancreatitis.

A 24-year-old female suffered from acute pancreatitis, followed by simultaneous onset of painless goiter, elevation of thyroid hormones and diabetic ketoacidosis. Two months later, her insulin secreting function was severely decreased and positive for anti-GAD and anti-islet cell antibodies, whereas the serum glucagon level was normal, suggesting an autoimmune-related destruction specifically of beta cells. In addition, the initial hyperthyroid state was followed by a hypothyroid phase which later recovered to an euthyroid state, suggesting an initial destruction of thyroid cells. Because anti-thyroidal antibodies were positive, it is likely that the thyroidal destruction was also autoimmune-related. This case implies common pathogenic mechanisms in the autoimmunity related destruction of beta cells and thyroid cells.

Acute Disease↗

PubMed2001

Primary adenosquamous carcinoma of the liver which produces granulocyte-colony-stimulating factor and parathyroid hormone related protein: association with leukocytosis and hypercalcemia.

A 55-year-old man was admitted to our hospital with fever and vomiting. Abdominal computed tomography (CT) revealed multiple low density masses in the liver. A diagnosis of primary adenosquamous carcinoma of the liver was confirmed by histological examination of a necropsy specimen. The present case showed leukocytosis and hypercalcemia with high levels of serum granulocyte-colony-stimulating factor (G-CSF) and parathyroid hormone related protein (PTHrP). Recent studies have shown that G-CSF and PTHrP are responsible for the paraneoplastic syndromes with leukocytosis and hypercalcemia. The tumor cells demonstrated positive cytoplasmic immunohistochemistry staining with anti-G-CSF and anti-PTHrP antibodies. This result suggested that the tumor produced G-CSF and PTHrP.

Carcinoma, Adenosquamous↗

PubMed2001

Bilateral massive pleural effusions caused by uremic pleuritis.

A 61-year-old man was started on hemodialysis in June 1998. Just after the commencement of dialysis, a chest X-ray film revealed bilateral pleural effusions. The effusions were hemorrhagic and exudative, and did not respond to dialysis. He was transferred to our university hospital on October 8,1998. Repeated thoracentesis demonstrated hemorrhagic and exudative characteristics without any diagnostic evidence. Pleural biopsies showed fibrosis and lymphocyte infiltration. The effusions were massive and did not respond to treatments including hemodialysis, repeatedly performed pleurodesis and the administration of antituberculous drugs. He died of respiratory failure on December 30, 1998. The autopsy confirmed bilateral fibrinous pleuritis without any underlying infections or malignancy. We diagnosed this case as uremic pleuritis from this clinical course and the autopsy findings. The clinical entity of uremic pleuritis was recognized as a complication of patients with hemodialysis in 1969. Uremic pleuritis generally responds to continued hemodialysis and the prognosis is usually good. However, some case reports demonstrated that surgical decortication is only indicated in cases with a severe clinical course. The clinical course of the present case was progressive and fatal. Uremic pleuritis is a serious complication of hemodialysis, which may lead to death.

Fatal Outcome↗

PubMed2001

Rheumatoid factor positive hypertrophic cranial pachymeningitis in association with hypopituitarism and multiple cranial nerve palsies.

This is the first report of a patient presenting with rheumatoid factor (RF) positive hypertrophic cranial pachymeningitis (HCP) in association with hypopituitarism and multiple cranial nerve palsies. Our patient developed palsies of the left II and III, bilateral VI and VII, and right IX, X, and XII cranial nerves. A stimulation test showed hypopituitarism due to hypothalamic failure. The patient was seropositive for RF but had no multiple joint pain or deformities. Magnetic resonance imaging (MRI) showed thickened dura of the sellar and parasellar region, hypothalamus, bilateral cavernous sinuses and the tentorium all of which were enhanced by gadolinium (Gd). Treatment with prednisone improved clinical symptoms and MRI findings concomitant with reduction of RF titer. Although the exact mechanism of HCP has not been clearly elucidated, the present case suggests an autoimmune mechanism associated with RF.

Aged↗

PubMed2001

Evolution of the periodicity and the self-similarity in DNA sequence: a Fourier transform analysis.

Fourier transform analysis was applied to elucidate the periodical and self-similar properties in the DNA sequences mainly of beta-globin genes in different species, and the evolutionary change in those properties was then investigated. Map patterns of a two-dimensional DNA walk showed that the stretches of exons are significantly shorter than those of introns, suggesting that the evolution of exons is driven by natural selection, whereas that of introns is generated by unknown internal rules. Using a monomer analysis, we obtained the power spectra of four different bases, A, G, C, and T, in DNA sequences. Periodicities in the short- (2 to 10 base pairs [bp]), medium- (10 to 50 bp) and long-range order (50 to 300 bp) of beta-globin gene sequences could be observed, and power spectral densities of these periodicities were increased with evolution. These results suggest the existence of the internal rules in the occurrence of the synonymous and nonsynonymous substitutions in the sequences, the destabilization of the interaction between DNA and histone protein, and the stabilization of the chromatin structure, respectively. Moreover, 1/f(alpha) analysis of the power spectra (log-log plot) in the far long-range region (160 to 16,000 bp) suggested the increase in the self-similarity (the fractal structure) of DNA sequences with evolution. A general trend of the increase in a 3 bp periodicity with evolution might be functionally related to the CAG trinucleotide repeat diseases such as Huntington chorea, where a marked periodicity of 3 bp could be observed. Fourier transform analysis applied to a DNA sequence offers a great new avenue for extracting information on the evolution of a DNA sequence.

Animals↗

PubMed2001

Endarterectomy for narrowing of the external carotid artery in a patient who underwent extracranial-intracranial bypass for occlusion of the internal carotid artery--case report.

A 56-year-old man had undergone extracranial-intracranial (EC-IC) bypass surgery for occlusion of the right internal carotid artery. Six years later, he complained of transient episodes of numbness in the left arm, occurring periodically over the previous 3 months. Neuroimaging showed the right external carotid artery was severely narrowed and cerebral blood flow (CBF) was diffusely low. Endarterectomy of the right external carotid artery was performed. Postoperative CBF was markedly improved, suggesting that EC-IC bypass became effective again by endarterectomy of a parent artery.

Carotid Artery, External↗

PubMed2001

Interhemispheric cyst causing leg monoparesis in the elderly--case report.

A 64-year-old female presented with a rare case of interhemispheric cerebral cyst manifesting as progressive monoparesis in the right lower extremity for 2 years. Surgical excision of the cyst wall was performed and communication to the subdural space was created. Postoperatively, the cyst was greatly reduced in size, and the neurological signs and symptoms were markedly improved. Interhemispheric cyst often presents with motor disturbances such as hemisparesis or paraparesis. These symptoms tend to progress slowly and sometimes years are required for a proper diagnosis. Interhemispheric cyst can also cause slowly progressive monoparesis in the lower extremity.

Arachnoid Cysts↗

PubMed2001

Troglitazone not only increases GLUT4 but also induces its translocation in rat adipocytes.

Thiazolidinediones, insulin-sensitizing agents, have been reported to increase glucose uptake along with the expression of glucose transporters in adipocytes and cardiomyocytes. Recently, we have further suggested that the translocation of GLUT4 is stimulated by thiazolidinediones in L6 myocytes. However, the direct effects of thiazolidinediones on translocation of glucose transporters have not yet been determined. In this study, using hemagglutinin epitope-tagged GLUT4 (GLUT4-HA), we provide direct evidence of the effect of troglitazone on the translocation of GLUT4 in rat epididymal adipocytes. Primary cultures of rat adipocytes were transiently transfected with GLUT4-HA and overexpressed eightfold compared with endogenous GLUT4 in transfected cells. A total of 24 h of treatment with troglitazone (10(-4) mol/l) increased the cell surface level of GLUT4-HA by 1.5 +/- 0.03-fold (P < 0.01) without changing the total amount of GLUT4-HA, whereas it increased the protein level of endogenous GLUT4 (1.4-fold) without changing that of GLUT1. Thus, the direct effect on the translocation can be detected apart from the increase in endogenous GLUT4 content using GLUT4-HA. Troglitazone not only increased the translocation of GLUT4-HA on the cell surface in the basal state but also caused a leftward shift in the dose-response relations between GLUT4-HA translocation and insulin concentration in the medium (ED(50): from approximately 0.1 to 0.03 nmol/l). These effects may partly contribute to the antidiabetic activity of troglitazone in patients with obesity and type 2 diabetes.

Adipocytes↗

PubMed2001

Ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway.

Ghrelin, an endogenous ligand for growth hormone secretagogue (GHS) receptor originally isolated from the stomach, occurs in the hypothalamic arcuate nucleus and may play a role in energy homeostasis. Synthetic GHSs have activated the hypothalamic arcuate neurons containing neuropeptide Y (NPY), suggesting the involvement of NPY in some of ghrelin actions. This study was designed to elucidate the role of ghrelin in the regulation of food intake. A single intracerebroventricular (ICV) injection of ghrelin (5-5,000 ng/rat) caused a significant and dose-related increase in cumulative food intake in rats. Ghrelin (500 ng/rat) was also effective in growth hormone-deficient spontaneous dwarf rats. Hypothalamic NPY mRNA expression was increased in rats that received a single ICV injection of ghrelin (500 ng/rat) (approximately 160% of that in vehicle-treated groups, P < 0.05). The ghrelin's orexigenic effect was abolished dose-dependently by ICV co-injection of NPY Y1 receptor antagonist (10-30 microg/rat). The leptin-induced inhibition of food intake was reversed by ICV co-injection of ghrelin in a dose-dependent manner (5-500 ng/rat). Leptin reduced hypothalamic NPY mRNA expression by 35% (P < 0.05), which was abolished by ICV co-injection of ghrelin (500 ng/rat). This study provides evidence that ghrelin is an orexigenic peptide that antagonizes leptin action through the activation of hypothalamic NPY/Y1 receptor pathway.

Animals↗

PubMed2001

Troglitazone induces GLUT4 translocation in L6 myotubes.

A number of studies have demonstrated that insulin resistance in the skeletal muscle plays a pivotal role in the insulin resistance associated with obesity and type 2 diabetes. A decrease in GLUT4 translocation from the intracellular pool to the plasma membranes in skeletal muscles has been implicated as a possible cause of insulin resistance. Herein, we examined the effects of an insulin-sensitizing drug, troglitazone (TGZ), on glucose uptake and the translocation of GLUT4 in L6 myotubes. The prolonged exposure (24 h) of L6 myotubes to TGZ (10(-5) mol/l) caused a substantial increase in the 2-deoxy-[3H]D-glucose (2-DG) uptake without changing the total amount of the glucose transporters GLUT4, GLUT1, and GLUT3. The TGZ-induced 2-DG uptake was completely abolished by cytochalasin-B (10 micromol/l). The ability of TGZ to translocate GLUT4 from light microsomes to the crude plasma membranes was greater than that of insulin. Both cycloheximide treatment (3.5 x 10(-6) mol/l) and the removal of TGZ by washing reversed the 2-DG uptake to the basal level. Moreover, insulin did not enhance the TGZ-induced 2-DG uptake additively. The TGZ-induced 2-DG uptake was only partially reversed by wortmannin to 80%, and TGZ did not change the expression and the phosphorylation of protein kinase B; the expression of protein kinase C (PKC)-lambda, PKC-beta2, and PKC-zeta; or 5'AMP-activated protein kinase activity. a-Tocopherol, which has a molecular structure similar to that of TGZ, did not increase 2-DG uptake. We conclude that the glucose transport in L6 myotubes exposed to TGZ for 24 h is the result of an increased translocation of GLUT4. The present results imply that the effects of troglitazone on GLUT4 translocation may include a new mechanism for improving glucose transport in skeletal muscle.

Animals↗

PubMed2001

Transgenic overexpression of leptin rescues insulin resistance and diabetes in a mouse model of lipoatrophic diabetes.

Lipoatrophic diabetes is caused by a deficiency of adipose tissue and is characterized by severe insulin resistance, hypoleptinemia, and hyperphagia. The A-ZIP/F-1 mouse (A-ZIPTg/+) is a model of severe lipoatrophic diabetes and is insulin resistant, hypoleptinemic, hyperphagic, and shows severe hepatic steatosis. We have also produced transgenic "skinny" mice that have hepatic overexpression of leptin (LepTg/+) and no adipocyte triglyceride stores, and are hypophagic and show increased insulin sensitivity. To explore the pathophysiological and therapeutic roles of leptin in lipoatrophic diabetes, we crossed LepTg/+ and A-ZIPTg/+ mice, producing doubly transgenic mice (LepTg/+:A-ZIPTg/+) virtually lacking adipose tissue but having greatly elevated leptin levels. The LepTg/+:A-ZIPTg/+ mice were hypophagic and showed improved hepatic steatosis. Glucose and insulin tolerance tests revealed increased insulin sensitivity, comparable to LepTg/+ mice. These effects were stable over at least 6 months of age. Pair-feeding the A-ZIPTg/+ mice to the amount of food consumed by LepTg/+:A-ZIPTg/+ mice did not improve their insulin resistance, diabetes, or hepatic steatosis, demonstrating that the beneficial effects of leptin were not due to the decreased food intake. Continuous leptin administration that elevates plasma leptin concentrations to those of LepTg/+:A-ZIPTg/+ mice also effectively improved hepatic steatosis and the disorder of glucose and lipid metabolism in A-ZIP/F-1 mice. These data demonstrate that leptin can improve the insulin resistance and diabetes of a mouse model of severe lipoatrophic diabetes, suggesting that leptin may be therapeutically useful in the long-term treatment of lipoatrophic diabetes.

Animals↗

PubMed2001

[Efficacy of tonsillectomy on psoriasis and tonsil histology].

Treatment outcomes of tonsillectomy were studied in 7 Japanese patients with psoriasis--3 males and 4 females aged 9 to 46 years (median: 23 years)--followed up 2 to 9 years after tonsillectomy. All skin lesions disappeared in 3 patients, 80% of those in 2, and no change in the remaining 2 during follow-up. Of 5 in whom skin lesions improved, 4 were females and had a history of tonsillitis making skin lesions worse. In quantitative immunohistologic analysis on tonsillar tissues by CD20 and anti-ssDNA antibodies, areas of T cell-nodules were significantly expanded, but those of the B-lymphoid follicles were smaller, and the number of apoptotic cells increased in tonsils from patients with psoriasis and PPP compared to those with recurrent tonsillitis. The area of T cell-nodules and the number of apoptosis cells were significantly larger in tonsils from 4 patients with complete recovery after tonsillectomy compared to the remaining 9 without complete recovery. This suggests that histologic evaluation may be helpful in estimating the effectiveness of tonsillectomy.

Adolescent↗

PubMed2001

Pharmacokinetic and pharmacodynamic evaluations of a potent analgesic, dihydroetorphine, in hairless rat.

To evaluate the pharmacokinetic and pharmacodynamic characteristics of a novel opioid analgesic, dihydroetorphine (DHE), concentrations of DHE and its glucuronide (DG) in plasma and central nervous system (by liquid chromatography-tandem mass spectrometry) and the antinociceptive effect (by tail-immersion test) were measured after intravenous (i.v., 2 microg/kg), intracutaneous (i.c., 2 microg/kg), subcutaneous (s.c., 2 microg/kg), intraperitoneal (i.p., 10 microg/kg), and oral (p.o., 200 microg/kg) administrations in hairless rats. An elimination half-life of plasma DHE concentration was 37.2 min after i.v. injection. Brain DHE concentration reached a maximum within 6 min after i.v. injection, and the concentration ratio in brain to plasma was 5.17. Relative bioavailabilities of DHE to i.v. injection (100%) were 70.8, 79.8, 16.7, and 0.37% after i.c., s.c., i.p., and p.o. administrations, respectively. Area under the plasma concentration-time curve ratios of plasma DG to DHE concentrations after i.v., i.c., s.c., i.p., and p.o. were 1.76, 3.26, 4.74, 14.5, and 290, respectively. Antinociceptive effects appeared rapidly after i.v., i.c., and s.c. administrations but were diminished after i.p. and p.o. administrations, and these effects were closely related to the brain DHE concentrations. DHE was excreted mainly as DG in bile (89.5% of the dose) by 240 min after i.v. injection. Serum protein binding of DHE was 83.4%, which was not influenced by DG. Glucuronidation of DHE was detected in the liver, intestine, and kidney in vitro but was minimal in the skin and brain. In conclusion, DHE was rapidly distributed to the brain in relation to producing the antinociceptive effect, and then it was rapidly metabolized to the pharmacologically inactive DG.

Algorithms↗