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Biomedical subjects

K Yoshimoto

Publications and source records attributed to K Yoshimoto.

At least 19 recordsLinked to original sources
PubMed2003

Trazodone hydrochloride attenuates thermal hyperalgesia in a chronic constriction injury rat model.

BACKGROUND AND OBJECTIVE: Trazodone hydrochloride is used in the treatment of neuropathic pain. However, the analgesic effects of trazodone on neuropathic pain are controversial. The study was undertaken to determine the analgesic effect of trazodone on a chronic constriction injury model. METHODS: We tested the effect of trazodone on thermal hyperalgesia due to a chronic constriction injury of the sciatic nerve in rats and examined the effects of lesions in the descending and ascending serotonergic system induced by 5,7-dihydroxytriptamine (5,7-DHT). RESULTS: The analgesic effects of trazodone showed a clear dose dependency. Furthermore, the analgesic effect of trazodone was observed in rats injected with 5,7-DHT into the dorsal raphe nucleus and medial raphe nucleus. CONCLUSIONS: The results suggest that a mainly serotonergic descending pain control pathway mediates the analgesic effects of trazodone.

Animals↗
PubMed2002

Defective expression and tyrosine phosphorylation of the T cell receptor zeta chain in peripheral blood T cells from systemic lupus erythematosus patients.

We have reported that tyrosine phosphorylation and expression of the T cell receptor zeta chain (TCR zeta) was decreased in two systemic lupus erythematosus (SLE) patients with an abnormal TCR zeta lacking exon-7. To examine further the TCR zeta defect and any possible relationship with specific clinical features, we studied the expression of TCR zeta in peripheral blood T cells from 44 patients with SLE, 53 with other rheumatic diseases (30 rheumatoid arthritis (RA), 11 systemic sclerosis (SSc) and 12 primary Sjögren's syndrome(SjS)) and 39 healthy individuals. Flow cytometric analysis demonstrated a significant decrease in the expression of TCR zeta in SLE (P < 0.001), but not in the other rheumatic diseases. Immunoprecipitation experiments confirmed that the expression of TCR zeta in SLE T cells was decreased dramatically (normal: 111.4 +/- 22.6%, SLE: 51.6 +/- 37.4%, P < 0.0001). The decrease in TCR zeta did not correlate with disease activity, or with the dose of prednisolone (PSL). There were, however, three SLE patients in whom the level of TCR zeta expression normalized after treatment, suggesting that mechanisms responsible for the TCR zeta defect appear to be heterogeneous. These results confirm the defective expression and altered tyrosine phosphorylation of TCR zeta in a large proportion of SLE patients, suggesting that it may play an important role in T cell dysfunction in SLE.

Adult↗
PubMed2001

Histological changes in monoaminergic neurons of Long-Evans Cinnamon rats.

The Long-Evans Cinnamon rat, an animal model of Wilson's disease, is an inbred mutant strain with spontaneous hepatitis isolated from Long-Evans rats. The copper concentration in the brains of Long-Evans Cinnamon rats at 4 weeks of age was lower than that of controls, but higher than that of controls at 20 weeks of age. We investigated the tyrosine hydroxylase and 5-hydroxytryptamine immunoreactive fiber densities in the brains of Long-Evans Cinnamon rats aged 4, 10, and 20 weeks by immunohistochemistry, comparing them with Long-Evans Agouti rats used as controls. Tyrosine hydroxylase immunoreactive fiber densities in the cingulate cortex, hippocampus and cerebellum in Long-Evans Cinnamon rats were significantly lower than those of Long-Evans Agouti rats at 4 and 10 weeks of age. On the other hand, 5-hydroxytryptamine immunoreactive fiber densities in the cingulate cortex, caudate-putamen, hypothalamus, and hippocampus in Long-Evans Cinnamon rats were significantly higher than those of controls at 4, 10 and 20 weeks of age. In the cingulate cortex and caudate-putamen, 5-hydroxytryptamine immunoreactive fiber densities became gradually higher with age. The number of aberrant 5-hydroxytryptamine immunoreactive fibers in the cingulate cortex, caudate-putamen, hypothalamus and hippocampus in LEC rats was significantly higher than that of controls. The number of another type of aberrant 5-hydroxytryptamine immunoreactive fibers, which were detected only at 20 weeks of age in the caudate-putamen in LEC rats was significantly higher than that of controls. These results suggest that age-dependent changes in copper concentrations of Long-Evans Cinnamon rats were related to changes in monoaminergic neuron systems.

Animals↗
PubMed2001

A possible role for BDNF, NT-4 and TrkB in the spinal cord and muscle of rat subjected to mechanical overload, bupivacaine injection and axotomy.

Neurotrophins play a crucial role in the regulation of survival and the maintenance of specific functions for various populations of neurons. Neurotrophin-4 (NT-4) is most abundant in skeletal muscle, and is thought to promote sciatic nerve sprouting, inhibit agrin-induced acetylcholine receptor (AChR) clustering, evoke postsynaptic potentiation and induce mitochondrial proliferation. Using Western blot analysis, immunoprecipitation and immunohistochemistry, we investigated the distribution of NT-4 in slow- and fast-type muscles. We also tested the adaptive response of this protein in the mechanically overloaded muscle, in the regenerating muscle following bupivacaine injection and in the denervated muscle. Additionally, we investigated whether TrkB phosphorylation in the spinal cord and in the sciatic nerve occurs through the interaction with BDNF or NT-4 when the innervating muscle is damaged. Markedly more NT-4 was expressed in fast-type muscles compared with the slow types. TrkB protein was more frequently observed around the edge of myofibers (neuromuscular junction) of the soleus muscle compared with the gastrocnemius muscle. TrkB tyrosine phosphorylation occurred in the spinal cord but not in the sciatic nerve 24 h after bupivacaine injection of the innervating muscle. At the same time, the amount of TrkB co-precipitating with BDNF was markedly increased in the spinal cord. A rapid activation of TrkB (1-8 h) was also observed in the spinal cord after axotomy,while the amount of TrkB co-precipitating with NT-4 was markedly lower after axotomy. These results indicate that NT-4 is preferentially distributed in fast-type muscles. Furthermore, by interacting with BDNF and NT-4, the TrkB in the spinal cord may be important for the survival of motoneurons and outgrowth of injured peripheral axons following muscle damage.

Animals↗
PubMed2001

Acute inhibition of proinsulin biosynthesis at the translational level by palmitic acid.

The effects of fatty acids on pancreatic beta cell are still controversial. Here, in order to determine whether free fatty acids acutely affect beta cell functions, we studied the effect of palmitic acid (PA) on proinsulin biosynthesis and insulin secretion using rat islets in vitro. Exposure of islets to PA for 1 h reduced glucose-stimulated proinsulin biosynthesis in a dose-dependent manner; in contrast, no change in insulin secretion was observed after 1 h incubation with PA. Furthermore, PA treatment did not cause any change of preproinsulin mRNA level during 1-h incubation period. Thus, our data indicate that PA primarily suppresses glucose-induced proinsulin biosynthesis within 1 h at the translational level.

Animals↗
PubMed2001

Dopamine and serotonin uptake inhibitors on the release of dopamine and serotonin in the nucleus accumbens of young and aged rats.

Nucleus accumbens (ACC) of young (4 months old) and aged (24 months old) Wistar rats were perfused with dopamine (DA) uptake blocker, cocaine, or the serotonin (5-HT) selective reuptake inhibitor, fluoxetine, through the microdialysis probe membrane, used to assess the dopamine transporter (DAT) or serotonin transporter (SERT) modulation. The basal extracellular DA release in the ACC was significantly lower in aged rats than young rats. Analysis of DA and 5-HT concentrations in the ACC with increased positive GFAP revealed that DA and DOPAC levels of aged rats were decreased to 55 and 60% of those in young rats, respectively. After co-perfusion with cocaine, both DA and 5-HT releases in the ACC were increased in the young and aged groups. However, the magnitude of the increased DA release was lower in aged rats than young rats. Co-perfusion with fluoxetine showed lower magnitude of the increased DA release in aged rats. It appears that the DAT and SERT system responds initially to ACC cell loss with age, and that especially ACC DAT in the aged rat is more degenerative compared with the young rats. These findings suggest that the serotonergic system with SERT in the remaining ACC neurons show an early adaptive response and resistance to the normal aging and maintain the multiple regulatory system in the ACC despite neural loss since the dopaminergic neurons in the aged animals are vulnerable to aging.

Aging↗
PubMed2001

In vivo analysis of mammary and non-mammary tumorigenesis in MMTV-cyclin D1 transgenic mice deficient in p53.

Overexpression of the cyclin D1 oncogene and inactivation of the p53 tumor suppressor have both been implicated in substantial proportions of sporadic human breast cancers. Transgenic mice with cyclin D1 overexpression targeted to mammary tissue by the MMTV enhancer-promoter have been shown to develop mammary cancers. To investigate the relationship between pathways driven by cyclin D1 overexpression and p53 loss during the development of breast cancers, we crossed MMTV-cyclin D1 mice with p53 heterozygous null (p53+/-) mice. In such crossed mice, cyclin D1-driven mammary neoplasia would need to be substantially accelerated by p53 loss in order for mammary tumors to develop prior to the expected onset of non-mammary tumors characteristic of the p53-deficient background alone. Instead, in mice heterozygous or homozygous for p53 deficiency and simultaneously carrying the MMTV-cyclin D1 transgene, only tumors typically found in p53-deficient mice developed and mammary tumors were not observed. Interestingly, MMTV-cyclin D1/p53+/- mice appeared to develop these non-mammary tumors more rapidly than p53+/- mice, and a majority of the sampled non-mammary tumors from MMTV-cyclin D1/p53+/- mice showed 'ectopic' expression of the MMTV-driven cyclin D1 transgene. Within the constraints of possible genetic background effects and limited sensitivity due to the early emergence of non-mammary tumors, these observations provide no evidence that inactivation of p53 confers a major additional selective advantage to mammary cells overexpressing cyclin D1 in this animal model of human breast cancer. Interestingly, the results do raise the possibility that p53 inactivation might complement or cooperate with cyclin D1 deregulation during the development of some types of non-mammary tumors.

Animals↗
PubMed2001

Colour Doppler ultrasonography of a segmental branch of the portal vein is useful for early diagnosis and monitoring of the therapeutic course of veno-occlusive disease after allogenic haematopoietic stem cell transplantation.

We report two cases in which visualization of the segmental branch of the hepatic portal vein with the colour Doppler ultrasonography (US) technique was useful for the early diagnosis of veno-occlusive disease. The change in blood flow in the segmental branch of the portal vein occurred 5 and 6 d before the clinical criteria were fulfilled in the two cases. Reverse flow in the segmental branch began partially in the liver at first, and then spread to the whole liver several days later. All the US findings in both cases disappeared after thrombolytic therapy.

Adult↗
PubMed2001

Electroacupuncture stimulation suppresses the increase in alcohol-drinking behavior in restricted rats.

BACKGROUND: Although a number of studies on traditional eastern or Chinese medicine, such as acupuncture, moxibustion, and herbal drugs, have been reported, few reports describe electroacupuncture (EAC) effects on drug- and alcohol-seeking behaviors in animal models. The purpose of the present study was to investigate the effect of EAC on changes in alcohol-drinking behavior in rats challenged with restriction and immobilization stress. MATERIAL AND METHODS: Male Sprague Dawley rats (260-280 g) were tightly hung and immobilized in restriction models for 10 min. These immobilization stresses were performed twice a week for 1 week and for 3 consecutive weeks for the short- and long-restricted stress groups, respectively. EAC was applied for 10 min to the hindlimb point, Tsu-San-Li (ST 36), and the lumbar point, Shen-Shu (BL 23). These points are used to treat mental and psychosomatic disorders and are known clinically to produce a sedation effect. Time-access alcohol-drinking behavior was determined at 24 hr after the termination of EAC. Finally, brain dopamine (DA) levels were assayed in the two groups. A sham-control group underwent only restricted stress without EAC. RESULTS: Time-access alcohol-drinking behavior increased significantly in the long-restricted group compared with the short-restricted group and controls. EAC applied to the ST 36 (Tsu-San-Li) point suppressed the increased alcohol-drinking behavior in restricted rats. However, EAC applied to the Shen-Shu (BL 23) point was not effective, because alcohol-drinking behavior was significantly increased in long-restricted rats compared with short-restricted rats. Striatal DA levels of restricted rats with EAC stimulated at Tsu-San-Li were increased significantly compared with the rats with EAC applied to the Shen-Shu point. CONCLUSION: These findings suggest that EAC applied at ST 36 (Tsu-San-Li) was more effective for reducing the increased alcohol-drinking behavior in restricted rats, and they showed that a point specific in EAC procedure was associated with an increase of striatal DA levels. These findings provide new information for understanding alcohol-drinking behavior and for treating human alcoholics.

Alcohol Drinking↗
PubMed2001

Upregulation of fractalkine in human crescentic glomerulonephritis.

BACKGROUND/AIM: To evaluate the importance of fractalkine, a novel member of the CX3C chemokine, and natural killer (NK) cells in human crescentic glomerulonephritis, we determined the presence of fractalkine in the diseased kidneys immunohistochemically, and the correlation among fractalkine, NK cells and the degree of renal damage. METHODS: Twenty-three patients (13 males and 10 females) with primary or secondary crescentic glomerular disease were evaluated in this study. Fractalkine and CD16-positive cells including NK cells were detected immunohistochemically. RESULTS: Fractalkine-positive cells were detected in the interstitium of 23 patients with crescentic glomerulonephritis, while they were not detected in the glomeruli. In addition, CD16-positive cells were detected in both the glomeruli (1.3 +/- 0.2/glomerulus) and interstitium (1.3 +/- 0.2/visual field). The number of fractalkine-positive cells in the interstitium correlated with the number of CD16-positive cells before glucocorticoid therapy (r = 0.43, p = 0.047, n = 23). The number of fractalkine-positive cells in the interstitium before glucocorticoid therapy (0.2 +/- 0.1/visual field) decreased after therapy (0.1 +/- 0.1/visual field, p = 0.050) in 11 cases tested. The number of CD16-positive cells in the diseased kidneys did not change after glucocorticoid therapy. CONCLUSION: These results suggest that the local production of fractalkine may explain the presence of CD16-positive cells including NK cells, which may participate in the interstitial lesions of human crescentic glomerulonephritis before corticoid therapy.

Adult↗
PubMed2001

Primary hyperparathyroidism caused by parathyroid-targeted overexpression of cyclin D1 in transgenic mice.

The relationship between abnormal cell proliferation and aberrant control of hormonal secretion is a fundamental and poorly understood issue in endocrine cell neoplasia. Transgenic mice with parathyroid-targeted overexpression of the cyclin D1 oncogene, modeling a gene rearrangement found in human tumors, were created to determine whether a primary defect in this cell-cycle regulator can cause an abnormal relationship between serum calcium and parathyroid hormone response, as is typical of human primary hyperparathyroidism. We also sought to develop an animal model of hyperparathyroidism and to examine directly cyclin D1's role in parathyroid tumorigenesis. Parathyroid hormone gene regulatory region--cyclin D1 (PTH--cyclin D1) mice not only developed abnormal parathyroid cell proliferation, but also developed chronic biochemical hyperparathyroidism with characteristic abnormalities in bone and, notably, a shift in the relationship between serum calcium and PTH. Thus, this animal model of human primary hyperparathyroidism provides direct experimental evidence that overexpression of the cyclin D1 oncogene can drive excessive parathyroid cell proliferation and that this proliferative defect need not occur solely as a downstream consequence of a defect in parathyroid hormone secretory control by serum calcium, as had been hypothesized. Instead, primary deregulation of cell-growth pathways can cause both the hypercellularity and abnormal control of hormonal secretion that are almost inevitably linked together in this common disorder.

Adenoma↗
PubMed2001

Increases in plasma ACTH and cortisol after hypertonic saline infusion in patients with central diabetes insipidus.

To clarify the mechanism for the potentiation of CRH-induced ACTH response by the infusion of hypertonic saline, we investigated changes in plasma ACTH concentration after infusion of 5% hypertonic saline in five patients with untreated central diabetes insipidus (DI). Basal levels of plasma ACTH and cortisol in the DI group were not significantly different from those in normal control subjects. The infusion of hypertonic saline produced an increase in plasma arginine vasopressin (AVP) in controls, but did not elevate ACTH. However, in patients with DI, the plasma AVP concentration did not change, but circulating ACTH increased 3.6-fold (7.7 +/- 1.5 to 23.0 +/- 2.7 pmol/liter; P < 0.01), and plasma cortisol also increased significantly (298 +/- 99 to 538 +/- 124 nmol/liter; P < 0.05). Moreover, a positive correlation was observed between plasma ACTH and osmolality (r = 0.72; P < 0.005). These results indicate that ACTH secretion in DI patients is regulated by a mechanism distinct from that in healthy subjects. It seems possible that the increase in plasma osmolality promotes ACTH secretion in DI patients through AVP and/or urocortin via the hypophyseal portal system, independent of the AVP secretion from magnocellular neurons.

Adrenocorticotropic Hormone↗
PubMed2001

Serum levels of KL-6 reflect disease activity of interstitial pneumonia associated with ANCA-related vasculitis.

OBJECTIVE: KL-6 is reported to be excreted from the lung alveolar and bronchial epithelial cells and may be a good marker for monitoring disease activity of interstitial pneumonia. This study was designed to ascertain the clinical significance of serum KL-6 levels in interstitial pneumonia associated with anti-neutrophil cytoplasmic antibody (ANCA)-related vasculitis. METHODS: Serum KL-6 levels were determined by an enzyme-linked immunosorbent assay. PATIENTS: We examined 20 healthy subjects, 13 patients with perinuclear (myeloperoxidase, MPO) ANCA-related vasculitis and 12 dermatomyositis (DM)/polymyositis (PM) patients as disease controls in this study. Six out of 13 patients with ANCA-related vasculitis had interstitial pneumonia. RESULTS: Serum levels of KL-6 in ANCA-positive patients with interstitial pneumonia were significantly elevated, while they remained as low as those of healthy subjects in ANCA-positive patients without interstitial pneumonia. Similarly, KL-6 levels in sera were higher in 12 dermatomyositis/polymyositis patients with interstitial pneumonia, while they remained low in DM/PM patients without interstitial pneumonia. Moreover, the elevated serum KL-6 level was reduced during the convalescence induced by glucocorticoid therapy and reflected the disease activity of interstitial pneumonia associated with ANCA-related vasculitis. CONCLUSION: These data suggest that the measurement of serum KL-6 levels may be a good monitoring system for the diagnosis and follow-up of interstitial pneumonia of patients with ANCA-related vasculitis.

Aged↗
PubMed2001

Multi-level disruption of the spinal nerve root sleeves in spontaneous spinal cerebrospinal fluid leakage--two case reports.

A 37-year-old male and an 18-year-old male presented with spontaneous spinal cerebrospinal fluid (CSF) leakage from multiple nerve root sleeves. Both patients suffered abrupt onset of intense headache followed by nausea, dizziness, and one patient with and one without positional headache. Radioisotope spinal cisternography of both patients revealed that the CSF leaks were not localized in a special zone but distributed to multiple spinal nerve root sleeves. Magnetic resonance (MR) myelography suggested that the spinal CSF column was fully expanded to the root sleeves. The extraspinal nerve bundles demonstrated numerous high intensity spots. Both patients were treated conservatively, and their symptoms resolved within one month. Repeat radioisotope cisternography and MR myelography confirmed the spine was normal after recovery. We suggest that spreading disruption of the arachnoid membrane occurs at the nerve root sleeves due to CSF overflow into the spinal canal.

Adolescent↗
PubMed2001

[Effect of interferon therapy on hepatitis B virus related membranous nephropathy associated with focal segmental glomerulosclerosis].

We experienced a 24-year-old Japanese man, who was a hepatitis B virus carrier with nephrotic syndrome. Liver biopsy showed that he was suffering from chronic hepatitis (activity 2, fibrosis 2). Renal biopsy revealed membranous nephropathy(MN) with focal segmental glomerulosclerosis(FGS). Immunofluorescentic findings revealed the presence of HBe antigen along the glomerular capillaries as well as HBe antigenemia in circulation. Therefore, we diagnosed this case as HB virus-related membranous nephropathy associated with FGS lesions. He was treated with interferon(IFN) alpha-2b for over a month and angiotensin converting enzyme inhibitor. These therapies reduced urinary protein excretion from 4-6 g/day to 1-2 g/day, in accordance with a decrease in the titer of HBV DNA polymerase. The second renal biopsy revealed that the histological change from MN to membranoproliferative glomerulonephritis Type III after IFN therapy. These results suggest that IFN therapy might be effective for HB virus-related MN associated with FGS.

Adult↗
PubMed2001

[Acute hepatitis B virus after chemotherapy for a case with germinoma].

A 28-year old man with HCG-producing germinoma had undergone chemotherapy and radiotherapy. On admission for the fifth session of maintenance chemotherapy, he was found to be positive for hepatitis B (HB)s antigen, but negative for HBs antibody. HBs antigen had been negative during previous admissions. Since liver function was normal, the patient underwent chemotherapy. During myelosuppression after chemotherapy, liver dysfunction developed and acute HB was diagnosed. He fortunately showed seroconversion 2 months after onset. Serum immunological examinations are required for patients receiving chemotherapy.

Acute Disease↗