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T Otsuka

Publications and source records attributed to T Otsuka.

At least 109 records · Page 6Linked to original sources
PubMed1999

Endothelin-1 stimulates heat shock protein 27 induction in osteoblasts: involvement of p38 MAP kinase.

We previously reported that endothelin-1 (ET-1) activates p42/p44 mitogen-activated protein (MAP) kinase in osteoblast-like MC3T3-E1 cells and consequently induces synthesis of interleukin-6. In the present study, we investigated the effect of ET-1 on the induction of heat shock protein 27 (HSP 27) in MC3T3-E1 cells. ET-1 time and dose dependently stimulated HSP 27 accumulation. ET-1 induced an increase in the levels of mRNA for HSP 27. Both staurosporine and calphostin C, inhibitors of protein kinase C (PKC), suppressed the ET-1-induced HSP 27 accumulation. 12-O-tetradecanoylphorbol 13-acetate (TPA), a PKC activator, induced the HSP 27 accumulation and the expression of mRNA for HSP 27. The ET-1-stimulated HSP 27 accumulation was reduced in PKC-downregulated MC3T3-E1 cells. The HSP 27 accumulation by ET-1 was not suppressed by PD-98059, an inhibitor of the upstream kinase that activates p42/p44 MAP kinase. ET-1 or TPA induced the phosphorylation of p38 MAP kinase. SB-203580, an inhibitor of p38 MAP kinase, reduced the ET-1-stimulated HSP 27 accumulation. Calphostin C and U-73122, a phospholipase C inhibitor, suppressed the ET-1-induced phosphorylation of p38 MAP kinase. U-73122 and propranolol, a phosphatidic acid phosphohydrolase inhibitor, reduced the ET-1-stimulated HSP 27 accumulation. SB-203580 suppressed the ET-1-stimulated increase in the mRNA levels for HSP 27. These results strongly suggest that ET-1 stimulates HSP 27 induction in osteoblasts and that p38 MAP kinase activation is involved in the HSP 27 induction.

Animals↗
PubMed1999

Aerobically generated CO(2) stored during early exercise.

Previous studies have shown that a metabolic alkalosis develops in the muscle during early exercise. This has been linked to phosphocreatine hydrolysis. Over a similar time frame, the femoral vein blood pH and plasma K(+) and HCO(-)(3) concentrations increase without an increase in PCO(2). Thus CO(2) from aerobic metabolism is converted to HCO(-)(3) rather than being eliminated by the lungs. The purpose of this study was to quantify the increase in early CO(2) stores and the component due to the exercise-induced metabolic alkalosis (E-I Alk). To avoid masking the increase in CO(2) stores by CO(2) released as HCO(-)(3) buffers lactic acid, the transient increase in CO(2) stores was measured only for work rates (WRs) below the lactic acidosis threshold (LAT). The increase in CO(2) stores was evident at the airway starting at approximately 15 s; the increase reached a peak at approximately 60 s and was complete by approximately 3 min of exercise. The increase in CO(2) stores was greater, but the kinetics were unaffected at the higher WR. Three components of the change in aerobically generated CO(2) stores were considered relevant: the carbamate component of the Haldane effect, the increase in CO(2) stores due to increase in tissue PCO(2), and the E-I Alk. The Haldane effect was calculated to be approximately 5%. Physically dissolved CO(2) in the tissues was approximately 30% of the store increase. The remaining E-I Alk CO(2) stores averaged 61 and 68% for 60 and 80% LAT WRs, respectively. The kinetics of O(2) uptake correlated with the time course of the increase in CO(2) stores; the size of the O(2) deficit correlated with the size of the E-I Alk component of the CO(2) stores. We conclude that a major component of the aerobically generated increase in CO(2) stores is the new HCO(-)(3) generated as phosphocreatine is converted to creatine.

Adult↗
PubMed1999

Plasma endothelin-1 level in chronic obstructive pulmonary disease: relationship with natriuretic peptide.

BACKGROUND AND OBJECTIVE: Endothelin-1 (ET-1) is a potent vasoconstrictor peptide produced by the vascular endothelium. The purpose of this study was to elucidate the pathophysiological role of ET-1 in patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease (COPD). METHOD: We measured plasma ET-1 levels during right heart catheterization both at rest and during exercise on room air and while breathing oxygen in patients with COPD. In addition, we simultaneously measured plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). RESULTS: Plasma ET-1 levels at rest were significantly higher in 21 patients with COPD than in 16 control subjects (p < 0.001). For COPD patients, there was no correlation between the plasma ET-1 level and pulmonary arterial pressure or pulmonary vascular resistance at rest. On the other hand, there was a significant negative correlation between plasma ET-1 level and mixed venous oxygen tension (r = -0. 503, p < 0.05). Also, the plasma ET-1 level was positively correlated with those of ANP (r = 0.540, p < 0.05) and BNP (r = 0. 533, p < 0.05) at baseline. Oxygen administration significantly decreased plasma ET-1 levels at rest (p < 0.05). Plasma ET-1 levels did not change significantly with exercise despite the progression of pulmonary hypertension and hypoxemia. In contrast, plasma ANP and BNP levels both increased markedly with exercise (p < 0.01). CONCLUSION: We conclude that in patients with COPD, the plasma ET-1 level is not affected by acute progression of pulmonary hypertension and hypoxemia during exercise, and persistent hypoxemia may be associated with an increase in the plasma ET-1 level. In addition, our findings suggest that ANP and BNP may modulate the pulmonary vascular tone by interacting with ET-1 in these patients.

Aged↗
PubMed1999

WF14861, a new cathepsins B and L inhibitor produced by Colletotrichum sp. II. Biological properties.

WF14861, 3-(N-(1-(N-(4-aminobutyl)-N-(3-aminopropyl)carbamoyl)-2-(4-hydroxyphenyl )ethyl)carbamoyl)oxirane-2-carboxylic acid, was obtained from the culture mycelium of Colletotrichum sp. as a novel cathepsins B and L inhibitor. WF14861 also showed inhibitory activities against bone derived crude protease and other cysteine proteases in vitro. The compound ameliorated the tissue damage and the bone destruction models of low-calcium-diet-fed mouse and adjuvant arthritis rat model.

Animals↗
PubMed1999

[One case of chronic pyothorax with MRSA infection cured by air-plombage method].

It is very difficult to cure a chronic pyothorax with MRSA infection. We experienced one such case with low pulmonary function (VC 1700 ml, %VC 50.7%), 73 years old man, who had a history of esophageal cancer and was operated two years ago. As the control of bacteria and the surgical intervention are both important in the treatment of pyothorax cases, we tried to reduce MRSA by washing with Povidone-Iodine solution through the drain. Then, we selected Air-plombage method as it is expected to maintain or to increase the pulmonary function after operation. We could easily close the bronchial fistula with a muscle flap, as it was located at the centre of the cavity. During the operation we frequently used acidic electrolyzed NaCl solution against MRSA. For one month after the operation, we used Vancomycin which is effective against MRSA, however, rather severe side effects were seen, and finally and MRSA vanished. Pulmonary function has improved from the initial VC 1700 ml, %VC 50.7% to VC 2120 ml, %VC 63.6% one year later. We recommend Air-plombage method for such cases with low pulmonary function under the control of MRSA by using acidic solution.

Aged↗
PubMed1999

[Case of stage IVb gastric cancer in which favorable anti-tumor effect and good QOL were observed due to UFTP therapy after low-dose CDDP-tegafur therapy].

A patient with stage IVb advanced gastric cancer, who was Group 4 lymph node metastasis positive, underwent two postoperative courses of low-dose CDDP-tegafur therapy (800 mg/body/day of tegafur + 5 mg/body/5 administrations, 2 days of rest, of cisplatin). UFTP therapy (400 mg/body/day of UFT + 5 mg/body/twice weekly of cisplatin) was thereafter given on an outpatient basis. The patient has now been receiving this therapy for one year and six months. The anti-tumor effect has been maintained and the tumor has been reduced in size by 89% without any adverse reactions. A good QOL has been observed. The present therapy can be performed safely at home and appears to be a favorable treatment from the viewpoint of QOL.

Adenocarcinoma↗
PubMed1998

c-Met autocrine activation induces development of malignant melanoma and acquisition of the metastatic phenotype.

The molecular and genetic events that contribute to the genesis and progression of cutaneous malignant melanoma, a complex and aggressive disease with a high propensity for metastasis, are poorly understood due in large part to the dearth of relevant experimental animal models. Here we used transgenic mice ectopically expressing hepatocyte growth factor/scatter factor (HGF/SF) to show that the Met signaling pathway is an important in vivo regulator of melanocyte function, whose subversion induces malignant melanoma. Tumorigenesis occurred in stages, beginning with the abnormal accumulation of melanocytes in the epidermis and dermis and culminating in the development of metastatic melanoma. Oncogenesis in this model was driven by creation of HGF/SF-Met autocrine loops through forced expression of the transgenic ligand and apparent selection of melanocytes overexpressing endogenous receptor, rather than paracrine stimulation or mutational activation of c-met. Preference for liver as a metastatic target correlated with high HGF/SF-Met autocrine activity, consistent with the notion that such activity may influence colonization. Although basic fibroblast growth factor and its receptor were both weakly expressed in the majority of melanomas examined, high levels were found only in those rare neoplasms with low or undetectable HGF/SF and Met expression, suggesting that these two tyrosine kinase receptor autocrine loops serve a critical overlapping function in melanocytic tumorigenesis. Our data support a causal role for HGF/SF-Met signaling in the development of melanoma and acquisition of the metastatic phenotype. Moreover, this transgenic mouse should serve as a highly useful model, facilitating our understanding of mechanisms by which human melanoma progresses to malignancy and expediting the development of efficacious therapeutic modalities designed to constrain metastasis.

Animals↗
PubMed1998

MAP kinase pathways as a route for regulatory mechanisms of IL-10 and IL-4 which inhibit COX-2 expression in human monocytes.

Mitogen-activated protein kinases (MAPKs) are activated by various extracellular stimuli and play an important role in regulating the expression of proinflammatory molecules in monocytes/macrophages. We first questioned whether MAPK activation in involved in cyclooxygenase (COX)-2 expression in lipopolysaccharide (LPS)-stimulated human monocytes. LPS induced the expression of COX-2 protein and COX-2 mRNA as well as the phosphorylation and activation of extracellular signal-regulated protein kinase (ERK)2 and p38 MAPK in monocytes. The induction of COX-2 mRNA, COX-2 protein, and prostaglandin (PG)E2 by LPS was inhibited by the specific inhibitors of ERK and p38 MAPK, suggesting that the activation of ERK2 and p38 MAPK is involved in COX-2 expression in LPS-stimulated monocytes. Since we previously showed that interleukin (IL)-10 and IL-4 similarly inhibited COX-2 expression in LPS-stimulated monocytes, we next questioned whether these cytokines regulate the phosphorylation and activation of ERK2 and p38 MAPK in LPS-stimulated monocytes. Interestingly, LPS-induced phosphorylation and activation of ERK2 was significantly inhibited by IL-4 and IL-10, while that of p38 MAPK was inhibited by IL-10, but not IL-4. These results suggest that the mechanisms of inhibition by IL-10 and IL-4 of the LPS-induced expression of proinflammatory molecules could be ascribed to the regulatory effects of both cytokines on MAPK activation.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1998

Magnetic resonance imaging of experimental subacute spinal cord compression.

STUDY DESIGN: Subacute compression of the spinal cord was applied to rats. The animals were chronologically observed using magnetic resonance imaging for more than 8 weeks after surgery and were killed for histopathologic examination. OBJECTIVES: To investigate the correlation of changes in signal intensity on magnetic resonance images with those observed in histopathologic study and with the degree of spinal cord compression and paralysis. SUMMARY OF BACKGROUND DATA: No consensus has been reached concerning the correlation of magnetic resonance images to clinical symptoms of compressive myelopathy. Few reports are available in which magnetic resonance imaging findings are compared with histopathologic features in chronic or subacute experiments. METHODS: In rats under general anesthesia, the T11 lamina was thinned and a slow increase in volume was applied. Hind limb paralysis appeared 1 week after the procedure and spontaneously subsided thereafter. The degree of spinal compression and signal intensity was observed chronologically using magnetic resonance imaging. The signal intensity on the final MR images was rated on a four-point scale and compared with histopathologic findings. RESULTS: As spinal compression increased, the incidence of high signal intensity on long spin-echo images became higher. Low signal intensities on short spin-echo images were visible in animals in which compression and paralysis were the most severe. In these animals, cavitation and a dilated central canal were visible. High signal intensities on long spin-echo images reflected various pathologic changes. CONCLUSIONS: Changes in signal intensity on MR images are visible after the induction of myelopathy by high-pressure compression. These signal intensities may be useful in predicting the outcome of compressive myelopathy.

Animals↗
PubMed1998

Activation of STAT5 by lipopolysaccharide through granulocyte-macrophage colony-stimulating factor production in human monocytes.

LPS is a potent stimulator of monocytes, inducing many of their functions. Although the details of how LPS exerts such functions remain largely unknown, transcription factors such as nuclear factor-kappaB, nuclear factor-IL-6, and activator protein-1 have been shown to be involved in this process. However, to date it has been thought that no known STAT molecule plays a role in the activation of monocytes by LPS. In this study we examined whether some known STAT molecule is stimulated by LPS, based on the finding that a GAS motif sequence is conserved in the promoter regions of human, mouse, and rat cyclo-oxygenase-2 (COX-2) genes. Consequently, LPS induced activation of STAT5 in human monocytes, and this STAT5 activation occurred in an indirect way via granulocyte-macrophage CSF (GM-CSF) secreted by LPS-stimulated monocytes. Expression of COX-2 protein was partially reduced by treatment of anti-human GM-CSF Ab. Activation of STAT5 was inhibited by either IL-10 or dexamethasone (Dex), but not by aspirin. IL-10 blocked activation of STAT5 indirectly by suppressing GM-CSF production, while Dex inhibited this activation both directly and indirectly. Taken together, these results suggest that in addition to other transcription factors, STAT5 plays an important role in activation of monocytes by LPS, and that STAT5 is another target for IL-10 and Dex to inhibit COX-2 expression in activated monocytes.

Cyclooxygenase 2↗
PubMed1998

Median raphe (parameatal) cysts of the penis.

PURPOSE: Although median raphe cysts of the penis have been widely reported the pathogenesis is obscure. We describe the microstructural detection of 3 cases of median raphe to study the true pathogenesis. MATERIALS AND METHODS: Three patients presented to our clinic of plastic surgery complaining of abnormal shape of the penis or mass recurrence. High magnification light microscopy and electron microscopy were performed. RESULTS: Microstructural study revealed that all 3 cases had similar findings to those of the common urethral mucosa. CONCLUSIONS: Median raphe cysts are derived from the external paraurethral ducts and contain features that to our knowledge have not been previously reported.

Adolescent↗
PubMed1998

Growth inhibition of leukemic cells by (-)-epigallocatechin gallate, the main constituent of green tea.

In this report, we presented the results that EGCG, the main constituent of the polyphenols present in Japanese green tea inhibited growth of leukemic cell lines of both human and mice. The proliferation of human leukemic cell lines and mouse NFS60 cell line was inhibited by EGCG. Sensitivity of each line to EGCG was different, and more than 50% of DNA synthesis was reduced in all the cell lines in the presence of 50 microM EGCG. On the other hand, normal hematopoietic progenitor cells retained their natural function of supplying mature cells of various lineages in the presence of less than 10 microM EGCG in vitro. Even in the presence of 100 microM EGCG, half the colonies containing all the lineages of cells were developed. All the dead cells of each line showed characteristics of apoptosis, which might be due to inhibition by EGCG of growth factors' signaling. Besides anticarcinogenic activity, EGCG is expected to have a new function for leukemia therapy without side effects.

Animals↗
PubMed1998

Rotation plasty for osteosarcoma of the femur.

A 20-year-old female with right femoral osteosarcoma noted severe pain and swelling of the right thigh, and was transferred to the authors' hospital after suffering a pathologic fracture of the right femur. Plain x-ray disclosed a tumor shadow extending from the pathologic fracture of the distal portion of the femur to the center of the diaphysis. MRIs showed a broad lesion and hematoma, and invasion to the femoral vascular bundle was suspected. Angiograms revealed vascularization coincidental to the tumor, and an irregular vascular wall of the femoral artery, which was shifted posteriorly. After consultation with the patient and her family, rotation plasty was performed. The sciatic nerve was isolated and preserved; major vessels were sectioned proximally and distally because of tumor tissue invasion to the femoral artery and vein. After wide excision of the tumor, the leg was rotated outward 180 degrees, and osteosynthesis was performed between the remaining femur and the tibia, followed by microsurgical anastomosis of vessels. Five years postoperatively, no local recurrence or metastasis has been observed. The patient has excellent functional recovery without pain, and no other complications.

Adult↗
PubMed1998

Trimethoprim-sulfamethoxazole for the prevention of methicillin-resistant Staphylococcus aureus pneumonia in severely burned patients.

BACKGROUND: Patients with severe burns are at increased risk of developing methicillin-resistant Staphylococcus aureus (MRSA) ventilator-associated pneumonia. This study was designed to determine whether MRSA pneumonia can be prevented by prophylactic administration of trimethoprim-sulfamethoxazole (TMP-SMX). METHODS: We conducted a prospective, randomized, placebo-controlled study in patients with severe burns (> or = 20%), who required ventilator support. Prophylaxis was done with oral TMP-SMX (80 mg/400 mg) three times daily for 10 days from 4 to 6 days after burn injury. The incidence of MRSA pneumonia and the side effects were evaluated during the administration period. RESULTS: Twenty-one patients were assigned to receive TMP-SMX, and 19 patients to receive placebo. The incidence of MRSA pneumonia was 4.8% in the TMP-SMX group and 36.8% in the placebo group, showing a significant difference (p = 0.017). No major side effects of therapy were seen in the TMP-SMX group. CONCLUSION: Prophylactic treatment with TMP-SMX can prevent MRSA pneumonia in severely burned patients.

Administration, Oral↗
PubMed1998

Current status of and challenges for dementia in Japan.

With an increase in the elderly population in Japan, the number of elderly with dementia increases each year. There were about 1.26 million elderly people with dementia in 1995. Dementia is untreatable, requiring protracted care. Enhancing and improving the social services for the demented elderly are strongly recommended. The available social services for the elderly with dementia in Japan are measures for health and institutional care. In the former, there are consultations, guidance services and welfare services (home help services, day services, short stay services). The latter mainly consists of mental hospitals, hospitals for the elderly, health facilities for the elderly and special nursing homes for the elderly. As future challenges to improve measures for the demented elderly, the following measures must be offered to demented elderly: (i) urgent, quantitative improvements in social services; (ii) establishing a comprehensive service system in the community; (iii) clarifying the concept of role sharing and closer cooperation among hospitals and institutions; (iv) training human resources in the fields of health medical care and welfare to give expertise and skill; (v) improvement of the system for dementia research; and (vi) securing and training volunteers for home care.

Aged↗
PubMed1998

Role of IL-10 in the crossregulation of prostaglandins and cytokines in monocytes.

In the present study we have focused mainly on the role of IL (interleukin)-10 in the crossregulation of prostaglandins and cytokines in human monocytes. We first determined the effects of tumor necrosis factor-alpha (TNF-alpha) and IL-10 on monocyte prostaglandin E2 (PGE2) production. Unstimulated monocytes constitutively produced a small but significant amount of PGE2 in the culture supernatants. Both TNF-alpha and lipopolysaccharide (LPS) caused a remarkable increase in monocyte PGE2 production. On the other hand, IL-10 alone was without effect on constitutive PGE2 production but drastically inhibited LPS-induced PGE2 production in monocytes. Moreover, this inhibitory effect of IL-10 was not simply attributable to its inhibition of TNF-alpha production in LPS-stimulated monocytes. Next, we determined the effect of PGE2 on TNF-alpha mRNA expression in monocytes. Treatment of monocytes with or without PGE2 showed no detectable TNF-alpha mRNA. Activation of monocytes by LPS resulted in a remarkable accumulation of TNF-alpha mRNA and PGE2 efficiently inhibited this expression. Finally, we determined the effect of PGE2 on IL-10 mRNA expression in monocytes. Similar to TNF-alpha mRNA, unstimulated monocytes showed no detectable IL-10 mRNA. Interestingly, PGE2 alone drastically induced IL-10 mRNA. Besides, activation of monocytes by LPS resulted in a remarkable accumulation of IL-10 mRNA, and PGE2 further enhanced this expression. These results indicate that TNF-alpha and PGE2 are key molecules for the induction of IL-10 in monocytes, and that IL-10, in turn, plays a crucial role in terminating the inflammatory cascade via downregulation of production of proinflammatory molecules including TNF-alpha and PGE2.

Cells, Cultured↗
PubMed1998

Isolated partial growth hormone deficient short stature with syringomyelia not associated with birth injury.

A 59-year-old female with 20-year history of slowly progressing muscle atrophy and sensory disturbance of upper extremities showed short stature, scoliosis, hunger type of sensory dissociation of the upper extremities and pyramidal tract sign of the lower extremities. Magnetic resonance imaging (MRI) clarified hypoplasia of the anterior pituitary lobe, Arnold-Chiari malformation and cervical syringomyelia. Insulin and arginine stimulating tests revealed partial type of isolated growth hormone (GH) deficiency but GH gene analysis detected no defects of GH genes. It was considered to be a rare case of non-hereditary hypopituitarism with Chiari malformation and syringomyelia not associated with perinatal injury, namely a midline anomaly syndrome.

Arnold-Chiari Malformation↗