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N Takeda

Publications and source records attributed to N Takeda.

At least 163 records · Page 9Linked to original sources
PubMed1999

Pharmacological treatments for GH-induced insulin resistance.

Troglitazone (T) and d-chiroinositol (DCI) have been reported to improve insulin resistance associated with obesity and NIDDM. We tested whether these compounds counteract the insulin antagonistic effects of recombinant human GH. Male Wistar rats were allocated to 4 different treatment groups, rhGH (n=8), rhGH+T (n=7), rhGH+DCI (n=8) and control (saline, n=8). rhGH (2 IU/100 g/day) was injected sc twice daily for 2 days. T and DCI were given (20 mg/day) po for 5 days preceding and 2 days along with rhGH. Euglycemic hyperinsulinemic clamp studies were done to assess the hepatic glucose output (HGO) and glucose disappearance rate (GDR). Fasting plasma glucose, insulin, serum FFA and basal HGO were similar in all 4 treatment groups. During the hyperinsulinemic clamp which raised plasma insulin levels to 7.2 +/- 0.4 ng/ml, HGO was suppressed in the control and rhGH+T treated rats but not in the rats treated with rhGH and rhGH+DCI. GDR decreased in the rats which received rhGH (18.1 +/- 5.8 vs 30.3 +/- 5.2 mg/kg/min) compared to the control rats. The rats given either T (24.7 +/- 2.7) or DCI (31.4 +/- 2.7) along with rhGH showed comparable GDR to the control rats. These results indicated that rhGH induced hepatic and peripheral insulin resistance. Troglitazone counteracted the insulin-antagonistic action of rhGH both in the liver and the peripheral tissues. DCI was effective in offsetting peripheral insulin resistance but without any effect on hepatic insulin resistance associated with rhGH treatment.

Animals↗
PubMed1999

A controlled trial of combined therapy for newly diagnosed severe childhood IgA nephropathy. The Japanese Pediatric IgA Nephropathy Treatment Study Group.

The most appropriate treatment for patients with IgA nephropathy is controversial. Treatment with prednisolone, azathioprine, heparin-warfarin, and dipyridamole early in the course of disease may prevent immunologic renal injury in children with severe IgA nephropathy. To determine whether similar results can be obtained with a combination of just heparin-warfarin and dipyridamole, the effects of such treatment were compared to those of treatment with prednisolone, azathioprine, heparin-warfarin, and dipyridamole in 78 children with newly diagnosed IgA nephropathy showing diffuse mesangial proliferation. The patients were randomly assigned to receive either prednisolone, azathioprine, heparin-warfarin, and dipyridamole for 2 yr (group 1) or heparin-warfarin and dipyridamole for 2 yr (group 2). All of the 40 patients in group 1 and 34 of the 38 patients in group 2 completed the trial. The mean urinary protein excretion fell in group 1 patients (P < 0.0001), but remained unchanged in group 2 patients. The mean serum IgA concentration was reduced in group 1 patients (P = 0.0002), but was unchanged in group 2 patients. BP and creatinine clearance were normal at the end of the trial in all but one group 2 patient, who developed chronic renal insufficiency. The percentage of glomeruli showing sclerosis was unchanged in group 1 patients, but increased in group 2 patients (P = 0.006). The intensity of mesangial IgA deposits decreased in group 1 patients (P = 0.02), but remained unchanged in group 2 patients. In conclusion, the present study shows that treatment of children with severe IgA nephropathy with prednisolone, azathioprine, heparin-warfarin, and dipyridamole for 2 yr early in the course of disease reduces immunologic renal injury and prevents increase of sclerosed glomeruli.

Adolescent↗
PubMed1999

[A young male of systemic lupus erythematosus with hepatic lesions showing multiple low density spots in CT of liver].

A 19-year-old man was admitted to our hospital due to low grade fever and polyarthralgia with history of photosensitivity. Laboratory findings showed the elevated transaminases, leukocytopenia and thrombocytopenia. Examinations in regard to autoimmune diseases revealed the positive antinuclear antibody and positive LE test. The computed tomography (CT) showed the multiple low density spots in liver. CT guided liver biopsy specimens regarding to these low density spots showed the hepatic lesions with mild inflammatory cell infiltration and subtle piecemeal necrosis. The patient was diagnosed as systemic lupus erythematosus (SLE) with hepatic lesions based on the clinical symptoms and the laboratory data. Rheumatoid arthritis was excluded because of intact joints X-ray findings. Autoimmune hepatitis was also denied because of the fulfillment of definite diagnostic criteria of SLE and minimal histological changes of liver. Prednisolone therapy improved his clinical manifestations and normalized both the laboratory data of liver function and the immunological abnormalities in SLE, so the multiple spots in CT of liver also disappeared.

Adult↗
PubMed1999

Hot flushes and other menopausal symptoms in relation to soy product intake in Japanese women.

OBJECTIVE: To examine the relationships between dietary intake of soy products and hot flushes and other menopausal symptoms. METHODS: Subjects were 284 women aged 40-59 years who attended a health check-up program provided by a general hospital in Gifu, Japan. They completed a health questionnaire including the Kupperman test of menopausal distress. Diet was assessed by a semiquantitative food frequency questionnaire. RESULTS: Fermented soy product intake but not total soy product intake was significantly negatively correlated with hot flush severity (r = -0.16, p = 0.01) after controlling for age and menopausal status. Neither total soy product intake nor fermented soy product intake was significantly correlated with menopausal index score. Estimated isoflavone intake from total and fermented soy products was significantly lower by 15% (p = 0.02) and 19% (p = 0.01), respectively, in women with hot flushes, compared to those without hot flushes after controlling for covariates. CONCLUSION: The data support a hypothesis that intake of fermented soy products alleviates the severity of hot flushes.

Adult↗
PubMed1999

Evidence for the role of oxidative stress in acute ischemic heart disease: a brief review.

BACKGROUND: Although contractile performance of the acutely damaged ischemic heart is invariably depressed on reperfusion (myocardial stunning), the mechanisms of cardiac dysfunction in stunned myocardium are poorly understood. OBJECTIVES: To review briefly the current state of knowledge and to provide further experimental evidence of whether oxidative stress plays a crucial role in cardiac dysfunction and membrane abnormalities due to ischemia-reperfusion. MATERIALS AND METHODS: Isolated rat hearts perfused in the absence or presence of superoxide dismutase (SOD) plus catalase, a well known oxyradical scavenger system, were subjected to 30 mins of global ischemia and 60 mins of reperfusion. Cardiac performance, hydrogen peroxide and calcium contents, lipid peroxidation and membrane activities associated with calcium transport were measured in the control, ischemic and ischemic- reperfused hearts. RESULTS: Cardiac dysfunction, as reflected by depressed left ventricular developed pressure, +dP/dt and -dP/dt as well as elevated left ventricular end-diastolic pressure, in the ischemic-reperfused heart was associated with increased hydrogen peroxide, calcium and malondialdehyde contents as well as increased formation of conjugated dienes. These changes due to ischemia-reperfusion were attenuated in hearts treated with SOD plus catalase. Both ischemia and ischemic-reperfused hearts showed depressions in sarcolemmal Na+/K+-ATPase and sodium-calcium exchange, as well as sarcoplasmic reticular calcium uptake and calcium release activities; these membrane abnormalities were also partially prevented by the presence of SOD plus catalase. CONCLUSIONS: Oxidative stress due to the formation of hydrogen peroxide leading to lipid peroxidation and sulfhydryl group oxidation during ischemia-reperfusion seems to be one of the mechanisms that may produce membrane defects and result in intracellular calcium overload and cardiac contractile dysfunction in the stunned myocardium.

Animals↗
PubMed1999

[Progress in the treatment of colorectal cancer].

The chemotherapeutic management of advanced colorectal cancer has been a challenge to oncologists for the last 30 years, with 5-fluorouracil (5-FU) being used as the core drug. However, its effectiveness is far from satisfactory, and there has been no evidence of improved survival. Recently, a method of biochemical modulation was used to enhance the effect of 5-FU. In colorectal cancer patients with recurrent or metastatic sites, survival was significantly prolonged for a group receiving LV.5-FU therapy, based on biochemical modulation, compared with a group receiving no chemotherapy (best supportive care). Still more, LV.5-FU therapy was proved to be beneficial for survival when it was used as a postoperative adjuvant. In this way, the most recent chemotherapy for colorectal cancer was proved to be effective.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Inhibition of serotonin-induced vascular smooth muscle cell proliferation by sarpogrelate.

Antiproliferative behavior of sarpogrelate (Anplag, MCI-9042, (+/-)-1-[2-[2-(3-methoxyphenyl)ethyl]phenoxy]-3-(dimethylamino)-2-pro pyl hydrogen succinate hydrochloride), a serotonin 2A (5-HT2A) receptor antagonist, was established using radioactive incorporation of [(3)H]thymidine, [(3)H]uridine, and [(3)H]phenylalanine in cultured rat aortic smooth muscle cells in response to a 5-HT-induced cytokine trigger. Fluorescence-activated cell sorting was used to confirm these observations. 5-HT-induced DNA, RNA, and protein synthesis were inhibited maximally at a concentration of 1 microM sarpogrelate. Although other cytokines such as platelet-derived growth factor and endothelin also induced DNA, RNA, and protein synthesis in rat aortic smooth muscle cells, cell proliferation was not influenced by sarpogrelate, even at large pharmacological concentrations (10 microM). Sarpogrelate's antiproliferative actions were found to be more potent than ketanserin. These data indicate that sarpogrelate operates as a specific inhibitor of 5-HT-mediated cell proliferation and is a good candidate for preventing serotonin-induced neointimal hyperplasia.

Animals↗
PubMed1999

[Cotinine].

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Cotinine↗
PubMed1999

Image and DNA analysis of hypertrophic myocytes in hypertensive heart disease and hypertrophic cardiomyopathy.

OBJECTIVE: To investigate differences in the pathophysiology of cardiac hypertrophy between patients with hypertensive heart disease (HHD) and hypertrophic cardiomyopathy (HCM). STUDY DESIGN: The study group consisted of 30 autopsied heart disease patients (10 HHD, 10 HCM and 10 noncardiac heart disease). DNA synthesis by hypertrophic cardiac myocytes was examined, and three-dimensional myocyte structure image was investigated. DNA synthesis and the cell cycle were investigated by flow cytometry using autopsy material. Three-dimensional myocyte structure image was visualized. RESULTS: The percentage of cells in G2M phase of the cell cycle was significantly decreased in the myocardium of autopsied hearts with HCM as compared with hearts with HHD (HCM:HHD = 1.2 +/- 1.1%: 7.7 +/- 2.6%, mean +/- SD). Hypertrophic myocytes of HCM characteristically possessed myocardial disarray and irregular side-to-side branch connections between myocytes. No myocyte disarray or irregular connections could be observed in HHD. CONCLUSION: These results suggest that the mechanism of cardiac hypertrophy differs between patients with HHD and HCM and also suggest dissimilar cell vitality and latent proliferative viability of hypertrophic myocytes in a hypertrophic process between HHD and HCM. That is, hypertrophic myocytes may be called "restricted" myocytes in a morphologic and biochemical sense.

Aged↗
PubMed1999

[The significance of color duplex ultrasonography for the diagnosis of temporal arteritis].

We examined the usefulness of color duplex ultrasonography in patients suspected of having temporal arteritis. Five patients, who were all aged 70 or older, developed a new onset of localized headache with temporal artery abnormalities, and had an elevated erythrocyte sedimentation rate of > 100 mm/hour. The final diagnoses were temporal arteritis in three patients, polymyalgia rheumatica in one, and probable healed temporal arteritis in one. Color duplex ultrasonography showed stenoses, which were confirmed histologically as well, in the superficial temporal artery of all patients. The characteristic findings of active temporal arteritis were, however, demonstrated in only three biopsy specimens, and in the remaining two the stenoses were thought to be related to previous arteritis. The hypoechoic halo, which has been reported to be a characteristic finding of color duplex ultrasonography in active temporal arteritis, was detected in only one patient with active temporal arteritis and another one with probable healed temporal arteritis. No stenoses were demonstrated in the superficial temporal arteries of 30 control subjects (20 with at least one risk factor of atherosclerosis and 10 without it). Color duplex ultrasonography can therefore be considered a powerful method for detecting stenoses in the superficial temporal artery. Its ability to identify their etiology is, however, unsatisfactory, so that temporal artery biopsy remains undoubtedly the most reliable test for etiological evaluation. We thus recommend color duplex ultrasonography as a supplementary method for the diagnosis of temporal arteritis, because it can provide useful information concerning the appropriate site of temporal artery biopsy.

Aged↗
PubMed1998

Pressure-denatured state of Escherichia coli ribonuclease HI as monitored by Fourier transform infrared and NMR spectroscopy.

Pressure denaturation of Escherichia coli ribonuclease HI (RNase HI) was studied by Fourier transform infrared (FTIR) and two-dimensional NMR spectroscopy at pD* 3.0 and 25 degrees C. A reversible transition in the pressure range of 0.1-1090 MPa was observed with second-derivative FTIR experiments. A cooperative and gradual denaturation, involving both the secondary and tertiary structures, was observed between 240 and 450 MPa. The two peaks at 1629 and 1652 cm(-1), due to beta-strands and alpha-helices, respectively, did not fully disappear after the denaturation, and are different from the spectra of the random coil peptides. The hydrogen-deuterium exchange rates of the individual backbone amide protons were determined by heteronuclear NMR combined with the pressure-jump technique at 500, 650, and 850 MPa. Although most of the amides protected in the native structure are also highly protected in the pressure-denatured state, the rate constants (0.048 +/- 0.007 min(-1)) for the amide protons at 500 MPa are similar regardless of their locations, which is an indication of the EX1 mechanism of hydrogen-deuterium exchange. The pressure-denatured state of RNase HI at 500 MPa represents a novel denatured state, which is different from a typical molten globule state at atmospheric pressure (0.1 MPa), from the viewpoint of the homogeneous rate constants. The observations at 650 MPa are essentially the same as those at 500 MPa. However, at 850 MPa, the amide exchange rates for the highly hydrophobic C-terminal half of alpha-helix I are significantly slower than those for the other part of the protein, which can be interpreted as a hydrophobic collapse centered at the C-terminal half of alpha-helix I.

Amides↗
PubMed1998

Obesity and mild hyperinsulinemia found in neuropeptide Y-Y1 receptor-deficient mice.

To elucidate the role of neuropeptide Y (NPY)-Y1 receptor (Y1-R) in food intake, energy expenditure, and other possible functions, we have generated Y1-R-deficient mice (Y1-R-/-) by gene targeting. Contrary to our hypothesis that the lack of NPY signaling via Y1-R would result in impaired feeding and weight loss, Y1-R-/- mice showed a moderate obesity and mild hyperinsulinemia without hyperphagia. Although there was some variation between males and females, typical characteristics of Y1-R-/- mice include: greater body weight (females more than males), an increase in the weight of white adipose tissue (WAT) (approximately 4-fold in females), an elevated basal level of plasma insulin (approximately 2-fold), impaired insulin secretion in response to glucose administration, and a significant changes in mitochondrial uncoupling protein (UCP) gene expression (up-regulation of UCP1 in brown adipose tissue and down-regulation of UCP2 in WAT). These results suggest either that the Y1-R in the hypothalamus is not a key molecule in the leptin/NPY pathway, which controls feeding behavior, or that its deficiency is compensated by other receptors, such as NPY-Y5 receptor. We believe that the mild obesity found in Y1-R-/- mice (especially females) was caused by the impaired control of insulin secretion and/or low energy expenditure, including the lowered expression of UCP2 in WAT. This model will be useful for studying the mechanism of mild obesity and abnormal insulin metabolism in noninsulin-dependent diabetes mellitus.

Animals↗
PubMed1998

Unilateral labyrinthectomy downregulates glutamate receptor delta-2 expression in the rat vestibulocerebellum.

The differential display method was applied to identify genes expression of which is altered in the flocculus after unilateral labyrinthectomy (UL). Total RNA from sham operated and labyrinthectomized rat flocculi was isolated, amplified by PCR using an arbitrary primer set and separated by electrophoresis on a polyacrylamide gel. PCR products the amounts of which were significantly lower in samples from labyrinthectomized animals than those from controls, were cut out of the gel and sequenced. One of the cDNA fragments showed 100% nucleotide sequence identity to the rat glutamate receptor (GluR) delta-2 subunit mRNA. In situ hybridization autoradiography showed that GluR delta-2 mRNA expression was intensely located to the floccular Purkinje cell layers. Furthermore, northern blot analysis showed that the delta-2 mRNA expression was decreased for at least two days after UL in accordance with diminishing UL-induced behavioral deficits. Therefore, it is suggested that the downregulation of delta-2 mRNA is involved in vestibular compensation. UL-induced spontaneous nystagmus (SN) was then examined in GluR delta-2 mutant mice. The frequency of SN in mutant mice was significantly more than that in wild mice until 12 h after UL. GluR delta-2-associated synaptic efficacy may be changed for the induction of vestibular compensation at the initial stage.

Animals↗
PubMed1998

Pathologic features of spinal disorders in patients treated with long-term hemodialysis.

STUDY DESIGN: Pathologic features of hemodialysis-associated spinal disorders were evaluated using preoperative radiographic images and histologic findings of the spinal lesions resected during surgery. OBJECTIVES: To investigate the pathology of hemodialysis-related spinal disorders and to determine the role of amyloidosis in the establishment of severe destruction of the spine. SUMMARY OF BACKGROUND DATA: The pathologic events leading to hemodialysis-associated spinal disorders are poorly understood. The distribution of amyloid deposits in the spine also has not been clarified. METHODS: Twenty patients with hemodialysis-associated spinal disorders were investigated regarding pathologic features of neural compression and spinal destruction. Preoperative radiographic images such as plain radiography, tomography, computed tomography, magnetic resonance imaging, and scintigraphy were assessed for the existence of an intracanal mass, hypertrophy of the ligamentum flavum, and destructive changes of the spinal components. Histologic examination also was conducted by light microscopy and scanning electron microscopy to determine the distribution pattern of amyloid deposits in the spinal components. RESULTS: Six patients with no destructive changes in the spine showed spinal canal stenosis. In the cervical spine, a main factor associated with spinal canal stenosis was the presence of intracanal amyloid deposits in three patients. In the lumbar spine, a main factor associated with spinal canal stenosis was hypertrophied ligamentum flavum in three patients. Destructive changes of the facet joints, intervertebral disc, and vertebral body were seen in the other 14 patients. Amyloid deposits were densely distributed at the enthesis of capsular fibers to the bone and in anular tears in the intervertebral discs. Vertebral end plates were destroyed by penetration of amyloid granulation into the vertebral body. Osteoclast activity in the destroyed vertebral bodies was enhanced, with no evidence of new bone formation. CONCLUSIONS: Amyloid deposits played an important role in the progression of spinal destruction and severe instability.

Adult↗
PubMed1998

Auditory evoked off-response: its source distribution is different from that of on-response.

Offset auditory responses were investigated by electroencephalography mainly in the 1970s, but since then no particular attention has been paid to them. Among the studies using magnetoencephalography (MEG) devices there are, to our knowledge, only three studies of the auditory off-response, and no significant variance has ever been observed between the source locations of on- and off-responses elicited from pure tones. We measured auditory evoked magnetic fields (AEFs) to various frequency pure tone stimulation in 5 healthy subjects with a 122-channel helmet-shaped magnetometer, and compared the distributions of the source locations of auditory N100m-Off (magnetic off-response around 100 ms) with those of N100m-On. Their spatial distributions were quite close to each other, and yet they were significantly different.

Acoustic Stimulation↗