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T Ishihara

Publications and source records attributed to T Ishihara.

At least 181 records · Page 10Linked to original sources
PubMed1998

Pharmacophore identification of a chemokine receptor (CXCR4) antagonist, T22 ([Tyr(5,12),Lys7]-polyphemusin II), which specifically blocks T cell-line-tropic HIV-1 infection.

We have previously found that T22 ([Tyr(5,12), Lys7]-polyphemusin II) has strong anti-human immunodeficiency virus (HIV) activity, and that T22 inhibits T cell-line-tropic HIV-1 infection mediated by CXCR4/fusin. T22 is an 18-residue peptide amide, which takes an antiparallel beta-sheet structure that is maintained by two disulfide bridges. Structure-activity relationship (SAR) studies on T22 have disclosed the contributions of each region of T22 to activity or cytotoxicity, and have provided the following useful information to develop new CXCR4 antagonists: The number of Arg residues in the N-terminal and C-terminal regions of T22 is closely related to anti-HIV activity. Addition of a variety of functional groups at the N-terminal end results in increases in activity. Disulfide rings, especially the major disulfide loop, are indispensable for anti-HIV activity and maintenance of the beta-sheet structure. Trp3 can be replaced by other aromatic residues (Tyr, Phe and L-2-naphthylalanine). Between two repeats of Tyr-Arg-Lys, which are a characteristic structure in T22, Tyr-Arg-Lys in the N-terminal portion is more closely associated with anti-HIV activity and maintenance of the beta-sheet structure. A positive charge in the side chain at the (i + 1) position of the beta-turn region is necessary for strong activity. Through these studies, we have found several compounds having higher selectivity indexes (50% cytotoxic concentration/50% effective concentration) than that of T22.

Amino Acid Sequence↗
PubMed1998

Actions of novel antidiabetic thiazolidinedione, T-174, in animal models of non-insulin-dependent diabetes mellitus (NIDDM) and in cultured muscle cells.

1. The antihyperglycaemic effect and the possible mechanism of action of T-174, a novel thiazolidinedione derivative, was determined in vivo and in vitro. 2. Oral administration of T-174 markedly improved hyperglycaemia, hyperinsulinaemia, hyperlipidaemia, and glucose intolerance in genetically obese and diabetic yellow KK (KK-Ay) mice (0.2-15.5 mg kg(-1) day(-1), for 7 days) and Zucker fatty rats (1.4-11.4 mg kg(-1) day(-1), for 6 days). The ED50 values for the glucose lowering action of T-174 and pioglitazone, another thiazolidinedione antidiabetic, were 1.8 and 29 mg kg(-1) day(-1), respectively in KK-Ay mice; T-174 was about 16 times more potent than pioglitazone. 3. The hypoglycaemic effect of exogenous insulin in KK-Ay mice was enhanced after the administration of T-174. A hyperinsulinaemic euglycaemic clamp study in Zucker fatty rats showed an amelioration of whole-body insulin resistance by the T-174 treatment. 4. Insulin-stimulated glucose metabolism was enhanced in adipocytes from KK-Ay mice treated with T-174. The insulin receptor number of the adipocytes was increased without a change in the affinity of the receptor. 5. The hypomagnesaemia in KK-Ay mice was completely restored by T-174. 6. In cultured L6 myotubes, glucose consumption and [3H]-2-deoxy-glucose transport were enhanced by T-174 (EC50; 6 and 4 microM, respectively). Combination of insulin with T-174 was additive to stimulate glucose disposal. 7. These results suggest that the antihyperglycaemic effect of T-174 was mediated by enhanced insulin action. This was associated with amelioration of the hypomagnesaemia and T-174 directly increased basal and insulin-stimulated glucose utilization by cultured muscle cells.

Animals↗
PubMed1998

Apolipoprotein E is present in primary localized cutaneous amyloidosis.

Apolipoprotein E (apoE) is one of the amyloid associated proteins that is found in the amyloid plaque of Alzheimer's disease and systemic amyloidosis. ApoE might play an important part in the etiology of Alzheimer's disease by functioning as a "pathologic chaperone" to promote the formation of amyloid filaments. In this study, we investigated whether apoE is associated with amyloid deposits of primary localized cutaneous amyloidosis using immunohistochemistry, immunogold electron microscopy, and immunoblotting. The subjects consisted of 12 patients with lichen amyloidosus and one patient with macular amyloidosis. Light microscopically, amyloid deposits in the dermal papillae were round in shape and stained with Congo red. Immunohistochemically, apoE was detected in amyloid deposits in all the cases examined. Immunogold electron microscopy showed apoE immunoreactivity on the amyloid deposition. Immunoblots of amyloid-positive skin showed 35K and 14K proteins, which were taken to be apoE and its fragment, respectively. In normal skin extract, only the 35K protein was detected by the anti-human apoE. Moreover, the intensity of the amyloid-positive skin sample was stronger than that of the normal skin sample. Monoclonal anti-cytokeratin antibody reacted with the 45K protein of the amyloid-positive skin extract. These results indicate that apoE is a component of primary localized cutaneous amyloidosis, and that it might play an important role in primary localized cutaneous amyloidosis.

Adult↗
PubMed1998

Nine-year follow-up study of heart rate variability in patients with Duchenne-type progressive muscular dystrophy.

OBJECTIVES: The purpose of this study was to investigate the progression of autonomic dysfunction in patients with Duchenne-type progressive muscular dystrophy (DMD) over time by using heart rate variability. BACKGROUND: Although previous studies suggest the presence of autonomic dysfunction in patients with DMD, the precise cause is not known. On the other hand, it is well known that analysis of heart rate variability provides a useful, noninvasive means of quantifying autonomic activity. High frequency power is determined predominantly by the parasympathetic nervous system, whereas low frequency power is determined by both the parasympathetic and sympathetic nervous systems. METHODS AND RESULTS: Frequency and time domain analyses of heart rate variability during ambulatory electrocardiographic monitoring were performed in 17 patients with DMD over a 9-year period. At the time of entry, the mean patient age was 11 years and the mean Swinyard-Deaver stage was 4. In the first year, high frequency power was significantly lower and the ratio of low frequency to high frequency was significantly higher in patients with DMD than in the normal control subjects. These differences become significantly greater as the disease progressed. At the time of entry, low and high frequency powers increased at night in both groups. However, over time, high and low frequency powers at night tended to decrease. All of the time domain parameters were significantly lower in the patients with DMD at all time points compared with the normal control subjects. CONCLUSIONS: We concluded that DMD patients have either a decrease in parasympathetic activity, an increase in sympathetic activity, or both as their disease progresses.

Adolescent↗
PubMed1998

Multihormone-producing islet cell tumor of the pancreas associated with somatostatin-immunoreactive amyloid: immunohistochemical and immunoelectron microscopic studies.

Pancreatic islet cell tumors, especially insulinomas, are often associated with amyloid deposition in the tumor tissue. Biochemical analysis has demonstrated that the amyloid protein from insulinoma is derived from islet amyloid polypeptide (or amylin) that is produced by tumor cells originating from beta cells of the islet of Langerhans. We examined a case of malignant pancreatic islet cell tumor with amyloid deposition in the tumor tissue using immunohistochemistry and double-labeling immunogold electron microscopy. The tumors were composed of cells producing multiple hormones, including somatostatin, gastrin, amylin, insulin, calcitonin gene-related polypeptide, and calcitonin. Amyloid deposits reacted with antisomatostatin antiserum but not with other antisera, including antiamylin. The present study demonstrated for the first time that amyloid associated with islet cell tumors is not always derived from amylin and can come from somatostatin.

Aged↗
PubMed1998

Immunohistochemical study of transforming growth factor-beta 1, matrix metalloproteinase-2,9, tissue inhibitors of metalloproteinase-1,2, and basement membrane components at pancreatic ducts in chronic pancreatitis.

Little is known about the pathogenesis of fibrosis in chronic pancreatitis. To reach a better understanding of this problem, we investigated the immunolocalizations of type IV collagen (Col-IV) and laminin around pancreatic ducts, and those of matrix metalloproteinase-2,9 (MMP-2,9), tissue inhibitors of metalloproteinase-1,2), and transforming growth factor-beta 1 (TGF beta 1) at the ductal epithelia in chronic pancreatitis. This study included 20 surgical specimens of fibrotic pancreas from patients with chronic pancreatitis and five normal samples from autopsy cases. Immunostaining was performed by the streptavidin-biotin method after antigen retrieval. We evaluated the staining patterns and the percentage of positive cells of each antigen. In chronic pancreatitis, the immunostainings of Col-IV and laminin along the basement membrane (BM) of pancreatic ducts were disrupted in 11 (55%) of 20 and eight (40%) of 20, respectively, whereas no disruption was detected in normal pancreas. Positive immunostainings for MMP-2, MMP-9, TIMP-1, and TIMF-2 in ductal epithelia were 15 (75%) of 20, five (25%) of 20, four (20%) of 20, and 10 (50%) of 20, respectively, whereas no immunostaining was seen in normal pancreas. The staining intensity of MMP-2 in ductal epithelia was associated with the staining intensity of Col-IV around the pancreatic ducts. Also, the staining intensity of MMP-2 was progressively increased in proportion to the staining intensity of TGF beta 1. These findings suggest that TGF beta 1 induced in pancreatic duct cells also induced MMP-2 in an autocrine or paracrine manner, and that this MMP-2 decomposed Col-IV of the BM of pancreatic ducts in chronic pancreatitis.

Adult↗
PubMed1998

Preliminary study of percutaneous alcohol injection into the lung.

Although percutaneous ethanol injection is widely used to treat hepatic tumors, this technique has not been applied to lung tumors. We performed a preliminary experiment with percutaneous ethanol injection into the rabbit lung, and evaluated the local and systemic effects of absolute ethanol injection on pulmonary structures in order to assess the feasibility and safety of this technique as a local treatment for human lung tumors. Percutaneous injection of absolute ethanol into the rabbit lung was performed under CT guidance. The volume of ethanol injected ranged from 0.6 to 1.0 ml (approximately 0.2-0.5 ml/kg). Follow-up CT scans were performed 1, 2, 7 and 30 days after the injection. The animals were killed at intervals (range: 3 h-30 days), and the lung was examined histologically. The ethanol was well tolerated and did not induce significant systemic side-effects. All doses induced necrosis in the injected lung, but none was lethal. Although ethanol spilling into the thoracic cavity induced effusion and pleuritis, these reactions were manageable. Alcohol injection produced an area of necrosis surrounded by pulmonary edema associated with polymorphonuclear cells invasion within 24 h; moreover, granulation change, epithelial regeneration, and alveolar septal fibrosis had appeared by one week. The necrosis was sometimes multifocal, probably due to transbronchial spread of the injected ethanol. In conclusion, the feasibility and safety of absolute ethanol injection were confirmed. Neither severe systemic side effects nor lethal extensive necrosis were observed with injected ethanol; however, an unexpected side effect, multifocal necrosis, was seen. The latter reaction suggests that careful observation and care would be essential after alcohol injection into the lung.

Administration, Cutaneous↗
PubMed1998

Confocal observation of senile plaques in Alzheimer's disease: senile plaque morphology and relationship between senile plaques and astrocytes.

Senile plaques in the brains of Alzheimer's disease (AD) were examined by confocal laser scanning microscopy (CLSM) with the following three findings. First, in sections stained with Congo red, the serial CLSM images of optical sections clearly revealed that a classic plaque is composed of a plaque core and a corona. Radially arranged process-like structures, corresponding to bundles of amyloid fibrils, formed amyloid cores and stronger signals were detected in the center of some cores. Second, in sections stained with Congo red and anti-glial fibrillary acidic protein (GFAP), reactive astrocytes were found around the senile plaques and many astrocytic processes surrounded the plaque cores and some processes had penetrated into them. Third, three-dimensional reconstruction on classic plaque revealed that the surface of classic plaque showed a 'coral-like' appearance.

Aged↗
PubMed1998

An immunohistochemical study of amyloid P component, apolipoprotein E and ubiquitin in human and murine amyloidoses.

Amyloid P component (AP) and apolipoprotein E (Apo E), which are known to be minor constituents of amyloid deposits, commonly are associated with almost all types of amyloid deposits. In this study, the distribution of AP-, Apo E- and ubiquitin (Ub)-immunoreactivity (IR) in amyloid deposits in the liver and spleen of human systemic amyloidosis (34 autopsy cases: 17 immunoglobulin light chain derived, 17 amyloid A protein derived) and experimental murine amyloidosis is examined using an immuno-histochemical technique. In human cases, all of the amyloid deposits examined showed colocalization of AP- and Apo E-IR with individual amyloid proteins. In experimental amyloidosis, AP-IR of amyloid deposits in the liver and spleen and Apo E-IR in the liver were seen uniformly throughout this experiment. In contrast, Apo E-IR in the spleen was not uniform at the phase of amyloid deposition. At 4 weeks and at 16 weeks after casein injection, Apo E-IR was unevenly distributed in amyloid deposits in the perifollicular area; however, from 6 to 12 weeks it was seen to be uniform. Ubiquitin-IR of amyloid deposits in human cases was seen in 22 of 34 livers and in 22 of 33 spleens. In experimental amyloidosis, Ub-IR of amyloid deposits was demonstrated in the space of Disse in all mice examined, and there appeared to be a gradual increase in intensity with the amount of amyloid deposition. However, in the spleen, amyloid deposits did not react with anti-Ub antibody in any phase of amyloid induction. These results suggest that Apo E and Ub are not always associated with the process of amyloid deposition and may appear in a deposit after the deposition.

Adult↗
PubMed1998

Activation of peripheral blood monocytes and macrophages in Kawasaki disease: ultrastructural and immunocytochemical investigation.

Monocytes/macrophages are considered to play an important role in the pathogenesis of Kawasaki disease (KD). However, the morphological and immunocytochemical features of the cells in acute KD have not been investigated. The ultrastructural and immunocytochemical characteristics of peripheral blood CD14+ monocytes/macrophages sorted by a magnetic cell sorter (MACS) during the course of KD were, therefore, studied to evaluate their role in the disease pathogenesis. Electron microscopy showed that CD14+ monocytes/macrophages from patients with acute KD had nuclei with complex shapes, apparent nucleoli and abundant intracytoplasmic granules, some of which were positive for acid phosphatase. The quantity of intracytoplasmic granules was correlated with disease severity, in terms of the duration of fever, maximum level of C-reactive protein and the presence of coronary artery lesions (CAL), suggesting that the monocytes/macrophages were activated and showed increased phagocytosis. Immunocytochemical staining of smears made from cell suspensions of sorted CD14+ monocytes/macrophages was carried out using a monoclonal antibody against tumor necrosis factor (TNF)-alpha. The cytoplasm of monocytes/macrophages from patients with acute KD was strongly positive in comparison to that of cells from control subjects, suggesting that intracytoplasmic granules secrete TNF-alpha.

Acid Phosphatase↗
PubMed1998

Prevalence of ventricular preexcitation in Japanese schoolchildren.

BACKGROUND: Wolff-Parkinson-White syndrome is thought to be a congenital disease, however, its exact prevalence is not known. This may be because of the intermittent activity of accessory pathways in some cases and fluctuations in autonomic tone. AIMS: To investigate the prevalence of ventricular preexcitation by electrocardiography and reported symptoms in each school age child in Yamanashi prefecture. METHODS: From 1994 to 1996, answers to a questionnaire, results of physical examination, and electrocardiography were obtained from all schoolchildren in Yamanashi prefecture (n = 92,161; total population 880,000) on admission to elementary school (age 6 to 7 years, n = 28,395), junior high school (age 12 to 13 years, n = 31,206), and high school (age 14 to 15 years, n = 32,837). RESULTS: Elementary and junior high school students had a significantly lower prevalence of preexcitation than high school students (0.073% and 0.070% v 0.174%, p < 0.001). The prevalence of left free wall pathway was highest in high school students (n = 27) compared with elementary (n = 6) and junior high school students (n = 5) (p < 0.005). The only symptom noted in the answers to the questionnaire was palpitations. The symptomatic cases were more frequent in high school (n = 13) than in elementary (n = 1) and junior high school (n = 2) children, but not significantly. No student with preexcitation had associated heart disease or family history of Wolff-Parkinson-White syndrome or sudden death. CONCLUSIONS: The prevalence of preexcitation in younger schoolchildren was less frequent than previously reported. The prevalence of preexcitation and left free wall pathways increased with age. The symptoms were few and there was no significant morbidity.

Adolescent↗
PubMed1998

Hypercalcemia in a patient with malignant melanoma arising in congenital giant pigmented nevus. A case of increased serum level of parathyroid hormone-related protein.

We describe a 43-year-old Japanese female who developed hypercalcemia associated with malignant melanoma. The patient underwent three resections of tumors on her groin and buttock secondary to a bathing trunk congenital nevus, and the histopathological findings showed benign congenital nevi. At the age of 42 years, she developed a malignant melanoma under the giant pigmented nevus in her groin. Fourteen months after the diagnosis of melanoma, she developed metastases to the lung, para-aortic lymph nodes and bones accompanied by hypercalcemia resulting from a remarkable increase in the serum level of parathyroid hormone-related protein (PTHrP). The patient died from acute renal and respiratory failure. In addition, we analyzed serum levels of calcium and PTHrP in 19 patients with advanced malignant melanoma. Seven patients had hypercalcemia, and 3 had increased serum levels of PTHrP.

Adult↗
PubMed1998

Dipyridamole thallium-201 single-photon emission computed tomography for prediction of perioperative cardiac events in patients with arteriosclerosis obliterans undergoing vascular surgery.

The aim of the study was to determine whether or not dipyridamole thallium-201 single-photon emission computed tomography (201Tl-SPECT) has significant additive value for predicting perioperative cardiac events in patients with arteriosclerosis obliterans (ASO) undergoing vascular surgery. Routine preoperative 201Tl-SPECT was performed in 106 consecutive patients with ASO (age 68+/-8.9 years; 91 men and 15 women). The frequency of reversible defects in a clinical high-risk group (n=44) was significantly higher than in a low-risk group (n=62; 55% vs 24%, p<0.01). Perioperative cardiac events occurred in 9 patients, including 4 cardiac deaths, 1 non-fatal myocardial infarction, and 4 cases of unstable angina. Although clinical risk stratification was useful in predicting cardiac events (19% in the high-risk group vs 2% in the low-risk group, p<0.01), the positive predictive value was low. When considering a combination of 2 or more than 2 risk factors and a large reversible defect as a predictor, the positive predictive value and specificity increased from 19% to 47% and from 64% to 91%, respectively, whereas the sensitivity remained unchanged (89%). These results suggest that the addition of 201Tl-SPECT data to clinical risk-stratified patients with ASO allows better prediction of perioperative cardiac events.

Adult↗
PubMed1998

Exercise-induced monomorphic ventricular tachycardia from the left ventricle outflow tract.

A case of exercise-induced idiopathic ventricular tachycardia (VT) arose from the left ventricular outflow tract. The QRS morphology of the VT was Rs pattern in V1 and R pattern in the lateral leads with inferior axis. The pacing at the superior interventricular septum near the mitral anulus produced the best pace mapping. Radiofrequency application to this site suppressed the VT.

Exercise↗
PubMed1998

Thyroxine (T4) metabolism in an athyreotic patient who had taken a large amount of T4 at one time.

As we had an opportunity to take blood samples from a totally thyroidectomized patient who had attempted suicide by taking 2,000 microg of Levothyroxine (L-T4), the serum levels of thyroid hormones were sequentially measured to investigate the metabolism of circulating thyroid hormones in an athyreotic human. The serum concentrations of most thyroid hormones reached a peak on the second day, but the serum T3 level showed a peak one day later. The maximum concentrations of T4 (315 microg/l), FT4 (48.8 ng/l) and rT3 (0.80 microg/l) were very high, while the peak T3 level (1.92 microg/l) did not exceed the upper limit of the normal range. The serum T4 and rT3 levels returned to their normal range 13-17 days after the suicide attempt. The TSH level was suppressed rapidly and reached its nadir (0.044 mU/l) on the 6th day. During this period, the T1/2 and MCR of serum T4 were 10.4 days and 0.64 l/day, respectively, which values were almost equivalent to those observed during 15 days after discontinuation of the maintenance L-T4 therapy. In summary, the oral intake of a large amount of L-T4 at one time does not induce a proportional increase in the T3 level in an athyreotic person. The MCR of serum T4 is decreased and the T1/2 of serum T4 is prolonged, probably due to the lack of intrathyroidal deiodination. These findings support the conclusion that the D1 activity in the thyroid is one of the major determinants in the metabolic clearance of serum T4.

Adult↗
PubMed1998

The interaction between vitamin A and thiazolidinedione on bovine adipocyte differentiation in primary culture.

We studied the effects of a thiazolidinedione (T-174) and retinoids on adipocyte differentiation in beef cattle. Stromal-vascular (SV) cells containing preadipocytes were prepared from perirenal adipose tissue of 21-mo-old Japanese Black steers. After confluence, these cells were cultured in 25 microM T-174, which is a specific ligand for an adipogenesis stimulating nuclear receptor (i.e., gamma subtype of peroxisome proliferator-activated receptor [PPARgamma]), with 1 microM all-trans retinoic acid (RA) or .4 to 40 microg/100 mL of retinol for 10 to 14 d. The number of cells accumulating lipid droplets was counted as morphologically differentiated adipocytes, and the activity of glycerol-3-phosphate dehydrogenase (GPDH), a biochemical index for the differentiation, was determined. The number of lipid-laden cells and GPDH activity were increased by the addition of T-174. All-trans retinoic acid completely blocked the stimulative action of T-174. The addition of retinol also decreased the number of lipid-laden cells and GPDH activity in a dose-dependent manner. These results showed that the thiazolidinedione stimulated adipocyte differentiation and the retinoids blocked the adipogenesis induced by the thiazolidinedione in primary culture of bovine SV cells. Peroxisome proliferator-activated receptor gamma may play an important role in adipocyte differentiation, and retinoids may interfere with the action of PPARgamma in cattle.

Adipocytes↗