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H Hashimoto

Publications and source records attributed to H Hashimoto.

At least 397 records · Page 22Linked to original sources
PubMed1997

A specific loss of growth hormone abolished sex-dependent expression of hepatic cytochrome P450 in dwarf rats: reversal of the profiles by growth hormone-treatment.

A spontaneous dwarf rat derived from a colony of Sprague-Dawley (SD) strain has no detectable level of growth hormone (GH) in pituitary, although it contained other hormones like prolactin and ACTH. Hepatic profile of cytochrome P450 (P450) differed clearly between dwarf and normal SD rats. A male-specific form of P450, CYP2C11, was detected in dwarf male rat livers, while the level was one-third of the normal SD livers. This P450 was also detected in dwarf females. Other male-specific CYP3A2 and CYP3A18 were also contained in both sexes of dwarf rats, whereas a female-specific form, CYP2C12, was not detectable in dwarf females. Phenobarbital-inducible CYP2B1 and CYP2B2 were constitutively expressed in dwarf rats, although substantially absent in normal SD rats. To assess the role of GH on hepatic P450 expression, GH was given to dwarf rats for 7 to 9 days. The intermittent injection (mimicking the male secretory pattern) resulted in the elevation of CYP2C11 to a level as observed in normal SD males. Continuous infusion of GH (mimicking the female secretory pattern) evoked CYP2C12 in livers of both sexes of dwarf rats, whereas the treatment decreased levels of CYP3A2, CYP3A18, and CYP2B1. These results clearly demonstrate that specific defect of GH, but not pituitary, cause the clear changes in hepatic P450 forms including sex-specific forms. The present study provides evidence further to strengthen the principal role of GH on the regulation of expression of P450 in rat livers.

Animals↗
PubMed1997

In vivo direct gene transfer into articular cartilage by intraarticular injection mediated by HVJ (Sendai virus) and liposomes.

OBJECTIVE: To establish a system for efficient, direct in vivo gene transfer into joints. METHODS: A hemagglutinating virus of Japan (HVJ; Sendai virus)-liposome suspension containing SV40 large T antigen (SVT) gene was injected intraarticularly into knee joints of 6-week-old female Lewis rats. Rats were killed at various times for immunohistochemical analysis of the expression of SVT gene. RESULTS: The expression of SVT gene was detected immunohistochemically in chondrocytes in the superficial and middle zones of articular cartilage in the knee joints. The average percentage of SVT-positive cells was estimated to be approximately 30% on days 3, 7, 14, and 21 after transfection. Moreover, no pathologic change caused by HVJ-liposome injection was observed in the joints. CONCLUSION: The transfection frequency and stability of expression recognized in this study indicate the possibility of a strategy for treatment of joint disorders, including arthritis, using direct gene transfer.

Animals↗
PubMed1997

Differential influences of gold sodium thiomalate and bucillamine on the generation of CD14+ monocyte-lineage cells from bone marrow of rheumatoid arthritis patients.

An adequate supply of peripheral blood monocytes, granulocytes, and platelets is necessary for an optimal inflammatory process. We have previously demonstrated that the generation of CD14(+) monocyte-lineage cells from the bone marrow is accelerated in patients with rheumatoid arthritis (RA). The current studies examined the influences of gold sodium thiomalate (GST) and bucillamine (BUC), two potent disease-modifying antirheumatic drugs (DMARDs), on the capacity of bone marrow progenitor cells to generate CD14(+) cells in patients with RA, in order to delineate their mechanisms of action. CD14(-) cells purified from bone marrow specimens of 13 patients with active RA who were not taking DMARDs were cultured in the presence or absence of pharmacologically attainable concentrations of GST (25 microM) or intramolecular disulfide form of bucillamine (BUC-ID, 3 microM), a major metabolite of BUC. After incubation for 14 days, the cells were analyzed by flow cytometry for expression of CD14, HLA-DR, and CD54. The generation of CD14(+) cells from RA bone marrow CD14(-) progenitor cells was significantly suppressed by GST, but not by BUC-ID. The expression of HLA-DR on the bone marrow-derived CD14(+) cells was also significantly inhibited by GST, but not by BUC-ID. Of note, neither GST nor BUC-ID influenced the expression of CD54 on the bone marrow-derived CD14(+) cells, indicating that the expression of HLA-DR and CD54 on the bone marrow-derived CD14(+) cells is regulated by different mechanisms. The results are consistent with the hypothesis that one of the effects of DMARDs may involve the interference with monocyte differentiation in the bone marrow. Moreover, the data emphasize that in contrast with BUC, GST is a potent inhibitor of monopoiesis in RA patients.

Adult↗
PubMed1997

Postoperative delirium easily develops in patients with intramitochondrial inclusion bodies in colonic neurons.

Patients whose colons were resected for carcinoma were studied in order to determine the relationship between clinical findings-which included development of postoperative delirium- and intramitochondrial inclusion bodies (MI) in the neurons in the colon. Twenty-three patients had MI and 24 patients did not. Preoperative dementia was present in 9 (39.1%) of the 23 patients with MI, and in 7 (29.2%) of the 24 without it. Postoperative delirium developed in 13 (56.3%) of the 23 with MI, and in 5 (20.8%) of the 24 without it (p < 0.05). Excluding preoperative dementia, postoperative delirium developed in 5 (35.7%) of the 14 with MI, and in none of the 17 without it. Changes in the neurons in the colon were not related to dementia. The changes may have been related to the functions of the central nervous system, because patients with MI were likely to develop postoperative delirium.

Aged↗
PubMed1997

Maffucci's syndrome associated with spindle cell hemangioendothelioma.

The case of a 49-year-old man with Maffucci's syndrome, who developed multiple spindle cell hemangioendotheliomas, is presented. The case provides support for recent reports suggesting an association between this peculiar vascular lesion and skeletal enchondromatosis.

Angiography, Digital Subtraction↗
PubMed1997

Peripheral primitive neuroectodermal tumour with ganglioneuroma-like areas arising in the cauda equina.

Peripheral primitive neuroectodermal tumour (pPNET or peripheral neuroepithelioma) is one of the malignant small round cell tumours of peripheral nerves, soft tissues and bones, but rarely originates in the spinal canal. We report an example of pPNET arising in the cauda equina of a 14-year-old Japanese boy. At surgery, a well-demarcated tumour measuring 2 x 4 cm in diameter and involving one of the nerve roots of the cauda equina was located within the intradural space with no evidence of extradural extension. Microscopically the tumour was made up of sheets of closely packed small round cells, associated with ganglioneuroma-like islands. Immunohistochemically, the small round tumour cells were intensely positive for neuron-specific enolase (NSE), an MIC2 gene product (O13) and beta 2-microglobulin, whereas the foci with ganglion cell-like cells reacted positively to NSE, synaptophysin and beta 2-microglobulin but were negative for O13. A chimeric transcript of the EWS/FLI-1 fusion gene detected by a nested reverse transcriptase-polymerase chain reaction using formalin-fixed paraffin-embedded tissue justified the diagnosis of pPNET. Only 6 cases of PNET in the cauda equina have been described in the literature, and this is the first case of a pPNET with ganglio-neuroma-like areas. This finding suggests that the primitive tumour cells of pPNET may respond to unknown inductive effects and express a ganglion cell-like morphology.

Adolescent↗
PubMed1997

Influence of PF1022A on the motility of Angiostrongylus cantonensis in vitro.

Our previous in vivo studies on angiostrongyliasis showed that PF1022A had stronger killing effects against female adults than against males. No killing effects were observed against young adult worms in the central nervous system. To characterize the former in vivo action of PF1022A, in vitro effects of PF1022A on the motility of Angiostrongylus cantonensis were studied directly. Few differences in the efficacy were observed between male and female worms, but dose- and time-dependent inhibition was observed in adults treated with PF1022A at 10(-7)-10(-11) g/ml. PF1022A was slightly less effect we against young-adult worms than against adult worms. Minor effects of PF1022A were observed on the third-stage larvae. These results suggest that selectivity against adult females in vivo could be attributable to non-neuropharmacological mechanisms and that PF1022A does not pass through the blood-brain barrier in host animals.

Angiostrongylus cantonensis↗
PubMed1997

The pharmacokinetics of water-in-oil-in-water-type multiple emulsion of a new tacrolimus formulation.

We developed a water-in-oil-in-water-type (W/O/W)-type multiple emulsion of a new tacrolimus formulation. A potential approach to avoid the complications of systemic immunosuppression and simultaneously enhance immunosuppressive efficacy is to deliver immunosuppressive agents locally to the site of the target organs. The W/O/W emulsion is dispersed oil drops containing smaller water droplets that allow the delivery of drugs preferentially to the reticuloendothelial systems (RES). Since the liver and the spleen are primary components of the RES, and the brain and the kidney have a poor RES, we hypothesized that a W/O/W emulsion of tacrolimus would possess the pharmacokinetic benefits of local immunosuppression. We evaluated this hypothesis in a rat model. The tacrolimus levels of whole blood, the liver, spleen, brain, and kidney in rats given intravenous emulsions of tacrolimus (W/O/W group) were compared with a group administered tacrolimus alone (T group). There were no significant differences between the pharmacokinetic parameters of W/O/W group and T group based on whole blood data. However, the W/O/W group had significantly decreased tacrolimus levels in the brain and kidney, and significantly increased levels in the liver and spleen compared with the T group. These data suggest that the W/O/W emulsion is applicable as an intravenous drug carrier for local immunosuppression.

Animals↗
PubMed1997

Inhibitory effect of prostaglandin E1 on intimal thickening following photochemically induced endothelial injury in the rat femoral artery.

The inhibitory effect of prostaglandin E1, which has an anti-platelet action and a vasodilating action via intracellular cyclic AMP elevation, was studied on intimal thickening in the rat femoral artery. A segment of the femoral artery was occluded by a platelet and fibrin-rich thrombus due to photochemical reaction between systemically administered Rose Bengal and transluminal green light which causes endothelial injury followed by platelet adhesion and aggregation at the site of photochemical reaction. Three weeks after endothelial injury, intimal thickening occurred at the irradiated site. Prostaglandin E1 (0.3 microgram/kg per min), administered as a continuous infusion 10 min before photochemical reaction significantly (P < 0.05) prolonged the time to occlusion of the femoral artery. In a separate experiment, prostaglandin E1 (0.3 microgram/kg per min) administered as a continuous infusion for 7 days just after endothelial injury significantly (P < 0.05) inhibited intimal thickening compared with a control group. In cultured rat-derived vascular smooth muscle cells, prostaglandin E1 produced concentration-dependent inhibition of migration and proliferation, stimulated by platelet-derived growth factor. These results suggest that prostaglandin E1 may be effective in preventing vascular restenosis after vascular surgery and angioplasty.

Alprostadil↗
PubMed1997

Impact of 3-dimensional helical computerized tomography on selection of operative methods for ureteropelvic junction obstruction.

PURPOSE: We studied the feasibility of imaging the direct correlation between crossing vessels and obstructed ureteropelvic junction with helical (spiral) computerized tomography (CT) for selecting surgical repair of symptomatic ureteropelvic junction obstruction. MATERIALS AND METHODS: From July 1995 to December 1995, 4 select patients with symptomatic ureteropelvic junction obstruction underwent contrast enhanced helical CT. In addition to transaxial images, 3-dimensional reformatted images were used for evaluation. RESULTS: We identified 2 cases of ureteropelvic junction obstruction due to crossing vessels regarded as ureterovascular hydronephrosis, which is characterized by the spatial relationship between malrotated renal pelvis and anterior crossing vessels. Laparoscopic or open repair was performed in these 2 patients and operative findings were in agreement with prospective helical CT interpretation. Antegrade endopyelotomy was performed successfully for the remaining 2 patients. CONCLUSIONS: The 3-dimensional helical CT is reliable in detecting ureterovascular hydronephrosis preoperatively and in presenting better operative methods for ureteropelvic junction obstruction.

Adult↗
PubMed1997

A note on the preparation of whole mount samples suitable for observation with the confocal laser scanning microscope.

The effects of fixatives and pretreatment on the immunofluorescence of whole mount specimens prepared for confocal laser scanning microscopy (CLSM) were examined. Intact villi were obtained from the proximal small intestine of mice fixed with 4% paraformaldehyde (4P) or 0.5% paraformaldehyde and 15% of saturated picric acid (PPa). Before immunostaining for laminin and tenascin, each specimen was pretreated with deoxycholate, while some 4P-fixed specimens received further pepsin pretreatment. Regardless of the fixatives employed, laminin and tenascin showed adequate immunofluorescence. Without pepsin pretreatment, the 4P-fixed specimens emitted conspicuous background fluorescence, and immunofluorescence was weak in the lamina propria. Pepsin pretreatment reduced the background fluorescence, but also diminished the immunofluorescence, especially that of tenascin. The PPa-fixed specimens displayed intense immunofluorescence of laminin and tenascin with very little background, even deeply within the lamina propria. When the PPa-fixed specimens were immunostained for vasoactive intestinal peptide, immunopositive nerve fibres were observed within the lamina propria. Ultrastructural investigation of the PPa-fixed specimens revealed that membranous structures in all cells were almost lost while tissue architecture was well preserved. These results indicate that PPa fixation and pretreatment with deoxycholate are suitable for preparing whole mount specimens for CLSM studies.

Animals↗
PubMed1997

Cardiac and hemodynamic effects of TZC-5665, a novel pyridazinone derivative, and its metabolite in humans and dogs.

1. TZC-5665 is a novel pyridazinone derivative with vasodilatory and beta-adrenergic blocking activities and type III phosphodiesterase inhibitory action. 2. In healthy volunteers, TZC-5665 was rapidly absorbed and immediately metabolized. Its main metabolite, M-2, remained at a higher concentration in plasma. Orally administered TZC-5665 reduced end-diastolic left ventricular volume (20.16 ml) and exhibited a tendency to increase ejection fraction (0.04). 3. In dogs, M-2 dose-dependently increased cardiac contractility and reduced both preload and afterload. These effects appeared more potent in the failed heart than in the normal heart. At the same dose (30 micrograms/kg), the effects of M-2 seem to be more potent than those of milrinone. 4. We concluded that TZC-5665 is a useful medication for treating patients with chronic congestive heart failure (CHF) because of the positive inotropic and vasodilating effects due to its active metabolite in addition to its own beta-adrenergic blocking actions.

Adult↗
PubMed1997

Non-insulin- and insulin-mediated glucose uptake in dairy cows.

Four mid-lactation Holstein dairy cows (mean milk yield on day of experiments 26.1 kg/d) were used in a series of experiments to establish the contribution of non-insulin-mediated glucose uptake to total glucose uptake at basal insulin concentrations. A secondary objective was to determine whether somatostatin affects the action of infused insulin. In part I of the experiment a primed continuous infusion [6,6-2H]glucose (45.2 micrograms/kg per min) was begun at time 0 and continued for 5 h. After 3 h of [6,6-2H]glucose infusion (basal period) a primed continuous infusion of insulin (0.001 i.u./kg per min) was administered for 2 h. Coincidental with the insulin infusion, normal glucose was also infused in order to maintain the plasma glucose concentration at euglycaemia. Part II of the experiment was the same as part I except that somatostatin was infused for 2 h (0.333 micrograms/kg per min) instead of insulin. In part III of the experiment both insulin and somatostatin were infused for the final 2 h. Plasma insulin levels were increased by insulin infusion (to 0.1476 to 0.1290 i.u./l for parts I and III respectively) and were reduced by somatostatin infusion in part II (to 0.006 i.u./l) relative to the basal periods (mean 0.021 i.u./l). Glucose uptake during somatostatin infusion (2.50 mg/kg per min; part II) was 92.0% of that observed in the respective basal period (2.72 mg/kg per min). Circulating insulin levels were much lower than the dose of insulin that causes a half maximal effect on glucose uptake (0.06-0.10 i.u./l for ruminants); consequently insulin-mediated glucose uptake was probably absent in part II. Secondly, glucose uptake following insulin only infusion (4.05 mg/kg per min) was significantly lower than that observed when insulin plus somatostatin was infused (4.69 mg/kg per min), indicating that somatostatin either directly or indirectly enhanced the action of insulin on glucose uptake.

Animals↗
PubMed1997

Syncytial cell formation in vivo by type C retroviral particles in the systemic lupus erythematosus (SLE) lung.

Significant numbers of syncytial cells were observed in the bronchoalveolar lavage fluid (BALF) of a 42-year-old patient who had SLE with interstitial pneumonia. Electron microscopic study of the BALF cells and positive reverse transcriptase activity in the supernatant of the cultured cells revealed unknown retroviral particles in the BALF cells. No antibodies to known human retroviruses or proviral sequences were detected. Type C retroviral particles and positive reverse transcriptase activity were also observed in co-cultured U937 cells. To evaluate the pathogenic role of unknown type C retroviral particles, screening for antibodies to this retroviral particle was performed by immunofluorescence in 26 patients with idiopathic pulmonary fibrosis, 17 patients with SLE, 22 patients with lung cancer, and 58 healthy volunteers. Serum antibody to this putative type C retrovirus was detected in 24% of SLE patients, 27% of idiopathic pulmonary fibrosis patients, none of the lung cancer patients and 2% of healthy volunteers. Although no direct evidence of this virus as the pathogen for SLE could be demonstrated, a possible role in the development of SLE and interstitial pneumonia might be suggested.

Adult↗
PubMed1997

Role of tumour necrosis factor-alpha (TNF-alpha) in the induction of HIV-1 gp120-mediated CD4+ T cell anergy.

The HIV-1 envelope glycoprotein (gp 120) is known to induce antigen-specific and non-specific CD4+ T cell anergy. We found that early T cell activation, as indicated by HLA-DP expression in the early G1 (G1A) phase of the cell cycle, and the inhibition of mitogen-mediated IL-2 production induced by gp120, required TNF-alpha produced by gp120-stimulated macrophages. In the presence of an antibody to TNF-alpha, these changes induced by gp120 were inhibited, while recombinant TNF-alpha induced similar abnormalities of CD4+ T cells, even in the absence of gp120. On the other hand, inhibition of the mixed lymphocyte reaction (MLR) in CD4+ T cells by gp120, which may be related to gp120-mediated down-regulation of CD4 expression on T cells and activation of protein tyrosine kinase p56(lck) in CD4+ T cells, was observed even in the absence of macrophage-derived TNF-alpha induced by gp120. These observations indicate that both TNF-alpha-dependent and independent events contribute to gp120-mediated CD4+ T cell anergy, and TNF-alpha appears to play an important role in inducing CD4+ T cell anergy in HIV-1 infection.

CD4-Positive T-Lymphocytes↗
PubMed1997

Clinicopathological and interphase cytogenetic analysis of desmoid tumours.

AIMS: Recurrence of desmoid tumours is difficult to predict from only histological findings. In this study, immunohistochemistry for counting stromal blood vessels and proliferative activity, DNA flow cytometry, and interphase cytogenetic analysis of chromosome 8 by fluorescence in-situ hybridization (FISH) were performed to assess the correlation between their parameters and the recurrence of desmoid tumours. METHODS AND RESULTS: The cases examined included 16 extra-abdominal desmoid and eight abdominal desmoids, comprising 14 recurrent and 10 non-recurrent cases. Eleven (69%) of the 16 extra-abdominal desmoids and three (38%) of the eight abdominal desmoids recurred. Patients with recurrent lesions (mean age, 20 years) were younger than those with non-recurrent tumours (34 years). Histologically, tumours with hypervascular areas frequently recurred after surgery in comparison with those with hypovascularity. There was no significant correlation between tumour size, the labelling index of the proliferating cell nuclear antigen (PCNA) and the recurrence. In flow cytometric analysis, all the cases examined showed a diploid pattern. The FISH study revealed that the incidence of trisomy 8 was significantly higher in the recurrent (72.7%) than in the non-recurrent cases (12.5%). CONCLUSIONS: These results suggest that a subgroup of desmoid tumours at risk of recurrence may be hypervascular lesions associated with trisomy 8.

Adolescent↗
PubMed1997

Isoform-specific up-regulation by ouabain of Na+,K+-ATPase in cultured rat astrocytes.

There are two alpha-subunit isoforms (alpha1 and alpha2) and two beta-subunit isoforms (beta1 and beta2) of Na+,K+-ATPase in astrocytes, but the functional heterodimer composition is not known. Ouabain (0.5-1.0 mM) increased the levels of alpha1 and beta1 mRNAs, whereas it decreased those of alpha2 and beta2 mRNAs in cultured rat astrocytes. The increases in alpha1 and beta1 mRNAs were observed at 6-48 h after addition of the inhibitor. Immunochemical analyses showed that ouabain increased alpha1 and beta1, but not alpha2 and beta2, proteins, and that the isoforms in control and ouabain-treated cultures were of glial origin. Low extracellular K+ and monensin (20 microM) mimicked the effect of ouabain on alpha1 mRNA. The ouabain-induced increase in alpha1 mRNA was blocked by the protein synthesis inhibitor cycloheximide (10 microM), the intracellular Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetraacetoxymethyl ester (30 microM), and the calcineurin inhibitor FK506 (1 nM). These findings indicate that chronic inhibition of Na+,K+-ATPase up-regulates the alpha1 and beta1, but not alpha2 and beta2, isoforms in astrocytes, suggesting a functional coupling of alpha1beta1 complex. They also suggest that intracellular Na+, Ca2+, and calcineurin may be involved in ouabain-induced up-regulation of the enzyme in astrocytes.

Animals↗