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Biomedical subjects

T Hirano

Publications and source records attributed to T Hirano.

At least 325 records · Page 18Linked to original sources
PubMed1999

A metalloproteinase inhibitor prevents acute graft-versus-host disease while preserving the graft-versus-leukaemia effect of allogeneic bone marrow transplantation.

We examined the effect of a hydroxamic acid-based matrix metalloproteinase inhibitor (KB-R7785), which we previously demonstrated to have a potent ameliorating effect on acute graft-versus-host disease (GVHD), and on the graft-versus-leukaemia (GVL) effect of allogeneic bone marrow transplantation (BMT). KB-R7785 was administered to (C57BL/6 x BALB/c) F1 (CBF1) mice that had been inoculated with IgE-producing B53 hybridoma cells of BALB/c origin as a model tumour, along with or without transplantation of C57BL/6 (B6) bone marrow cells and spleen cells (BMS). Administration of KB-R7785 without BMS significantly prolonged the survival of B53-inoculated CBF1 mice by inhibiting the infiltration of B53 cells into the liver and spleen. Transplantation of B6 BMS without KB-R7785 resulted in the death of most recipients due to acute GVHD while efficiently eliminating B53 cells. Administration of KB-R7785 along with B6 BMS resulted in a 50% survival of B53-inoculated CBF1 mice over 50 d without histological manifestations of acute GVHD or residual B53 cells. These results indicate the beneficial effects of KB-R7785 that inhibit tumour infiltration and prevent acute GVHD while preserving the GVL effect of allogeneic BMT.

Animals↗
PubMed1999

Enhanced antitumor potency of polyethylene glycolylated tumor necrosis factor-alpha: a novel polymer-conjugation technique with a reversible amino-protective reagent.

We attempted to develop a novel method for the chemical modification of cytokines with synthetic polymers to increase in vivo therapeutic efficacy. A pH-reversible amino-protective reagent, dimethylmaleic anhydride (DMMAn), was used for polymer conjugation of tumor necrosis factor-alpha (TNF-alpha) with polyethylene glycol (PEG). The novel PEGylated TNF-alpha, PEG-TNF-alpha(+), which was pretreated with DMMAn before PEGylation, had 20% to 40% higher specific activity than PEG-TNF-alpha(-) (not treated with DMMAn) in vitro. Moreover, PEG-TNF-alpha(+) more potently caused tumor necrosis in Meth-A solid tumors in mice than did PEG-TNF-alpha(-). The middle fraction (M) of PEG-TNF-alpha(+), which was of the optimal degree of modification among PEG-TNF-alpha(+)s with different molecular weights, caused the highest degree of tumor hemorrhagic necrosis: 30-fold higher than native TNF-alpha and 2-fold higher than the most potent MPEG-TNF-alpha(-) that also had nearly the same molecular weight. Significantly, improvements in antitumor activity in vivo were more marked than were changes in specific activity. Furthermore, native TNF-alpha caused a dose-dependent body weight loss in mice, whereas no obvious side effects were observed in any PEG-TNF-alpha-treated mice. These results suggest that PEGylation using DMMAn is a useful for clinical cytokine delivery.

Animals↗
PubMed1999

The relationship between p21/waf1 expression patterns and cell proliferation during the tumorigenesis of the bronchus.

Each developmental stage in the process towards bronchial squamous cell carcinoma (normal epithelium, squamous metaplasia and early stage squamous cell carcinoma including in situ carcinoma) was examined for p21/waf1 protein expression and cell proliferation using MIB1. P21/waf1 immunoreactivity was classified into four patterns: predominantly cytoplasmic staining, exclusively nuclear staining, both nuclear and cytoplasmic staining and negative. The cases with predominantly cytoplasmic staining showed suppression of cell proliferation. Most cases with either negative or exclusively nuclear staining revealed high cell proliferation. The simultaneous evaluation of p21/waf1 and cell proliferation is valuable for clinical determination of the high risk for malignant transformation.

Blotting, Western↗
PubMed1999

Probing for the threshold energy for visual transduction: red-shifted visual pigment analogs from 3-methoxy-3-dehydroretinal and related compounds.

While azulenic retinal analogs failed to yield a red-shifted visual pigment analog, the 9-cis isomers of the push-pull polyenals 3-methoxy-3-dehydroretinal and 14F-3-methoxy-3-dehydroretinal yielded iodopsin pigment analogs with absorption maxima at, respectively, 663 and 720 nm. The former gave a relatively stable batho product (700 nm) and was able to activate transducin. A lower activity was observed for the latter. One possible explanation for the combined results is that the excitation energies of these red-shifted pigments are approaching the threshold energy for visual transduction (although at this time we cannot rigorously exclude a role of the added F-atom in reducing the transducin activity).

Retinal Pigments↗
PubMed1999

[Early and mid-term results of endovascular stent grafting for aortic aneurysms].

Early and mid-term clinical results of 28 cases of endovascular stent grafting for descending thoracic aortic aneurysms and 11 cases of abdominal aortic aneurysms are reported. Early clinical results: Among 28 patients (7 true thoracic aortic aneurysms, 3 pseudothoracic aortic aneurysms and 8 acute, 4 subacute, and 6 chronic aortic dissections), two patients (7.1%) with ruptured acute aortic dissection or ruptured infected pseudoaneurysm died in the perioperative period. Two of the remaining 26 patients experienced minor complications. Aneurysmal sacs or false lumens at the descending thoracic aorta were completely thrombosed in the 26 patients. One patient (9.1%) with a ruptured abdominal aneurysm died, and one of the remaining 10 patients had renal and peripheral emboli and peripheral vascular trauma. Inadvertent covering of the renal arteries occurred in another patient. Unless one patient had persistent endoleak, aneurysmal sacs in the 10 surviving patients were thrombosed. Mid-term clinical results: One aortic dissection at a different section of the descending aorta occurred 6 months after stent grafting for aortic dissection, and one patient died of pneumonia 3 months after stent grafting for an abdominal aortic aneurysm. CT scanning 6 months after stent grafting revealed a decrease in maximal aneurysmal size in 3 of 9 patients with true or pseudothoracic aneurysms and in 2 of 5 patients with abdominal aortic aneurysms. Five of 9 patients with stent grafting for acute or subacute dissection showed elimination of the false lumen in the descending thoracic aorta in a CT scan 6 months after grafting. One patient with a true thoracic aneurysm and one patient with an abdominal aortic aneurysm showed an increase in aneurysmal size in a CT scan 2 years and one year after treatment, respectively.

Aged↗
PubMed1999

[Left ventricular relaxation in lone atrial fibrillation and atrial fibrillation with heart disease].

Atrial fibrillation with organic heart disease shows a steady value for the time constant of left ventricular isovolumetric relaxation (TC), whereas left ventricular contractility varies from beat to beat. However, there is no report on left ventricular relaxation in lone atrial fibrillation. This study assessed left ventricular relaxation in 5 patients with lone atrial fibrillation, 3 with ischemic heart disease and one with hypertrophic cardiomyopathy. Left ventricular pressure was recorded at 3 msec intervals, with a high fidelity micromanometer-tipped catheter. Maximal positive dP/dt (dP/dtmax) and TC of isovolumetric left ventricular relaxation period [P(t) = (P0-P infinity) exp (-t/TC) + P infinity] were measured as indices of left ventricular contractility and left ventricular relaxation, respectively. Correlation coefficients of dP/dtmax and TC versus the ratio of the preceding to the pre-preceding RR-interval (RR2/RR1) were calculated. A good correlation was found between dP/dtmax and RR2/RR1 in all patients (r = 0.71-0.84, p < 0.0001). No correlation between TC and RR2/RR1 was found in patients with atrial fibrillation with organic heart disease, but a good correlation was found between TC and RR2/RR1 in patients with lone atrial fibrillation (r = 0.74-0.95, p < 0.0001). The correlation between TC and RR2/RR1 is well preserved in lone atrial fibrillation. The mechanism of the variation of TC with the RR2/RR1 interval in lone atrial fibrillation may be similar to the change of TC in postextrasystolic potentiation, which is attributed to the change of intracellular Ca2+ concentration. Absence of correlation between TC and RR2/RR1 interval may indicate that left ventricular relaxation is disturbed in patients with atrial fibrillation with organic heart disease.

Aged↗
PubMed1999

[A case of gustatory disturbance caused by ipsilateral pontine hemorrhage].

We reported a 71-year-old woman with sudden-onset hypogeusia. The patient showed no other neurological signs or symptoms except for the taste disturbance. She lost bitter, salty, sour or sweet sensation on the right half of the tongue. A brain CT scan revealed a small hemorrhage in the right tegmentum of the middle pons. The hematoma was adjacent to the forth ventricle, affecting the gustatory tract running from the nucleus solitalius to the pontine taste area (PTA) in the upper pons. The gustatory pathway is generally said to exist around the medial lemniscus and the reticular formation. In this case, however, the gustatory tract would lay in the dorsal portion near the forth ventricle, as no defect other than taste disturbance was accompanied.

Aged↗
PubMed1999

[New clinical application of direct and chemical measurement of low density lipoprotein cholesterol-estimation of compositional changes in triglyceride-rich lipoprotein fraction].

Recently several new direct assay systems for chemical measurement of LDL-cholesterol (Ch) have been developed. These systems allow us to estimate LDL-Ch value even in samples under non-fasting condition as well as samples from prominent hypertriglyceridemics without ultracentrifugation. Since it is possible that the difference between LDL-Ch value measured using new direct method and that calculated using Friedewald's formula can indicate compositional abnormalities of triglyceride-rich lipoprotein (TGRL) fraction (if VLDL-Ch equal to 1/5 of plasma triglyceride, this difference must always be zero), this difference (estimated remnant-Ch) may represent the presence of remnant or intermediate density lipoprotein (IDL) fraction. LDL-Ch is not detected by means of this direct method (LDL-EX, Denka Seiken Co.) in the eluate of the affinity column, which contains anti-apoA1 and anti-B100 antibody, indicating that RLP fraction can be excluded from the assay system. Estimated remnant-Ch correlated well with RLP-Ch, IDL-Ch and apoE. Furthermore, there is no significant correlation between LDL-Ch measured by LDL-EX and Lp(a), indicating that this direct assay system does not include Lp(a) in plasma. Thus, this new direct assay method for LDL-Ch enables us to measure LDL-Ch value with ease and also to estimate compositional abnormalities of TGRL fraction and/or appearance of remnant or IDL fraction without ultracentrifugation.

Cholesterol, LDL↗
PubMed1999

A case of late onset cyclosporine-induced hemolytic uremic syndrome resulting in renal graft loss.

A case of late onset hemolytic uremic syndrome (HUS) associated with cyclosporine (CYA) is described in this report. A 50-yr-old man with end-stage renal failure due to immunoglobulin A (IgA) nephropathy received a renal transplant from his wife. Human leucocyte antigen was completely unmatched. Immunosuppressant was a combination of prednisolone, azathioprine, and CYA. He was discharged 1 month after transplantation, with no episode of acute rejection. Twenty-one months after transplantation, his platelet count and hematocrit began to decrease and lactate dehydrogenase began to increase. Graft biopsy showed thrombotic microangiopathy and recurrent IgA nephropathy. Graft function was rapidly deteriorated and methylprednisolone pulse therapy was not effective. Twenty-five months after transplantation, he returned to a regular hemodialysis. Hemolysis was immediately improved after a reduction of the dose of CYA to 50 mg/d. The trough level of CYA was less than 200 ng/mL in most periods of his clinical course. Blood pressure was high throughout the clinical course. Although acute vascular rejection or malignant hypertension could also cause a thrombotic microangiopathy, CYA was most likely a cause of HUS in the present case because of the following reasons: neither anti-acute rejection therapy nor an adequate control of his blood pressure was effective in improving clinical features of HUS; hemolysis and thrombocytopenia disappeared immediately after the reduction of the dose of CYA to 50 mg/d. It has been reported that HUS carried poor prognosis only when occurring shortly after transplantation in cadaver kidney recipients. The present transplant was from a living donor and HUS occurred 21 months after transplantation and was severe enough to result in graft loss. High blood pressure might be one of the predisposing factors of HUS associated with CYA in the present case. CYA should be stopped and other alternative immunosuppressants should be given in cases of acute graft deterioration with hemolysis and thrombocytopenia, irrespective of the interval from transplantation, CYA dose, or CYA trough level.

Cyclosporine↗
PubMed1999

Thromboxane A2 receptor antagonist prevents pancreatic microvascular leakage in rats with caerulein-induced acute pancreatitis.

This study was designed to evaluate the protective effect of thromboxane A2 (TXA2) receptor antagonist, seratrodast, against pancreatic injuries during acute pancreatitis. Acute pancreatitis was induced in rats by intravenous infusion of a supramaximal dose of caerulein (5 microg/kg x h for 4 h). In this model, marked hyperamylasemia, a significant increase in pancreatic water content, and a significant increase in pancreatic micro-vascular leakage of Evans blue dye were observed. Pancreatic subcellular redistribution of a lysosomal enzyme, cathepsin B from the lysosomal fraction to the zymogen fraction as well as a significant increase in pancreatic trypsin content were also observed. Pretreatment with seratrodast at a dose of 2 mg/kg (twice, 8 and 4 h before caerulein infusion) significantly inhibited these pancreatic injuries including hyperamylasemia, increased pancreatic microvascular leakage, redistribution of cathepsin B and increased pancreatic trypsin content. These results suggest that TXA2 may be involved in the pathogenesis of acute pancreatitis in the early stage of the disease and that TXA2 receptor antagonist might be of therapeutic value for treatment of acute pancreatitis.

Acute Disease↗
PubMed1999

Effect of 5-fluorouracil (5-FU) on the isolated perfused rat pancreas.

This study was designed to evaluate the effect of anticancer agent 5-fluorouracil (5-FU)) on the exocrine pancreas by using isolated perfused rat pancreas at three different doses (2.5, 5.0 and 10 microg/ml). 5-FU at doses of 5 and 10 microg/ml for 1 h caused significant increases in amylase levels in pancreatic effluent and significant decreases in amylase outputs. Moreover, 5-FU caused significant increases in pancreatic trypsin contents in pancreatic tissue. 5-FU also caused significant redistribution of cathepsin B activity from the lysosomal fraction to the zymogen fraction in pancreatic subcellular fractionation study. These changes were almost dose-dependent. These results suggest that the exocrine pancreas might be injured by 5-FU, and that lysosomal enzymes seem to play an important role in the pathogenesis of the pancreatic injuries induced by 5-FU, since cathepsin B can activate trypsinogen.

Amylases↗
PubMed1998

Increased uncoupling protein-2 and -3 gene expressions in skeletal muscle of STZ-induced diabetic rats.

Streptozotocin (STZ)-induced diabetic animals are vulnerable to cold stress. Uncoupling proteins (UCPs) play an important role in regulating thermogenesis. We investigated the gene expressions of UCPs in brown adipose tissue (BAT), white adipose tissue (WAT), liver and gastrocnemius muscle of STZ-diabetic rats using Northern blot. UCP-1, -2 and -3 mRNA expressions in BAT were all remarkably lower in STZ-diabetic rats than those in control rats. Both UCP-2 and -3 gene expressions in gastrocnemius muscle were substantially elevated in STZ-diabetic rats and insulin treatment restored UCP gene expressions to normal levels. These results suggest that in STZ-diabetic rats, the overexpression of UCP-2 and UCP-3 in skeletal muscle provides a defense against hypothermogenesis caused by decreased UCPs in BAT.

Adipose Tissue, Brown↗
PubMed1998

ATP-dependent aggregation of single-stranded DNA by a bacterial SMC homodimer.

SMC (structural maintenance of chromosomes) proteins are putative ATPases that are highly conserved among Bacteria, Archaea and Eucarya. Eukaryotic SMC proteins are implicated in a diverse range of chromosome dynamics including chromosome condensation, dosage compensation and recombinational repair. In eukaryotes, two different SMC proteins form a heterodimer, which in turn acts as the core component of a large protein complex. Despite recent progress, no ATP-dependent activity has been found in individual SMC subunits. We report here the first biochemical characterization of a bacterial SMC protein from Bacillus subtilis. Unlike eukaryotic versions, the B.subtilis SMC protein (BsSMC) is a simple homodimer with no associated subunits. It binds preferentially to single-stranded DNA (ssDNA) and has a ssDNA-stimulated ATPase activity. In the presence of ATP, BsSMC forms large nucleoprotein aggregates in a ssDNA-specific manner. Proteolytic cleavage of BsSMC is changed upon binding to ATP and ssDNA. The energy-dependent aggregation of ssDNA might represent a primitive type of chromosome condensation that occurs during segregation of bacterial chromosomes.

Adenosine Triphosphatases↗
PubMed1998

Hydrocarbon uptake by Streptomyces.

Oligocarbophilic Streptomyces strains capable of hydrocarbon uptake and utilization were isolated from the polluted desert of Kuwait and used in this study. Transmission electron-microscopy of hyphae revealed that they become enriched with large less electron dense areas in the cytoplasm, when biomass samples were incubated with alkanes. The Streptomyces isolate could utilize n-hexadecane as sole carbon and energy source and their fatty acid content showed an increase in the fatty acids with chain length equivalent to those of the alkane substrates. Fluorescence measurements of diphenylhexatriene dissolved in the representative alkane, n-hexadecane, showed that the kinetics of hydrocarbon uptake are quite different in hydrocarbon-utilizer compared with non-utilizer Streptomyces strain. Microviscosity of the cellular membrane of the utilizer strain was also different from that of the non-utilizer control strain Streptomyces griseus after incubation in the presence of n-hexadecane. Very likely the hydrocarbon utilizer transported these compounds more efficiently across their membranes and accumulated them as inclusions in the cytoplasm.

Alkanes↗
PubMed1998

STAT3 orchestrates contradictory signals in cytokine-induced G1 to S cell-cycle transition.

The signal transducer and activator of transcription molecules (STATs) play key roles in cytokine-induced signal transduction. However, their role in cell growth has not been clear. In the present study, we show that STAT3 plays a key role in the G1 to S phase cell-cycle transition induced by the cytokine receptor subunit gp130, through the upregulation of cyclins D2, D3 and A, and cdc25A, and the concomitant downregulation of p21 and p27. Furthermore, unexpectedly, we found that gp130 could induce the expression of p21 when STAT3 activation was suppressed. Such contradictory signals regulating cell-cycle progression could be simultaneously delivered from distinct cytoplasmic regions of gp130. We propose an 'orchestrating model' for cytokine and growth factor action in which contradictory signals are orchestrated to produce a specific effect in a target cell.

Cell Line↗
PubMed1998

Phosphorylation and activation of 13S condensin by Cdc2 in vitro.

13S condensin is a multisubunit protein complex essential for mitotic chromosome condensation in Xenopus egg extracts. Purified 13S condensin introduces positive supercoils into DNA in the presence of topoisomerase I and adenosine triphosphate in vitro. The supercoiling activity of 13Scondensin was regulated by mitosis-specific phosphorylation. Immunodepletion, in vitro phosphorylation, and peptide-mapping experiments indicated that Cdc2 is likely to be the kinase that phosphorylates and activates 13S condensin. Multiple Cdc2 phosphorylation sites are clustered in the carboxyl-terminal domain of the XCAP-D2 (Xenopus chromosome-associated polypeptide D2) subunit. These results suggest that phosphorylation of 13Scondensin by Cdc2 may trigger mitotic chromosome condensation in vitro.

Adenosine Triphosphatases↗
PubMed1998

Deletion of bone marrow stromal cell antigen-1 (CD157) gene impaired systemic thymus independent-2 antigen-induced IgG3 and mucosal TD antigen-elicited IgA responses.

Bone marrow stromal cell Ag-1 (BST-1; CD157)-deficient mice were generated to examine the immunologic roles of the molecule in vivo. In BST-1(-/-) mice, the development of peritoneal B-1 cells was delayed, and CD38(low/-) B-lineage cells were increased in the bone marrow and spleen. Partial impairment of thymus-independent (TI-2) and thymus-dependent (TD) Ag-specific immune responses was noted in the systemic and mucosal compartments of BST-1(-/-) mice, respectively. Although serum Ig levels as well as TD and TI-1 Ag-specific systemic immune responses were normal, the TI-2 Ag-induced IgG3 response was selectively impaired. Oral immunization of BST-1(-/-) mice with cholera toxin, a potent TD Ag for the induction of IgA response, resulted in the poor production of Ag-specific Abs at the intestinal mucosa accompanied by the reduced number of Ag-specific IgA-producing cells in the lamina propria. These results indicate that BST-1 has roles in B cell development and Ab production in vivo.

ADP-ribosyl Cyclase↗