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T Furuya

Publications and source records attributed to T Furuya.

At least 127 records · Page 7Linked to original sources
PubMed1996

Novel 5-hydroxytryptamine (5-HT3) receptor antagonists. III. Pharmacological evaluations and molecular modeling studies of optically active 4,5,6,7-tetrahydro-1H-benzimidazole derivatives.

The R- and S-enantiomers of the 4,5,6,7-tetrahydro-1H-benzimidazole derivatives 3-8 were prepared by optical resolution. Each R-isomer, except for 3, was almost two orders of magnitude more potent than its S-isomer as a 5-hydroxytrptamine (5-HT3) receptor antagonist, as judged from they effect on the von Bezold-Jarisch reflex (B. J. reflex) in rats, the contraction of isolated guinea-pig colon and the receptor-binding affinity. The (--)-(R)-5-[(1-methyl-1H-indol-3-yl)carbonyl] derivative 6R.HCl (ramosetron = YM060) and (--)-(R)-5-[(1-indolinyl)carbonyl] derivative 4R.HCl (YM114 = KAE-393) given p.o. were hundreds of times more potent than 1 (ondansetron) and 2 (granisetron) in their inhibitory effects on cisplatin-induced emesis in ferrets and restraint stress-induced increases in fecal pellet output in rats. Three-dimensional molecular modeling studies suggested that the 'chiral selection' of the enantiomers might be influenced by the steric repulsion between the aromatic ring part and the conformationally restricted 4,5,6,7-tetrahydro-1H-benzimidazole ring in "equatorial-twist" conformation. In our pharmacophore model for the 5-HT3 receptor antagonist, a basic center exists at the left side of the aromatic-carbonyl plane when viewing from the aromatic part with the carbonyl oxygen atom upwards, whereas the "handedness" is ambiguous in the previously proposed model.

Animals↗
PubMed1996

Novel 5-hydroxytryptamine (5-HT3) receptor antagonists. I. Synthesis and structure-activity relationships of conformationally restricted fused imidazole derivatives.

We prepared a novel series of conformationally restricted fused imidazole derivatives 4b, 4c and 4d (possessing 4,5,6,7-tetrahydroimidazo[4,5-c] pyridine and substituted 4,5,6,7-tetrahydro-1H-benzimidazole for 4b, 5,6,7,8-tetrahydroimidazo[1,2-a]pyridine for 4c and 5,6,7,8-tetrahydroimidazo[1,5-a]pyridine for 4d as a basic amine part and (2-methoxyphenyl)aminocarbonyl group as an aromatic-carbonyl part). Their activities were then evaluated as an 5-hydroxytryptamine (5-HT3) receptor antagonist which may be useful for the treatment of irritable bowel syndrome (IBS) as well as for nausea and vomiting associated with cancer chemotherapy. The most potent compound was N-(2-methoxyphenyl)-4,5,6, 7-tetrahydro-1H-benzimidazole-5-carboxamide 14 in this series with an ID50 value of 0.32 microgram/kg on the von Bezold-Jarisch reflex in rats and an IC50 value of 0.43 microM on the isolated colonic contraction in guinea pig, approximately ten and two times more potent than ondansetron 1, respectively. The structure activity relationships (SAR) study suggested that the high potency of 14 may be attributed to the suitable position and direction of the N-C-N centroid in the conformationally restricted imidazole ring against the planar (2-methoxyphenyl)aminocarbonyl part in the binding of 14 to the receptor.

Animals↗
PubMed1996

Surgical treatment of abdominal aortic aneurysms in octogenarians.

Due to the increase in life span and the decrease in mortality associated with aortic surgery, many geriatric patients now undergo surgery for abdominal aortic aneurysms (AAAs). Therefore, we studied our surgical results for AAAs in an elderly population to assess the value of such operations. Twenty-six patients aged 80 years or older underwent surgery during an 11-year period from 1984 to 1994 at our institutions, and their outcomes were compared with those of 212 younger patients. The ratio of ruptured to non-ruptured AAAs was significantly higher in the older patients (aged 80 years or older) than in the younger patients (aged 79 years or younger), and aneurysm size in cases of non-rupture was greater in older patients than in younger patients. For octogenarians with non-ruptured AAAs, the survival rate was 85.7% at 5 years, compared with 43.6% at 3 years for those with ruptured AAAs, and these figures were not significantly different from those in younger patients. The present findings support the value of our active surgical approach for octogenarians with AAAs. We believe that an aggressive approach for octogenarians will decrease the incidence of ruptured AAAs and contribute to better patient survival.

Adult↗
PubMed1996

A consideration on the relationship between worm age and mortality of Setaria marshalli recovered from the peritoneal cavity of calves born in Tottori prefecture, Japan.

Eight calves born in November-December of 1992 were necropsied at the age of 29-230 days in an attempt to estimate the life span of Setaria marshalli in Japan. Worm ages were estimated on the base of active season for mosquitoes. Thirty worms estimated 4-9 months old recovered from 4 calves were all alive in the peritoneal cavity. Thirty-five out of 50 worms estimated 7-13 months old were dead with being entrapped by fibrin on the peritoneum. It is speculated that this is a normal fate of this parasite at the end of its life, and therefore, the life span of S. marshalli would be approximately one year after prenatal infection.

Aging↗
PubMed1996

Increased production of inflammatory cytokines in cultured CD4+ cells from patients with HTLV-I-associated myelopathy.

We investigated the production of inflammatory cytokines derived from cultured T cells of peripheral blood lymphocytes (PBL) in 14 patients with HTLV-I-associated myelopathy (HAM). The production of inflammatory cytokines, such as tumor necrosis factor-alpha, interferon-gamma, and granulocyte-macrophage colony stimulating factor, was significantly increased in patients with HAM, compared to HTLV-I seronegative controls. On the contrary, interleukin-4 production in cultured T cells was detected in only two patients with HAM, and not detected in HTLV-I seronegative controls. These results suggest that the production of inflammatory cytokines derived from TH1 cell population was simultaneously exaggerated in HAM patients. Interestingly, accelerated production of these cytokines was derived from CD4+ cells, which are main target cells in HTLV-I infection. These findings suggest that an inflammatory state in the central nervous system might be related to the pathogenesis of HAM.

Adult↗
PubMed1996

Spontaneous proliferation of and cytokine production by T cells adherent to human endothelial cells in patients with human T-lymphotropic virus type I-associated myelopathy.

We previously reported increased adherence of T cells to human endothelial cells (EC) in patients with HTLV-I-associated myelopathy (HAM). To define the immunological function of EC-adherent T cells from HAM patients, we investigated the degree of spontaneous proliferation and the production of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and granulocyte-macrophage colony stimulating factor (GM-CSF). Both the degree of spontaneous proliferation and the production of TNF-alpha, IFN-gamma, and GM-CSF by EC-adherent T cells of HAM patients were significantly increased, compared to anti-HTLV-I seronegative controls. Furthermore, in HAM patients, spontaneous proliferation and production of inflammatory cytokines by EC-adherent T cells were significantly higher than that of EC-non-adherent T cells. Conversely, those functions of EC-non-adherent T cells were significantly lower than that of unseparated cells, which were T cells before application to EC. We demonstrated that EC-adherent T cells were qualitatively and quantitatively more hyperactive than those of anti-HTLV-I seronegative controls and the population of activated T cells of HAM patients was concentrated in EC-adherent T cells rather than in EC-non-adherent T cells. Our results suggest that EC-adherent T cells in the peripheral blood of HAM are intimately involved in the immunopathogenesis of HAM.

Adult↗
PubMed1996

[Primary autoimmune hemolytic anemia (warm antibody)].

Primary autoimmune hemolytic anemia (warm-reacting auto antibodies), may occur at any age and affects both sexes. The onset may be sudden or insidious. If the hemoglobin has dropped suddenly or to very low level and there is cardio-respiratory emborassment, patient would need a blood transfusion. And a close watch should be kept on urine output, also to keep the urine alkaline. Corticosteroid are the mainstay of treatment. The dose is 1-2 mg/kg/day. The hemoglobin has reached normal level, steroid are reduced 5 mg every week. If patient fails to respond to corticosteroids or the maintenance dose required for corticosteroids causes unacceptable side effects, methylprednisolone pulse therapy, alternative are immunosuppression therapy or splenectomy. As a life saving temporary need, plasmapheresis may be utilized to bring down the titre of antibodies.

Anemia, Hemolytic, Autoimmune↗
PubMed1996

[Adverse effects of low-dose methotrexate therapy in rheumatoid arthritis].

To analyze the possible adverse effects of low dose methotrexate (MTX) therapy, 276 patients with rheumatoid arthritis (RA) were examined retrospectively. One hundred and seven patients (39%) experienced 113 adverse events : 57 showed liver dysfunction, 24 gastrointestinal complaints, 13 cutaneous symptoms, 6 respiratory symptoms, and 6 malignancies. Interestingly, 3 patients developed a dry cough without infiltration nor interstitial shadow on chest X-ray. The cough was rapidly resolved by discontinuation of MTX, but it recurred in 1 patient when MTX was re-administered. This finding might suggest a close association between MTX administration and the occurrence of dry cough. Of the 6 patients with malignancies diagnosed during MTX therapy, 2 showed malignant lymphoma, 2 lung cancer, 1 breast cancer and 1 colon cancer. MTX might have an oncogenic potential in RA because the coincidence rate, especially with respect to lymphoma, was significantly higher than estimated in a normal population.

Adult↗
PubMed1996

Reproductive and developmental toxicity studies of toluene. II. Effects of inhalation exposure on fertility in rats.

Male and female Sprague-Dawley rats were exposed to toluene vapor at 600 and 2000 ppm for 6 h/day, and effects on their fertility were investigated. Females were exposed from 14 days before mating until day 7 of gestation. Males were exposed for a total of 90 days, including the mating period; treatment was begun 60 days before pairing, and toxicity with respect to testicular and reproductive functions was examined. In females of the 2000 ppm-treated group, salivation and lacrimation that may have been caused by CNS depression were observed starting 20 days after exposure. Although no abnormalities were seen in mating behavior or fertility, fetal mortality and the number of dams with dead fetuses increased in the 2000 ppm group. In the males exposed to 2000 ppm toluene for 90 days, an increase in kidney weights and a decrease in thymus weights were observed. Basophilic changes and necrosis of kidney tubules were greater at the higher exposure level. Additionally, decreases in the weights of the epididymides and spermatic count were observed, indicating toxicity of toluene to the male reproductive system in vivo for the first time. In conclusion, embryo-fetal toxic effects were apparent in female rats exposed to toluene before and during the early stage of pregnancy. Subacute exposure to a high level (2000 ppm) of toluene vapor elicited mild toxic changes in the kidneys, thymus, and reproductive organs of males. Toxic effects on fertility and reproduction were thus demonstrated not only in females but also in males exposed to toluene vapor in the present study.

Administration, Inhalation↗
PubMed1995

Synthesis of beta-D-GlcpNAc-(1-->2)-5a-carba-alpha-D-Man p-(1-->6)-beta-D- Glcp-O(CH2)7CH3: a reactive acceptor analog for N-acetylglucosaminyltransferase-V.

The branching enzyme N-acetylglucosaminyltransferase-V (GlcNAcT-V) recognizes the trisaccharide beta-D-GlcpNAc-(1-->2)-alpha-D-Man p-(1-->6)-beta-D-Glcp-O(CH2)7CH3 (1) as its minimum substrate. We report here the chemical synthesis of beta-D-GlcpNAc-(1-->2)-5a- carba-alpha-D-Manp-(1-->6)-beta-D-Glcp-O(CH2)7CH3 (2), a carbocyclic analog of 1 where the ring oxygen of the alpha-D-Manp residue is replaced by a methylene group. Trisaccharide 2 was found to be fully active as an acceptor for GlcNAcT-V, both with the enzyme isolated from hamster kidney and the one cloned from rat kidney. The kinetic parameters Km and Vmax for 1 and 2 were functionally equivalent. A preparative glycosylation reaction was performed using 2 as the acceptor with the cloned rat kidney enzyme. A tetrasaccharide formed by the addition of a Glc pNAc residue was the sole product as detected by 1H NMR spectroscopy and FAB mass spectrometry and was assigned the structure beta-D-GlcpNAc-(1-->2)-[beta-D-GlcpNAc-(1-->6)]-5a- carba-alpha-D-Manp-(1-->6)-beta-D-Glc p-O(CH2)7CH3 (13).

Animals↗
PubMed1995

Evolution of Mirizzi syndrome with biliobiliary fistula.

The mechanisms of fistula formation were analyzed in eight patients with Mirizzi syndrome with biliobiliary fistula. The fistula was type 1 in three patients and type 2 in five, according to the Corlette-Bismuth classification. The apparent mechanisms of fistula formation include inflammation of the gallbladder, its subsequent fusion to the bile duct, and increase in the internal pressure due to either contraction of the gallbladder or multiple stones. However, no predisposing conditions other than a longstanding history of cholelithiasis have been suggested. Differences in the type of fistula are considered to be due to the mode of fusion of the gallbladder to the bile duct, and the size of the perforation, which is apparently determined by the area in contact with the stone.

Adult↗
PubMed1995

Synthesis and structure-activity studies of a series of 1-oxa-8-azaspiro[4.5]decanes as M1 muscarinic agonists.

2,8-Dimethyl-1-oxa-8-azaspiro[4,5]decan-3-one (17), designed by incorporating the tetrahydrofuran ring moiety of muscarone into an 8-azaspiro[4,5]decane skeleton, and related 1-oxa-8-azaspiro[4.5]decanes were synthesized and assessed as M1 muscarinic agonists for the symptomatic treatment of dementia of Alzheimer's type. The compounds were tested for central muscarinic M1 and M2 receptor affinity and in vivo muscarinic activities: namely, amelioration of scopolamine-induced impairment in rat passive avoidance tasks, and induction of hypothermia, tremor, and salivary secretion. Compound 17 exhibited potent muscarinic activities in vitro and in vivo with no selectivity. Systematic modifications of 17 were conducted, and a number of compounds, including the 2-ethyl analogue (18), 3-methylene analogue (29), 3-dithioketal analogues (26, 28), and 3-oxime analogue (37) were found to display preferential affinity for M1 receptors over M2 receptors and, in addition, to exhibit potent antiamnesic activity sufficiently separated from hypothermia-inducing activity, taken as an index of cholinergic side effects, compared with the reference compound RS86 (1). Structure-activity relationships are discussed in comparison with those for muscarone analogues. Of these compounds only two, 2-ethyl-8-methyl-1-oxa-8-azaspiro[4.5]decan-3-one (18) and 2,8-dimethyl-3-methylene-1-oxa-8-azaspiro[4.5]decane (29), stimulated phosphoinositide hydrolysis in rat hippocampal slices, indicating partial agonistic activity for M1 muscarinic receptors. The optical resolution of 18 and 29 was performed. Eudismic ratios of both compounds in binding affinity were low, but M1 agonist activity resided preferentially in the (-)-isomers. The absolute configuration of (-)-29 was determined by X-ray crystal structure analysis to be S, being the same as that of muscarone. Based on the in vivo selectivity, (-)-29 was selected for clinical studies.

Alkanes↗
PubMed1995

Evaluation of anthelmintic efficacy of doramectin against gastrointestinal nematodes by fecal examination in cattle in Japan.

The nematocidal effect of doramectin was assessed by subcutaneous injection of 200 micrograms/kg (single dosage) in cattle with naturally acquired gastrointestinal nematode infection in Japan. This study consisted of two experiments. In experiment 1, animals were randomly divided into a doramectin group (n = 21) and a non-treated control group (n = 21) by fecal egg count. In experiment 2, another group of ivermectin treatment (n = 12) was prepared in addition to doramectin (n = 23) and control (n = 10) groups, by random assignment as in study 1. After doramectin or ivermectin treatment, the egg count/5 g of feces was measured by the sucrose centrifugal flotation method at intervals of 7 days until Day 21 in experiment 1 and at Days 7, 14, 21, 35, 42, 49 and 63 in experiment 2. Coproculture was also carried out using some of the fecal samples. In the 2 doramectin-treated groups, 96.1%-100% egg reduction rates were obtained for Haemonchus, Cooperia, Mecistocirrus, Trichostrongylus, Ostertagia, Bunostomum, Strongyloides and Trichuris from the 7th day until the 49th day after treatment. Thus doramectin was confirmed to be highly effective against those species of adult nematoda. The effect against Mecistocirrus has not been previously determined. The nematocidal effect against Nematodirus was lower (egg reduction rate approximately 50%) than other species. No adverse reactions to treatment were seen in any animal during either study.

Animals↗
PubMed1995

Reproductive and developmental toxicity studies of toluene. I. Teratogenicity study of inhalation exposure in pregnant rats.

Toluene is a widely used solvent in industry which is the subject of abuse among the younger generation. A teratogenicity study of toluene by inhalation exposure was carried out in Sprague-Dawley rats and the effects on dams, fetuses and offspring were assessed. Pregnant females were exposed to 600 or 2000 ppm toluene for 6 h/day from day 7 to day 17 of pregnancy. The control group inhaled conditioned clean air under the same exposure conditions. Maternal exposure to 2000 ppm toluene caused significant toxic effects such as body weight suppression of dams and offspring, high fetal mortality and embryonic growth retardation, but no external, internal or skeletal anomalies were observed in the fetuses of any treated group. In addition, there were no differences in the results of pre- and postweaning behavioral tests of the offspring. However, no toxic or teratogenic changes which could be related to toluene exposure were apparent in the 600 ppm group. Further studies are warranted with toluene at higher concentrations applied during the period of organogenesis.

Abnormalities, Drug-Induced↗
PubMed1995

[Effects of polychlorinated biphenyls on regeneration of the peripheral nerve in rats].

The effects of polychlorinated biphenyls (PCB) on regeneration of the peripheral nerves were investigated in rats. The sciatic nerves were crushed at the mid-thigh level on the last day of 32 days of oral administration of PCB. The sciatic nerves were biopsied from the crushed regions at 1, 2, 4, 8 and 12 weeks after crushing. Myelin thickness on the axon diameter was smaller in the PCB administered group than in the control group. There was no difference between the experimental group and the control group in the density of regenerating fibers and distribution of fiber diameters in unmyelinated fibers. After 12 weeks the number of large diameter myelinated fiber densities was lower in the experimental group than in the control group. These results indicate that PCB may affect the remyelination of the regenerating nerve.

Animals↗
PubMed1995

[The enzymatic character of myeloma cell].

Thymidine kinase (TK) is a cellular enzyme required for the incorporation of thymidine into DNA. It catalyses the conversion of deoxythymidine to deoxythymidine monophosphate (dTMP). The synthesis of dTMP from deoxythymidine is called the salvage pathway. There are two types of thymidine kinase, distinguished by there biochemical and physico-chemical characteristics. Cytosolar TK is found in dividing cells in stages G1-S. Mitochondrial TK is found in mitochondria. Serum thymidine kinase (S-TK) levels can be determined by the use of a radioenzyme assay method. These are increased in proliferating cells (S phase). It is a useful tool for the clinical evaluation, staging, and follow-up of patients with multiple myeloma.

Adult↗
PubMed1995

[Complete resection of superior mediastinal seminoma, following reconstruction of superior vena cava--a case report].

The patient was a 37-year-old man with superior mediastinal seminoma, which invaded the bilateral brachiocephalic vein, superior vena cava, pericardium and left lung. These invaded organs were resected with the tumor and a vascular reconstruction was performed with EPTFE graft and pericardial patch. EPTFE graft was interposed between the left brachiocephalic vein and right atrium. Superior vena cava was reconstructed by means of pericardial patch. Histologically, the tumor was diagnosed as pure seminoma. He received the prophylactic irradiation (45 Gy). Although venography two years after operation demonstrated the obstruction of the EPTFE graft and marked stenosis of the pericardial patch, the patient remains free from the symptom and is doing well without recurrence 45 months after operation.

Adult↗