Biomedical subjects

T Horie

Publications and source records attributed to T Horie.

At least 613 records · Page 34Linked to original sources

PubMedDate not supplied

A new tactile skin sensor for measuring skin hardness in patients with systemic sclerosis and autoimmune Raynaud's phenomenon.

We used a new tactile sensor to measure the elastic properties of skin in patients with systemic sclerosis or Raynaud's phenomenon. The sensor consists of a piezoelectric vibrator with vibration pickup to measure frequency changes when the sensor is placed on the skin. The mean frequency change at the skin surface of the proximol third phalanx in patients with systemic sclerosis was significantly lower than in age- and sex-matched controls. The results in systemic sclerosis patients were statistically correlated to the Modified Rodnan Skin Thickness Score. This technique was also used to measure the therapeutic efficacy of salpogrelate, a new specific serotonin receptor antagonist. A greater mean frequency change was seen after treatment. We conclude that this new tactile sensor is useful for quantitatively measuring skin sclerosis and may help determine the efficacy of therapeutic treatments.

Benzene Derivatives↗

PubMedDate not supplied

Detection of Grb-2-related adaptor protein gene (GRAP) and peptide molecule in salivary glands of MRL/lpr mice and patients with Sjögren's syndrome.

The pathogenesis of Sjögren's syndrome (SS) is poorly understood. In this study we used an in-house mouse spleen cDNA microarray to analyse genes in spleens from MRL/lpr (an SS mouse model) mice. We have previously demonstrated that GRAP genes were up-regulated in salivary glands of the same mice. The microarray analysis showed that seven out of 2304 genes were highly expressed in spleens from the MRL/lpr mice, one of which was the GRAP gene. In other words, the GRAP gene is highly expressed in the salivary glands and spleen of MRL/lpr mice. We also carried out immunohistochemical studies. Mouse and human Grb-2-related adaptor protein (GRAP) antigens were expressed on ductal cells and infiltrating lymphocytes in salivary glands of MRL/lpr mice and SS patients, but only weakly in controls (MRL/+ mice and individuals with salivary cysts). These results suggest that the GRAP gene might have a role in the pathogenesis of SS.

Adaptor Proteins, Signal Transducing↗

PubMedDate not supplied

Huge IgD plasmacytoma in the abdomen presenting coagulation necrosis.

A 65-year-old Japanese woman was diagnosed in 1996 with a pathological fracture of the left femur caused by immunoglobulin D-type myeloma (IgD myeloma). She responded well to combination chemotherapy followed by irradiation. The patient experienced renal failure and became dependent on haemodialysis. In 1999, large plasmacytomas developed in the abdomen and left humerus. The abdominal tumour appeared to induce gastroduodenal ulcers and jejunal obstruction. We initiated irradiation therapy without chemotherapy to prevent further growth of the plasmacytoma, although treatment-resistant gastroduodenal ulcers developed. Continued blood loss from the gastroduodenal ulcers resulted in a deterioration in the patient's health, which prevented successful haemodialysis. An autopsy showed that the plasmacytoma had undergone coagulation necrosis. We conclude that the use of combination chemotherapy with topical irradiation was an acceptable treatment measure against IgD plasmacytoma; irradiation without chemotherapy was the most likely cause of the coagulation necrosis seen in the plasmacytoma at autopsy.

Abdominal Neoplasms↗

PubMedDate not supplied

Pure red cell aplasia and myelofibrosis in B-cell neoplasm.

We describe an unusual case of B-cell neoplasm accompanied by pure red cell aplasia (PRCA) and myelofibrosis in a 67-year-old male presenting with severe anaemia. A few unclassified, myeloperoxidase-negative blastoid cells were seen on bone marrow aspiration, and erythroid cell hypoplasia and myelofibrosis on bone marrow biopsy. An autoimmune PRCA was suspected, as serum CH50, C3 and C4 levels were consistently low. Ciclosporin was effective in treating the anaemia, but anaemia returned when the drug was discontinued. Thirteen months later, the patient was admitted with pleural effusion and ascites that contained monoclonal CD19+ CD20+ immature blast cells with a complex karyotype, thought to be neoplastic B-cells. The unclassified blastoid cells seen earlier may therefore have been from the same origin. The patient deteriorated rapidly and died. Only one case of non-Hodgkin's lymphoma with PRCA and myelofibrosis has been reported previously. We discuss the possibility that dysregulated T-cells induced by neoplastic B-cells may have given rise to concomitant PRCA and myelofibrosis.

Aged↗

PubMedDate not supplied

Moderate dose-intensive chemotherapy for patients with non-small cell lung cancer: randomized trial, can it improve survival of patients with good performance status?

Advanced non-small cell lung cancer (NSCLC) has proven to be remarkably resistant to standard chemotherapy regimens. One potential alternative approach is the use of dose-intensive chemotherapy with supportive therapy such as granulocyte-colony stimulating factor (G-CSF). We conducted a randomized study of dose-intensive cisplatin/vindesine/mitomycin C chemotherapy (DI-PVM) and standard cisplatin/vindesine/mitomycin C chemotherapy (PVM). A total of one hundred patients with III-IV NSCLC was randomized. The DI-PVM consisted of 3 cycles of cisplatin: 80 mg/m2 (day 1), vindesine: 3 mg/m2 (days 1 and 8) and mitomycin C: 8 mg/m2 (day 1) in 3-week intervals with concurrent G-CSF. The PVM consisted of 2 cycles of the same chemotherapy in 4-week intervals. Blood cell counts were checked twice a week, and G-CSF (2 microgram/kg, SC) was administered when the count was </=2000/microliter. Eligibility criteria for this study were: no previous therapy, no active concomitant malignancy, ECOG PS </=1, age </=75 and adequate hematologic functions. The response rate for DI-PVM (26/50, 52%) was not significantly higher than that for PVM (22/50, 44%, chi2; p=0.423). However, progression-free survival for patients on DI-PVM was significantly longer than that of patients on PVM (23.7 versus 13.9 weeks, log-rank and generalized Wilcoxon test; p=0.006), as was overall median survival (57.0 versus 37.7 weeks, generalized Wilcoxon test; p=0.036). In addition, the difference in survival of patients with metastatic disease was significant (DI-PVM versus PVM; 48.9 weeks versus 23.9; p=0.032). Multivariate analysis showed that only ECOG PS was an independent prognostic variable in predicting response and survival on DI-PVM regimen. Hematological and non-hematological toxicities were equally frequent. The DI-PVM archived a longer survival than the PVM. The DI-PVM regimen should be considered a standard regimen for patients with metastatic NSCLC.

Adult↗

PubMedDate not supplied

Long-term case study of myelodysplastic syndrome in a dog.

A 10-year-old, female shih tzu was diagnosed as having myelodysplastic syndrome (MDS) based on the presence of a nonregenerative anemia, dysplastic changes in the three hematopoietic cell lines, a normal to hypercellular bone marrow, and less than 30% blast cells of all nucleated cells in the bone marrow. Low-dose aclarubicin, a differentiation-induction therapy for MDS and atypical leukemias in humans, was administered. Hematological improvement was observed, and the dog lived for 809 days after the first presentation.

Aclarubicin↗

PubMedDate not supplied

Endoscopic pericardial fenestration for a patient with sustained lupus pericarditis.

A 57-year-old woman was diagnosed in January 1982 with SLE based on ANA 1:640, positive LE cell preparation, proteinuria (3+), and pericarditis. In 1984, 1994, and 1997, the pericardial effusion was noted to have increased without signs of disease exacerbation or cardiac tamponade, and pericardial drainage was repeated to control the effusion. A massive pericardial effusion developed in August 1997. After tuberculosis, hypothyroidism, neoplasm, and progression of SLE were ruled out, we decided to perform pericardial fenestration. A safe and minimally invasive pericardial fenestration was successfully completed endoscopically. Pathologic study of the specimen revealed chronic pericarditis. We consider endoscopic pericardial fenestration to be useful for at risk patients with pericarditis to control the effusion and establish a differential diagnosis.

Endoscopy↗

PubMedDate not supplied

Dose-intensive weekly alternating chemotherapy for patients with small cell lung cancer: randomized trial, can it improve survival of patients with good prognostic factors?

We conducted a randomized trial of dose-intensive weekly alternating chemotherapy (CAV/PE-W) and standard alternating chemotherapy (CAV/PE) in small cell lung cancer (SCLC) patients with good prognostic factors. A total of 76 patients with SCLC was randomized. The CAV/PE-W consisted of 4 alternating cycles of cyclophosphamide: 500 mg/m2, doxorubicin: 30 mg/m2, and vincristine: 1 mg/m2 (day 1) and cisplatin: 50 mg/m2 (day 8) and etoposide: 75 mg/m2 (days 8 and 9). The CAV/PE consisted of 2 alternating cycles of cyclophosphamide: 800 mg/m2, doxorubicin: 50 mg/m2, and vincristine: 1.4 mg/m2 (day 1), cisplatin: 100 mg/m2 (day 22) and etoposide: 100 mg/m2 (days 22, 23 and 24). Eligibility criteria were no prior therapy, no active concomitant malignancy, ECOG PS of 0 or 1, age < or =75, adequate hematologic functions and no brain metastasis. The complete response (CR) rate for CAV/PE-W (14/38, 36.8%) was significantly higher than that for CAV/PE (6/38, 15.8%, chi2; p=0. 032). However, the response rate in patients on CAV/PE-W (36/38, 94. 7%) was not significantly higher than the rate for CAV/PE (31/38, 81. 6%, chi2; p=0.076). Progression-free survival for patients on CAV/PE-W was significantly longer than that of patients on CAV/PE (41.4 weeks vs. 21.3 weeks, log-rank; p=0.0007, generalized Wilcoxon; p=0.0034) as was overall median survival (67.0 weeks vs. 51.2 weeks, log-rank; p=0.028). Actual dose-intensity of CAV/PE-W was 1.74 times that of CAV/PE. Hematological toxicities were equally frequent and G-CSF contributes to treatment efficacy by allowing administration of dose-intensive chemotherapy. The CAV/PE-W achieved a higher CR rate and longer survival, than the CAV/PE.

Adult↗

PubMedDate not supplied

Protective effect of prostaglandins on the methotrexate induced damage of small intestine in rats.

Methotrexate (MTX) treatment causes the damage of the small intestine, resulting in malabsorption. The aim of this study was to investigate the effect of prostaglandins (PGs), prostaglandin E1 (PGE1) and prostaglandin I2 (PGI2) analogues, on the MTX-induced damage of rat small intestine by examining the permeability of the small intestinal epithelium. The rats were treated as follows: MTX (15 mg/kg/day), MTX and PGE1/PGI2 analogues (0.5 and 5 micrograms/kg/twice a day), PGE1/PGI2 analogues alone, and sterile saline (control). All drugs were given orally for 5 days. The intestinal permeability of fluorescein isothiocyanate labeled dextran with average molecular mass 4.4 KDa (FD-4) was examined to evaluate the dysfunction of the small intestine by the in vitro everted small intestine technique. The permeation clearance of FD-4 obtained from the in vitro experiment of the MTX-treated rats increased remarkably, but that of the MTX and PGE1/PGI2 analogue-treated rats was significantly lower than that of the MTX-treated rats. These results indicated that PGE1 or PGI2 analogues possibly alleviated the MTX-induced damage of the small intestine of rats.

Alprostadil↗

PubMedDate not supplied

Increased Na(+)-dependent D-glucose transport in small intestine of retinyl palmitate treated rats.

The administration of retinyl palmitate (RP) to rats enhanced Na(+)-dependent D-glucose transport in the small intestine. Effects of RP on Na(+)-dependent D-glucose cotransporter (SGLT1) in rat small intestine were investigated in this study. RP was orally administered (1000 IU/kg/day) to rats for 3 days. The uptake of [3H]D-glucose into the brush-border membrane vesicles (BBMV) of the RP-treated rats, was 1.7-fold larger than that of the control rats. The western blot analysis of SGLT1 protein in BBMV indicated that the amount of SGLT1 was unaffected by the RP treatment. Scatchard analysis of phlorizin binding to both BBMV also showed that the dissociation constant (Kd) and number of phlorizin binding site (Bmax) were unchanged by the RP treatment. The fluidity of the brush-border membrane (BBM) was examined by measuring the fluorescence anisotropy of BBM labeled with 1, 6-diphenyl-1, 3, 5-hexatriene (DPH). The membrane fluidity decreased in the RP-treated rats compared with that of the control rats. In conclusion, the RP treatment increased the glucose transport in BBMV. This enhancement of glucose transport is unlikely due to the change in the amount of SGLT1 protein in BBM. The decrease of the BBM fluidity may contribute to the enhancement of glucose transport in BBM of the RP-treated rats by changing the affinity of SGLT1 for glucose and/or the turnover rate of SGLT1.

Animals↗

PubMedDate not supplied

Effect of a synthetic analog of prostaglandin E1 on the intestinal mucosa of methotrexate-treated rats.

Administration of methotrexate to rats sometimes induces small intestinal damage. A synthetic analog of prostaglandin E1, OP-1206 [17S,20-dimethyl-trans-delta2-prostaglandin E1] may possibly provide therapeutic benefits to help recovery from such small intestinal damage. The purpose of this study was to evaluate the effect of OP-1206 on methotrexate-induced small intestinal damage in rats. Methotrexate (15 mg/kg body weight) was orally administered to rats once daily for 5 days. OP-1206 (0.5 microg/kg body weight) was orally administered to rats twice a day for 5 days and on the 6th day the small intestine of the rats were examined histologically and biochemically. The methotrexate treatment of rats caused a severe histological change in the small intestinal mucosa, whereas the treatment combined of OP-1206 with methotrexate showed similar histological features of the small intestinal mucosa as that of the control rats. On the other hand, an acute intestinal inflammation was evaluated by determining myeloperoxidase activity. The myeloperoxidase activity in the small intestinal mucosa of the methotrexate-treated rats increased remarkably, whereas that of the methotrexate and OP-1206-treated rats was significantly lower than that of the methotrexate-treated rats. Thus, it was shown histologically and biochemically that OP-1206 was effective in protecting the small intestine from methotrexate-induced damage.

Alprostadil↗

PubMedDate not supplied

Enhanced absorption of 3-O-methyl-D-glucose through the small intestine of rats administered retinyl palmitate.

All-trans retinyl palmitate (RP) (1000 IU/kg body weight) was orally administered to rats for three days. The absorption of 3-O-methyl-D-glucose (3-OMG), which is actively transported by Na+-dependent D-glucose co-transporter (SGLT1), in the small intestine of the control and RP-treated rats was investigated by the in vito everted sac and in situ closed loop of intestine techniques. The absorption of [3H]3-OMG in both experiments of the in vito everted sac and in situ closed loop of intestine significantly increased in the RP-treated rats. AUC(0-120min) obtained from the [3H]3-OMG plasma concentration vs. time curve in the RP-treated rats was significantly larger than that in the control rats. On the other hand, the activity of Na+-K+-adenosinetriphosphatase (ATPase) and the transport rate of D-glucose mediated by Na+-independent facilitative glucose transporter (GLUT2) on the basolateral membrane (BLM) were similar between the control and RP-treated rats. Thus it is suggested that RP treatment of rats enhance the small intestinal absorption of glucose mediated by SGLT1.

3-O-Methylglucose↗

PubMedDate not supplied

6-Fluoro-2-methylspiro(chroman-4,4'-imidazolidine)-2',5'-dione and related compounds as inducers of monooxygenase in rat liver microsomes.

The relationship between the structure of spirohydantoin derivatives and their inducing effects on hepatic monooxygenase system was studied. At the dose of 1 mumol/kg (0.3 mg/kg), 6-fluoro-2-methylspiro(chroman-4,4'-imidazolidine)-2',5'-dione (M79175) was found to exhibit an inducing effect on benzphetamine N-demethylase. On the contrary, the inducing effect of Sorbinil, in which the 2-methyl group on the chroman ring of M79175 was replaced by hydrogen atom, on benzphetamine N-demethylase was 100 times less than that of M79175. The substitution of the methyl group of M79175 with the dimethyl group did not affect the inducing effect, whereas the substitution with the hexyl group resulted in the loss of the inducing effect on drug oxidation activities tested at a dose of 10 mg/kg. Furthermore, cyclohexane spiro-2,6-chloro-1'-(3-dimethylaminopropyl)spiro(chroman-4,4'-imidazolid ine)-2' , 5'-dione (M79193) had an inducing effect on total cytochrome P-450 content, but had no inducing effect on benzphetamine N-demethylase. In addition, M79175 was found to induce cytochrome P-450 which is immunochemically related to one of the major forms of phenobarbital-inducible cytochrome P-450 (P-450(PB-1], but not cytochrome P-450 which is immunochemically related to the major form of 3-methylcholanthrene-inducible cytochrome P-450 (P-450(MC-1]. On the other hand, M79193 was found to induce neither P-450(PB-1) nor P-450(MC-1).

Animals↗

PubMedDate not supplied

Ectopic calcinosis possibly due to 1 alpha (OH) vitamin D3 in a patient with systemic lupus erythematosus.

A 30-year-old woman with systemic lupus erythematosus (SLE) developed ectopic calcinosis. She had been receiving prednisolone since 1980 with the addition of vitamin D3 in 1986. Despite this therapy, her renal function had gradually deteriorated. Right gonalgia was noted in September 1991. X-ray findings revealed calcinosis of the arteries of the femur, poplitea, cubitus, hands, and feet. Her finger pads and joint sacs were also involved. Calcinosis seen in SLE has only rarely been reported, and that observed in association with vitamin D intoxication or arteriosclerosis has a different distribution of calcium deposits. The use of vitamin D3 in our patient with renal disability may have induced calcinosis with a unique distribution.

Adult↗

PubMedDate not supplied

Cytochrome P450 isozymes involved in propranolol metabolism in human liver microsomes. The role of CYP2D6 as ring-hydroxylase and CYP1A2 as N-desisopropylase.

Oxidative metabolic pathways of propranolol consist of naphthalene ring-hydroxylations (at the 4-, 5-, and 7-positions) and side-chain N-desisopropylation in mammals. We characterized cytochrome P450 isozymes responsible for propranolol metabolism, especially N-desisopropylation and 5-hydroxylation, in human liver microsomes. 4-Hydroxy, 5-hydroxy-, and N-desisopropylpropranolol were detected as primary metabolites, whereas 7-hydroxypropranolol was in trace amounts. Good correlations were obtained for activities of propranolol 4- and 5-hydroxylases with immunochemically determined CYP2D6 content, whereas correlations of these activities with CYP1A2, CYP2C, or CYP3A4 content were relatively low. The activities also correlated highly with debrisoquine 4-hydroxylase, compared with other metabolic activities such as phenacetin O-deethylase, hexobarbital 3'-hydroxylase, and testosterone 6 beta-hydroxylase, which are typical reactions for CYP1A2, CYP2C, and CYP3A4, respectively. Propranolol N-desisopropylase activity in the samples highly correlated with CYP1A2 content and phenacetin O-deethylase activity, but not with the other P450 isozyme contents or metabolic activities. Quinidine, a specific inhibitor of CYP2D6, inhibited propranolol 4- and 5-hydroxylase activities selectively and in a concentration-dependent manner. alpha-Naphthoflavone, a potent inhibitor of CYP1A2, inhibited all of the propranolol oxidation activities, and the IC50 value for N-desisopropylase activity was much smaller than the values for ring-hydroxylase activities. Antibody directed to CYP2D inhibited propranolol 4- and 5-hydroxylase activities by 70% at an antibody/microsomal protein ratio of 1.0. Anti-CYP2C9 antibody did not inhibit any activity determined. These results indicate that propranolol 5-hydroxylation, as well as 4-hydroxylation, is mainly catalyzed by CYP2D6 in human liver microsomes.(ABSTRACT TRUNCATED AT 250 WORDS)

Benzoflavones↗

PubMedDate not supplied

Restriction fragment length polymorphism (RFLP) analysis in the TNF genes of patients with systemic lupus erythematosus (SLE).

Although systemic lupus erythematosus (SLE) is known to be positively associated with certain major histocompatibility complex (MHC) class I and/or class II antigens, it is not clear whether the MHC genes are the predisposing genes of the disease rather than markers for other closely linked gene(s). Because of the involvement of tumor necrosis factor (TNF) in the inflammation process and localization of the TNF genes in the proximity of the HLA-B locus, we studied the restriction fragment length polymorphism (RFLP) of the TNF-alpha and -beta genes in 20 SLE patients and 23 normal individuals using restriction endonuclease NcoI. The frequency of a 5.5 kb NcoI fragment from SLE patients was significantly higher than that from normal controls. This result suggests that the polymorphic TNF genes may be involved in the pathogenesis of SLE.

Alleles↗

PubMedDate not supplied

[Histopathological findings of coronary artery lesions resected by directional coronary atherectomy].

Eleven directional coronary atherectomy procedures were performed in seven patients with angina pectoris and four patients with myocardial infarction, 10 men and 1 woman aged 41 to 69 years (mean 57 +/- 7 years). The onset of angina pectoris or myocardial infarction had occurred 2 months to 17 years previously. The preoperative mean diameter of stenosis was 80 +/- 8%, and the mean residual diameter of stenosis was 6 +/- 9% (p < 0.01). Seven left anterior descending arteries and four right coronary arteries were treated. Five of the 11 patients received partial-thickness resections of medial tissue and two of the five patients received full-thickness resections of the media with adventitial tissue. No lesions showed aneurysms or perforations during coronary arteriography after the procedure. The resected tissue was examined microscopically. Intimal tissues stained with Masson's trichrome were classified into four groups according to the characteristics fibrous tissue and the amount of proliferative cells: Type I was old dense fibrous tissue, type II was relatively old fibrous tissue containing many proliferative cells, type III was new loose fibrous tissue containing many proliferative cells, and type IV was atheromatous plaque. The intimal tissues were type I in 48.0%; type II in 35.5%; type III in 14.8%; and type IV in 1.7%. Resected lesions without prior treatment (primary lesions) from five patients with histories of 3 months or less were characterized by much type II and type III tissue; (type I tissue, 33.8%; type II tissue, 51.1%; type III tissue, 14.5%; type IV tissue, 0.6%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMedDate not supplied

Increased soluble CD23 molecules in serum/saliva and correlation with the stage of sialoectasis in patients with primary Sjögren's syndrome.

OBJECTIVE: We examined the soluble CD23 (sCD23) molecules in sera and saliva from patients with Sjögren's syndrome. METHODS: The determination of sCD23 and other soluble molecules were made by the enzyme-linked immunosorbent assay. RESULTS: The amounts of sCD23 in the sera/saliva were significantly increased in the patients compared to the controls and the levels were significantly correlated with sialoectasis. CONCLUSION: The findings suggest that increased sCD23 molecules in saliva from patients with Sjögren's syndrome may reflect active sialoectasis.

Adult↗