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Biomedical subjects

S Naitoh

Publications and source records attributed to S Naitoh.

At least 19 recordsLinked to original sources
PubMed2001

The transient receptor potential protein homologue TRP6 is the essential component of vascular alpha(1)-adrenoceptor-activated Ca(2+)-permeable cation channel.

The Drosophila transient receptor potential protein (TRP) and its mammalian homologues are thought to be Ca(2+)-permeable cation channels activated by G protein (G(q/11))-coupled receptors and are regarded as an interesting molecular model for the Ca(2+) entry mechanisms associated with stimulated phosphoinositide turnover and store depletion. However, there is little unequivocal evidence linking mammalian TRPs with particular native functions. In this study, we have found that heterologous expression of murine TRP6 in HEK293 cells reproduces almost exactly the essential biophysical and pharmacological properties of alpha(1)-adrenoceptor-activated nonselective cation channels (alpha(1)-AR-NSCC) previously identified in rabbit portal vein smooth muscle. Such properties include activation by diacylglycerol; S-shaped current-voltage relationship; high divalent cation permeability; unitary conductance of 25 to 30 pS and augmentation by flufenamate and Ca(2+); and blockade by Cd(2+), La(3+), Gd(3+), SK&F96365, and amiloride. Reverse transcriptase-polymerase chain reaction and confocal laser scanning microscopy using TRP6-specific primers and antisera revealed that the level of TRP6 mRNA expression was remarkably high in both murine and rabbit portal vein smooth muscles as compared with other TRP subtypes, and the immunoreactivity to TRP6 protein was localized near the sarcolemmal region of single rabbit portal vein myocytes. Furthermore, treatment of primary cultured portal vein myocytes with TRP6 antisense oligonucleotides resulted in marked inhibition of TRP6 protein immunoreactivity as well as selective suppression of alpha(1)-adrenoceptor-activated, store depletion-independent cation current and Ba(2+) influx. These results strongly indicate that TRP6 is the essential component of the alpha(1)-AR-NSCC, which may serve as a store depletion-independent Ca(2+) entry pathway during increased sympathetic activity.

Adrenergic alpha-Agonists↗
PubMed2000

[Evaluation of F1 + 2/TAT ratios in Japanese patients with antiphospholipid syndrome].

The clinical manifestations of the antiphospholipid syndrome(APS) include arterial and venous thrombosis and a fetal loss, but the pathogenic mechanisms remain unclear. To clarify the mechanism of thrombogenic state in APS, we investigated the markers for thrombosis including thrombin-antithrombin complex(TAT) in patients with antiphospholipid antibodies(aPL). Prothrombin fragment 1 + 2(F1 + 2) in patients with APS and in autoimmune disease patients with aPL increased significantly compared with those obtained in autoimmune disease patients without aPL or in control subjects. However, there was not a significant difference in the TAT level of each group, suggesting that the formation of TAT was impeded in APS. To investigate which aPL is responsible for the disturbance of the TAT formation, the ratio of F1 + 2/TAT was calculated. The ratio increased in patients with lupus anticoagulant, especially with prolonged kaolin clotting time, and furthermore the ratio strongly increased in patients with IgG type-anticardiolipin antibodies(aCL). Our results suggest that IgG-aCL is associated with thrombogenic state in APS because free thrombin is present in patients' blood by impeding the formation of TAT by mainly IgG-aCL.

Adult↗
PubMed1997

[A case of malignant mesothelioma of the pleura and the peritoneum detected by sudden onset of back pain and pleural effusion and ascites].

A case of malignant mesothelioma of the pleura and the peritoneum is reported. In April 1996, a 40-year-old men noticed sudden onset of back pain. Radiographic examinations and MRI revealed pleural effusions, ascites, ringed enhanced tumorous lesions in the right posterior diaphragm along the abdominal aorta, and marked thickening of the right diaphragm with moderate signal intensity. On thoracoscopic surgery, there were white small nodules on the intercostal parietal pleura. Tumor cells of a tubulopapillary pattern had large rounded nuclei and eosinophilic cytoplasms in a partially glandlike arrangement. Cytoplasms of tumor cells stained for alcian blue disappeared after hyaluronidase digestion. Immunohistochemical examinations showed positive staining for keratin but negative for CEA. Electron micrographs showed numerous long thin microvilli, desmosomes and intermediate tonofilaments. From these findings, malignant mesothelioma was diagnosed. The malignant mesothelioma cells of the pleura in this case were considered to disseminate the peritoneum directly through the diaphragm or its lymphatic canals. MRI and thoracoscopic surgery were useful for the demonstration of the pleural disseminations and abdominal invasions.

Adult↗
PubMed1996

Cold activation of complement for monitoring the response to interferon in patients with chronic hepatitis C.

OBJECTIVES: Because of its specific association with hepatitis C virus (HCV) infection, the cold activation of complement is an easy and inexpensive indicator of HCV viremia. It was evaluated for eligibility as a marker of response to interferon in patients with hepatitis C. METHODS: The cold activation of complement was determined by the loss or decrease of hemolytic activity with the microtitration method in sera that had been stored at 4 degrees C overnight. RESULTS: We observed the loss of hemolytic activity by the cold activation of complement in 236 (72%) and a decrease in 56 (17%) of 327 sera from patients with HCV-associated chronic liver disease, which was much more (p < 0.001) that in 1 (1%) and 13 (14%), respectively, of 49 sera from patients with chronic liver disease associated with hepatitis B virus infection. Interferon-alpha (total dose 516 x 10(6) units) or interferon-alpha 2b (774 x 10(6) units) was given to 67 patients with chronic hepatitis C, of whom 56 had the cold activation of complement. The response to interferon was evaluated by the clearance of serum HCV RNA at 6 months after the completion of therapy. The cold activation of complement disappeared in 18 patients, of whom 15 (86%) responded. It persisted or fluctuated in the remaining 38 patients, only six (16%) of whom responded to interferon (p < 0.001). The cold activation of complement once disappeared at the completion of interferon and then reappeared in patients who relapsed after completing interferon therapy. CONCLUSIONS: These results indicate that the cold activation of complement may be associated with the presence of HCV in blood and a lower rate of durable response after completion of interferon therapy.

Adult↗
PubMed1996

[Clinical early phase II study of bicalutamide (Casodex) in patients with prostatic cancer].

To investigate the efficacy and safety of bicalutamide (Casodex) with its clinically recommended dose, the randomized early phase II study was performed in 124 patients with prostatic cancer (stage C, D). The patients were given 50, 80 or 100 mg of bicalutamide orally once a day in fixed doses for 12 weeks; 122 patients were eligible for evaluation. The overall response rate was 50.0% (20/40), 61.0% (25/41) and 53.7% (22/41) in the 50 mg, 80 mg and 100 mg groups, respectively. The response rate in prostate lesion, bone and lymph node metastases was slightly higher in the 80 mg group than in the 50 mg and 100 mg groups. The proportion of patients showing a response with regard to serum PSA (CR and PR) was 84.2, 92.7 and 97.6% in the 50, 80 and 100 mg groups, respectively. The incidence of adverse reactions was 65.0, 61.0 and 61.0% in the 50, 80 and 100 mg groups, respectively, and there was no significant difference in overall safety rating in the three groups. Frequent adverse reactions were gynecomastia and breast pain. Only one patient in the 80 mg group was withdrawn due to shortness of breath. Serum concentrations of LH, testosterone and estradiol increased significantly after treatment. Bicalutamide was concluded to be effective and well tolerated in patients with prostatic cancer, and its recommended dose was 80 mg once daily.

Administration, Oral↗
PubMed1995

A huge immature cervical teratoma in a newborn: report of a case.

A neonate with a large cervical mass was transferred to our hospital at 4 days of age. A computed tomography scan showed a contrast-enhanced solid mass with multiple cystic elements and fine calcification. Ultrasonography also revealed a predominantly solid mass with calcification, containing multiple cysts. These studies suggested a teratoma, but could not rule out a hemangioma. The tumor was removed on the 12th day of life. A pathological study revealed an immature teratoma that demonstrated fetal type cartilage and an immature neural tube. The operative complete removal of a cervical teratoma in neonates is recommended as soon as possible. The management of a pediatric cervical teratoma should also be similar to that of a sacrococcygeal teratoma. The incidence of cervical teratoma in all pediatric teratomas ranges from 2.3%-9.3% in the West, and from 1.6%-8.3% in Japan.

Cartilage↗
PubMed1995

A comparison of three methods used for treatment of ranula.

PURPOSE: This report compares the treatment results for oral and plunging ranulas. PATIENTS AND METHODS: Twenty-seven patients were retrospectively examined concerning treatment methods and recurrence on the basis of their medical records. The surgical specimens were also examined microscopically. RESULTS: Four patients had excision of the ranula only, 22 had marsupialization, and nine had removal of the sublingual gland combined with the excision of the ranula. These treatments showed a 25.0%, 36.4% and 0% recurrence rate, respectively. Histological observation revealed no epithelial lining in any of the examined specimens. CONCLUSIONS: Removal of the sublingual gland combined with the ranula was the most reliable method among the above three used.

Humans↗
PubMed1995

[Intestinal motility after massive small bowel resection].

To evaluate intestinal motility after 80% massive distal small bowel resection (MSBR), we continuously monitored interdigestive and postprandial bowel motility using bipolar electrodes and/or contractile strain gage force transducers in conscious beagle dogs before, and at 0-4 weeks and 8-13 months after the surgery. Fasting duodenal migrating myoelectric (or motor) complexes (MMCs) occurred at longer intervals in the short-term after 80% MSBR than in controls, and were simulated in long-term that in controls. MMCs arising from the duodenum were often migrated to the proximal jejunum, the jejunum above the anastomosis, and to the terminal ileum beyond the anastomosis. The velocity of duodenal MMC propagation was slowed in every intestinal segment in the short-term, and had not recovered even long after the operation. The duration of the postprandial period without duodenal MMCs was prolonged significantly in the short-term, and still remained longer in the long-term than in controls. These findings suggest that changes in gut motility after MSBR tend to compensate for the shorter intestine and maintain small bowel absorption early postoperatively, and adaptations of motility would occur over the long-term to increased intestinal absorption.

Animals↗
PubMed1994

Prompt decrease of circulating hepatitis C virus in patients with chronic hepatitis C after treatment with interferon.

Patients with chronic hepatitis C were treated with interferon (IFN) and followed for hepatitis C virus (HCV) RNA and antibody to HCV (anti-HCV) in serum. The response was correlated with decrease in serum levels of HCV RNA, as well as HCV genotypes and liver histopathology. Response to IFN, estimated by clearance of HCV RNA and normalization of aminotransferase levels at 6 months after the withdrawal of IFN, was observed in 11 (31%) of 35 patients infected with HCV of genotype II/1b, 13 (72%) of 18 with genotype III/2a, and 2 (33%) of 6 with genotype IV/2b; a single patient with genotype I/1a responded while the one doubly infected with HCV of genotypes II/1b and IV/2b did not. Response was seen in 10 (71%) of 14 patients with chronic persistent hepatitis, 14 (39%) of 36 with chronic active hepatitis 2A, and 3 (27%) of 11 with 2B. Response was achieved less often in patients with high than low pretreatment levels of HCV RNA. HCV RNA dropped sharply on a day after the start of IFN, and continued to decrease during the 2 weeks, irrespective of the response to IFN or HCV genotypes. In contrast, anti-HCV decreased more gradually and only in responders to IFN. These results support the rapid development of an IFN-mediated antiviral effect on HCV, and support therapeutic effects of IFN dependent on histopathology of liver as well as HCV RNA titers and genotypes.

Alanine Transaminase↗
PubMed1993

Functional roles of cyclic guanosine 3',5'-monophosphate analogue in cerebral vasodilation.

1. Vasodilating effects of cyclic nucleotides in cerebral vasculature were examined using membrane permeable cyclic nucleotide analogues, 8-bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP) and 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP). 2. In isolated canine basilar artery (CBA), 8-Br-cGMP but not 8-Br-cAMP, significantly inhibited Ca(2+)-induced and agonist [serotonin(5-HT), prostaglandin(PG)F2 alpha or endothelin]-induced contraction, in a concentration-dependent manner. 3. When Ca2+ was depleted from intracellular store sites by pretreatment with A23187, 8-Br-cGMP but not 8-Br-cAMP strongly attenuated contractions induced by Ca(2+)-influx. 4. Neither 8-Br-cGMP nor 8-Br-cAMP modified contraction induced by caffeine which elicits Ca2+ release from intracellular Ca2+ store. 5. 8-Br-cGMP lowered the high K(+)-induced sustained [Ca2+]i elevation. 6. These results suggest that, at least in CBA, cGMP exerts its inhibitory effect on the contraction induced by influx of Ca2+, by reducing the level of [Ca2+]i and reducing [Ca2+]i sensitivity of the contractile machinery.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1992

[Assessment of alveolar epithelial permeability in progressive systemic sclerosis (PSS) using 99mTc-DTPA (diethylene triamine penta acetate) aerosol inhalation].

To evaluate alveolar epithelial damage in PSS, we studied pulmonary epithelial permeability by measuring the clearance of inhaled 99mTc-DTPA aerosol and performing thin slice CT scan, pulmonary function tests and right heart catheterization in 28 patients with PSS. The 99mTc-DTPA clearance rate (kep value) in PSS was greater than in 11 non-smoking normal subjects (18.2 +/- 7.63 x 10(-3)/min vs. 9.12 +/- 0.77 x 10(-3)/min, p less than 0.01). In PSS, the kep value did not correlate with age, sex, duration of illness, dermal lesions, % vital capacity, or PaO2. In contrast, the kep value showed significant correlations with %DLco (diffusing capacity for carbon monoxide), extent of interstitial lesions evaluated by CT scan (CT score), and mean pulmonary artery pressure. On the other hand, the kep value was high in some patients with normal CT scan and normal %DLco. These findings indicate that pulmonary interstitial lesions in PSS are accompanied by alveolar epithelial damage, and that the clearance of 99mTc-DTPA may be an early predictor of interstitial change.

Administration, Inhalation↗
PubMed1991

Phorbol 12,13-diacetate-induced contraction of the canine basilar artery: role of protein kinase C.

The pharmacological and biochemical mechanisms of contractile responses to the protein kinase C (PKC) activator phorbol-12,13-diacetate (PDA) were investigated in canine basilar arteries. In the normal medium, PDA elicited a strong, dose-related, and slow-developing sustained contraction. Among the constrictors examined, including serotonin, prostaglandin F2 alpha, and endothelin, only PDA yielded contractions in a Ca2(+)-free medium. In both media, the PDA-induced contractions were virtually inhibited by either staurosporine, H-7, or quinacrine, while neither neurotransmitter blockades nor R24571 (calmidazolium) exerted significant effects. In addition, it was shown that 8-bromocyclic GMP, but not 8-bromocyclic AMP, markedly curtailed the PDA-induced contractions. Biochemical analysis, furthermore, showed that PDA induced increased phosphorylations of 27- and 96-kDa and proteins other than the myosin light chain (MLC) 20-kDa protein. Thus, the present results open up a novel mechanism of sustained cerebral artery contractions, where PKC activation rather than Ca2+/calmodulin/MLC system plays a key role that is regulated both by phospholipase A2 and by cyclic GMP.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1990

A case of pseudo-Bartter's syndrome associated with hypergastrinemia, thrombocytosis and increased serum thyroxine-binding globulin.

A housewife, 40 years of age, was admitted with dysesthesia of the extremities, muscle weakness, and attacks of adynamia and thirst. She had been taking a laxative for more than 20 years. On physical examination, blood pressure was 94/56 mmHg. Laboratory tests revealed thrombocytosis, low serum K and marked increases in both plasma renin activity and serum aldosterone. Serum TBG was increased. Serum gastrin was also markedly increased and could not be enhanced by exogenous secretin. Both angiotensin 11 loading test and noradrenalin loading test failed to increase blood pressure. Ammonium chloride loading to examine the disturbance of urinary acidification was abnormal in the short term test and borderline in the long term test. Following a diagnosis of pseudo-Bartter's syndrome induced by long term intake of laxative and repeated diarrhea, the administration of laxative was interrupted and potassium, indomethacin and spironolactone were administered. However, serum K remained low. Hypergastrinemia, thrombocytosis and a high serum TBG level also persisted, the causes of which remain unknown. This is the first reported case of pseudo-Bartter's syndrome associated with hypergastrinemia, thrombocytosis and increased serum TBG.

Adult↗
PubMed1990

[Establishment of permanent atrial fibrillation and time course of the amplitude of the f wave].

Atrial fibrillation is one of the arrhythmias that increase with increasing age. In this study we compared transition intervals from sinus rhythm to permanent atrial fibrillation and the time course of the f wave amplitude immediately after the transition between 32 younger (less than 65 years) and 44 elderly patients (greater than or equal to 65 years) in whom transition from sinus rhythm to permanent atrial fibrillation was confirmed on serial ECG recordings. Each group was classified into three categories according their underlying diseases: hypertensive heart disease, valvular disease, and lone atrial fibrillation. In patients with hypertensive heart disease or lone atrial fibrillation, there was no significant difference in the transition intervals between the younger and the elderly groups. In both groups the transition intervals were significantly (p less than 0.05) longer in patients with lone atrial fibrillation than those in patients with hypertensive heart disease (44.6 vs. 12.5 months in younger and 26.8 vs. 12.9 months in elderly). A significant positive correlation (r = 0.58, p less than 0.01) was observed between the final P wave and the initial f wave amplitude on establishment of permanent atrial fibrillation in all patients. In the younger group, the initial f wave amplitude of patients with valvular disease (0.27 +/- 0.04 mV, mean +/- SE) was significantly larger than those of patients with hypertensive heart disease (0.15 +/- 0.03 mV, p less than 0.05) and of patients with lone atrial fibrillation (0.16 +/- 0.01 mV, p less than 0.05). The f wave amplitude of valvular disease was significantly decreased after 1 year (0.22 +/- 0.03 mV, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗