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N Kurihara

Publications and source records attributed to N Kurihara.

At least 73 records · Page 4Linked to original sources
PubMed1996

Macrophage-stimulating protein activates STK receptor tyrosine kinase on osteoclasts and facilitates bone resorption by osteoclast-like cells.

Recently we cloned a novel receptor tyrosine kinase, STK. STK belongs to the hepatocyte growth factor receptor family and was identified as the receptor for macrophage-stimulating protein (MSP). STK is expressed on a restricted, macrophage population such as peritoneal macrophages, but not on mononuclear phagocytes of peripheral blood, bone marrow, or alveoli. Using an anti-STK monoclonal antibody, we observed STK expression on multinuclear osteoclast-like cells (OCLs) formed by murine bone marrow cultures in the presence of 1,25-dihydroxyvitamin D3, and interleukin-3. The OCLs expressed both the calcitonin receptor and STK. We also detected STK expression in bone-derived mouse osteoclasts. The addition of MSP to OCLs induced rapid morphologic changes such as cytoplasmic contraction and formation of ruffled border. In addition, MSP caused rapid redistribution of src to the borders of cytoplasm. These phenomena were associated with enhanced bone resorption. MSP caused a threefold increase in pit formation compared with control OCLs. These findings suggest that by involving src kinase, the MSP/STK signal transduction pathway induces rapid cytoskeletal reorganization in osteoclasts and facilitates bone resorption by osteoclasts.

Animals↗
PubMed1996

Antitumour activity of cis-diamminedichloroplatinum (II) against human tumour xenografts depends on its area under the curve in nude mice.

A pharmacodynamic analysis of cis-diamminedichloroplatinum(II) (DDP) was conducted using two human gastric cancer xenografts, SC-1-NU and MKN-45, and one human breast cancer xenograft, MX-1, grown serially in BALB/c nu/nu mice. DDP was administered intraperitoneally (i.p.) at a total dose of 5, 10, or 20 mg/kg in a schedule of q7d x 3 or (qd x 5) x 3. DDP was also administered i.p. to BALB/c +/? mice, whose plasma was used for the assay of total and free platinum by the atomic absorption method. A total dose of 20 mg/kg DDP seemed to be the maximum tolerated dose that was effective on MX-1 and SC-1-NU. When the totally administered doses were equivalent, the antitumor effects of the q7d x 3 and (qd x 5) x 3 schedules were similar to each other. The antitumor activity of DDP against MKN-45 was dependent on the total administered dose as well as the area under the curve of free and total platinum in the plasma. Side effects were significantly reduced using a schedule of (qd x 5) x 3 in terms of body and spleen weight loss when a total of 10 or 20 mg of DDP per kg was administered. These results suggest that DDP would be useful when administered using a daily schedule for obtaining the same antitumor activity as that of bolus injection but with reduced adverse effects.

Animals↗
PubMed1996

Pharmacokinetics of cis-diamminedichloroplatinum (II) given as low-dose and high-dose infusions.

A pharmacokinetic analysis of cis-diamminedichloroplatinum (II) (DDP) was conducted comparing low-dose daily bolus infusions, and high-dose drip infusions. Eight patients with gastric cancer were treated with low-dose daily bolus infusions of DDP to a total daily dose of 75 mg/m2 bid for 5 days. Four patients with esophageal cancer and one patient with gastric cancer were treated with high-dose drip infusions of DDP to a total daily dose of 70-80 mg/m2. Side effects were assessed in all the patients, and the platinum concentration in plasma was determined by an atomic absorption method. The peak plasma concentration (Cmax) and area under the curve (AUC) were calculated in four cases of the low-dose therapy, and three cases of the high-dose therapy. The side effects of DDP were evaluated according to the World Health Organization (WHO) grading, paying particular attention to nausea/vomiting, appetite loss, renal toxicity, and bone marrow suppression. The incidence of nausea/vomiting and appetite loss was significantly reduced with low-dose daily bolus infusions when compared to the high-dose drip infusions. Bone marrow toxicity and renal toxicity were similar with both administration methods, although hydration was required for the high-dose drip infusions to prevent renal toxicity. The peak plasma concentration (Cmax) of total and free platinum, and the area under the curve (AUC) of total platinum, were similar with both administration methods, while the AUC of free platinum was higher with the low-dose daily bolus infusions compared to the high-dose drip infusions. The time when the concentration of total platinum was > 1 microgram per ml (holding time) was significantly longer with the high-dose drip infusions than with the low-dose daily bolus infusions. The present study suggests that low-dose daily bolus infusions of DDP would be useful in reducing gastrointestinal toxicity, without reducing the area under the curve which is important for antitumor activity.

Adult↗
PubMed1996

Congenital absence and aberrant course of the internal carotid artery.

We retrospectively reviewed the imaging features of an aberrant course of the internal carotid artery (ICA) in one patient and its unilateral absence in four. Absence of the ICA was initially detected by MRI and MR angiography in both patients who underwent these examinations. CT revealed an abnormal or absent carotid canal in all cases. Radiological diagnosis by MRI and MR angiography could play an important role in the diagnosis.

Adult↗
PubMed1996

Serial growth of human malignant fibrous histiocytoma xenografts in immunodeficient mice.

Malignant fibrous histiocytoma (MFH) is on of the most common soft tissue sarcomas of adulthood, the only treatment for which involves surgical resection of the extremities and retroperitoneum, while no standard postoperative adjuvant chemotherapy has been established. We report herein on the establishment of a serially transplantable MFH strain in immunodeficient mice. An intraperitoneal tumor was resected from a patient with multiple recurrent MFH, inoculated into the subcutaneous tissue of mice with severe combined immunodeficiency (SCID), and established as a serially transplantable MFH strain, MH-1. The chemosensitivity of MH-1 was similar to that of the original fresh surgical specimen, as confirmed by the 3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) test. We believe that this serially transplantable strain will be useful for further studies on chemotherapy effective against MFH.

Abdominal Neoplasms↗
PubMed1996

Gastric plasmacytoma: report of a case.

A 54-year-old man with primary gastric plasma-cytoma is herein reported. After the patient had been diagnosed as having malignant lymphoma by gastrofiberscopy and a radiologic upper GI examination, a total gastrectomy was performed. Both histological and immunohistochemical studies showed plasmacytoma cells infiltrating the entire stomach wall, producing IgM-lambda, and indicating a final diagnosis of primary gastric plasmacytoma. Monoclonal immunoglobulin was not detected in the serum throughout the course. The case is discussed with reference to other reported cases of primary gastric plasmacytoma.

Gastrectomy↗
PubMed1996

The modulating effect of interferon alpha-2a on the antitumor activity of UFT against a human gastric carcinoma xenograft, SC-1-NU, in nude mice.

The modulating effect of recombinant human interferon alpha-2a (IFN) on the antitumor activity of UFT, a mixed compound of tegafur and uracil at a molar ratio of 1:4, was investigated against SC-1-NU, a human gastric cancer xenograft serially transplanted in nude mice. IFN was administered subcutaneously at a dose of 60,000 IU/mouse daily for 14 days, and UFT was given at a dose of 15 mg/kg as tegafur daily, except on Sundays, for 3 weeks. The agents were administered either alone or simultaneously. Synergistic antitumor activity on SC-1-NU was produced by the combination of IFN and UFT without any increment of side effects, and the combination therapy also increased intratumoral thymidylate synthetase (TS) inhibition and the amount of 5-fluorouracil (5-FU) in the intratumoral RNA. Thus, IFN seems to modulate the antitumor activity of UFT against SC-1-NU through an inhibition of DNA synthesis and RNA distortion, and therefore this combination could be useful for clinical application.

Adenocarcinoma↗
PubMed1996

Phase II study of recombinant human interleukin 3 administration following carboplatin and etoposide chemotherapy in small-cell lung cancer patients. SDZ ILE 964 (IL-3) Study.

Recombinant human interleukin 3 (rhIL-3) has been suggested to be a useful agent for the treatment of chemotherapy-induced thrombocytopenia. For evaluation of this possibility, rhIL-3 was given subcutaneously for 10 days to patients with small-cell lung cancer (SCLC). Chemotherapy consisted of carboplatin (CBDCA) given at 400 mg/m2 to previously untreated patients or at 350 mg/m2 to previously treated patients on day 1 and etoposide (VP-16) given at 100 mg/m2 on days 1-3 every 4 weeks. If the platelet count nadir was < 75,000/microliters in the control cycle of chemotherapy, patients were randomly assigned for the next cycle to rhIL-3 given at 5 or 10 micrograms/kg per day on days 4-13. A total of 41 patients (32 previously untreated patients and 9 previously treated patients) were enrolled in the study. The platelet count nadir in the cycles including rhIL-3 was significantly higher at both dose levels (P < 0.01) than in the control cycle. The duration of thrombocytopenia (< 75,000/microliters) and the mean time from the 1st day of chemotherapy to thrombocyte recovery (> 100,000/microliters) in the rhIL-3 cycle were significantly shorter than those in the control cycle (P < 0.01). The neutrophil count nadir and the duration of neutropenia (<1,000/microliters) were also significantly improved in the rhIL-3 cycle (P < 0.05). The major side effects were fever (80.5%), headache (24.3%), and fatigue (14.6%). All side effects were tolerable and of less than grade II. There was no difference in the efficacy of the two dose levels, but the 5-micrograms/kg dose appeared to be better tolerated than the 10-micrograms/ kg dose. We conclude that rhIL-3 administration following chemotherapy consisting of CBDCA and VP-16 reduces the incidence and severity of chemotherapy-induced thrombocytopenia and neutropenia with an acceptable adverse-events profile.

Adult↗
PubMed1996

Role of pulmonary vascular disorder in determining exercise capacity in patients with severe chronic obstructive pulmonary disease.

In patients with chronic obstructive pulmonary disease (COPD), the primary cardiovascular complication is the development of pulmonary hypertension, especially during exercise. The purpose of this study was to determine whether pulmonary vascular disorder plays an important role in determining exercise capacity in patients with severe COPD. Twenty-one male patients with severe COPD (mean FEV1 = 0.91 +/- 0.26 1) performed a progressive incremental exercise test, until symptom-limited maximum, to determine maximal exercise capacity, and then a constant-load exercise test for 5 min at a workload (20-60 W) corresponding to 60% of maximal workload during right heart catheterization to characterize the haemodynamic behavior of pulmonary circulation during exercise. The severity of the pulmonary vascular disorder was assessed using the slope of the mean pulmonary arterial pressure (PAP) - cardiac index (CI) relationship during constant-load exercise (P-Q slope). A significant inverse correlation was found between the maximal oxygen consumption (VO2max) and P-Q slope (r = -0.669), but not between VO2max and indices of expiratory airflow obstruction. In addition, the P-Q slope was inversely correlated with mixed venous oxygen tension (PvO2) at the end of constant-load exercise (r = -0.679) and with the change in oxygen delivery relative to oxygen consumption (delta DO2/delta VO2) during constant-load exercise (r = -0.671). These findings suggest that in patients with COPD, the functional impairment of the pulmonary vasculature is associated with disturbance in oxygen transport to the peripheral muscle during exercise, resulting in reduction of exercise capacity. We conclude that pulmonary vascular disorder may be an important factor in determining the exercise capacity of patients with severe COPD.

Aged↗
PubMed1996

Potentiation of the bronchoprotective effects of vasoactive intestinal peptide, isoprenaline, and theophylline against histamine challenge in anaesthetised guinea pigs by adrenomedullin.

BACKGROUND: Adrenomedullin is a hypotensive peptide recently discovered in human phaeochromocytoma which has been found to inhibit bronchoconstriction induced by histamine and acetylcholine. This study was designed to determine the manner in which adrenomedullin and other bronchodilators interact in modulating airway function. METHODS: A study was undertaken to determine whether adrenomedullin potentiated the bronchoprotective effects of isoprenaline, vasoactive intestinal peptide (VIP), and theophylline against histamine-induced bronchoconstriction in anaesthetised guinea pigs in vivo. RESULTS: Adrenomedullin in a concentration of 10(-9) M significantly inhibited histamine-induced bronchoconstriction but in a concentration of 10(-10) M it did not exhibit the bronchoprotective effect against histamine. VIP (10(-9) M) did not affect histamine-induced bronchoconstriction but it markedly inhibited the bronchoprotective effect against histamine in the presence of adrenomedullin (10(-10) M). VIP (10(-6) M) significantly inhibited histamine-induced bronchoconstriction but this effect was short lived. Adrenomedullin in a concentration of 10(-10) M potentiated bronchoprotection induced by VIP (10(-6) M) and prolonged it. Isoprenaline (10(-8) M) also significantly inhibited histamine-induced bronchoconstriction and this effect was enhanced in the presence of adrenomedullin (10(-10) M). Similarly, adrenomedullin (10(-10) M) significantly potentiated theophylline-induced bronchoprotection, and a sub-bronchoprotective dose of theophylline (20 mg/kg i.p.) was effective in preventing histamine-induced bronchoconstriction in the presence of adrenomedullin (10(-10) M). CONCLUSIONS: This study shows that adrenomedullin potentiates the bronchoprotective effects of different classes of bronchodilators against histamine challenge in anaesthetised guinea pigs.

Adrenomedullin↗
PubMed1996

Effect of loratadine, an H1 antihistamine, on induced cough in non-asthmatic patients with chronic cough.

BACKGROUND: H1 antihistamines have been shown to have an antitussive effect in patients with asthma, postnasal drip, and allergic rhinitis. No study has been performed to determine whether orally administered H1 antihistamines can reduce the number of coughs induced by stimulation of cough receptors in non-asthmatic patients with chronic dry cough. METHODS: The effect of loratadine (10 mg) on the number of coughs induced by ultrasonically nebulised distilled water (UNDW) was examined in 10 patients with nasal disease and in seven patients with unexplained chronic cough using a randomised, double blind crossover method. Eleven normal volunteers were also studied. Each subject inhaled UNDW for one minute, and the numbers of coughs during the one minute inhalation and the 30 seconds following it were counted. RESULTS: There was no difference in the results of pulmonary function tests performed before and one minute after UNDW inhalation for either patients or normal subjects. There was also no significant difference between the results of pulmonary function tests before or after oral administration of loratadine. Loratadine significantly reduced the number of coughs in patients with nasal disease and in those with unexplained chronic cough, but not in normal subjects. CONCLUSIONS: The H1 antihistamine loratadine reduces cough induced by UNDW. The release of histamine may contribute to the chronic cough in patients with unexplained chronic cough or nasal disease.

Adult↗
PubMed1996

Clinical significance of serum concentration of interleukin 8 in patients with bronchial asthma or chronic pulmonary emphysema.

Interleukin-8 (IL-8) belongs to the family of chemotactic cytokines and has been shown to activate neutrophils in vitro and in vivo. In this study, we measured IL-8 concentration in the serum of patients with pulmonary emphysema or bronchial asthma. IL-8 concentration in serum of emphysema patients was significantly higher than in asthmatics; in emphysema patients it was significantly correlated with the smoking index and the annual decrease of FEV1.0. In asthmatics IL-8 concentration was below the level of detection, but was markedly increased during exacerbation of asthma. Our findings suggest that IL-8 may be one of the causal factors in these diseases.

Adolescent↗
PubMed1996

Rate parameter changes by added albumin in the microsomal oxidative demethylation of deuteriated and non-deuteriated 4-methoxyanisole.

Bovine serum albumin (BSA) added to the reaction medium for the oxidative demethylation of 4-methoxyanisole and its "di-CD3" isotopomer ([d6]methoxyanisole), when catalyzed by liver microsomes from untreated rats, decreased the Km values and increased the V(max)/Km (= V/K) values. The Vmax values were not markedly altered. The values for the deuterium isotope effect on V(max) and V/K for the reaction with this isotopomer were between 2.2 and 2.8, and that on Km was close to unity. The magnitude of the isotope effect was not significantly changed by adding BSA. The intramolecular isotope effect with [mono-CD3]4-methoxyanisole ([d3]methoxyanisole) in liver microsomes from untreated rats was between 10.3 and 10.8, which was not significantly changed by BSA. Liver microsomes from rats treated with phenobarbital resulted in the intramolecular isotope effect value in the absence of BSA being between 7.2 and 9.1, which was not significantly altered by BSA. Based on these data, the calculated apparent rate constant for the enzyme-substrate complex formation was markedly increased by up to about 1.9- and 3.5-fold by 1% and 2% of BSA added, respectively.

Animals↗
PubMed1996

[Multiple bronchial varices].

A 54-year-old man was referred to our hospital because of hemoptysis. Fiberoptic bronchoscopy revealed irregular mucosa of the right B1, B2, B3, B8, B9, and B10, and the left B1+2 and B3. Bronchoscopic and histological findings indicated bronchial varices.

Bronchi↗
PubMed1996

[Small-cell lung cancer and subacute sensory neuropathy in a patient positive for the anti-Hu antigen].

We encountered a case of small-cell lung cancer in a patient with subacute sensory neuropathy that began 5 months before the cancer was diagnosed. A 60-year-old man complained of abnormalities in the functioning of his peripheral sensory systems (senses of pain, touch, position, and vibration). A chest X-ray film obtained on admission showed an anterior mediastinal tumor. The anti-Hu antibody was found in his serum. The diagnosis was small-cell lung cancer. Combination chemotherapy (cisplatin and irinotecan, CPT-11) was begun and the response was a complete remission. The symptoms of neuropathy continued. The anti-Hu antibody was useful in the diagnosis in the case of small-cell lung cancer combined with subacute sensory neuropathy.

Acute Disease↗
PubMed1996

[Leigh syndrome: serial CT and MR imaging findings].

Serial CT and MRI findings in five patients (two boys and three girls) with Leigh syndrome were retrospectively reviewed in a follow-up period lasting from six months to 10 years. The two boys were found to have cytochrome c oxidase deficiency and one of the girls to have mitochondrial DNA mutation, while the remaining two girls had no detectable enzyme deficiency. CT and MRI revealed symmetrical involvement of the brain bilaterally in all cases. The focal lesions were found most frequently in putamina and caudate nuclei (four cases each), followed by thalami (three cases), globi pallidi, and midbrain (two cases each). In addition, diffuse white matter and/or cortical lesions were disclosed in three cases. MRI and CT at an early stage of the disease revealed swollen, symmetrical lesions which showed shrinkage in size accompanied by the adjacent brain atrophy on later images. Some lesions were detected only in the early stage and were not shown in later images. Thus, careful reading of sequential changes appears to be required for accurate diagnosis of Leigh syndrome.

Brain↗
PubMed1996

[MR imaging of carbon monoxide intoxication: evaluation of 13 cases to discuss the relation between MR findings and clinical course].

MR images of the brain were retrospectively reviewed in 13 patients with carbon monoxide (CO) poisoning to examine the relation between the MR findings and clinical course. The patients included 11 men and 2 women whose ages ranged from 6 to 88 years (mean, 38 years). Repeated MR studies of at most five times were performed on 9 patients. Lesions in the bilateral globus pallidi were found in 5 cases showing hyperintensity on T2-weighted images (T2WI) and iso-to hypointensity on T1-weighted images (T1WI). The patients with only pallidi lesions clinically recovered well. Hyperintense white matter lesions were recognized on T2WI in 8 patients, including all 5 with delayed encephalopathy. Sequential studies generally showed a tendency of regression of these hyperintense lesions with improvement of symptoms, indicative of reversible demyelination as documented in the pathological literature. One patient with poor prognosis revealed white matter lesions, that were hyperintense on T2WI and very hypointense on T1WI, which may represent irreversible change. Thus, clinical course seems to be closely related with white matter lesions, but not with pallidi lesions. In cases of CO intoxication, therefore, MR study provides valuable information on patients' clinical prognoses.

Adolescent↗