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Biomedical subjects

M Masaki

Publications and source records attributed to M Masaki.

At least 19 recordsLinked to original sources
PubMed2001

Identification and characterization of functional domains in a mixed lineage kinase LZK.

The mixed lineage kinase (MLK) family is a recently described protein kinase family. The MLKs contain a kinase domain followed by a dual leucine zipper-like motif. We previously reported the molecular cloning of LZK (leucine zipper-bearing kinase), a novel MLK, and that LZK activated the c-Jun NH2 terminal kinase (JNK)/stress-activated protein kinase (SAPK) pathway through MKK7 in cells. Here, we reveal that LZK forms dimers/oligomers through its dual leucine zipper-like motif, and that this is necessary for activation of the JNK/SAPK pathway. We also identify the C-terminal functional region of LZK, which is indispensable for the activation of SEK1, but not that of MKK7.

Amino Acid Sequence↗
PubMed2000

Suppression of polypogenesis in a new mouse strain with a truncated Apc(Delta474) by a novel COX-2 inhibitor, JTE-522.

Mutations of the adenomatous polyposis coli gene (Apc) have been implicated in the occurrence of sporadic colon cancer. Various Apc knockout strains of mice have been created to better understand the function of this gene. In the present study, using gene targeting, we disrupted the mouse Apc gene at the end of exon 10 to compare its effect with the effects of other types of Apc gene disruption, all of which are on exon 15. The mice expressed a mutant form of mRNA that encoded 474 amino acids instead of 2845 amino acids due to exon duplication. In addition, these Apc(Delta474) knockout mice developed intestinal and mammary tumors. Since the most severe cases of familial adenomatous polyposis are associated with mutations on exon 15, our mutation at exon 10 was expected to result in a mild phenotype. However, the number of polyps that our mice developed was similar to that of other Apc knockout mice such as Apc(Min) and Apc(1309) mice. Cyclooxygenase-2 (COX-2) has been implicated in colorectal carcinoma. Apc(Delta474) mice treated with JTE-522, a novel COX-2-selective inhibitor, showed a significantly reduced number of polyps. These results suggest that COX-2 plays an important role in polypogenesis and COX-2-selective inhibitors can be used as new preventive therapeutics against colorectal tumors.

Adenomatous Polyposis Coli↗
PubMed1999

Heart rate variability and left ventricular dilatation early after myocardial infarction.

To assess clinically whether alterations of autonomic tone precede left ventricular dilatation, heart rate variability and early left ventricular dilatation after a first myocardial infarction were assessed. Low-frequency power (LF), high-frequency power (HF), and total power (TP) were obtained by ambulatory electrocardiogram on day 1 in 53 patients with a first acute myocardial infarction. Left ventricular end-diastolic volume determined by echocardiography was obtained on day 1 and day 14. Stepwise linear regression analysis was used to assess the associations of early left ventricular dilatation with heart rate variability adjusted for clinical variables. Higher LF and TP were significantly associated with early left ventricular dilatation after adjustment for age, sex, site of myocardial infarction, acute revasucularization, peak creatine kinase level, history of hypertension, and use of angiotensin-converting enzyme inhibitors and beta-blockers. Higher LF and TP preceded early left ventricular dilatation after myocardial infarction.

Echocardiography↗
PubMed1998

[Three cases of pulmonary embolism incorrectly diagnosed as lung cancer].

Pulmonary embolism is commonly misdiagnosed as lung cancer, since sputum cytological tests often show atypical or malignant cells. We report three operated cases of pulmonary embolism incorrectly diagnosed as lung cancer. The first patient is a 39-year-old male with chest pain an bloody sputum. Chest x-ray revealed abnormal shadows and subsequent sputum cytological tests identified malignant cells. The second patient is a 63-year-old male with the same diagnostic pattern as the first case. The third patient is a 72-year-old male whose routine chest x-ray showed an abnormal shadow; malignant cells were identified by cytological tests on transbronchial fiberscope brushings. These three patients were histopathologically diagnosed as suffering pulmonary embolism by wedge resection under thoracotomy. When a patient has chest pain or bloody sputum with showing temporarily malignant cells on cytology, the possibility of pulmonary embolism should be taken into consideration.

Adult↗
PubMed1998

Inhibitory effects of JTE-522, a novel prostaglandin H synthase-2 inhibitor, on adjuvant-induced arthritis and bone changes in rats.

OBJECTIVE AND DESIGN: To investigate the effect of JTE-522, a novel selective prostaglandin H synthase (PGHS)-2 inhibitor, on adjuvant-induced arthritis and bone changes. SUBJECTS: Male Lewis rats at 8 weeks old were immunized with heat-killed mycobacteria. TREATMENT: JTE-522 (0.1-30 mg/kg) and indomethacin (0.1-3 mg/kg) were administered orally once-daily after immunization. METHODS: Paw swelling, bone changes in arthritic paws and vertebrae, urinary levels of deoxypyridinoline and pyridinium crosslinks, and the incidence of gastric lesions were determined in arthritic rats. RESULTS: JTE-522 (from 0.3 mg/kg) suppressed the development of paw swelling, and also reduced bone damage (score and bone mineral density) in arthritic paws and the urinary excretion of deoxypyridinoline and pyridinium crosslinks. However, JTE-522 did not cause gastric lesions even at 30 mg/kg in arthritic rats. CONCLUSIONS: These results suggest that JTE-522 possesses potent anti-arthritic activities and suppressive activity on inflammatory bone resorption without gastric side effects.

Administration, Oral↗
PubMed1998

Nasal polyps in the olfactory cleft.

OBJECTIVES: Nasal polyps frequently arise from the middle meatus in patients with nasal polyposis, but caution is required when polyps are seen protruding from the olfactory cleft. The purpose of this study was to evaluate a method to achieve effective and safe access to the olfactory cleft, and to determine the actual incidence of polyps arising from the olfactory cleft in patients with nasal polyposis. PATIENTS: Eighty-four patients with bilateral or unilateral nasal polyps (n = 143) ranging in age from 16 to 72 years underwent endoscopic sinus surgery in the period from January 1994 to December 1996. METHODS: To observe and gain access to the olfactory cleft, septoplasty combined with endoscopic sinus surgery was needed in patients with nasal polyposis. RESULTS: The endoscopy during the combined septoplasty and endoscopic sinus surgery revealed that 36.4% (n = 52) of bilateral or unilateral nasal polyps (n = 143) arose from the olfactory cleft. Of 52 polyps of olfactory cleft origin, 45 (86.5%) arose from the superior turbinate and/or superior meatus, 32 (67.3%) from the medial side of the middle turbinate, 24 (46.2%) from the anterior face of the sphenoid sinus, and 17 (32.7%) from the mucosa of the nasal septum. CONCLUSIONS: These findings suggest that for surgeries of nasal polyposis an approach to the olfactory cleft as well as to the middle meatus is required.

Adolescent↗
PubMed1998

Profile of JTE-522 as a human cyclooxygenase-2 inhibitor.

Inhibitory activity and the mechanism of action of JTE-522 (4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamid e), a novel selective cyclooxygenase (COX)-2 inhibitor, on human COX-1 and COX-2 were investigated and compared with those of reference compounds. In an enzyme assay, JTE-522 inhibited yeast-expressed human recombinant COX-2 with an IC50 value of 0.085 microM. In contrast, JTE-522 did not inhibit human COX-1 prepared from human platelets at concentrations up to 100 microM. In a cell-based assay, JTE-522 diminished lipopolysaccharide-induced prostaglandin E2 production in human peripheral blood mononuclear cells (COX-2) (IC50 value = 15.1 nM). On the other hand, JTE-522 was less potent at inhibiting calcium ionophore-induced thromboxane B2 production in washed human platelets (COX-1) (IC50 value = 6210 nM). JTE-522 showed highly selective inhibition of human COX-2, and its activity was more selective than that of other COX-2 inhibitors (NS-398 and SC-58635). Human recombinant COX-2 activity was attenuated by JTE-522 in a dose-dependent and time-dependent manner. In contrast, the inhibitory activity of JTE-522 on human COX-1 was not affected by preincubation time. COX-2 inhibition by JTE-522 could not be recovered by gel filtration. These results indicate that JTE-522 is a highly selective, time-dependent and irreversible inhibitor of human COX-2.

Benzenesulfonates↗
PubMed1998

[A case of rectal cancer metastatic to the tonsil].

Metastatic tumors of the tonsils are rarer than primary tumors. Few cases of metastatic tonsillar tumor have been reported. A 51-year-old man expectorated a portion of a tumor from the left side of the pharynx after an operation for cancer metastatic to the lung. Biopsy revealed that the pharyngeal tumor was rectal cancer (adenocarcinoma) metastatic to the tonsil. To our knowledge, this is the first case of primary rectal cancer metastatic to the tonsil to be reported in Japan. The clinical features of metastatic tonsillar tumor are discussed.

Adenocarcinoma↗
PubMed1998

[Case of multiple posterior mediastinal and retroperitoneal neurinomas].

We report a case of multiple neurinomas arising in the posterior mediastinum and the retroperitoneum. A 49-year-old man was admitted to our department for operation after an abnormal shadow appeared on routine chest X-ray film. A left adrenal tumor was found incidentally with ultrasonography at the time of a previous thoracic surgery. First, the posterior mediastinal tumor was surgically removed. Histologic diagnosis was neurinoma. After resection, endocrinologic findings were within normal limits. A left adrenal tumor was diagnosed, and surgery was performed. The tumor was separated from the adrenal gland; the histologic diagnosis was neurinoma. Neurinomas are usually solitary; multiple neurinomas are extremely rare.

Humans↗
PubMed1998

[Aortic valvular vegetation in annuloaortic ectasia due to idiopathic cystic medial necrosis: a case report].

Annuloaortic ectasia is often accompanied by Marfan syndrome and associated with infective endocarditis usually involving the mitral valves. We treated a patient with annuloaortic ectasia due to idiopathic cystic medial necrosis who developed congestive heart failure with aortic valvular vegetation. A 56-year-old man had dyspnea on effort since the beginning of January, 1997 and was admitted to our hospital on April 6, 1997 because of orthopnea. The diagnosis was congestive heart failure due to severe aortic regurgitation with annuloaortic ectasia detected by echocardiography. Medication and rest after hospitalization relieved his symptoms but congestive heart failure deteriorated after he had a high fever. At this time, a vegetation attached to the noncoronary cusp of the aortic valve was found which had not been detected on admission. Blood culture yielded Streptococcus sanguis. The diagnosis was infective endocarditis involving the aortic valve. Surgical correction (Bentall method) improved congestive heart failure and he was discharged on August 4, 1997 without recurrence of endocarditis. Infective endocarditis involving the aortic valves is a possible cause of development or deterioration of congestive heart failure in patients with annuloaortic ectasia.

Aortic Diseases↗
PubMed1998

[Effect of concurrent use of ondansetron hydrochloride and dexamethasone against nausea and vomiting in lung cancer patients receiving cisplatin].

We examined the efficacy of concurrent use of ondansetron hydrochloride and dexamethasone, and the effective dose of dexamethasone against nausea and vomiting in lung cancer patients receiving chemotherapy including single high dose cisplatin. The study was carried out on total of 44 courses of chemotherapy in either initial onset or recurrence of lung cancer. The patients were given 4 mg of ondansetron injection on the day of cisplatin injection (Day 1), and 4 mg/day of ondansetron tablet for Days 2 to 4. These patients were randomly allocated into 2 groups, i.e., those who, on Day 2, concomitantly received 10 mg of dexamethasone (D10 Group, 22 courses) or 20 mg (D20 Group, 22 courses), for comparing the antiemetic effects in a different concomitant dose of dexamethasone. An efficacy rate of 70% or more was achieved in each group for acute emesis on Day 1. The efficacy rate was 80% or above for emesis on Day 2 when dexamethasone was concurrently administered, and Days 3 and 4 in both groups. No significant difference was observed between the groups. A higher complete suppression rate against nausea was seen in D20 Group even though the difference from D10 Group was not significant. Furthermore, food intake rate on Day 2 was significantly better in D20 Group. However, in the cases that were graded effective or markedly effective for acute emesis on Day 1, the efficacy rate was also high in both groups through Days 2-4. It was notable that the efficacy rate of Days 2-4 was 100% in D2 Group. The high efficacy rate was shown in male patients regardless of which dose of dexamethasone was used. However, control of emesis was unfavorable in female patients on Day 1 and was still unfavorable even though dexamethasone was combined from Day 2. We considered from the above results that 10 mg/day of concurrent dexamethasone is sufficient in suppression of delayed emesis on Day 2. However, in order to improve nausea or food intake, or to suppress emesis in patients who are highly likely to show unfavorable control for Day 2 and onward, 20 mg/day should also be effective.

Aged↗
PubMed1997

Pharmacological profile of JTE-522, a novel prostaglandin H synthase-2 inhibitor, in rats.

OBJECTIVE AND DESIGN: The antinociceptive, antipyretic, and anti-inflammatory effects of JTE-522, a novel selective prostaglandin H synthase (PGHS)-2 inhibitor, were examined in rats. MATERIALS: Sheep seminal vesicle PGHS-1 and placenta PGHS-2 were used for in vitro assay, while for in vivo experiments, male rats (4-8 weeks old) were used. TREATMENT: JTE-522 and reference compounds (0.01-100 microM) were subjected to enzyme assay. JTE-522 (0.3-30 mg/kg) and indomethacin (0.3-10 mg/kg) were administered orally. RESULTS: JTE-522 inhibited PGHS-2 (IC50: 0.64 microM) without affecting PGHS-1 activity at 100 microM. In rats with yeast-induced hyperalgesia, JTE-522 showed a dose-dependent antinociceptive effect (ED50: 4.4 mg/kg). In rats with yeast-induced pyrexia, JTE-522 significantly reversed the pyrexic response (ED50: 3.9 mg/kg). Orally administered JTE-522 dose-dependently inhibited carrageenin-induced rat paw edema (ED30: 4.7 mg/kg). In rats with adjuvant-induced arthritis, JTE-522 showed a significant inhibitory effect at daily doses of 0.3-3 mg/kg. JTE-522 did not cause severe gastric lesions at oral doses up to 300 mg/kg. CONCLUSIONS: Our results indicate that the selective PGHS-2 inhibitor JTE-522 may represent a novel type of anti-inflammatory drug without adverse effects on the gastrointestinal tract. JTE-522 may thus be a promising agent for treating both acute inflammatory disease and chronic inflammatory diseases such as rheumatoid arthritis.

Administration, Oral↗
PubMed1997

[A case of asymptomatic posterior mediastinal pheochromocytoma diagnosed during the procedure of video-assisted thoracic surgery (VATS)].

The patient was a 20-year-old male. On routine check-ups, a posterior mediastinal tumor was found radiologically and referred to our hospital for the operation. During the Video-Assisted Thoracic Surgery (VATS), sudden elevation of the blood pressure up to 270 mmHg was observed by the tumor palpation. At once we diagnosed as pheochromocytoma. Changing the VATS to usual thoracotomy the tumor was completely removed and histologically confirmed. After the operation the patient was uneventful and the value of norèpinephrine reduced to normal range from 2912 pg/ml. The posterior mediastinal pheochromocytoma is rare and this report is the 6 th case in Japan. Clinical characteristics were discussed in addition to the review of the literature.

Adult↗
PubMed1996

[Influence of smoking on medical care expense of middle-aged workers].

An analysis was made to elucidate influence of smoking habits on medical care expense. Subjects were 4,795 male workers aged 40 to 73 who participated in the routine medical check-up in 1988 at a health insurance society in Tokyo. Their daily habits including smoking habit were also surveyed. Data on medical care utilization were derived from the medical records for 1989 provided by the health insurance society. The data on medical care fees were examined, and hospitalization costs analyzed separately. Compared to other subjects, ex-smokers had a higher frequency of having a history of medical care. Ex-smokers showed higher and current smokers lower values of both visiting (percentage of subjects utilizing medical facilities at least once a year) and monthly rate of receiving examinations when compared to non-smokers. Current smokers had the lowest average number of days utilized for medical services, lowest average medical care fee per visit and annual medical care fee per person. The average number of days utilized and annual medical care fee per person was weakly correlated to smoking index. Ex-smokers had the highest average medical care fee per visit. There was a weak correlation to smoking index. Annual medical care fees per person decreased with age in non-smokers, but not in current smokers whose total fees were generally already low. In ex-smokers, fees increased until age fifties. From these results it would be difficult to identify on increase of medical care fees in middle-aged current smokers, especially in active businessmen. While the effect of smoking on health were still subclinical, average medical care fee per visit relate to and reflect the health effects of smoking.

Adult↗
PubMed1995

Synthesis and structure-activity relationships of 2-(4-benzhydryl-1-piperazinyl)-1-phenylethanols as new calcium blockers.

A series of 2-(4-benzhydryl-1-piperazinyl)-1-phenylethanols (4) was synthesized and evaluated for calcium entry-blocking activity, assessed as inhibitory activity on calcium current in rat hippocampal pyramidal neurons by using a patch-clamp technique (10(-5) M), and cerebral vasodilating activity, assessed in terms of increase of vertebral blood flow after intravenous administration (1 mg/kg) in anesthetized dogs. Alkoxy substituents on the phenyl ring of the phenylethanol moiety conferred potent calcium entry-blocking activity and potent cerebral vasodilating activity. Among these compounds, 4i (NC-1100) was selected as the best analog. Some pharmacological properties of 4i are presented.

Animals↗
PubMed1995

[Characteristics of medical institutions visited by patients with 26 intractable diseases who are residents of Saitama Prefecture (comparison of the data for 1984 and 1988)].

To obtain basic data concerning the availability of medical care for intractable diseases in a large city and its environs, we analyzed the data of Saitama Prefecture. These data were selected from a nationwide survey conducted by the Epidemiology of Intractable Diseases Research Committee of the Ministry of Health and Welfare in Japan. The characteristics of medical institutions visited by patients with 26 intractable diseases were analyzed. The patients were receiving financial aid for treatment. The subjects were 4234 patients in 1984 and 6804 patients in 1988. In addition, we compared the data of 1984 with those of 1988. The results are as follows: 1) In both years, the characteristics of medical institutions which were visited varied in terms of the individual disease. The proportion of patients who visited medical institutions in the same medical service area and in the same prefecture were both very low. The percentage of patients who visited medical institutions in Tokyo was more than 30% of the total, and was more than 50% for the disease with the highest proportion of patients. The dependency on Tokyo for medical institutions was inversely proportional to the distance from Tokyo. Most patients were highly dependent on a large hospital, but the proportion of patients with SMON and ulcerative colitis who visited a large hospital was markedly lower than that for other diseases. 2) A comparison of the data of 1984 with those of 1988 showed that in most of medical service areas, the proportion of patients who visited medical institutions in the same medical service area and in Saitama Prefecture increased, but in Tokyo Prefecture the proportion decreased. We continuously observed a high dependency on a university hospital located about 60km distance from downtown Tokyo, but the dependency slightly decreased in 1988. When a new branch of a university hospital opened, many intractable disease patients then depended on that branch. These results suggest that the self-sufficiency levels of medical services for intractable diseases gradually rose in Saitama Prefecture. The illness behavior of intractable disease patients in Saitama Prefecture did not show any remarkable changes, therefore those results in Saitama Prefecture might indicate a universal characteristic of medical institutions visited by intractable disease patients who live in the envirous of a large city (Tokyo).

Critical Illness↗
PubMed1995

[Clinicopathological study on reported case for bronchogenic carcinoma].

After a primary operation for bronchogenic carcinoma, eight out of 253 patients (3.2%) underwent reoperation for local recurrence or intrathoracic metastasis. The histology was well or moderately differentiated adenocarcinoma in all cases. The average interval between the first and second operation was 34 months (range: six to 63 months). There were three local recurrences, two lung metastases and one mediastinal lymph node metastasis (#3a) ipsilaterally two lung metastases contralaterally. Completion pneumonectomy was underwent in one, wedge or segmental resection in five and excision of lymph node in one case after an initial ipsilateral lobectomy. Two patients underwent contralateral wedge or segmental resection after initial lobectomy. Four of eight patients died of brain, liver, or bone metastases after reoperation, the time of survival averaging 63 months. Two patients died of pneumonia, the time survival averaging 92 months. Two patients are still alive, one in 52 months and another in 20 months after reoperation.

Adult↗