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Biomedical subjects

H Inoue

Publications and source records attributed to H Inoue.

At least 199 records · Page 11Linked to original sources

Characterization of a membrane-bound arginine-specific serine protease from rat intestinal mucosa.

Previously we isolated and characterized a membrane-bound, arginine-specific serine protease from pig intestinal mucosa [J. Biol. Chem. 269, 32985-32991 (1994)]. For further characterization of this type of enzyme, we cloned a cDNA from rat intestinal mucosa encoding the precursor of a similar protease. The partial amino acid sequences determined for the pig enzyme were found to be shared almost completely by the rat enzyme. The serine protease domain of the rat enzyme, heterologously expressed in Escherichia coli, specifically cleaved Arg (or Lys)-X bonds with a marked preference for Arg-Arg or Arg-Lys, similar to the pig enzyme. The mRNA for the rat enzyme was shown to be distributed mainly in intestine, and the enzyme was detected in the duodenal mucosa as a 70 kDa protein. Immunohistochemical analysis of the small intestinal tissue showed that the enzyme is localized mainly on brushborder membranes.

Amino Acid Sequence↗

Molecular cloning of beta-galactosidase from Japanese pear (Pyrus pyrifolia) and its gene expression with fruit ripening.

We have cloned a cDNA fragment encoding a beta-galactosidase from Japanese pear (Pyrus pyrifolia) fruit (JP-GAL). It contained an untranslated sequence of 182 nucleotides at the 5' end, a presumptive coding sequence of 2,193 nucleotides and an untranslated sequence of 268 nucleotides including a polyadenylation signal and a poly (A) tail at the 3' end. It encoded a protein with a calculated molecular weight of 80.9 kDa which consists of 731 amino acids. Both the nucleotide and the deduced amino acid sequences showed a 98% sequence identity with that obtained from the apple beta-galactosidase cDNA. The peptide sequence obtained from the purified Japanese pear beta-galactosidase III matched the deduced amino acid sequence of SVSYDHKAIIINGQKRILISG (amino acid 25-45). Northern blot analysis showed that the probe derived from JP-GAL hybridized to a single 2.6 kb RNA. The mRNA was detected solely in the fruit; none was detected in the buds, leaves, roots or shoots of the Japanese pear. The steady-state level of the beta-galactosidase mRNA was measured during fruit ripening in three cultivars, Housui, Kousui (early ripening) and Niitaka (late ripening). The results showed that regardless of the cultivar, no JP-GAL mRNA was detected in the immature fruit. Increment of the mRNA level with fruit ripening coincided with the increase in the beta-galactosidase III activity. Our results showed that the expression of JP-GAL correlated with fruit softening and JP-GAL may be beta-galactosidase III.

Amino Acid Sequence↗

Reconstruction of the proximal humerus with the clavicle after tumor resection: a case report.

Reconstruction of the proximal humerus after resection for tumor and modification of the clavicular transposition procedure is described in which the blood supply of the clavicle is preserved and the clavicle is used to bridge the defect. An 11-year-old boy presented with shoulder pain, and the diagnosis was osteosarcoma of the right proximal humerus. After resection of the sarcomatous proximal humerus, the clavicle was released with its periosteum remaining intact, and the clavicle was rotated downward around the acromioclavicular joint. A vascularized fibula supplemented the reconstruction in trying to gain length of the arm. The acromioclavicular joint and the vascular supply of the clavicle were preserved. Internal fixation from the clavicle and the fibula to the distal humerus was made with an AO plate and screws. Muscles around the proximal humerus were reattached to the clavicle. Range of motion of the shoulder was 80 degrees flexion, 85 degrees abduction, 30 degrees external rotation, and 90 degrees internal rotation. Although the postoperative followup is relatively short, only 2 years, the functional advantages of this operation over other forms of reconstruction can be observed.

Bone Neoplasms↗

Development of acute myeloid leukemia after chemotherapy for osteosarcoma.

The current study describes two patients with osteosarcoma who had acute myeloid leukemia develop after treatment with multiagent chemotherapy. The incidence density for the chemotherapy protocol was 129.8 per 10,000 person-year of followup. Karyotype analysis of 16 reported patients (including the current two patients) indicated that most leukemias after treatment of osteosarcoma correlated with the use of topoisomerase II inhibitors, such as doxorubicin. The deoxyribonucleic acid-damaging activity of doxorubicin reinforced by the use of alkylating agents is highly suspected as a causative event in the development of leukemia after treatment of osteosarcoma. As the next step in the development of treatment for patients with osteosarcoma, the type and intensity of treatment must be evaluated to minimize possible leukemogenic effects without compromising the potential for cure.

Acute Disease↗

Dynamic magnetic resonance imaging of femoral head perfusion in femoral neck fracture.

A prospective followup study of 36 femoral neck fractures according to the assessment of femoral head perfusion using dynamic magnetic resonance imaging is reported. Patients were divided into three groups based on the dynamic magnetic resonance imaging findings (dynamic curve pattern and relative enhancement ratio) that were conducted within 48 hours of the injury. Traction was used to achieve anatomic reduction and to prevent additional damage to vascularity until minimally invasive internal fixation could be done. The fractures of all 17 patients whose femoral head perfusion was normal (Type A; n = 11) or was impaired but not totally absent (Type B; n = 6) healed without complications. Among the 19 patients whose femoral head perfusion was absent (Type C), 15 had complications (osteonecrosis, n = 10; nonunion, n = 5). Assuming that fractures with a Type A or Type B curve pattern would unite successfully and that those with a Type C curve pattern would not, the sensitivity, specificity, and accuracy of the predictions of successful osteosynthesis of the femoral neck fractures using this method were 81%, 100%, and 89%, respectively. The current classification of femoral neck fractures using dynamic magnetic resonance imaging may be useful in selecting an appropriate treatment method for the fractures.

Adult↗

Expression of MAGE-B genes in esophageal squamous cell carcinoma.

The MAGE-B (MAGE-B1, -B2, -B3, and -B4) genes share strong homology with the MAGE-A gene family. MAGE-B1 and -B2 encode common tumor-specific peptide antigens. There is, however, still very little information about the expression of these genes in human gastro-intestinal carcinomas. We investigated the expression of MAGE-B1 and -B2 genes in 29 cell lines and 53 clinical tumor samples of esophageal squamous cell carcinoma by reverse transcription polymerase chain reaction (RT-PCR). MAGE-B1 and -B2 gene transcripts were detected by RT-PCR in 1 (3%) and 6 (21%) cell lines, and in 9 (17%) and 17 (32%) clinical samples, respectively. Among them, 7 / 29 (24%) cell lines and 19 / 53 (36%) clinical samples expressed at least either MAGE-B1 or -B2. A significant correlation was found between negative MAGE-B gene expression and vascular invasion (P = 0.008). In 45 out of 53 esophageal carcinoma RNA samples, the MAGE-A1, -A2, and -A3 genes were detected in 27 (60%), 23 (51%), and 30 (67%) samples, respectively, while the MAGE-B genes were detected in 18 (40%) samples. The frequency of MAGE-B gene expression in esophageal carcinoma was relatively higher than that observed for gastric or colorectal carcinomas (12% and 2%, respectively). Therefore, the MAGE-B genes could be used as targets in specific immunotherapy of esophageal squamous cell carcinomas.

Antigens, Neoplasm↗

Modulation of ventricular repolarization and R-R interval is altered in patients with globally impaired cardiac 123I-MIBG uptake.

BACKGROUND: Cardiac (123)I-metaiodobenzylguanidine (MIBG) imaging is widely used to assess cardiac sympathetic neuronal function. However, physiologic significance of impaired cardiac MIBG uptake is not fully elucidated. The purpose of the present study was to determine influences of abnormal cardiac sympathetic neuronal function on heart rate variability (HRV) and ventricular repolarization process. METHODS: Twenty-nine patients with prior myocardial infarction were divided into two groups by a heart-to-mediastinum ratio (H/M) of MIBG scintigraphy. Ten patients with globally decreased MIBG uptake (group I: H/M < 1.5), 19 patients with partially decreased MIBG uptake (group II: H/M >or= 1.5), and 17 control subjects with normal MIBG uptake (group III) were studied. Holter recording and a standard 12-lead electrocardiography were used for evaluation of HRV, QT-RR relation, and QT dispersion. RESULTS: Low, high, and total frequency components decreased in groups I and II, as compared to that of group III. The reduction of these frequency domain measures was more severe in group I than in group II, but the differences did not reach statistical significance. Circadian variation of frequency domain measures disappeared in group I. The slope of QT-RR relation was significantly greater in group I than in groups II and III. QT dispersion was also greater in group I (64 +/- 25 msec) than in group II (43 +/- 19 msec) and group III (28 +/- 9 msec). CONCLUSION: These results suggest that patients with sympathetic neuronal dysfunction inferred from globally impaired cardiac MIBG uptake have an altered modulation of ventricular repolarization process as well as decreased HRV.

3-Iodobenzylguanidine↗

Genetic polymorphism of N-acetyltransferase 2 in patients with esophageal cancer.

OBJECTIVE: N-Acetylation polymorphism is a representative genetic trait related to an individual's susceptibility to several cancers. However, there remains a controversy and no consensus concerning whether there is a true association between esophageal cancer and N-acetylation polymorphism. METHODS: To analyze the distribution of N-acetyltransferase 2 polymorphism in Japanese patients with esophageal squamous cell cancer, a molecular genotyping method using a polymerase chain reaction-based restriction fragment length polymorphism was used. RESULTS: Based on an analysis of 71 Japanese patients with esophageal squamous cell cancer and 329 healthy control subjects, the distribution of the slow acetylator phenotype was significantly higher in esophageal cancer patients than in the controls (19.7% and 9.4%, respectively, p = 0.040). The odds ratio of esophageal cancer for the slow phenotype was 2.55 (95% CI = 1.15-5.65, p = 0.023) compared with the rapid type. Furthermore, a significant difference between the distribution of acetylator phenotype and the incidence of lymph node metastasis and lymphatic involvement was found based on the clinicopathological features of these cancers. Esophageal cancer patients with a higher smoking exposure history tended to have the rapid acetylator phenotype. CONCLUSION: These results suggest that N-acetylation polymorphism may be implicated as a genetic trait affecting an individual's susceptibility and biological behavior of esophageal squamous cell cancer.

Aged↗

Reciprocal interactions between human T-lymphotropic virus type 1 and prostaglandins: implications for viral transmission.

Human T-lymphotropic virus type 1 (HTLV-1), the etiologic agent of adult T-cell leukemia/lymphoma, is transmitted through breast milk and seminal fluid, which are rich in prostaglandins (PGs). We demonstrate that PGE(2) upregulates the HTLV-1 long terminal repeat promoter through the protein kinase A pathway, induces replication of HTLV-1 in peripheral blood mononuclear cells (PBMC) derived from asymptomatic carriers, and enhances transmission of HTLV-1 to cord blood mononuclear cells (CBMC). Furthermore, HTLV-1 Tax transactivates a promoter for cyclooxygenase 2, a PG synthetase, and induces PGE(2) expression in PBMC or CBMC. Thus, HTLV-1 interacts with and benefits from PGs, constituents of its own vehicle for transmission.

CCAAT-Enhancer-Binding Protein-beta↗

Stress fracture of the ulnar styloid process in kendo player--a case report.

We present a case report of a 15-year-old kendo (Japanese fencing) player who suffered a stress fracture of the ulnar styloid process. Exercise of the kendo requires the athlete to flex his non-dominant wrist repeatedly in an ulnar direction, and causes the disorder. Excision of the osteochondral fragment relieved the symptoms. This lesion is likely to occur with other sports or activities which demand similar motion of the wrists.

Adolescent↗

PAF mediates cigarette smoke-induced goblet cell metaplasia in guinea pig airways.

Goblet cell metaplasia is an important morphological feature in the airways of patients with chronic airway diseases; however, the precise mechanisms that cause this feature are unknown. We investigated the role of endogenous platelet-activating factor (PAF) in airway goblet cell metaplasia induced by cigarette smoke in vivo. Guinea pigs were exposed repeatedly to cigarette smoke for 14 consecutive days. The number of goblet cells in each trachea was determined with Alcian blue-periodic acid-Schiff staining. Differential cell counts and PAF levels in bronchoalveolar lavage fluid were also evaluated. Cigarette smoke exposure significantly increased the number of goblet cells. Eosinophils, neutrophils, and PAF levels in bronchoalveolar lavage fluid were also significantly increased after cigarette smoke. Treatment with a specific PAF receptor antagonist, E-6123, significantly attenuated the increases in the number of airway goblet cells, eosinophils, and neutrophils observed after cigarette smoke exposure. These results suggest that endogenous PAF may play a key role in goblet cell metaplasia induced by cigarette smoke and that potential roles exist for inhibitors of PAF receptor in the treatment of hypersecretory airway diseases.

Animals↗

N-omega-nitro-L-arginine methyl ester increases airway responsiveness to serotonin but not to acetylcholine in cats in vivo.

BACKGROUND: We previously reported that N(omega)-nitro-L-arginine methyl ester (L-NAME) enhances airway responsiveness to inhaled serotonin in cats treated with atropine and propranolol. OBJECTIVE: To further elucidate the role of nitric oxide (NO) in airway responsiveness, we investigated whether L-NAME induces airway hyperresponsiveness to serotonin and acetylcholine (ACh) in animals with intact innervation. METHODS: Cats were anesthetized with pentobarbital sodium (50 mg/kg, i.p.), and mechanically ventilated. To assess airway responsiveness, we measured increase in total pulmonary resistance (RL) produced by delivering serotonin or ACh aerosol to the airway, and determined PC200 (the concentration which caused a 200% increase in RL). RESULTS: The following results were obtained: (1) Airway responsiveness to serotonin was significantly enhanced by the administration of L-NAME (100 mg/kg) in animals treated with atropine and propranolol. (2) Airway responsiveness to serotonin was also significantly enhanced by L- NAME in animals with intact innervation. (3) In contrast, airway responsiveness to ACh was not changed by the addition of L-NAME in cats with intact innervation. CONCLUSION: These results suggest that NO modulates nonspecific airway responsiveness in animals with intact innervation, presumably by a reflex mechanism.

Acetylcholine↗

Type II alveolar epithelial cells and interstitial fibroblasts express connective tissue growth factor in IPF.

Connective tissue growth factor (CTGF) is a growth and chemotactic factor for fibroblasts encoded by an immediate early gene that is transcriptionally activated by transforming growth factor-beta. Previous studies have shown that both CTGF messenger ribonuclear acid (mRNA) and protein are expressed in renal fibrosis and bleomycin-induced pulmonary fibrosis in mice. The aim of the present study was to investigate the localization of CTGF protein and its mRNA expression in the fibrotic lung tissue of patients with idiopathic pulmonary fibrosis (IPF). Using human fibrotic lung tissue obtained from eight autopsy cases and four biopsy cases with IPF, immunohistochemical staining, in situ hybridization, and reverse transcription-polymerase chain reaction (RT-PCR) were performed. The cellular immunoreactivity for CTGF was markedly increased in the lung tissue of patients with IPF, compared to normal lungs. The immunolocalization of CTGF was confined predominantly to proliferating type II alveolar epithelial cells and activated fibroblasts. In the normal lung, type II alveolar epithelial cells stained for CTGF were sparsely distributed. CTGF mRNA was localized in proliferating type II alveolar epithelial cells and activated fibroblasts in the interstitium of fibrotic lung tissues. RT-PCR analysis showed that CTGF mRNA was expressed at a higher level in fibrotic lungs than in normal lungs. In both an autocrine and a paracrine manner, type II alveolar epithelial cells and activated fibroblasts may play a critical role in pulmonary fibrosis by producing connective tissue growth factor which modulates fibroblast proliferation and extracellular matrix production.

Adult↗

Spectral characteristics of human atrial fibrillation waves of the right atrial free wall with respect to the duration of atrial fibrillation and effect of class I antiarrhythmic drugs.

The aim of this study was to use fast Fourier transform analysis to clarify the characteristics of human atrial fibrillation (AF) waves with respect to the duration of AF and the effect of class I antiarrhythmic drugs. Twenty-two patients (10 paroxysmal AF, 12 persistent AF) without organic heart disease were studied by conventional electrophysiological methods. Electrograms were recorded from the right atrial free wall during AF and spectral analysis was performed for 35s (16 consecutive 4096-ms epochs with 50% overlap) and the fibrillation cycle length (FCL) was calculated from the peak frequency. Mean FCL and SD were determined from 16-epoch data, and the temporal variability of FCL was defined as the SD of FCL. Paroxysmal AF had a longer mean FCL than persistent AF (178+/-26ms vs 139+/-16 ms, p<0.001) and AF duration had a significant inverse correlation with mean FCL (r=-0.79, p<0.001). The temporal variability of FCL was significantly greater in paroxysmal AF than in persistent AF (p<0.05) and there was a significant positive correlation between the mean FCL and the temporal variability of FCL (r=0.66, p<0.001). In 8 of 18 patients given a class I antiarrhythmic drug (cibenzoline or procainamide), AF was terminated and in those patients the mean FCLs before administration of class I drugs were significantly greater than in patients without AF termination. With respect to mean FCL before drug administration, conversion occurred in 100% of patients with FCL > or =168 ms and in 17% of those with FCL <168 ms. A longer duration of AF shortens the mean FCL, which is consistent with atrial electrical remodeling. Class I drugs prolong the mean FCL above a critical level and will terminate AF, which can be estimated from the mean FCL before drug administration.

Adult↗

Spontaneous onset of torsade de pointes in long-QT syndrome and the role of sympathovagal imbalance.

The net effects of sympathetic and vagal activity on the QT interval and the mode of spontaneous onset of torsade de pointes (TdP) are still unclear in long-QT syndrome. Two patients with long-QT syndrome had syncope while undergoing Holter ECG investigation. The spontaneous onset of TdP in these patients was analyzed with respect to the relation between the RR and QT intervals. Both patients were high-school students (16- and 17-year-old boys) who had been diagnosed as long-QT syndrome and followed up without medical treatment because they had had neither a history of syncope nor arrhythmia induction by treadmill exercise tests. The first episode of syncope in both patients occurred during ordinary daily life and was not related to exercise or psychological stress. The dynamic changes between the RR and QT intervals associated with the spontaneous onset of TdP were analyzed by Holter ECG. Both patients showed sinus tachycardia followed by abrupt sinus bradycardia immediately before the onset of TdP. The enhanced rate of the adaptive response of the QT interval that occurred during the deceleration of the heart rate preceded the onset of TdP. These observations suggest that the complex situation that follows sympathovagal imbalance may have an important role in the dynamic change in the QT interval and initiation of TdP in patients with long-QT syndrome.

Adolescent↗