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Biomedical subjects

Y Fukuchi

Publications and source records attributed to Y Fukuchi.

At least 37 records · Page 2Linked to original sources
PubMed2001

Compound heterozygosity for alpha-1-antitrypsin (S(iiyama) and QO(clayton)) in an Oriental patient.

Alpha-1-antitrypsin (alpha1AT) deficiency is extremely rare among Orientals. We treated a 37-year-old man with severe pulmonary emphysema associated with a low serum concentration of alpha1AT. Mutation analysis of the alpha1AT gene was performed using a reverse transcription-polymerase chain reaction followed by sequencing. The patient proved to be a compound heterozygote carrying a S(iiyama) deficient allele and a QO(clayton) null allele. This is the first Japanese case of alpha1AT deficiency to arise from such compound heterozygosity in a family with no apparent consanguineous marriage, suggesting that the gene frequency for deficient alleles might be somewhat higher than previously estimated.

Adult↗
PubMed2001

[Gene therapy for pulmonary hypertension].

Pulmonary hypertension is a life-threatening disease characterized by progressive vascular remodeling, ultimately producing right ventricular failure. Recently, continuous intravenous infusion of prostacyclin has become recognized as a therapeutic breakthrough that can improve hemodynamics and surgical in patients with pulmonary hypertension. Nevertheless, gene therapy is also expected as a valuable therapeutic approach in pulmonary hypertension for the reason that transgene expression is located mainly in the lung. Previous study demonstrated that intratracheal gene transfer of endothelial derived nitric oxide synthase, prostacyclin I synthase, vascular endothelial growth factor etc. resulted in a reduction of pulmonary arterial pressure in experimental animals with pulmonary hypertension. Major hurdle in current gene therapy for pulmonary hypertension may be the limited duration of transgene expression in lung tissue. However, rather than a limitation, this feature may be a advantage in some situations where expression during only a few weeks may provide both adequate therapeutic efficacy and limited side effects. Development of second-generation gene delivery system will provide new tools to prolong the duration of transgene expression.

Animals↗
PubMed2001

[Genetic variation of NADPH/NADH oxidase and susceptibility to diffuse panbronchiolitis (DPB) and chronic obstructive pulmonary disease (COPD)].

Diffuse panbronchiolitis (DPB) and chronic obstructive pulmonary disease (COPD) are both characterized by chronic airflow obstruction of unknown etiology. It is hypothesized that neutrophils play the major role in the pathogenesis of these diseases. Recent studies have suggested that genetic factors may be related to individual susceptibility to these diseases. We have investigated the association between the C 242 T polymorphism of p 22 phox, a critical subunit of superoxide-generating NADH/NADPH oxidase, and susceptibility to DPB and COPD. Blood samples obtained from both patients with DPB (n = 82), COPD (n = 53), and control subjects (n = 82) were used for this genotyping assay; and the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were performed to genotype the gene. The frequency of the C allele was 0.91, 0.92, 0.92 in the DPB, COPD, and control groups, respectively. There were no differences in the distribution of the genotype of p 22 phox among these groups, either. We concluded that there is no association between the C 242 T polymorphism of p 22 phox, and susceptibility to DPB and COPD.

Bronchiolitis↗
PubMed2001

[Health status and lifestyle issues of homeless people in Sapporo city, 2000].

OBJECTIVE: To clarify the health status and lifestyle issues of homeless people in Sapporo city, voluntary "health consultations and medical examinations" were carried out near an emergency kitchen. METHODS: The voluntary activities were held in a park near the shelter tents of homeless people seven times from December 1999 to December 2000. The homeless people who consulted us, medical doctors, were asked detailed questions about past history, present illness, subjective symptoms, lifestyles and so on, and were examined for their blood pressure and urinary parameter. RESULTS: A total of 60 homeless people, including 59 men and 1 woman, were consulted and examined, Fifty-seven percent of them were 50 years old of older, and 30% had been homeless for less than half a year. Forty percent had some dental problems, 28% suffered neck stiffness, and 27% back pain. The medical examination found 53% of them to be hypertensive and 26% to be diabetic. Twenty-five percent had meals only once a day, 55% had meat or fish in their diet not more than twice a week and 57% had vegetables in their diet not more than twice a week. Forty-two percent slept not more than 5 hours a day, 13% often drank alcohol in the daytime, and 83% were smokers. CONCLUSION: The present results suggest that lifestyle-related chronic diseases are more significant problems among homeless people in Sapporo city than common infectious diseases such as tuberculosis or dysentery, probably because it is colder and therefore there are fewer homeless people in Sapporo city than in other major cities in Japan such as Tokyo and Osaka. Further studies of the homeless people living in such a cold environment are warranted to develop better health policies for them in the context of their social and economical determinants. In addition, it is important to establish a more reliable registration system for these people in order to plan and provide a comprehensive social and health support network as needed.

Adult↗
PubMed2001

[A case of chondrosarcoma originating from the rib and presenting as a posterior mediastinal tumor-like shadow].

A 66-year-old man was admitted to our hospital because of induction therapy of interferon for chronic hepatitis due to hepatitis C virus. On routine investigation, a mass-like lesion was detected at the level of the hilum of the left lung on the chest plain radiograph. On the thoracic CT, the heterogeneous tumor, including calcification, was 6 cm in diameter in the posterior mediastinal area, and the rib and vertebra had been damaged by it. The tumor extended to the descending aorta and the left main bronchus. A small nodule in the left S1 + 2 was noted on another slice section of this thoracic CT. The possible diagnoses, based on these radiological findings, for this tumor were primary lung cancer, posterior mediastinal tumor and malignant tumor originating from the chest wall. The diagnosis of chondrosarcoma was made based on the histological findings of the specimen obtained from the tumor. This tumor could not be resected in this case, because it had extensively damaged the rib and vertebra, and the nodular lesion in the left S1 + 2 was regarded as a metastasis from it. Although reports of chondrosarcoma originating from a rib and presenting as a posterior mediastinal tumor-like shadow are rare, chondrosarcoma should be considered as a possible diagnosis for such tumors-posterior mediastinal masses with characteristic findings such as a large tumor in contact with the chest wall, and containing calcification, with destruction of bone and dissection of the rib as shown in our CT findings.

Aged↗
PubMed2001

[Evaluation of spontaneous pneumothorax in patients with pulmonary lymphangioleiomyomatosis].

We retrospectively evaluated the development of spontaneous pneumothorax in patients with pulmonary lymphangioleiomyomatosis (LAM). Fifteen patients with LAM, whose diagnosis was confirmed histopathologically, were enrolled. All were women, and had a mean age at diagnosis of 31.6 +/- 7.3 years. They were divided into two groups according to the presence or absence of pneumothorax at the time of onset, Group A consisting of nine patients with pneumothorax, and Group B, of six without pneumothorax. Spontaneous pneumothorax developed in 15 out of a total of 18 hemithoraces in Group A patients in whom 13 hemithoraces were surgically treated for pneumothorax (eight open thoracotomies and five video-assisted thoracoscopic surgeries). Bullectomy with either parietal pleurectomy, pleural abrasion, or instillation of chemical irritants to prevent the recurrence of pneumothorax offered better outcomes than bullectomy alone in terms of the postoperative recurrence rate of pneumothorax (p < 0.05). On the other hand, three of the five Group B cases developed pneumothorax during the course of LAM, but none was operated because of severely impaired lung function. The other patient in Group B was not only free of pneumothorax at onset, but also did not develop pneumothorax or suffer from impaired lung function. There were no deaths due to pneumothorax recorded among Group A patients, but two patients in group B died. A better survival rate was noted in Group A than in Group B by Kaplan-Meier analysis, suggesting that these two groups may represent the broad clinical spectrum of LAM.

Adult↗
PubMed2000

Bone morphogenetic protein-2 induces apoptosis in human myeloma cells with modulation of STAT3.

Bone morphogenetic proteins (BMPs), members of the transforming growth factor (TGF)-beta superfamily, are a group of related proteins that are capable of inducing the formation of cartilage and bone but are now regarded as multifunctional cytokines. We show in this report a novel function of BMPs in hematopoietic cells: BMP-2 induces apoptosis not only in human myeloma cell lines (U266, RPMI 8226, HS-Sultan, IM-9, OPM-2, and KMS-12 cells), but also in primary samples from patients with multiple myeloma. The mechanism of BMP-2-induced apoptosis was investigated with the use of U266 cells, which are dependent on the interleukin-6 autocrine loop. We showed that BMP-2 caused cell-cycle arrest in the G1 phase and the subsequent apoptosis of myeloma cells. BMP-2 up-regulated the expression of cyclin-dependent kinase inhibitors (p21(CIP1/WAF1) and p27(KIP1)) and caused hypophosphorylation of retinoblastoma (Rb) protein. In studies of apoptosis-associated proteins, BMP-2 was seen to down-regulate the expression of Bcl-x(L); however, BMP-2 had no effects on the expression of Bcl-2, Bax, or Bad. Therefore, BMP-2 induces apoptosis in various human myeloma cells by means of the down-regulation of Bcl-x(L) and by cell-cycle arrest through the up-regulation of p21(CIP1/WAF1) and p27(KIP1) and by the hypophosphorylation of Rb. Further analysis showed that the signal transducer and activator of transcription 3 (STAT3) was inactivated immediately after BMP-2 treatment. We conclude that BMP-2 would be useful as a novel therapeutic agent in the treatment of multiple myeloma both by means of its antitumor effect of inducing apoptotis and through its original bone-inducing activity, because bone lesions are frequently seen in myeloma patients.

Apoptosis↗
PubMed2000

Arsenic trioxide (As2O3)-induced apoptosis and differentiation in retinoic acid-resistant acute promyelocytic leukemia model in hGM-CSF-producing transgenic SCID mice.

Recent clinical studies in China and USA showed that arsenic trioxide (As2O3) is an effective treatment of acute promyelocytic leukemia (APL) patients refractory to all-trans retinoic acid (RA). We here investigate the effects of As2O3 on RA-resistant APL in vivo and in vitro using our RA-resistant APL model system. As2O3 can induce inhibition of cellular growth of both RA-sensitive NB4 and RA-resistant UF-1 APL cells via induction of apoptosis in vitro. The expression of BCL-2 protein decreased in a dose- and time-dependent manner in NB4 cells. Interestingly, the levels of BCL-2 protein were not modulated by As2O3, but it did upregulate BAX protein in UF-1 cells. UF-1 cells (1x10(7)) were transplanted into hGM-CSF-producing transgenic SCID mice and successfully formed subcutaneous tumors. After 40 days of implantation, mice were treated with As2O3, all-trans RA and PBS for 21 days. In all-trans RA- and PBS-treated mice, tumors grew rapidly, with a 4.5-fold increase in volume at day 21 compared to the initial size. In marked contrast, tumor size was decreased to half of the initial size by the treatment of As2O3, which resulted in cells with the typical appearance of apoptosis. Interestingly, one of the As2O3-treated mice showed mature granulocytes in the diminished tumor, suggesting that As2O3 had dual effects on RA-resistant APL cells in vivo: both inducing apoptosis and differentiation of the leukemic cells. We conclude that our RA-resistant APL model will be useful for evaluating novel therapeutic approaches to patients with RA-resistant APL, and for further investigation of the metabolism of As2O3 in vivo.

Animals↗
PubMed2000

Association between alpha-1-antichymotrypsin polymorphism and susceptibility to chronic obstructive pulmonary disease.

BACKGROUND: The antiproteases, including alpha-1-antitrypsin, are supposed to prevent lungs from becoming emphysematous. Genetic susceptibility to smoking injury may confer a risk for the development of chronic obstructive pulmonary disease (COPD). METHODS: We have investigated the association between the polymorphism of alpha-1-antichymotrypsin (AACT), one of the antiproteases, and susceptibility to the development of COPD among heavy smokers. Blood samples obtained from both patients with COPD (n = 53) and control subjects (n = 65) at the Tokyo University Hospital, the Juntendo University Hospital and the Tokyo Kenbikyoin Clinic were used for this genotyping assay. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were performed to genotype the AACT biallelic polymorphism in the signal peptide (-15 alanine to threonine), and the two polymorphisms of the exon (Pro229Ala and Leu55Pro). RESULTS: The proportion of AACT/Ala-15 homozygotes was significantly higher in the COPD patients than in the control subjects (COPD 37.7% vs. control 18.5%). The odds ratio for AACT/Ala-15 homozygotes vs. all other genotypes was 2.7 (95% CI 1.2-6.2) for the COPD group. We could not find any association between the other two polymorphisms and COPD. CONCLUSIONS: Genetic polymorphism in the signal peptide of AACT may be associated with individual susceptibility to the development of COPD, because the AACT/Ala-15 genotype is predominantly found in patients with COPD. It is suggested that AACT/Ala-15 genotype may be less protective against smoking injury.

Adult↗
PubMed2000

Detection of aspiration and swallowing disorder in older stroke patients: simple swallowing provocation test versus water swallowing test.

OBJECTIVE: To assess the sensitivity and specificity of a simple swallowing provocation test (SPT) and a water swallowing test (WST) in detecting aspiration pneumonia in elderly patients with stroke. DESIGN: Retrospective comparative study involving a simple 2-step SPT and WST on all subjects. PARTICIPANTS: Twenty-six stroke patients with aspiration pneumonia (mean age, 72.1 +/- 4.1 yr) and 26 age-matched stroke patients without aspiration pneumonia (mean age, 69.4 +/- 3.9 yr). INTERVENTIONS: The normal response to SPT was determined by inducing swallowing reflex within 3 seconds after water injection into the suprapharynx. In WST, subjects drank quantities of 10 and 30 mL of water from a cup within 10 seconds. The subject who drank water without interruption-without evidence of aspiration-was determined as normal. RESULTS: The sensitivity and specificity of first-step SPT for the detection of aspiration pneumonia were 100% and 83.8%, respectively. Those of the second-step SPT were 76.4% and 100%, respectively. The sensitivity and specificity of first-step WST using 10 mL of water for the detection of aspiration pneumonia were 71.4% and 70.8%, respectively. Those of the second-step WST using 30 mL of water were 72% and 70.3%, respectively. CONCLUSION: SPT is more useful than WST in differentiating patients predisposed to aspiration.

Aged↗
PubMed2000

Neither IL-1beta, IL-1 receptor antagonist, nor TNF-alpha polymorphisms are associated with susceptibility to COPD.

The cytokines that contribute to airway inflammation, including interleukin-1beta (IL-1beta) and tumour necrosis factor alpha (TNFalpha), might have key roles in the development of chronic obstructive pulmonary disease (COPD). Interleukin-1 receptor antagonist (IL-1RN), the physiological antagonist of IL-1beta, is also known to play a crucial role in several chronic inflammatory diseases. In this study, we investigated the association of the polymorphisms of IL-1beta, IL-1RN and TNFalpha with susceptibility to COPD. To elucidate the genotype of the IL-1beta polymorphisms at position -511 base and at the amino acid residue 105, the IL-1RN polymorphism in intron 2, and TNFalpha polymorphism at position -308, polymerase chain reaction (PCR) and restriction enzyme fragment length polymorphism (RFLP) were performed on blood samples from both patients with COPD (n = 53) and control subjects (n = 65). There were no differences on the allele and genotype frequency of IL-1beta, IL-1RN, and TNFalpha between the two groups. We could not find a significant link between the polymorphism of TNFalpha, which was previously reported to be associated with chronic bronchitis, and COPD. Furthermore, no association between genetic polymorphisms of IL-1beta and IL-1RN and individual susceptibility to COPD was found.

Aged↗
PubMed2000

Osteopontin is induced by nitric oxide in RAW 264.7 cells.

Nitric oxide (NO) produced by macrophages is thought to contribute to various pathological conditions. Osteopontin (OPN) is a phosphorylated glycoprotein produced principally by macrophages. OPN inhibits inducible nitric oxide synthase (iNOS), which generates large amounts of NO production. However, the relationship between NO and endogenous OPN in activated macrophages has not yet been elucidated. We therefore examined expression of endogenous iNOS and OPN in a murine macrophage cell line, RAW 264.7 cells, by treating the cells with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). Treatment of cells with LPS and IFN-gamma resulted in an increase of iNOS mRNA to maximum at 12 h after stimulation. In contrast, OPN mRNA was induced more slowly than iNOS mRNA. Induction of both iNOS and OPN mRNA in RAW 264.7 cells was markedly suppressed by addition of the specific iNOS inhibitor S-2-aminoethyl isothiourea dihydrobromide. The NOS inhibitor NG-methyl-L-arginine also suppressed induction of OPN mRNA but hardly affected iNOS mRNA expression. The NO-releasing agent spermine-NONOate but not peroxynitrite enhanced induction of OPN mRNA. These results suggest that NO directly up-regulates the endogenous OPN in macrophages stimulated with LPS and IFN-gamma. This up-regulation of endogenous OPN may represent a negative feedback system acting to reduce iNOS expression.

Animals↗
PubMed2000

Effects of angiotensin-converting enzyme inhibitors on spontaneous or stimulated generation of reactive oxygen species by bronchoalveolar lavage cells harvested from patients with or without chronic obstructive pulmonary disease.

We examined the effects of angiotensin-converting enzyme (ACE) inhibitors on spontaneous or stimulated generation of reactive oxygen species (ROS) by bronchoalveolar lavage (BAL) cells prepared from 6 patients with chronic obstructive pulmonary disease (COPD) and from age-matched control subjects without COPD. The ROS produced by BAL cells were measured by the lucigenin-dependent chemiluminescence method. The application of ACE inhibitors into culture media containing BAL cells inhibited spontaneous and stimulated generation of ROS by BAL cells from COPD patients and control subjects in an ambroxol-concentration-dependent manner. Alacepril, an ACE inhibitor bearing SH-group, inhibited the oxygen radical production and generation by BAL cells from COPD patients in a dose-dependent fashion. Approximately 0.6-0.7 mM of alacepril inhibited 50% of the ROS production by BAL cells from COPD patients, whereas a slightly higher concentration (3 mM) of lisinopril, an ACE inhibitor not bearing an SH-group, was necessary to inhibit the production of ROS. These results suggest that an ACE inhibitor may act as an pulmonary antioxidant in patients with COPD.

Aged↗
PubMed2000

Recombinant adeno-associated virus vectors efficiently transduce foreign gene into bovine aortic endothelial cells: comparison with adenovirus vectors.

Because the features and kinetics of adeno-associated virus (AAV)-mediated gene transfer to endothelial cells (EC) are yet to be ultimately determined, we tested variables pertinent to the efficiency of AAV-mediated gene transfer to bovine aortic endothelial cells (BAEC). The variables with AAV vectors were compared with the better characterized adenovirus (Ad) vectors. There is a dose-response relationship between multiplicity of infection (moi) of AAV or Ad vectors and transduction efficiency in BAEC. The higher moi of AAV vectors achieved more than 80% of transduction efficiency in cultured BAEC. AAV and Ad vectors showed an incubation-time-dependent increase in transduction efficiency of LacZ gene to the BAEC up to 12 h of vector exposure. Although the similar kinetics of transduction efficiency of LacZ gene to BAEC was found in both vectors, the duration of gene expression was longer in AAV vector than that in Ad vectors in vitro. These results indicate that AAV-vector is efficient for gene transfer to EC, and higher moi of vectors or a longer period exposure of vectors to EC can facilitate efficient transduction of a foreign gene into cultured EC. For the duration of gene expression, the AAV vectors may be better than Ad vectors.

Adenoviridae↗
PubMed2000

[A senile case of acute necrotizing myopathy presenting prolonged severe muscle paralysis due to high dose glucocorticoid and muscle relaxant].

An 82-year old man was admitted with dyspnea, productive cough and wheezing. In addition to antibiotics (meropenem trihydrate 0.5 g/day), glucocorticoids (hydrocortisone 1.250 mg, methylpredonisolone 4.250 mg) were administered for the severe bronchospasms. Since his respiratory condition deteriorated, he underwent mechanical ventilation using a muscle relaxant (vecuronium bromide, total dose 776 mg) in combination with high dose glucocorticoid. As his pneumonia improved on the 10th hospital day, we started weaning him from the ventilator. However, we were unable to complete weaning from the ventilator because of prolonged quadriplegia and paralysis of the respiratory muscles. A few days later, myoglobinuria appeared. Electrophysiological examinations suggested the involvement of both neuromuscular junctions and muscles. Muscle biopsy showed rhabdomyolysis. Acute necrotizing myopathy was diagnosed due to high doses of glucocorticoid, muscle relaxant, or both. He required about 3 months to be weaned from the mechanical ventilation, and another 3 months to leave the hospital. Based on our experience, we should consider acute myopathy as an adverse effect of glucocorticoids, muscle relaxants or both in elderly patients who require mechanical ventilation.

Acute Disease↗
PubMed2000

[Sleep apnea syndrome and hypertension using desaturation index].

To examine the roles of obstructive apnea (OA) and central apnea (CA) in oxygen desaturation on hypertension and sleep apnea syndrome (SAS), we performed a sleep study on 41 elderly subjects (mean age 69.5 +/- 6.8 years, male:female = 31:10). Nocturnal oxygen desaturation was documented with a pulse oximeter and apneas (OA and CA) were diagnosed on the basis of results of respiratory inductive plethysmography and oronasal flow. Significant desaturation (SDS, greater than 5% drop in SpO2 from baseline value) and desaturation index (DI; epsilon SDS (%) x duration (hour)) were calculated using the continuous nocturnal monitoring system with a pulse oximeter. We defined central type apnea above 50% as the central type group (n = 8, mean age 58.6 +/- 2.9, mean BMI 21.3 +/- 1.0, male:female = 7:1), and obstructive type and mixed type apnea above 50% as the obstructive type group (n = 21, mean age 70.0 +/- 3.2, mean BMI 25.3 +/- 1.0, male:female = 17:4). Other subjects were assigned to the control group (n = 12, mean age 64.3 +/- 2.3, mean BMI 23.8 +/- 1.2, male:female = 7:5). The DI (delta 5%) of the central type was 0.34 +/- 0.17, and that of the obstructive type was 1.78 +/- 0.7 showing a significant increase in the latter compared to the control group (p < 0.02). The DI (< 90%) of the central type was 0.14 +/- 0.07, and that of the obstructive type was 1.72 +/- 0.75, and that of the obstructive type was significantly greater than in the control group (p < 0.05) and central type (p < 0.05). There were 4 cases (33.3%) with hypertension in the control group and 4 cases (50.0%) with hypertension in the central type group, but there were 15 cases (71.4%) with hypertension in the obstructive type group. Hypertensive prevalence in the obstructive group was significantly more than in the control group (p < 0.05). No significant difference in body mass index or age were seen in the obstructive group and control group. There was a significant correlation between mean blood pressure and apnea index (AI). The AI of the hypertensive group was significantly higher than that of the normotensive group (p < 0.001). These results suggest that subjects with significant obstructive apneas may be at greater risk for hypertension than subjects with central apneas and that hypertension in the pathogenesis of SAS may be related to the severity of apneas rather than oxyhemoglobin desaturation.

Adult↗
PubMed2000

[Hospitalization reduction by an asthma tele-medicine system].

We examined an effectiveness of a new asthma telemedicine system in reducing hospitalizations using a multi-site randomized control study. In this program, a nurse under physician supervision monitors the patient's airway status at home and provides instructions to individuals via the telephone, helping them manage exacerbations as well as reinforcing proper use of a zone-controlled management plan. Patients with a high risk for hospitalization were screened based on the numbers of emergency room visits and hospitalizations found in a previous study and randomly assigned to either the telemedicine or control group. After a six-month study period, an 83% reduction in hospitalization was demonstrated in the telemedicine group versus the control group, with a P value of 0.01. Improvement of peak expiratory flow and symptoms were also shown in the study group. We conclude that the key success factors in home asthma management for poorly controlled asthma patients are early detection of exacerbations through daily peak flow monitoring, compliance with prescribed daily prophylactic anti-inflammatory steroid medications, and immediate action as specified by a zone-controlled action plan upon the first signs of deterioration.

Aged↗