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Biomedical subjects

Hiroshi Hayakawa

Publications and source records attributed to Hiroshi Hayakawa.

At least 19 recordsLinked to original sources
PubMed2006

Human polynucleotide phosphorylase protein in response to oxidative stress.

8-Oxo-7,8-dihydroguanine (8-oxoGua) is generated in nucleic acids as well as in their precursors due to the actions of oxygen radicals produced through a normal cellular metabolism. Since oxidized guanine can pair with both cytosine and adenine, it causes alterations in the phenotypic expression when it is present in RNA. To prevent such an outcome, organisms must have some mechanism for eliminating such oxidized guanine nucleotides from RNA and its precursors. In mammalian cells, MTH1 and NUDT5 proteins degrade 8-oxoGTP and 8-oxoGDP to 8-oxoGMP, which is an unusable form for RNA synthesis. In a search for proteins functioning at the RNA level, polynucleotide phosphorylase (PNP) protein has been suggested to be a good candidate for such a role. The human PNP protein has an ability to bind specifically to RNA containing 8-oxoGua. When human cells are exposed to agents that induce oxidative stress, such as hydrogen peroxide and menadion, the amounts of PNP protein decrease rapidly while amounts of other proteins in the cells do not change after such treatments. No specific decrease in the PNP protein level is observed when cells are treated with ACNU and cycloheximide at doses sufficient to provide the same degree of growth suppression. These results imply that the PNP protein might thus play a role in excluding oxidized forms of RNA from the translation mechanism.

Base Sequence↗
PubMed2006

Influenza vaccination in severely multiply handicapped persons/children.

BACKGROUND: Many reports about the preventative effects of inactivated influenza vaccine have been published, targeting persons with underlying medical conditions. However, the effectiveness for severely multiply handicapped persons/children (SMHPs) is not yet well established. METHODS: The study group consisted of 79 SMHPs (36 males and 43 females, aged 18-66 years), with long-term hospitalization in Niigata National Hospital. We compared serum antibody responses before and after two-doses vaccination. RESULTS: Before vaccination for the 2004-2005 season, SMHPs showed continuously high HAI titer in A/New Caledonia/20/99(H1N1)-strain from March to October in 2004. The seroprotection rates were increased after the first dose, but no remarkable change was seen after the second dose in all three strains. Subjects less than 30 years old (< or = 29 group) had a high antibody titers against all three strains compared with subjects aged >40 years old. On the other hand, in the seroconversion rates, there were no significant differences in age, gender, and severity of symptoms. CONCLUSIONS: According to our study, SMHPs are low responders except < or = 29 group and the influenza vaccine effectiveness is more affected by their age than severity of symptoms. We suggest a recommendation for influenza vaccination especially in SMHPs; inactivated influenza virus vaccine (one dose) should be performed during the previous fall. In addition, further studies are needed about chemoprophylaxis, which can prevent influenza outbreaks in SMHPs.

Adolescent↗
PubMed2006

Exogenous 8-oxo-dG is not utilized for nucleotide synthesis but enhances the accumulation of 8-oxo-Gua in DNA through error-prone DNA synthesis.

7,8-Dihydro-8-oxoguanine (8-oxo-Gua) and its nucleoside in cytosol are derived from the repair of oxidative DNA and the cleanup of oxidatively damaged DNA precursors, respectively. While the harmful effects of 8-oxo-Gua present in DNA have been studied extensively, few have reported its effects on cytosolic function. Our previous study showed that the addition of 8-oxo-dG to culture media caused an accumulation of 8-oxo-Gua in nuclear DNA in several leukemic cells including KG-1, which lack 8-oxoguanine glycosylase 1 (OGG1) activity due to mutational loss. However, the mechanism underlying 8-oxo-Gua level increases in DNA has not been addressed. In this study, we elucidated the metabolic fate of 8-oxo-Gua-containing nucleotide and the effect of exogenous 8-oxo-dG on DNA synthesis in KG-1 cells. We found that 8-oxo-dGMP was rapidly dephosphorylated to 8-oxo-dG rather than phosphorylated to 8-oxo-dGDP, thus indicating that 8-oxo-Gua-containing molecule is not used as a substrate for DNA synthesis in KG-1 cells. In fact, radiolabeled 8-oxo-dG was incubated but radioactivity was not detected in nuclear DNA of KG-1 cells, showing that 8-oxo-dG is not directly incorporated into DNA. Interestingly, the activity of DNA polymerase beta, which synthesize DNA with low fidelity increased in KG-1 cells treated with 8-oxo-dG, whereas the expression of DNA polymerase alpha decreased. In addition, the accumulation of 8-oxo-Gua in KG-1 DNA was completely inhibited by a specific inhibitor of DNA polymerase beta. Thus, our findings address that the insertion of 8-oxo-dG into KG-1 DNA is not due to the direct incorporation of exogenous 8-oxo-dG, but rather to the inaccurate incorporation of endogenous 8-oxo-dGTP by DNA polymerase beta. It further suggests that 8-oxo-dG in the cytosol may function as an active molecule itself and perturb the well-defined DNA synthesis.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2006

Urinary liver-type fatty acid binding protein as a useful biomarker in chronic kidney disease.

BACKGROUND: We reported that urinary L-FABP reflected the progression of chronic kidney disease (CKD). This study is aimed to evaluate the clinical significance of urinary liver type fatty acid binding protein (L-FABP) as a biomarker for monitoring CKD. METHODS: Urinary L-FABP was measured using human L-FABP ELISA kit (CMIC.Co., Ltd., Tokyo, Japan). The relations between urinary L-FABP and clinical parameters were evaluated in non-diabetic CKD (n = 48) for a year. In order to evaluate the influence of serum L-FABP derived from liver upon urinary L-FABP, both serum and urinary L-FABP were simultaneously measured in patients with CKD (n = 73). RESULTS: For monitoring CKD, the cut-off value in urinary L-FABP was determined as 17.4 microg/g.cr. by using a receiver operating characteristics (ROC) curve. Renal function deteriorated significantly more in patients with 'high' urinary L-FABP (n = 36) than in those with 'low' L-FABP (n = 12). The decrease in creatinine clearance was accompanied by an increase in urinary L-FABP, but not in urinary protein. Serum L-FABP in patients with CKD was not correlated with urinary L-FABP. CONCLUSION: Urinary excretion of L-FABP increases with the deterioration of renal function. Serum L-FABP did not influence on urinary L-FABP. Urinary L-FABP may be a useful clinical biomarker for monitoring CKD.

Adult↗
PubMed2006

[A case of severe intestinal tuberculosis, treated with ciprofloxacin, kanamycin and prednisolone].

A 31-year-old man was admitted to our hospital because of frequent diarrhea. Colonoscopy showed ring ulcers on the rectum and ascending colon and chest X-ray showed abnormal shadows which were diagnosed as tuberculosis by sputum PCR. He started treatment with isoniazid (INH), rifampicin (RFP), pyrazinamide (PZA) and streptomycin (SM), however, eruption and ileus were seen. Then, he was retreated with ciprofloxacin (CPFX), kanamycin sulfate (KM) and prednisolone (PSL). Subsequently, we added RFP and further added calcium para-aminosalicylate (PAS). All these treatment was effective, and he was discharged from the hospital.

Adult↗
PubMed2005

Mammalian enzymes for preventing transcriptional errors caused by oxidative damage.

8-Oxo-7,8-dihydroguanine (8-oxoGua) is produced in cells by reactive oxygen species normally formed during cellular metabolic processes. This oxidized base can pair with both adenine and cytosine, and thus the existence of this base in messenger RNA would cause translational errors. The MutT protein of Escherichia coli degrades 8-oxoGua-containing ribonucleoside di- and triphosphates to the monophosphate, thereby preventing the misincorporation of 8-oxoGua into RNA. Here, we show that for human the MutT-related proteins, NUDT5 and MTH1 have the ability to prevent translational errors caused by oxidative damage. The increase in the production of erroneous proteins by oxidative damage is 28-fold over the wild-type cells in E.coli mutT deficient cells. By the expression of NUDT5 or MTH1 in the cells, it is reduced to 1.4- or 1.2-fold, respectively. NUDT5 and MTH1 hydrolyze 8-oxoGDP to 8-oxoGMP with V(max)/K(m) values of 1.3 x 10(-3) and 1.7 x 10(-3), respectively, values which are considerably higher than those for its normal counterpart, GDP (0.1-0.5 x 10(-3)). MTH1, but not NUDT5, possesses an additional activity to degrade 8-oxoGTP to the monophosphate. These results indicate that the elimination of 8-oxoGua-containing ribonucleotides from the precursor pool is important to ensure accurate protein synthesis and that both NUDT5 and MTH1 are involved in this process in human cells.

DNA Repair Enzymes↗
PubMed2005

Multiple enzyme activities of Escherichia coli MutT protein for sanitization of DNA and RNA precursor pools.

8-OxoGua (8-oxo-7,8-dihydroguanine) is produced in nucleic acids as well as in nucleotide pools of cells, by reactive oxygen species normally formed during cellular metabolic processes. MutT protein of Escherichia coli specifically degrades 8-oxoGua-containing deoxyribo- and ribonucleoside triphosphates to corresponding nucleoside monophosphates, thereby preventing misincorporation of 8-oxoGua into DNA and RNA, which would cause mutation and phenotypic suppression, respectively. Here, we report that the MutT protein has additional activities for cleaning up the nucleotide pools to ensure accurate DNA replication and transcription. It hydrolyzes 8-oxo-dGDP to 8-oxo-dGMP with a K(m) of 0.058 microM, a value considerably lower than that for its normal counterpart, dGDP (170 microM). Furthermore, the MutT possesses an activity to degrade 8-oxo-GDP to the related nucleoside monophosphate, with a K(m) value 8000 times lower than that for GDP. These multiple enzyme activities of the MutT protein would facilitate the high fidelity of DNA and RNA syntheses.

DNA Replication↗
PubMed2005

Duplication of chromosome 4q: renal pathology of two siblings.

We report on two sibs with partial 4q trisomy: dup (4)(q35.2-q31.22) and their renal biopsy findings. Both of them show renal hypoplasia, although their chromosomal aberration lacks the minimal duplicated region 4q22-q23 and/or 4q25-q31.3, which had been shown to be associated with urogenital abnormalities and thumb malformations in previous reports. From the renal biopsy findings, the two sibs were diagnosed as oligonephronia. We summarize the 13 having published cases of duplication of chromosome 4q, and examine which segments have a close relationship to renal hypoplasia. We suggest that renal hypoplasia may be female-prone, and may have a close relationship with duplication of 4q33-q34.

Adolescent↗
PubMed2005

Clinical evaluation of urinary excretion of liver-type fatty acid-binding protein as a marker for the monitoring of chronic kidney disease: a multicenter trial.

To confirm the clinical usefulness of the measurement of urinary liver-type fatty acid-binding protein (L-FABP) in chronic kidney disease (CKD), we carried out a multicenter trial. Clinical markers were measured in patients with nondiabetic CKD (n = 48) every 1 to 2 months for a year. We divided patients retrospectively into progression (n = 32) and nonprogression (n = 16) groups on the basis of the rate of disease progression, then assessed several clinical markers. Initially creatinine clearance (Ccr) was similar in the 2 groups; however, the urinary L-FABP level was significantly higher in the former group than in the latter (111.5 vs 53 microg/g creatinine, P < .001). For the monitoring CKD, we set the cutoff values for urinary L-FABP and urinary protein at 17.4 microg/g creatinine and 1.0 g/g creatinine, respectively. Urinary L-FABP was more sensitive than urinary protein in predicting the progression of CKD (93.8% and 68.8%, respectively). However, urinary protein showed greater specificity than did urinary L-FABP (93.8% and 62.5%, respectively). Over time, the progression of CKD tended to correlate with changes in urinary L-FABP (r = - .32, P < .05), but not in urinary protein (r = .18, not significant). The dynamics of urinary protein differed from that of urinary L-FABP, which increased as Ccr declined. Urinary L-FABP is more sensitive than urinary protein in predicting the progression of CKD. Urinary excretion of L-FABP increases with the deterioration of kidney function. Urinary L-FABP is therefore a useful clinical marker in the monitoring of CKD.

Adult↗
PubMed2005

Long-term effect of imidapril hydrochloride compared with dilazep hydrochloride administration on blood pressure and renal function in patients with chronic glomerulonephritis.

The objective of the present study was to compare the effects of imidapril hydrochloride, an angiotensin converting enzyme inhibitor, and dilazep hydrochloride, an antiplatelet agent, on urinary protein excretion and renal function in patients with chronic glomerulonephritis. Imidapril (2.5 or 5 mg/day) or dilazep (300 or 450 mg/day) was administered for 3 years. Blood pressure, proteinuria, and renal function were measured before and during the treatment. In the group administered imidapril (n = 11), urinary protein decreased by approximately 50% (2.16 +/- 1.57 versus 0.90 +/- 0.53 g/g Cr, P < 0.01) and blood pressure by 14/10 mmHg (139.6 +/- 17.4/93.6 +/- 8.7 mmHg versus 122.7 +/- 10.5/81.8 +/- 9.9 mmHg, P < 0.01) and both remained at low levels during the three years of treatment. No correlation was observed between the extent of blood pressure reduction and changes in urinary protein. Serum creatinine concentrations did not change significantly (1.3 +/- 0.3 versus 1.3 +/- 0.3 mg/dL, NS). In the dilazep group (n = 12), there were no significant changes in blood pressure, urinary protein, or serum creatinine. These findings demonstrate that imidapril reduces proteinuria and contributes to preserve renal function, suggesting its usefulness in the treatment of patients with chronic glomerulonephritis.

Adult↗
PubMed2005

Differences in clinical features and prognosis of interstitial lung diseases between polymyositis and dermatomyositis.

OBJECTIVE: To assess the difference in clinical features and prognosis of patients with interstitial lung disease (ILD) comparing polymyositis (PM) and dermatomyositis (DM). METHODS: Medical records of 28 ILD patients with PM/DM (16 PM-ILD, 12 DM-ILD) were reviewed retrospectively. RESULTS: Serum CPK concentrations were significantly higher in PM-ILD than in DM-ILD. Bronchoalveolar lavage analysis showed that the percentages of lymphocytes and eosinophils were significantly higher in DM-ILD than in PM-ILD. Ten patients (5 PM-ILD, 5 DM-ILD) underwent surgical lung biopsy, and 3 (3 DM-ILD) had an autopsy. Nonspecific interstitial pneumonia (NSIP) was found in 7 (4 PM-ILD, 3 DM-ILD) and usual interstitial pneumonia (UIP) in 3 (1 PM-ILD, 2 DM-ILD). Interestingly, diffuse alveolar damage (DAD) was found in 3 patients with DM-ILD, who all died of deterioration of ILD; but no one with PM-ILD had DAD. Corticosteroid treatment alone achieved a favorable response in 6 patients (37.5%) with PM-ILD, but in only one (8.3%) with DM-ILD. Administration of cyclosporine in the early phase of onset benefited 4 corticosteroid-resistant patients with DM-ILD. Conclusively, survival in DM-ILD was significantly worse than that in PM-ILD. CONCLUSION: DM-ILD is more refractory to corticosteroid therapy, resulting in poorer prognosis compared with PM-ILD. These data indicate that intensive therapy, including cyclosporine, should be considered for DM-ILD.

Bronchoalveolar Lavage Fluid↗
PubMed2005

[Dialysis as bridge therapy for renal transplantation: single center experience, a comparison of hemodialysis and continuous ambulatory peritoneal dialysis].

BACKGROUND: Kidney transplantation is the most ideal treatment in renal replacement therapy for patients with end-stage renal disease. However, the prevalence of transplantation is extremely low and most patients with ESRD should continue dialysis for their whole life. Recently, high transposition rate of renal transplantation from peritoneal dialysis (PD) was reported, however, it was unclear whether a difference in dialytic modality can influence the outcome. Therefore, we evaluated the influence of dialytic modality on the rate of kidney transplantation and outcome in our single center. METHODS: Forty-two kidney transplants were carried among 1,573 dialysis patients from the years 1986 to 2004 in our center. Transposition rates from two modalities (HD and PD) and graft survival were compared. The incidence of acute rejection episode, complications after receiving transplantations, and coexisting diseases were also evaluated between the two modalities prior to transplantation. RESULT: The number of patients who received HD was larger than PD (HD 77.1%, PD 22.9%, respectively). Forty-two patients undergoing dialytic therapy received a living-donor kidney transplantation. Overall graft survival was 92% at 5 years and 75% at 10 years. Among these cases, dialytic modality prior to transplantation was 57.1% in HD, and 42.9% in PD. The transfer rate from PD to transplantation was significantly (p = 0.0036) higher (4.7%) than that of HD (1.9%). The reason for the high transfer rate of PD patients might be cooperation with their family and the provision of relevant information by nephrologists during PD. There were no differences between the two modalities prior to transplantation in the graft survival rate, incidence of acute rejection, and complications before and after transplantation. CONCLUSION: Difference in pretransplant dialysis modality did not affect the outcomes, however, the transfer rate from PD was significantly higher than from HD. Accordingly, PD is useful compared to HD as bridge therapy for kidney transplantation from the high feasibility of living-donor kidney transplantation.

Adult↗
PubMed2004

The incidence and clinical characteristics of bronchiolitis obliterans organizing pneumonia syndrome after radiation therapy for breast cancer.

STUDY OBJECTIVE: Bronchiolitis obliterans organizing pneumonia (BOOP) syndrome after adjuvant radiation therapy for breast cancer has been recently recognized. However, the precise incidence of this syndrome remains to be determined. The aim of this study was to clarify the incidence and clinical characteristics of radiation-induced BOOP syndrome. METHODS: We conducted a retrospective analysis of 206 consecutive patients wit breast cancer undergoing tangential-field radiation therapy at our institution from 1992 to 2002. RESULTS: Among the patients, five (2.4%) developed BOOP syndrome. These five patients began with flu-like symptoms 2-7 months after the completion of radiation therapy. Four of them had received tamoxifen, an estrogen receptor antagonist, and the other one underwent cytotoxic chemotherapy. Their chest radiographs revealed peripheral alveolar opacities with migration outside the irradiated fields. Increased lymphocyte counts and elevated CD4/CD8 ratios were observed in the bronchoalveolar lavage fluid. Transbronchial biopsy revealed organizing pneumonia. The serum levels of KL-6, a marker of interstitial pneumonia, did not increase in any patients. Treatment with corticosteroids resulted in a rapid improvement, but two patients relapsed after the cessation of corticosteroids. CONCLUSIONS: These results suggest that BOOP syndrome after tangential-field radiation therapy for breast cancer is not rare and more attention should be directed to this condition as a radiation-induced pulmonary toxicity.

Biopsy↗
PubMed2004

[Outcome of pulmonary Mycobacterium avium complex (MAC) disease treated with clarithromycin (CAM)-containing regimens].

We retrospectively investigated the efficacy of regimens including clarithromycin (CAM) in 129 patients with Mycobacterium avium complex (MAC) pulmonary disease and their outcomes. None of the patients suffered from acquired immunodeficiency syndrome. All were observed for over 12 months. We studied the factors that may affect sputum conversion and fatal outcomes by logistic regression analysis. The results indicated that the presence of either cavitation or bronchiectasis was significantly correlated with persistent MAC-positive culture results in sputum (Odds ratio, 4.71, 95%; CL, 1.21-18.5; P<0.05). Regimens including antituberculous drugs and CAM were administered to 118 patients, 11 of whom received CAM alone because of the adverse events of antituberculous agents. There was no difference in sputum conversion or mortality between the two groups, suggesting that the pattern of drug combination should be further investigated.

Aged↗
PubMed2004

[Therapy for ROD and measurement of the bone mass].

The kidney deeply takes part in phosphorus and vitamin D metabolism. The chronic kidney disease patients usually suffer from serious bone disease. They are prescribed the glucocorticoid medication for primary kidney disease, as nephrotic syndrome and collagen renal disease, with aging. The end of therapeutic target is normal bone structure with normal bone turnover in CKD patients. The control of serum Ca and phosphorus level is important step and also another target. This issue describes the problem and the advancement of treatment and the measurement of the bone mass from this viewpoint.

Absorptiometry, Photon↗
PubMed2004

[A case with pulmonary epithelioid hemangioendothelioma found on school medical check].

A 15-year-old man was incidentally found to have abnormal shadows in bilateral lungs on a chest X-ray film obtained at a school medical examination, and was referred to our hospital for a close investigation. Several lymph nodes were palpable in his cervical region. Chest X-ray and CT showed multiple and various sized nodules up to 20 mm in diameter in bilateral lung field. Abdominal CT showed multiple calcified lesions and low density areas in the liver. We performed video-assisted thoracoscopic lung biopsy, and diagnosed this case histologically as pulmonary epithelioid hemangioendothelioma. The tumor cells showed immunohistochemically positive staining for Factor VIII-related antigen that was one of endothelial cell marker. He has been followed up for 2 years and 11 months after the surgical lung biopsy without specific medication and remains asymptomatic at the time of writing this paper.

Adolescent↗