Search PubMed⌕ Search

Biomedical subjects

M Hata

Publications and source records attributed to M Hata.

At least 19 recordsLinked to original sources

Hemofiltration during cardiopulmonary bypass for high risk adult cardiac surgery.

AIMS: The role of hemofiltration (HF) during cardiopulmonary bypass (CPB) in adult cardiac surgery is controversial. It may be beneficial during prolonged CPB in high-risk surgery. Accordingly, we sought to compare two groups of patients undergoing high-risk cardiac surgery with or without HF. METHODS: One hundred and eighteen patients who underwent complex cardiac surgical procedures during a 12-month period were divided into two groups. Group I (n=61) comprised patients who were treated with hemofiltration during CPB. Group II (n=57) were not filtered. Estimated risk of death, standard demographic, clinical and surgical features were obtained and predetermined outcomes were studied. Statistical comparisons were made. RESULTS: Age, procedure times and mortality rates were similar in both groups. The mean volume of fluid removed in group I was 3.4 L. The preoperative mean Parsonnet score was 24.8 in group I and 22.5 in group II (ns). Postoperative serum hemoglobin, hematocrit, platelet, and albumin levels were all significantly higher in group I patients (p=0.0015) indicating hemoconcentration. Post-operative chest drainage showed a trend toward decreased post-operative bleeding in group I (p=0.065). Postoperative pleural effusions requiring chest tube drainage were significantly less in group I (9.8% vs. 29.8% 6; p = 0.0062). The incidence of lung infection was also decreased from 26.3% to 13.1% (p=0.05). Operative mortality was similar in both groups (11.4% in group 1, 10.5% in group II, ns). CONCLUSION: Hemofiltration during CPB attenuates postoperative anemia, thrombocytopenia and hypoalbuminemia, may reduce post-operative bleeding and appears to decrease post-operative pulmonary complications.

Aged↗

[Reoperation for a Starr-Edwards ball valve prosthesis implanted in mitral position 31 years ago].

The patient is a 61-year-old woman who had undergone mitral valve replacement with the Starr-Edwards cloth-covered ball valve 31 years ago. She had dyspnea on effort 1 month before admission. The echocardiography revealed mitral and tricuspid regurgitation. Re-replacement of the mitral prosthetic valve with an ATS valve and tricuspid annuloplasty were successfully performed without any complication. The cloth wear of the Starr-Edwards ball valve cage was recognized and no thrombus was found at operation. To our knowledge, there has been no such a reoperative case who underwent so long postoperative period after initial implantation of the Starr-Edwards ball valve in Japan. This experience made us realize again the importance of attention to the complications related to a prosthetic valve like a cloth wear during long-term follow-up for the Starr-Edwards ball valve.

Female↗

Detailed characterization of neuroprotection by a rescue factor humanin against various Alzheimer's disease-relevant insults.

A novel factor, termed Humanin (HN), antagonizes against neurotoxicity by various types of familial Alzheimer's disease (AD) genes [V642I and K595N/M596L (NL) mutants of amyloid precursor protein (APP), M146L-presenilin (PS) 1, and N141I-PS2] and by Abeta1-43 with clear action specificity ineffective on neurotoxicity by polyglutamine repeat Q79 or superoxide dismutase 1 mutants. Here we report that HN can also inhibit neurotoxicity by other AD-relevant insults: other familial AD genes (A617G-APP, L648P-APP, A246E-PS1, L286V-PS1, C410Y-PS1, and H163R-PS1), APP stimulation by anti-APP antibody, and other Abeta peptides (Abeta1-42 and Abeta25-35). The action specificity was further indicated by the finding that HN could not suppress neurotoxicity by glutamate or prion fragment. Against the AD-relevant insults, essential roles of Cys(8) and Ser(14) were commonly indicated, and the domain from Pro(3) to Pro(19) was responsible for the rescue action of HN, in which seven residues turned out to be essential. We also compared the neuroprotective action of S14G HN (HNG) with that of activity-dependent neurotrophic factor, IGF-I, or basic FGF for the antagonism against various AD-relevant insults (V642I-APP, NL-APP, M146L-PS1, N141I-PS2, and Abeta1-43). Although all of these factors could abolish neurotoxicity by Abeta1-43, only HNG could abolish cytotoxicities by all of them. HN and HN derivative peptides may provide a new insight into the study of AD pathophysiology and allow new avenues for the development of therapeutic interventions for various forms of AD.

Alzheimer Disease↗

Monooxygenation mechanism by cytochrome p-450.

The substrate oxygenation mechanism by an ultimate species in monooxygenation by cytochrome P-450 (compound I) was investigated by the density functional theory method. An initial model compound was constructed from a structure obtained by 300-ps molecular dynamics simulation of compound I-formed P-450cam under physiologic conditions, and it consisted of porphine for protoporphyrin IX, S(-)-CH(3) for the side chain of Cys357 of the fifth ligand of heme, a methane molecule for the substrate, a heme iron, and an oxygen atom of the sixth ligand of heme. The results of the calculation revealed that the substrate oxygenation mechanism had four elementary processes, i.e., (1) formation of [FeOH](3+) and a substrate radical by hydrogen atom abstraction from the substrate caused by [FeO](3+), (2) rotation of the OH group of the sixth ligand of [FeOH](3+) produced by process 1, (3) substrate radical binding with the [FeOH](3+), and (4) elimination of the oxygenated substrate formed at the sixth ligand binding site. The rate-determining step is process 1, hydrogen atom abstraction from the substrate, and the activation energy was determined to be about 15 kcal/mol. For this reason, it is thought that this reaction occurs in vivo.

Binding Sites↗

Mechanisms of neuroprotection by a novel rescue factor humanin from Swedish mutant amyloid precursor protein.

We report a novel gene, designated Humanin (HN) cDNA, that suppresses neuronal cell death by K595N/M596L-APP (NL-APP), a mutant causing familial Alzheimer's disease (FAD), termed Swedish mutant. Transfection of neuronal cells with HN cDNA or treatment with the coding HN polypeptide abrogated cytotoxicity by NL-APP. HN suppressed neurotoxicity by Abeta1-43 in the absence of N2 supplement, but could not inhibit Abeta secretion from NL-APP. HN could also protect neuronal cells from death by NL-APP lacking the 41st and 42nd residues of the Abeta region. Therefore, HN suppressed neuronal cell death by NL-APP not through inhibition of Abeta42 secretion, but with two targets for its inhibitory action: (i) the intracellular toxic mechanism directly triggered by NL-APP and (ii) neurotoxicity by Abeta. HN will contribute to the development of curative therapy of AD, especially as a novel reagent that could mechanistically supplement Abeta-production inhibitors.

Alzheimer Disease↗

Secreted Abeta does not mediate neurotoxicity by antibody-stimulated amyloid precursor protein.

Antibodies against APP, a precursor of Abeta deposited in Alzheimer's disease brain, have been shown to cause neuronal death. Therefore, it is important to determine whether Abeta mediates antibody-induced neurotoxicity. When primary neurons were treated with anti-APP antibodies, Abeta40 and Abeta42 in the cultured media were undetectable by an assay capable of detecting 100 nM Abeta peptides. However, exogenously treated Abeta1-42 or Abeta1-43 required >3 microM to exert neurotoxicity, and 25 microM Abeta1-40 was not neurotoxic. Glutathione-ethyl-ester inhibited neuronal death by anti-APP antibody, but not death by Abeta1-42, whereas serum attenuated toxicity by Abeta1-42, but not by anti-APP antibody. Using immortalized neuronal cells, we specified the domain responsible for toxicity to be cytoplasmic His(657)-Lys(676), but not the Abeta1-42 region, of APP. This indicates that neuronal cell death by anti-APP antibody is not mediated by secreted Abeta.

Alzheimer Disease↗

Prophylactic cranial irradiation of acute lymphoblastic leukemia in childhood: outcomes of late effects on pituitary function and growth in long-term survivors.

It is well known that prophylactic cranial irradiation is highly effective in preventing central nervous system (CNS) relapse of acute lymphoblastic leukemia (ALL). Nevertheless, there have been very few reports on the late effects, especially pituitary function and growth, in long-term survivors who were treated with 18 Gy cranial irradiation in childhood. The subjects consisted of 35 children with ALL who were treated with prophylactic 18 Gy cranial irradiation at Kanagawa Children's Medical Center between October 1981 and February 1995. All patients received cranial irradiation after first attaining complete remission with induction chemotherapy, according to the treatment protocols prescribed by the Tokyo Children's Leukemia Study Group (TCLSG) and Tokyo Children's Cancer Study Group (TCCSG). Their ages at the time of cranial irradiation ranged from 2.2-15.0 years (mean 6.8). We evaluated their pituitary functions by measuring their pituitary hormone values 0.7-11.3 years (mean 6.0) after cranial irradiation and their growth by analyzing their height standard deviation score (SDS) at diagnosis of ALL and their final height SDS at the mean follow-up period of 8.2 years after cranial irradiation. Height SDS is defined as the difference between the patient's height and the mean height of their age and sex, divided by the standard deviation of their age and sex. Eight of 35 patients had ALL relapse, involving the bone marrow in seven patients and the CNS in only one. Six of the eight patients with relapse died 1.5-6.6 years after cranial irradiation and the other two patients were salvaged by further intensive therapies. The remaining 27 relapse-free patients have survived for 1.4-15.8 years (mean 10.1) after cranial irradiation. Twenty-six of the 29 survivors are long-term survivors of more than 5 years. Although there was one patient with an abnormal result in each value of growth hormone (GH), adrenocorticotropic hormone (ACTH), and prolactin (PRL), and two patients with abnormal results in thyroid-stimulating hormone (TSH) values, none of the patients had clinical symptoms of pituitary hormone abnormality and none required hormone supplements. The final height SDS decreased significantly compared with the height SDS at diagnosis of ALL in the long-term survivors (P = 0.001) and the height SDS of the patients who had received cranial irradiation at a young age tended to decrease gradually (P = 0.019). However, no patient showed severe growth failure. It is considered that prophylactic 18 Gy cranial irradiation plus chemotherapy for ALL in childhood can effectively prevent CNS relapse and is unlikely to produce clinically significant late effects, although it may cause slight pituitary hormone abnormality.

Adolescent↗

Successful lamivudine therapy for post-chemotherapeutic fulminant hepatitis B in a hepatitis B virus carrier with non-Hodgkin's lymphoma: case report and review of the literature.

Reactivation of hepatitis B virus (HBV), especially after withdrawal of corticosteroids is a well-known complication during chemotherapy for lymphoma. The high mortality makes this complication one of the major obstacles to completing the standard treatment for lymphoma in HBV carriers. We report a 58-year-old Japanese male HBV carrier who developed fulminant hepatitis after chemotherapy with cyclophosphamide and doxorubicin. Lamivudine was introduced since his hepatitis was progressive under supportive treatment and showed an elevated level of HBV DNA. After initiation of lamivudine, HBV DNA decreased to be below the limit of detection within 3 weeks, and all chemical tests for liver function recovered to the normal level within 4 weeks, except for a slight elevation of total-bilirubin. There were no remarkable adverse effects observed. To the best of our knowledge, six cases of post-chemotherapeutic fulminant hepatitis including ours have been treated with lamivudine. A review of these cases indicated that lamivudine induced a prompt antiviral, biochemical, and clinical response. Lamivudine is highly recommended for post-chemotherapeutic fulminant hepatitis caused by reactivation of HBV.

Antineoplastic Combined Chemotherapy Protocols↗

Detection of IL-2 receptor gene expression in peripheral blood from renal transplant patients.

Cytokine monitoring is a potentially useful tool in the management of transplant patients. This study was conducted to analyze interleukin (IL)-1, tumor necrosis factor (TNF), IL-2, and IL-2 receptor gene expression by reverse transcriptase-polymerase chain reaction (RT-PCR) in peripheral whole blood from healthy volunteers and patients who underwent laparotomy or renal transplantation. In the patients who underwent laparotomy, IL-1 and TNF expression was detected postoperatively, but IL-2 and IL-2 receptor expression was not. IL-1, TNF, and IL-2 receptor gene expression was detected in all the renal transplant patients, including those with signs of rejection. No cytokine gene expression was detected preoperatively, pretransplant, or in the healthy volunteers. We were able to discriminate transplantation from laparotomy by the cytokine profile. These results indicate that our method may be a useful tool for the immunological monitoring of transplant patients.

Adult↗

Theoretical studies of the ATP hydrolysis mechanism of myosin.

The ATP hydrolysis mechanism of myosin was studied using quantum chemical (QM) and molecular dynamics calculations. The initial model compound for QM calculations was constructed on the basis of the energy-minimized structure of the myosin(S1dc)-ATP complex, which was determined by molecular mechanics calculations. The result of QM calculations suggested that the ATP hydrolysis mechanism of myosin consists of a single elementary reaction in which a water molecule nucleophilically attacked gamma-phosphorus of ATP. In addition, we performed molecular dynamics simulations of the initial and final states of the ATP hydrolysis reaction, that is, the myosin-ATP and myosin-ADP.Pi complexes. These calculations revealed roles of several amino acid residues (Lys185, Thr186, Ser237, Arg238, and Glu459) in the ATPase pocket. Lys185 maintains the conformation of beta- and gamma-phosphate groups of ATP by forming the hydrogen bonds. Thr186 and Ser237 are coordinated to a Mg(2+) ion, which interacts with the phosphates of ATP and therefore contributes to the stabilization of the ATP structure. Arg238 and Glu459, which consisted of the gate of the ATPase pocket, retain the water molecule acting on the hydrolysis at the appropriate position for initiating the hydrolysis.

Adenosine Diphosphate↗

Design of an SHD-distributed database over IP to support telemedicine.

We have conducted tests utilizing superhigh-definition CRTs (hereafter, referred to as a "super high-definition image system," or "SHD ": 2,048 x 2,048 pixels, 24-bit RGB gradation, noninterlace system) for autonomous and distributed medical image database systems. The system is capable of providing six times the image definition of a hi-vision television (HDTV). The aim in designing and testing the system is to enable gigabit network connectivity while displaying images on a DOS- V machine. This paper discusses how we devised an integrated environment for managing and operating distributed an SHD image database to support Telemedicine linking with ATM, with INS-1500, and with dial-up IP connection.

Computer Communication Networks↗

Surgical treatment for an idiopathic renal arteriovenous fistula with a large aneurysm.

Interventional embolization is currently the first line treatment for arteriovenous fistulas; however, the efficacy of repeated embolization remains controversial. A case is reported of an idiopathic renal arteriovenous fistula with large aneurysmal dilatation treated by surgery following the failure of interventional embolization. A 42-year-old woman was admitted to Ichikawa General Hospital, Japan, with gross hematuria containing many clots. Right renal arteriogram showed an aberrant vessel arising from the main trunk of the renal artery, which was followed by the formation of an aneurysm and rapidly ended in arteriovenous shunting. The aneurysm was approximately 35 mm in size. As interventional embolization had failed, surgical treatment including extracorporeal renal surgery was performed. Postoperative renal angiography revealed excellent renal function and beautiful vascular architecture. Although the indication for surgical treatment of renal vascular disease has decreased owing to the advancement of interventional techniques, there are still some risky cases for which surgical repair should be recommended.

Adult↗

Body mass index for chronic hemodialysis patients: stable hemodialysis and mortality.

Body mass index (BMI) is used as a reference for weight control programs in the general population and in morbidity and mortality studies in diabetes patients. However, the implications of BMI in chronic hemodialysis patients is unclear. We studied the BMI of chronic hemodialysis patients, focusing on problems encountered during outpatient hemodialysis therapy and on 2-year mortality. Outpatients with chronic hemodialysis (n = 258; 144 men, 114 women) were divided into four groups: (i) patients with stable hemodialysis; (ii) patients with marked hypotension requiring catecholamine infusion during hemodialysis; (iii) patients with excessive interdialysis weight gain requiring occasional additional hemodialysis; and (iv) patients with troublesome hemodialysis due to other causes. The statistical differences between the average BMI among these groups were evaluated, and were subdivided into sex, age and the duration of hemodialysis history. The 2-year mortality rates of these patients were also studied according to their BMI. In patients under 60 years of age, those with excessive interdialysis weight gain had statistically larger BMI (23.2; n = 35) compared to patients with good hemodialysis control (20.1; n = 178), regardless of gender and hemodialysis history. The mortality rate was at a minimum at approximately 20 BMI in patients under 60 years of age. However, lower BMI was associated with a greater mortality rate in patients 60 years or over. For chronic hemodialysis patients, the BMI associated with stable hemodialysis and minimum mortality is approximately 20, in those under 60 years of age. The BMI of aged hemodialysis patients should be considered separately in morbidity and mortality studies.

Body Mass Index↗

A typical Y1 receptor regulates feeding behaviors: effects of a potent and selective Y1 antagonist, J-115814.

Neuropeptide Y (NPY) is a potent feeding stimulant. The orexigenic effect of NPY might be caused in part by the action of Y1 receptors. However, the existence of multiple NPY receptors including a possible novel feeding receptor has made it difficult to determine the relative importance of the Y1 receptor in feeding regulation. Herein we certified that the Y1 receptor is a major feeding receptor of NPY by using the potent and selective Y1 antagonist (-)-2-[1-(3-chloro-5-isopropyloxycarbonylaminophenyl)ethylamino]-6-[2-(5-ethyl-4-methyl-1,3-thiazol-2-yl)ethyl]-4-morpholinopyridine (J-115814) and Y1 receptor-deficient (Y1-/-) mice. J-115814 displaced (125)I-peptide YY binding to cell membranes expressing cloned human, rat, and murine Y(1) receptors with K(i) values of 1.4, 1.8, and 1.9 nM, respectively, and inhibited NPY (10 nM)-induced increases in intracellular calcium levels via human Y1 receptors (IC(50) = 6.8 nM). In contrast, J-115814 showed low affinities for human Y2 (K(i) > 10 microM), Y4 (K(i) = 640 nM) and Y5 receptors (K(i) = 6000 nM). Intracerebroventricular (ICV) (10-100 microg) and intravenous (IV) (0.3-30 mg/kg) administration of J-115814 significantly and dose-dependently suppressed feeding induced by ICV NPY (5 microg) in satiated Sprague-Dawley rats. Intraperitoneal (IP) administration of J-115814 (3-30 mg/kg) significantly attenuated spontaneous feeding in db/db and C57BL6 mice. Feeding induced by ICV NPY (5 microg) was unaffected by IP-injected J-115814 (30 mg/kg) in Y1-/- mice and was suppressed in wild-type and Y5-/- mice. These findings clearly suggest that J-115814 inhibits feeding behaviors through the inhibition of the typical Y1 receptor. We conclude that the Y1 receptor plays a key role in regulating food intake.

Animals↗

Involvement of stringent factor RelA in expression of the alkaline protease gene aprE in Bacillus subtilis.

Expression of Bacillus subtilis aprE, encoding an extracellular alkaline protease, is positively regulated by phosphorylated DegU, the regulator of a two-component regulatory system, DegS-DegU. We found that the expression of an aprE'-'lacZ fusion was greatly reduced in a disruption mutant with a mutation of relA, which encodes the stringent factor RelA. The level of DegU in the relA mutant was similar to that in the wild-type cell. A relA degU double mutation did not result in a further decrease of the aprE'-'lacZ level found in a degU single mutant. The expression of the aprE'-'lacZ fusion in the relA mutant was stimulated by multicopy degR or the degU32(Hy) and degS200(Hy) mutations that cause the stabilization of phosphorylated DegU. Furthermore, the expression of sacB'-'lacZ, which is also dependent on phosphorylated DegU, was stimulated by the relA mutation, and this stimulation was not seen in the relA degU double mutant. These results show that RelA (or its product guanosine-3',5'-bisdiphosphate [pp Gpp]) does not affect the phosphorylation of DegU and suggest that it participates in the expression of aprE and sacB through the regulation of DegU-dependent transcription.

Artificial Gene Fusion↗

Radiation therapy for life- or function-threatening infant hemangioma.

PURPOSE: To assess the effectiveness and long-term results of radiation therapy in infants with life- or function-threatening hemangiomas. MATERIALS AND METHODS: Thirteen patients with life- or function-threatening hemangiomas (eight male, five female; age range, 0-8 months; median age, 2 months) were treated with radiation therapy. Life-threatening hemangiomas were treated with five fractions of radiation per week, and function-threatening hemangiomas were treated with two fractions per week. A median dose of 10 Gy was delivered to each hemangioma. The presence of residual hemangiomas, skin changes, functional problems, and growth delay was evaluated. RESULTS: All patients with Kasabach-Merritt syndrome (KMS) showed regression of the hemangioma and an increase in platelet counts to greater than 100,000 per cubic millimeter (1.0 x 10(11) per liter) within 40 days after radiation therapy. The treatment field was inadequate in two patients who required reirradiation or a change of treatment portal. With the exception of the patients with KMS, all but one patient experienced relief from symptoms in 40 days. Severe long-term radiation-related morbidity was noted in one patient who required reirradiation for a relapsed hemangioma. CONCLUSION: Radiation therapy (in doses of < or = 10 Gy in 2-Gy fractions) is indicated for life-threatening hemangiomas and for some function-threatening hemangiomas.

Adolescent↗