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Biomedical subjects

M Ohashi

Publications and source records attributed to M Ohashi.

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

Cardio-aortic operation in octogenarians.

OBJECTIVE: Aging of the population is a current phenomenon in Japan, and life expectancy at 80 years old is getting longer. So we reviewed cardio-aortic operations on octogenarians at our institution. SUBJECTS AND METHODS: Thirty-three consecutive octogenarian patients who had undergone cardio-aortic operations from 1992 to 1998 were studied. There were 14 men and 19 women. The mean age was 81.9 years. Of the 33, 19 patients (58%) were in New York Heart Association class IV, and 21 patients (64%) were operated on urgently or in emergency. The procedures undergone were operation for coronary artery disease in 17 patients, operation for valvular disease in 7 patients, operation for thoracic-aorta in 7 patients, and others in 2 patients. RESULTS: The hospital mortality rate was 27% (9 patients). However, 89% of patients experiencing hospital death were in New York Heart Association class IV preoperatively and had required an emergency/urgent operation. On the other hand, there was only one hospital death (1/12, 8.3%) among the elective patients. The statistically significant risk factors for hospital death were renal insufficiency, shock, New York Heart Association class IV, intra-aortic balloon pumping, and longer cardiopulmonary bypass time. The one-, three-, and five-year-survival rate was 73%, 68%, and 55%, respectively. Of the survivors, 77% were in class I or II. CONCLUSION: Although octogenarians' hospital mortality was still very high, the mid-term results were acceptable and the survivors' quality of life was satisfactory. These data suggested that we should operate on cardio-aortic patients before they reach a very serious state, especially in octogenarians.

Age Factors↗
PubMed2001

Differences in DNA synthesis in vitro using isolated nuclei from regenerating livers of young and aged rats.

To detect changes in DNA synthesis during ageing, we compare DNA synthesis in the livers of young and aged rats. As an intermediate between an in vivo system using intact cells and an in vitro system using purified DNA polymerases, isolated nuclei were prepared and used as the machinery for DNA synthesis. The DNA synthesizing capacity of nuclei from regenerating liver was higher than that of nuclei from normal liver and these capacities from liver and regenerating liver were lower in nuclear preparations from aged rats. DNA synthesis using isolated nuclei was stimulated by ATP and the cytoplasmic preparation. The cytoplasmic preparation from regenerating rat liver was found to stimulate DNA synthesis more than the preparation from normal liver. The activity in regenerating liver from young rats was also greater than in that from aged rats. It is well known that DNA replication is inhibited by aphidicolin and DNA repair by ddTTP. We examined the effects of aphidicolin and ddTTP on DNA synthesis using the nuclear system. Surprisingly, the inhibition by aphidicolin was 30% of total DNA synthesis using the nuclear system from young rats. On the other hand, the inhibition by ddTTP was approximately 80%. We measured the sizes of the DNA synthesized in the presence of both inhibitors. DNA synthesis was allowed to proceed for 10 min using isolated nuclei from regenerating liver of young rats and the size of the DNA was determined by sucrose density gradient centrifugation analysis. DNA products appeared in two fractions. Following a chase of 50 min in the presence or absence of aphidicolin, the short DNA product grew larger in both cases, although the amount of DNA in the presence of aphidicolin was approximately 90% that in its absence. In the same experiment using nuclei from aged rats, the amount in the presence of aphidicolin was approximately 60% that in its absence. These results suggest that DNA polymerase beta is closely related to abnormal replication when DNA polymerases alpha and delta are inhibited and that the effect of cytosol on DNA synthesis, as well as the DNA synthetic capacity of isolated nuclei, becomes lower in regenerating rat liver during ageing.

Aging↗
PubMed2001

Biliary excretion of temocapril in zone 1- and zone 3-injured rat.

Temocapril is a prodrug of an angiotensin-converting enzyme inhibitor, temocaprilat, a substrate of multidrug resistance protein 2. Hepatocytes in zone 1 play a role in the uptake and biliary excretion of bile acids under physiological condition, and those in zone 3 may play a role only with their high-dose load. To investigate the pharmacokinetics of temocapril in liver injury, biliary excretion of temocapril was studied in zone 1- and zone 3-injured rats, caused by allyl alcohol and bromobenzene, respectively. Biliary excretion of a tracer dose of radiolabeled temocapril was delayed both in zone 1 and the zone 3 injury, but the extent of inhibition was more prominent in zone 3 injury. Since biliary excretion of organic anions was decreased only in zone 1 injury in our previous study, the present findings indicate that decreased biliary excretion of temocaprilat in zone 3 injury is caused by the inhibition of the metabolism from temocapril to temocaprilat.

Journal Article↗
PubMed2001

Primary leptomeningeal lymphoma.

Primary leptomeningeal lymphoma is a rare disorder, and the neuroradiological characteristics or the complication of this rare disorder have not been well reported. We reported herein a patient with a primary leptomeningeal lymphoma who has complication with subdural hematoma. The patient complained of headache and vomiting. Neurological examination revealed progressive cranial nerve palsy. Cerebrospinal fluid examination disclosed monoclonal proliferation of atypical B-lymphocytes. Cranial computed tomographic scans showed a left frontal mass with convex form to the brain parenchyma. T1-weighted magnetic resonance (MR) images disclosed subacute subdural hematoma. However, proton-weighted MR images showed high signal intensity in subarachnoid space, which suggested leptomeningeal lymphoma. He underwent craniotomy, and the diagnosis of leptomeningeal lymphoma complicated with subdural hematoma was confirmed. Systemic examinations disclosed no lymphomatous lesions except for leptomeningus, and the diagnosis of primary leptomeningeal lymphoma was established. We suggested that subdural hematoma was associated with primary leptomeningeal lymphoma in this patient. Cerebrospinal fluid examination and proton-weighted MR imaging should be performed when progressive neurological abnormalities are found in patients with subdural hematoma.

Aged↗
PubMed2001

Late dissemination of fourth ventricle ependymoma: a case report.

Dissemination of benign ependymoma is relatively rare, especially when a local tumor is under control. The majority of the failures take place within a few years after surgery. However, we experienced a case in which multiple spinal cord dissemination was found 13 years after resection of the fourth ventricle ependymoma without a local failure. A 38-year-old man had undergone a subtotal resection of the fourth ventricle ependymoma and radiation therapy to the posterior fossa when he was 25 years old. Follow-up MR imaging repeated once every one or two years detected no recurrence until he began to complain of lumbago and numbness of the right foot 13 years after the surgery. MR imaging revealed multiple nodules along the whole spinal cord. Examination of the cerebrospinal fluid detected tumor cells with ependymal cell features. He underwent radiation therapy to the whole spine, and remained stable at 18 months after the therapy. This case alerts us to the necessity for long-term radiological follow-up including the spinal cord even in benign ependymomas, although it is still not certain for how long and how often we should do it.

Adult↗
PubMed2001

Validation of DNA-based HLA-A and HLA-B testing of volunteers for a bone marrow registry through parallel testing with serology.

A total of 42,160 individuals were typed for HLA-A and HLA-B by both serology and PCR-based typing. The HLA assignments included all of the known serological equivalents. The majority of the individuals (99.9%) were from U.S. minority population groups. The serologic typing was performed between 1993 and 1997 at the time of recruitment for the National Bone Marrow Program (NMDP) registry. The polymerase chain reaction (PCR)-based typing was carried out in two phases. In phase I, DNA typing was performed by PCR using sequence-specific oligonucleotide probes (PCR-SSOP) or PCR using sequence-specific primers (PCR-SSP) without knowledge of the serologic assignments. Discrepancies were identified between the serologic and DNA assignments in 24% of the volunteers (8% of volunteers differed for only HLA-A assignments, 13% for HLA-B, and 3% for both HLA-A and -B) and a potential explanation was assigned each discrepant serology/DNA pair. In phase II, a random sampling scheme was used to select a statistically significant number of individuals for repeat DNA typing from each of these categories. The categories included antigens missed by serology, nonexpressed (null) alleles, PCR amplification failures, misassignment of antigens and nomenclature issues. Only a single individual was found to carry a null allele. DNA-based testing correctly typed nearly 99% of the donors at HLA-A, more than 98% at HLA-B, and more than 97% at both HLA-A and -B validating this methodology for registry typing.

Bone Marrow Examination↗
PubMed2001

Correlation between HHV-6 infection and skin rash after allogeneic bone marrow transplantation.

We investigated whether a causal relationship exists between human herpesvirus 6 (HHV-6) and skin rash resembling acute graft-versus-host disease (GVHD) following bone marrow transplantation (BMT). Isolation of HHV-6 was used to monitor active HHV-6 infection in this study. We analyzed 25 episodes of skin rash in 22 recipients. All recipients were seropositive for HHV-6 before BMT. The onset of skin rash started prior to 30 days post transplantation (group A) in 15 of 25 cases, but after that (group B) in the remaining 10 cases. Twenty-five skin tissue samples were obtained from 22 recipients. The HHV-6 genome was detected in four of 15 skin samples from group A, but not detected in those from group B. HHV-6 was isolated from 11 of 22 recipients around 2 to 3 weeks after BMT (range 14 to 28 days after BMT). HHV-6 was isolated at a time between 10 days before and after the onset of skin rash (skin rash-related viremia) in nine cases in group A. Meanwhile, no skin rash-related viremia was observed in group B. Of the four recipients with positive detection of HHV-6 genome in their skin tissue (group A), two had HHV-6 viremia at the same time. The association between the timing of HHV-6 infection and the onset of skin rash was analyzed statistically. HHV-6 viremia (skin rash-related viremia) was found in nine of 15 (60%) cases in group A, compared with none of 10 (0%) cases in group B. This difference was statistically significant (P = 0.008). Moreover, HHV-6 infection (skin rash-related viremia and/or positive detection of HHV-6 DNA in skin tissue) was demonstrated in 11 of 15 (73.3%) cases in group A, compared with none of 10 (0%) cases in group B (P = 0.001). Thus, this study suggests that HHV-6 may be involved in the development of skin rash in the first month after allogeneic BMT.

Adolescent↗
PubMed2001

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↗
PubMed2001

Transfer of human herpesvirus 6 and 7 antibodies from mothers to their offspring.

Placental transfer of maternal human herpesvirus (HHV) 6 and HHV 7 antibodies to infants was examined simultaneously in 69 paired plasma samples by an indirect immunofluorescence assay. All the mothers had antibodies to both viruses. The mean HHV 6 and HHV 7 antibody titers of infants were significantly higher than those of the mothers. The mean ratio of cord blood antibody titer to the maternal titer for both viruses was 1.89, suggesting active transport by placenta.

Antibodies, Viral↗
PubMed2001

Correlation between human herpesvirus 6 and 7 infections after living related liver transplantation.

Human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7) are closely related to each other. Interaction between the two viruses at the time of primary HHV-7 infection is suggested by in vivo and in vitro studies. However, interaction between the two viruses in organ transplant recipients has not been analyzed. We analyzed serially collected plasma samples obtained from 40 living related liver transplant recipients by serological assay (indirect immunofluorescence assay, IFA) and polymerase chain reaction (PCR). Significant increase or seroconversion of HHV-6 IgG and HHV-7 IgG antibody titers were observed in 45% and 58% of recipients respectively. Positive rate of IgM HHV-6 antibody increased up to 35% at 4 weeks after transplantation. However, no remarkable peak in the positive rate of HHV-7 IgM antibody was demonstrated. HHV-6 and HHV-7 DNA were detected in plasma in 15 (38%) and 16 (40%) of the 40 recipients respectively. HHV-6 DNA was detected in 10 (26%) of the 38 recipients at 2 weeks after transplantation. The positive rate of the virus genome in plasma gradually decreased after that time. HHV-7 DNA was detected in 5 (14%) of the 37 recipients at 2 weeks after transplantation; no obvious peak in the positive rate of HHV-7 DNA was demonstrated. Antibody responses involving both HHV-6 and HHV-7, including either a significant increase in IgG antibody titers or positive identification of IgM antibody were observed in 17 (43%) of the 40 recipients. Thirteen out of the 17 recipients demonstrated concurrent antibody response against both viruses. HHV-7 antibody response preceded the HHV-6 antibody response in 2 of the remaining 4 recipients, whereas the opposite was true in the other 2 recipients. Both HHV-6 and HHV-7 DNA were detected in 7 (18%) of the 40 recipients. In 4 of those 7 recipients, DNA from both viruses was concurrently detected, 3 of whom had HHV-7 DNA repeatedly detected after first detection of the virus DNA. The detection of HHV-7 DNA preceded the detection of HHV-6 DNA in 2 recipients, whereas HHV-6 DNA appeared first in 1 recipient.

Antibodies, Viral↗
PubMed2001

Cholesterol requirement for cation-independent mannose 6-phosphate receptor exit from multivesicular late endosomes to the Golgi.

The regulation of endocytic traffic of receptors has central importance in the fine tuning of cell activities. Here, we provide evidence that cholesterol is required for the exit of cation-independent mannose 6-phosphate receptor (CI-MPR) from the endosomal carrier vesicle/multivesicular bodies (ECV/MVBs) to the Golgi. A previously established Chinese hamster ovary cell mutant, LEX2, exhibits arrested ECV/MVBs in which CI-MPR and lysosomal glycoprotein-B (lgp-B) are accumulated. The abnormal accumulation of CI-MPR within the ECV/MVBs in LEX2 cells was corrected in a post-translational manner by the supplementation of medium with cholesterol. Furthermore, it was shown that, by expression cloning using LEX2 mutant, the introduction of the NAD(P)H steroid dehydrogenase-like protein, an enzyme involved in the later stage of cholesterol biosynthesis, allows the exit of CI-MPR from the MVBs to the Golgi and reduces the number of arrested ECV/MVBs in LEX2 cells. The recovery of the exit transport of CI-MPR from the ECV/MVBs was associated with the restoration of the normal cellular free cholesterol level and segregation between CI-MPR and lgp-B, both of which had been localized at the internal small vesicles of the arrested ECV/MVBs. By contrast, the restoration of cholesterol failed to correct the defective processing of endocytosed LDL to a degradative compartment in LEX2 cells. These results suggest that cholesterol is required for ECV/MVB reorganization that drives the sorting/transport of materials destined for the Golgi out of the pathways towards lysosomes.

Animals↗
PubMed2001

Synthesis and evaluation of 1-arylsulfonyl-3-piperazinone derivatives as factor Xa inhibitor.

Intravascular clot formation is an important factor in a number of cardiovascular diseases. Therefore, the prevention of blood coagulation has become a major target for new therapeutic agents. One attractive approach is the inhibition of factor Xa (FXa), which is a key enzyme in coagulation cascade responsible for the generation of thrombin by limited proteolysis of its zymogen, prothrombin. We have investigated 1-arylsulfonyl-3-piperazinone derivatives, containing a 4-(piperidino)pyridine group in place of guanidino and/or amidino groups, and discovered compound M55113 (30a: 4-[(6-Chloro-2-naphthalenyl)sulfonyl]-1-[[1-(4-pyridinyl)-4-piperidinyl]methyl]piperazinone), as a potent inhibitor of FXa (IC50=0.06 microM) with high selectivity for FXa over trypsin and thrombin.

Anticoagulants↗
PubMed2001

Reaction kinetics and modeling of the enzyme-catalyzed production of lactosucrose using beta-fructofuranosidase from Arthrobacter sp. K-1.

Lactosucrose synthesis from sucrose and lactose was carried out by using beta-fructofuranosidase from Arthrobacter sp. K-1. The transfructosylation mechanism was found to be of an ordered bi-bi type in which sucrose was bound first to the enzyme and lactosucrose was released last. Hydrolysis side-reaction experiments indicated that the reactions were uncompetitively inhibited by glucose and lactose, while no inhibition by fructose was apparent. The overall reaction rates were formulated. The reaction rate constants, equilibrium constant, and dissociation and Michaelis constants were determined at 35 degrees C and 50 degrees C by fitting the experimental concentration changes with the calculated values by a nonlinear least-square method. The average relative derivation for the concentrations was 9.67%. The kinetic parameters were also calculated for 43 degrees C and 60 degrees C by assuming the Arrhenius law, and the course of reaction was predicted. The obtained reaction rate equations well represented the concentration changes during the experiment at all temperatures.

Algorithms↗
PubMed2001

Lightning injury as a blast injury of skull, brain, and visceral lesions: clinical and experimental evidences.

The present study attempts to better understand the mechanism of injuries associated with direct lightning strikes. We reviewed the records of 256 individuals struck by lightning between 1965 and 1999, including 56 people who were killed. Basal skull fracture, intracranial haemorrhage, pulmonary haemorrhage, or solid organ rupture was suspected in three men who died. Generally these lesions have been attributed to current flow or falling after being struck. However, examination of surface injuries sustained suggested that the true cause was concussion secondary to blast injury resulting from vaporization of water on the body surface by a surface flashover spark. To investigate this hypothesis, an experimental model of a lightning strike was created in the rat. Saline-soaked blotting paper was used to simulate wet clothing or skin, and an artificial lightning impulse was applied. The resultant lesions were consistent with our hypothesis that the blast was reinforced by the concussive effect of water vaporization. The concordance between the clinical and experimental evidence argues strongly for blast injury as an important source of morbidity and mortality in lightning strikes.

Adult↗
PubMed2001

Effect of colestimide on intestinal absorption of ursodeoxycholic acid in men.

Colestimide is a new anion-exchange resin which is used to lower serum cholesterol levels in Japan. Because of its excellent compliance, colestimide can replace cholestyramine in the treatment of pruritus. However, there may be an interaction in cholestatic patients undergoing treatment with ursodeoxycholic acid (UDCA). Therefore, we studied the effect of colestimide on the absorption of UDCA in men. Five healthy men took two 100 mg tablets of UDCA after a test meal following an overnight fast, and blood samples were collected every 30 min for 3 h. Two weeks later, the same study was repeated just after taking colestimide granules (1.5 g). Bile acid subfractions in serum were measured by HPLC. Serum UDCA levels after 30 min (mainly unconjugated), which reflect the initial absorption, were decreased > 50% by colestimide in 4 out of 5 subjects. Serum total bile acid levels after 30 min, which reflect the initial absorption of bile acids due to postprandial bile secretion, were decreased by colestimide in all subjects. These results indicate that colestimide administration before the meal inhibits UDCA absorption.

Adult↗
PubMed2000

Changes in susceptibility to Fas-mediated apoptosis during differentiation of HL-60 cells.

The Fas-mediated pathway has been implicated as an important cellular pathway mediating apoptosis in diverse cell types. We conducted studies to examine the susceptibility to Fas-mediated apoptosis of HL-60 cells treated with differentiation-inducing factors such as dimethyl sulfoxide (DMSO), retinoic acid (RA), and 1alpha, 25 dihydroxyvitamin D3 (VD3). Although the expression of Fas antigen (Ag) and its mRNA showed a marked increase in HL-60 cells with cell differentiation, that of Bcl-2 protein and its mRNA revealed the reverse. The expression of caspase proteins such as caspases-3 and -8 was also enhanced during cell differentiation. DNA fragmentation, annexin V binding, and caspase activities increased in differentiated HL-60 cells with the addition of anti-Fas Ag antibody. These findings were more clearly demonstrated in DMSO- or RA-induced neutrophil-like cells than in VD3-induced monocyte-like cells. Therefore, susceptibility to Fas-mediated apoptosis showed an increase with differentiation of HL-60 cells, especially in the neutrophil lineage. These results suggest that the difference of susceptibility to Fas-mediated apoptosis among cell populations depends on the expression of Fas Ag, Bcl-2, and caspases. Cell maturation and susceptibility to Fas-mediated apoptosis may be linked in hematopoietic cells.

Annexin A5↗