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Biomedical subjects

N Ohshima

Publications and source records attributed to N Ohshima.

At least 19 recordsLinked to original sources

Transient decreases in Bispectral Index without associated changes in the level of consciousness during photic stimulation in an epileptic patient.

This case report describes a patient with a history of epileptic seizures who showed unusual decreases in the Bispectral Index (BIS) attributable to the induction of abnormal slow electroencephalographic (EEG) waves by photic stimulation, without any associated decrease in his level of consciousness. After starting anticonvulsive therapy, photic stimulation no longer induced abnormal EEG activity nor decreased BIS values. These findings suggest that BIS values may not accurately reflect a patient's actual level of consciousness in the presence of epilepsy-related abnormal EEG activity and that the BIS monitor may be able to track such EEG changes.

Adult↗

[Aortic regurgitation caused by rupture of a fibrous strand; report of a case].

Rupture of a fibrous strand of a tricuspid aortic valve is extremely rare. We describe a patient with aortic regurgitation due to spontaneous rupture of the fibrous strands that suspend the aortic valve leaflets. The fibrous strands were recognized between the left and right coronary cusps, and between the left coronary and non-coronary cusps during the operation. The fibrous strand between the left coronary and non-coronary cusps had been ruptured, and thus the left coronary and non-coronary cusps were prolapsed into the left ventricle. Since a degenerative change was observed histologically in the resected specimen, these fibrous strands were considered to be an embryonic remnant of the aortic valve.

Aged↗

System design of a bioartificial liver with a high performance hemodialyzer as an immunoisolator using a mathematical kinetic model.

We propose a new bioartificial liver (BAL) system equipped with a high performance hemodialyzer to act as an immunoisolation device. We discuss the design of the BAL system using a mathematical kinetic model with the experimentally obtained mass-transfer performances of various hemodialyzers. The mass transfer resistances of the hemodialyzers did not adversely influence the ammonia-removal and bioactive-substance-supply performances of the BAL system. A suitable hemodialyzer for the BAL system is available even at present using an engineering design. The remaining problems to be overcome before realizing clinical use of the BAL system are to increase the rate constant of the first order reaction of the BAL for ammonia metabolism and to develop a new method of blood access that can be used safely with long term reliability at a high blood flow rate (ca. 556 ml/min).

Cell Separation↗

Novel cell immobilization method utilizing centrifugal force to achieve high-density hepatocyte culture in porous scaffold.

Cell seeding is one of the key procedures in the construction of tissue-engineered organs. In our previous efforts to create a bioartificial liver, high-density cultures of hepatocytes (>1 x 10(7) cells/1 cm(3)-substrate) and long-term maintenance of metabolic function were achieved with a packed-bed reactor utilizing porous poly(vinyl formal) (PVF) resin as a scaffold. However, a low seeding efficiency of about 30% remains a major obstacle to the scaleup of the reactor. In the present study, a new cell seeding method, centrifugal cell immobilization (CCI), which is based on alternating centrifugation and resuspension, was used to achieve high-density seeding and improve the seeding efficiency. Using the CCI method, the maximum density of the immobilized hepatocytes reached 3.8 x 10(7) cells/1 cm(3)-PVF, and the seeding efficiency was improved to about 43% after a relatively short immobilization process (about 15 min). Moreover, further improvement of the seeding efficiency was obtained by serial immobilization procedures. Thus, we concluded that this method is useful and effective for seeding cells into 3-dimensional scaffolds.

Animals↗

Somatosensory nociceptive mechanical stimulation modulates systemic and mesenteric microvascular hemodynamics in anesthetized rats.

The effects of somatosensory nociceptive pinch stimulation of the hindpaw on mesenteric microvascular hemodynamics and systemic circulatory parameters were investigated in anesthetized rats using an intravital microscope-television system. Blood flow velocity in the terminal (18-40 microm in diameter) or precapillary (10-20 microm in diameter) arterioles of the mesentery was monitored by the dual sensor method developed by the authors. In the proximal terminal arterioles, blood flow velocity decreased substantially along with arteriolar constriction induced by pinching of the hindpaw for 30 s. In the distal terminal arterioles and precapillary arterioles, blood flow velocity increased after pinching. In the proximal terminal arterioles, the decrease of velocity in response to reflex vasoconstriction was abolished by intravenous injection of an alpha-blocker (phentolamine, 10 mg/kg). The increase in mesenteric precapillary arteriolar blood flow velocity (43+/-9%, p < 0.01) associated with the increase in mean arterial pressure (MAP) (22+/-1%, p < 0.01) was observed within a few seconds after the onset of the stimulation, and then the response in blood flow velocity returned to the baseline ahead of MAP response recovery after the end of the stimulus. These responses were diminished by alpha-adrenergic receptor blockade. The heart rate (HR) increase (4+/-1%, p < 0.01) induced by pinching was abolished by beta-adrenergicreceptor blockade (propranolol, 3 mg/kg, i.v.). There was a strong correlation between the increase in MAP and the decrease in renal blood flow measured by laser Doppler flowmeter (r = 0.87-0.98). Pinch stimulation of the rat hindpaw evoked changes in mesenteric arteriolar blood flow velocity that were mediated via the somato-sympathetic reflex vasoconstriction and the pressor response.

Adrenergic alpha-Antagonists↗

Improvement of metabolic performance of cultured hepatocytes by high oxygen tension in the atmosphere.

Maintaining metabolic functions of cultured hepatocytes at higher levels is an essential requirement for the development of a bioartificial liver. We investigated the effect of oxygen tension (10--40%) of the medium on immobilization efficiency and metabolic functions of cultured hepatocytes obtained from a rat for up to 4 days. Immobilization efficiencies of cultures in 10% oxygen showed a significantly lower value from those for the other conditions. The ammonium metabolic rate and the albumin secretion rate were significantly improved with an increase of dissolved oxygen tension for up to 2 days. These values remained similar in the later stage of the culture. The urea secretion rate showed similar values in all conditions. In conclusion, higher oxygen tension improved immobilization efficiency and metabolic functions of cultured rat hepatocytes in the earlier stage of culture for up to 2 days.

Alanine Transaminase↗

The effects of 30% and 60% xenon inhalation on pial vessel diameter and intracranial pressure in rabbits.

UNLABELLED: Xenon may increase cerebral blood flow and intracranial pressure (ICP). To evaluate the effects of xenon on brain circulation, we measured pial vessel diameter changes, CO(2) reactivity, and ICP during xenon inhalation in rabbits. Minimum alveolar anesthetic concentration (MAC) for xenon was established in rabbits (n = 6). By using a cranial window model, pial vessel diameters were measured at 30% and 60% xenon inhalation and in time control groups (n = 15). ICP, mean arterial blood pressure, and heart rate were recorded during 30% and 60% xenon inhalation (n = 5). Pial vessel diameters were measured during hypocapnia and hypercapnia conditions in 60% Xenon and Control groups (n = 14). MAC for xenon was 85%. Xenon (0.35 and 0.7 MAC) dilated the arterioles (10% and 18%, respectively) and venules (2% and 4%, respectively) (P < 0.05). Dilation of arterioles was more prominent than that of venules. ICP, mean arterial blood pressure, and heart rate did not change during xenon inhalation. No difference in CO(2) reactivity was observed between Xenon and Control groups (P = 0.79). Sixty percent xenon (0.7 MAC) dilated brain vessels, but venule changes were small. Xenon did not increase ICP and preserved CO(2) reactivity of the brain vessels. IMPLICATIONS: Xenon might increase cerebral blood flow; however, 0.7 minimum alveolar anesthetic concentration xenon preserved both low intracranial pressure and CO(2) reactivity of the cerebral vessels in the normal rabbit.

Administration, Inhalation↗

Ectopic expression of DREF induces DNA synthesis, apoptosis, and unusual morphogenesis in the Drosophila eye imaginal disc: possible interaction with Polycomb and trithorax group proteins.

The promoters of Drosophila genes encoding DNA replication-related proteins contain transcription regulatory element DRE (5'-TATCGATA) in addition to E2F recognition sites. A specific DRE-binding factor, DREF, positively regulates DRE-containing genes. In addition, it has been reported that DREF can bind to a sequence in the hsp70 scs' chromatin boundary element that is also recognized by boundary element-associated factor, and thus DREF may participate in regulating insulator activity. To examine DREF function in vivo, we established transgenic flies in which ectopic expression of DREF was targeted to the eye imaginal discs. Adult flies expressing DREF exhibited a severe rough eye phenotype. Expression of DREF induced ectopic DNA synthesis in the cells behind the morphogenetic furrow, which are normally postmitotic, and abolished photoreceptor specifications of R1, R6, and R7. Furthermore, DREF expression caused apoptosis in the imaginal disc cells in the region where commitment to R1/R6 cells takes place, suggesting that failure of differentiation of R1/R6 photoreceptor cells might cause apoptosis. The DREF-induced rough eye phenotype was suppressed by a half-dose reduction of the E2F gene, one of the genes regulated by DREF, indicating that the DREF overexpression phenotype is useful to screen for modifiers of DREF activity. Among Polycomb/trithorax group genes, we found that a half-dose reduction of some of the trithorax group genes involved in determining chromatin structure or chromatin remodeling (brahma, moira, and osa) significantly suppressed and that reduction of Distal-less enhanced the DREF-induced rough eye phenotype. The results suggest a possibility that DREF activity might be regulated by protein complexes that play a role in modulating chromatin structure. Genetic crosses of transgenic flies expressing DREF to a collection of Drosophila deficiency stocks allowed us to identify several genomic regions, deletions of which caused enhancement or suppression of the DREF-induced rough eye phenotype. These deletions should be useful to identify novel targets of DREF and its positive or negative regulators.

Animals↗

A new model of lung metastasis for intravital studies.

We created anexperimental model of pulmonary metastasis based on subcutaneously implanted Lewis lung cancer in mice and observed in vivo the microcirculation of spontaneously metastasized tumors in the lung. The mice lung was held by a small handmade suction ring to stop cardiac and respiratory movement. Using fluorescent microscopy, tumor microcirculation and normal lung microcirculation in the same lung lobe were compared by measuring microvessel diameter and blood flow velocity [red blood cell (rbc) velocity]. In normal microcirculation, the mean values of microvessel diameter and rbc velocity were 10.4 +/- 2.7 microm and 188 +/- 63 microm/s, respectively. In tumor microcirculation, the mean values of the same were 10.6 +/- 3.3 microm and 105 +/- 40 microm/s. The rbc velocity in normal microcirculation was significantly higher (P < 0.001) than that in tumor microcirculation. The calculated shear rates of normal microcirculation and tumor microcirculation were 73.4 +/- 23.4 (/s) and 41.2 +/- 16.1 (/s), respectively. The shear rate of the tumor microcirculation was significantly slower (P < 0.001) than that of the normal microcirculation. We demonstrated a feasibility of observation and measurement of tumor microcirculation in the lung and confirmed that the physiologic data were compatible to those in the brain or in the liver reported by others. This model might be useful for studying metastatic tumor pathophysiology in the lung microcirculation.

Animals↗

Safety and efficacy of blood donation prior to elective cardiac surgery in anemic patients.

OBJECTIVE: To determine the safety and effectiveness of blood donation in anemic patients, we harvested blood from cardiac patients with baseline hemoglobin levels below 11.0 g/dl. METHODS: Subjects were 118 patients who underwent elective cardiac surgery between January 1994 and October 1997. We assigned patients to 1 of 2 groups based on their entry hemoglobin level: an anemic group (hemoglobin < 11.0 g/dl, n = 20) and a nonanemic group (hemoglobin > or = 11.0 g/dl, n = 98). All patients received subcutaneous administration of recombinant human erythropoietin, and autologous blood was collected once a week for at least 3 weeks before the scheduled surgery date if the hemoglobin level exceeded 10.5 g/dl. RESULTS: No statistically significant differences were seen between the 2 groups in patient profiles or surgical data. The estimated hemoglobin increase did not differ significantly between groups at any time point. The total collected blood volume per patient was greater in the nonanemic group than in the anemic group (1098 +/- 224 ml vs. 712 +/- 334 ml), but the difference in volume was not statistically significant. The percentage of patients who received allogeneic blood did not differ significantly between groups. No side effects were associated with hemoglobin level prior to donation because the incidence of side effects was similar across hemoglobin levels. CONCLUSIONS: This study suggests that autologous blood donation reduces the need for allogeneic blood in patients with baseline hemoglobin levels below 11.0 g/dl.

Aged↗

Relationships between age of onset, antisocial history and general psychopathological traits in Japanese alcoholics.

This study investigated the relationships of age of onset, antisocial history and general psychopathological traits measured by the Minnesota Multiphasic Personality Inventory (MMPI) in Japanese alcoholics (n = 84). A 2 (earlier vs later onset) x 2 (antisocial vs non-antisocial) multivariate analysis of covariance showed that age of onset had a significant correlation with some subscales of the MMPI such as L (lie), Sc (schizophrenia), and Si (social introversion), whereas history of antisocial behavior had no significant correlation with any MMPI clinical subscales. This result indicated that age of onset was a more significant variable than was antisocial history with regard to the current general psychopathological traits on MMPI in Japanese alcoholics.

Adult↗

[Coronary arterial revascularization in dialysis patients].

It is recently reported that among chronic renal dialysis patients myocardial infarction accounts 7.4% of all the cause of death in Japan. In order to improve the mortality of dialysis patients the treatment of ischemic heart disease (IHD) is a major problem. We review previous reports and discuss about the treatment of IHD in dialysis patients. The collected data from the previous reports written about CABG in dialysis patients shows that the mortality of CABG is 7.8% (30/387), the probability of perioperative myocardial infarction (PMI) 8.6% (21/243), brain infarction 1.6% (4/243) and major infection 5.8% (14/243). 3-year and 5-year mortality rate after CABG is reported to be 69-80% and 48-56%, respectively. The result of CABG is excellent and shows that this procedure improves the mortality of dialysis patients with IHD. The procedural mortality of PTCA is 5.6% (8/143), the probability of PMI is 7% (10/143). Many reports shows the high probability of the recurrence of chest pain (60-86%). This procedure when performed in dialysis patients is incomplete because of the calcification of the coronary artery. Even among the dialysis patients it is preferable to perform CABG positively.

Coronary Artery Bypass↗

Real time observation of platelet adhesion to opaque biomaterial surfaces under shear flow conditions.

We developed a new system which enables direct observation of platelet adhesion on opaque biomaterials under shear flow conditions, by combining a thin quartz cone which produces laminar shear flows, with an upright epifluorescence microscope which visualizes stained platelets through the rotating cone. This is the first report on the observation of platelets adhered to opaque biomaterials in real time under shear flow conditions. The direct observation of platelet adhesion to expanded polytetrafluoroethylene (ePTFE) as an opaque biomaterial revealed that the kinetics of platelet adhesion to ePTFE depended greatly on shear stresses, showing that the shear stress of 5.0 dyne/cm2 induced higher adhesiveness of platelets to ePTFE than that of either 0.1 or 15 dyne/cm2. The observation also showed a difference in platelet adhesiveness among ePTFEs with different fibril lengths--0, 3.2, 18, and 35 microm--indicating that ePTFEs with shorter fibril length had lower adhesiveness of platelets under a shear stress of 5.0 dyne/cm2. It is indispensable for analyzing the phenomena of platelet adhesion to opaque biomaterials to observe in real-time rolling, adhesion, and detachment of platelets under shear stresses without disturbing shear flow conditions. The results showed that the mechanical and optical design of the system could serve this purpose.

Algorithms↗

Novel polymorphism of the 5-lipoxygenase activating protein (FLAP) promoter gene associated with asthma.

The human 5-lipoxygenase activating protein (FLAP) gene is one of the key genes involved in the production of the cysteinyl-leukotrienes. We studied novel polymorphism of the FLAP promoter gene and attempted to clarify the relationship between this polymorphism and asthma. We sequenced the FLAP promoter region, containing the -170 to +46-bp sequence from the translational start codon, and found two homozygotes of novel alleles in the polyadenyl region which showed 21 A repeats and 18 A repeats, respectively. The frequency of the 21 A repeats was 52/71 (73.2%) in asthmatics and 39/71 (54.9%) in control subjects. The difference between these frequencies was statistically significant (P = 0.035). This is the first report of FLAP promoter gene polymorphism associated with asthma. Our data suggest that FLAP promoter gene polymorphism might play a crucial role in the pathogenesis of asthma.

5-Lipoxygenase-Activating Proteins↗

Autologous blood donation with recombinant human erythropoietin in anemic patients.

BACKGROUND: Various blood management strategies can be used to reduce the need for allogeneic blood in cardiac surgery. In anemic patients, however, avoidance of allogeneic blood transfusion is difficult to achieve. This study was performed to assess the safety and effectiveness of preoperative blood collection using recombinant human erythropoietin (rHuEPO) for reducing the exposure to allogeneic blood in anemic patients. METHODS: Thirty-two anemic patients undergoing cardiac surgery at our hospital between January 1994 and October 1997 were divided into two groups according to preoperative strategies: 3-week treatment with rHuEPO and blood donation (group 1, n = 16) or iron supplementation alone (group 2, n = 16). RESULTS: There were no statistically significant differences between the two groups in patients' characteristics and surgical data. The number of reticulocytes was increased at just before surgery in group 1, whereas group 2 showed no significant increase. The estimated hemoglobin increases in group 1 were higher at 7 days and just before surgery. The mean number of required allogeneic blood for patients during surgery was 0.59 +/- 1.12 U in group 1 and 5.01 +/- 2.63 U in group 2. In 75% of group 1 patients, allogeneic blood transfusion was successfully avoided, whereas all patients in group 2 received allogeneic blood. CONCLUSIONS: This study suggests that the combination of rHuEPO administration and autologous blood donation can reduce the need for allogeneic blood in anemic patients.

Aged↗

Isolation of cDNAs encoding cellular drug-binding proteins using a novel expression cloning procedure: drug-western.

A rapid and convenient new method for isolating the genes encoding cellular drug-binding proteins is described. This method, drug-western, is based on the use of the drug conjugated with a marker molecule as a probe for the screening of a cDNA library. Unlike the other methods, this method allows us to identify the genes for trace amounts of cellular drug-binding proteins without purification. We have used this approach to isolate human cDNA clones encoding binding proteins of HMN-154 ((E)-4-[2-[2-(p-methoxy-benzene-sulfonamide) phenyl]ethenyl] pyridine), a novel benzenesulfonamide anticancer compound (Katoh and Hidaka 1997). The proteins encoded by two of the isolated clones are identical to NF-YB, B subunit of nuclear transcription factor NF-Y, and thymosin beta-10, respectively. Recombinants of both proteins bind specifically to HMN-154 in vitro. Comparison of amino acid sequences between these proteins shows the sequence similarity in a short amino acid stretch [K(X)AKXXK]. Deletion or mutation of this region causes the significant loss of binding of both proteins to HMN-154. Furthermore, HMN-154 inhibits DNA binding of NF-Y to the human major histocompatibility complex class II human leukocyte antigen DRA Y-box sequence in a dose-dependent manner. Interestingly, other binding proteins identified by this method also possess the same or a similar motif. These results clearly demonstrate that NF-YB and thymosin beta-10 are specific cellular binding proteins of HMN-154 and that this shared region is necessary for the binding to HMN-154. Hence, this new method is thought to be useful for the identification of drug-binding proteins.

Amino Acid Sequence↗