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Biomedical subjects

Y Takada

Publications and source records attributed to Y Takada.

At least 415 records · Page 23Linked to original sources

Receiver operating characteristic (ROC) analysis of the ability of arterial ketone body ratio to predict graft outcome after liver transplantation--its sensitivity and specificity.

To evaluate the ability of arterial ketone body ratio (AKBR; acetoacetate/3-hydroxybutyrate) to predict graft prognosis after liver transplantation, the diagnostic value as a predictive index was compared between AKBR and conventional liver function tests using receiver operating characteristic (ROC) analysis. The ROC curves were determined for AKBR, GOT, GPT, total bilirubin, serum lactate level, and prothrombin time, all of which were measured on the 1st and 2nd postoperative days in 88 cases of liver transplantation. Comparisons of the areas under the ROC curves between AKBR and other tests revealed the significant superiority of AKBR to other tests in predicting graft death within 1 month after transplantation. The present study suggests that AKBR can be used as an accurate index to predict graft prognosis after liver transplantation.

Adolescent↗

Kasabach-Merritt syndrome in two neonates.

Two neonates with a giant hemangioma associated with thrombocytopenia (Kasabach-Marritt syndrome) have been managed at Kure National Hospital. The first case was initially difficult to distinguish from overwhelming infection or other tumors but improved after radiotherapy. The second case was resistant to radiation and steroid therapy. Magnetic resonance imaging determined a tumor extending into the surrounding soft tissues better than did enhanced computed tomography. Subtotal excision of the tumor and various drugs were effective only transiently and 51Cr-labeled platelets sequestrated into the residual hemangioma. Severe thrombocytopenia persisted for approximately 15 months requiring extra care for head and body contusions, but finally improved by treatment with platelet-active drugs such as acetylsalicylic acid, dipyridamole, and pentoxifylline.

Disseminated Intravascular Coagulation↗

Relationship between serotonergic measures in periphery and the brain of mouse.

Circadian rhythm and the relationship between the concentration of serotonin (5HT) and related substances (5-hydroxyindoleacetic acid; 5HIAA and tryptophan; Trp) in mouse brain, stomach and blood have been studied. All factors underwent circadian changes in the brain and blood. 5HT and 5HIAA levels in the stomach showed no circadian fluctuation. The concentrations of 5HT in the brain and blood did not correlate. Significant correlations were found between other serotonergic parameters analyzed in brain, stomach and blood. A significant negative correlation was observed between brain 5HIAA and blood 5HIAA. The concentration of tryptophan in the brain was correlated with the plasma total tryptophan level. There was fairly significant correlation (p less than 0.06) between brain serotonin and plasma tryptophan levels. The brain serotonin and tryptophan levels were strongly correlated (R = 0.410, p less than 0.03). Significant negative correlation was found between serotonin in the blood and serotonin in the stomach as well as between its level in the brain and in the stomach. The significance of these findings and their relationship to the use of peripheral serotonergic system as a model of neurons are discussed.

Animals↗

A simple method to assess osteoclast-mediated bone resorption using unfractionated bone cells.

To determine osteoclastic bone resorption we established a simple assay system in which unfractionated cells obtained from femora of 13-day-old mice were cultured on a dentine slice and the number of osteoclasts and their induced pit area on the slices were measured. When the bone cells (1 x 10(5) cells/dentine slice) were cultured in the presence of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] or human parathyroid hormone (hPTH) for 4 days, at which time newly-formed osteoclasts were not detected, the pit area was dose-dependently increased, being a 4.3- or 4.1-fold respective increase over the control at a 10(-8) M concentration of hormones. Chick calcitonin (cCT) inhibited the osteoclastic bone resorption induced by either of these hormones. cCT alone also suppressed the bone resorption by the cells (3 x 10(5) cells/dentine slice). These findings indicate that 1,25(OH)2D3 or hPTH may mainly activate pre-existing osteoclasts, resulting in increased bone resorption, and that cCT may suppress this osteoclastic activity. When 1,25(OH)2D3 or hPTH was added to the cells pre-cultured in factor-free medium for 6 days, at which time pre-existing osteoclasts had almost degenerated, new osteoclasts were formed, resulting in an increase in pit formation. Thus this system is a useful method which could more sensitively evaluate the effects of hormones or factors on osteoclast formation and activation than other previous systems.

Animals↗

A point mutation of integrin beta 1 subunit blocks binding of alpha 5 beta 1 to fibronectin and invasin but not recruitment to adhesion plaques.

A point mutation in a highly conserved region of the beta 1 subunit, Asp130 to Ala (D130A) substitution, abrogates the Arg-Gly-Asp (RGD)-dependent binding of alpha 5 beta 1 to fibronectin (FN) without disrupting gross structure or heterodimer assembly. The D130A mutation also interferes with binding to invasin, a ligand that lacks RGD sequence. In spite of the lack of detectable FN binding by alpha 5 beta 1(D130A), it was recruited to adhesion plaques formed on FN by endogenous hamster receptors. Thus, intact ligand binding function is not required for recruitment of alpha 5 beta 1 to adhesion plaques. Overexpression of beta 1(D130A) partially interfered with endogenous alpha 5 beta 1 function, thus defining a dominant negative beta 1 integrin mutation.

Adhesins, Bacterial↗

A mixture of nucleosides and a nucleotide alters hepatic energy metabolism 24 hours after hepatectomy in rabbits.

The effect of administering a nucleoside-nucleotide mixture on hepatic energy metabolism was evaluated at 24 h after hepatectomy in rabbits that had had 70% of their livers removed. After hepatectomy, animals were administered continuous intravenous infusion of 2 mL/(kg body wt-h) of 9 g/L NaCl (Group S), 5.99 mmol/L nucleoside-nucleotide mixture (Group N1) or 11.98 mmol/L nucleoside-nucleotide mixture (Group N2). At 24 h after hepatectomy, the hepatic adenylate energy charge in Group S (0.83 +/- 0.01, mean +/- SEM) was significantly lower than that before hepatectomy (0.90 +/- 0.01). By contrast, the values in Groups N1 and N2 after hepatectomy (0.74 +/- 0.04 and 0.73 +/- 0.04, respectively) were significantly lower than that in Group S. The hepatic mitochondrial phosphorylation rate before hepatectomy was 46.40 +/- 4.88 nmol ATP/(mg mitochondrial protein-min). After hepatectomy, significantly greater values were observed in Groups N1 and N2 (69.53 +/- 7.20 and 63.31 +/- 6.11, respectively), yet those values were less than observed in Group S (109.14 +/- 4.80). These results suggest that the nucleoside-nucleotide mixture suppressed the enhancement of hepatic mitochondrial phosphorylative activity at a time when hepatic adenylate energy charge is compromised. Such enhancement is needed to compensate for the increased energy expenditure due to surgical intervention.

Adenosine Diphosphate↗

The introduction of microvascular surgery to hepatic artery reconstruction in living-donor liver transplantation--its surgical advantages compared with conventional procedures.

Microvascular surgery for the reconstruction of the graft artery has been used since the 8th case in our series of 14 liver transplantations using living-related donors, and the clinical results have been compared between the first seven cases (the Loupe group) and the last seven cases (the Micro group). Seven arteries in 7 grafts were reconstructed with the use of loupe magnification in the Loupe group, while 8 arteries in 7 grafts were anastomosed with microscopic techniques in the Micro group. Statistically, there was no difference between the two groups in general background, including age, body weight and primary disease of the recipient, and in medical and surgical factors possibly relating to postoperative thrombosis of the hepatic artery. In two cases in the Loupe group, one or two additional reconstructions were necessary to obtain sufficient blood flow, while 8 arteries were anastomosed in the Micro group without any arterial complication in the postoperative period. There was no difference in time required for completing the arterial reconstruction (45.1 +/- 18.1 min in the Loupe versus 44.4 +/- 6.9 min in the Micro [mean +/- SEM]). Postoperative ultrasonic Doppler duplex study demonstrated a temporary decrease in the arterial flow in 2 cases of the Loupe group, and partial thrombosis of the artery was suspected. Additionally there were two episodes of hepatic artery thrombosis in 1 case of the Loupe group, in which emergent revision for thrombectomy and reanastomosis was performed at the first episode. This illustrated the higher incidence of arterial complications in the Loupe group compared with the Micro group (4 episodes/7 arteries in the Loupe versus 0/8 arteries in the Micro, P less than 0.05). In the present series there were no graft failures or arterial complications in the three deaths in the series. The clinical improvements achieved by microvascular surgery in living-donor liver transplantation suggest an alternative technical strategy for dealing with problematic arterial reconstruction in adult liver transplantation.

Child↗

Analyses of the risk and operative stress for donors in living-related partial liver transplantation.

Operative risk and stress were analyzed in 28 parent-donors whose children received partial liver transplantations at the Second Department of Surgery, Kyoto University Hospital between June 1990 and December 1991. Graft-harvesting operations were classified into three types: left lobectomy (group L, n = 12), left lateral segmentectomy (group S, n = 15), and right lobectomy (n = 1). Since donor safety is a primary concern, great care was taken to minimize potential damage to the remaining lobes of the donor liver as well as the graft liver by avoiding stressful maneuvers such as hepatic vascular clamping during the transection of the hepatic parenchyma. In all cases the arterial ketone body ratio, which reflects the hepatic mitochondrial redox potential, was maintained at over 0.7 throughout the donor operation as well as postoperatively. There was no significant difference in the postoperative RBC, WBC, serum GOT, and total bilirubin between groups L and S, although the abnormalities exhibited by the single right lobectomy case tended to be larger and more prolonged. All cases were within the range acceptable for immediate discharge, and all donors of groups L and S were subsequently discharged within 14 days without any postoperative complications. The single right lobectomy donor was discharged on POD17 because of transient slight icterus, which is the only postoperative complication encountered in this series thus far. The present analyses would indicate that the risk and operative stress to the donor in living-related partial liver transplantation can be minimal when the left lobe or left lateral segment of the liver is used for the graft.

Aspartate Aminotransferases↗

VLA-4 molecules on tumor cells initiate an adhesive interaction with VCAM-1 molecules on endothelial cell surface.

To elucidate the role of VLA-4 (alpha 4 beta 1 integrin) in tumor metastasis, we have transfected cDNA coding alpha 4 subunit into human fibrosarcoma (HT1080) cells. VLA-4-overexpressing HT-VC1 cells exhibited increased ability to interact with known ligands for VLA-4, such as CS1 peptide and VCAM-1 (vascular cell adhesion molecule-1). In addition, the in vitro invasive ability of HT-VC1 cells was augmented and the mRNA for type IV collagenase was increased in HT-VC1 cells. The induction of VCAM-1 molecules on lung endothelial cells of nude mice by tumor necrosis factor-alpha treatment resulted in augmentation of in vivo HT-VC1 cell adhesion to the lung endothelial cells. Thus, the VLA-4 molecules on tumor cells initiate an adhesive interaction with VCAM-1 molecules on endothelial cells, that is important for hematogenous metastasis.

Animals↗

Facilitated transport of the neurotoxin, beta-N-methylamino-L-alanine, across the blood-brain barrier.

beta-N-Methylamino-L-alanine (BMAA) is a neurotoxic plant amino acid that has been implicated in the pathogenesis of the high incidence amyotrophic lateral sclerosis and related parkinsonism dementia of the western Pacific. Previous studies have demonstrated that BMAA is taken up into brain following intravenous or oral administration. To examine the kinetics and mechanism of brain transfer, BMAA influx across the blood-brain barrier was measured in rats using an in situ brain perfusion technique. BMAA influx was found to be saturable with a maximal transfer rate (Vmax) of 1.6 +/- 0.3 x 10(-3) mumol/s/g and a half-saturation constant (Km) of 2.9 +/- 0.7 mM based on total perfusate BMAA concentration. Uptake was sodium independent and inhibitable by excess L-leucine, but not by L-lysine, L-glutamate, or methylaminoisobutyric acid, indicative of transfer by the cerebrovascular large neutral amino acid carrier. L-BMAA competitively reduced brain influx of L-[14C]leucine, as expected for cross-inhibition. The results demonstrate that BMAA is taken up into brain by the large neutral amino acid carrier of the blood-brain barrier and suggest that uptake may be sensitive to the same factors that affect neutral amino acid transport, such as diet, metabolism, disease, and age.

Amino Acid Transport Systems↗

Evaluation of ketogenesis in seriously reduced hepatic mitochondrial redox state. An analysis of survivors and non-survivors in critically ill hepatectomized patients.

Ketogenesis was evaluated in 33 critically ill hepatectomized patients in relation to the arterial ketone body ratio (acetoacetate to 3-hydroxybutyrate), which reflects hepatic mitochondrial redox state. In 15 patients whose arterial ketone body ratio decreased to below 0.4, blood ketone body levels were significantly increased concomitant with marked increase of blood lactate and plasma alanine levels. In the 6 survivors of these 15 patients, the arterial ketone body ratio was restored within the next 2 days, and blood ketone body levels were decreased. By contrast, in the nine non-survivors, the arterial ketone body ratio remained below 0.4, and blood ketone body levels were decreased, accompanied by significant increases in blood lactate and plasma alanine levels in the terminal stages. These results suggest that ketogenesis acts as an alternative process for ATP synthesis in the liver in critically ill patients. Death occurs when the liver falls into an energy crisis concomitant with the cessation of ketogenesis.

Adult↗

Decrease in arterial ketone body ratio indicating graft dysfunction after liver transplantation.

In 3 cases of living related liver transplantation, arterial ketone body ratio (AKBR) showed secondary decrease in the early postoperative period, indicating the graft dysfunction more rapidly and sensitively than other liver function tests. Significance of AKBR for monitoring the graft function in postoperative management after liver transplantation is discussed.

3-Hydroxybutyric Acid↗

Protective effect of platelet-activating factor antagonist on hepatic energy metabolism following transient hepatic inflow occlusion in rabbits.

To investigate whether or not platelet-activating factor (PAF) is a mediator of the liver injury resulting from transient hepatic inflow occlusion (Pringle's maneuver), the effect of pretreatment with a potent PAF antagonist (CV6209) on hepatic energy metabolism was evaluated following 30 min of inflow occlusion in rabbits. At 60 min after declamping, the arterial ketone body ratio (AKBR; acetoacetate/3-hydroxybutyrate), reflecting hepatic mitochondrial redox state (NAD+/NADH), increased to 1.10 +/- 0.05 (mean +/- SEM) in the CV6209 (5 mg/kg)-pretreated group (group 1, n = 5) compared with 0.72 +/- 0.06 (P less than 0.01) in the untreated group (group 2, n = 5). Hepatic energy charge at 60 min after declamping was significantly higher in group 1 than in group 2 (0.871 +/- 0.010 vs. 0.800 +/- 0.023; P less than 0.05). Pretreatment with CV6209 had no significant influence on these parameters in sham-operated animals. The present study demonstrates that pretreatment with CV6209 has a protective effect against the impairment of hepatic energy metabolism following transient hepatic inflow occlusion.

Animals↗

[Histological changes in the retinal pigment epithelium and Bruch's membrane in senescence accelerated mouse].

Senescence associated changes of the retinal pigmented epithelium (RPE) and Bruch's membrane were investigated in senescence accelerated mouse (SAM), which is an aging model mouse, by light and electron microscopy. The most characteristic changes in RPE were swelling of basal infoldings, extension of intercellular space and accumulation of lipofuscin granules. In Bruch's membrane, discontinuation of elastic layer and abnormal increase of fine fibrils in the outer collagenous layer were observed. The aging changes in SAM were severer in the posterior retina than in the peripheral one. Moreover, these changes were seen younger age than in those of the normal BALB/c mouse.

Aging↗

A role of cytoplasmic free adenosine diphosphate in regenerating rabbit liver.

Cytosolic free adenosine diphosphate (ADP) concentration in remnant rabbit liver 24 hours after 70% hepatectomy was calculated from the measured components of the glyceraldehyde-3-phosphate dehydrogenase:3-phosphoglycerate kinase/lactate dehydrogenase reaction. The concentration of free cytoplasmic ADP of the remnant liver increased from the control value of 76.9 +/- 6.0 mumol/L to 208.8 +/- 31.9 mumol/L (mean +/- SEM) at 24 hours after hepatectomy. The calculated free ADP provides the following three interpretations with respect to mitochondrial respiration acceleration as a result of liver regeneration. First, the Michaelis-Menten equation for physiologic respiration relative to maximal respiration gave 1.16 as the value of acceleration. Next, the classical thermodynamic theory showed that the logarithm of [adenosine triphosphate]/[free ADP] [free inorganic phosphate], which is reciprocally correlated with mitochondrial respiration, was decreased by a factor of 0.78 after hepatectomy. Finally, the irreversible thermodynamic theory indicated that chemical affinity, which is linearly correlated to mitochondrial respiration, was increased 1.36 times. These interpretations suggest that the rate of mitochondrial respiration is accelerated after major hepatectomy.

Adenosine Diphosphate↗

[Serum catecholamine concentrations and hemodynamics during operations on 23 children with neuroblastoma].

The purpose of the present report is to reveal the relation between hemodynamic changes and serum catecholamine concentrations during operation of 23 neuroblastoma patients. The patients were aged from 6 months to 7 years (mean 1.2 year), and 20 patients (86%) were under 1 year of age. All the patients were in early stage of tumor development because they were diagnosed as neuroblastoma mainly by mass screening test for VMA and HVA in urine utilizing HPLC. This urinary mass screening test for infants is performed routinely in Japan. Operative manipulation of tumor provoked the significant elevation of blood pressure, and the increasing tendency of heart rate and rectal temperature. The mean concentrations of three kinds of serum catecholamine, epinephrine, norepinephrine and dopamine, were all very high during manipulation of tumor. Especially, the norepinephrine concentration was 90.2 times higher than the preoperative value. The children who showed high blood pressure, over 70% of the control level, showed high urinary VMA and VMA/HVA ratio preoperatively and a high norepinephrine secretion during operation. We conclude that for the anesthetic management of neuroblastoma, it is necessary to control the elevation of blood pressure even in small children, especially in the patients who have showed high values of urinary VMA and VMA/HVA ratio preoperatively.

Child↗