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Biomedical subjects

Y Kuroda

Publications and source records attributed to Y Kuroda.

At least 541 records · Page 30Linked to original sources
PubMed1994

Effect of neuroprotective N-methyl-D-aspartate antagonists on increased intracranial pressure: studies in the rat acute subdural hematoma model.

Glutamate antagonists are the most powerful neuroprotective drugs in laboratory studies of focal cerebral ischemia. Because the majority of clinical conditions in which focal brain ischemia occurs are associated with high intracranial pressure (ICP), we have used the rat acute subdural hematoma model to evaluate the effects of three glutamate N-methyl-D-aspartate antagonists, MK-801, CGS 19755 (SELFOTEL), D-CPP-ene, and mannitol, upon ICP and also upon the volume of ischemic brain damage. Only mannitol produced a significant reduction in ICP and improved cerebral perfusion pressure. The three glutamate antagonists did not significantly affect ICP or cerebral perfusion pressure, but they were associated with a significantly smaller zone of focal brain damage, when compared to the mannitol and saline groups. N-methyl-D-aspartate antagonists do not increase ICP or jeopardize cerebral perfusion pressure when administered under anesthesia with a controlled PaCO2 level. Further studies in humans are indicated.

Acute Disease↗
PubMed1994

Interaction between dibucaine and pig erythrocyte membranes as studied by NOESY experiments in 1H-NMR spectroscopy. Which form of dibucaine interacts more strongly, cationic or uncharged?

The interaction between amine local anesthetic dibucaine and pig erythrocyte membranes has been studied by 1H-NMR spectroscopy. Two-dimensional NOESY spectra were observed to obtain the conformations of cationic and uncharged forms of dibucaine. The NMR spectra were measured at pH 7.4, and the temperature was raised (318-348 K) to increase the concentration of the uncharged form of dibucaine, taking the temperature dependence of the pKa value of dibucaine into consideration. The dibucaine in a buffered solution showed the presence of two kinds of distinctly different species; one is assignable to the cationic form and the other to the uncharged form of dibucaine, suggesting that the protonation equilibrium between the two forms is slow in the presently employed experimental condition. The uncharged dibucaine showed well-defined NOE cross-peaks in the NOESY spectra of the solution containing no erythrocyte membranes, suggesting that its conformation is relatively fixed. Interestingly, however, it was only the cationic dibucaine that showed NOE cross-peaks when the solution contained the membranes, and experiments were performed at a much shorter mixing time for the buildup of NOEs, suggesting that it appeared only the cationic form of dibucaine is interacting with the membranes. It was concluded that the uncharged form of dibucaine, which was produced by raising the temperature, formed micelles in a buffered solution. Thus formed micelles didn't interact with membranes owing to the repulsive forces between the structured water surrounding the micelles and those at the surface of the membranes. This conclusion could be a promising reason why the cationic local anesthetics are much more active than their uncharged counterparts in blocking nerve conduction.

Animals↗
PubMed1994

Aggregation of amyloid beta-protein and its neurotoxicity: enhancement by aluminum and other metals.

The aggregation of amyloid beta-protein has been suggested to enhance its neurotoxicity in cultured hippocampal neurons. We found that aluminum, an epidemiologic risk factor for Alzheimer's disease, promoted the aggregation of synthetic amyloid beta-protein (beta 1-40) using immunoblotting and centrifugation. There were no significant changes by Ca or Mg. Other metals including Zn, Fe caused the small degree of aggregation compared to Al. Furthermore, beta 1-40 which was aggregated by aluminum was applied on cultured rat hippocampal neurons, and the characteristic deposition of amyloid fibrils was observed on cultured neurons. These results suggested that the degeneration of neurons and the deposition of amyloid beta-protein were enhanced by aluminum.

Aluminum↗
PubMed1994

Non-insulin and non-exercise related increase of glucose utilization in rats and mice.

The effects of high-energy phosphate contents in muscles on glucose tolerance and glucose uptake into tissues were studied in rats and mice. Enhanced glucose tolerance associated with depleted high-energy phosphates and elevated glycogen content in muscles and liver was observed in animals fed creatine analogue beta-guanidinopropionic acid (beta-GPA). Distribution of infused 2-[1-14C]deoxy-D-glucose in tissues especially in the soleus muscle, kidney, and brain was greater in mice fed beta-GPA than controls. The glucose uptake was decreased when the contents of ATP and glycogen were normalized following creatine supplementation. Plasma insulin in animals at rest was lower and its concentration after intraperitoneal glucose infusion tended to be less in animals fed beta-GPA than controls (p > 0.05), although the pattern of insulin response to glucose loading was similar to the control. The daily voluntary activity in beta-GPA fed mice was also less than controls. These results suggest that improved glucose tolerance is not related to elevated insulin concentration and/or decreased glycogen following exercise. Such improvement may be due to an increased mitochondrial energy metabolism caused by depletion of high-energy phosphates.

Animals↗
PubMed1994

Cell processing protocol for allogeneic peripheral blood stem cells mobilized by granulocyte colony-stimulating factor.

Although there is a growing body of information available regarding restoration of hematopoiesis with peripheral blood stem cell (PBSC) autografts, few studies have explored this procedure using allografts. In this study with healthy donors, we investigated the feasibility of a protocol for mobilizing PBSC using recombinant human granulocyte colony-stimulating factor (G-CSF) and subsequent bulk depletion of T cells from apheresis-harvested cells. Nine informed healthy donors were given G-CSF subcutaneously at two different dosing schedules (5 micrograms/kg/d in five donors and 2 micrograms/kg/d in four) for 5 consecutive days, and serial changes in blood components, including hematopoietic progenitor cells, were monitored. After 5 days of stimulation with G-CSF, PBSCs were collected by apheresis, and yields were compared. The number of white blood cells (WBC) reached a plateau level on either day 2 (5 micrograms) or 3 (2 micrograms), but the numbers of red blood cells and platelets were not affected. Circulating colony-forming unit-granulocyte/macrophage (CFU-GM) levels started to increase 1 or 2 days after the increase in the WBC count. By performing a 3L apheresis, the number of CFU-GM harvested was 4.6 +/- 3.3 x 10(6) (mean +/- standard error of the mean [SEM]) in the 5-micrograms group and 1.8 +/- 0.7 x 10(6) in the 2-micrograms group. Different procedures for depleting T cells, including the use of L-phenylalanine methyl ester (PME) and flasks coated with anti-CD5/CD8 monoclonal antibodies or neuraminidase-treated sheep red blood cells (SRBC), were also tested on the harvested cells. We found that cell lysis with PME before selective removal of T cells was very effective in reducing the number of cells that required further processing and was suitable for routine use. However, our current procedure resulted in unsatisfactory depletion of T cells (99.5% removal) while retaining hematopoietic progenitor cells (7.5% recovery). Further research is required in this area.

Adult↗
PubMed1994

Effects of rhG-CSF (filgrastim) on the recovery of hematopoiesis after high-dose chemotherapy and autologous peripheral blood stem cell transplantation in children: a report from the Children's Cancer and Leukemia Study Group of Japan.

In a nonrandomized study, hematopoietic recovery kinetics were evaluated in 98 consecutive patients who underwent high-dose chemotherapy without total body irradiation (TBI) and autologous peripheral blood stem cell transplantation (PBSCT). Fifty-three patients received recombinant human granulocyte colony-stimulating factor (rhG-CSF) (filgrastim) therapy after PBSCT, and the data were compared by actuarial analysis to those of 45 historic controls. The number of days required to achieve a white blood cell count (WBC) of 1 x 10(9)/L, an absolute granulocyte count (AGC) of 5 x 10(8)/L, and a platelet count (PLT) of 5 x 10(10)/L were, respectively, 12.8 +/- 6.4 (mean +/- standard deviation [SD]), 13.4 +/- 6.4, and 49.2 +/- 78.2 in treated patients vs. 12.8 +/- 4.6, 14.4 +/- 10.3, and 31.4 +/- 38.8 days in historic controls, with no significant differences. There was no significant difference between the average number of days with fever in the treated group (6.0 +/- 6.6) and that in the control group (4.0 +/- 2.8). All febrile episodes responded promptly and successfully to parenteral antibiotic therapy. Thus, the data may suggest the possibility that therapy with filgrastim has only a limited ability to enhance hematopoietic recovery after PBSCT. To confirm this notion, we initiated a prospective randomized trial by recruiting a larger number of patients.

Adolescent↗
PubMed1994

Reinforcement of cyclosporin A-induced red cell destruction by superoxide.

To determine the mechanism of hemolysis following organ transplantation, we studied the effect of immunosuppressants and/or superoxide (SO) on the in vitro destruction of red cells. The immunosuppressants tested included cyclosporin A (CyA), deoxyspagarine (DSG), and FK506. SO was obtained from the hypoxanthine-xanthine oxidase reaction. Of the three immunosuppressants studied, only CyA affected the size of red cells and directly produced hemolysis in an isotonic buffer without the involvement of an immune mechanism. In addition, SO and CyA showed a synergistic effect on hemolysis during prolonged incubation. Catalase and allopurinol prevented hemolysis by counteracting the activity of SO. In that SO is produced in excess during the recovery of blood flow after organ transplantation, the prolonged contact of red cells with CyA and SO may be involved in the development and reinforcement of hemolysis in vivo.

Adult↗
PubMed1994

Amelioration of rewarming ischemic injury of the pancreas graft during vascular anastomosis by increasing tissue ATP contents during preservation by the two-layer cold storage method.

Rewarming ischemic injury during vascular anastomosis severely compromises posttransplant pancreas graft survival because the graft has already been subjected to warm and cold ischemia before vascular anastomosis. We examined whether preservation of the pancreas graft by the two-layer method ameliorates rewarming ischemic injury of the graft during vascular anastomosis and also investigated the energy metabolism of the pancreas graft before, during and after rewarming ischemic period. After flushing with cold University of Wisconsin solution (UW), the pancreas grafts were preserved by the two-layer (UW/perfluorochemical [PFC]) method (group 1) or simple cold storage in UW (group 2) for 24-hr and then autotransplanted. In control, the pancreas grafts were flushed out with cold UW and immediately autotransplanted without preservation (group 3). After completion of vascular anastomosis, vascular clamp was not released until 90, 120, or 150 min of rewarming ischemia, including anastomosis time, has elapsed. After 90 min of rewarming ischemia, graft survival rates were 5/5, 100%, 5/5, 100%, and 5/5, 100% in groups 1, 2 and 3, respectively. After 120 min, all the grafts in groups 2 and 3 failed (0/5, 0%, and 0/5, 0%, respectively), however, all the grafts in group 1 survived (5/5, 100%). Even after 150 min, 1 of 3 grafts in group 1 survived (1/3, 33%). After 24 hr preservation, tissue adenosine triphosphate (ATP) and total adenine nucleotides (TAN) levels of the grafts in group 1 were about 2-fold the reference values before harvesting and significantly higher compared with group 2(p < 0.05; p < 0.05). After 120 min of rewarming ischemia, tissue ATP levels in group 1 were 84% of the reference values and significantly higher compared with group 2(p < 0.05). TAN levels of group 1 were also significantly higher compared with group 2(p < 0.05). Two hours after reperfusion, ATP and TAN levels in group 1 were significantly higher than group 2(p < 0.05). There were no remarkable difference between group 1 and group 2 concerning adenosine diphosphate (ADP), adenosine monophosphate (AMP) levels. We conclude that the two-layer (UW/PFC) method ameliorates rewarming ischemic injury of the pancreas graft during vascular anastomosis by increasing tissue ATP concentration and TAN levels during preservation and maintaining tissue ATP and TAN levels during vascular anastomosis. Consequently, ATP levels are rapidly recovered after reperfusion and the graft survives.

Adenosine Triphosphate↗
PubMed1994

[Development of the brainstem and cerebellum in autistic children].

Studies of magnetic resonance images have revealed morphological disorders of the brainstem and cerebellum in autistic children and adults. When we studied development of the brainstem and cerebellum in autistic patients, these structures were significantly smaller in autistic patients than in controls. Although the brainstem and cerebellum significantly increased in size with age in both groups, the development of the pons, cerebellar vermis I-V and cerebellar vermis VI-VII was significantly more rapid in autistic patients than in controls. However, the development of the other brain structures in the posterior fossa did not differ between autistic patients and controls. The regression intercepts of the brainstem and cerebellum as well as those of their components were significantly smaller in autistic patients than in controls. These results suggested that significant anatomical changes took place in the posterior fossa brain structures in the prenatal period in autistic children, but were not progressive.

Adolescent↗
PubMed1994

[A new method of high-dose intraarterial chemotherapy of the pancreas using direct hemoperfusion (DHP) under portal venous isolation (PVI)].

Surgical resection for pancreatic cancer is severely limited by the extent of the disease at the time of diagnosis. Chemotherapy has been the treatment of choice for unresectable cases. We developed a new method of intraarterial chemotherapy for pancreatic body and tail cancers using direct hemoperfusion (DHP) under portal venous isolation (PVI). Adriamycin (ADR, 3 mg/kg) was infused into the splenic arteries of mongrel dogs for 5 min after clamping off blood flow to the stomach and the duodenum. In group A (n = 5), this was simply done, and in group B (n = 5) the portal venous blood was isolated by clamping at the porta hepatis and pumped through the DHP circuit to the jugular vein for 20 min from the start of drug infusion. The peak systemic level (microgram/ml) of group B (0.78 +/- 0.03) was significantly reduced by PVI.DHP as compared to that of group A (3.49 +/- 1.15, P < 0.01). The pancreatic tissue levels (microgram/g. tissue) 30 min after drug infusion of group A (61.2 +/- 13.4) were slightly lower than those in group B (88.9 +/- 27.8), although not statistically significant. However, tissue levels of group B in the liver (27.3 +/- 9.2) and heart (1.8 +/- 0.8) were significantly lower than those of group A (liver; 52.3 +/- 18.5, heart; 4.9 +/- 0.6, P < 0.05). In conclusion, PVI.DHP achieved a significant reduction in systemic drug exposure during intraarterial chemotherapy. Therefore, we consider that this system will allow dose escalation of ADR during intraarterial chemotherapy for pancreatic body and tail cancers.

Animals↗
PubMed1994

Serologic, virologic, and histologic characteristics of chronic phase hepatitis C virus disease in children infected by transfusion.

OBJECTIVE: We studied the time course of hepatic dysfunction, seropositivity to hepatitis C virus (HCV) antibodies, viremia, and histologic evidence of hepatic injury to evaluate the course of HCV infection in children infected by blood transfusion. PATIENTS AND METHODS: Twenty-nine patients (ages 4 to 18 years) who underwent open-heart surgeries for congenital heart disease were grouped into three categories based on alterations in serum alanine aminotransferase (ALT) levels: Group A, acute infection; Group B, subacute infection; and Group C, chronic infection. RESULTS: In Group C, all 13 patients had detectable HCV RNA in serum. In contrast, all patients in Group A had no detectable HCV RNA: In Group B, one of nine patients had detectable HCV RNA and two of four patients examined had persistent chronic hepatitis by histologic criteria. Antibodies directed against C100-3 antigen or core-antigen were more useful than second-generation HCV antibody assays in determining the relationship between viremia and immunologic response. Infection with HCV genotype II and the presence of higher HCV RNA copy numbers were associated with histologic evidence of hepatic damage. CONCLUSION: An abnormal ALT value is frequently associated with viremia, and biochemically resolved acute infection reflects clearance of HCV. However, a normal ALT does not always reflect an absence of hepatocyte damage and HCV replication in patients with subacute disease. The measures outlined in this study are useful indicators of disease activity during the chronic

Acute Disease↗
PubMed1994

[A case of dementia associated with multiple iron deposits in the brain on MRI].

We report a 63-year-old man presenting with dementia and cerebellar ataxia associated with multiple iron deposits in the brain on MRI. Numerous small lesions of low-intensity on both T1- and T2-weighted images were found in the parenchyma and surface of the cerebrum, cerebellum and brain stem. The number and size of lesions were increased on MRI with the method of gradient recalled acquisition in the steady state (GRASS), indicating that they were composed of iron. The similar lesions were not found in any organs on the abdominal GRASS-MRI. Any abnormalities were also not found in the cerebral angiography. Meanwhile, the protein and IgG levels and activated CD4-cells were increased in the cerebrospinal fluid, indicating the involvement of chronic inflammation in the iron deposits in this case.

Brain↗
PubMed1994

[Gut mucosal immunity and oral tolerance].

The biological phenomenon that experimental animals become hyporesponsive to a particular protein antigen, when orally administered, is called oral tolerance. A breakdown of oral tolerance to dietary antigens may be related to food allergy. Conversely, the induction of oral tolerance by feeding autoantigens, such as myelin basic protein, protects animals from subsequent immunization by this antigen resulting in development of experimental autoimmune encephalomyelitis, which is a disease model of the human demyelinating disease, multiple sclerosis (MS). The mechanism of oral tolerance could be an induction of suppressor cells, which release inhibitory cytokines including transforming growth factor beta, when triggered antigen-specifically and/or clonal anergy to fed antigen. Against this background, patients with MS and rheumatoid arthritis are on a clinical trial with bovine myelin and type II collagen feeding, respectively. Oral tolerance could be a part of the mainstream in future treatment strategies for human diseases with autoimmune etiologies.

Administration, Oral↗
PubMed1994

[CD classification of lymphocytes and the function: significance of flow cytometric analysis in immunoneurological disorders].

We reviewed flow cytometric studies of lymphocyte subsets by using monoclonal antibodies in various immunoneurological disorders. In multiple sclerosis, most studies indicated decreases of suppressor T cells and suppressor-inducer T cells in both peripheral blood and cerebrospinal fluid (CSF). In HTLV-I-associated myelopathy, our studies showed an increase of CD28-negative cytotoxic T cells in the CSF, indicating the involvement of dysfunctioned cytotoxic T cells in the spinal cord lesion formation. In myasthenia gravis, the disease-specific finding is the appearance of CD4+ CD8+ (double positive) T cells in the peripheral blood, which may be associated with thymic abnormalities. These flow cytometric studies in immunoneurological disorders thus provide an insight in the pathogenesis of immunoneurological disorders.

Antigens, CD↗