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Biomedical subjects

Y Kuroda

Publications and source records attributed to Y Kuroda.

At least 523 records · Page 29Linked to original sources
PubMed1994

Do patients with Down's syndrome recognize Mickey Mouse?

In 47 patients with Down's syndrome who were too retarded to understand a conventional oddball paradigm, we studied event-related potentials (ERPs) by using task-irrelevant visual stimuli. As the patients had expressed interest in Disney cartoons and books, five pictures of Disney characters such as Mickey Mouse or Peter Pan were employed as the rare stimuli, and nine ordinary scenes such as mountains as the frequent stimuli. Five sets were constructed by intermingling each rare picture with nine frequent pictures, and each picture was presented on a TV screen. ERPs to the rare stimuli (N270-P380), which were different from the averaged waveforms to frequent stimuli and electrooculograms (EOGs), were clearly recorded in 35 out of 47 patients. Only 24 of these patients had ERPs using a conventional auditory oddball paradigm. The peak latencies in patients were significantly prolonged relative to age-matched normal controls, probably due to a slowed neural processing. The amplitude in patients was slightly larger than normal controls, probably due to the patients' greater interest or surprise when confronted with the Disney characters.

Adolescent↗
PubMed1994

Periodic maternal deprivation alters stress response in adult offspring: potentiates the negative feedback regulation of restraint stress-induced adrenocortical response and reduces the frequencies of open field-induced behaviors.

The effects of periodic maternal deprivation (PMD) treatment on the adrenocortical stress response and on open-field behavior in adult offspring were investigated. Sprague-Dawley rat pups were deprived of mothers daily for 4.5 h during the first 3 weeks of life. PMD treatment resulted in lower corticosterone levels during restraint stress later in life. The result of dexamethasone suppression test indicated that PMD treatment caused a potentiation of the negative feedback function of adrenocortical response. These effects of PMD were not accompanied by an increased density of the hippocampal glucocorticoid receptor which has been reported to be induced in neonatal handling treatment (brief 15-min maternal deprivation). Serotonin (5-HT)-2 and beta-adrenergic binding sites were also examined in cerebral cortex and no change of binding capacities were induced by PMD treatment. In the open-field test, PMD treatment decreased the number of ambulations and rearings but did not affect a frequency of defecation. From these results, it is suggested that PMD treatment leads rats to be insensitive to environmental stimuli in adulthood.

Adrenal Cortex↗
PubMed1994

Restraint stress suppresses experimental allergic encephalomyelitis in Lewis rats.

We studied the effect of restraint stress on experimental allergic encephalomyelitis (EAE), a model for the human disease multiple sclerosis (MS), in Lewis rats. Rats were subjected to 12 h restraint stress for 3 consecutive nights from the first (day 1) or the eighth day (day 8) after sensitization with the antigen (guinea-pig spinal cord). All controlled rats exhibited clinical and histologic signs of EAE. The mean +/- SD of incubation time, clinical score (0-4) and histologic score (0-3) for this group were 12.8 +/- 1.0 days, 2.7 +/- 0.6, and 2.3 +/- 0.7, respectively. Restraint stress from day 8 significantly suppressed EAE: the mean +/- SD of incubation time, clinical score, and histologic score for this group were 17.2 +/- 2.2 days (p < 0.001), 1.8 +/- 1.3 (p < 0.05), and 1.5 +/- 0.9 (p < 0.02), respectively. Restraint stress from day 1 did not modify EAE. The findings suggest that stressful factors may exert an influence on the clinical course of MS.

Animals↗
PubMed1994

Infantile spasms with predominantly unilateral cerebral abnormalities.

To investigate the pathogenesis of infantile spasms, 12 children underwent a combination of neurophysiologic and neuroimaging studies including brainstem evoked potentials and single photon emission computed tomography with 99mTcHMPAO. Three of the children had localized cerebral abnormalities on neuroimaging, i.e. right frontotemporal cortical microdysgenesis, left frontotemporal polymicrogyria, and right parietooccipitotemporal porencephalic cyst. Neurophysiologic studies also indicated that a single cerebral hemisphere was predominantly involved, while the other hemisphere and the brainstem were relatively spared, a result compatible with the clinical findings of hemiparesis and hemiconvulsion. In these three patients, administration of carbamazepine was followed by marked improvement of the clinical and electroencephalographic findings. Our results suggest that a combination of noninvasive examinations can distinguish a particular subtype of infantile spasms associated with a localized cerebral abnormality and responsive to carbamazepine.

Carbamazepine↗
PubMed1994

Cooperative deformation of a de novo designed protein.

A de novo protein design has been made to understand the unique packing of natural proteins that have a beta/alpha-barrel fold. A carefully designed 207 amino acid sequence was synthesized using an Escherichia coli expression system and the structural and thermodynamic characteristics of the purified protein were studied. At neutral pH the protein is soluble and monomeric, with large amounts of secondary structure and a hydrophobic core, although the broad resonance peaks of its NMR spectrum suggest that the designed protein does not have a unique structure with tightly packed side chains. In an H-D exchange experiment, no amido protons of the designed protein exchanged slowly with deuterons. At acidic pH, thermal unfolding was observed with a remarkable change in the excess heat capacity measured directly by a differential scanning microcalorimeter. The enthalpy and entropy differences at 110 degrees C, extrapolated from analyzed thermodynamic parameters, are approximately 1/3 of the common values for natural proteins. These measurements indicate that the folding is significantly cooperative as expected, but that the protein is still loosely packed.

Amino Acid Sequence↗
PubMed1994

Splenectomy for treatment of immunoblastic lymphadenopathy.

A 5-month-old girl was diagnosed with immunoblastic lymphadenopathy (IBL) on the basis of clinical symptoms and pathological findings. alpha-interferon, immunosuppressive agents such as cyclosporin A, deoxyspagarine, and azathioprine, and an alternating regimen of low-dose 6-mercaptopurine, cyclophosphamide and methotrexate were tried with partial success. Finally, splenectomy was carried out at 58 months of age, inducing prolonged complete remission without any medication.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Effect of cold aerobic perfusion on nonparenchymal cell viability of rat livers.

We investigated the effect of oxygen supply on hepatic cellular viability during cold perfusion storage of rat livers. A perfluoro-N-methyldecahydroisoquinoline (FMIQ) emulsion is used as an oxygen carrier. The composition of the perfusate containing 20 w/v% FMIQ is essentially the same as the University of Wisconsin (UW) solution except for the exclusion of hydroxyethyl starch. Rat livers were perfused at 4 degrees C for up to 24 h with either UW solution (group I, oxygenated; group II, unoxygenated) or FMIQ solution (group III, oxygenated; group IV, unoxygenated). After perfusion storage, the livers were reperfused with warm (37 degrees C) oxygenated or cold (4 degrees C) unoxygenated Krebs-Henseleit bicarbonate buffer, and nuclear trypan blue uptake was measured as the index of cell death. With warm oxygenated reperfusion, there remained less than 2% noviable parenchymal cells up to 24 h, regardless of perfusate or oxygenation. In UW-perfused livers, the proportion of nonviable nonprenchymal cells (NPC) increased progressively regardless of oxygenation, the values in groups I and II in the periportal field at 24 h being 39.9 +/- 4.7% (mean +/- SD) and 36.5 +/- 4.2%, respectively. By contrast, in FMIQ-perfused livers, dye uptake by NPC was significantly reduced with oxygenation (16.9 +/- 5.7% and 39.4% +/- 9.1% at 24 h in groups III and IV; P < 0.001). With cold unoxygenated reperfusion, livers in groups I, II, and IV showed a significant decrease of nonviable NPC, while those in group III showed no significant changes. These data indicate that oxygen supply during perfusion storage of the liver may ameliorate lethal injury to NPC precipitated during reperfusion.

Adenosine↗
PubMed1994

Metabolic intervention to affect canine pancreas recovery following ischemia during preservation by the two-layer method.

We have demonstrated that a high adenosine triphosphate (ATP) level in a canine pancreas during preservation by the two-layer method is an important determinant for the ultimate success of pancreatic transplantation. In this study, we investigated (a) the effect of factors that seemed to have an influence on energy metabolism in the canine pancreas at the tissue ATP level and (b) graft viability during preservation by the two-layer method. ATP tissue concentration was determined by high-performance liquid chromatography and graft viability was assessed on the basis of survival rate following autotransplantation. First, the pancreas was harvested from either 72-h-fasted (n = 5) or fed dogs (n = 5) and preserved by the two-layer Euro-Collins solution (EC)/perfluorochemical (PFC) method for 24 h. All the pancreatic grafts were viable in both fed and fasted groups. There was also no significant difference in ATP tissue concentration between the two groups (7.48 +/- 0.55 vs. 7.03 +/- 0.74 micromol/g dry weight, NS). Second, the pancreatic grafts subjected to 60 min of warm ischemia were preserved by either the two-layer (EC/PFC) or (EC + adenosine/PFC) method for 24 h. Without adenosine, ATP tissue concentration did not recover (1.62 +/- 0.26 after warm ischemia vs. 1.56 +/- 0.40 micromol/g dry weight after preservation, NS) and all the pancreatic grafts failed. However, provision of adenosine led to restoration of ATP tissue levels (1.90 +/- 0.53 vs. 7.23 +/- 2.17 micromol/g dry weight, P < 0.01) and four of five grafts functioned immediately and maintained normoglycemia after transplantation. These results clearly demonstrated that the nutritional state of the pancreatic graft before procurement had no influence on ATP tissue level as well as graft viability during 24-h preservation by the two-layer method. On the other hand, provision of adenosine during 24-h preservation enhanced ATP synthesis of the pancreatic tissue, thereby improving viability of the ischemically damaged pancreas.

Adenosine↗
PubMed1994

Difference in energy metabolism between fresh and warm ischemic canine pancreases during preservation by the two-layer method.

We have demonstrated that adenosine triphosphate (ATP) is synthesized within a canine pancreas during preservation by the two-layer method and there is a direct correlation between a high ATP tissue level and good posttransplant outcome. The purpose of this study was to examine the difference in energy metabolism between fresh and warm ischemic pancreases during preservation by this method. First, fresh pancreases were preserved with simple cold storage in Euro-Collins solution (EC; group 1A), or by the two-layer method using EC (group 1B), EC with 2,4 dinitrophenol (DNP; group 1C), an uncoupler of oxidative phosphorylation, or modified EC (ECM; group 1d), which contained mannitol in place of glucose for 48 h. ATP tissue concentrations in group 1B were significantly higher than in group 1A (7.91 +/- 1.21 vs. 1.21 +/- 0.31 micromol/g dry weight, P < 0.01) but almost equal to group 1d (7.91 +/- 1.21 vs. 7.59 +/- 0.97 micromol/g dry weight, NS). DNP (group 1C) caused a significant decrease in tissue ATP levels in group 1A (0.61 +/- 0.07 vs. 7.91 +/- 1.21 micromol/g dry weight, P < 0.01). Second, pancreases subjected to 60 min of warm ischemia were preserved by simple cold storage with EC (group 2A) or the two-layer method using EC (group 2B) or EC with adenosine (group 2C) for 24 h. ATP tissue levels in groups 2A and 2B after preservation were 1.40 +/- 0.46 and 1.56 +/- 0.40 micromol/g dry weight and graft survival rates were 0/5 (0%) and 0/3 (0%), respectively. However, tissue ATP levels in group 2C after preservation were significantly higher compared with the value before preservation (7.23 +/- 2.17 vs. 1.90 +/- 0.53/g dry weight, P < 0.01) and graft survival rate was 4/5, 80%. Other nucleosides, hypoxanthine, inosine, and adenine did not substitute for adenosine. In addition, studies with [2-3 H] adenosine demonstrated that almost all of the adenosine was converted to adenine nucleotides. This study clearly demonstrated that fresh grafts synthesize ATP mainly via mitochondrial oxidative phosphorylation using endogenous substrates. However, after significant warm ischemia, pancreases produce ATP mainly via direct phosphorylation of exogenous adenosine during preservation by the two-layer method.

2,4-Dinitrophenol↗
PubMed1994

Post-transfusion chronic hepatitis C in children.

Two hundred and twenty-six patients who received blood products for open-heart surgery in childhood were screened by a second-generation enzyme-linked immunosorbent assay and with surrogate markers for hepatitis C virus (HCV) infection, such as alanine aminotransferase (ALT). Twenty-two (14%) of the 161 recipients who received blood products before 1989 and none of the subjects who had received blood products after 1990 (the year that the blood bank began to screen for HCV antibody) were HCV seropositive. Virologic and histologic studies showed that 10 (45%) of 24 seropositive patients had persistent hepatitis C virus infection, many with ongoing hepatitis. The remaining 12 seropositive patients with absent HCV RNA had normal ALT levels, indicating resolved hepatitis C infection. Enrolment in screening is important to detect chronic hepatitis C in children who received blood products prior to screening of blood donors for HCV antibody.

Acute Disease↗
PubMed1994

Importance of recall and follow-up screening for chronic hepatitis C in children receiving blood products prior to 1990 in Japan.

The objective was to detect chronic hepatitis C virus infection in recipients of blood products using retrospective analysis by recall and enrollment of recipients. 226 patients who received blood products for open heart surgery from January 1983 to June 1992 were examined for HCV antibody by using a second generation assay and liver function test. 22 (14%) of the 161 patients who received blood products before November 1989 had detectable HCV antibody, but none of the 65 recipients receiving blood products after 1990, the year the Japanese blood bank began to screen for HCV-antibody. Abnormal alanine aminotransferase (ALT) levels, more than 25 iu/L, during the chronic phase of HCV infection was recognized in nine of 22 (41%) seropositive patients. The liver function test and second generation HCV antibody in the serum are effective markers to screen for chronic hepatitis C in blood product recipients transfused before 1990.

Adolescent↗
PubMed1994

Atrial natriuretic factor and isosorbide dinitrate modulate the gating of ATP-sensitive K+ channels in cultured vascular smooth muscle cells.

The effects of atrial natriuretic factor (ANF) and isosorbide dinitrate (ISDN), activators of particulate and soluble guanylate cyclase, respectively, on K+ currents were investigated in patch-clamp recordings of smooth muscle cells cultured from rat thoracic aorta. In the cell-attached patch configuration, ANF enhanced Ca(2+)-activated K+ (KCa) channel activities as reported previously. When KCa channels were blocked with 1 mmol/L tetraethylammonium or 10(-7) mol/L charybdotoxin, ANF and ISDN applied to the bathing solution activated ATP-sensitive K+ (KATP) channels without altering channel conductance. Pretreatment with methylene blue, a guanylate cyclase inhibitor, abolished the effects of ISDN on KATP channels, whereas 8-bromo-cGMP activated these channels, suggesting that the effects of ISDN on KATP channels were mediated by cGMP. Our results suggest that vasorelaxant agents that increase intracellular cGMP concentrations modulate the gating of two major potassium channels, ATP sensitive and Ca2+ activated, that might play an important role in controlling vascular tone by changing the membrane potential.

Adenosine Triphosphate↗
PubMed1994

Molecular analysis of abnormal pyruvate dehydrogenase in a patient with thiamine-responsive congenital lactic acidemia.

A patient who responded to thiamine therapy with reduction of lactate in the blood and cerebrospinal fluid and clinical improvement was studied. Cultured lymphoblastoid cells of this patient were found to show reduced activities of pyruvate dehydrogenase complex (PDHC) and pyruvate dehydrogenase, decreased affinity of PDHC for thiamine pyrophosphate, and defective activation of PDHC by pyruvate dehydrogenase phosphatase. PDHC deficiency in fibroblasts and biopsied muscle of this patient was also due to the decreased affinity of PDHC for thiamine pyrophosphate. A mutation in the E1 alpha subunit containing the thiamine binding site and serine phosphorylation site regulating the activation/inactivation of PDHC was characterized by the polymerase chain reaction and DNA sequencing. A single A-->G transition was identified at position 131, resulting in the substitution of Arg-44 for His-44. This mutation must be a de novo mutation because it was not found in either parent's genomic DNA. In this study, we have obtained the first evidence at the molecular level for a mutation of thiamine-responsive PDHC deficiency.

Acidosis, Lactic↗
PubMed1994

In situ demonstration of the HTLV-I genome in the spinal cord of a patient with HTLV-I-associated myelopathy.

Using polymerase chain reaction (PCR) and in situ hybridization, we investigated the HTLV-I genome in the CNS of an HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patient with a 20-year disease duration. Neuropathologically, there was severe white matter degeneration throughout the spinal cord, but lymphocytic infiltrates were not evident in any lesion. PCR amplification of the pX region of HTLV-I DNA detected its sequence in the spinal cord and all extra-CNS tissue samples. In situ hybridization using probes complementary to the pX and gag regions detected the HTLV-I genome in the cytoplasm and nucleus of cells in the thoracic cord. The findings indicate a direct involvement of HTLV-I in the neurodegeneration of HAM/TSP.

Aged↗