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Biomedical subjects

Y Kuroda

Publications and source records attributed to Y Kuroda.

At least 433 records · Page 24Linked to original sources
PubMed1996

Recurrent demyelinating transverse myelitis in a high titer HBs-antigen carrier.

A 46-year-old man who was an extremely high titer hepatitis B surface (HBs)-antigen carrier had three attacks of acute demyelinating transverse myelitis associated with signs of meningeal irritation. Each episode showed good response to corticosteroid therapy. The cerebrospinal fluid was characterized by elevated levels of myelin basic protein (MBP) and predominating CD4+CD29+ helper-inducer T cells during the acute stages, and also by persistently positive HBs antigen. There were neither autoantibodies nor evidence of vasculitis. However, circulating immune complexes composed of HBs antigen disappeared after treatment, indicating that immunity to hepatitis B virus played a role in the demyelinative lesion formation in the central nervous system (CNS). In light of the animal studies demonstrating autoimmunity triggered by molecular mimicry between MBP and hepatitis B virus antigens, this patient may serve as a rare example of CNS demyelination in humans with the same autoimmune etiology.

Autoantigens↗
PubMed1996

The long-term suppressive effect of prior activation of synaptic inputs by low-frequency stimulation on induction of long-term potentiation in CA1 neurons of guinea pig hippocampal slices.

We have investigated the effects of prior activation of afferent inputs by a train of low-frequency stimulation (LFS) on the induction of long-term potentiation (LTP) induced by high-frequency stimulation (tetanus, 100 Hz, 100 pulses) in CA1 neurons of guinea pig hippocampal slices. The parameters of the LFS were altered systematically: the frequency (1 or 5 Hz); the number of pulses (80, 200 or 1000); and the time lag from the LFS to the tetanus (20, 60 or 100 min). Conditioning effects of the LFS on the induction of LTP were evaluated in terms of the slope of the field excitatory postsynaptic potential (S-EPSP) and the amplitude of the population spike (A-PS). LTP could reliably be induced by 100 Hz tetanic stimulation delivered to a naive slice. In contrast, the attempt to induce LTP 60 min after LFS of 200 or 1000 pulses at 1 Hz resulted only in short-term potentiation while the LFS itself produced no significant change in the responses. The suppressive effect on LTP was significantly reduced for 1 Hz LFS with a smaller number of pulses (80 pulses), or a shorter (20 min) or longer (100 min) time lag from the LFS to the tetanus, or with LFS at a higher frequency (5 Hz). When the LFS of 1000 pulses at 1 Hz was delivered in the presence of the N-methyl-D-aspartate (NMDA) receptor antagonist AP5 (D,L-4-amino-5-phosphonovalerate, 50 microM), which was washed out after the end of the LFS, the tetanus given 60 min after application of the LFS produced stable LTP, indicating the involvement of NMDA receptor/channels in the mechanisms of this particular form of synaptic plasticity-long-term suppression of LTP.

2-Amino-5-phosphonovalerate↗
PubMed1996

[Defects of pyruvate metabolism in cultured lymphoblastoid cells of 20 patients with Leigh syndrome].

Lymphoblastoid cells are useful materials for the diagnosis and basic studies of many human genetic disorders. To elucidate the etiology of Leigh syndrome, biochemical analyses and mitochondrial DNA analyses were performed on cultured lymphoblastoid cells from 20 patients with the clinical characteristics of this disorder. In 9 of 20 cases, we were able to define the following defects. Eight patients had biochemical defects, including 3 with pyruvate dehydrogenase complex (PDHC), 3 with cytochrome c oxidase (complex IV), and 2 with NADH-cytochrome c reductase (complex I) deficiencies. Two of 3 patients with PDHC deficiency were diagnosed with thiamine-responsive PDHC deficiency. One patient had a point mutation (T-->G) of mitochondrial DNA at nucleotide position 8993. These results indicate that the underlying defects in Leigh syndrome are heterogeneous and cultured lymphoblastoid cells are very useful materials for diagnosis of the etiology of Leigh syndrome.

Biomarkers↗
PubMed1996

[Improvement of ophthalmoplegia by 5-hydroxytryptophan in two cases of progressive supranuclear palsy].

We report two patients with clinically diagnosed progressive supranuclear palsy (PSP): a 69-year-old man and a 73-year-old woman. Both patients showed supranuclear ophthalmoplegia, postural instability, pseudobulbar palsy, and Parkinsonism. In the first patient, we administered L-dopa/carbidopa (300 mg/30 mg/ day), which moderately improved gait disturbance, but exerted no beneficial effects on gaze palsy. Then, we administered amitriptyline, bromocriptine, pergolide, l-threo-DOPS or 5-hydroxytryptophan (5-HTP) in addition to L-dopa/carbidopa. The second patient was treated by the monotherapy of L-dopa/carbidopa, amitriptyline, l-threo-DOPS or 5-HTP. We interposed two to three weeks between administration of each drug. In both patients, amitriptyline (75 mg/day) markedly improved both gait disturbance and horizontal gaze palsy. 5-HTP (600 mg/day) also improved horizontal gaze palsy, but failed to alleviate gait disturbance. The results suggest the involvement of impaired serotonergic system in ophthalmoplegia of PSP.

5-Hydroxytryptophan↗
PubMed1996

The effect of preservation temperature and period on resuscitation of the ischemically damaged canine pancreas during preservation by the two-layer (University of Wisconsin solution/perfluorochemical) method.

We have shown that 24 to 48 hour-preservation by the two-layer (University of Wisconsin solution (UW)/perfluorochemical (PFC)) method at 4 degrees C resuscitates a canine pancreas subjected to 90 min of warm ischemia. However, it is necessary to shorten preservation period for resuscitation of the ischemically damaged pancreas in a clinical simultaneous pancreas-kidney transplantation. The purpose of this study was to clarify the effect of preservation temperature and period on the resuscitation of the ischemically damaged pancreas during preservation by the two-layer method. First of all, we examined the possibility of resuscitation of the ischemically damaged pancreas during short-term preservation by the two-layer method. After 90 minutes of warm ischemia, canine pancreases were preserved by the two-layer method at 4, 20, or 37 degrees C. In control group, the pancreas graft was autotransplanted without preservation. Graft viability was judged by graft survival after autotransplantation. Pancreas grafts subjected to 90 min of warm ischemia were not viable (0/5). At 4 degrees C, 5 to 12 hr-preservation did not resuscitate the grafts (0/3 and 0/3 respectively). At 20 degrees C, 3 and 5 hr-preservation resuscitated the grafts (3/5 and 5/5 respectively), although 1 and 8 hr-preservation were not successful (0/3 and 0/3 respectively). At 37 degrees C, all the grafts were not resuscitated irrespective of preservation period. It was clear that the ischemically damaged pancreas was resuscitated during shot-term preservation by the two-layer method only at 20 degrees C. Secondly, we measured tissue adenine nucleotide levels by high performance liquid chromatography and pancreatic tissue perfusions using H2 clearance technique on reperfusion and examined the viability of vascular endothelium by nuclear trypan blue staining to make clear the necessary conditions for resuscitation of the ischemically damaged pancreas at 20 degrees C. ATP tissue levels in one hr-preserved grafts were 2.55 +/- 0.38 mumol/g dry weight and were significantly lower compared with the levels in 5 and 8 hr-preserved grafts, 9.40 +/- 2.09 (P < 0.01) and 7.37 +/- 1.06 mumol/g dry weight (P < 0.01) respectively. On the other hand, nuclear trypan blue uptakes of endothelial cells in 8 hr-preserved grafts were 37.6 +/- 11.6% and were significantly higher than 1 hr- and 5 hr-preserved grafts 5.6 +/- 4.5 (P < 0.01) and 5.0 +/- 3.0% (P < 0.01) respectively. As a consequence, pancreatic tissue perfusions in 8 hr-preserved grafts, 31.0 +/- 3.5 ml/min/g, were significantly lower than 1 hr- and 5 hr-preserved graft 72.0 +/- 11.6 (P < 0.01), 63.9 +/- 13.3 ml/min/g (P < 0.01) respectively. However, thromboxane A2 synthesis inhibitor (OKY046 0.1 mM/L) decreased the percentage of trypan blue uptake (8.2 +/- 3.6%) without interfering ATP synthesis (8.44 +/- 0.92 mumol/g dry weight) in 8 hr-preserved pancreas and tissue perfusions after reperfusion were dramatically improved (99.6 +/- 11.8 ml/min/g). As a result the ischemically damaged pancreas was resuscitated (4/5, 80%). It was suggested that 1 hr-preservation was not enough to synthesize ATP, which was essential to repair damaged cells, although vascular endothelial cells were maintained. Eight hr-preservation incurs endothelial cell damage although ATP tissue levels were maintained and consequently microcirculation was disturbed at reperfusion but OKY046 protects endothelial cells against preservation/reperfusion injury. As a consequence, the ischemically damaged pancreas was resuscitated. We conclude that short-term (3 to 8 hr) preservation at 20 degrees C by the two-layer method with OKY046 accelerates ATP synthesis, which is essential for repairing damaged cells and protects microvascular endothelial cells. This makes it possible to resuscitate the canine pancreas graft subjected to 90 min warm ischemia. This method holds promise for pancreas-kidney transplantation from cardiac arrest donors.

Animals↗
PubMed1996

Adenine nucleotide metabolism of canine pancreas graft preserved by the two-layer (euro-collins' solution/perfluorochemical) method after reperfusion.

We have demonstrated that oxygenation of a pancreas during preservation by the two-layer method leads continued ATP production to maintain cellular integrity and produces an extended period of preserved pancreatic viability. In this study, we examined whether the pancreas grafts preserved by the two-layer method maintained adenine nucleotides pool as substrates for ATP synthesis before reperfusion and had the ability to synthesize ATP promptly and to recover energy charge potential (ECP) of the pancreas graft on reperfusion. After preservation by the two-layer cold storage method using EC for 48 hrs (group 1, n = 5), or simple cold storage in EC for 48 hrs (group 2, n = 5), canine pancreas grafts were autotransplanted. In control (group 3, n = 5), canine pancreas grafts were autotransplanted without preservation. Tissue adenine nucleotides concentrations were measured using high performance liquid chromatography (HPLC) before and after preservation, before reperfusion and after 1 hr- and 2 hr-reperfusion. Graft survival rates were 5/5, 0/5, and 5/5, in groups 1, 2 and 3, respectively. Total adenine nucleotides before reperfusion in group 1 was almost same levels as group 2 (7.41 +/- 1.47 vs 6.64 +/- 2.23 mumol/g dry weight, N.S.). Furthermore, ATP tissue levels in group 1 before reperfusion was 2.90 +/- 0.51 mumol/g dry weight and almost same levels as group 2 (2.03 +/- 0.68 mumol/g dry weight, N.S.). However, tissue ATP levels in group 1 after 2 hrs of reperfusion (6.71 +/- 1.19 mumol/g dry weight) were significantly higher than group 2 (4.51 +/- 0.51 mumol/g dry weight, P < 0.05), and almost same levels as control (group 3) (6.32 +/- 1.62 mumol/g dry weight, N.S.). In addition, ECP in group 1 and 3 (0.90 +/- 0.03 and 0.83 +/- 0.09, respectively) after 2 hr-reperfusion, were significantly higher than the value in group 2 (0.73 +/- 0.09, P < 0.01 and P < 0.05, respectively). It was clear that recovery of ATP on reperfusion was not depend on the residual nucleotides pool before reperfusion but the ability of the pancreas graft to recover tissue ATP levels and energy charge potential after reperfusion. We conclude that oxygenation of the pancreas graft during preservation by the two-layer method allows for ATP synthesis which is essential in maintaining cellular integrity and leads to maintain the graft's ability to recover ATP levels and energy charge potential promptly after reperfusion. Consequently the pancreas graft survives.

Adenine Nucleotides↗
PubMed1996

[Therapy with azithromycin in pediatric infections].

Azithromycin (AZM) was orally administered to 12 pediatric patients with the following bacterial infections: pharyngitis in four cases, tonsillitis in one, pharyngo-bronchitis in two, and mycoplasmal pneumonia in five. In eleven of the twelve cases (91.7%) was the drug found effective. Neither abnormal clinical findings nor abnormal laboratory test results changes were observed. Eleven of the twelve pediatric patients claimed that the formulation of the drug is easy to take. The above results suggest that AZM is a useful antibiotic drug in the treatment of pediatric patients with bacterial infections.

Anti-Bacterial Agents↗
PubMed1996

Interleukin-2 activated lymphocytes show improved sensitivity for class 1 HLA typing.

The use of phytohemagglutinin (PHA)/interleukin-2 (IL-2) activated lymphocytes for HLA typing and the comparison with those of fresh peripheral blood lymphocytes are described. For detecting class 1 HLA antigens, PHA/IL-2 activated lymphocytes showed higher sensitivity than fresh lymphocytes of the peripheral blood in serological microcytotoxicity testing method. Their reaction specificity for the panel of alloantisera for class 1 HLA antigens was the same. On the contrary, for detecting class 2 HLA antigens, PHA/IL-2 activated lymphocytes showed lower sensitivity than those with fresh B-cells. For class 2 HLA typing, the typing with DNA methods showed the best results. Thus, we conclude that a combination of a serological typing method using PHA/IL-2 activated lymphocytes for class 1 HLA antigens with a DNA method for typing class 2 HLA antigens currently offers the best approach for the detection of HLA antigens.

Adult↗
PubMed1995

High helical propensity of the peptide fragments derived from beta-lactoglobulin, a predominantly beta-sheet protein.

It is generally assumed that peptide fragments derived from globular proteins are either unfolded, or adopt native-like secondary structures, in particular alpha-helix, which are similar to those occurring in the early stages of protein folding. Since the structured conformations of short peptides are unstable, 2,2,2-trifluoroethanol (TFE) is often used to stabilize them. To examine the folding process of beta-proteins, we synthesized three fragments of beta-lactoglobulin corresponding to two beta-strands and one helix region, and examined their conformation by circular dichroism and nuclear magnetic resonance. These regions were chosen because, according to secondary structure prediction, all three should have high helix propensities. In aqueous solution, the three peptides had only a little ordered structure, but when TFE was added, they exhibited marked helical propensities, as also observed for the whole molecule of beta-lactoglobulin. These results indicate that the intrinsic helical propensity of a peptide fragment elucidated by the addition of TFE is not necessarily related to the secondary structure in the native state. The results further suggest a case of non-hierarchical protein folding model, in which non-native structures may be involved in the early stage of folding.

Amino Acid Sequence↗
PubMed1995

TTX-resistant Ca2+ oscillation in cultured hypothalamus: similarity to the mammalian circadian pacemaker.

Dissociated cultures of rat hypothalamic cells showed spontaneous oscillations in intracellular Ca2+ with periods of 5-8 s (ultradian rhythm). Replacement of H2O by deuterium oxide in the culture medium lengthened the period of this oscillation, while tetrodotoxin did not inhibit the deuterium oxide sensitive Ca2+ oscillation. Since these characteristics resemble those of the mammalian circadian pacemaker, the ultradian Ca2+ rhythms may be involved in the circadian rhythm or have a similar rhythm generation mechanism. The gap junction inhibitor, halothane, stopped this oscillation. Gap junctions may be necessary in order to generate rhythmic oscillations.

Animals↗
PubMed1995

Evidence that portal vein decompression improves survival of canine quarter orthotopic liver transplantation.

The minimum graft volume still remains unclear in reduced-size liver transplantation (RLT). This study reports the improved survival of canine RLT using a quarter graft with the aid of a portahepatic vein shunt (PHVS). In beagles, the donor liver was reduced to the right lateral and caudate lobes (quarter graft) with or without provision of PHVS, and transplanted orthotopically in the recipient. The PHVS was established by an end-to-end anastomosis of the portal vein branch and the hepatic vein in the resected left lateral lobe. Liver chemistries including arterial blood ketone body ratio (AKBR) were serially measured during and after surgery. All seven animals with PHVS survived more than 3 days (mean +/- SD; 5.3 +/- 1.7 days), whereas all six without PHVS died within 3 days (1.8 +/- 0.8 days, P < 0.01). Portal vein pressures immediately after recirculation in animals with and without PHVS were 8.5 +/- 1.2 mmHg and 16.9 +/- 3.1 mmHg, respectively (P < 0.01). Regardless of the presence or absence of PHVS, AKBR dropped to a level lower than 0.7 during the anhepatic period and returned promptly to above 1.0 as early as 30 min after recirculation. Thereafter, the AKBR values in animals with PHVS remained higher than 1.0, whereas those in animals without PHVS showed a progressive decrease, showing a statistically significant difference between the two groups after 12 hr (P < 0.05). Graft function, as assessed by AKBR, was well correlated with survival and other liver chemistries. These results indicate that, in an extreme RLT, portal hypertension is a risk factor predisposing to graft failure, most likely by increasing microvascular injury after recirculation.

Animals↗
PubMed1995

Stability of alpha-helices in a molten globule state of cytochrome c by hydrogen-deuterium exchange and two-dimensional NMR spectroscopy.

To distinguish between intrinsically stable helices and those stabilized by the protein three-dimensional structure, we report the hydrogen-deuterium exchange (H2H) rates of 29 amide protons of ferricytochrome c in a molten globule state (at 35 degrees C, pH 2.0 with 0.5 M KCl), monitored by 2D-NMR. The results of the H2H-exchange experiments have been analyzed to calculate the protection factors. The helices were not uniformly stable and amide protons of residues belonging to the N and C-terminal helices had high protection factors. The protection factors of amide protons involved in the 50's helix were low, and could not be determined quantitatively. In the 60's helix we found two amide protons with protection factors comparable to those of the N and C-terminal helices. These results, compared with previously reported intrinsic helicities of peptide fragments, indicate that the relative helicities of isolated fragments are not directly reflected in the stability of the helices in the molten globule state, even though this state has no rigid tertiary structure. This suggests that loose interactions between helices are present in the molten globule state of cytochrome c, and that they are essential for keeping the helicity of the helical segments. The loose tertiary interactions discussed here differ from the usual tertiary interaction found in the native state in that the specific interdigitization between side-chains is absent.

Amino Acid Sequence↗
PubMed1995

Heart preservation using a cavitary two-layer (University of Wisconsin solution/perfluorochemical) cold storage method.

To reduce cold ischemic injury of the heart by supplying sufficient oxygen to the heart during preservation, we have developed a new cavitary, two-layer (University of Wisconsin solution/perfluorochemical) cold storage method. The oxygenation of the heart during preservation by this method allows ATP production within the graft and makes it possible to extend preservation time up to 48 hr in the heterotopic rat heart transplant model.

Adenosine↗
PubMed1995

Extracellular phosphorylation of membrane protein modifies theta burst-induced long-term potentiation in CA1 neurons of guinea-pig hippocampal slices.

The involvement of ecto-protein kinase activity in activity-dependent long-term potentiation (LTP) was studied in CA1 neurons of guinea-pig hippocampal slices. Application of 5 microM K-252b, an ecto-protein kinase inhibitor, blocked LTP induced by a theta-burst stimulation (3 bursts composed of 5 pulses at 100 Hz with inter-burst intervals of 200 ms). On the other hand, under 10 microM RK682, an ecto-phosphatase inhibitor, a robust LTP was induced by a weak theta-burst stimulation (3 bursts composed of 3 pulses) which was just at the threshold for the induction of LTP in the control perfusate. These findings suggest that ATP released from presynaptic terminals during the burst stimulation plays an important role in the induction of LTP through phosphorylation of extracellular domains of synaptic membrane proteins, as the substrate for ecto-protein kinase.

Animals↗
PubMed1995

The mechanism of ATP-induced long-term potentiation involves extracellular phosphorylation of membrane proteins in guinea-pig hippocampal CA1 neurons.

The mechanism of ATP-induced long-term potentiation was studied pharmacologically using guinea-pig hippocampal slices. Application of 1-10 microM ATP for 10 min transiently depressed and then slowly augmented the synaptic transmission in CA1 neurons leading to long-term potentiation (LTP). This ATP-induced LTP was blocked by the addition of K-252b, an ecto-protein kinase inhibitor, but was enhanced by the addition of RK682, an ecto-phosphatase inhibitor, both of which do not permeate the cell membrane. These results suggest that ATP applied to the perfusate provides enough substrate for ecto-protein kinase to induce LTP through phosphorylation of extracellular domains of membrane proteins in CA1 neurons.

Adenosine Triphosphate↗
PubMed1995

Fibrin glue sealing for the prevention of pancreatic fistulas following distal pancreatectomy.

OBJECTIVE: To evaluate the use of fibrin glue sealing of the pancreatic stump for the prevention of postoperative pancreatic fistulas. DESIGN: A prospective, randomized clinical trial. PATIENTS AND METHODS: Fibrin glue is a biologic adhesive consisting of highly concentrated human fibrinogen, thrombin, and factor VIII. Twenty-six of 56 patients who underwent distal pancreatectomy for gastric cancer or pancreatic disease were randomly assigned to the fibrin glue group. Fibrin glue was applied to the suture line of the pancreatic stump with the ligated main pancreatic duct. Pancreatic fistula was defined as a pancreatic fluid discharge for over 7 post-operative days diagnosed by local findings, with amylase concentration in the discharge fluid more than three times the serum amylase concentration, a level low enough that even a small pancreatic leakage could be diagnosed. RESULTS: The overall incidence of pancreatic fistula was 28.6%. Postoperative pancreatic fistulas occurred in four patients (15.4%) in the fibrin glue group and 12 (40.0%) in the control group (P = .04). The lower pancreatic fistula rate was seen in the fibrin glue group also when analyzing patients with gastric cancer or pancreatic disease only, although there was no statistically significant difference. CONCLUSIONS: Intraoperative use of fibrin glue following distal pancreatectomy could prevent pancreatic fistula formation. This method was feasible, safe, and reliable and will complement other prophylactic methods.

Adult↗