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Biomedical subjects

Y Kuroda

Publications and source records attributed to Y Kuroda.

At least 631 records · Page 35Linked to original sources
PubMed1993

Chemoembolotherapy for recurrent hepatocellular carcinoma in the residual liver after hepatectomy.

The efficacy of transcatheter arterial chemoembolization using Lipiodol (TACE) to treat recurrent hepatocellular carcinoma (r-HCC) in the residual liver after radical hepatic resection was evaluated. During the last 8 years, TACE was performed in 68 patients with r-HCC for an aggregate total of 150 times. Of the 68 patients, 4 had a massive type r-HCC with tumor thrombus in the main portal vein (PVTT) at the time of the first TACE. Among the remaining 64 patients without PVTT, multiple r-HCCs were revealed in 46, and a single r-HCC in 18 by angiography and/or follow-up CT scans after the initial TACE. In 26 of the 68 patients (38.2%), at least one or more r-HCCs were fed not only by the hepatic arteries, but also by the extrahepatic collateral arteries, such as branches of the right inferior phrenic artery. The cumulative survival rates of these patients after hepatectomy and after the initial TACE for r-HCC were 98.6% and 87.1% for one year, 89.7% and 62.9% for 2 years, 74.0% and 34.3% for 3 years, 53.1% and 20.0% for 4 years and 40.3% and 0% for 5 years (mean survival duration: 1,647 days and 947 days), respectively. These results indicate that repeat TACE against r-HCC can help obtain long-term survival in patients with r-HCC. However, during TACE, we must give consideration to the newly developed collateral feeding artery to the r-HCC.

Adult↗
PubMed1993

Mechanism of the discrepant effect of a combination of methotrexate plus dipyridamole on human hematologic cell lines.

Mechanisms of the discrepant effect of methotrexate and dipyridamole on human hematologic cultured cell lines were investigated by analyzing intracellular methotrexate levels and thymidine incorporation through the salvage pathway, since the combination of methotrexate and dipyridamole has different effects according to cell type: additive effects on ML-1 and THP-1 (myelo-monocytoid cells); reduced effects on MOLT-3, SKW-3, P32/ish and BL-TH (lymphoid cells). Dipyridamole reduced the toxicity of methotrexate by diminishing intracellular methotrexate levels in MOLT-3 and BL-TH (lymphoid cells), in which the reduction of intracellular methotrexate affected more than just the blocking of the salvage pathway required for growth by dipyridamole. On the other hand, dipyridamole enhanced the toxicity of the combination by blocking the salvage pathway in an ML-1 (myelo-monocytoid cell) and in a methotrexate-resistant subline of BL-TH/MTX (lymphoid cell), in which the salvage pathways were considered activated. Dipyridamole could prove to be a useful drug for reversing the drug resistance caused by the activation of the salvage pathway.

Adult↗
PubMed1993

Measurement of serum levels of macrophage colony-stimulating factor (M-CSF) in patients with uremia.

Serum levels of monokines, including macrophage colony-stimulating factor (M-CSF), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha) and IL-1 beta (IL-1 beta), were measured in patients with chronic renal failure in an attempt to clarify the kinetics of these cytokines in the course of renal anemia. M-CSF was the only monokine detectable in the serum from all patients as well as healthy donors, making this cytokine feasible and reliable for serial evaluations. On all occasions, the level of M-CSF in uremic patients was significantly higher than that in healthy donors (29.4 +/- 12.3 vs. 5.5 +/- 1.1 ng/mL). In patients undergoing hemodialysis, the serum level of M-CSF was greater than that in patients undergoing continuous ambulatory peritoneal dialysis or in uremic patients without dialysis therapy. No difference was observed, however, in the levels of IL-1 alpha, IL-1 beta and TNF-alpha levels in these groups. Patients with severe anemia were subsequently treated with 60 to 80 U/kg per week of human recombinant erythropoietin (rhEpo) for 3 months. After this replacement therapy, hemoglobin levels increased with a variable change ranging from 0 to 3.5 g/dL. The pretherapy M-CSF level, however, was found to predict statistically the response to the therapy (p < 0.05). Patients with a lower pretherapy value responded better to rhEpo therapy; those with a higher level showed a minor degree of response. From these results, we postulate that the elevated M-CSF serum level in uremic patients is in part a consequence of the dialysis procedure and that rhEpo therapy is more effective in patients who are under sophisticated dialysis protocol and have a lower M-CSF level.

Erythropoietin↗
PubMed1993

[Comparison of hepatic tissue extraction rates of cytotoxic anticancer drugs during hepatic arterial chemotherapy--evaluation using direct hemoperfusion under hepatic venous isolation].

Hepatic extraction rates (ER) of anticancer drugs during hepatic arterial infusion were investigated with the aid of direct hemoperfusion (DHP) under hepatic venous isolation (HVI). Using mongrel dogs (n = 6), adriamycin (ADR), mitomycin C (MMC) and cisplatin (CDDP) were simultaneously administered to the hepatic artery at each dosage of 1 mg/kg in 10 minutes under HVI.DHP. Hepatic venous flow and plasma concentrations of each drug at the carotid artery, the inlet and outlet sides of DHP were periodically determined during HVI.DHP. Based on these data, drug adsorption and removal rates were estimated. In addition, hepatic tissue uptakes of each drug were calculated from the amounts of drug administered and leaked in the hepatic effluent. Subsequently, the percentage of tissue uptake of each drug to the amount of drug administered was determined as ER of each drug. Drug adsorption rates during the first 10 minutes after infusion showed no significant difference among three drugs. Drug removal rate of CDDP tended to be higher than those of other two drugs. ER of CDDP (54.8 +/- 18.3%) were significantly lower (p < 0.01) as compared to ADR (84.4 +/- 16.2%) and MMC (83.1 +/- 15.7%). These results indicate that ER of each drug should be taken into consideration to determine appropriate drug for hepatic arterial chemotherapy.

Adsorption↗
PubMed1993

[Signal-averaged electrocardiogram in right bundle branch block patients after surgical repair for congenital heart disease].

Right bundle branch block (RBBB) type was investigated using signal-averaged electrocardiogram (SAECG) in 35 RBBB patients after surgical repair of ventricular septal defect and tetralogy of Fallot. The type of RBBB was first identified by body surface mapping; 12 patients had proximal RBBB, and 23 had peripheral RBBB. The control group consisted of 20 healthy volunteers. The following three findings were seen in most patients with proximal RBBB, and were useful for determining the type of RBBB; a filtered QRS duration equal to or longer than 160 msec, a fragmented signal number equal to or greater than 10 and the whole type of filtered QRS pattern. The sensitivity and specificity of SAECG for proximal RBBB were shown to be high. In conclusion, SAECG was found to be useful for non-invasive determination of RBBB types.

Adolescent↗
PubMed1992

Functional and morphological changes in cultured neurons of rat cerebral cortex induced by long-term application of aluminum.

Aluminum is an environmental neurotoxin and a suspected risk factor for Alzheimer's disease. The neurotoxicity of aluminum on cultured neurons of rat cerebral cortex was investigated using an assay system for synapse formation and immunohistochemistry. The frequency of spontaneous oscillations of intracellular Ca2+, which is correlated to the number of synapses, was decreased after exposure to 100 microM of aluminum chloride for 22 days. Long-term application of aluminum (48 days) caused aggregation of cell bodies and fasciculation of processes. Processes and cell bodies were strongly stained by antibody to tau protein, which is one of the main components of Alzheimer's neurofibrillary tangles. It is suggested that the characteristics of the degeneration of cultured neurons induced by aluminum show some similarities to the pathology observed in brains with Alzheimer's disease.

Aluminum↗
PubMed1992

Adenosine A2 receptor antagonist facilitates the reversal of long-term potentiation (depotentiation) of evoked postsynaptic potentials but inhibits that of population spikes in hippocampal CA1 neurons.

The effects of the adenosine A2 receptor antagonist CP-66713 on the reversal of long-term potentiation (LTP) were studied in CA1 neurons of guinea pig hippocampal slices. Reduction of LTP (depotentiation, DP) was effected by delivering a train of low-frequency afferent stimuli (depotentiation stimulation, DPS) which was given 20 min after tetanus (100 Hz, 100 pulses). DPS (1 Hz, 1000 pulses) was applied during perfusion of CP-66713 (10 microM). In the presence of CP-66713, DPS reduced the potentiated component of the slope of the field EPSP (S-EPSP) and the amplitude of the population spike (A-PS) by 101.7% and 19.1% of the potentiated amount, respectively (mean, n = 8). The reduction of LTP of the S-EPSP was significantly larger than the control (68.5% (mean, n = 6)) while that of the A-PS was significantly smaller than the control (80.1% (mean, n = 6)). Based on these results, we conclude that the inhibition of DP in the EPSP, the facilitation of DP in the PS, and the consequent attenuation in the EPSP-PS relationship follow from activation of adenosine A2 receptors.

Animals↗
PubMed1992

[MR imaging of bone metastasis].

One hundred and three patients with known malignancy and suspected bone metastasis underwent magnetic resonance imaging. In 93%, the metastatic lesions, detected both on plain films and radionuclide bone scans, showed decreased signal intensity on T1-weighted images and increased signal intensity on T2-weighted images. All lesions, except one lesion showing much blastic change on plain films, showed contrast enhancement with Gd-DTPA administration. Although further investigation is needed, a correlation between the type of primary malignancy and the signal intensity of the metastatic lesion is suggested. Among 312 metastatic lesions detected by MR imaging, 272 lesions (87%) and 134 lesions (40%) were also detected by radionuclide bone scans and plain films, respectively. In five cases, MR imaging clearly revealed the lesion compressing the spinal cord, which helped us formulate a therapeutic plan. We conclude that MR imaging is the most sensitive examination for detecting bone metastasis and is necessary for planning treatment.

Bone Neoplasms↗
PubMed1992

Decrease of pyruvate dehydrogenase phosphatase activity in patients with congenital lactic acidemia.

We developed an assay method for pyruvate dehydrogenase phosphatase activity using [1-14C]pyruvate and measured pyruvate dehydrogenase phosphatase activity in cultured skin fibroblasts from three patients with congenital lactic acidemia due to a defect in activation of the pyruvate dehydrogenase complex. The enzyme activity of their fibroblasts was significantly reduced to 50.7%, 64.6% and 63.1% of that of control fibroblasts. These observations suggest that the defect in activation of the pyruvate dehydrogenase complex in these patients might be due to a reduction in pyruvate dehydrogenase phosphatase activity.

Acidosis, Lactic↗
PubMed1992

Thermodynamic characterization of cytochrome c at low pH. Observation of the molten globule state and of the cold denaturation process.

Several reports have pointed out the existence of intermediate states (both kinetic and equilibrium intermediate) between the native and the denatured states. The molten globule state, a compact intermediate state in which the secondary structure is formed but the tertiary structure fluctuates considerably, is currently being studied intensively because of its possible implication in the folding process of several proteins. We have examined the thermal stability of horse cytochrome c at low pH between 2.0 and 3.2 and different potassium chloride concentrations by absorbance of the Soret band, far and near-ultraviolet circular dichroism (u.v. c.d.) and tryptophan fluorescence using a multidimensional spectrophotometer. The concentration of potassium chloride ranged from 0 M to 0.5 M. The experimental thermal denaturation curves show that: (1) the helical content of cytochrome c remains stable at higher temperature when the concentration of salt is increased; whereas (2) the extent of ordering of the tertiary structure is weakly dependent on salt concentration; and (3) for cytochrome c, the stabilization of the molten globule state is induced by the binding of anions. Other salts such as NaCl, LiCl, potassium ferricyanide (K3Fe(CN)6) and Na2SO4 may also be used to stabilize the molten globule state. The thermodynamic analysis of the denaturation curves of c.d. at 222 nm and c.d. at 282 nm shows that, whereas a two-state (native and denatured) transition is observed at low-salt concentration, the far and near-u.v. c.d. melting curves of cytochrome c do not coincide with each other at high-salt concentration, and a minimum of three different thermodynamic states (IIb, intermediate or IIc, and denatured) is necessary to achieve a sufficient analysis. The intermediate state (called IIc) is attributed to the molten globule state because of its high secondary structure content and the absence of tertiary structure. Therefore, at low pH, cytochrome c is present in at least four states (native, IIb, IIc and denatured) depending on the salt concentration and temperature. The thermodynamic parameters, i.e. the Gibbs free energy differences (delta G), the enthalpy differences (delta H), the midpoint temperatures (Tm) of the transition (IIb in equilibrium intermediate (IIc in equilibrium denatured) are determined. We also give estimates of the heat capacity differences (delta Cp) from the temperature dependence of the enthalpy differences. The enthalpy change and the heat capacity difference of the IIc in equilibrium denatured transition are non-zero. The number of charges (protons or chloride anions) released upon transitions are determined by analysing the pH and chloride anion concentration dependence of the Gibbs free energy.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Block of synapse formation between cerebral cortical neurons by a protein kinase inhibitor.

Synchronized Ca2+ transients in cultured hippocampal neurons reflect the pattern of underlying electrical activity. Here we demonstrate a similar synchronization of cerebral cortical neurons in culture, and show that this functional coupling is correlated to the appearance of morphologically identified synapses using electron microscopy. During screening of a series of drugs for inhibition of in vitro synaptogenesis, the continuous presence of a protein kinase inhibitor (K-252b) in the culture medium was found to block the synchronous firing and to decrease significantly the number of morphologically identifiable synapses. Since K-252b does not permeate the cell membrane, the results strongly suggest that phosphorylation of cell surface protein(s) by a K-252b sensitive-protein kinase is an essential process in synapse formation.

Animals↗
PubMed1992

Successful 96-hour preservation of the canine pancreas.

We tested the preservation of the pancreas for 96 h by a modified two-layer (UW solution/perfluorochemical) cold storage method (group 1) in the canine model of pancreas autotransplantation and compared this with an original two-layer (Euro-Collins' solution/perfluorochemical) cold storage method (group 2) and simple cold storage method with UW solution (group 3). A graft was considered functioning if the dog had a normal blood glucose for at least 5 days after transplantation. The functional success rates after preservation for 72 h were 100%, 100% and 80% for groups 1, 2 and 3 respectively. On the other hand, the functional success rates for groups 1, 2 and 3 after preservation for 96 h were 75%, 0% and 0% respectively. The mean K value of 96-hour preserved grafts for group 1 at 2 weeks after transplantation was 1.52 +/- 0.30 compared with 1.98 +/- 0.48 before preservation. Biopsies of grafts from group 1 showed almost normal pancreatic architecture even after preservation for 96 h. In addition, biopsies of grafts preserved for 96 h in group 1 at 4 weeks after transplantation showed almost normal endocrine tissue with mild fibrosis of the exocrine tissue. This study demonstrated the possibility of preserving the pancreas for 96 h prior to transplantation.

Animals↗
PubMed1992

The mechanism of action of the two-layer (Euro-Collins' solution/perfluorochemical) cold storage method in canine pancreas preservation.

To clarify the mechanism of action of a two-layer [Euro-Collins' solution (EC)/perfluorochemical (PFC)] cold storage method in the preservation of the pancreas, pancreatic viability and tissue concentrations of adenosine triphosphate (ATP) were examined in the canine model of pancreatic autotransplantation after preservation for 24 and 48 h by simple cold storage in EC (group 1), the two-layer, EC/PFC, method (group 2) and the two-layer, EC+2, 4 dinitrophenol (DNP)/PFC, method (group 3). DNP is an uncoupler of oxidative phosphorylation. Maintenance of normoglycemia for at least 5 days after transplantation was considered a successful preservation. After preservation for 24 h, the functional success rates of groups 1, 2 and 3 were 100% (4/4), 100% (5/5) and 80% (4/5) respectively. One of five dogs in group 3 died of a cause unrelated to the pancreas. ATP tissue concentrations in group 2 were significantly higher than in group 1 (7.47 +/- 0.47 micromol/g dry weight vs 1.41 +/- 0.53 micromol/g dry weight, P < 0.01) and ATP tissue concentrations in group 3 were significantly lower than in group 2 (1.25 +/- 0.37 micromol/g dry weight vs 7.47 +/- 0.47 micromol/g dry weight, P < 0.01). It was apparent that ATP was not an essential factor for successful 24-hour preservation of the canine pancreas in EC because all the pancreatic grafts except one of five grafts in group 3 remained viable after preservation for 24 h, regardless of ATP tissue concentrations. On the other hand, after preservation for 48 h, the functional success rates for groups 1, 2 and 3 were 0% (0/4), 100% (4/4) and 0% (0/3) respectively. ATP tissue concentrations in group 2 were significantly higher than in group 1 (7.91 +/- 1.21 micromol/g dry weight vs 1.21 +/- 0.31 micromol/g dry weight, P < 0.01) and ATP tissue concentrations in group 3 were significantly lower than in group 2 (0.61 +/- 0.07 micromol/g dry weight vs 7.91 +/- 1.21 micromol/g dry weight, P < 0.01). It was clear that preservation of the pancreas for 48 h was unsuccessful by simple cold storage in EC (group 1) and the two-layer method (group 2) made preservation for 48 h possible by increasing ATP tissue concentrations. However, DNP (group 3) inhibited the synthesis of ATP and the effectiveness of the two-layer method for 48-hour preservation of the pancreas. It was clear that maintenance of high ATP tissue concentrations during preservation was essential for the successful preservation of the canine pancreas in EC by the two-layer method for more than 48 h. We concluded that an adequate supply of oxygen to the pancreas during preservation by the two-layer method led to sufficient production of ATP to maintain cellular integrity and permitted the improvement of pancreatic preservation.

Animals↗
PubMed1992

Mutation of E1 alpha gene in a female patient with pyruvate dehydrogenase deficiency due to rapid degradation of E1 protein.

A mutation of an insertion of 4 bp in the gene for the alpha subunit of pyruvate dehydrogenase (E1 alpha) was found in a female with pyruvate dehydrogenase deficiency due to the rapid degradation of alpha and beta subunit proteins of pyruvate dehydrogenase. This mutation caused a frameshift that altered the amino acid sequence and created a premature stop codon. This 4-bp insertion has been found in an unrelated female patient with E1 alpha deficiency. It is rare that the same mutation is found in unrelated patients with this rare inborn error of metabolism. Furthermore, short deletions or duplications in the E1 alpha gene of patients with E1 alpha deficiency have been found only in exons 10 and 11. These exons may be hot spots for the mutations by the recombinational processes. This patient was heterozygous for the normal and a mutant allele. However, in most of the cultured skin fibroblasts from this patient, the mutant allele was expressed. These observations suggest that the X chromosome containing the normal allele was predominantly inactivated so that she developed lactic acidaemia and neurological abnormalities despite being heterozygous. The mutant alpha subunit protein failed to form a stable structure of pyruvate dehydrogenase, so that both alpha and beta subunit proteins were degraded rapidly.

Alleles↗
PubMed1992

Kawasaki-like disease in early course of acute monocytic leukaemia.

We report a rare occurrence of Kawasaki-like disease in an 11-year-old boy with acute monocytic leukaemia (AML). After 1 week of induction therapy with daunorubicin, etoposide, and cytosine arabinoside, the patient sequentially developed persistent fever, lymphadenopathy, conjunctival injection, exanthema, redness of the lips, and desquamation of the hands. Chest roentgenology showed cardiomegaly and an echocardiogram revealed a dilation of the left coronary artery. The patient was treated with high doses of gamma globulin and steroids. All symptoms except the coronary artery dilation improved. The symptoms did not recur on reinstatement of the original antileukaemia drugs.

Child↗