[Roles of gangliosides on synapse formation].
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Animals↗
Biomedical subjects
Y Kuroda
Publications and source records attributed to Y Kuroda.
[Multicenter cooperative study of pre- and post-operative adjuvant chemotherapy in the treatment of colorectal cancer. North Kyushu Co-operative Study Group for Cancer Chemotherapy].
The usefulness of pre- and post-operative adjuvant chemotherapy in colorectal cancer patients was studied by the North Kyushu Co-operative Study Group for Cancer Chemotherapy (21 participating institutions). Comparisons were made among group I given a tegafur suppository preoperatively+tegafur oral preparation postoperatively, group II given a tegafur suppository preoperatively+UFT oral preparation postoperatively and group III given a tegafur oral preparation postoperatively. No differences were seen in the incidence of postoperative complications depending on whether or not tegafur suppositories were administered preoperatively. There were also no differences in the symptom or incidence of side effects due to postoperative administration of tegafur or UFT. In a study of 5-FU concentration in the lymph nodes due to preoperative tegafur administration and recurrences, the concentration of 5-FU was significantly higher in the lymph nodes of cases without recurrences than in those with recurrences, and it was suggested that a relation exists between the concentration of agent and recurrences. The concentration of 5-FU in the lymph nodes of Dukes B patients was significantly higher in cases without recurrences than in those with recurrences. The non-recurrence rate (healthy rate) was better in the group given UFT postoperatively than in that administered tegafur postoperatively although the difference was not significant.
Administration, Oral↗
[Abnormalities in the signal-averaged electrocardiogram in Ebstein's anomaly].
Abnormalities in the signal-averaged electrocardiogram (SAECG) of patients with Ebstein's anomaly were studied. A SAECG was obtained in 4 patients with Ebstein's anomaly, aged 3 to 25 years. The control groups included 8 patients with atrial septal defect (ASD group), 10 with right bundle branch block (RBBB group), 8 with Wolff-Parkinson-White (WPW) syndrome (WPW group), and 40 normal subjects (Normal group). The SAECG was calculated by the vector-magnitude method using the VCM-3000. The root-mean-square during the initial 20 msec of the filtered QRS (i-RMS) was very small in 2 older patients with Ebstein's anomaly compared to the ASD group, the RBBB group and the Normal group, and was as small as that in the WPW group. This probably was affected by the delta wave associated with Ebstein's anomaly or concealed accessory pathway. The root-mean-square during the terminal 40 msec of the filtered QRS (t-RMS) was small in the patients with Ebstein's anomaly and the RBBB group. Two patients with Ebstein's anomaly had a smaller t-RMS than the RBBB group, suggesting pathological changes of an atrialized right ventricle. In conclusion, SAECG is useful for evaluating patients with Ebstein's anomaly, especially older patients.
Adolescent↗
[A case of gastric cancer with multiple liver metastases effectively treated with PMUE (CDDP, MMC, UFT, etoposide) hepatic arterial chemotherapy].
A 62-year-old male patient with progressive gastric cancer and multiple liver metastases (H3, P0, ss gamma, n4) underwent total gastrectomy (R1). After 2 years and 2 months, he was re-hospitalized with epigastric tumor caused by re-manifestation of liver metastasis as well as inappetence. Since a large focus of liver metastasis and intraportal tumor embolism was identified, a continuous intraarterial infusion tube utilizing Infuse-A-Port was inserted in the hepatic artery. After conducting 2 cycles of PMUE intra-arterial chemotherapy, the tumor size was reduced by 84% (PR); and CEA, which had been high upon rehospitalization, recovered to the normal level. After discharge, the patient has been receiving 5-FU arterial infusion as an outpatient and undergoing UFT oral chemotherapy. The efficacy has continued and he has been well for 3 years since operation. Often operations for gastric cancer accompanied with multiple liver metastasis meet with little success, and almost no case of prolonged survival has been reported. In this case, the effectiveness of PMUE arterial infusion chemotherapy was clear, the patient has been well for 3 years since operation, and is an interesting example with seemingly good prospects for long-survival.
Antineoplastic Combined Chemotherapy Protocols↗
Evaluation of the viability and energy metabolism of ischemically damaged canine pancreas during preservation by the two-layer (University of Wisconsin solution/perfluorochemical) cold storage method.
We evaluated the viability and energy metabolism of ischemically damaged pancreas during preservation by the two-layer (University of Wisconsin solution (UW)/perfluorochemical (PFC)) cold storage method. The pancreas grafts subjected to 60-120 min warm ischemia were preserved by the two-layer (UW/PFC) cold storage method for 24 hours (group 3), a simple cold storage in UW for 24 hours (group 2) or without preservation (control) (group 1). The tissue concentration of adenine nucleotides (ANs) were determined using high performance liquid chromatography (HPLC) and the viability of the pancreas graft was tested in the canine model of segmental pancreas autotransplantation. The functional success rates of pancreas grafts of groups 1, 2 and 3 after 60 min of warm ischemia were 5/5 (100%), 4/5 (80%) and 5/5 (100%). After 90 min warm ischemia, the success rates of groups 1, 2 and 3 were 0/5 (0%), 0/5 (0%) and 5/5 (100%) respectively. Only the two-layer method (group 3) was effective for functional recovery of the pancreas suffered 90 min warm ischemia. However, after more than 105 min, the result was 0/5 (0%) in group 3. In groups 1 and 2, there was no correlation between the posttransplant viability and tissue concentration of ANs and energy charge potential (ECP) at the end of preservation. However, in group 3, there was an excellent correlation between the posttransplant viability and tissue concentration of adenosine triphosphate (ATP) and total adenine nucleotides (TAN) at the end of preservation. We conclude that tissue concentration of ATP and TAN at the end of 24 hour preservation by the two-layer (UW/PFC) method will predict the posttransplant outcome of pancreas graft subjected to significant warm ischemia.
Adenine Nucleotides↗
Long-term preservation of canine pancreas by a new simple cold storage method using perfluorochemical--the two-layer cold storage method (Euro-Collins' solution/perfluorochemical).
Long term preservation of canine pancreas by a new simple cold storage method using perfluorochemical (PFC), two-layer (Euro-Collins' solution (EC)/PFC) cold storage method, was tested in the canine model of segmental pancreas autotransplantation. The functional recovery of the graft preserved by this method (group 1) was determined by daily fasting blood glucose concentration and intravenous glucose tolerance test at two weeks after autotransplantation and compared with simple cold storage with EC (group 2), cold storage in EC with simple bubbling of oxygen (group 3), and control (no preservation) (group 4). Maintenance of normoglycemia at least 5 days after transplantation was considered a success of preservation. The functional success rates after 24 hour preservation were 4/4 (100%), 4/4 (100%) and 4/5 (80%) for groups 1, 2 and 3 respectively, and the functional success rates of groups 1, 2 and 3 after 48 hour preservation were 5/6 (86%), 1/5 (20%) and 1/5 (20%) respectively. In addition the functional success rates after 72 hour preservation were 6/6 (100%), 0/6 (0%) and 0/5 (0%) for groups 1, 2, and 3 respectively. It was clear that the two-layer cold storage method had made it possible to preserve the canine pancreas for up to 72 hours although the upper limit of reliable preservation time of groups 2 and 3 was 24 hours. The mean K value of group 1 after 72 hour preservation was 1.78 +/- 0.42 compared with 2.05 +/- 0.32 of group 4 at two weeks after transplantation. Biopsies of grafts of group 2 and 3 after 72 hours preservation showed remarkable autolytic changes in exocrine and endocrine tissues. In contrast, biopsies of grafts of group 1 after 72 hour preservation showed almost normal architecture in both tissues. In addition, biopsies of 72 hour preserved grafts of group 1 at 4 weeks after autotransplantation showed almost normal pancreatic architecture with minimal fibrotic changes in the exocrine tissue. This study demonstrated the possibility of long-term preservation of the pancreas for transplantation.
Animals↗
[Serum concentration of HCFU and 5-FU after oral administration of HCFU in postoperative digestive cancer patients].
In an attempt to establish the optimum dose of HCFU, the effect of the presence of stomach on the absorption of HCFU and both the rise and maintenance of blood HCFU levels was evaluated in patients with gastric cancer (total gastrectomy group) and with colorectal cancer (non-gastrectomy group). The blood concentrations of HCFU fractions and 5-FU were determined in terms of pharmacokinetic parameters in these groups. The Tmax was significantly different between the two groups, with HCFU fraction and 5-FU levels that were significantly higher in the total gastrectomy group 30 minutes after administration. No differences were found in Cmax or AUC. There were no significant differences in Cmax or AUC among the various subgroups given different doses of HCFU (100, 150 and 200 mg) in either group, although dose-dependency was observed. Similar results were obtained in crossover tests. The 5-FU remained at an effective concentration of 0.05 microgram/ml, 4 hours after a single dose of 100 mg HCFU.
Administration, Oral↗
Adenosine (A2) antagonist inhibits induction of long-term potentiation of evoked synaptic potentials but not of the population spike in hippocampal CA1 neurons.
The effects of adenosine A2 receptor antagonist (CP-66713) on long-term potentiation were studied using guinea pig hippocampal slices in a perfusion system. Tetanic stimulation of Schaffer collateral input which was applied during perfusion of CP-66713 (10 microM), did not induce long-term potentiation but rather long-term depression of evoked synaptic potentials (field EPSP), but induced long-term potentiation of the population spike in CA1 neurons. Thus, adenosine derivatives which accumulate in the synaptic cleft during the tetanic stimulation may be involved in induction of the long-term potentiation via A2 receptors at the synapse. The clear discrimination between long-term depression of the field EPSP and long-term potentiation of the population spike suggests EPSP-spike potentiation at the postsynaptic sites.
Animals↗
Characterization of antibodies to advanced glycosylation end products on protein.
Antibodies directed against advanced glycosylation end products (AGEs) formed during a Maillard reaction have been generated and characterized. Since protein-bound AGEs recognized by the antibodies were labile to acid hydrolysis, the antibodies were further characterized by using the AGE-alpha-acetyl-L-lysine methyl ester (AGE-ALME) with a brown and fluorescent property as well as the AGE-proteins. The antibodies reacted with fluorescent compounds, rather than brown pigment compounds, in the AGE-ALME. The fluorescent compounds in the AGE-ALME were separated into four fluorescent compounds by reversed-phase thin layer chromatography (TLC). Of the fluorescent compounds tested, compound 3 (Rf = 0.63), as designated on a TLC plate, showed the highest affinity for the antibodies. In addition, the antibody recognition to the cross-linked oligomers with fluorescence in the AGE-protein was investigated by using bovine pancreatic ribonuclease A (RNase), which is known as a model protein for studying AGE-induced cross-linking. Fluorescence in the AGE-RNase existed in both of the oligomers and the monomer. The cross-linked oligomers exhibited higher affinity to the antibodies than did the monomer, which has a similar degree of fluorescent intensity. These results indicate that our antibodies against cross-linked protein-bound AGEs may serve as a useful tool to elucidate pathophysiological roles of advanced Maillard reaction in diabetic complications and aging processes.
Antibodies↗
Screening for disorders of pyruvate metabolism by measuring the ratio of the rates of lactate production and pyruvate decarboxylation in cultured skin fibroblasts.
We assayed the rates of lactate production from [1-14C]pyruvate and decarboxylation of [1-14C]pyruvate in cultured skin fibroblasts from 8 patients with disorders of pyruvate metabolism and 16 control subjects. The disorders of pyruvate metabolism could be more readily detected by measuring the ratio between the rates of lactate production and pyruvate decarboxylation by cultured skin fibroblasts than by measuring either the rate in isolation.
Acidosis, Lactic↗
Synergistic effect of recombinant interferon-gamma and interleukin-3 on the growth of immature human hematopoietic progenitors.
Purified peripheral blood hematopoietic progenitors from children in early remission from cancer respond to recombinant human interleukin-3 (IL-3), but not to granulocyte colony-stimulating factor (G-CSF). With these purified cells as a target, we studied the effect of recombinant human interferon-gamma (IFN-gamma) on progenitor growth, using both liquid-suspension limiting dilution assay (LDA) and regular methylcellulose culture of progenitors. We found that in LDA with IL-3, IFN-gamma directly stimulated the growth of blood progenitors in a dose-dependent manner with single-hit kinetics, whereas IFN-gamma suppressed the growth of G-CSF-supported progenitors obtained from bone marrow. The stimulatory effect was also observed in methylcellulose culture, but the addition of antibodies for G-CSF, granulocyte-macrophage CSF, IL-1 alpha, IL-1 beta, IL-6, or tumor necrosis factor did not result in a decrease of the colony number, supporting further the possible direct effect of IFN-gamma on progenitor growth. These results suggest that the inhibitory effect of IFN-gamma on hematopoietic progenitors is limited to those in an advanced stage of maturation. IFN-gamma may be one of the essential lymphokines upregulating the growth of human hematopoietic progenitor cells.
Blood Component Removal↗
Effectiveness of high-dose MCNU therapy and hematopoietic stem cell autografts treatment of childhood acute leukemia/lymphoma with high-risk features.
Clinical and pharmacokinetic studies were performed regarding the toxicity of methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU) with other drugs, in conjunction with a peripheral blood stem cell autograft (PBSCT), for treating 26 children with acute leukemia or lymphoma associated with high-risk features. In the early phase of the study, MCNU (300 to 500 mg/m2) was administered with cytosine arabinoside (Ara-C) (1.6 to 16 g/m2), etoposide (VP-16) (0.8 to 1.6 g/m2), cyclophosphamide (CY) (100 to 200 mg/kg), or busulfan (16 mg/kg). No acute toxicity was noticed after this high-dose therapy. The dose-limiting factor of the regimens was significant but reversible interstitial pneumonitis (IP). In a subsequent trial with an MCNU/VP-16/Ara-C/CY (MCVAC) regimen in which the dose of MCNU was reduced, the risk of IP diminished. This study is still in progress, but the clinical response has so far been encouraging. Fifteen of 26 children are alive and well in unmaintained complete remission (CR) with a median follow-up period of 11 months (range, 3 to 34 months) after transplantation. This MCNU-based regimen without total body irradiation (TBI) is especially important in children to avoid the serious sequelae of irradiation. Our results justify a broader clinical trial to evaluate the effects of the MCVAC regimen followed by PBSCT.
Adolescent↗
A simplified and rapid limiting dilution assay of T lymphocytes.
We report here the development of an alternative limiting dilution assay (LDA) of T lymphocytes (T cells). Blood mononuclear cells were first stimulated for 60 hr with PHA and then cultured in microwells in the presence of recombinant interleukin-2 without feeder cells. After 4 days of culture, wells were scored for proliferation. Clonal expansion of T cells followed the single-hit model of the Poisson distribution. The progenitor frequency (f) in the mononuclear cells and E-rosette-positive cells from normal donors were 0.082 +/- 0.025 (n = 12) and 0.236 +/- 0.029 (n = 5), respectively, but this was markedly decreased in patients who underwent marrow-ablative chemotherapy and autografts with blood hematopoietic stem cells. This LDA system should be of value in routine use for the evaluation of T cell proliferative activities.
Bone Marrow Transplantation↗
The structure of a neural specific carbohydrate epitope of horseradish peroxidase recognized by anti-horseradish peroxidase antiserum.
Antiserum raised against horseradish peroxidase (HRP) recognizes a neural specific carbohydrate antigen in Drosophila and other insects. The epitopic activity of the carbohydrate moiety of HRP recognized by anti-HRP antiserum was measured by a newly developed enzyme-linked immunosorbent assay, in which HRP glycopeptides conjugated with bovine serum albumin were coated onto the wells and then reacted with goat anti-HRP antiserum. HRP sugar moieties released by almond glycopeptidase A digestion of HRP pepsin digests were subjected to pyridylamination. Pyridylamino oligosaccharides were separated into seven fractions by reverse-phase high performance liquid chromatography. The major fraction, which comprised about 80% of the total sugars, reacted strongly with anti-HRP antiserum. The carbohydrate structure of this fraction was determined by sugar composition analysis and 600-MHz 1H NMR spectroscopy as follows: Man alpha 1----6(Man alpha 1----3)(Xyl beta 1----2)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----3)GlcNAc. Analyses of reactivity with anti-HRP antiserum of various oligosaccharide derivatives obtained from the major fraction by exoglycosidase digestion and partial acid hydrolysis indicated that alpha 1----6-linked mannose and alpha 1----3-linked fucose are predominantly involved in the epitopic structure.
Carbohydrate Sequence↗
Apparent response of subacute sclerosing panencephalitis to intrathecal interferon alpha.
An 8-year-old boy with subacute sclerosing panencephalitis (SSPE) was treated with 1.0 to 3.0 x 10(6) IU human interferon alpha (IFN) by the intrathecal route weekly or fortnightly. Pronounced improvement of clinical and electroencephalographic findings were observed in a dose-dependent manner. Our patient raises hope that IFN can induce sustained remission in patients with SSPE.
Child↗
Central sleep apnea and arterial compression of the medulla.
We report a 5-year-old with central sleep apnea associated with compression of the medulla oblongata by abnormal looping of the left vertebral artery. The magnetic resonance imaging findings raise the possibility that compression of the respiratory center by an aberrant vertebral artery might cause central sleep apnea.
Brain Diseases↗
CO2 laser-induced pain-related somatosensory evoked potentials in peripheral neuropathies: correlation between electrophysiological and histopathological findings.
Pain-related somatosensory evoked potentials (pain SEPs) following CO2 laser stimulation as well as conventional electrically stimulated SEPs (electric SEPs) were examined in 10 patients with peripheral neuropathies in whom the histopathological examination of the sural nerve was done. Results of pain SEPs showed a positive relationship with clinical impairment of pain sensation and densities of small myelinated fibers of the sural nerve. In contrast, results of electric SEPs showed a positive relationship with clinical impairment of deep and tactile sensations and with densities of large myelinated fibers of the sural nerve. Therefore, pain SEPs are considered to be generated by ascending signals mediated through nociceptive receptors and A delta fibers. The pain SEP is only one noninvasive and objective method currently available to investigate a physiological condition of the sensory pathway responsible for pain sense, and is especially useful when combined with the conventional electric SEPs.
Adolescent↗
Estimation of conduction velocity of A delta fibers in humans.
Conduction velocity of A delta fibers of the human peripheral nerves was measured by using pain-related somatosensory evoked potentials following CO2 laser stimulation. It was found to be approximately 9 m/s in the forearm as well as in the lower leg. Because conventional conduction study using electric stimulation reflects only functions of large myelinated fibers related to deep proprioceptive and tactile sensations, the present noninvasive and simple, novel method is the only laboratory examination currently available to investigate physiological functions of the small diameter fibers mediating pain-temperature sensations.
Adult↗