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Biomedical subjects

S Yoshikawa

Publications and source records attributed to S Yoshikawa.

At least 199 records · Page 11Linked to original sources
PubMed1985

Resonance Raman spectra for catalytic intermediates of cytochrome c oxidase detected with a mixed flow transient apparatus.

A novel technique was employed to collect resonance Raman spectra of an oxygenated intermediate of cytochrome c oxidase. Instead of laser pulses of high peak power, which may cause photodissociation, a continuous wave laser and a mixed flow apparatus were used. An intermediate formed within 450 microseconds after the reaction of cytochrome c oxidase with molecular oxygen could be detected. From the spectra it could be deduced that the most likely candidate for the intermediate would be a transient oxygenated species having the Fe2+ - O2 or Fe4+ = O heme in cytochrome a3 and the Fe2+ heme in cytochrome a.

Animals↗
PubMed1985

Investigations of cyanide as an infrared probe of hemeprotein ligand binding sites.

The measurement of infrared spectra for cyanide liganded to hemeproteins and hemins has been investigated. The hemeproteins included human methemoglobin A, lamprey methemoglobin, metchlorocruorin, horse metmyoglobin, and horseradish peroxidase. The hemins were dicyanide and monopyridine monocyanide species of deuteroporphyrin IX iron(III) and its 2,4-divinyl(proto) and 2,4-diacetyl derivatives. C-N stretch bands of low intensity detected near 2100 cm-1 exhibit changes in frequency, width, intensity, and isotope shift with changes in cyanide compound structure. Infrared band parameters are particularly sensitive to a change in oxidation state (Fe2+ versus Fe3+) and are affected to a lesser extent by changes in porphyrin ring substituent, ligand trans to the cyanide, and protein structure. Evidence of multiple conformers (i.e. multiple C-N stretch bands) was found for several hemeproteins. The cyanide infrared spectra provide direct evidence for cyanide binding as a metal cyanide (Fe--C identical to N) and against HCN being the ligand in nitrile-like bonding (Fe--N identical to C--H) in all the hemeprotein and hemin cyanides studied. With the reduced horseradish peroxidase cyanide, differences between infrared spectra for D2O and H2O solutions can result from hydrogen bonding between a protein amino acid residue and the distal atom of the cyanide (Fe--C identical to N...H+--R). The binding of cyanide to reduced iron (Fe2+) of a hemeprotein was only observed in the case of the reduced peroxidase. These findings demonstrate that cyanide infrared spectra can not only determine when cyanide is bound to a metalloprotein but can also provide information on how the cyanide is bonded to metal and on characteristics of the ligand binding site.

Animals↗
PubMed1985

Oxygen-binding characteristics of Potamilla chlorocruorin.

Accurate oxygen equilibrium curves of chlorocruorin of a marine polychaete annelid, Potamilla leptochaeta, were determined under a variety of experimental conditions. Like chlorocruorins from other species Potamilla chlorocruorin exhibited a low oxygen affinity, a large Bohr effect, and high cooperativity compared to those of human hemoglobin. However, in contrast to chlorocruorins from other species, the shape of the oxygen equilibrium curve for Potamilla chlorocruorin varied dramatically upon changes of pH or temperature. As observed in hemocyanins and annelid hemoglobins, cations, especially divalent ones such as Mg2+ and Ca2+, caused marked increase in oxygen affinity and cooperativity of Potamilla chlorocruorin. This finding together with the determination of cations in Potamilla blood has made clear the physiological role of chlorocruorin as an oxygen carrier. A graphical analysis based on the Monod-Wyman-Changeux allosteric model indicated that the number of sites for oxygen binding involved in heme-heme interactions is six, defining the functional unit of chlorocruorin molecule.

Allosteric Regulation↗
PubMed1985

Implication of acidic lipids in 5-hydroxytryptamine receptor mechanisms.

To establish the possible involvement of acidic lipids in 5-HT receptor mechanisms, we subjected whole rat brain synaptic plasma membranes to treatment with several kinds of lipid-modifying reagents and examined the [3H]5-HT and [3H]spiperone binding properties of the membranes. [3H]5-HT binding was decreased by treatment with Azure A, while [3H]spiperone binding was not altered. Similarly, prior treatment with arylsulphatase reduced the former binding, but had no effect on the latter binding. On the other hand, neither [3H]ligand binding was sensitive to phospholipases C and D. In contrast, prior treatment with phospholipase A2 (unheated) drastically decreased the [3H]5-HT binding and also affected the [3H]spiperone binding to some extent. Chelation of Ca2+ by EGTA (5 mM) prior to incubation of membranes with the unheated phospholipase A2 did not completely prevent the inhibitory effect of this enzyme on [3H]5-HT binding, while in the heated enzyme (at 100 degrees C for 10 min) EGTA exhibited this preventive effect perfectly. Furthermore, it was an interesting find that at least a low concentration of the heated phospholipase A2 (0.01 U) had no effect on the [3H]spiperone binding, as contrasted with the case of [3H]5-HT binding. In addition, the reduction of [3H]5-HT binding capacity in membranes treated with phospholipase A2 (heated and unheated) was restored only slightly by treatment with BSA (1%). Scatchard analysis of the [3H]5-HT binding showed that Azure A and phospholipase A2 (heated) decreased the Bmax values with no significant alteration in the KD values, whereas arylsulphatase increased only the KD value. All these observations infer that certain acidic lipids may play a role as the recognition site(s) or modulator(s) of 5-HT1 receptor molecules.

Animals↗
PubMed1985

[3H]5-hydroxytryptamine binding to reconstituted fraction with sulphatides, phosphatidylserine and phosphatidylinositol.

As a first step toward the examination of the involvement of sulphatides, phosphatidylserine and phosphatidylinositol in 5-HT receptor mechanisms, we performed [3H]5-HT binding experiments on the various reconstituted fractions with these acidic lipids. A binding assay of [3H]5-HT to these fractions was carried out by Sephadex LH20 column chromatography. Among various reconstituted fractions, only the reconstitution system with the three acidic lipids exhibited a saturable [3H]5-HT binding capacity, whereas no binding was seen with [3H]-spiperone. When the binding of [3H]5-HT to this fraction was plotted as a function of the ligand concentration, a multiple binding mode with three classes of binding components (or sites) was observed. Furthermore, the double reciprocal plot indicated that this reconstitution system had three apparent KD values of 4.7, 15 and 59 nM. The displacement studies with various compounds indicated that only a few 5-HT agonists (5-methoxytryptamine and tryptamine) and neurotransmitters (DA and ACh) inhibited the [3H]5-HT binding to this fraction, but 5-HT antagonists, LSD analogues and neuroleptics had no effect. Moreover, GTP, GDP and Gpp(NH)p clearly inhibited the [3H]5-HT binding in spite of their weak potencies, while GMP did not have any effect.

Animals↗
PubMed1985

[Prognostic factors influencing the improvement of allogeneic bone marrow transplantation in acute leukemia based on a national survey in Japan].

The records of 115 patients with acute leukemia who underwent allogeneic bone marrow transplantation from 1975 through August 1984 were collected by a national survey in Japan. One-year survival significantly improved from 9% in group I (before 1980) to 52% in group II (after 1981). Multivariate analysis indicated that selection of the patients in remission without infection at the time of transplant, as well as progress in technology of total body irradiation and selection of a platelet donor with negative cytomegalovirus titer resulted in the significant improvement in survival after 1981.

Acute Disease↗
PubMed1985

[Treatment of severe infection in patients with hematological disorders by cefminox. Tokai Infection Study Group].

Sixty-three infectious episodes in 61 patients with hematological disorders were treated with cefminox (CMNX, MT-141), a new antibiotics in the cephamycin group. CMNX was given by 1 hour infusion every 8 to 12 hours in a dose of 4 to approximately 6 g per day for 3 to 12 days, not being combined with other antibiotics. CMNX was effective in 45% of total cases. In 24 cases, the number of granulocytes at the start of CMNX were less than 500/mm3, and 11 cases (46%) of them responded to CMNX. Thus, CMNX was found effective in severe infections in patients with hematological disorders. No serious side effects attributable to CMNX were noted.

Adolescent↗
PubMed1985

Serological study for in vitro use of monoclonal antibody for autologous bone marrow transplantation in null cell-type acute lymphocytic leukemia.

In connection with autologous bone marrow transplantation (BMT) in null cell-type acute lymphocytic leukemia (Null-ALL) patients, the optimal conditions for in vitro elimination of leukemia cells from transplanted bone marrow cells with monoclonal antibodies (MoAb) plus rabbit complement (C) were investigated. Three monoclonal antibodies, NL-1, NL-22 and HL-47, which were produced in our laboratories and shown to react predominantly to Null-ALL cells, were used. In most cases, 10 micrograms/ml of MoAb and 50% of C were required for optimal killing of leukemia cells. Combined use of MoAbs and multiple treatments were studied, but generally no significant increase in the cytotoxicity to the target leukemia cells was observed as compared with a single treatment with the most effective single MoAb. Selection of C was very important, because some lots had lower C activity from the beginning or after incubation with normal bone marrow mononuclear cells. Nonspecific cytotoxicity to human hematopoietic cells was also observed in some lots of C. Under the optimal conditions thus defined, the three MoAbs did not inhibit the growth of granulocyte-macrophage colony-forming units (CFU-GM) or three other types of hematopoietic stem cells. Modulation of the antigens was also examined, and NL-1 antigen showed mild modulation, whereas NL-22 and HL-47 antigen did not. The results obtained indicated that these three MoAbs may be useful for eliminating Null-ALL cells in vitro from bone marrow in autologous BMT.

Antibodies, Monoclonal↗
PubMed1985

Preliminary clinical trial of autologous bone marrow transplantation after in vitro monoclonal antibody and complement treatments in null cell-type acute lymphocytic leukemia.

Autologous bone marrow transplantation (BMT) in null cell-type acute lymphocytic leukemia (Null-ALL) was carried out after depletion of leukemia cells from transplanted bone marrow. Patients' autologous bone marrow cells were harvested during remission and treated in vitro with complement and three monoclonal antibodies (NL-1, NL-22 and HL-47) reactive to Null-ALL cells, and then cryopreserved. Three patients were transplanted with the antibody-treated bone marrow cells during the first remission period after preconditioning with intensive chemotherapy and total body irradiation, while transplantations in two other patients, who were in poor clinical condition, were done during the fourth remission period and the third relapse, respectively. Good preservation of hematopoietic stem cells after antibody treatment and cryopreservation of bone marrow cells was demonstrated in all five cases studied. Clinically, prompt recovery of white blood cells and platelets was observed in the three patients who received BMT during the first remission period; two of them have continued remission (2 and 15 months), while the other relapsed after 7 months of remission. these results suggested that autologous BMT with these three antibodies may be an effective mode of therapy for Null-ALL patients.

Antibodies, Monoclonal↗
PubMed1985

[Calcinosis universalis with hyperphosphataemia--successful treatment with phosphorus deprivation].

Seven year old boy with calcinosis universalis associated with high serum phosphorus was reported. Over one year's treatment with aluminum hydroxide up to 18 grams per day have reduced calcified mass remarkably, while serum phosphorus levels were remaining still above the normal range. Concomitant use of probenecid seemed to be effective in reducing serum phosphorus levels as well as decreasing the calcified mass. Pathogenetic mechanisms of soft tissue calcification in calcinosis universalis is not clear, but in this case hyperphosphataemia is considered to be one important factor accelerating soft tissue calcification. Although hyperphosphataemia associated with tumoral calcinosis has been frequently observed, no report is yet available on calcinosis universalis associated with hyperphosphataemia. This case might represent one unique type of calcinosis.

Aluminum Hydroxide↗
PubMed1984

Effect of ingestion of thermally oxidized frying oil on peroxidative criteria in rats.

Thermally oxidized rapeseed oils (4 levels of deterioration; used by a manufacturer of fried fish paste in a conventional manner) were fed to rats at a practical level of concentration. Rats were fed a diet ad libitum for 13 weeks that contained 15% of a test oil. The effects of the diet on several biochemical criteria related to peroxidative alterations were investigated. In groups given thermally oxidized oils relative liver weight, relative kidney weight, thiobarbituric acid-reactive substances (TBA-RS) in the liver and reduced glutathione content were increased significantly in proportion to the degree of deterioration of the oil, compared with the group given fresh oil. Tocopherol contents in both serum and liver were decreased considerably in proportion to the deterioration level of the supplied oils. The above criteria correlated well with various deterioration indices of the oil. For instance, TBA-RS was well correlated (p less than 0.001) with petroleum ether-insoluble oxidized fatty acid (r = 0.9191), column chromatographically separated polar fraction (r = 0.9056), glyceride dimer fraction (r = 0.9023) and carbonyl value (r = 0.8647).

Animals↗
PubMed1984

Selective labelling of high affinity 5-hydroxytryptamine1 receptors in whole rat brain.

In synaptic membranes prepared from whole rat brain, cinanserin produced a relatively shallow inhibition curve of [3H] 5-HT binding with Hill slope of 0.68, as compared with that observed in the [3H]spiperone binding (Hill slope = 0.99). Furthermore, nonlinear regression analysis demonstrated that the former inhibition curve is best fitted by a two-site model. Regional and Scatchard analyses both clearly revealed that, in rat brain, at least two populations of binding sites were labelled by [3H]5-HT; however, high affinity binding sites (K(D) = 1.90 nM, Bmax = 0.188 pmoles/mg protein) could apparently be differentiated from the others by the action of 5 nM cinanserin.

Animals↗
PubMed1984

Screening of sugars inhibitory against sucrose-dependent synthesis and adherence of insoluble glucan and acid production by Streptococcus mutans.

Various sucrose derivatives and a sucrose analogue were enzymatically synthesized on the assumption that structural similarities of the sugars to sucrose would endow them with an ability to inhibit the cariogenicity of sucrose. The effect of these sugars on sucrose-dependent synthesis and adherence of insoluble glucan and on acid fermentation of sucrose by Streptococcus mutans was examined in vitro. Although none of them inhibited the acid fermentation, several sugars not only inhibited the synthesis and adherence of insoluble glucan, but were themselves only slightly fermented as well.

Acids↗