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Biomedical subjects

S Tsuda

Publications and source records attributed to S Tsuda.

At least 199 records · Page 11Linked to original sources

[Clinical evaluation of a combination treatment with cefbuperazone and amikacin in infections complicating with hematological disorders].

The efficacy and the safety of a combination regimen using cefbuperazone (CBPZ) and amikacin (AMK) were evaluated in severe infections in patients with hematological diseases. Twenty two patients were subjected to this combination therapy; among these, 18 patients were evaluable for the effectiveness. They included 9 cases of leukemia, 5 cases of malignant lymphoma, 2 cases of aplastic anemia, and 2 cases of angio-immunoblastic lymphadenopathy with dysproteinemia. Excellent responses were obtained in 5 patients and good responses in 5 patients, with a total effectiveness of 55.6%. Efficacy rates for individual types of infections were; 2/2 in sepsis, 6/14, or 42.9% in suspected sepsis, 1/1 in urinary tract infection, and and 1/1 in upper respiratory infection. The combination treatment was also effective in 4 of 6 cases in which neutrophil counts were less than 500/mm3 prior to therapy. Side effects were observed in only one patient. Mild proteinuria occurred in a 80-year-old male in 6 days after the regimen was started, but was not serious. These results indicate that a combination of CBPZ and AMK is safe and effective for the treatment of infections even in patients with compromised immunodefenses.

Adolescent↗

[Relation of karyotypic findings to chemotherapy response in patients with preleukemia].

In 1982, the French-American-British (FAB) Cooperative Group proposed the myelodysplastic syndrome (MDS), which comprised a group of heterogeneous hematologic disorders characterized by various degrees of cytopenias and a possibility of leukemic transformation. And chromosome findings of bone marrow cells from patients with this syndrome are reported to have one of the greatest prognostic significance. In our chromosome study of 97 patients with MDS, we found clonally abnormal karyotypes in 61 patients (63%), including the whole chromosome or partial loss of long arm of chromosome 7 (-7/7q-) in 18 patients and a partial loss of chromosome 5 (5q-) in 14 patients. Among these 97 patients, 26 received cytostatic chemotherapy (small dose of cytarabine; 23 patients, small dose of behenoyl Ara-C; 2, and intensive combined chemotherapy; 1) as well as supportive care. Among these 26 treated cases, pretreatment hematological characteristics or FAB subclassifications were not associated with response to chemotherapy. In contrast, only one of 9 patients with -7/7q- and/or 5q- achieved a partial remission, while 5 of 8 patients with other abnormal karyotypes and 4 of 9 patients with normal karyotype achieved a complete (4 patients) or a partial remission. In conclusion, pretreatment cytogenetic findings can predict the potential responders to this chemotherapy, and may be one of the most important factors in the selection of the treatment for this ill-managed syndrome.

Adult↗

[Clinical evaluation of cefpiramide for infections in leukemia and related disorders].

Forty one patients with infections associated with leukemia and related disorders were treated with cefpiramide (CPM). In 26 patients among them, we were able to evaluate the effectiveness of CPM against infections. Fifteen patients were not evaluated, because 6 patients were subjected to additional therapy such as gamma-globulin and other antibiotics, 5 were prophylactically treated, 2 had fever episode which were retrospectively reviewed to be originated from tumor mass, 1 received too short a duration of administration of CPM (2 days) to evaluate its effectiveness, and 1 with whom no precise data were recorded. Excellent responses were observed in 10 patients (38.5%) and good responses in 6 (23.1%) among these 26, with a total efficacy rate of 61.5%. Whereas, we found only one patient who showed an unfavorable side effect out of 31 patients including the 26 and 5 other patients who were prophylactically treated. The side effect observed was a mild bleeding tendency occurred in 77 years old female at 11 days after CPM was administrated. The bleeding tendency was easily diminished with the cessation of CPM treatment and a parenteral use of vitamin K. These results suggest that CPM is an effective and safe antibiotic for the treatment of infections in patients with leukemia and related disorders.

Adolescent↗

[Clinical evaluation of a combination therapy with aztreonam and clindamycin for severe infections in leukemia and related disorders].

A combination of aztreonam (AZT) and clindamycin (CLDM) was evaluated for severe infections associated with leukemia and related disorders. AZT is a monobactam antibiotic which has strong bactericidal effect against Gram-negative bacteria including Pseudomonas aeruginosa. CLDM which has strong antibacterial spectrum against Gram-positive and anaerobic bacteria, was chosen as a partner of AZT in order to complement the weak points of AZT. Fifty six patients were treated with the combination therapy. Among them, 51 patients were evaluable for the effectiveness. Five patients were excluded from the evaluation because 3 patients were subjected to additional therapy with other agents such as amikacin, miconazole and pulse therapy of a large dose of methylprednisolone, one had a fever episode apparently due to primary disease, and the remaining one was discontinued of the combination therapy of administration due to mild nausea after 3 days. Excellent responses were obtained in 17 (33.3%) patients and good responses in 20 (39.2%) patients, with a total rate of effectiveness of 72.5%. One patient with whom the combination therapy was stopped due to nausea, was included in the final evaluation of side effects. Side effects were observed in 2 patients of 50 and 40 years of ages (2/52, 3.8%), both of whom suffered with nausea. In the 50 years patient of acute myeloblastic leukemia, nausea occurred in a slight degree in 3 hours after the combined regimen was started. But, it disappeared during the continuation of the combination therapy. In the 40 years patient of acute myelomonocytic leukemia, mild nausea occurred after 3 day administration of the combined regimen. It disappeared soon after the cessation of the treatment. These results indicated that a combination of AZT and CLDM was an effective and safe regimen for the treatment of severe infections in patients with hematological disorders.

Adult↗

Nuclear magnetic resonance study on rabbit skeletal troponin C: calcium-induced conformational change.

Rabbit skeletal muscle troponin C (TnC) was investigated by means of 1H NMR in the presence of dithiothreitol that prevents dimerization of the protein. Two-dimensional (2D) 1H NMR spectra were observed in order to assign resonances to specific amino acids. One-dimensional 1H NMR spectra were observed as a function of Ca2+ concentration. The Ca2+-induced spectral change is categorized into two types: type 1 corresponds to the conformational change of the C-terminal-half domain (Ca2+ high-affinity sites) and type 2 to that of the N-terminal-half domain (Ca2+ low-affinity sites). From the 2D NMR spectra and Ca2+ titration data, it was suggested that (1) amide protons of Gly-108, Ile-110, Gly-144, and Ile-146 are hydrogen-bonded when the C-terminal-half domain binds 2 mol of Ca2+ and (2) hydrogen bonds of Gly-108, Ile-110, Gly-144, and Ile-146 are destroyed or weakened when the C-terminal-half domain releases 2 mol of Ca2+. Nuclear Overhauser enhancement difference spectra as well as the Ca2+ titration data suggested that a hydrophobic cluster is formed in the C-terminal-half domain when the C-terminal-half domain binds 2 mol of Ca2+. A hydrophobic cluster exists in the N-terminal-half domain without regard to Ca2+ binding to the N-terminal-half domain. The spectra of Tyr-10 showed both types of spectral change during the Ca2+ titration. The results suggested that Tyr-10 of apo-TnC interacts with the C-terminal-half domain.

Animals↗

Detection of karyotypic abnormalities in most patients with acute nonlymphocytic leukemia by adding ethidium bromide to short-term cultures.

A modified short-term culture method, in which cultured bone marrow cells were treated with ethidium bromide to prevent chromosome condensation was used to study the chromosomes of 70 patients with acute nonlymphocytic leukemia. Clonal karyotypic abnormalities were detected in 60 patients. Among these, 35 patients showed one of recurrent type specific alterations. A close relationship between karyotypes and clinical outcome was shown: thus, t(8;21) or a single miscellaneous chromosomal defect associated with a favourable prognosis whereas t(9;11) or a complex karyotype related to a poor prognosis. The ten cytogenetically normal patients did not appear to have a favourable prognosis.

Adult↗

Decreased membrane fluidity of erythrocytes and cultured vascular smooth muscle cells in spontaneously hypertensive rats: an electron spin resonance study.

1. Membrane fluidity of erythrocytes and cultured vascular smooth muscle cells was studied in spontaneously hypertensive rats (SHR; Okamoto and Aoki strains) by means of an electron spin resonance (e.s.r.) and a spin-label technique. 2. The values of outer hyperfine splitting (2T') and of the order parameter (S) determined from e.s.r. spectra for a fatty acid spin-label agent (5-nitroxy stearate) were significantly higher in erythrocytes of SHR (4 and 10-13 weeks of age) than in those of age-matched Wistar-Kyoto rats (WKY). This finding suggests that the membrane fluidity of erythrocytes might be decreased in SHR. 3. The fluidity of cultured vascular smooth muscle cells obtained from 10-13-week-old SHR was also reduced compared with that from WKY. 4. These results suggest that the decreased membrane fluidity might be a genetically determined abnormality of the cell membranes in SHR.

Animals↗

Effects of calcium antagonists on membrane fluidity in hypertension--an electron spin resonance study.

We examined alterations in membrane fluidity of hypertension and the effects of calcium antagonists on these changes by means of an electron spin resonance (ESR) and spin-label technique. Washed erythrocytes from spontaneously hypertensive rats (SHRs; aged 4 and 10-13 weeks) and from patients with essential hypertension, or cultured vascular smooth muscle cells from SHRs were examined and compared with those from normotensive controls. Electron spin resonance spectra for a fatty acid spin label-agent (5-nitroxy stearate) in the membranes were obtained. The values of hyperfine splitting and other parameters of the spectra were significantly higher in erythrocytes from hypertensive rats than in normotensive controls. Similar results were obtained in cultured vascular smooth muscles. These findings indicate that the membrane fluidity might be decreased in hypertension. When calcium was loaded to erythrocytes with Ca-ionophore A23187, the fluidity was decreased. The alternative degrees were greater in hypertensive rats than in controls, and these hypertensive changes were antagonized by diltiazem or verapamil. The results revealed that abnormalities of membrane fluidity in hypertension might be more prominent in the presence of calcium. Further, it is suggested that calcium antagonists could correct these membrane abnormalities in hypertension.

Adult↗

Ketanserin decreases sympathetic nervous activity in hypertension.

This study was performed to investigate whether ketanserin (a serotonergic receptor antagonist) might affect the sympathetic nerve activity in resistance vessels of hypertension. Isolated perfused mesenteric vasculatures were prepared from spontaneously hypertensive rats (SHRS, Okamoto and Aoki, 20-22 weeks old) and age-matched Wistar Kyoto rats (WKY), and effects of ketanserin on norepinephrine overflow from the adrenergic nerve endings as well as on vascular responsiveness were examined. Pressor responses to electrical nerve stimulation or exogenous norepinephrine were inhibited by ketanserin, in a dose-dependent manner. Norepinephrine overflow during electrical nerve stimulation was also suppressed by ketanserin. Inhibitory degrees of pressor responses and norepinephrine overflow during electrical nerve stimulation by ketanserin were significantly greater in SHRs than those in WKY rats. These results suggest that ketanserin could affect presynaptic neurotransmitter release from the adrenergic nerve endings in resistance vessels. These sympatho-depressive actions might contribute, at least partially, to the hypotensive mechanisms of ketanserin.

Animals↗

Membrane fluidity of erythrocytes and its relevance to renin profile in essential hypertension.

This study was performed to investigate the membrane fluidity of hypertension by means of an electron spin resonance (E.S.R.) and a spin-labeling technique. Erythrocytes from patients with untreated essential hypertension (WHO I, II) and secondary hypertension were compared with those from normotensive subjects, and E.S.R. spectra for a fatty acid spin label agent (5-nitroxy stearate) incorporated into the erythrocyte membranes were obtained. The values of outer hyperfine splitting (2T'parallel) and order parameter (S) were significantly higher in erythrocytes from patients with essential hypertension than in those from normotensive subjects. However, these values were not significantly changed in patients with secondary hypertension compared with those in the normotensive subjects. This finding may indicate the reduced erythrocyte membrane fluidity in essential hypertension. Calcium-loading to erythrocytes with calcium-ionophore caused a greater decrease in the membrane fluidity of erythrocytes in patients with essential hypertension than in those from the normotensive subjects. This Ca-induced change in membrane fluidity was inversely correlated with plasma renin activity in essential hypertension. In addition, changes in membrane fluidity by Ca-loading in essential hypertension were inhibited by Ca-antagonists (diltiazem, verapamil). These results demonstrate that the membrane fluidity of erythrocytes might be decreased in essential hypertension, and that this abnormality could be accelerated by calcium, especially in low renin essential hypertension. Furthermore, it is suggested that Ca-antagonists might correct this Ca-abnormality at cellular levels of hypertension.

Adult↗

Effects of ouabain on adrenergic neurotransmission in spontaneously hypertensive rats.

The purpose of the present study is to determine the role of Na+,K+-ATPase in adrenergic neurotransmission of hypertension. Isolated perfused mesenteric vasculatures were prepared from spontaneously hypertensive rats (SHR, Okamoto and Aoki, 7-10 weeks old) and age-matched normotensive Wistar Kyoto rats (WKY). The effects of ouabain, a Na+,K+-ATPase inhibitor, on the norepinephrine overflow from the sympathetic nerve endings were examined. Norepinephrine overflow from the nerve endings as well as pressor responses during electrical nerve stimulation were significantly greater in SHR than in WKY. Ouabain increased the norepinephrine overflow evoked by electrical nerve stimulation, even in the presence of an uptake-blocker of norepinephrine. Further, the facilitatory effect of ouabain on stimulation-induced norepinephrine overflow was more prominent in SHR than in WKY. These results suggested that ouabain-sensitive Na+,K+-ATPase on sympathetic nerve terminals could have an important role in the regulation of neurotransmitter release, and that its activity might be enhanced in SHR compared with WKY.

Animals↗

The role of dopamine in the regulation of neurotransmitter release in spontaneously hypertensive rats.

The purpose of the present study was to analyze the influence of dopamine on norepinephrine release in resistance vessels in spontaneously hypertensive rats (SHR). Perfused mesenteric vasculature preparations from spontaneously hypertensive rats (7-10 weeks old) and age-matched normotensive Wistar Kyoto rats (WKY) were used to compare the effects of dopamine on both pressor responses and norepinephrine release. Both responses to electrical nerve stimulation were significantly greater in SHR than in WKY rats. Dopamine reduced these responses in a dose-dependent manner in WKY. However, this suppression of responses to electrical stimulation was attenuated in SHR. These results suggest that the enhanced adrenergic transmission in SHR may partly reflect impaired dopamine-mediated inhibition of nerve terminals, which would contribute to the pathogenesis of hypertension.

Animals↗

Inhibitory actions of captopril on norepinephrine release from adrenergic nerve endings in spontaneously hypertensive rats.

The purpose of the present study was to investigate the mechanisms of the hypotensive actions of an angiotensin converting enzyme inhibitor of the hypotensive actions of an angiotensin converting enzyme inhibitor (captopril) in hypertension. In perfused mesenteric vasculatures from spontaneously hypertensive rats (SHR, Okamoto and Aoki strain, 10-13 weeks of age) and age-matched normotensive Wistar Kyoto rats (WKY), the effects of captopril on vascular responsiveness and norepinephrine release from the adrenergic nerve endings were examined. The vasoconstrictor responses and norepinephrine release during the electrical nerve stimulation were significantly enhanced in SHR compared to those in age-matched WKY. Captopril reduced both vasoconstrictor responses and norepinephrine release during the electrical nerve stimulation, dose-dependently. These inhibitory effects of captopril were significantly greater in SHR than in WKY. The results demonstrate that captopril affects presynaptic sites on the resistance vessels and causes a decrease in electrically-stimulated norepinephrine release from the adrenergic nerve endings. The marked reduction of both pressor responses and norepinephrine release by captopril in SHR suggests an enhanced renin-angiotensin system in the vascular walls of hypertension.

Animals↗