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Biomedical subjects

K Tsubaki

Publications and source records attributed to K Tsubaki.

At least 19 recordsLinked to original sources
PubMed1992

Diversity among mouse motor nerve terminals with respect to release transmitter quanta.

1. The aim of this work was to reexamine whether a positive correlation exists between the frequency (F, sec-1) of miniature endplate potentials (m.e.p.ps) and the quantal content (m) of endplate potentials (e.p.ps) or between quantal content, frequency and twin-pulse facilitation of transmitter release at a large number of neuromuscular junctions in the mouse. 2. The values of F and m were both measured intracellularly at endplates of mouse diaphragm in a high Mg2+/low Ca2+ bathing solution. 3. Values of both F and m varied from junction to junction. Smaller values of F were correlated with smaller values of m, and vice versa, resulting in a linear relationships. Histograms of F and m were skewed towards smaller values. 4. E.p.ps evoked by twin pulses gave the quantal contents of the first (m1) and second (m2) responses. 5. The ratio of m2 to m1 varied from junction to junction. A histogram of this ratio was skewed towards smaller values. 6. The ratio of m2 to m1 showed larger fluctuations at junctions with smaller values of F or m1 but was focused around 1 at junctions with larger values of F or m1. 7. The skewed parts of the histograms of F, m and m2/m1 accounted for the major population of junctions. 8. These results support the hypothesis that an intrinsic ability to release transmitter plays a role in regulation of the evoked output of transmitter at neuromuscular junctions in the mouse. 9. Such an ability is not correlated with the twin-pulse facilitation of transmitter release.

Animals↗
PubMed1992

Agents for the treatment of overactive detrusor. III. Synthesis and structure-activity relationships of N-(4-amino-2-butynyl)acetamide derivatives.

A series of N-(4-amino-2-butynyl)acetamides were synthesized and examined for their inhibitory activity on detrusor contraction and mydriatic activity as an index of anticholinergic side effect. Among those compounds synthesized, (+)-2-cyclohexyl-N-(4-dimethylamino-2-butynyl)-2-hydroxy-2-phenylacet amide hydrochloride ((+)-13b.HCl), 2-cyclohexyl-2-hydroxy-N-(4-methylamino-2-butynyl)-2-phenylacetamide+ ++ hydrochloride (13c.HCl), N-(4-dimethylamino-2-butynyl)-2,2-diphenyl-2-hydroxyacetamide hydrochloride (14a.HCl), and 2,2-diphenyl-N-(4-ethylamino-2-butynyl)-2-hydroxyacetamide hydrochloride (14b.HCl) showed equipotent inhibitory activity on detrusor contraction to oxybutynin (1) and less mydriatic activity. Further evaluation of these compounds as an agent for the treatment of overactive detrusor has been examined.

Alkynes↗
PubMed1992

Study of immune-responsiveness to wheat antigen by IgG, IgA, and IgE immunoblotting with sera from patients with atopic dermatitis.

To investigate the immune mechanism underlying the IgE-mediated hypersensitivity to food antigens, wheat-flour proteins were extracted in mild condition, and IgG antibodies were detected by the ELISA method. Atopic dermatitis patients who had high scores for IgE-RAST were shown to have increased levels of IgG antibodies to wheat proteins. To define the allergenic polypeptides or epitopes in wheat proteins, each patient's serum was subjected to determination of IgG, IgA, and IgE antibodies to each protein component, using a highly sensitive immunoblotting method. Low molecular weight polypeptides bind specifically IgG, IgA, and IgE antibodies in serum from atopic dermatitis patients. Thus, there are specific components or epitopes in wheat proteins which are closely related to the disease states.

Antigens↗
PubMed1992

[Co-operative on salvage chemotherapy with VP-16 for malignant lymphoma. Hanshin Study Group on Treatment for Hematological Disorders].

Forty one patients with refractory malignant lymphoma were treated with a combination of VP-16, ACM, BH-AC, MTX and PDN as a salvage chemotherapy. These patients were either resistant to frontline therapy or refractory in their relapses. Three patients (7%) achieved a complete remission and 14 patients (34%) attained a partial remission. An overall response rate was 41%. Major toxicities were myelosuppression, nausea, and vomiting. However, they were well tolerated. This regimen has been effective in the treatment for the patients with refractory malignant lymphoma.

Aclarubicin↗
PubMed1992

Randomized study of individualized induction therapy with or without VCR, and of maintenance of 4 or 12 courses in adult AML: JALSG-AML87. Japan Adult Leukemia Study Group (JALSG).

We asked 2 questions in this study. First was the additional effect of VCR in induction therapy, and the second was the duration of maintenance therapy. Adult AML were treated by an individualized response-oriented induction therapy with behenoyl Ara-C 200 mg/m2 daily + 6MP 70 mg/m2 daily + prednisolone 40 mg/m2 on days 1-4 + DNA 40 mg/m2 on days 1-3 and additionally on days 7, 8, 11, 12 (for M3, DNR 50 mg/m2 daily) (BHAC-DMP) until bone marrow became severely hypoplastic with less than 5% of blasts. Patients were randomized to BHAC-DMP or BHAC-DMP + VCR 0.35 mg/m2 on days 1-4. After obtaining CR, 3 courses of intensive consolidation therapy were given together with I.T. MTX+Ara-C+PSL. Maintenance intensification therapy was randomized to either 4 or 12 courses given every 2 months. Patients of age greater than or equal to 60 received about 2/3 reduced doses. From June 1987 to Sept. 1989, 265 consecutive adult AML were registered from 19 institutions and 258 were evaluable. Age ranged from 15 to 79 (med., 48). Out of 258, 200 (77.5%) achieved CR (80% in 209 of age less than 60 and 65% in 49 of age greater than or equal to 60). Unexpectedly, addition of VCR reduced the high CR rate of BHAC-DMP significantly (84% to 70%, p = 0.007). At the median follow-up of 37 mo., overall survival is 37%, and event-free survival (EVS) 27%. Survival, continuing CR and disease-free survival (DFS) rates of 200 CR cases are 45%, 40% and 35%, respectively. Patients received 12 courses of maintenance therapy showed better DFS (P = 0.0555). The VCR group had significantly worse EFS. By multivariate analysis, significant prognostic factors for the achievement of CR were age less than 60, PS 0-2 and no addition of VCR. Significant factors for longer DFS were induction of CR by one course, FAB M3 or M5 and age less than 50. The present multi-institutional study confirmed the high CR rates of the response-oriented individualized therapy reported from several centers in Japan, but failed to support an additional effect of VCR reported from one center.

Acute Disease↗
PubMed1992

[Efficacy of leukocyte-depleted platelet concentrates for prevention of HLA-alloimmunization in patients with frequent platelet transfusions: a prospective multi-institutional study using a polyester platelet filter].

A prospective multi-institutional study was conducted to assess the efficacy of leukocyte-depleted platelet concentrates, prepared by a method using a newly developed polyester filter, in the prevention of HLA-alloimmunization in patients with hematological disorders. Patients who were expected frequent platelet transfusions, were assigned into two groups, receiving either standard platelet concentrates (control group) or leukocyte-depleted platelet concentrates prepared through a polyester platelet filter, Sepacell-PL (filtered group). All patients received leukocyte-depleted red cell products. Of III patients enrolled, 72 were evaluable, 23 in the control and 49 in the filtered group. Both groups were comparable according to age, sex ratio, underlying disorders, previous exposure to alloantigens by transfusion and/or pregnancy. There was no statistically significant difference in the number and duration of transfusion in the two groups. There were significant differences in HLA-alloimmunization rate (9 cases out of 23, 39% in the control group versus 4 cases out of 49, 8% in the filtered group; p less than 0.01) and refractoriness to platelet transfusion from random donors (6 cases out of 23, 26% in the control group versus 2 cases out of 49, 4% in the filtered group; p less than 0.05). These results indicated that leukocyte-depleted platelet concentrates prepared through the polyester platelet filter are beneficial to reduce HLA-alloimmunization in patients with frequent platelet transfusions.

Adolescent↗
PubMed1991

Inhibition of CFU-G formation by human serum during granulopoiesis after chemotherapy: purification of CFU-G-inhibitory factor and its activities.

We found that the sera obtained from patients with acute leukemia (AL) in complete remission or malignant lymphoma (ML) during the recovery phase after chemotherapy completely inhibited the GCT-CM-stimulated growth of allogenic and autologous bone marrow colonies in vitro. We investigated 5 AL patients and 6 ML patients from whom blood samples were taken either every day or every 6 h during the recovery phase after chemotherapy. Colony-inhibitory sera, were detected in all patients, more frequently when the peripheral leukocyte count recovered to about 2,500 x 10(6)/l, but then transiently and at intervals. The colony-inhibitory factor purified from the inhibitory sera inhibited the growth of G-CSF-responsive colonies in a dose-dependent manner, but no effect on the growth of GM-CSF-responsive colonies, CFU-E, or BFU-E, was observed. These results suggest that this factor may play a role in regulating granulopoiesis by inhibiting the differentiation of G-CSF-responsive precursor cells.

Acute Disease↗
PubMed1991

[Detection and analysis of IgG antibodies in sera of patient with atopic dermatitis (AD) to individual wheat polypeptides by immunoblotting techniques].

To detect IgG antibodies in sera of patients with atopic dermatitis (AD) to individual wheat polypeptides, wheat flour proteins were extracted with tris-citrate buffered saline containing urea and 2-mercaptoethanol (UTC solvent), and fractionated as polypeptides of molecular weights between 12 and 100 KDa. By means of the immunoblotting techniques, specific IgG antibodies to fractionated proteins could be detected in sera from healthy individuals and AD patients. Twenty AD patients' sera with high titers of wheat specific RAST (scores of more than 3) reacted not only to five major wheat components (33-38, 40-45, 55-60, 80, 90-98 KDa), which stained intensively with Coomassie brilliant blue G-250, but also to polypeptides of 14, 16, 22, 29, 70 KDa. Twelve control sera reacted to a limited number of the five major wheat components, and levels of specific IgG antibodies increased with age. The sera of AD patients in the present study contained increased level of IgG antibodies to the five major components, and additionally to several minor components, 70 KDa, 29 KDa and much smaller proteins.

Adolescent↗
PubMed1990

Chloramphenicol acetyltransferase expression in marine Rhodobacter sp. NKPB 0021 by use of shuttle vectors containing the minimal replicon of an endogenous plasmid.

A vector, pUK318, was constructed to allow the expression of foreign genes in the marine photosynthetic bacterium Rhodobacter sp. NKPB 0021. This strain has been cured of its two endogenous plasmids. pUK318 consists of a 2.3-kb PstI-BamHI restriction fragment, containing a marine Rhodobacter plasmid replication region, cloned into pUC18. This fragment was derived from plasmid pRD31, a 3.1-kb endogenous plasmid purified from the marine strain Rhodobacter sp. NKPB 043402. A kanamycin resistance gene from Tn903 was cloned into the PstI restriction site to provide antibiotic selection. pUK318 was transferred to Rhodobacter sp. NKPB 0021 by transformation, and efficiencies of 7.2 x 10(-5) were obtained. Furthermore, pUK318 was stably maintained when transformants were grown either heterotrophically or photosynthetically in the absence of antibiotics. pUK318 was used to express the Escherichia coli chloramphenicol acetyl transferase (CAT) gene in Rb. NKPB 0021. Transformants expressed a maximum CAT activity of 1.12 mmol/min/g dry cells. In addition, the DNA region essential for pUK318 replication in Rb. NKPB 0021 was localized to a 1.36-kb HincII-PstI fragment. This is the first report of a plasmid vector containing a marine Rhodobacter-specific replicon that allows stable expression of foreign genes in the absence of antibiotic selection.

Chloramphenicol O-Acetyltransferase↗
PubMed1990

Ryanodine facilitates calcium-dependent release of transmitter at mouse neuromuscular junctions.

1. Quantal release of transmitter was measured intracellularly at mouse neuromuscular junctions in the presence and absence of ryanodine (Rnd). 2. Rnd at concentrations up to 1 microM did not significantly alter the frequency of miniature endplate potentials (m.e.p.ps) in the presence or absence of Ca2+, suggesting that Rnd is unlikely to alter the internal concentration of Ca2+ ([Ca2+]i) at rest. 3. In a high-K+ (10 mM) bathing solution, Rnd further potentiated the facilitatory effect of Ca2+ on the frequency (F, s-1) of m.e.p.ps. Rnd shifted the relationship between 1n(F) and 1n[Ca2+]o to lower concentrations. 4. In a high-Mg2+ bathing solution, Rnd did not affect the frequency of m.e.p.ps at any value of [Ca2+]o. However, Rnd slightly but significantly increased the quantal content (m) of e.p.ps. It shifted the relationship between 1n(m) and 1n[Ca2+]o to lower concentrations. These results suggest that Rnd potentiates the quantal release of transmitter after depolarization of the membrane or nerve impulse, in keeping with the cooperativity of Ca2+ at the active site. 5. A series of two closely spaced nerve impulses produced a facilitation of transmitter release, as judged by the quantal content (m2) of the second response in relation to that of the first one (m1), m2/m1. Rnd did not change the ratio m2/m1. Thus Rnd is unlikely to affect the rapid phase of the sequestration of Ca2+ inside the nerve terminal. 6. High levels of K+ (5 mM) and caffeine (2 mM) potentiated both modes of transmitter release, in a manner dependent on [Ca2+]o. Caffeine did not potentiate facilitation of transmitter release. 7. These results indicate that Rnd facilitates the quantal release of transmitter presumably via an increase in [Ca2 ]i by a manner different from that of high-K+ or caffeine. The results suggest that Rnd probably affects calcium turnover in neuronal cells.

Alkaloids↗
PubMed1990

[Analysis of anti-platelet antibody].

Results obtained by analysis of anti-platelet antibody using flow cytometry (FCM) were as follows. The use of nest gating is useful in analysis of anti-platelet antibody and frequency of antibody production were 32.7% in patients with hematological disorders using FCM method. This method was much correlated to AHG-LCT method. The rate of coincidence was 92.1%. And effective rate of platelet transfusion of cross match carried out only by FCM method was 81.3%. Concentration of globulin fraction in patient's serum and avidin-biotin assay are useful for increasing the sensitivity of detection of anti-platelet antibody. Elimination of HLA (Class 1) antigen from platelet's surface is effective in both chloroquine and acid treatment. Background of fluorescent intensity was tendency to low by the acid treatment than by chloroquine one. It is possible that high titer serum of allogeneic anti-platelet specific antibody is able to be identified by means of its fluorescent intensity.

Blood Grouping and Crossmatching↗
PubMed1989

Sudden death in hypertrophic and dilated cardiomyopathy.

The long-term prognosis for 314 patients with hypertrophic cardiomyopathy (HCM) and 82 with dilated cardiomyopathy (DCM) was investigated in an attempt to elucidate clinical variables predicting sudden death (SD). In the patients with HCM, 68% of cardiac deaths occurred suddenly and unexpectedly. Variables associated with an increased risk to SD were young age (less than 30 years), reduced fractional shortening (less than 35%) and elevated left ventricular end-diastolic pressure (greater than or equal to 20 mmHg). Eight of the 10 patients who died suddenly during or immediately after strenuous exercise were less than 30 years old, and the collapse tended to be associated with exercise-induced ST-depression. In contrast, SD occurring during mild activities, resting or sleep was mainly observed in those aged 30 years or more. Ventricular tachycardia was observed on electrocardiographic monitoring in 24% of those 30 years or more, while it was rare in those under 30 years (5%). On the other hand, no SD was found in patients with apical hypertrophy nor in those 50 years or more. These observations suggest that HCM patients at a young age, with impaired left ventricular systolic and diastolic function, have an increased risk to SD. Since exercise-induced myocardial ischemia rather than ventricular arrhythmias appears to be the more likely mechanism for SD for those under 30 years old, restriction of strenuous exercise should be strongly advised for these patients. For those aged from 30 to 50 years, ventricular tachycardia should be controlled by antiarrhythmic agents for the prevention of SD. In patients with DCM, 24% of all cardiac deaths were attributed to SD. Although no variables reliably predicted SD, it was of note that only one patient out of 26 with SV1 + RV5 greater than or equal to 35 mm died suddenly. Whereas ventricular arrhythmias are known to be a contributing cause for SD, the prognostic significance of ventricular tachycardia on electrocardiographic monitoring in predicting SD has not yet been established. In addition, antiarrhythmic agents often precipitate hemodynamic deterioration. It therefore appears that use of antiarrhythmic agents is not a therapy of first choice and that primary treatment should be focused upon improvement in ventricular function in order to prevent SD in patients with DCM.

Adult↗
PubMed1989

[Effect of recombinant human granulocyte colony-stimulating factor on white blood cell count and neutrophil functions in patients with malignant lymphoma].

We studied the in vivo effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on white blood cell (WBC) count and neutrophil functions in nine patients with malignant lymphoma. The WBC count and absolute neutrophil count were rapidly increased without a nadir phase after chemotherapy. Neutrophil alkaline phosphatase (NAP) scores also markedly increased following chemotherapy in all patients. Phagocytosis of India ink and nitroblue tetrazolium (NBT) reduction were revealed tend to be increased, but not exceeded significantly to normal range. RhG-CSF repaired neutrophil function in patients with decreasing that. Thus, rhG-CSF may be useful for prevention and treatment of infection after chemotherapy.

Adult↗