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Biomedical subjects

K Konno

Publications and source records attributed to K Konno.

At least 379 records · Page 21Linked to original sources

Two different preparations of subfragment-1 from scallop adductor myosin.

Chymotryptic digestion of scallop myosin yielded two different preparations of subfragment-1, having the following features. The major product from chymotryptic digestion of scallop myosin was subfragment-1 (S1) either in Ca-medium or in EDTA-medium. However, the S1 preparations obtained from the digestion in Ca-medium, abbreviated as Ca-S1(CT), had both types of light chain subunits (regulatory light chains (R-LC) and essential light chains (SH-LC], and 100 Kdaltons (Kd) heavy chain subfragments (HCs), whereas the S1 preparations obtained from the digestion in EDTA-medium, ED-S1(CT), had no R-LC, partially fragmented SH-LC (SH-LC), and 90 Kd HCs. On the other hand, Ca-S1(CT) and ED-S1(CT) were practically identical with each other in ATPase activity and in actin-binding ability. The two S1 preparations were also identical in that the Mg-ATPase activity of both S1 and acto-S1 was insensitive to calcium ions. Ca-S1(CT), which contained both R-LC and SH-LC in a stoichiometric amount, was further digested with trypsin, which is known to cleave rabbit skeletal myosin not only at the head-tail junction but also in the head. The tryptic digestion of Ca-S1(CT) appeared, in terms of the SDS-gel electrophoretic pattern, to occur at a much faster rate in Ca-medium than in EDTA-medium, and with a different digestion profile. It is therefore suggested that association of R-LC induces changes in the heavy chain conformation which result in an increase in the proteolytic digestibility of heavy chains and in an alteration of the site of proteolytic cleavage on heavy chains.

Actins↗

Heavy meromyosin and subfragment-1 from squid mantle myosin, and Ca-sensitivity of their Mg-ATPases.

Heavy meromyosin (HMM) and subfragment-1 (S1) were obtained from squid mantle myosin by tryptic digestion and chymotryptic digestion, respectively. Squid HMM(T) and S1(CT) preparations contained stoichiometric amounts of the two types of light chain subunit; regulatory light chain, LC-2, and essential light chain, LC-1. No difference was detected in the chymotryptic digestibilities of squid mantle myosin in Ca-medium and in EDTA-medium. This is in contrast to the digestibility of scallop adductor myosin. The Mg-ATPase activity of HMM(T) alone and that of acto-HMM(T) were both sensitive to calcium ions. In contrast, the activity of S1(CT) alone and that of acto-S1(CT) were both insensitive to calcium ions. The affinity of HMM(T) for actin was not affected by calcium ions, but the amount of HMM(T) bound to actin was increased by calcium ions from 20% to 60% of the total amount of HMM(T). On the other hand, the actin affinity of S1(CT) and the amount of S1(CT) bound to actin were both unaffected by calcium ions. The role of calcium ions in the regulation of contraction in molluscan muscles is discussed.

Actins↗

Simultaneous determination of five androgens in early neonatal urine by selected ion monitoring GC-MS using 19-d3 steroids as internal standards.

Androgen levels in early neonatal urine were measured by GC-MS using trideuterated steroids at C-19 as internal standards. The deuterated steroid is not only stable in the process of analysis but also behaves chemically the same as the corresponding steroid to be measured so that the reliability in the method of analysis is satisfactory. The following results were obtained by this method: Androsterone levels in early neonatal urines were significantly higher in male than in female on the 1st, 3rd and 5th day, though the levels fell significantly from the 1st to 3rd day. Testosterone values were also higher in male than in female on the 1st, 3rd and 5th day. No sex difference in dehydroepiandrosterone or dihydrotestosterone was observed. The sex difference of the androgen levels indicated a testicular steroidogenesis in male neonates.

Androgens↗

Estimation of alveolar deposition ratio of inhaled radioaerosol.

The lung retention ratio (LRR) and the alveolar deposition ratio (ALDR) are mandatory to calculate the other three indices for quantitatively evaluating mucociliary clearance function of the ciliated airways; the airway deposition ratio (ADR), the airway retention ratio (ARR) and the airway clearance efficiency (ACE). According to our original method, the LRR required 2-hr continuous measurement of radioactivity in the thorax and the ALDR a repeat measurement at 24-hr after radioaerosol inhalation. The 2-hr continuous measurement is, however, too long for a clinical examination and the 24-hr repeat measurement cumbersome. The purpose of the study was to find a way to get the ALDR by calculation without repeating the 24-hr measurement and by counting radioactivity for the shortest possible period and yet without sacrificing the visual evaluation by compiling radioaerosol inhalation lung cine-scintigraphy. By using the derived formulae listed in Table 1, the ALDR was calculable. Forced expiratory volume (FEV) in one sec divided by FEV in per cent (FEV1.0%), the initial 60 min measurement of radioactivity without repeating 24-hr measurement, and smoking history were the minimum requirements to calculate the ALDR. The calculated ALDR appeared reliable enough to estimate the other indices.

Aerosols↗

Changes in the immunological parameters after a single dose of forphenicinol, a new small molecular immunomodifier.

Forphenicinol [L-2-(3-hydroxy-4-hydroxymethyl-phenyl) glycine, M.W. 197.19] is a derivative of forphenicine, an inhibitor of alkaline phosphatase discovered by Umezawa. In order to find an optimal dose, a single dose of the drug ranging from 10 to 600 mg per body was orally administered to a total of 55 patients (36 cancer, 13 tuberculosis, and 6 others). The possible changes in the percentages of the peripheral T and B lymphocytes, natural killer (NK) activity, and the proliferative response to phytohemaglutinin (PHA) were studied as immunological parameters. A significant effect of forphenicinol was demonstrated in restoring the normal proportion of T and B cells, especially in those who had 'low'-T and/or 'high'-B before administration of the drug. No difference was found between cancer and tuberculosis. The mean percentage of T cells increased from the low initial level of 68.0 to 75.6 in cancer (n = 12, p less than 0.05) or from 63.1 to 78.5 in tuberculosis (n = 7, p less than 0.05), while that of B cells decreased from the high initial level of 34.6 to 26.9 in cancer (n = 7) or from 34.9 to 14.3 in tuberculosis (n = 6, p less than 0.025). The effect of a single dose of the drug tended to disappear by day 8, a peak response being found on day 3 in most cases. With respect to this parameter, an optimal dose was found in a range from 60 to 100 mg. Forphenicinol was rather inhibitory on the NK activity, while it exerted diverse effect on the lymphocyte proliferation. No evidence of adverse effect was observed.

Adjuvants, Immunologic↗

Antitumor effect of the yeast polysaccharide preparation in syngeneic mouse tumor models.

Antitumor effect of our Candida utilis glucomannan preparation (YPS) was evaluated in two syngeneic transplantable tumors; the Lewis lung carcinoma (3LL) in C57BL/6 (B6) mice and the 3-methylcholanthrene (MCA)-induced fibrosarcoma in C3H/He mice. YPS inhibited preferentially the 3LL pulmonary metastases only when optimal dosage was given at an earlier stage; 7 daily intraperitoneal (i.p.) doses of 100 mg/kg per dose from the next day of tumor inoculation (1 X 10(5)/mouse, subcutaneously, s.c.) substantially reduced the number of metastatic nodules, yielding the inhibition ratio 54% on day 21. However, the same treatment delayed until day 8 markedly facilitated the metastatic spread (-105%). Postsurgical-adjuvant therapy with YPS (10 daily i.p. doses of 100 mg/kg per dose from the next day of surgery) was effective in improving the survival rate with no evidence of metastatic growth on day 200, even though the amputation of the tumor-bearing legs was performed after the pulmonary metastases had been established (on day 20). In the MCA-fibrosarcoma model, YPS treatment from day 3 (10 daily doses of 100 mg/kg per dose) was effective in prolonging the survival period. The 3LL local tumor was affected only marginally and temporarily, while the MCA-tumor was not at all.

Animals↗

Antitumor effect of the organogermanium compound Ge-132 on the Lewis lung carcinoma (3LL) in C57BL/6 (B6) mice.

Effects of the organogermanium compound Ge-132 (i.p.) were examined on the 3LL local tumor (1 X 10(5)/mouse, s.c.) and its pulmonary metastases in B6 mice. A characteristic feature of its action was the preferential antimetastatic effect under strictly defined conditions. Either inhibition or facilitation was observed depending on the treatment schedules; 7 daily doses of 100 mg/kg yielded the inhibition ratio 49% when started from day 1, whereas the treatment from day 8 resulted in the ratio -99%. The maximum inhibition was obtained at 100 mg/kg. The postsurgical-adjuvant treatment with Ge-132 was of no beneficial effect. The local tumor growth was affected only marginally and temporarily. When inoculum size was minimized (1 X 10(4)), a single dose of 300 mg/kg on day 1, but not on day 8, was effective in prolonging the latency before tumor take. The antitumor action of Ge-132 was discussed with reference to its interferon (IFN)-inducing activity.

Adjuvants, Immunologic↗

Imbalance of T cell subsets in cancer patients and its modification with bestatin, a small molecular immunomodifier.

The peripheral T lymphocyte subsets and natural killer (NK) cells of patients with cancer were studied by monoclonal antibody assays in comparison with those of non-cancer individuals. An imbalance of immunoregulatory T cell subsets was frequently found in the group of cancer patients (n = 26), being characterized by a relatively high proportion of OKT8+ cells (45.0 +/- 12.0%, p less than 0.01) and a low OKT4+/OKT8+ ratio (1.29 +/- 0.56, p less than 0.05). T cell level showed no significant difference as assessed by either OKT3 or rosette formation with sheep erythrocytes (E). The effect of bestatin was examined in 10 of these cancer patients. The relative proportion of T cell subsets tended to normalize 2 to 6 weeks after starting the daily doses of 30 mg per body. The mean percentage of OKT8+ cells decreased from 47.2 to 33.4 (p less than 0.01), while the helper to suppressor ratio increased from 1.18 to 1.79 (p less than 0.01). A significant increase was also found in the percentage and number of OKT4+ cells and HNK-1+ cells after the drug administration, while T cell level tended to converge to a normal range.

Adjuvants, Immunologic↗

The role of airflow in mucous transport in the trachea.

The role of airflow in mucous transport in the respiratory tract was studied. Seven mongrel dogs were tracheostomised at the caudal end of the neck, and the following two procedures were performed. In procedure (1), a small radiopaque plastic disc was placed on the mucous membrane of the right side wall of the trachea through the tracheostoma, which was then closed to let the dog breathe through the normal respiratory tract. Roentgenograms of the trachea were taken three times at 5-min intervals. Procedure (2) was designed to eliminate airflow from around the disc. A canula was placed in the trachea through the tracheostoma to bypass airflow, and the disc was placed on the mucous membrane slightly more proximal than the cannula. The transport rate was 11.1 +/- 4.1 mm/min (mean +/- S.D.) in procedure (1) and 5.4 +/- 2.7 mm/min in procedure (2), which showed a significant difference. The present results seem to indicate an important role of airflow in mucous transport in the trachea.

Animals↗

[Phase I trial of 4'-O-tetrahydropyranyl-doxorubicin (THP)--a multi-institutional cooperative study].

A phase I trial of a new anthracycline derivative, 4'-O-tetrahydropyranyldoxorubicin (THP), was conducted in 54 patients with various advanced solid tumors and malignant lymphomas. Starting dose was 5 mg/m2 i.v. and dose escalations were made by a modified Fibonacci search scheme. There were 40 evaluable courses. The dose-limiting toxic effect was leukopenia which was dose-related and reversible. The maximum tolerated dose for a single i.v. injection was estimated to be 55 mg/m2. The median nadir day for leukopenia was day 12 with recovery occurring 13 days (median) after reaching the nadir. Thrombocytopenia was less commonly observed than leukopenia. Other toxic effects were mild gastrointestinal disturbances, fever and general malaise. Ventricular extrasystole was observed in a case of pancreatic cancer who received 5 mg/m2 of the drug. There were no cases with alopecia, or with hepatic or renal dysfunction. With regard to objective tumor response, CR was observed in 2 cases with NHL, and MR in 2 cases with lung cancer, and 1 case each with breast cancer and NHL. Response occurred at a dose of more than 35 mg/m2. The recommended dose schedule for phase II trial is 35-45 mg/m2 by single i.v. injection at 3-4-week intervals.

Aged↗