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M Takeshima

Publications and source records attributed to M Takeshima.

At least 37 records · Page 2Linked to original sources

High density lipoprotein cholesterol as a mechanistic probe for the side chain cleavage reaction.

Cholesterol side chain cleavage reaction catalyzed by purified cytochrome P-450scc was stimulated 4-5 fold when cholesterol in rat high density lipoprotein was used as a substrate as compared to the case where cholesterol plus 0.1% Emulgen 911 was used. In the case of the cholesterol-Emulgen system, the Vmax value of activity was not obtained even when a 20 times molar excess of adrenodoxin over the cytochrome was used. However, in the case of the lipoprotein, a 2-3 times molar excess of adrenodoxin over the cytochrome was enough to obtain the half value of Vmax. HPLC gel filtration experiments showed that the three enzymes were eluted from the column as a complex regardless of adding the lipoprotein as judged by the activity and the blotting analysis. However, the activity with the lipoprotein was detected significantly earlier than that in the absence. These and other lines of evidence suggest that the lipoprotein vesicles promote a complex formation among the three enzyme components and serve as a probe for emphasizing a significance of a cluster mechanism in the reaction.

Adrenal Cortex↗

[Clinical evaluation of lenampicillin in the treatment of superficial suppurative skin and soft tissue infection. A double-blind study comparing amoxicillin].

A double-blind controlled clinical study between lenampicillin (LAPC), a newly developed oral ampicillin (ABPC) prodrug, and amoxicillin (AMPC) was conducted for the treatment of suppurative skin and soft tissue infection as grouped in 6 disease types. LAPC or AMPC were orally administered at a daily dose of 1,000 mg, in 4 equally divided doses. Each group was treated for 14 days. The results indicated that LAPC was equal to AMPC in evaluations of effectiveness and usefulness, although incidence of severe side effects was slightly lower in LAPC. The number of cases studied was 235 (115 in the LAPC group, 120 in the AMPC group). Among these, 10 patients (4 in LAPC, 6 in AMPC) were excluded and 12 patients (5 in LAPC, 7 in AMPC) dropped out. Final global improvement rating was evaluated in 213 patients (106 in LAPC, 107 in AMPC). General usefulness rating was evaluated in 215 patients (106 in LAPC, 109 in AMPC), and overall safety rating was evaluated in 231 patients (115 in LAPC, 116 in AMPC). Final global improvement rating of LAPC was, "cured", 55.7% and "cured" and "remarkably improved", 79.2%. The rate increased to 88.7% when "improved" was included. On the other hand, in the AMPC group, "cured" was 50.5%, and "cured" and "remarkably improved" was 76.6%. The rate increased to 91.6% when "improved" was included. No significant difference was found between the 2 drug groups. In overall safety rating of LAPC, "safe" was 93.9%, while in the AMPC group, "safe" was 94.0%. No significant difference was found between the 2 drug groups. Side effects were noted in 2 of 115 patients (1.7%) among the LAPC group and in 5 of 116 patients (4.3%) among the AMPC group. Incidence of severe side effects was slightly lower in LAPC (P less than 0.1). General usefulness rating of LAPC was, "remarkably useful", 56.6% and the rate increased to 86.8% when "useful" was included. In the AMPC group, "remarkably useful" was 51.4%, and increased to 84.4% when "useful" was included. No significant difference was found between the 2 drug groups.

Adult↗

[Clinical studies on lenampicillin in the therapy of skin and soft tissue infections].

Clinical evaluation of newly developed oral ampicillin prodrug lenampicillin (LAPC, KBT-1585) applied to patients with superficial purulent infection at a dosage of 750 approximately 1,500 mg daily was conducted. Additionally, as part of the basic study, transition of the compound to the human skin tissue was observed. With regard to transition to human skin tissue in 11 presurgery dermatitis cases, 250 mg or 500 mg of LAPC was administered to 2 approximately 3 hours before surgery. Comparison was made between concentrations in serum and in skin tissue. Results in the case of 250 mg application showed serum concentration to be 1.28 approximately 3.32 micrograms/ml, and in skin tissue, 0.13 approximately 0.82 micrograms/g. At 500 mg, serum concentration was found to be 2.23 approximately 10.05 micrograms/ml, with skin tissue concentration at 0.45 approximately 1.34 micrograms/g. Rate of clinical efficacy in the treatment of the 183 cases of superficial purulent infection was 79.2%. By grouping of the infections (Table 3), high efficacy rates were obtained in the second group, at 85.7%; in the third at 88.9%; and in the fourth group at 96.4%. Evaluation of usefulness from the standpoint of safety was 77.6%. Good results were obtained in the third group with 88.9%; and in the fourth group with 96.4%. LAPC's efficacy rates against individual strains of bacteria in simple infection are as follows: Staphylococcus aureus, 74.6%; Staphylococcus epidermidis, 76.3%; GPC, 100%; anaerobes, 87.5%. In polymicrobial infections the rate was 84.6%. The rate of efficacy against all strains of bacteria was 76.0%. Adverse reactions were found in 13 cases (14 incidences) out of 193. The rate of incidence was 7.3%, with allergic response accounting for 5 cases, digestive tract disorders, 7 cases, and mouth odor, 1 case. There were 5 cases (6 incidences) of abnormal deviation of laboratory findings. In all cases, abnormal deviations were mild and their relation to the drug was unclear.

Administration, Oral↗

[An autopsy case of membranous lipodystrophy (Nasu)].

Membranous lipodystrophy (Nasu) is characterized by polycystic osteodysplasia associated with dementia. We recently experienced a 9th autopsy case in Japan. This 50 year-old male, eldest in the reported autopsied case in Japan, presented bone fracture at 35 year of age and dementia started at 45. His parents were cousins. His sister, died with carcinoma of the bladder at 35, developed marked osteoporosis with multiple pathological fractures and "membrano-cystic" lesions were found in her adipose tissue. The roentgenogram of the patient's long bone revealed radiolucent and cystic areas with irregular boundaries at the metaphyses. Computer tomography of the brain examined during the last 3 years showed slowly progressive brain atrophy. Calcifications of the basal ganglia or low density area in the white matter were not found. Autopsy showed typical "membrano-cystic" lesions in the adipose tissue of the whole body including bone marrow. Brain weighed 1,030 g. There was a mild convolutional atrophy at the frontal lobe. White matter was diffusely atrophic. Demyelination was limited to the frontal lobe, where only small number of perivascular sudanophilic lipid-laden macrophages were found. Fibrillary astrocytes were rather diffusely proliferated, consistent with sclerosing leukoencephalopathy. Many spheroids were found in the frontal and occipital deep white matters, and external capsule. Ultrastructural study of spheroid revealed increased amount of neurofilament, vesicles with free patchy dense materials and degenerated mitochondria, which were consistent with primary axonal degeneration.

Adipose Tissue↗