Biomedical subjects
Publications and source records attributed to S Kawabata.
A method to determine risk factors for particular outcomes using trained multilayer neural networks is proposed. The basic idea is to measure the partial differentials of the output with respect to input variables of the network. Differentiable activation functions and continuity of input variables is assumed.
Cells from benign and borderline malignant mucinous cystadenomas surgically resected from three postmenopausal women with elevated serum estradiol levels were found to have different abilities to synthesize estrogen from [14C]-cholesterol. Addition of gonadotropins to cultured cells with low levels of estrogen synthesis did not result in any significant increase in estrogen synthesis. Immunohistochemical studies of these mucinous cystadenomas showed that LDL receptors were distributed in the benign cystadenoma cells and in the stromal cells of borderline tumors, but not in the cystadenoma cells of borderline tumors. Sterol regulatory element binding protein was immunohistochemically shown to be distributed in the mucinous cystadenoma cells of borderline tumors, but not in the benign cystadenoma cells.
The effects of YM-14673, a new thyrotropin-releasing hormone (TRH) derivative (N alpha-[[(S)-4-oxo-2-azetidinyl]carbonyl]- L-histidyl-L-prolinamide dihydrate), on the pyramidal motor system were studied in comparison with those of TRH in rats subjected to electrical destruction of the left internal capsule, a brain region of the pyramidal motor tract. In this model, neurological deficits such as hemiplegia and decrease of amplitude of electromyographic activity evoked by electrical stimulation of the left sensory motor cortex, were observed on the right legs. Drug administrations were started from 1 day after the surgical operation on and conducted once or several times a day for 13 days. YM-14673 (0.1 mg/kg, i.p., i.v., i.m.; 1 mg/kg, p.o.), unlike its metabolite (M-1) (10 mg/kg, i.p.), accelerated the recovery from neurological deficits. Decrease of evoked EMG activity on the 6th day after surgery was improved by administration of YM-14673 (0.1 mg/kg, i.p.). Intraperitoneal administration of TRH (1-10 mg/kg) once a day did not show any influence on neurological deficits. However, multiple i.p. administrations of TRH seven times in 1 hr accelerated recovery from deficits. These TRH activities are supported by metabolic studies which indicated that a high plasma level of TRH was maintained by multiple administrations of TRH. These results suggest that YM-14673 has a facilitatory effect on the pyramidal motor system which is due, in part, to its TRH-like properties.
Effects of YM-14673, a new thyrotropin-releasing hormone (TRH) analogue, on neurological deficits were observed in comparison with those of TRH and citidine diphosphate choline (CDP-choline) in rats with an experimental hematoma. Unilateral cerebral hematoma was prepared by injection of 0.25 ml of autologous blood into the region around capsula interna, putamen and caudate nucleus of the left cerebral hemisphere of the rats. The drug was administered once or multiple times a day immediately after the surgical operation for 7 days and measurement of neurological deficits was conducted every day for 7 days. Neurological deficits, such as hemiplegia, were observed maximally on the 3rd day after the operation and then gradually recovered in the saline-treated group. YM-14673 (0.1, 0.3 mg/kg i.p.) accelerated the recovery of neurological deficits. Single i.p. administration of TRH did not affect the neurological deficits; however, multiple administration (7 times a day for 7 days) of TRH accelerated the recovery of neurological deficits. CDP-choline, a cerebral metabolic enhancer, even in a dose of 300 mg/kg (i.p.) did not show any influence on neurological deficits. These results suggest that YM-14673 ameliorated neurological deficits in the cerebral hematoma models, presumably due to TRH-like activity. Possible mechanisms of the pharmacological actions of YM-14673 are also discussed.
The clinical efficacy in preoperative assessment with CA72-4 for gastric cancer was studied in comparison with CA19-9 and CEA. These three tumor markers were examined simultaneously, preoperatively in 100 cases (44: early cancer, 56: advanced cancer) of gastric cancer. Additionally the efficacy of CA72-4 in follow-up postoperative monitoring for the recurrence was investigated. Positive rate of CA72-4, CA19-9 and CEA for early cancer was 2.3%, 11.4% and 9.1% and that for advanced cancer was 37.5%, 17.9% and 35.7% respectively, thus CA72-4 gave the highest positive rate for advanced cancers. And CA72-4 revealed higher positive findings in stage IV, in infiltrating type, in diffuse type, in cancer invading deeper than p-T3. Further, CA72-4 was positive in 50% for cancer with peritoneal dissemination, whereas CEA was positive in 8.3%, CA19-9 in 16.3%. The most beneficial combination among these three tumor markers was CA72-4 and CEA, and by which, positive rate was 53.6%. Regarding follow-up, CA72-4 showed first elevation prior to other markers in some cases before clinical recurrence was confirmed. CA72-4 appeared to be a useful marker for managing gastric cancer.
Lung resistance-related protein (LRP) is the human major vault transporter protein and is suggested to confer anticancer drug resistance. We quantitated the level of LRP mRNA expression in 10 gastric and 14 lung cancer cell lines by RT-PCR, and examined the relationship between its level in these cells and their sensitivities to anticancer drugs. HT1080 fibrosarcoma cells were used as positive controls for LRP. LRP mRNA was expressed in all gastric and lung cancer lines, and its level in each cell type was less than two-fold that of HT1080 cells, except for two lung cancer lines. The correlation between the level of LRP mRNA expression and cisplatin sensitivity was significant in lung cancer lines (r = 0.762, P = 0.028), and borderline in gastric cancer lines (r = 0.631, P = 0.129). There was no correlation between the level of LRP mRNA expression and etoposide, doxorubicin, vincristine, or SN-38. Our results suggest that LRP is commonly expressed in gastric and lung cancers, and may confer their resistance to cisplatin.
Systemic and topical antimicrobial treatment for acne vulgaris remains the mainstay method of therapy in Japan. Strains of Propionibacterium acnes (P. acnes) resistant to erythromycin (EM), clindamycin (CLDM), tetracycline (TC), doxycycline (DOXY) and minocycline (MINO) have been reported. The aim of the present study was to examine the antimicrobial susceptibility to 10 currently used antimicrobial agents of 50 strains of P. acnes isolated from acne lesions and identified using a Rap ID ANA II panel. Minimum inhibitory concentrations (MIC) were determined by the agar dilution method according to the criteria of the Japan Society of Chemotherapy. EM, ampicillin (ABPC), and CLDM were the most potent drugs, followed by MINO, nadifloxacin (NDFX), cephalexin (CEX), DOXY, ofloxacin (OFLX), and TC. In terms of the MIC80, EM and ABPC were the most potent, followed by CLDM, NDFX, MINO, CEX, DOXY, OFLX, TC and gentamycin (GM). Although most of the strains used were susceptible to the antimicrobial agents tested, strains of P. acnes resistant (MIC 12.5 mug/ml) to EM (4%), CLDM (4%), DOXY (2%) and TC (2%) were observed. In this study, no strains of P. acnes resistant to MINO were seen, suggesting that oral MINO is the most useful treatment for acne vulgaris with minimal risk of bacterial resistance.