Biomedical subjects
Publications and source records attributed to M Oka.
In spite of the small experiences, silicone capping with gap osteoarthroplasty in high level is thought to be one of the valuable procedures for TMJ ankylosis. In the view of kinesiology, a normal joint cannot be reconstructed, because the mandibular movement in ankylosis is far from the normals.
The gastrokinetic effects of AS-4370, 4-amino-5-chloro-2-ethoxy-N-([4-(4-fluorobenzyl)-2-morpholinyl] methyl) benzamide citrate, were compared with those of metoclopramide in experimental animals. In rats, AS-4370 increased the gastric emptying of a semi-solid meal and of resin pellets at dose ranges of 0.03-30 mg/kg and 1-10 mg/kg p.o., respectively. The minimal effective doses were 3-10 times lower than those of metoclopramide. Gastric emptying, delayed by gastroduodenal surgical intervention, was improved with AS-4370 (0.3-3 mg/kg p.o.). In conscious dogs with strain gauges implanted, AS-4370 (0.5 and 1.0 mg/kg i.v.) enhanced antral and duodenal motility without affecting ileal and colonic motility, indicating a selective enhancing effect on upper gastrointestinal motility. AS-4370 (10(-7) - 3 x 10(-5) M) increased electrically evoked, cholinergically mediated contractions in isolated guinea-pig ileum. AS-4370 (3 mg/kg i.v.) was without effect on gastric acid secretion in anesthetized rats. Unlike metoclopramide, AS-4370 neither depressed the active avoidance response in mice nor the food-reinforced lever pressing response in rats, even at 100 mg/kg p.o. Moreover, AS-4370 (10(-4) M) showed no affinity for D2, alpha 1, alpha 2, 5-HT1 and 5-HT2 binding sites in rat brain synaptic membranes. These results suggest that AS-4370 is a new and potent gastrokinetic agent that lacks dopamine D2 receptor antagonist properties.
As sex hormones are considered to play a role in the etiology of the slipped upper femoral epiphysis, the influence of sex hormones on the mechanical strength of the epiphyseal plate was investigated in 310 female and 70 male rats. Ovariectomy weakened the strength of the growth plate while orchiectomy strengthened it. Estrogen given after ovariectomy, markedly strengthened the plate. Histologic examination revealed that the width of the growth plate was narrower in the mechanically stronger group. Hydroxyproline content increased and hexosamine content decreased in the epiphyseal plates of the mechanically stronger group. These observations confirm the view that sex hormones, especially estrogen, regulate the mechanical, morphologic, and biochemical functions of the growth plate.
A MEMR syndrome occurred in a 9-year-old boy with cerebral atrophy and was established by computed tomography scans of the cranium. The patient had mental retardation, delayed speech development and microcephaly, and high levels of urinary dermatan sulfate and heparin sulfate, which are characteristics of this inborn error of mucopolysaccharide metabolism.
The effect of physiological concentrations of zinc on the in vitro pressor responses of male Wistar rat mesenteric preparations to norepinephrine was systematically studied over a 2-year period. A marked seasonal variation in the response of the preparations was observed over a range of zinc concentrations from 3.5 X 10(-11) to 3.5 X 10(-6) M. All concentrations of zinc inhibited pressor responses during the winter (November to March), but during the spring months (April to May) zinc became very much less effective and low concentrations of zinc potentiated the response. Inhibition of the pressor response at this time only occurred at zinc concentrations above 3.5 X 10(-7) M. In the summer months. (June to September) the zinc effect shifted back towards the winter situation with lower concentration of zinc potentiating and higher concentrations inhibiting vasoconstriction. Pinealectomy of the rats a week prior to preparation of the mesenteric beds very significantly enchanced pressor responses to norepinephrine in the winter months but had much less effect in the summer. The seasonal variation noted in preparations from control rats was maintained following pinealectomy but the amplitude was reduced. Perfusion of melatonin (4.3 X 10(-10) M through preparations from pinealectomized rats enhanced the inhibitory effect of zinc compared to the response to zinc from similarly perfused preparations from control rats. Thus, the rat mesenteric vascular bed is an in vitro model of seasonal variation in vascular reactivity which is sensitive to physiological concentrations of zinc. The origin of the seasonal rhythmicity remains speculative particularly in view of the fact that the rats were maintained under constant photoperiod. That the pineal may modulate the seasonal effect of zinc is suggested by the shift in response to zinc following pinealectomy. Melatonin reversed the effect of pinealectomy on this preparation implicating it as a possible mediator of normal vascular reactivity to zinc. A possible influence of magnetic radiation in evaluating the occurrence of seasonally varying phenomena in vitro should be considered.
We determined the in vitro cytotoxicities of promising new platinum complexes, an inhibitor of topoisomerase I, and novel anthracycline derivatives, and examined using clonogenic assay whether these compounds are cross-resistant in CDDP-resistant sublines derived from human non-small cell lung cancer (NSCLC) cell lines. Cytotoxicities were evaluated by means of the relative antitumor activity (RAA = peak plasma concentration/IC50 values), which we reported previously as a model for predicting antitumor activity. Of the CDDP analogues tested, including carboplatin (CBDCA), [(glycolate-0,0') diammineplatinum (II) (254-S)], ormaplatin [tetrachloro-(d,1-trans)- 1,2-diaminocyclohexaneplatinum (IV) (OP)] and oxaliplatin [oxalato (trans-1-1,2-diaminocyclohexane) platinum (II) (1-OHP)], no agent showed superior antitumor activity compared to CDDP. ME2303 [7-O-(2,6-dideoxy-2-fluoro-alpha-L-talopyranosyl) adriamycinone-14-O -pimelate], a new anthracycline derivative, showed higher antitumor activity than adriamycin (ADM). The CDDPresistant sublines, PC-9/CDDP and PC-14/CDDP, were 18.3- and 7.7-fold more resistant to CDDP compared to the respective parent cell lines. The CDDP analogues were all cross-resistant to CDDP and the order of relative resistance values was CBDCA > 254-S > 1-OHP > OP for PC9/CDDP and 254-S > CBDCA > 1-OHP > OP for PC-14/CDDP. Although OP showed cross-resistance to CDDP, OP was the most active against the CDDP-resistant sublines with relative resistance values of 3.8 and 1.6 for PC-9/CDDP and PC-14/CDDP, respectively. ME2303 and CPT-11, [7-ethyl-10-(4-[1-piperidino]-1-piperidino) carbonyloxycamptothecin], an inhibitor of topoisomerase I, was active against CDDP-resistant human NSCLC cell lines. These results suggest that OP, ME2303 and CPT-11 could be active in patients with, NSCLC clinically resistant to CDDP.
Multidrug resistance-associated protein (MRP) is a 190 kD transmembrane protein and a potentially important drug-transporter protein in human cancers. While the MRP gene is expressed in normal cells and tissues, the expression in solid tumors is not sufficiently determined. MRP and mdr1 mRNA expressions were examined in normal lung parenchyma and in tumor tissues from six small cell lung cancer (SCLC) patients who had received preoperative chemotherapy and eleven nonsmall cell lung cancer (NSCLC) patients. The reverse transcriptase polymerase chain reaction was used. Normal lung tissues and all SCLCs expressed abundant levels of MRP mRNA, while the NSCLCs expressed a wide range of levels from low to high. Most tumor tissues coexpressed both MRP and mdr1, but the levels of mdrl expression was low except in two SCLCs and one NSCLC. MRP is more likely than mdr1 to be one of the clinical multidrug resistance mechanisms found in lung cancer.
BACKGROUND/AIMS: We have previously reported the efficacy of intraarterial combined immunochemotherapy for 24 patients with unresectable hepatocellular carcinoma. This therapy consists of recombinant interleukin-2, OK-432, adriamycin, cyclophosphamide, and famotidine. We observed a complete response (CR) in 4, partial response (PR) in 3, minor response (MR) in 7, no change (NC) in 7, and progressive disease (PD) in 3. The response rate (CR+PR+MR) was 58.3%. The overall 2-year survival rate was 52%. The present study was designed to analyze the phenotype of tumor infiltrating lymphocytes and apoptosis-related antigen (Ley and Fas antigen) expression in tumor cells. MATERIALS AND METHODS: The analysis of phenotype of tumor infiltrating lymphocytes and apoptosis-related antigen (Ley and Fas antigen) expression in tumor cells were performed by immunohistochemical stain using resected specimens. RESULTS: Lymphocytes markedly infiltrated into the tumor lesions in treated patients compared with untreated patients. Phenotypes of tumor infiltrating lymphocytes were CD8+ and HLA-DR+. Ley-positive and Fas-positive tumor cells were observed as well. Furthermore, in the strong lymphocyte infiltrating area, the Fas antigen in tumor cells were strongly expressed. CONCLUSION: In conclusion, the antitumor effect of intraarterial combined immunochemotherapy may be related with the activation of tumor infiltrating lymphocytes. These lymphocytes may kill tumor cells in an apoptotic fashion. Fas ligand expression of TILs should be determined in future.
Human P-glycoprotein (Pgp) encoded by the MDR1 gene confers multidrug resistance to cancer cells. The clinical role of MDR1/Pgp in lung cancer is not fully understood. A total of 87 lung cancer surgical tissue samples, including previously untreated 84 non-small-cell (NSCLC) and three small-cell lung carcinoma (SCLC), were analyzed for levels of MDR1 mRNA determined by Northern blotting and compared with MDR1-positive cell lines. Fifteen percent (13/87) of the tumors were positive for the MDR1 gene, but the level was low in all samples except in one adenocarcinoma which expressed a high level of MDR1. The gene expression in these tumors did not relate with any pathologic factors such as histologic type, pathologic stage and tumor size. The SCLC and only one of the 14 MDR1-negative NSCLC responded to adjuvant chemotherapy after surgery. The present results indicate that the MDR1 gene is not associated in NSCLC with tumor progression and drug resistance.
We conducted a study of 1,143 nurses working at hospitals in the southern part of Ibaraki prefecture in Japan to clarify the path diagram of the relationship between life style, mental health and psychosocial factors. General health questionnaire, life practice index, social support, number of night shifts and perceived health-status were used in this study. The data were analyzed using multivariate analysis and path analysis. The results are as follows: 1) The path analysis showed that General health questionnaire was directly affected by perceived health-status and social support. 2) General health questionnaire was directly and indirectly affected by Life practice index and social support. 3) Social support and number of night shifts were indirectly affected the General health questionnaire through the perceived health-status.
Multidrug resistance-associated protein (MRP) mRNA expression and drug sensitivity in lung cancer cells were examined, and the effects of verapamil, a modulating agent for MRP, on drug sensitivity were also tested. Nine cell lines expressed various levels of MRP gene expression but not the MDR1 gene. The levels were higher in non-small cell carcinoma cells (NSCLC) than in small cell carcinoma cells (SCLC). Clear correlations between the MRP gene level and the sensitivity to etoposide (VP-16) and doxorubicin (Dox) were observed except for one cell line which highly expressed DNA topoisomerase II. Positive correlations between the MRP gene levels in three cell lines and the modulation effects of verapamil in VP-16, Dox, and vincristine were observed. The present results indicate that MRP probably confers intrinsic multidrug resistance in NSCLC rather than in SCLC.
Metallothioneins (MTs) are induced by various stimuli and probably confer drug resistance in tumor cells in vitro. To investigate whether MT expression in lung cancer is induced by chemotherapy, ninety-seven surgical specimens from patients who had or not received chemotherapy containing cisplatin, were stained immunohistochemically for MT. In untreated tumors, 23% (15/64) of all tumors and 27% (15/56) of non-small-cell carcinoma (NSCLC) stained positive, while all eight small-cell carcinoma (SCLC) were negative. In treated tumors, 52% (17/33) of all tumors, 80% (12/15) of NSCLC and 28% (5/18) of SCLC stained positive. The proportion of positively-stained tumors was significantly higher in treated NSCLC compared with untreated NSCLC (P = 0.0005) and treated SCLC (P < 0.005). Our results indicate that MT expression increases following chemotherapy and that such expression may confer during resistance in lung cancer, especially NSCLC.
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.
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