MHC class I restricted T-cell mediated cytotoxicity (CTL) in patients with Crohn's disease.
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Biomedical subjects
Publications and source records attributed to Y Nakazawa.
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The effects of methyl vitamin B12 (5-6 mg/kg, p.o.) on the entrainment of circadian running wheel activity rhythm to a new lighting schedule were measured in rats. After the light-dark (LD) cycle was abruptly reversed, rats given vitamin B12 took less time to entrain their circadian locomotor activity rhythm to the new cycle than did controls. This result indicates that vitamin B12 accelerates the reentrainment of the mammalian circadian activity rhythm following an abrupt change in the environmental LD cycle.
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We investigated the effects of acute and repeated alcohol ingestion on plasma levels of hormones associated with the functioning of the hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-adrenal (HPA) systems in normal males. In the first experiment, 7 normal male subjects were given ethanol (1.3 g/kg) in the form of a 43% alcohol solution of whiskey and water over a 30-min period (from 19:00 h to 19:30 h); blood samples were collected 30 min and immediately before the beginning of alcohol ingestion and then at intervals of 30 min for 180 min. Blood ethanol levels rose sharply and reached their maximum at 60 min, remaining above 1.0 mg/ml until 180 min. Prolactin levels increased, reaching a peak at 60 min, gradually returning to the initial value at 180 min. Decreased testosterone levels were observed only at 30 min. Luteinizing hormone (LH), adrenocorticotrophic hormone (ACTH) and cortisol levels did not show any increases. In the second experiment, 9 normal males were given the same dose of alcohol, but this was given on 7 consecutive evenings and the hormonal changes were examined on the 1st and 7th days, only at 30 and 60 min after alcohol ingestion began (during the period that blood ethanol levels were ascending to their peak). The results on the 1st day reconfirmed the findings in the first experiment and on the 7th day, the last alcohol ingestion produced increases in prolactin levels and decreases in testosterone levels at 30 and 60 min, but did not change other hormone levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Nine males with sleep apnea DOES syndrome and three males with sleep apnea DIMS syndrome were treated with prosthetic mandibular advancement (PMA). The method uses a prosthesis, which is designed to advance the mandible 3-5 mm to prevent upper airway occlusion during sleep. The apnea index in the obstructive-type apnea and the percentage of time spent in obstructive apnea decreased significantly with PMA. Although the apnea index showed merely a tendency to decrease in central apnea (p < 0.1), the percentage of time spent in central apnea decreased significantly with PMA. A marked improvement in sleep structures was observed with PMA; a significant increase was seen in total sleep time, percent slow wave sleep (SWS) and percent rapid eye movement (REM) sleep, and the time spent in intra-sleep awakening decreased remarkably. PMA had excellent effects on snoring, and daytime hypersomnolence was reduced in almost all patients. Moreover, a survey on the therapeutic effects of PMA on sleep apnea syndrome and problems associated with wearing PMA was performed with a questionnaire for the sample of nine DOES patients and an additional 22 patients who were treated over a long time. The therapeutic effects could be maintained without any problems in about 2/3 of these patients. The therapeutic mechanisms of PMA in its reduction of both obstructive and central apnea are discussed.
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The effects of sodium-4-[2-(2,3-dimethyl-4-[1-(4-isobutylphenyl) ethoxy]benzolamino)phenoxy]butyrate (ONO-3805), newly developed as a non-steroidal 5 alpha-reductase inhibitor, on rat accessory sex organs was compared with chlormadinone acetate (CMA) and non-steroidal antiandrogen, flutamide (FLU). ONO-3805 demonstrated excellent antiandrogenic activity which was similar to that of CMA in reducing the accessory sex organ weight. Moreover this agent did not show any significant effects on the serum testosterone level, but CMA and FLU changed it significantly. We previously reported the androgenic activity of antiandrogen (CMA, FLU, AA560, cyproterone acetate, medroxy progesterone, estrogen), but ONO-3805 is free of androgenic activity.
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It was reported that a new steroidal anti-androgen, TZP4238 (17 alpha-acetoxy-6-chloro-2-oxapregna-4,6-diene-3,20-dione), was 10 times stronger than chlormadinone acetate (CMA) as the in vivo anti-androgenic potential. To confirm this result, the effect of TZP4238 and CMA on ventral prostates of intact rats, or castrated ones treated by testosterone, was investigated. Our experiments demonstrated that TZP4238 was 3-5 times stronger than CMA. The effects of this compound on the androgen-receptor complex formation in the human and rat prostates were investigated and compared to the other anti-androgen and related compounds. An aliquot of cytosol or KCl extract from rat or human prostate was incubated with [3H]R1881 in the presence of various tested compounds. By means of dextran coated charcoal assay and sucrose density gradient centrifugation analysis, TZP4238 and TZP4239 showed a stronger inhibitory effect than other compounds except dihydrotestosterone. Judging from all these results, it was estimated that TZP4238 was 2-3 times stronger than CMA. The Scatchard plot analysis revealed that the inhibitory effect of TZP4238 was a competitive type. Between CMA and TZP4238, the difference of in vivo anti-androgenic potential was not identical with that of the inhibitory effect on the androgen-receptor complex formation.
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One hundred thirty-six alcoholic inpatients were studied with regard to the association between alcoholism and depression. They fell into three groups: primary depression, secondary depression and non-depressive alcoholism. The main results obtained are as follows: (1) Depression was found in 46 patients (33.8%) in the present or past history; 13 were regarded as primary depression and 33 as secondary depression. (2) The clinical symptoms and the background of the primary group resembled those of endogenous depression. (3) The clinical features, including the duration of depressive episodes in the secondary depression group differed from those in the primary group. (4) No statistically significant differences were noted as to the rates of family-history of alcoholism and depression among the three groups. Clinical and biological differences between the primary and secondary groups were discussed on the basis of these results.
The fact that the elderly are usually aware of early sleep onset and early morning awakening shows that the phase of sleep-wake rhythms in the elderly is more advanced than that in young adults. Since it has been suggested that human sleep onset, morning awakening, sleep period and depth of sleep are highly influenced by body temperature rhythms, rectal temperature rhythms were analyzed in 7 healthy elderly and 7 healthy young adults under the condition with time cue. Although a significant 24-hour period was found in the rhythms for all subjects, the phase of the rhythms in the elderly was more advanced than in the young adults. Moreover, a significant inverse correlation was observed between age and acrophase time in the elderly.
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Eight patients with recurrent prostate cancer were treated with Etoposide and CDDP or Etoposide alone. Etoposide was administered at a dose of 20 approximately 50 mg/m2/day for 5 consecutive days and CDDP was administered at a dose of 30 approximately 50 mg/m2 on the first day. Treatment was repeated every 3 or 4 weeks. Patients who were treated with combination chemotherapy (Etoposide + CDDP) were those with no hematological abnormalities, no renal dysfunction and good performance status. Three patients were treated with Etoposide and CDDP and five were treated with Etoposide alone. Clinical evaluation was as follows: 3 patients (2 with Etoposide and CDDP, 1 with Etoposide alone) had PR (37.5%) and 5 patients had PD (62.5%). We obtained the impression that lesions of soft tissue metastasis responded well to this chemotherapy and that this combination chemotherapy was more effective than Etoposide alone. Major complications were myelosuppression, gastrointestinal upset and loss of hair. However, they were tolerable in patients with good performance status. This combination chemotherapy (Etoposide + CDDP) seems to be worth further clinical trials to patients who were tolerable.
It is well known that some adrenal androgens are converted into testosterone and dihydrotestosterone which are more powerful androgens than the adrenal androgens. However, most of the experiments to investigate the antiprostatic agents have been done on rats which secrete only a marginal amount of adrenal androgen. A study was performed to investigate the effects of antiprostatic agents on the action of the adrenals in rats. Non-sterodidal antiandrogens flutamide and 1-chloro-2-hydroxy-2-methyl-N-(3,4,5-trichlorophenyl)propanamide (AA560), steroidal anti-androgens, chlormadinone acetate (CMA) and 17 alpha-acetoxy-6-chloro-2-oxapregna-4,6-diene-3,20-dione (TZP-4238) and 5 alpha-reductase inhibitor, sodium (-)-4[2-[2,3-dimethyl-4-[1-(4-isobutylphenyl)ethoxy]benzolamino ] phenoxy]butyrate (ONO-3805) and N-(2-methyl-2-propyl)-3-oxo-4-aza-5 alpha-androst-l-ene-17 beta-carboxamide (MK-906) were tested in rats treated with dehydroepiandrosterone sulfate (DHEA-S) and androstenendione (A). In the noncastrated rats not treated with DHEA-S and A, all of these agents decreased the accessory organ weights in a dose dependent manner. In the rats treated with LHRH agonist and DHEA-S and A, all agents (3.3 mg/day) showed similar effects in intact rats. However nonsteroidal antiandrogens and TZP-4238 were stronger than the others. It was not clear whether this effect was mediated through the suppression of adrenal androgen action or the inhibition of physiological increase in testosterone caused by an LHRH agonist. The effects of Flu, ONO-3805, CMA and TZP-4238 on the accessory sex organs were investigated in castrated rats receiving DHEA-S and A.(ABSTRACT TRUNCATED AT 250 WORDS)