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Biomedical subjects

S Honma

Publications and source records attributed to S Honma.

At least 109 records · Page 6Linked to original sources
PubMed1996

Melatonin rhythm is not shifted by lights that suppress nocturnal melatonin in humans under entrainment.

Effects of a single light exposure on the circadian rhythm in plasma melatonin were, examined in young males to obtain the threshold of light intensity for suppressing the nocturnal melatonin level on the one hand and to understand the relationship between the light-induced phase shift of melatonin rhythm and the melatonin suppression on the other hand. Eight subjects spent 3 days in an experimental living facility where light intensity was set below 200 lx and were exposed to light for 3 h in the early morning on the 2nd day. The same procedure was repeated five times in each subject with an interval of at least 3 wk, and one of five light intensities was tested in each trial. As a result, nocturnal melatonin level was not suppressed by light of 200 lx but significantly suppressed by light of intensity > or + 500 lx. On the other hand, the circadian melatonin rhythm was not shifted by any light intensity up to 10,000 lx. It is concluded that the threshold of light intensity for suppressing the melatonin level is located between 200 and 500 lx in young Japanese males, and the threshold for phase shifting the circadian melatonin rhythm was much greater than that for suppressing the nocturnal melatonin level in humans under entrained conditions.

Adult↗
PubMed1996

Circadian rhythm and response to light of extracellular glutamate and aspartate in rat suprachiasmatic nucleus.

Extracellular concentrations of glutamate and aspartate were measured in the vicinity of rat suprachiasmatic nucleus (SCN) by means of in vivo microdialysis. The concentrations of both excitatory amino acids (EAAs) were higher during the dark phase than during the light under the light-dark cycle, showing pulsatile fluctuations throughout the day. When rats were released into the complete darkness, the 24-h pattern in the aspartate continued for at least one cycle, whereas that in the glutamate disappeared. The nocturnal increases in the EAA levels were not due to the increase of locomotor activity during the nighttime, because the 24-h rhythms were also detected in animals under urethan anesthesia. The patterns of extracellular EAA levels were changed when rats were released into the continuous light. Circadian rhythm was not detected in the glutamate, whereas the 24-h pattern was maintained in the aspartate with the levels increased to various extents. A 30-min light pulse given either at zeitgber time (ZT) 1 or ZT 13 elevated the EAA levels during the latter half of the light pulse, except glutamate by a pulse at ZT 1. The extracellular EAA levels in the vicinity of the rat SCN showed the circadian rhythm with a nocturnal peak and increased in response to the continuous light and a brief light pulse. The aspartate level is considered to be regulated by the endogenous circadian rhythm, but the glutamate levels seems to be modified by the light-dark cycle.

Anesthesia↗
PubMed1996

Aging affects development and persistence of feeding-associated circadian rhythm in rat plasma corticosterone.

Effects of aging on development and persistence of feeding-associated circadian rhythm were examined with respect to the prefeeding plasma corticosterone peak under restricted feeding. Old (20 mo), middle-aged (12 mo), and young (2.5 mo) male rats were subjected to a restricted feeding schedule for 21 days in which free access to food was limited to 2 h/day in the light phase. Prefeeding corticosterone peak was detected 1 wk after the start of the schedule in the young and 3 wk after in the old and middle-aged rats. After the restricted feeding, a feeding/ fasting cycle composed of 7 days of ad libitum feeding and 3 days of fasting was imposed four times. The persistence of feeding-associated rhythm was evaluated by examining the reappearance of the corticosterone peak at the previous meal time during each fasting period of the feeding/fasting cycle. The corticosterone peak was not detected in the old and middle-aged rats even at the first cycle, but it was still distinct at the third cycle in the young rats. In conclusion, aging impaired the development and persistence of feeding-associated circadian rhythm in rats.

Aging↗
PubMed1996

Effects of interleukin-2 and cyclosporin A on pathologic features in Mycoplasma pneumonia.

To elucidate the immunopathologic mechanisms of Mycoplasma pneumonia, the effects of interleukin-2 (IL-2) and cyclosporin A (CYA) on Mycoplasma pneumonia in mice were investigated. Mice were intranasally inoculated with Mycoplasma pulmonis (M. pul) and treated with IL-2, CYA, or minocycline (MINO) every day between Days 3 and 9. They were killed at Days 7, 14, or 21 after the inoculation. Cell-mediated immunity (CMI) of the host was assessed by delayed-type hypersensitivity (DTH) to sheep red blood cells (SRBC). Peribronchial and perivascular lymphocyte cuffing and the accumulation of macrophages at the ends of bronchioles were exacerbated (p < 0.05) in IL-2-treated mice at Day 14 and reduced (p < 0.05) in CYA-treated mice at Day 7. Although the DTH responses to SRBC of saline-inoculated, IL-2-treated mice were increased at Days 7 (p < 0.01) and 14 (p < 0.05), those of M. pul-inoculated, IL-2-treated mice at Day 7 could not recover to the control level. The CMI levels of M. pul-inoculated, CYA-treated mice were decreased at Days 7, 14 (p < 0.05), and 21 (p < 0.01). Mycoplasma organisms in the lung showed the greatest decrease (p < 0.05) in MINO- and IL-2-treated mice, but increased at Day 21 (p < 0.05) in mice treated with IL-2 alone. These results suggest that the pathologic features of Mycoplasma pneumonia could be modified by the degree of host CMI.

Animals↗
PubMed1996

Relationships between radiological pattern and cell-mediated immune response in Mycoplasma pneumoniae pneumonia.

The aim of this study was to determine the relationship between the radiological pattern of Mycoplasma pneumoniae and the level of cell-mediated immunity of the host. Computed tomographic (CT) scans of the chest and the results of the purified protein derivative (PPD) test were studied during the acute stage of infection in 54 patients with M. pneumoniae pneumonia. The CT findings were used to divide the patients into two groups: one group had a predominance of nodular opacities with a centrilobular distribution (Group N; n = 29); and the other showed a predominance of an airspace consolidation (Group C; n = 25). Forty out of 54 subjects had negative tuberculin skin tests ( < 10 mm induration). The positive rate of PPD reaction was higher in Group N (13 out of 29) compared to Group C (1 out of 25) (p = 0.0005); whilst pleural effusion appeared more frequently in Group C (10 out of 25) than in Group N (3 out of 29) (p = 0.023). There was no significant difference between Groups N and C in white blood cell and lymphocyte counts, level of antibodies to M. pneumoniae in sera, and severity of the disease. These findings suggest that the characteristics of the host cell-mediated immunity might influence the pattern of pulmonary lesions in M. pneumoniae infection.

Adult↗
PubMed1996

Studies on agents with vasodilator and beta-blocking activities. IV.

A series of novel pyridazinone derivatives (II) having a phenoxypropanolamine moiety was synthesized. Their hypotensive and beta-blocking activities were evaluated after intravenous administration of the compounds to anesthetized rats. Among them, the 5-chloro-2-cyanophenoxy derivative (29) showed the promising dual activities and was selected for further studies.

Adrenergic beta-Antagonists↗
PubMed1996

Incomplete testicular feminization syndrome: studies on androgen receptor(AR) function, AR gene analysis, and aromatase activities at puberty and long-term observations of clinical and hormonal features from infancy to puberty.

A female infant with partial androgen insensitivity (PAIS) was first seen at 4 months of age with slight virilization of the genitalia and externally palpable testes. Sex chromosome was 46,XY. She received left orchidectomy and exploratory laparotomy at 2 yr of age. At exploratory laparotomy, neither a uterus nor fallopian tubes were found. The right testis was preserved by fixing it at the external inguinal ring expecting spontaneous pubertal maturation. After discharge, serum levels of LH, FSH, testosterone (T) and estradiol (E2) were measured annually, and the steroid responses to hCG stimulation were examined every two yr. At the age of 10 yr, she developed breasts and a very feminine body habitus. At 12 yr, she received a clitoroplasty and right orchidectomy. The fibroblast cultures were made from the genital skin whereby androgen receptor (AR) binding was assessed by radioreceptor assay using 3H-DHT as the ligand, and thermoinstability of AR was noted despite normal maximum binding (Bmax) and dissociation constant (Kd) at 22 degrees C. But another binding experiment with 3H-Mibolerone resulted in the lack of receptor binding. AR gene analysis with direct sequencing of coding exons of the gene revealed no abnormality of the AR gene. 5 alpha-reductase activity was normal. Aromatase activity appeared to be enhanced in the genital skin fibroblast (GSF) cells as well as in the testicular tissue. The results of these studies indicated that the patient had PAIS with impaired AR functions and increased aromatase activity. After the discharge, the patient has maintained feminine phenotype, receiving estrogen therapy with mestranol 0.02 mg/day po.

Aging↗
PubMed1996

Two-year follow-up study of the effect of acid fog on adult asthma patients.

Acid fog is a complex mixture of atomospheric pollutants containing multiple stimuli that may be capable of inducing bronchoconstriction. To investigate the effect of ambient acid fog on bronchoconstriction, we examined the relation between the hospital visit for asthma symptoms of 102 patients and various meteorological conditions for over the two-year period from January 1992 to December 1993. Dense fog occurs frequently every summer in Kushiro, a city located in Hokkaido, northernmost island in Japan. The acidity of the fog ranged from pH 3.32 to 6.91 (mean pH = 5.05) during this period. A significant increase (p < 0.05) of hospital visits on a foggy day was found in 9 cases, and a tendency (p < 0.10) was found in 10 cases. The odds ratio for a hospital visit on a high water vapor pressure day (> 12 h Pa) was significantly high (p < 0.01) in 5 cases among the above 19 cases. To exclude the effect of high water vapor pressure, the data was restricted to the condition of a foggy day with low water vapor pressure (< 12 hPa); 9 patients had a significant increase (p < 0.05) in hospital visits on such a day. These results indicated that hospital visits for asthma symptoms was increased on acid fog days in 8.8% of adult asthma patients. Inhalation of naturally occurring acid fog may have adverse effects on the respiratory tract of the asthmatic patient.

Acids↗
PubMed1996

Prevalence of Parkinson's disease in Hokkaido, the northernmost island of Japan.

The prevalence of Parkinson's disease (PD) was investigated in Hokkaido, the northernmost island of Japan. A pilot case-finding study was carried out to estimate the prevalence in the entire island of Hokkaido (population = 5,643,647) initially, then we surveyed the prevalence at one of the smaller cities, Iwamizawa City (population = 80,417). We ascertained 5,342 cases with PD in Hokkaido and 77 cases in Iwamizawa City, estimating the crude prevalence of 94.7/100,000 in Hokkaido (June 30, 1993) and 95.8/100,000 in Iwamizawa City (April 1, 1994), respectively. We calculated that the crude prevalence rate of PD in Japan in currently close to 100/100,000, but the age-adjusted prevalence is still low, compared with those in Europe and North America.

Adult↗
PubMed1996

[Differentiation of extravillous trophoblast during normal pregnancy].

The implantation site in 25 pregnant uteri was studied morphologically and immunohistochemically to clarify the developmental process of extravillous trophoblasts (EVTs). 1. Dense trophoblastic invasion of the decidua was observed. Multinuclear trophoblasts appeared in the deciduo-muscular junction from the 10th week. Trophoblasts infiltrated decidual vessel walls, where extensive perivascular degeneration existed. EVTs may be indispensable for construction of the placenta. 2. In villous trophoblasts (VTs) the location of hCG and hPL was limited to multinuclear cells, whereas in EVTs hCG was present in a few mononuclear cells and hPL was observed in most mononuclear and multinuclear cells. The immunoreactivity of trophoblast-related monoclonal antibodies also differed: neither anti-Tropl (reactive with cytotrophoblasts (CTs)) nor NDOG1 (reactive with syncytiotrophoblasts (STs)) was reactive with EVTs. 3. The absence of hCG and hPL in mononuclear trophoblasts of the cell column indicates that EVTs differentiate after invading the decidua. Kurman et al. proposed the term intermediate trophoblast, indicating cells in transition from CTs to STs and EVTs, and this is based on the concept that the developmental processes of EVTs and VTs are identical. But the results of this study suggested an independent developmental process for EVTs and therefore it seemed that the term intermediate trophoblast should not be employed for EVTs.

Cell Differentiation↗
PubMed1996

[MRI changes in spontaneous intracranial hypotension].

We report MRI changes in a spontaneous intracranial hypotension(SIH). The patient was 29-year-old woman, who developed headaches in upright position, nausea, and vomiting preceded by pressure feeling of ears. Neurological examination was unremarkable except for hyperreflexia in the lower extremities. Lumbar punctures revealed very low opening pressure, a mild elevated CSF protein and a mild pleocytosis. No evidence of underlying systemic or neoplastic diseases was noted. The brain and cervical MRI showed diffuse and continuous pachymeningeal enhancement with gadolinium. Her symptoms gradually improved within two months without any treatment, and follow-up MRI showed resolution of the abnormalities within five months. The dural enhancement with gadolinium seen in the SIH should be kept in mind in case of hypertrophic pachymeningitis of unknown etiology, and be differentiated from such diseases as hypertrophic pachymeningitis associated with infectious, neoplastic diseases or sarcoidosis.

Adult↗
PubMed1995

Two distinct oscillators in the rat suprachiasmatic nucleus in vitro.

In the rat suprachiasmatic nucleus slice culture, circadian rhythms in the release of arginine vasopressin and vasoactive intestinal polypeptide were measured simultaneously and longitudinally. The phase relationship between the two peptide rhythms was relatively constant in the culture without a treatment of antimitotic drugs but became diverse by an introduction of antimitotics, which is generally used to reduce the number of glial cells. By monitoring the two rhythms continuously for 6 days, different periods were detected in culture with the antimitotic treatment. Furthermore, N-methyl-D-aspartate shifted the phase of the two peptide rhythms in the same culture differently. These results indicate that the arginine vasopressin and vasoactive intestinal polypeptide release are under control of different circadian oscillators.

Animals↗
PubMed1995

[The effects of antiandrogen TZP-4238 on plasma testosterone and LH and steroidogenesis in rat and canine testis].

TZP-4238 suppresses plasma testosterone in humans, but its action on the androgen biosynthesis pathway has not been established. Therefore, we researched the testicular testosterone level and the testosterone biosynthesis pathway in vitro in rats before and after receiving a single or continuous oral dose of TZP-4238. The total testosterone fell to 60% of the basal level within 3-8 hr (p < 0.05) and then returned to the control concentration by 24 hr after a single administration of 32 mg/kg. The alteration of the plasma testosterone level correlated well with that of the intratesticular level, which was decreased to 50% at 3-8 hr and recovered to the control level by 24 hr. However, the decrement of the plasma LH level at 3-8 hr after a single oral administration was slight and it then returned to the original level at 12 hr. During the 8 weeks of daily administration of 0.5 mg/kg of TZP-4238 or chlormadinone acetate to dogs, the plasma testosterone levels were slightly lower than the basal extent. In vitro experiments were conducted on the rat testis using the exogenous precursor steroids 20 alpha-hydroxycholesterol, pregnenolone and progesterone, in various steps leading to the biosynthesis of testosterone. Trilostane acted at 3 beta-hydroxysteroid dehydrogenase (50% inhibition concentration, IC50 was 1 microM), ketoconazole inhibited the 17 alpha-hydroxylase, and C20, 22- and C17, 20-lyase activities, with an IC50 of 1-50 microM. Cyproterone acetate inhibited both the 3 beta-hydroxysteroid dehydrogenase (IC50;50 microM) and C17, 20-lyase. On the other hand, TZP-4238 exhibited a weaker inhibition of 3 beta-hydroxysteroid dehydrogenase (IC50; 100 microM) than cyproterone acetate, but not of hydroxylase and lyase. Though TZP-4238 did not inhibit the increased testosterone level induced by hCG, trilostane markedly inhibited the effect induced by hCG.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1995

Phase-dependent phase shift of methamphetamine-induced circadian rhythm by haloperidol in SCN-lesioned rats.

Haloperidol, a non-selective dopamine receptor antagonist, was injected intraperitoneally in to suprachiasmatic nucleus (SCN)-lesioned rats at various phases of the locomotor activity rhythm induced by methamphetamine (MAP) treatment. A single injection of haloperidol shifted the phase of MAP-induced locomotor rhythm phase dependently, while saline injection had no effect on the phase. A phase-response curve of MAP-induced rhythm for haloperidol had a small phase-advancing area at CT 13 to 15, a large phase-delaying area at CT 3 to 7 and a dead zone at CT 17 to 1. Although the day-to-day variation of MAP-induced locomotor rhythm was about 2.5-times as great as that of light entrainable circadian rhythm, the phase shifts of both directions were statistically significant. Phase delay shifts at CT 5 depended on the dose of haloperidol. In addition to the phase-shifting effect, haloperidol suppressed the MAP-induced locomotor activity for activity for about 10 h regardless of the phase of the injection. Pentobarbital also suppressed ther locomotor activity for a similar duration. However, significant phase shift was not detected with pentobarbital injected at CT 5 or CT 13, at the phase where haloperidol induced the maximal phase delay or advance, respectively. Present findings suggest that the dopaminergic mechanism is involved in the entrainment and/or oscillatory mechanism of the MAP-induced rhythm.

Animals↗
PubMed1995

Synergistic effects of estrogen and androgen on the prostate: effects of estrogen on androgen- and estrogen-receptors, BrdU uptake, immunohistochemical study of AR, and responses to antiandrogens.

To investigate the synergistic effects of estradiol (E2) and testosterone (T) on prostate growth, castrated Wistar rats were treated with 1 mg/day of T or with 1 mg/day of T and 0.01 mg/day of E2 for 6 weeks. The weight of the prostate in T + E2-treated rats was significantly higher than that in T-treated and normal rats, parallel with the bromodeoxy-uridine (BrdU) labeling index (LI). Nuclear androgen receptor (AR) content in the T + E2 group was significantly higher than that in the T group. But they were lower than that in normal rats. And there were no significant differences between the groups in nuclear estrogen receptor (ER) content. Immunohistochemical studies with the AR antibody revealed positive staining in the prostatic epithelium and stromal cells in the normal, T-treated, and T + E2-treated animals. However, castration led to loss of staining. Response to steroidal antiandrogens was also determined. Antiandrogen treatment abrogated the increases in nuclear AR content and BrdU LI, and prevented immunohistochemical staining. These results suggest that AR and ER, which were measured in this study, were not indicators of prostatic proliferation. We further need to investigate other factors, including other types of receptors, growth factors involved in epithelial-stromal interaction, and so on.

Androgen Antagonists↗
PubMed1995

Effects of a new steroidal antiandrogen, TZP-4238 (17 alpha-acetoxy-6-chloro-2-oxa-4, 6-pregnadiene-3, 20-dione), on spontaneously developed canine benign prostatic hyperplasia.

The effects of the new steroidal antiandrogen, TZP-4238 on spontaneously-developed canine prostatic hyperplasia (BPH) were studied in comparison with those of chlormadinone acetate (CMA), a steroidal antiandrogen used for the treatment of BPH and prostatic cancer in Japan. Aged beagle dogs (5-9 years old) with spontaneously developed BPH (mean prostate volume, 17.7ml) were treated orally with a placebo, TZP-4238 (0.1 mg/kg/day, 0.01 mg/kg/day), or CMA (3 mg/kg/day), for 25 weeks. Prostate volume was measured by transrectal ultrasonography before treatment and every 5 weeks during treatment. TZP-4238 produced a regression in spontaneously developed canine BPH, its effects being more potent than those of CMA. TZP-4238 reduced the content of testosterone, dihydrotestosterone (DHT) and androgen receptor in the prostates of these animals, suggesting antiandrogenic mechanisms of the agent. TZP-4238 also appeared to reduce 5 alpha-reductase activity by prevention of the androgen action in prostate as described above.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗