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Biomedical subjects

S Honma

Publications and source records attributed to S Honma.

At least 127 records · Page 7Linked to original sources

A clinicopathologic study of 30 patients with Paget's disease of the vulva.

Clinical and pathologic analyses were performed in 30 patients with Paget's disease of the vulva to investigate the risk factors for recurrence. From 1971 to 1993, we carried out histologic examinations in 27 resected vulvae to detect Paget's cells at the surgical margin. Prior to 1981, 9 patients underwent the examination, and 6 of them had positive surgical margins, and 2 of these 6 patients had local recurrence. After 1982, the preoperative multiple biopsy and intraoperative frozen section diagnosis of the surgical margins were performed, and as a result, cases of the lesions remaining as stumps on the vaginal side decreased in 7 of 18 examined patients. In these 7 cases, 2 cases had local recurrence. The patients were further divided into three groups according to histologic findings to investigate their prognosis: 10 patients with intraepithelial Paget's disease (IEP), 9 patients with minimally invasive Paget's disease (MIP), and 11 patients with underlying carcinoma (UC) including 2 cases of carcinoma in situ. Four locally recurrent cases were found in IEP or MIP, and the longest period from surgery to recurrence was 8 years and 4 months. The invasive UC lesions persisted or recurred shortly after surgery (median, 10 months) and 5 of the 6 patients with general metastasis. For IEP and MIP, surgical margins of the vaginal side should be carefully examined with preoperative multiple biopsy and intraoperative frozen section, and also a long-term follow-up is necessary. With regard to invasive UC patients, their prognosis was found to be very poor for general metastasis.

Aged↗

Circadian modulation in photic induction of Fos-like immunoreactivity in the suprachiasmatic nucleus cells of diurnal chipmunk, Eutamias asiaticus.

Photic induction of immediate early genes including c-fos in the suprachiasmatic nucleus (SCN) has been well demonstrated in the nocturnal rodents. On the other hand, in diurnal rodents, no data is available whether the light can induce c-fos or Fos in the SCN. We therefore examined whether 60 min light exposure induces Fos-like immunoreactivity (Fos-lir) in the SCN cells of diurnal chipmunks and whether the induction is phase dependent, comparing with the results in nocturnal hamsters. We also examined an effect of light on the locomotor activity rhythm under continuous darkness. Fos-lir was induced in the chipmunk SCN. The induction was clearly phase dependent. The light during the subjective night induced strong expression of Fos-lir. This phase dependency is similar to that in hamsters. However, unlike in hamsters, the Fos-lir was induced in some SCN cells of chipmunks exposed to light during the subjective day. In the locomotor rhythm, on the other hand, the light pulse failed to induce the phase shift at phases at which the Fos-lir was induced. These results suggest that the photic induction of Fos-lir in the diurnal chipmunks is gated by a circadian oscillator as well as in the nocturnal hamsters. However, the functional role of Fos protein may be different in the diurnal rodents from in the nocturnal rodents.

Animals↗

Differential effects of bright light and social cues on reentrainment of human circadian rhythms.

Reentrainment of human circadian rhythm to an 8-h advanced schedule of sleep and social contacts was assessed under two different conditions: with and without bright light (4,000-6,000 lx). Subjects spent 15 days without knowing the natural day-night alternation. On the fourth day, the social schedule was phase-advanced by 8 h. In one experiment, a bright light pulse of 3-h duration was given in every subjective morning, and in the other no light pulse was applied. Plasma melatonin and rectal temperature rhythms were measured. Seven of nine subjects showed an orthodromic phase shift, the rate of which was significantly larger with bright light pulses than without them. The maximum phase-advance shift by three consecutive light pulses was observed when the first pulse was applied approximately 4 h after the onset of melatonin rise. By contrast, the maximum phase shift of a similar extent was detected at 1 h after the onset of melatonin rise, when ordinary room light (300-500 lx) at the time corresponding to bright light was regarded as a dim light pulse. It is concluded that bright light accelerates the reentrainment of human circadian rhythm, and bright light and social schedule have differential effects on the reentrainment.

Adult↗

Endocrine environment of benign prostatic hyperplasia: prostate size and volume are correlated with serum estrogen concentration.

Estrogen plays an important role in the development of benign prostatic hyperplasia (BPH), as has been shown in both experimental and clinical studies. T determine the endocrine environment of BPH, serum total testosterone (Total-T), free testosterone (Free-T), and estradiol (E2) conceptions were measured, and the relationship between these levels and prostate size and volume was analyzed. Blood samples were collected from subjects who attended the mass screening for prostate disease performed by our institute. No significant correlations were found between Total-T levels, Free-T levels, and prostate size, as determined by digital rectal examination. However, E2 levels and the ratios for E2 levels and the ratios for E2/Total-T and E2/Free-T were significantly correlated with prostate size. To confirm these relationships, prostate volume was calculated from transrectal ultrasonographic images. E2 levels and these two ratios were, indeed, highly correlated with prostate volume. These results suggest that an estrogen-dominant environment plays an important role in the development of BPH.

Adult↗

[Effect of fog on diurnal changes in peak expiratory flow rates in an asthmatic].

To evaluate the effects of fog on asthmatics, we analyzed the symptoms of a 45-year-old female during the foggy season and the relation between diurnal peak expiratory flow rate (PEFR) and fog and other meteorological factors. Her asthma attacks had been induced by specific smells: perfume, smoke from burning grass or industrial smoke. Two years previously, she had moved to the suburbs of Sapporo, where fog frequently occurs. From that time her asthmatic symptoms had been exacerbated, so it was suspected that the fog might have had some influence. We analyzed 251 measures of PEFR from June to August 1994. The average and standard deviation of PEFR in the absence of fog and specific smells was 403 +/- 40 L/min (n = 195). PEFR was significantly lower (p < 0.01) when it was foggy (347 +/- 60 L/min; n = 40), when specific smells were present (333 +/- 60 L/min; n = 5) and when there were both fog and specific smells (340 +/- 53 L/min: n = 11). On the other hand, there were no changes associated with other meteorological factors: barometric pressures, relative humidity, mean temperature, minimal temperature and most frequent wind direction. These results suggested that the inhalation of fog decreases PEFR and is an exacerbating factor in bronchial asthma.

Asthma↗

[Changes in biological rhythm and sleep structure during the menstrual cycle in healthy women].

It is well known that clinical symptoms such as psychosis, epileptic seizures and sleep disturbances aggravate around the time of menstruation. In some healthy women, subjective sleep feelings or moods have been reported to change throughout the menstrual cycle, which suggests that sleep structure and sleep-wake rhythm may change during the menstrual cycle. We investigated a circadian pattern of plasma melatonin, sleep-wake rhythm and sleep characteristics in the different phases of the menstrual cycle in young healthy women under controlled environmental conditions. The subjects were seven healthy women, aged 18 to 19, with regular menstrual cycles. They stayed in an experimental facility, where temperature and humidity were kept within a narrow range, for three days in successive five weeks. They got up and went to bed at their preferable time. Polysomnography was performed using ambulatory cassette EEG system on the first and second night. Sleep stages were scored according to Rechtshaffen and Kales' criteria. Plasma melatonin was measured at 1-hour intervals for 24 hours on the third day. The menstrual cycle was divided into four phases (menstruation, follicular, early luteal and late luteal). Although the plasma melatonin level in the late luteal phase tended to be higher than in other phases, no significant difference was observed across four phases. The phase in plasma melatonin level did not change. As for sleep-wake rhythm, the time of getting up on the first day was significantly late in the late luteal phase (p < 0.05), although it showed no significant change on the second day. The time of going to bed did not change. Sleep characteristics changed during the menstrual cycle. There was a significant difference in the amount of stage 3 + 4, slow wave sleep (p < 0.05), which was more abundant in the follicular phase than in the luteal phase. TIB (time in bed), SPT (sleep period time), TST (total sleep time) seemed to increase in the menstrual and follicular phases, while stage W increased in the early and late luteal phases. However, there were no significant differences in these parameters. The other parameters did not show any changes. The changes in amount of stage 3 + 4 throughout the menstrual cycle seem to be due to endogenous factors, because environmental factors were controlled in this experiment. It is possible that the menstrual cycle also affect the plasma melatonin level and sleep-wake rhythm.

Adolescent↗

[The effect of antiandrogen TZP-4238 on corticosteroid hormone in the dog].

We studied the adrenosuppressive effect of antiandrogen TZP-4238 and its metabolites. The binding affinity for the corticosteroid receptor using rat hepatic cytosol was in the order 11-OH TZP-4238 > 11, 15-(OH)2 TZP-4238 >> TZP-4238 > or = 15-OH TZP-4238 > 11-keto TZP-4238. Male beagle dogs aged 1-6 years were randomly divided into TZP-4238 (0.05, 0.5mg/kg) treatment groups and CMA (0.5mg/kg) treatment group. Each group was administered the drug per os every day for 8 weeks. Plasma cortisol, TZP-4238 and its metabolite levels were measured by on-line coupling of liquid chromatography with thermospray or atmospheric pressure ionization mass spectrometry using selective ion monitoring (LC-MS/SIM). LC-MS/SIM provided a sensitive and reliable method of unequivocal confirmation of the presence of steroidal drugs in the plasma. The plasma cortisol level was lowered below 1 ng/ml at 1 week after oral administration of TZP-4238 at 0.5mg/kg or CMA at 0.5mg/kg. The decline continued throughout the treatment for 8 weeks. Upon termination of administration, the cortisol level returned to the normal level (6ng/ml) by 4 weeks. However in the group given 0.05mg/kg TZP-4238, the cortisol level remained within the normal range. To analyze the cortisol decreasing mechanism, we administered TZP-4238 at 0.5mg/kg for 7 days to one beagle dog. When the plasma 11-OH TZP-4238 level was increased, the cortisol level decreased time dependently and the concentration of plasma 11-OH TZP-4238 which induced 50% inhibition was 2ng/ml. The decrease in the plasma cortisol level was highly correlated to the extent of the increase of the plasma 11-OH TZP-4238 (r2 = 0.840). We conclude that the adrenosuppressive effect of antiandrogen TZP-4238 is not due to TZP-4238 itself but its metabolite 11-OH TZP-4238.

Adrenal Cortex↗

[Effects of antiandrogen TZP-4238 on the prostatic androgen receptor and prostatic androgen in rat].

TZP-4238, a new steroidal antiandrogen, is an orally active drug in rats and dogs. The effects of TZP-4238 on the androgen receptor and androgen content were examined in comparison with other antiandrogens in rats. The prostate DHT levels decreased markedly within 4-8 hr after a single oral administration of TZP-4238 8mg/kg. The prostatic testosterone concentrations fell below the detection limit (5pg/g of tissue) at 4-12 hr after the initiation of treatment. The plasma testosterone level also fell to 60% of the control level after 4-8 hr and then returned to the normal range. Eight percent of DHT present in normal prostatic tissue was located in the nuclear fraction. TZP-4238 reduced the concentration of DHT in nuclei to 50% of the normal level. The concentration of the plasma drug which induced a 50% decrease in the prostatic DHT, the IC50, was about 10ng/ml, while the IC50 value for plasma testosterone was 30-50ng/ml. After oral administration of 15-OH TZP-4238, the main metabolite, the level of plasma testosterone was significantly elevated above the control level. The androgen receptor level was markedly reduced at 24 hr following castration and returned to the normal range within 5 hr of a single injection of testosterone. TZP-4238 reduced the nuclear androgen receptor level to 60% at 24 hr after a single oral dose and then, the receptor content returned to its original level. Both 15-OH TZP-4238 and cyproterone acetate also reduced the androgen receptor and DHT contents to 50%. A series of in vivo studies demonstrated that TZP-4238 inhibited the uptake of testosterone and the decrease of DHT and testosterone, and decreased the nuclear androgen receptor in the rat prostate.

Androgen Antagonists↗

Biological-clinical significance of selective loss of HLA-class-I allelic product expression in squamous-cell carcinoma of the uterine cervix.

To determine possible correlations between the selective loss of HLA-class-I allelic forms on neoplastic cells and their biological-clinical characteristics, 89 squamous-cell carcinomas of the uterine cervix were evaluated immunohistochemically using monomorphic and polymorphic antibodies against HLA-A, -B, and -C molecules and analyzed clinico-pathologically. Four of the carcinomas exhibited a lack of detectable class-I heavy-chain expression associated with beta 2-microglobulin. In 19 of 42 HLA-A2-positive patients, tumor cells revealed loss of the HLA-A2 allelic product. Loss of HLA-B7 and/or 40 (B7/40) allelic product(s) on tumor cells was observed in 12 of 25 HLA-B7/40-positive cases. These alterations did not correlate with patient age, clinical stage (FIGO) of the disease, histological sub-type (WHO) or depth of cervical invasion. However, a statistically significant correlation was observed between lymph-node metastases and selective loss of HLA-B7/40 allelic product(s), but not with HLA-A2 allelic product on cancer cells of the primary lesion. Our results indicate that selective loss of certain HLA-class-I alleles on neoplastic cells can influence the nodal metastatic potential and suggest that these 2 class-I molecules may have different immune functions as restriction elements in T-cell-mediated cytotoxicity.

Adult↗

Circadian rhythms in the release of vasoactive intestinal polypeptide and arginine-vasopressin in organotypic slice culture of rat suprachiasmatic nucleus.

Temporal profiles of the amount of vasoactive intestinal polypeptide (VIP) were examined in the medium of organotypic suprachiasmatic nucleus (SCN) slice cultures over a 2-day period. Arginine-vasopressin (AVP) level was also measured in the same medium. The slices of the SCN were obtained from 7-8-day-old rats and cultured individually in tubes on a roller drum for 14 days. The VIP amount in the medium of SCN culture showed a circadian rhythm with a approximately 22-h period. Circadian rhythms with identical periods were also observed in AVP amount of the same culture. However, the peak time of the VIP rhythm was slightly ahead of that of the AVP rhythm. Furthermore, the total VIP amount in the medium over a 24-h period was six times as large as that of AVP. These results suggest that there is a circadian rhythm of VIP which is released from the ventrolateral SCN.

Animals↗

Synergistic effects of estrogen with androgen on the prostate--effects of estrogen on the prostate of androgen-administered rats and 5-alpha-reductase activity.

To clarify the effects of estrogen on the prostate of androgen-treated rats, we administered estradiol (E2; 0.01 mg/day) to testosterone (T; 1 mg/day)-treated Wistar rats under various conditions. There were three variable factors: the age of the rat, the untreated period after castration, and the presence of testes. Under all conditions, E2 stimulated the growth of the prostate in T-treated rats compared with growth in rats in treated with T only. To analyze the mechanism underlying this enhancement of prostate growth by estrogen, we measured 5-alpha-reductase activity and calculated its kinetic parameters, i.e., both Vmax and Km. The Vmax of the nuclear fraction was higher in E2-administered T-treated rats than in T only-treated rats. In contrast, the Vmax of the microsomal fraction was lower in E2-administered rats. Km values in the two groups showed no significant differences. Elevation of the nuclear fraction of 5-alpha-reductase activity could explain the synergistic effects of estrogen on the prostate growth of androgen-treated rats.

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

Dense innervation of human radicular dental pulp as revealed by immunocytochemistry for protein gene-product 9.5.

Protein gene-product 9.5 (PGP 9.5) is a novel neurone-specific protein. At light- and electron-microscopic levels, human radicular dental pulp was heavily innervated by PGP 9.5 nerve fibres. Thick nerve bundles showing intense PGP 9.5 immunoreactivity ascended in the centre of the pulp, with some nerve fibres extending from the trunk towards the peripheral pulp at regular intervals. However, the fibres did not form a plexus (of Raschkow) beneath the odontoblast cell layer. The PGP 9.5-positive nerve fibres penetrated into the predentine and dentine beyond the odontoblast cell layer where some nerves terminated. In the predentine, PGP 9.5-positive nerve fibres were densely distributed. In tangential sections along the pulpodentinal border, the nerve fibres ran in contact with odontoblast processes. Immunoelectron microscopy revealed that all nerve fibres were immunoreactive for PGP 9.5 in the radicular predentine and dentine, and terminated in contact with the odontoblast cell processes. The distribution pattern and terminal formation of predentinal and dentinal nerves were identical to those of coronal pulp, as reported previously. The dense innervation in radicular dental pulp, overlooked in previous reports, might be responsible for dentine hypersensitivity.

Adolescent↗

Choriocarcinoma in a term placenta with pulmonary metastasis.

This is a case report of choriocarcinoma in the placenta of a patient who had a term delivery at the 38th week of pregnancy. The pregnant woman had hemoptysis at the 26th week of pregnancy, and a chest X-ray revealed a tumor in the left lung. She had suffered from a hydatidiform mole in a previous pregnancy in 1989. The patient's serum level of beta-human chorionic gonadotropin (hCG) had been below the normal level before the present pregnancy. Choriocarcinoma was histologically found at 3 sites in the placenta. Her urine hCG levels decreased rapidly after delivery. A partial lobectomy was performed after 2 courses of chemotherapy, and no choriocarcinoma was recognized histologically, because the lesions were hemorrhagic and necrotic. At present, the mother is free of disease, and the baby is growing normally. The placenta should be examined in a detail in post-molar pregnancy.

Adult↗

Prefeeding increase in paraventricular NE release is regulated by a feeding-associated rhythm in rats.

Extracellular norepinephrine (NE) in the vicinity of the paraventricular nucleus was continuously measured over 24 h by means of in vivo microdialysis in rats under restricted daily feeding and ad libitum feeding. A 24-h rhythm in plasma corticosterone was monitored in separate rats under identical conditions. Under ad libitum feeding, the paraventricular NE showed a 24-h rhythm with lower levels in the light period and higher levels in the dark period. The temporal pattern was not affected by food deprivation for 3 days. The circadian peak of paraventricular NE lagged slightly behind that of plasma corticosterone under ad libitum feeding. On the other hand, when rats were fed for 2 h at a fixed time of day for 3 wk, the NE rhythm was changed and showed a major peak just before daily meals. To examine the nature of the prefeeding NE peak, a 24-hour variation of paraventricular NE was measured in rats under food deprivation that had been subjected to restricted daily feeding for 3 wk and subsequently to ad libitum feeding for 7 days. The paraventricular NE was high around the time when meal had been supplied under restricted daily feeding and low in the dark period. Similar changes were observed in plasma corticosterone. The findings indicate that the prefeeding increase in the paraventricular NE release is regulated by a feeding-associated circadian rhythm manifest in rats under restricted daily feeding.

Animals↗

Immediate response to light of rat pineal melatonin rhythm: analysis by in vivo microdialysis.

Melatonin in the extracellular space of the pineal gland was measured continuously for 4 consecutive days from single, freely moving rats by means of in vivo microdialysis. A robust circadian rhythm was observed in the pineal extracellular melatonin under both light-dark (LD) and continuous dark (DD) conditions, the patterns of which were almost identical for 4 days within individuals but varied substantially among individuals. The offset phase of melatonin rhythm was more stable than the onset phase. Light-induced phase shift of melatonin rhythm was measured in individual rats, which had been entrained to LD and subsequently released into DD. On the 1st day in DD, a 3-min light pulse of 200 lx was applied either at circadian time (CT) of 17 or 22 h (5 and 10 h after the dark onset, respectively). The light pulse rapidly suppressed the nocturnal melatonin level. The rate as well as the level of melatonin suppression was significantly greater by the pulse at CT22 than at CT17. A phase shift of the melatonin rhythm was calculated on the 2nd and 3rd days in DD. Significant phase delay shift was observed after the pulse at CT17 and advance shift after the pulse at CT22 of approximately 1 h in either case. Because the amount of phase shift was not different between the 2nd and 3rd days in DD, the phase shift of pineal melatonin rhythm by single light pulse seems to be completed immediately.

Animals↗

[Clinical results of UFT against ovarian carcinoma].

We carried out a phase II study on single oral administration of UFT in 17 patients with ovarian carcinoma. Two PR cases were observed out of 13 evaluable cases for a response rate was 15.4%. Side-effects, appearing in 10 of the cases (58.8%) were mainly anorexia (17.6%), stomatitis (17.8%), nausea/vomiting (11.8%), leukopenia (11.8%) and thrombocytopenia (11.8%), but they were not serious. UFT proved useful in the treatment of patients with ovarian carcinoma.

Administration, Oral↗