Cytochemical study of prolactin-releasing peptide (PrRP) in the rat brain.

Strong positive signals for PrRP mRNA and PrRP-like immunoreactivity (PrRP-LI) were detected in the nucleus of the solitary tract and ventral and lateral reticular formation of the caudal medulla oblongata. Weak mRNA signals and immunoreactivity were seen scattered from the hypothalamic dorsomedial nucleus (DMH) to ventromedial nucleus (VMH). Nerve processes and terminals with PrRP-LI were detected from the septal region to the diencephalon. These nerve processes were also clearly visible around capillary walls and in the vicinity of the ependymal cells of the third and lateral ventricles. These observations suggested that PrRP might be secreted into the systemic circulation and cerebrospinal fluid and may play functional roles other than in the release of prolactin from the anterior pituitary.

Trp64Arg mutation of beta3-adrenoceptor gene deteriorates lipolysis induced by beta3-adrenoceptor agonist in human omental adipocytes.

The recently described variant of the human beta3-adrenergic receptor (AR) gene located mainly in visceral adipocytes is associated with earlier onset of NIDDM, abdominal obesity, insulin resistance, and an increased capacity to gain weight. We investigated whether lipolysis in human omental adipocytes induced by a potent and selective human beta3-AR agonist (L-755,507) was affected by the Trp64Arg mutation of the beta3-adrenoceptor, using 18 omental fat samples obtained during total hysterectomy. The Trp64Arg mutation was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. Arg64 homozygous (n = 4) had a lower median effective concentration (EC50) and lower responsiveness compared with wild-type (n = 8) (EC50: -6.55 +/- 0.21 vs. -7.53 +/- 0.35 log mol/l, P = 0.007; responsiveness: 3.48 +/- 0.32 vs. 5.76 +/- 0.36 micromol x 10(5) cells(-1) x 90 min(-1), P = 0.014, respectively), although there was no difference in lipolysis induced by isoproterenol or CGP12177. Trp64Arg heterozygous (n = 6) also had a significantly lower EC50 and lower responsiveness (EC50: -6.18 +/- 0.09 log mol/l; responsiveness: 4.17 +/- 0.33 micromol x 10(5) cells(-1) x 90 min(-1)). We concluded that the Trp64Arg mutation of the beta3-AR gene is associated with lower lipolytic activities.

Intraobserver and interobserver variance in the measurement of ultrasound-estimated bladder weight.

Recently, we reported that ultrasound-estimated bladder weight (UEBW) could be used as a noninvasive tool in evaluating the degree of bladder hypertrophy. This study was designed to test the reproducibility of its measurement. The overall mean UEBW of the initial measurement and that of the second one by one observer in 36 cases was 42.8 +/- 22.6 g and 42.9 +/- 22.6 g, respectively. The paired differences between two measurements ranged from -3.4 to 2.7 g, with a mean difference of only -0.1 g. The interobserver variance was also slight. The paired differences between UEBW measurements derived from the two observers in 32 cases ranged from -6.0 to 7.9 g, with a mean difference of only 0.1 g. The Cochran's test statistic of the measurements of UEBW was 0.142 for one observer and 0.130 for two, which were less than its 5% critical value. Due to these favorable characteristics, UEBW could be reliable tool for the investigation of bladder hypertrophy with a sufficient reproducibility.

[Awareness and feelings of elderly patients and their families concerning disease during terminal hospitalization--malignancy versus non-malignancy].

We conducted a questionnaire survey on the awareness and feelings of elderly patients and their families concerning their diseases and prognosis during terminal hospitalization. Sixty-five families of 177 patients who died at our hospital in 1992 answered questions concerning estimation of the prognosis, understanding of the disease, satisfaction regarding explanation of the disease, wish to be informed of the diagnosis, feelings during hospitalization, and whether the family revealed the diagnosis to the patient. Patients with malignancy were not informed of the true diagnosis at this time. As to estimation of the prognosis, patients aged 70 or older who did not expect "cure" of their diseases at first were significantly fewer, and those anticipating "death" just before dying were significantly more frequent than those under age 70. In patients with malignancy, those aged 70 or older foresaw "incurability" at first significantly more frequently than those under age 70. Patients with malignancy knew the diagnosis in significantly fewer cases, believed the false diagnosis significantly more frequently, and showed dissatisfaction with the explanation of the disease significantly more frequently, than those with non-malignancy. Proportions of the family who told the diagnosis to the patient were 11.8% in malignancy and 38.8% in non-malignancy with statistical significance. These data indicate that medical care during terminal hospitalization should be modified principally based on informed consent, if that is the wish of the patient.

The effect of adjuvant therapy with or without tamoxifen on the endocrine function of patients with breast cancer.

The ovarian and pituitary functions of 64 operable breast cancer patients undergoing adjuvant therapy with cytotoxic chemotherapy and/or tamoxifen were investigated. The post menopausal patients, divided into 3 treatment groups, one with tamoxifen alone, one with tamoxifen and chemotherapy and the other with chemotherapy alone had serum estradiol 17-beta (E2) and progesterone levels lower than the evaluable limits. Although there was no significant difference in the level of estrone sulfate (E1-S) between these three groups, the level of lutainizing hormone (LH) and follicle stimulating hormone (FSH) in the patients treated with tamoxifen alone and tamoxifen and chemotherapy were significantly lower than those treated with chemotherapy alone. The decrease in gonadotropin levels induced by tamoxifen treatment was reversible as it appeared after the initiation of tamoxifen and recovered after its cessation. In the premenopausal patients, a group treated with tamoxifen and chemotherapy had significantly higher E1-S, E2 and progesterone levels and significantly lower gonadotropin levels than a group treated with chemotherapy alone or one treated with a cyclophosphamide regimen. These increases in the levels of estrogen and progesterone were also reversible, and induced by tamoxifen. Thus, adjuvant endocrinochemotherapy causes profound alteration in the hypothalamo-pituitary-ovarian axis and therefore, monitoring a variety of hormonal levels is thought to be necessary for assessing the consequences of adjuvant therapy in breast cancer patients, especially in premenopausal patients using tamoxifen.

[Serum estrone sulfate levels in patients with breast cancer].

Estrone and estradiol-17 beta concentration in breast cancer tissue are reported to be an order of magnitude higher than those of circulating plasma in breast cancer patients. This high level of estrogen is provided by local production from estrone sulfate (E1-S) through the sulfatase pathway. Then serum E1-S level was determined using direct radioimmunoassay method in order to monitor the estrogen kinetics of post-operative breast cancer patients. Peri-operative sequential E1-S determination was carried out in 10 patients. Among them, extremely higher level, as compared with normal menstruating level of 625-2670pg/ml, was observed just after an administration of tamoxifen (three weeks after operation) in two of 5 pre-menopausal patients. In order to evaluate the effect of tamoxifen on serum level of E1-S in post-operative pre-menopausal patients, serum E1-S level in 42 post-operative outpatients was examined. Although there was no difference in the average level of E1-S in post-menopausal patients treated with or without tamoxifen, average E1-S level in pre-menopausal patients treated with tamoxifen as adjuvant therapy was significantly higher than that in patients without tamoxifen. These results suggests that the administration of tamoxifen to premenopausal patients should be reconsidered from a view point of the estrogen kinetics.