Species differences in androgen receptor expression in the medial preoptic and anterior hypothalamic areas of adult male and female rodents.

The medial preoptic and anterior hypothalamic areas (MPO/AH) are important androgen targets regulating homeostasis, neuroendocrinology and circadian rhythm as well as instinctive and sociosexual behaviors. Although species differences between rats and mice have been pointed out in terms of morphology and physiology, detailed distributions of androgen receptor (AR) have never been compared between the two rodents. In the present study, AR distribution was examined immunohistochemically in serial sections of the MPO/AH and compared for adult rats and mice. Western blotting and immunohistochemistry clearly demonstrated that AR expression in the brain was stronger in mice than in rats and was stronger in males than in females. In addition, we found (1) an "obliquely elongated calbindin-ir cell island" in mice medial preoptic nucleus (MPN) expressed AR intensely, as well as the sexually dimorphic nucleus in the MPN (SDN-MPN) in rats, strongly supporting a "putative SDN-MPN" previously proposed in mice; (2) AR expression in the suprachiasmatic nucleus (SCN) was much more prominent in mice than in rats and differed in localization between the two species; (3) a mouse-specific AR-ir cell cluster was newly identified as the "tear drop nucleus (TDN)", with male-dominant sexual dimorphism; and (4) two rat-specific AR-ir cell clusters were also newly identified as the "rostral and caudal nebular islands", with male-dominant sexual dimorphism. The present results may provide basic morphological evidence underlying species differences in androgen-modified psychological, physiological and endocrinergic responses. Above all, the findings of the mouse-specific TDN and differing AR expression in the SCN might explain not only species difference in gonadal modification of circadian rhythm, but also distinct structural bases in the context of transduction of SCN oscillation. The current study could also serve as a caution that data on androgen-sensitive functions obtained from one species should not always be directly applied to others among rodents.

Characterization of the "sporadically lurking HAP1-immunoreactive (SLH) cells" in the hippocampus, with special reference to the expression of steroid receptors, GABA, and progenitor cell markers.

Huntingtin-associated protein 1 (HAP1) is a neural huntingtin interactor that is widely expressed as a core molecule of the stigmoid body (a neurocytoplasmic inclusion) in the limbic and hypothalamic regions and has putative protective functions against some neurodegenerative diseases (HAP1 protection hypothesis). Although HAP1 has been reported to be intimately associated with several steroid receptors, HAP1-immunoreactive (HAP1-ir) cells remain to be identified in the hippocampus, which is one of the major steroidal targets. In this study, we determined the distribution of hippocampal HAP1-ir cells in light and fluorescence microscopy and characterized their morphological relationships with steroid receptors, markers of adult neurogenesis, and the GABAergic system in adult male and female Wistar rats. HAP1-ir cells, which were sporadically distributed particularly in the subgranular zone (SGZ) of the dentate gyrus and in the interface between the stratum lacunosum-moleculare and stratum radiatum of Ammon's horn, were identified as the "sporadically lurking HAP1-ir (SLH)" cells. The SLH cells showed no clear association with neural progenitor/proliferating or migrating cell markers of adult neurogenesis, such as Ki-67, proliferating cell nuclear antigen, doublecortin, and glial fibrillary acidic protein in the SGZ, whereas all the SLH cells expressed a neuronal specific nuclear protein (NeuN). More than 90% of the SLH cells expressed nuclear estrogen receptor (ER) α but neither ERß nor the androgen receptor, whereas glucocorticoid receptor was differently stained in the SLH cells depending on the antibodies. More than 60% of them exhibited GABA immunoreactivity in the SGZ, suggestive of basket cells, but they were distinct from the ones expressing cholecystokinin or parvalbumin. We conclude that SLH cells, which should be stable against apoptosis due to putative HAP1 protectivity, might be involved in estrogen-dependent maturation, remodeling and activation of hippocampal memory and learning functions via ERα and partly through GABAergic regulation.

Distribution patterns of uterine glands and embryo spacing in the mouse.

To clarify the mechanism of implantation, relationship between positioning of the mouse embryo in the uterus and distribution of uterine glands along the long axis of the uterine horn was examined by three-dimensional remodelling of the uterine endometrium. There were two unique regions in the endometrium. Uterine glands were distributed widely from mesometrial to anti-mesometrial side in one region. It was localized from lateral to anti-mesometrial side in another. These different regions were alternately aligned throughout the uterine horn. The number and position of embryos was consistent with that of the latter region. This study suggests that the type of distribution of uterine glands is closely related to the positioning of the embryo in mice.

[Current alteration of Helicobacter pylori in gastro-duodenal diseases].

The current alteration of the detection rate of Helicobacter pylori (H. pylori) on mucous membranes of the stomach has been surveyed and reviewed for 49 cases of gastro-duodenal diseases. The survey has been conducted for 3 years and an endoscopic examinations have been performed 2-8 times. On the first visit, the diagnosis can be made endoscopically, and H2 blockers and another agents were used as therapeutic drugs. The detection rate was 67.3% (33 cases) for positive cases and positive reaction cases, while the rate was 32.6% (16 cases) in negative cases and negative reaction cases. Among them, the most commonly observed disease was atrophic gastritis, followed by duodenal ulcer, and acute gastric mucous lesions (AGML). Peptic ulcer was not seen. After administration of H2 blockers and anti-ulcer agents, the H. pylori-detection rate was found to fluctuate according to the diseases and alterations in the morbidity period. Some cases indicated the disappearance of H. pylori in accordance with the improvement of the lesion site.

Effects of ML-9 on experimental delayed cerebral vasospasm.

Experimental delayed cerebral vasospasm was produced in a two-hemorrhage canine model. The spastic basilar artery was exposed via the transclival route under a surgical microscope and was dilated by the topical application of 1-(5-chloronaphthalenesulfonyl)-1H-hexa-1,4-diazepine (ML-9), a selective antagonist of myosin light chain kinase. Dilation was dose-dependent, with a median effective dose (+/- standard deviation) of 51.4 +/- 6.9 microM. In addition, 50 microM of ML-9 was injected into the cisterna magna until the intracranial pressure (ICP) reached 200 mm H2O for 30 minutes, including a complete reversal of angiographic delayed vasospasm in three of seven dogs; in contrast, 150 microM of ML-9 was infused at 1.52 ml/min into the vertebral artery for 30 minutes, producing little dilation of the spastic basilar artery. In another study, the intracisternal perfusion of 50 microM of ML-9 at 1.48 ml/min for 30 minutes in dogs with an ICP of less than 200 mm H2O produced no serious electroencephalographic abnormalities, and the mean arterial blood pressure and pulse rate remained normal; no neurological deficits or significant histological abnormalities ascribable to the intracisternal ML-9 were found.

[Mechanical properties of nickel-titanium alloy wire developed by the diffusion method].

The present study was conducted to investigate mechanical properties of the nickel-titanium (Ni-Ti) alloy wire developed by the diffusion method, in comparison with the previous Ni-Ti wires. Two types of the wire, work hardening and super elastic wires, were used for three experiments; three-point bending test, tension test and torque test. The following findings were obtained. 1. A newly developed work hardening wire exhibited lower force level with a generous reduction of force at various wire deflections, in comparison with the previous work hardening Ni-Ti wires. It was also found that tension strength and extension ratio of this wire were greater, and its modulus of longitudinal elasticity was smaller than those of the previous wires, indicating high resistibility to breakage. 2. A super elastic wire, developed by the diffusion method, showed similar pattern of force reduction associated with varying wire deflections, although magnitude of force was slightly larger than those of the previous super elastic wires. 3. An interesting finding was that force and its reduction with various deflections were varied by controlling how the wire was ligated onto a bracket, which was more obvious in the work hardening type of the present Ni-Ti wire. 4. Magnitudes of force exerted by Ni-Ti wires were around 200 gf at a deflection of 2 mm with an interbracket distance of 7 mm, and seemed to be beyond an optimal orthodontic force for anterior teeth. A further refinement is expected in terms of improving mechanical properties and/or developing finer wires.

[Combination chemotherapy with UFT, etoposide, CDDP, adriamycin (FEPA) in advanced gastric cancer].

Fifteen patients with inoperable advanced gastric cancer were treated with UFT.etoposide.CDDP.adriamycin (FEPA). Six were males and 9 were females with an average age of 58 (range 40 to 80 years). Nine patients were in P.S. 2 and 6 in P.S. 3. FEPA regimen was performed every 4 weeks as follows: UFT 400 mg/m2 (p.o.) every day, etoposide 50 mg/m2 (i.v.), CDDP 25 mg/m2 (i.v.) and adriamycin 10 mg/m2 (i.v.) on days 1, 8, 15 and 22. Among 15 patients, 6 partial remissions and 4 minor responses were obtained. Gastrectomy was performed in 2 of 6 PR patients after FEPA chemotherapy. The overall response rate was 40.0%. As for side effects, mild myelosuppression was the most frequent (66.7%), followed by alopecia and nausea. We concluded that combination chemotherapy of FEPA is useful for inoperable advanced gastric cancer.

Effect of 5-lipoxygenase inhibitor on experimental delayed cerebral vasospasm.

Experimental delayed cerebral vasospasm was produced in canine basilar arteries by 2 successive injections, 2 days apart, of fresh autogenous arterial blood into the cisterna magna. When angiographic evidence of delayed vasospasm was confirmed 7 days after the initial intracisternal blood injection, a selective inhibitor of 5-lipoxygenase, 2-(12-hydroxydodeca-5,10-diynyl)-3,5,6-trimethyl-1,4-benzoqu inone (AA-861), was infused intravenously at 6.5 X 10(-4) mg/kg/min for 2 hours. However, angiographic evidence of delayed vasospasm was not reversed, and mean regional cerebral blood flow was not significantly increased. In other studies, oral doses of AA-861 at 100 mg/kg/day were given twice a day for 7 days after the initial intracisternal blood injection. In the treated group, angiographic evidence of delayed vasospasm was significantly reduced, and the contractile property of excised basilar arteries in response to vasoconstrictor agents was significantly improved. It is suggested that leukotrienes, 5-lipoxygenase products of arachidonic acid, might be important etiologic factors responsible for the development of delayed vasospasm and that AA-861 would have a therapeutic effect not on the reduction of delayed vasospasm once developed but on the prevention of the development of delayed vasospasm.

Determination by enzyme-linked immunosorbent assay (ELISA) of specific IgG antibody activities for diagnosis of farmer's lung disease.

The specific IgG antibodies to thermophilic actinomycetes in the sera from patients with farmer's lung disease were quantitated by an ELISA and the results thereof were compared with those obtained by the standard double immunodiffusion assay (Ouchterlony's method). All sera from patients with farmer's lung disease were precipitin positive to Thermoactinomyces vulgaris and/or Micropolyspora faeni by the Ouchterlony's method, and revealed significantly high levels of IgG antibody activities against these antigens by ELISA. We have found 18 precipitin-positive but asymptomatic subjects in a survey of the dairy farming population of the northern area of IWATE Prefecture. Their sera were precipitin positive to antigens related to the farmer's lung disease, however IgG antibody activities as determined by ELISA to these antigens was significantly lower in the group of asymptomatics than in the group of symptomatics. Precipitin negative dairy farming controls and normal controls living in the urban area revealed low antibody activities as determined by ELISA. From these studies, we concluded that the assay of specific IgG antibody activity to thermophilic actinomyces by ELISA is useful for the diagnosis and screening of farmer's lung disease.

Demonstration of immunoreactive somatostatin-like substance in villi and decidua in early pregnancy.

With the use of the radioimmunoassay for growth hormone--releasing inhibiting factor (GIF), it was found that measurable amounts of GIF-like substance existed in the chorionic villi and decidua of pregnant women. The indirect immunofluorescent method revealed that the higher intensity of GIF-like immunofluorescence was presented in cytotrophoblasts rather than in syncytiotrophoblasts of the villi and in stromal cells of the decidua.