Localization of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) in the Hypothalamus-Pituitary System in Rats: Light and Electron Microscopic Immunocytochemical Studies

The localization of pituitary adenylate cyclase-activating polypeptide (PACAP) in the hypothalamus-pituitary system in rats was examined in light and electron microscopic immunocytochemistry using a specific antiserum to synthetic PACAP 1–38 (R0831). In light microscopic study, intensely PACAP-immunostained perikarya were observed in the supraoptic and paraventricular magnocellular nucleus in the hypothalamus. In the median eminence, many immunoreactive nerve fibers were observed in the internal layer, but a few immunoreactive terminals were noticed in the external layer. In the pituitary gland, numerous immunoreactive nerve fibers were observed in the posterior lobe. In the intermediate lobe, moderately immunostained cells were observed, but in the anterior lobe no immunostained cells were noticed. In electron microscopic study, PACAP-immunoreactivity was examined by avidin-biotin peroxidase complex method. In the perikarya of the supraoptic and paraventricular magnocellular nucleus, DAB-reaction products were distributed diffusely in the cytoplasmic matrix, frequently attaching to the rough-surfaced endoplasmic reticulum. In the nerve terminals of the posterior lobe, reaction products were observed among the secretory granules, but sometimes upon them. In the cells of the intermediate lobe, reaction products were also distributed in the cytoplasmic matrix.     

Relative effect of steroid hormone receptors on the prognosis of patients with operable breast cancer. A univariate and multivariate analysis of 3089 Japanese patients with breast cancer from the Study Group for the Japanese Breast Cancer Society on Hormone Receptors and Prognosis in Breast Cancer.

In a retrospective multicenter study to investigate the correlation between estrogen (ER) and/or progesterone receptors (PgR) in primary breast cancer with patient prognosis, 3118 patients with operable breast cancer (International Union Against Cancer Stages I, II, and III) were investigated from ten hospitals in Japan who underwent surgery from October 1972 to December 1982; 3089 were evaluable. The ER-positive and PgR-positive cancers were found in 56% and 34% of patients, respectively. The positivities decreased as the tumor size increased but were independent on lymph node metastasis. There were no significant differences in relapse-free survival (RFS) in relation to receptor status (median follow-up, 89 months [ER], 84 months [PgR]). However, in patients with four or more positive nodes, those with PgR-positive cancer had a longer RFS. The patients with ER-positive cancer survived significantly longer than ER-negative ones, with the greatest difference seen in those with four or more positive nodes. There was a significantly longer postrelapse survival (PRS) for patients with ER-positive cancer because of the different distribution of the major metastasis and better responses to first-line and subsequent treatments. Cox's multivariate analysis showed that overall survival but not PRS was affected by ER (and more weakly by PgR) because of the longer PRS in patients with ER-positive cancer.     

Inhibitory effect of spiradoline, a kappa opioid receptor agonist, on Ca2+ induced contraction and the intracellular Ca2+ concentration in porcine coronary artery.

STUDY OBJECTIVE--The aim was to clarify the inhibitory effect of the selective kappa agonist, spiradoline, on coronary arterial smooth muscle in relation to the intracellular Ca2+ concentration. DESIGN--The inhibitory effect of spiradoline was investigated (1) on the contractile response of pig coronary artery to the readmission of Ca2+, following initial exposure to Ca2+ free medium and depolarisation with 40 mM K+; (2) on the intracellular Ca2+ concentration as assessed using the fluorescent calcium indicator fura-2. Relaxant responses to spiradoline in isolated porcine coronary artery strips contracted with K+ and prostaglandin F2 alpha were also examined. EXPERIMENTAL MATERIAL--Coronary arteries isolated from pigs of both sexes were used. The right and left circumflex coronary arteries were cut into 3 mm wide strips which were used to measure the change in contractile force and the intracellular Ca2+ concentration. MEASUREMENTS AND MAIN RESULTS--Prior treatment with spiradoline at 2 x 10(-6) mol.litre-1 or more inhibited the contractile response to the readmission of Ca2+ in porcine coronary artery exposed to Ca2+ free medium in the presence of high K+. Naloxone at 3 x 10(-4) mol.litre-1 did not reverse the inhibitory action of 2 x 10(-5) M spiradoline. Ca2+ induced contraction was inhibited completely by 10(-4) M spiradoline. Moreover, spiradoline caused relaxation in arterial preparations that had been contracted with K+ (15 to 25 mmol.litre-1) or prostaglandin F2 alpha (10(-6) to 3 x 10(-6) mol litre-1), greater relaxation being seen in the K+ induced contraction. The intracellular Ca2+ concentration was significantly lowered by 2 x 10(-5) M spiradoline. CONCLUSIONS--The relaxant response of coronary artery to spiradoline is, in part, attributable to interference with Ca2+ entry into the arterial smooth muscle.     

Significance of low perfusion with increased oxygen extraction fraction in a case of internal carotid artery stenosis.

BACKGROUND AND PURPOSE: Decreased cerebral blood flow with an increased oxygen extraction fraction, the so-called misery perfusion syndrome, suggests a vulnerability to reduction in cerebral perfusion pressure and a tendency to develop cerebral infarction. It is uncertain, however, whether the infarct would occur in the brain region specifically exhibiting this condition. CASE DESCRIPTION: We report the case of a patient with right intracranial internal carotid artery stenosis who presented with mild left hemiparesis resulting from a right frontal watershed infarct. Positron emission tomography 2 months after the stroke showed decreased cerebral blood flow with an increased oxygen extraction fraction in noninfarcted areas of the affected hemisphere. Maximal changes were detected in the watershed area between the middle cerebral artery and the posterior cerebral artery. Three months later, while on antiplatelet therapy, he suffered a new infarct in the right temporo-occipital watershed area that had shown the highest oxygen extraction fraction value on the first positron emission tomographic study. One month after the recurrence of stroke, a second study showed that low perfusion with increased oxygen extraction fraction persisted in the affected hemisphere to a lesser degree than in the first study. CONCLUSIONS: This observation suggests that the area of low perfusion exhibiting the highest oxygen extraction fraction has the highest risk for infarction. Increased oxygen extraction fraction may be an important factor in the development of hemodynamic infarction.     

Spontaneous mesenteric hemorrhage associated with ehlers-danlos syndrome

The vascular type of Ehlers-Danlos syndrome is a genetic disorder of connective tissue and is frequently associated with catastrophic arterial complications. Its surgical treatment is extremely difficult because of the fragility of vessels. This article describes three patients with vascular type of Ehlers-Danlos syndrome who developed mesenteric hemorrhage due to spontaneous arterial rupture. The clinical and molecular characteristics of the disease are briefly reviewed.     

Effects of herbal medicine Dai-Kenchu-to on anorectal function in children with severe constipation.

AIM: We administered the herbal medicine Dai-Kenchu-To (DKT) to children with severe chronic constipation or with severe constipation after surgery for anorectal malformations. We then objectively assessed the effect of DKT on anorectal function by manometric study in addition to using a clinical scoring system. PATIENTS AND METHODS: Ten children with severe chronic constipation and 5 children with severe constipation after surgery for anorectal malformations were assessed. These 15 children received 0.3 g/kg/day of DKT for periods ranging from 3 months to 1 year. We objectively assessed their bowel function, sphincter function and rectal reservoir function by anorectal manometry and clinical scoring. RESULTS: In 10 children with severe chronic constipation, the clinical score after administration of DKT (7.2 +/- 0.8) improved significantly compared with that before administration of DKT (4.6 +/- 2.9) (p < 0.02). The threshold sensation volume and the maximum tolerable volume after administration of DKT significantly (p < 0.05; p < 0.01) decreased (128 +/- 63 ml vs. 69 +/- 18 ml; 229 +/- 99 ml vs. 144 +/- 47 ml), and rectal compliance after administration of DKT also significantly (p < 0.05) decreased (12.4 +/- 10.9 ml/cmH(2)O vs. 4.7 +/- 3.9 ml/cmH(2)O). CONCLUSION: The present study demonstrated that DKT had a favorable clinical effect on severe constipation in children, and anorectal manometry showed an improvement in their rectal reservoir functions. It appears that the results were secondary to DKT-stimulated peristalsis of the intestine, which promoted regular bowel habits.     

Light microscopy of GTP-binding protein (Go) immunoreactivity within the retina of different vertebrates

To examine species differences in the distribution pattern of guanosine triphosphate (GTP)-binding protein (Go) within the vertebrate retina, paraffin-embedded retinae from a number of vertebrate species, including the goldfish, frog, turtle, chicken, monkey, and human, were immunohistochemically stained with affinity-purified antibody against the alpha-subunit of Go. Go-immunoreactive products were found to be located in the neuropil, but not in the cell bodies of neurons, in the retina of all these species. However, some species differences were observed. In the frog, monkey and human, the inner plexiform layer (IPL) was homogeneously stained with this antibody, but in the goldfish, turtle and chicken, the IPL was heterogeneously stained. In the frog, chicken, turtle and human, the outer plexiform layer (OPL) was densely stained with this antibody, but in the goldfish and monkey, the OPL was rather faintly immunoreactive to the antibody. In the goldfish, monkey and human, the outer nuclear layer (ONL) was not immunoreactive to the Go-antibody, whereas in the frog, turtle and chicken, the ONL was immunoreactive to it. The implications of these species differences in Go localization in the vertebrate retina are discussed.