Affinity of neuroleptics for D1 receptor of human brain striatum.

We determined the inhibition-dissociation constant (Ki) of a number of neuroleptics for D1 receptors of normal human brain tissue using [3H]SCH23390 [R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3[benzazepine-7- ol]. SCH23390 had the highest affinity with a Ki of 0.76 nM. Among clinically used drugs, propericiazine showed the highest affinity with a Ki of 10 nM. When neuroleptics were classified according to chemical structures, the Ki values were as follows. Phenothiazines ranged from 10 nM to 250 nM. Butyrophenones ranged from 45 nM to 250 nM. Thioxanthenes ranged from 12 nM to 340 nM. Orthopramines were more than 10,000 nM. The Ki values for the binding site of this study were significantly correlated with those reported in studies using animal brain. The possible relationship between D1 receptors and negative symptoms is discussed.     

Longitudinal decline in pulmonary function in atopic cough and cough variant asthma

OBJECTIVE: Cough variant asthma and atopic cough are different clinical manifestations of eosinophilic airway inflammation presenting with isolated chronic non-productive cough. The aim of this study was to examine the longitudinal change in pulmonary function in cough variant asthma and atopic cough. METHODS: Longitudinal change in FEV1 was prospectively examined in 20 patients with cough variant asthma, 14 patients with atopic cough and 271 asymptomatic healthy subjects. All were lifetime non-smokers. Of the 20 cough variant asthma patients, 13 were taking long-term inhaled corticosteroid therapy (ICS) (beclomethasone dipropionate 615 +/- 58 micro g/day) and the other seven were not. Spirometry was taken at first visit, after cough was almost completely relieved on therapy, and at least once every year for 5 or more years afterwards. RESULTS: The slope of longitudinal change in FEV1 was not significantly different among cough variant asthma patients (- 0.029 +/- 0.007/year), atopic cough patients (- 0.021 +/- 0.022/year) and asymptomatic subjects (- 0.028 +/- 0.002 L/year). In patients with cough variant asthma, the slope in patients not taking inhaled corticosteroids (ICS) was 0.032 +/- 0.007 L/year, which was not significantly different from that in patients taking ICS (- 0.027 +/- 0.010 L/year). CONCLUSION: Pulmonary function decline is not greater in cough variant asthma than atopic cough and the normal population, and long-term ICS has no effect on the decline in cough variant asthma.     

MRI of the brain in diabetes mellitus

We studied the MRI appearances of the brain in 159 patients with diabetes mellitus (DM) and 2566 agematched individuals without DM (controls). The images were reviewed for cerebral infarcts, hemorrhage, atrophy and subcortical arteriosclerotic encephalopathy. Cerebral atrophy was significantly more frequent in patients with DM than in controls (P>0.005) from the sixth to the eighth decade. The frequency of atrophy was 41.2% in the 6th decade, 60.0% in the 7th and 92.3% in the 8th decade in DM, and 19.8%, 38.9% and 56.8% respectively in controls. Unexpectedly, there was no statistically significant difference in the incidences of cerebrovascular diseases at any age.     

Prospective study of serum cholesterol and site-specific cancers.

From 1965 to 1968, 7716 Japanese-American men were examined and tested for serum cholesterol. After 22 years, 1380 incident cancer cases were identified. Of the site-specific cancers, only colon cancer cases had a significantly lower mean serum cholesterol value than that of noncases (213.0 mg/dl vs 219.0 mg/dl). When the study subjects were separated into either a low, middle or high group, based on their serum cholesterol values, there was a significant inverse trend for cases of oral/pharyngeal/esophageal cancer combined. The association was present for cases diagnosed within 10 years of examination (p = 0.012), but not for cases diagnosed after 10 years. This suggests that the inverse association is due to the metabolic effects of undiagnosed oral/pharyngeal/esophageal cancer upon serum cholesterol levels. These results are discussed in relation to other studies on serum cholesterol.     

Localization and developmental expression of a novel protein kinase C delta gene.

The expression and localization of a novel protein kinase C delta (nPKC delta) mRNA were investigated using Northern blotting and in situ hybridization in the developmental process of mouse brain. In adult mice, nPKC delta was abundantly expressed in the thalamus, moderately in the pons and the cerebellum, but faintly in the cerebral cortex and the spinal cord. By in situ hybridization, the signals were observed specifically at the sensory and motor relay nuclei of the thalamus, the dorsal cochlear nuclei of the pons, and the molecular layer of the cerebellum. When developmental changes in the expression of nPKC delta gene were analyzed by in situ hybridization, it was not detectable in embryonic and neonatal brains, very weakly expressed in the thalamus in the first week, and highly expressed at two weeks of age. These results suggest that the gene expression of nPKC delta is strictly controlled by both the cell type and the developmental process.     

Phenotypic and genetic analyses of T-cell-mediated immunoregulation in patients with Type 1 diabetes.

AIMS: To investigate the contribution of regulatory T cells and co-stimulatory molecules in CD4(+) T cells to the development of Type 1 diabetes (T1D). METHODS: Twelve patients with T1D, nine patients with systemic lupus erythematosus (SLE), and 12 age-matched healthy control subjects participated. We analysed the proportions of CD25(+)CD4(+) T cells and natural killer T cells (NKT cells), and the expression levels of Foxp3, CTLA-4, CD28, ICOS, PD-1 and BTLA in peripheral blood mononuclear cells and purified CD4(+) T cells. RESULTS: There were no significant differences in the proportions of CD25(+) CD4(+) T cells or NKT cells among the three groups. PD-1 expression levels of peripheral CD4(+) T cells from T1D patients were significantly lower than those from healthy control subjects (P = 0.00066). In contrast, PD-1 expression levels were similar in SLE patients and healthy control subjects. The expression levels of Foxp3, CTLA-4, CD28, ICOS and BTLA were similar in the three groups. CONCLUSIONS: Decreased expression of the PD-1 gene in CD4(+) T cells may contribute to the development and/or maintenance of autoimmune T1D. As the population studied was small and heterogeneous, further studies are required to confirm the findings.     

The inclusion of an omental flap in pancreatoduodenectomy

A technique for reducing the morbidity and mortality of pancreatoduodenectomy by using an omental flap to protect the anastomoses and splanchnic vessels exposed during dissection is described herein.     

Pre- and post-synaptic effects of spiradoline and U-50488H, selective kappa opioid receptor agonists, in isolated ileum.

In guinea pig ileum, spiradoline (2 x 10(-6) M or greater) and U-50488H (3 x 10(-6) M or greater) suppressed contractile responses to acetylcholine (ACh), histamine, and BaCl2. Inhibition by spiradoline (2 x 10(-5) M) of ACh-induced contractions was not antagonized by pretreatment with naloxone (3 x 10(-4) M). Spiradoline (2 x 10(-8) M or greater) and U-50488H (3 x 10(-8) M or greater) caused dose-dependent inhibition of the contractile response of guinea pig ileum to transmural electric stimulation. The inhibitory effect of spiradoline or of U-50488H at low concentrations was reduced by a high concentration of naloxone (3 x 10(-4) M). Spiradoline at low concentrations ranging from 2 x 10(-9) to 2 x 10(-7) M reduced spontaneous contractions in rabbit ileum. Naloxone (3 x 10(-4) g/ml) antagonized the spiradoline-induced inhibition, but marked inhibition by spiradoline at 10(-4) g/ml was not restored by naloxone. These results suggest that both kappa agonists exert presynaptic inhibitory action on cholinergic nerve endings in the myenteric plexus at a low concentration range of 10(-9) to 10(-7) M and directly inhibit the smooth-muscle motility of the gut at greater concentrations.     

Lipid analysis of normal dermis and hypertrophic scars

Hypertrophic scars (HS) are a consequence of abnormal wound healing. We examined fatty acids that are contained within, and participate in, every reaction through the membrane; then, we analyzed the percentage composition of the fatty acids in deepithelialized normal dermis (ND) and HS. In vivo HS samples were obtained from six patients undergoing surgical excision, and ND samples from five patients undergoing skin grafting surgery for excess. In vitro, cultured fibroblasts from HS and ND were also analyzed. The percentage composition of fatty acids extracted from all the samples was analyzed. In vivo, arachidonic acid (20:4) was significantly more abundant in HS than in ND, in the phospholipids from both whole tissue and cell membranes. In vitro, there were no significant differences among ND, HS, and 10% fetal calf serum. The results suggest that HS formation does not necessarily involve simple excess of 20:4; however, there are considerable differences in the percentage composition of 20:4 between ND and HS. Arachidonic acid probably participates in the formation and maintenance of HS, whereas in vitro cultured fibroblasts are affected largely by fetal calf serum.