Selective facilitatory effect of vasoactive intestinal polypeptide (VIP) on muscarinic firing in vesical ganglia of the cat

VIP immunoreactivity was identified in nerve fibers and in 10-13% of the neurons in pelvic and bladder ganglia of the cat. Ninety percent of the VIP positive neurons contained acetylcholinesterase. VIP immunoreactivity was not altered in decentralized ganglia 1 week to 8 months after transection of the pelvic and hypogastric nerves indicating that VIP fibers arose from neurons within the peripheral nervous system. The intra-arterial administration of VIP (1-50 micrograms/kg) enhanced the postganglionic discharge elicited by the muscarinic agonist, acetyl-beta-methylcholine, but did not alter the postganglionic firing elicited by the nicotinic agonist, tetramethylammonium or by electrical stimulation of preganglionic axons in the pelvic nerve. VIP did not elicit a postganglionic discharge in untreated ganglia, but did evoke a prolonged discharge in ganglia treated with an irreversible anticholinesterase agent, 217AO. This discharge was not affected by hexamethonium but was blocked by atropine. VIP suppressed the muscarinic inhibition of ganglionic transmission produced by acetyl-beta-methylcholine without altering the response to other inhibitory agents (norepinephrine, leucine-enkephalin and gamma-aminobutyric acid (GABA). VIP (0.1-0.3 micrograms/kg) also had a direct inhibitory effect on bladder smooth muscle. These findings raise the possibility that intraganglionic pathways containing VIP may exert a selective modulatory influence on muscarinic transmission in vesical parasympathetic ganglia.     

Clinical Significance of Prostate Specific Antigen for Early Stage Prostate Cancer Detection

The characteristics of serum prostate specific antigen (PSA)in normal Japanese men were studied in 1480 subjects examinedby mass screening (MS) for prostate cancer (Pea) in Gunma Prefecturein 1992. The serum PSA concentration was correlated with patientage. The average serum PSA level increased by 0.04 ng/ml/year.The upper normal limits (95 percentiles)of age specific PSAfor normal men are 1.33 ng/ml for those aged 39–49 years,3.65 ng/ml for those aged 50–59 years, 4.06 ng/ml forthose aged 60–69 years, 5.09 ng/ml for those aged 70–79years and 5.66 ng/ml for those aged 80–89 years. Among227 normal men examined by our MS in 1991 and 1992, the PSAvelocity (PSAV) was calculated to be 0.05 ng/ml/year. Among10 Pea patients with normal PSA levels ( < 6 ng/ml) detectedpreviously by our MS, three had an abnormal PSAV. We demonstratedthe possibility that PSA density could distinguish between Peaand benign prostate hypertrophy. The significance of PSA asa Pea screening modality should be evaluated across multipleage ranges and in combination with previous PSA data and/orprostate volume estimated by sonography.     

Modification of carboxyl-terminal region is the cause of activation of the src gene in avian sarcoma virus S2

Viral oncogene product of avian sarcoma virus S2 was reported to have two alterations from proto-src product; a substitution of its extreme carboxyl terminus with a peptide of helper viral protein and a point mutation which altered the 501st amino acid from arginine to lysine. However, the following data suggest that lysine501 is more common in proto-src product than arginine501. Proto-src from two independent embryos which we analyzed encoded lysine for the 501st amino acid. Rous sarcoma virus and S1, another isolate which had transduced proto-src, also coded for lysine at the same position. Thus, in the case of S2, the oncogenic activation of the src gene appeared to be achieved with only an alteration at its carboxyl terminus and enhanced expression by long terminal repeats.     

Correlation between Physiological and Transforming Activities of the c–mos Proto–oncogene Product and Identification of an Essential Mos Domain for These Activities

Using Xenopus eggs and NIH3T3 cells as assay systems, we have compared the physiological (i.e. maturation–inducing and cleavage–arresting) and in vitro transforming activities of the c– mos genes from various species as well as their mutant genes. These analyses show that the three biological activities all depend upon the intrinsic protein kinase activity of Mos and correlate well with each other. Furthermore, our results demonstrate that a well conserved N–terminal 14–amino acid sequence of Mos, termed the Mos–hox, is essential for all three activities. These results indicate that the in vitro transforming activity of Mos can he ascribed to the same kinase activity of Mos that exerts the physiological activities.     

Nicotine breaks down preformed Alzheimer's beta-amyloid fibrils in vitro.

BACKGROUND: Cerebral deposition of amyloid beta-peptide (Abeta) is a major neuropathologic feature in Alzheimer's disease (AD). A consistent protective effect of smoking on AD has been documented by many case-control studies. It has been suggested that nicotine, a major component of cigarette smoke, protects neurons against Abeta toxicity via the upregulation of nicotinic receptors, as well as via the inhibition of beta-amyloid fibril (fAbeta) formation from Abeta. METHODS: We used fluorescence spectroscopy with thioflavin T and electron microscopy to examine the effects of nicotine, pyridine, and N-methylpyrrolidine on the formation, extension, and disruption of fAbeta(1-40) and fAbeta(1-42) at pH 7.5 at 37 degrees C in vitro. RESULTS: Nicotine dose-dependently inhibited fAbeta(1-40) and fAbeta(1-42) formation from fresh Abeta(1-40) and Abeta(1-42), respectively, as well as the extension reaction of both fAbetas. Moreover, nicotine disrupted preformed fAbeta(1-40) and fAbeta(1-42). These effects of nicotine were observed at concentrations above 10 mmol/L and were similar to those of N-methylpyrrolidine. CONCLUSIONS: The antiamyloidogenic effect of nicotine may be exerted not only by the inhibition of fAbeta formation but also by the disruption of preformed fAbeta. Additionally, this effect may be attributed to N-methylpyrrolidine moieties of nicotine.     

Decreased Superoxide Dismutase Activity in Erythrocyte in Parkinson's Disease

Abstract: Superoxide dismutase (SOD) activities in Parkineon's disease (PD) were significantly lower than those in controls, especially in a treated PD group. However, SOD activities in an untreated PD group did not decrease. There was a signillcant correlation between SOD activities and the duration of illness in the treated PD group (p<0.05). There was a significant correlation between SOD activities and the present doses of L-DOPA/carbidopa in the treated PD group.     

Gene expression profiling in streptozotocin treated mouse liver using DNA microarray.

Streptozotocin (SZ) is known to exert toxic effects not only on pancreatic islet beta cells but also on other organs including liver. For analyzing changes in genes expression associated with SZ toxicity, we performed DNA microarray analyses on the liver obtained from SZ-treated mice. Eight-week-old male ICR mice were treated i.p. with 200 mg/kg of SZ, and the blood and liver were taken at 6, 24 and 48 h after the treatment. Labeled cRNA prepared from total RNA of the liver was hybridized to the GeneChip Murine Genome U74A V.2 (Affymetrix). The number of the probe sets, which were clearly up-regulated or down-regulated, were over 100 at 6 and 24h after the SZ-treatment, and it decreased at 48 h after the treatment. Many of the up-regulated genes were categorized into cell cycle/apoptosis related genes, immune/allergy related genes and stress response/xenobiotic metabolism related genes. On the other hand, genes related to glucose, lipid and protein metabolisms were down-regulated. These changes started prior to the elevation of the serum glucose levels, indicating the direct action of SZ on the liver rather than the secondary effect of diabetes. This may be related with the previously reported hepatic changes such as lipid peroxidation, mitochondrial swelling and inhibition of hepatocyte proliferation observed before the development of hyperglycemia.     

Cytokine secretion by peripheral blood mononuclear cells in myasthenia gravis.

We studied spontaneous secretion of anti-acetylcholine receptor antibody (AChRAb), IgG and cytokines by peripheral blood mononuclear cells (PBMC) from 19 MG patients without therapy and 10 normal controls. IgG secretion was higher in the culture medium of MG than in that of normal controls. AChRAb secretion was correlated with IgG secretion in MG. Interleukin (IL)-2, IL-4, IL-5, IL-6, IL-10, IL-13, interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha secreted by PBMC from MG patients were not different from those produced by those from normal controls. IgG secretion was, however, correlated with the secretions of IL-5 and IL-6 in MG. Spontaneous B cell activation was suspected in patients with MG.     

Proliferative response of rat accessory sex organs to dietary sex hormones after castration or initial dietary administration of estrogen

The hormone dependent proliferative response of five accessory sex organs was examined subsequent to castration-induced or estrogen-induced atrophy using male six-week-old F344 rats. Three weeks after castration, rats were treated with dietary methyltestosterone (300 ppm), ethinyl estradiol (0.75 ppm) or methyltestosterone plus ethinyl estradiol for up to 17 days. Cell proliferation was assessed by 3H-thymidine incorporation as determined from labelling indices using autoradiography. The maximum labelling indices which appeared on days 2 or 3 of administration of methyltestosterone were 24.3, 8.4, 9.6, 21.6 and 13.7% for the ventral, lateral and dorsal prostate, seminal vesicle and coagulating glands, respectively. Combined methyltestosterone and ethinyl estradiol induced mild proliferative responses whereas ethinyl estradiol did not. In a further group of non-castrated rats which were pretreated with dietary ethinyl estradiol for three weeks and then given methyltestosterone, the maximum labelling indices were about 70 to 80% of that in castrated rats.