Voltammetry in unanesthetized rat: Increases of striatal dopamine turnover after unilateral haloperidol injection into the substantia nigra

In freely moving rats, effects of unilateral haloperidol injection into the substantia nigra were monitored with in vivo voltammetry in the bilateral striata. The electrochemical responses at 120 mV versus Ag-AgCl, reflecting mainly a level of 3,4-dihydroxyphenylacetic acid (DOPAC), increased both in the striata within 1.5 h after 5 μg of haloperidol treatment. In the experiments of high-performance liquid chromatography with electrochemical detection, the ratio of DOPAC to dopamine in the striata significantly increased at 2.75 h after drug treatment. These data support the idea that unilateral injection of haloperidol into the substantia nigra in freely moving rats increases dopamine turnover in the bilateral striata.     

Coexistence of paired helical filaments and glial filaments in astrocytic processes within ghost tangles.

Ultrastructural examination of ghost tangles in an autopsy case of long-term Alzheimer's disease revealed, in addition to degenerate neurites containing paired helical filaments (PHF), astrocytic processes which included PHF. This finding suggests either that astrocytes in ghost tangles possess the capacity to produce PHF or that PHF are incorporated into astrocytes by endocytosis.     

IL-8 as an important chemoattractant for neutrophils in ulcerative colitis and Crohn's disease.

IL-8 is generating increasing interest as a powerful neutrophil chemoattractant and activator. To elucidate the mechanisms of neutrophil infiltration in inflammatory bowel disease, we examined 33 patients with ulcerative colitis (UC), 18 with Crohn's disease (CD), eight with some other type of colitis, and 18 normal control subjects for measurement of IL-8 in homogenates of colonic biopsy specimens. The affected colonic mucosa was found to contain significantly more IL-8 in patients with active inflammatory bowel disease than in patients with inactive disease (UC, P < 0.001; CD, P < 0.001), in patients with other types of colitis (UC, P < 0.05; CD, P < 0.01), or in normal control subjects (UC, P < 0.001; CD, P < 0.001). Colonic IL-8 levels correlated significantly with the macroscopic grade of local inflammation, especially in patients with UC (P < 0.001). Colonic IL-8 levels also correlated well with the neutrophil numbers in mucosal tissue (UC, r = 0.950, P < 0.001; CD, r = 0.940, P < 0.001), and with colonic IL-1 beta (r = 0.911, P < 0.001) and tumour necrosis factor-alpha (TNF-alpha) levels (r = 0.604, P < 0.001) in patients with these two conditions. These data suggest a potential role for IL-8 and its regulatory cytokines IL-1 and TNF-alpha in mediating neutrophil infiltration of the gut wall in inflammatory bowel disease.     

Eradication of established tumors by CD8+ T cell adoptive immunotherapy

We generated the DUC18 T cell receptor transgenic mouse expressing an H-2Kd -restricted transgenic T cell receptor specific for the syngeneic CMS5 fibrosarcoma rejection antigen mutated ERK2(136-144). DUC18 mice were capable of specifically eliminating lethal CMS5 tumor challenges, and transfer of DUC18 splenocytes to naive nontransgenic recipients conferred protection from subsequent and established CMS5 tumor burdens. Eradication of established tumor burdens by adoptive transfer of DUC18 splenocytes was dose and time dependent. Transferred tumor-specific T cells remained functional in vivo and capable of rejecting small tumors even in the presence of large, established tumor burdens. These findings highlight the kinetic battle between tumor growth and the production of a tumor-specific response and have critical implications for effective adoptive immunotherapy.     

Effects of drug adherence on patient outcomes to early treatment for Japanese cedar pollinosis]

Drug adherence is one of the important aspects in caring for patients with allergic rhinitis. To improve clinical efficacy of early treatment for Japanese cedar pollinosis (JCP), we evaluated the effect of drug adherence on patients' outcomes. Patients were randomly selected from 16 ENT clinical sites in Osaka and Wakayama between February 24 and March 8, 2003 (peak pollen season). Efficacy was assessed using patients' ratings of nasal and ocular symptoms and overall assessment in their condition compared with previous season ones. Costs include direct costs of the drugs used for treatment to JCP from January to February. Five hundred one patients taking early treatment were enrolled. Compared to low adherence patients, those who reported higher level of adherence significantly improved overall health condition, and achieved better symptom relief of rhinorrhea and nasal congestion. In multiple logistic regression analysis, the following factors were independent risk factors for low adherence: student (p=0.002), using OTC medications (p=0.006), and short-duration of medication (p=0.001). Low costs were also risk factor for low adherence. We conclude that taking medications for JCP for 22-28 days is the best way to enhance patients' outcomes.     

Hormone production andc-myc protein labeling in plurihormonal pituitary adenomas

The biological activity of plurihormonal pituitary adenomas was compared with that of tumors producing only one hormone by evaluating the percentage ofc- myc protein-labeled cells and ultrastructural characteristics. Twenty-five pituitary adenomas producing 3 or more hormones and 14 adenomas producing only I hormone were studied. Tissue sections were stained immunohistochemically using antibodies for pituitary hormones andc- myc protein, and they were examined by electronmicroscopy. DNA extracted from ethanol-fixed, paraffinembedded tissue was analyzed for p53 mutations by polymerase chain reaction and singlestrand conformation polymorphism analysis. The percentage ofc- myc protein-labeled cells in adenomas producing 4 or 5 pituitary hormones was significantly higher (p < 0.01 ) than in those producing 3 or 1 hormones. There were no p53 mutations in plurihormonal adenomas. Pituitary adenomas producing 4 or 5 pituitary hormones demonstrate biological aggressiveness; therefore, multihormone production reflects aggressive capacity rather than degree of differentiation.     

Active and inactive renin after exercise

Summary The effects of graded exercise on plasma concentrations of active and inactive renin were studied in seven healthy men. Exercise was performed on a cycle ergometer at four different exercise intensities (corresponding to 30%, 50%, 80% and 87% of ) for 10 min each. Concentrations of active renin and total renin after activation by trypsin were measured by direct immunoradiometric assay. Non-trypsin-activated renin concentration (inactive) was obtained by subtraction. Active renin concentrations at 30%, 50%, 80% and 87% of were 1.2, 1.9, 3.1 and 4.6 times higher than the control concentration, respectively. Similar increases in plasma renin concentration, determined by conventional enzymatic assay, were observed at every stage. In contrast, changes in inactive renin concentration were not significant at any stage. Significant increases in noradrenaline concentration were found at every exercise stage, but adrenaline, aldosterone and lactate concentrations were significantly elevated only after exercise at 50%, 80% and 87% of . The similarity between the changes in concentration of active renin and noradrenaline would suggest that sympathetic nerve activity may have been responsible either for the release of active renin or for the conversion of inactive renin to its active form in the kidney.