A complex program of striatal gene expression induced by dopaminergic stimulation

Dopamine acting in the striatum is necessary for normal movement and motivation. Drugs that change striatal dopamine neurotransmission can have long-term effects on striatal physiology and behavior; these effects are thought to involve alterations in gene expression. Using the 6-hydroxydopamine lesion model of Parkinson's disease and differential display PCR, we have identified a set of more than 30 genes whose expression rapidly increases in response to stimulation of striatal dopamine D1 receptors. The induced mRNAs include both novel and previously described genes, with diverse time courses of expression. Some genes are expressed at near-maximal levels within 30 min, whereas others show no substantial induction until 2 hr or more after stimulation. Some of the induced genes, such as CREM, CHOP, and MAP kinase phosphatase-1, may be components of a homeostatic response to excessive stimulation. Others may be part of a genetic program involved in cellular and synaptic plasticity. A very similar set of genes is induced in unlesioned animals by administration of the psychostimulant cocaine or the antipsychotic eticlopride, although in distinct striatal cell populations. In contrast to some previously described early genes, most of the novel genes are not induced in cortex by apomorphine, indicating specificity of induction. Thus we have identified novel components of a complex, coordinated genetic program that is induced in striatal cells in response to various dopaminergic manipulations.     

Myxobolus cerebralis in Tubifex tubifex from a whirling disease epizootic in Montana

Prolonged suppressive antibiotic therapy may be an alternative to removal of infected orthopedic prostheses in some patients. However, the efficacy of prolonged suppressive antibiotics is not well established. We retrospectively reviewed 18 patients with infected orthopedic prostheses who had been treated with prolonged antimicrobial suppression during the last 10 years. Eighteen episodes of infection were identified in these 18 patients. There were nine men and nine women, and the mean age was 66 years (range, 31-83 years). All patients had a functional prosthesis and were treated with surgical debridement, retention of the prosthesis, and administration of intravenous antibiotics for 6-8 weeks, followed by prolonged oral antibiotic suppression. Fifteen of the 18 patients appear to have had a good response and have been able to retain a functional prosthesis. Complications related to antibiotic suppression occurred in 22% but did not necessitate discontinuation of the antibiotic therapy. Prolonged antibiotic suppression is a reasonable alternative to surgery in selected patients with infected orthopedic prostheses.     

Usefulness of CT in patients with intestinal obstruction who have undergone abdominal surgery for malignancy

OBJECTIVE: The purpose of this study was to evaluate the usefulness of CT in determining the causes of intestinal obstruction in patients who have undergone abdominal surgery for malignancy. MATERIALS AND METHODS: We analyzed the CT scans of 55 patients with benign (n = 26) or malignant (n = 29) intestinal obstruction that developed after abdominal surgery for malignancy. After calculating the diagnostic accuracy of interpretations by three radiologists, we compared CT findings for benign and malignant intestinal obstructions with respect to peritoneal involvement patterns and other ancillary findings. Multivariate logistic regression analysis was used to determine the diagnostic performance of CT in revealing causes of obstruction. RESULTS: Diagnostic accuracies of the three radiologists were 67%, 75%, and 78%. CT findings indicating malignant obstruction were a mass at the site of obstruction or prior surgery, lymphadenopathy, or an abrupt transition zone and irregular bowel wall thickening at obstructed sites (p < .05). Conversely, the chance for benign obstruction increased when CT revealed mesenteric vascular changes, a large amount of ascites, or a smooth transition zone and smooth bowel wall thickening at the obstructed site (p < .05). With multivariate logistic regression analysis using two variables (a mass at the site of obstruction or prior surgery and lymphadenopathy), we calculated the overall accuracy of CT as 84% (46/55 patients). CONCLUSION: CT is useful in differentiating benign from malignant intestinal obstructions in patients who have undergone abdominal surgery for malignancy. However, CT has limitations in patients not having a demonstrable peritoneal mass.     

Androgens and masculinization of genitalia in the spotted hyaena (Crocuta crocuta). 1. Urogenital morphology and placental androgen production during fetal life

The pre-T cell receptor (TCR) associates with CD3-transducing subunits and triggers the selective expansion and maturation of T cell precursors expressing a TCR-beta chain. Recent experiments in pre-Talpha chain-deficient mice have suggested that the pre-TCR may not be required for signaling allelic exclusion at the TCR-beta locus. Using CD3-epsilon- and CD3-zeta/eta-deficient mice harboring a productively rearranged TCR-beta transgene, we showed that the CD3-gammadeltaepsilon and CD3-zeta/eta modules, and by inference the pre-TCR/CD3 complex, are each essential for the establishment of allelic exclusion at the endogenous TCR-beta locus. Furthermore, using mutant mice lacking both the CD3-epsilon and CD3-zeta/eta genes, we established that the CD3 gene products are dispensable for the onset of V to (D)J recombination (V, variable; D, diversity; J, joining) at the TCR-beta, TCR-gamma, and TCR-delta loci. Thus, the CD3 components are differentially involved in the sequential events that make the TCR-beta locus first accessible to, and later insulated from, the action of the V(D)J recombinase.     

Cardiovascular pharmacology of SKP-450, a new potassium channel activator, and its major metabolites SKP-818 and SKP-310

The cardiovascular effects of SKP-450, a newly synthesized potassium channel activator, and its two major metabolites SKP-818 and SKP-310 were evaluated on isolated rat aorta and in freely moving rats and anesthetized beagle dogs. The rank order of potency in relaxing rat aorta precontracted with norepinephrine was SKP-450 > SKP-818 > Lemakalim > SKP-310 (EC50: 0.12, 0.55, 0.71 and 5.89 mumol/l, respectively). In rats, SKP-450, SKP-818 and lemakalim (3-100 micrograms/kg, i.v.) induced a dose-dependent decrease in mean arterial pressure (MAP; ED20: 9.8, 11.7 and 22.4 micrograms/kg, respectively) followed by reflex tachycardia. In dogs, SKP-818 and SKP-310 (0.3-1,000 micrograms/kg, i.v.) had quite similar hemodynamic profiles to SKP-450 but with a smaller potency. SKP-450, SKP-818 and SKP-310 dose-relatedly decreased MAP (ED20: 2.6, 4.2 and 588.8 micrograms/kg, respectively). They slightly increased left ventricular positive dP/dtmax with a transient decrease at the highest dose, while inducing a dose-related decrease in rate-pressure product, tension time index and systolic time. SKP-450, SKP-818 and SKP-310 induced a marked dose-dependent increase in coronary blood flow (Emax: 172.8, 257.9 and 178.7%, respectively) with less effects on blood flow through other arteries. Glybenclamide antagonized all the hemodynamic effects of SKP-450 in rats and dogs, whereas propranolol antagonized its reflex tachycardia in rats. These results indicate that SKP-450 is a potent coronary and peripheral vasodilator in rats and dogs activating ATP-sensitive potassium channels and that SKP-818 and SKP-310 exert a similar hemodynamic profile to the parent compound with equi- and weaker potency, respectively.     

The SOCS proteins: a new family of negative regulators of signal transduction

An asymptomatic tumor in the pelvis was incidentally found by ultrasonography in a 67-year-old woman while being examined after presenting with a common cold. Further examinations revealed a presacral cystic tumor, which measured 10 x 12cm in size. The cyst was thus removed in the normal manner for such cases. The pathological diagnosis was an epidermoid cyst. An analysis of 15 other cases previously reported in the literature indicated that large epidermoid cysts should normally be excised through an abdominal approach alone, provided that the tumor is benign.     

Videolaparoscopic access in the surgical treatment of colorectal cancer: critical analysis]

Clozapine was approved by the U.S. Food and Drug Administration in 1989 for treatment of severely ill schizophrenic patients. It has activity against both the positive and negative symptoms of schizophrenia, which has made it an alternative to traditional antipsychotic medications such as haloperidol. However, clozapine must be used cautiously due to its side effect profile. These side effects include agranulocytosis, seizures, and cardiorespiratory symptoms. We report the case of a patient who developed polyserositis (pericardial effusion, pleural effusion, and pericarditis) after being started on clozapine, and whose symptoms remitted upon discontinuation of clozapine. The literature is reviewed and the treatment implications are discussed.     

SAMSON: a software package for the biopolymer primary structure analysis

One hundred and twenty seven patients belonging to Neurosurgery (49), Neuromedicine (48), Cardiac medicine (30) wards and Blood donors (30) as healthy controls were investigated for the prevalence of Toxoplasmosis by means of detecting specific IgM antibody against Toxoplasma gondii (T. gondii) employing Enzyme Immuno Assay (EIA). The detection rate of specific IgM antibody against T.gondii was found to be 32.7% (16/49) among Neurosurgery patients, 20.8% (10/48) among Neuromedical patients and 20% (6/30) among Cardiac medical patients. None of the voluntary blood donors tested was found to have T. gondii IgM antibody. Maximum prevalence rate was found among female patients undergoing Neurosurgery (42.3%) followed by Neuromedical patients (40%). There is an increasing rate of prevalence of Toxoplasmosis from the lower age group upto thirty years and a declining prevalence rate among the higher age groups. The present study revealed high prevalence rate of Toxoplasmosis in Neurosurgery patients (32.7%) and in particular among female (35.2%) than male (17.8%) patients.     

Carcinoma of the esophagus and esophagogastric junction: sensitivity of radiographic diagnosis

OBJECTIVE: The purpose of this study was to determine the sensitivity of barium studies in revealing carcinoma of the esophagus and esophagogastric junction. MATERIALS AND METHODS: We retrospectively reviewed 50 cases of squamous cell carcinoma of the esophagus (n = 25) and adenocarcinoma of the esophagus (n = 14) or esophagogastric junction (n = 11) in which double-contrast (n = 46) or single-contrast (n = 4) barium studies had been done. The original radiology reports were reviewed to determine whether the lesions had been seen on barium studies and whether cancer had been diagnosed. Records were also reviewed to determine the number of patients who underwent esophageal endoscopy because of findings suggestive of cancer on barium studies at some point from January 1992 through December 1992. Pathology records were then reviewed to determine the number of true- and false-positive barium studies during this same period. RESULTS: Lesions were shown on barium studies in 49 (98%) of 50 patients, and carcinoma of the esophagus or esophagogastric junction was diagnosed or suspected in 48 patients (96%). In a separate part of the study, we found that endoscopy had been recommended to rule out malignant tumor in only 26 (1%) of 2484 patients who underwent barium studies at some point from January 1992 through December 1992. Endoscopy revealed cancer in 11 of those 26 patients; the remaining 15 were assumed to have false-positive radiologic examinations. Barium studies therefore had a positive predictive value of 42%. CONCLUSION: The double-contrast barium study is a sensitive technique for the diagnosis of carcinoma of the esophagus and esophagogastric junction. This high sensitivity can be achieved while recommending endoscopy in only about 1% of all patients who undergo barium studies.