Expression of the 27,000 mol. wt heat shock protein following kainic acid-induced status epilepticus in the rat

Western analysis and immunohistochemistry were used to determine the time-course and the distribution of the 27,000 mol. wt heat shock protein, Hsp27, in rat brain following systemic administration of kainic acid. No Hsp27 immunoreactivity was detected in naive control animals or in rats that failed to develop status epilepticus. Hsp27 immunoreactivity was detected as early as 12 h in the parietal cortex, piriform cortex and the hippocampus of rats that developed status epilepticus. The number of cells expressing Hsp27 and the intensity of Hsp27 immunoreactivity were increased 24 h after kainic acid administration. Hsp27 immunoreactivity was still observed seven days post-kainic acid injection. The morphology of the Hsp27-positive cells and double immunofluorescence against Hsp27 and glial fibrillary acidic protein revealed that Hsp27-positive cells were astrocytes. In addition, the distribution of Hsp27 suggested that astrocytic Hsp27 was dependent on excitation-induced metabolic stress rather than the direct effect of kainic acid on astrocytes.     

Desmoid tumour of the thoracic outlet: an unusual cause of thoracic outlet syndrome

Several electrocardiographic anomalies have been described in association with hypoglycaemia. We report the case of a 70-year-old woman with hypoglycaemic coma whose electrocardiogram showed significant conduction anomalies, including atrioventricular block and intraventricular conduction disturbances, and repolarization abnormalities. These electrocardiographic changes disappeared after intravenous glucose administration.     

Dose-dense therapy with weekly 1-hour paclitaxel infusions in the treatment of metastatic breast cancer

PURPOSE: To evaluate the efficacy and toxicity of paclitaxel administered as a 1-hour infusion on weekly basis, without interruption, to patients with metastatic breast cancer who had received prior therapy. PATIENTS AND METHODS: Thirty patients with metastatic breast cancer received sustained weekly paclitaxel therapy at an initial dose of 100 mg/m2 until disease progression. Prior therapy included adjuvant only (n=17), metastatic only (n=7), or both (n=6). Eighteen patients had received prior anthracycline therapy, 12 of whom had demonstrated progression of disease within 12 months of it. All patients were assessable for efficacy; 29 patients were assessable for toxicity. Pharmacokinetic studies of paclitaxel were also performed. RESULTS: A total of 469 weekly paclitaxel infusions were administered to 30 patients (median, 14 infusions/patient). The median delivered dose-intensity was 91 mg/m2/wk (range, 80 to 108). The overall response rate was 53% (95% confidence interval [CI], 34% to 72%), with 10% complete responses (CRs) and 43% partial responses (PRs). Median response duration was 7.5 months (range, 2 to 11+). Responses were observed in nine of 18 (50%) patients with prior anthracycline therapy, including six of 12 (50%) with disease progression on anthracycline within 1 year (three of four within 6 months). Therapy was well tolerated and remarkable for a lack of overall and cumulative myelosuppression. Grade 3/4 neutropenia occurred in four patients; febrile neutropenia was not observed. Peripheral neuropathy prohibited dose escalation above 100 mg/m2, and grade 3 neuropathy was observed in two of 21 patients at < or = 100 mg/m2. CONCLUSION: Weekly paclitaxel therapy is active and well tolerated in patients with metastatic breast cancer. Weekly therapy should be considered as a current clinical option for these patients and should be incorporated into future comparative clinical trials.     

Identification of active-site histidine residues of a self-incompatibility ribonuclease from a wild tomato

The style component of the self-incompatibility (S) locus of the wild tomato Lycopersicon peruvianum (L.) Mill. is an allelic series of glycoproteins with ribonuclease activity (S-RNases). Treatment of the S3-RNase from L. peruvianum with iodoacetate at pH 6.1 led to a loss of RNase activity. In the presence of a competitive inhibitor, guanosine 3'-monophosphate (3'-GMP), the rate of RNase inactivation by iodoacetate was reduced significantly. Analysis of the tryptic digestion products of the iodoacetate-modified S-RNase by reversed-phase high-performance liquid chromatography and electrospray-ionization mass spectrometry showed that histidine-32 was preferentially modified in the absence of 3'-GMP. Histidine-88 was also modified, but this occurred both in the presence and absence of 3'-GMP, suggesting that this residue is accessible when 3'-GMP is in the active site. Cysteine-150 was modified by iodoacetate in the absence of 3'-GMP and, to a lesser extent, in its presence. The results are discussed with respect to the related fungal RNase T2 family and the mechanism of S-RNase action.     

Infrared and millimeter-wave sensors for military special operations and law enforcement applications

We consider the application of infrared and millimeter-wave sensors, developed for the most part during the Cold War, to the solution of problems encountered by military special operations units and law enforcement personnel. These problems include detection of weapons concealed beneath clothing, through-the-wall surveillance, and wide-area surveillance under poor lighting conditions. Key sensors used in these applications are infrared cameras, millimeter-wave passive and active cameras, and millimeter-wave real-aperture and holographic radars. This paper discusses each type of sensor, describes its operation, and gives an example of its output, except in those cases where the device is early in its development phase and thus no outputs are available. All of these sensors form images, but the images are of varying quality. We conclude with a brief discussion of methods of using multiple sensors to improve performance.     

The generation and interpretation of positional information within the vertebrate myotome

How somitic cells become restricted to the muscle fate has been investigated on a number of levels. Classical embryological manipulations have attempted to define the source of inductive signals that control the formation of the myotome. Recently, these studies have converged with others dissecting the role of secreted proteins in embryonic patterning to demonstrate a role for specific peptides in inducing individual cell types of the myotome. Collectively, these investigations have implicated the products of the Wnt, Hedgehog (Hh) and Bone morphogenetic protein (Bmp) gene families as key myogenic regulators; simultaneously controlling both the initiation of myogenesis and the fate of individual myoblasts.     

Notochord induction of zebrafish slow muscle mediated by Sonic hedgehog

The patterning of vertebrate somitic muscle is regulated by signals from neighboring tissues. We examined the generation of slow and fast muscle in zebrafish embryos and show that Sonic hedgehog (Shh) secreted from the notochord can induce slow muscle from medial cells of the somite. Slow muscle derives from medial adaxial myoblasts that differentiate early, whereas fast muscle arises later from a separate myoblast pool. Mutant fish lacking shh expression fail to form slow muscle but do form fast muscle. Ectopic expression of shh, either in wild-type or mutant embryos, leads to ectopic slow muscle at the expense of fast. We suggest that Shh acts to induce myoblasts committed to slow muscle differentiation from uncommitted presomitic mesoderm.     

2-Iminopyrrolidines as potent and selective inhibitors of human inducible nitric oxide synthase

A series of substituted 2-iminopyrrolidines has been prepared and shown to be potent and selective inhibitors of the human inducible nitric oxide synthase (hiNOS) isoform versus the human endothelial nitric oxide synthase (heNOS) and the human neuronal nitric oxide synthase (hnNOS). Simple substitutions at the 3-, 4-, or 5-position afforded more potent analogues than the parent 2-iminopyrrolidine 1. The effect of ring substitutions on both potency and selectivity for the different NOS isoforms is described. Substitution at the 4- and 5-positions of the 2-iminopyrrolidine yielded both potent and selective inhibitors of hiNOS. In particular, (+)-cis-4-methyl-5-pentylpyrrolidin-2-imine, monohydrochloride (20), displayed potent inhibition of hiNOS (IC50 = 0.25 microM) and selectivities of 897 (heNOS IC50/hiNOS IC50) and 13 (hnNOS IC50/hiNOS IC50). Example 20 was shown to be an efficacious inhibitor of NO production in the mouse endotoxin assay. Furthermore, 20 displayed in vivo selectivity, versus heNOS isoform, by not elevating blood pressure at multiples of the effective dose in the mouse.     

Even-weighted codes for error detection

For a binary symmetric channel, a code V with only evenweighted words performs better than a corresponding code V? with both odd- and even-weighted words, from the point of the probability of undetected errors. We derive an estimate of the improvement in the performance.     

Australian encephalitis in the Northern Territory: clinical and epidemiological features, 1987-1996

OBJECTIVES: The purpose of this study was to evaluate the contribution of the executive cognitive functions to self-reported and observed performance of activities of daily living and instrumental activities of daily living. DESIGN: These data were collected as part of a cross-sectional survey of community-dwelling older persons, using statistical sampling, in a two-county area of southern Colorado. SETTING: Participants were interviewed and administered measures of general cognition, depression, executive functioning, and performance of self-care and instrumental activities, either in their homes or at the study clinic. PARTICIPANTS: A total of 1158 community-dwelling persons between the ages of 60 and 99 participated. Of these, 657 were female, 501 were male, 637 were Hispanic, and 521 were non-Hispanic whites. MEASUREMENTS: Subjects were administered the Mini-Mental State Exam (MMSE), a measure of executive functioning (the Behavioral Dyscontrol Scale), the Center for Epidemiologic Studies Depression scale (CES-D), and the Structured Assessment of Independent Living Skills (SAILS, a measure of observed performance of daily tasks). They also were interviewed regarding their reported ADL and IADL status using measures from the Longitudinal Study on Aging. RESULTS: Both general mental status and executive functioning demonstrated statistically significant univariate associations with all seven functional status measures (both self-report and observed performance). In a series of ordinary least squares regression models, executive functioning was a predictor for self-reported ADLs and observed performance of complex IADL tasks such as managing money and medications. Mental status did not predict self-reported functioning but was a predictor of observed performance. Depression was a significant variable for self-report measures but not for observed performance. Executive functioning and general mental status demonstrated some degree of independence from one another. CONCLUSION: Executive functioning is an important determinant of functional status for both self-reported and observed ADLs and IADLs and should be assessed routinely when evaluating the mental status and functional abilities of older people. These results replicate and extend previous research on executive functioning among older persons by examining these factors in a large bi-ethnic community sample.