Pathogenesis of Mycobacterium bovis infection in cattle

This paper reviews the pathogenesis of Mycobacterium bovis infection in cattle, focusing on aspects relating to the host rather than the organism. A broad concept of pathogenesis has been considered and information is presented on sources and routes of infection, as well as the immune responses and pathology. In addition, data is presented on the excretion of M. bovis from tuberculous cattle.     

Motion patterns of Nabesna Glacier (Alaska) revealed by interferometric SAR techniques

Nabesna Glacier is one of the longest land-terminus mountain glaciers in North America. However, its flow has never been studied. We derived detailed motion patterns of Nabesna Glacier in winter and spring 1994–1996 from the synthetic aperture radar (SAR) images acquired by the European Remote Sensing satellites (ERS-1 and ERS-2) using interferometric SAR (InSAR) techniques. Special effort was made to assess the accuracy of the motion estimates, and remove data points with high uncertainty from the motion profiles, enabling us to obtain reliable glacier flow patterns along the highly curved main course of Nabesna Glacier. The results, covering 80 km of the 87 km main course of the glacier, were used to delineate four distinctive sections in terms of spatial and temporal variability of the glacier speed: (1) the upper section where glacier flow was apparently random both temporally and spatially presumably due to development of crevasses; (2) the upper-middle section with relatively steady flow around 0.27 to 0.4 m/day; (3) the middle section with a stable pattern of acceleration from 0.27–0.3 m/day to the maximum about 0.67–0.73 m/day, followed by a general deceleration to 0.17–0.33 m/day before reaching (4) the lower section where the glacier motion was generally slow yet highly variable although uncertainty in the estimation is high. Occurrence of the flow maximum, as well as many local maxima and minima at consistent locations over different periods suggests that the valley geometry affect the overall flow pattern. On top of this general trend, many small-scale temporal/spatial variations in the glacier flow patterns were observed along the glacier, especially in the lower sections. On average, the flow speeds were in the range of 0.3 to 0.7 m/day; however this lacks any measurements of summer flow speeds which are expected to be significantly higher.     

Behavioral and subjective effects of D-amphetamine and modafinil in healthy adults.

Modafinil is indicated for the management of excessive daytime sleepiness; however, recent studies have examined a broad range of potential uses. Given that clinical uses of modafinil may be expanding, this study compared modafinil and d-amphetamine effects on subjective and performance measures. Across 11 sessions, 11 healthy adults were tested after oral doses of placebo (5 sessions), modafinil (1.75 mg/kg, 3.50 mg/kg, or 7.00 mg/kg), and d-amphetamine (0.035 mg/kg, 0.070 mg/kg, 0.140 mg/kg) under double-blind, randomized conditions. Assessments of cognitive performance and subjective effects were completed before drug administration, 30 min after drug administration, and at hourly intervals after drug administration for 5 hr. Modafinil increased ratings on the Amphetamine and Morphine Benzedrine Group scales of the Addiction Research Center Inventory (ARCI) and increased ratings on the Vigor and Total Positive scales of the Profile of Mood States. d-Amphetamine increased visual analog ratings of feeling stimulated and liking the drug and increased ratings on the Morphine Benzedrine Group scale of the ARCI. Both medications significantly reduced visual analog scale ratings of feeling sleepy, and modafinil decreased ratings on the ARCI Pentobarbital-Chlorpromazine-Alcohol Group scale. Both medications sustained performance that deteriorated across time on the Sternberg Number Recognition Test. Modafinil also enhanced performance rate on the Digit-Symbol Substitution Task above baseline levels and increased response rate on the Repeated Acquisition of Response Sequences Task. These results suggest that modafinil engenders alerting effects and increases performance in healthy non-sleep-deprived individuals comparable with that of d-amphetamine. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An efficient implementation of SELF, a dynamically-typed object-oriented language based on prototypes

We have developed and implemented techniques that double the performance of dynamically-typed object-oriented languages. Our SELF implementation runs twice as fast as the fastest Smalltalk implementation, despite SELF's lack of classes and explicit variables.To compensate for the absence of classes, our system uses implementation-levelmaps to transparently group objects cloned from the same prototype, providing data type information and eliminating the apparent space overhead for prototype-based systems. To compensate for dynamic typing, user-defined control structures, and the lack of explicit variables, our system dynamically compilesmultiple versions of a source method, eachcustomized according to its receiver's map. Within each version the type of the receiver is fixed, and thus the compiler can statically bind andinline all messages sent toself.Message splitting andtype prediction extract and preserve even more static type information, allowing the compiler to inline many other messages. Inlining dramatically improves performance and eliminates the need to hard-wire low-level methods such as+, ==, andifTrue:.Despite inlining and other optimizations, our system still supports interactive programming environments. The system traverses internal dependency lists to invalidate all compiled methods affected by a programming change. The debugger reconstructs inlined stack frames from compiler-generated debugging information, making inlining invisible to the SELF programmer.This work has been generously supported by National Science Foundation Presidential Young Investigator Grant #CCR-8657631, and by IBM, Texas Instruments, NCR, Tandem Computers, Apple Computer, and Sun Microsystems.This paper was originally published inOOPSLA '89 Conference Proceedings (SIGPLAN Notices, 25, 10 (1989) 49–70).     

Preparation and characterization of high molecular weight poly(hydroxy ethers) with unusually high glass transition temperatures

A series of novel poly(hydroxy ethers) have been prepared via polymerization of the diglycidyl ethers of bisphenol-A ( 4 ), 4,4 ′-tribromotetramethylbiphenol ( 6a ), and 4,4 ′-tetrabromotetramethylbiphenol ( 6b ) with a variety of rigid diols in an effort to systematically modify structural features of the phenoxy repeat unit in order to control the torsional mobility of polymer backbones and produce materials with softening temperatures higher than are typical for the class. The resulting poly(hydroxy ethers) displyed glass transition temperatures ranging from 109 to 242°C. There of the polymers were characterized with respect to tensile and impact properties and were compared to the polymer sythesized from bisphenol-A ( 1 ) and bisphenol-A diglycidyl ether ( 4 ).     

Alcoholism: independent predictor of survival in patients with head and neck cancer

BACKGROUND: Despite recognition of the high prevalence of alcoholism among patients with head and neck cancer, the prognostic importance of alcoholism has not been evaluated adequately. Previous investigators have speculated that alcoholic patients may have a poorer prognosis than nonalcoholic patients because of more advanced stage of cancer, the immunosuppressive effects of alcohol, and an increased rate of death due to other alcohol-related diseases. PURPOSE: The goal of this population-based study was to identify the features of alcoholism that are associated with survival for patients with head and neck cancer and to develop an alcoholic severity staging system from a composite of the independent features of alcoholism. METHODS: This prospective study included 649 patients who were diagnosed with cancer of the oral cavity, oropharynx, hypopharynx, or larynx during the period from September 1, 1983, through February 28, 1987, in a three-county area of western Washington state that participates in the Surveillance, Epidemiology, and End Results Program of the U.S. National Cancer Institute. Details on lifetime alcohol consumption, treatment for alcoholism, abstinence from alcohol prior to the diagnosis of cancer, and alcohol-related health problems were ascertained through in-person interviews near the time of diagnosis. Patients were classified as either nonalcoholics or alcoholics according to their responses to questions from the Michigan Alcoholism Screening Test. The measures of alcohol consumption and abuse that were found to be independently associated with 5-year survival by logistic regression analysis were combined using conjunctive consolidation to create a final composite variable, called an alcoholic severity stage. Cox proportional hazards regression analysis was done to estimate the relative risk (R) of death within 5 years due to specific causes of death for each of the alcoholic severity stages. RESULTS: Alcoholism (RR = 2.06; 95% confidence interval [CI] = 1.43-2.98) and a history of alcohol-related systemic health problems (i.e., liver disease, pancreatitis, delirium tremens, or seizures) (RR = 2.76; 95% CI = 1.69-4.49) were associated with an increased risk of death, whereas abstinence (i.e., the consumption of fewer than one drink per week at 1 year prior to the diagnosis of cancer) (RR = 0.62; 95% CI = 0.39-0.97) was associated with a decreased risk of death. These associations were independent of age, site of cancer, anatomical stage, histopathologic grade, smoking, and type of antineoplastic treatment. Patients in the two worst alcoholic severity stages had an increased risk of dying not only of head and neck cancer but also of cardiovascular disease, pulmonary disease, and other alcohol-related causes. CONCLUSIONS: Alcohol abuse, measured by alcohol consumption, functional impairment, a history of alcohol-related health problems, or abstinence, can provide important prognostic information for patients with head and neck cancer. Our results suggest that sobriety among alcoholic patients can lead to prolonged survival.     

Comparison of PF4/heparin ELISA assay with the 14C-serotonin release assay in the diagnosis of heparin-induced thrombocytopenia

The diagnosis of heparin-induced thrombocytopenia (HIT) may be affirmed by demonstrating heparin-dependent anti-platelet antibodies using the 14C-serotonin release assay (SRA). In this study, results of the SRA was compared with the recently described platelet factor 4 (PF4)/heparin enzyme-linked immunosorbent assay (ELISA). Compared with the SRA, the sensitivity and specificity of a PF4/heparin ELISA was 87% and 92%, respectively, using an assay developed in our laboratory; and 90% and 98%, respectively, using a commercially developed kit (Diagnostica Stago, Asnieres, France). However, antibodies to PF4/heparin were also detected in up to 8% of patients whose plasma was negative by SRA, and 23% of patients receiving heparin who were not thrombocytopenic. These data indicate that results obtained with the PF4/heparin ELISA and the SRA are generally in accord in patients with a clinical diagnosis of HIT. However, discrepant results occur in approximately 20% of cases because of the greater sensitivity of ELISA and the possible involvement of other heparin-binding proteins. The fact that each assay contributes independent information in some cases must be considered in the sequence of test performance and in providing consultation to the practicing hematologist.     

The kappa opioid receptor expressed on the mouse R1.1 thymoma cell line down-regulates without desensitizing during chronic opioid exposure

The R1.1 mouse thymoma cell line expresses a single class of kappa opioid receptors that is negatively coupled to adenylyl cyclase through a Bordetella pertussis toxin-sensitive inhibitory guanine nucleotide-binding protein. The aim of the present study was to determine whether chronic opioid treatment of R1.1 cells altered either the binding properties or the functional response associated with the kappa opioid receptor. Culturing of R1.1 cells with the kappa-selective agonist (trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl] benzeneacetamide methane-sulfonate hydrate (U50,488) for 3 hr and longer, followed by extensive washing of R1.1 cell membranes, produced a concentration- and time-dependent reduction in the binding of the kappa-selective ligand (5 alpha,7 alpha,8 beta)-(-)-N-methyl-N-(7-(1-pyrrolidinyl)-1- oxaspiro(4,5)dec-8-yl) benzeneacetamide ([3H]U69,593). Culturing of R1.1 cells with 100 nM U50,488 for 24 hr produced approximately a 50% reduction in the Bmax value for [3H]U69,593 and [3H]naloxone binding. In contrast to the reduction in binding, there was no change in the inhibition of adenylyl cyclase activity by (-)-U50,488. To determine whether kappa opioid receptor function was maintained by spare receptors after agonist-induced down-regulation, membranes from untreated R1.1 cells were incubated with 400 nM of the irreversible opioid antagonist beta-chlornaltrexamine (beta-CNA) followed by extensive washing. beta-CNA produced a 50% reduction in the [3H]U69,593 binding and a 6-fold increase in the IC50 value for (-)-U50,488 inhibition of adenylyl cyclase activity, with no change in the maximal inhibition of cyclic AMP levels.(ABSTRACT TRUNCATED AT 250 WORDS)