Campylobacter jejuni and Arcobacter species associated with intussusception in a raccoon (Procyon lotor).
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Biomedical subjects
Publications and source records attributed to S Franklin.
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Antibodies were purified from normal rabbit, sheep, goat, rat, human and bovine serum using preparative electrophoresis on a Gradiflow in a single-step process using an asymmetrical cartridge with three different pore size polyacrylamide membranes. Recoveries in each case were over 80% and were higher than those obtained using affinity chromatography on protein A, protein G or protein L. Degree of purity was at least comparable with these methods. These results suggest that preparative electrophoresis can be considered a general method for the purification of research quantities of antibodies from multiple serum sources and may be particularly useful where the reactivity with protein A, G or L is unknown.
We presented a new model using the sensory/functional theory of semantic category deficits to explain noun/verb deficits in aphasia. The predictions arising from this model were tested on a small number of patients exhibiting grammatical and/or semantic category specific deficits in picture naming. The results lent support for the theory presented. Shapiro and Caramazza (this issue) raised several objections to this theory (which they call the "extended sensory functional theory," or ESFT). In this article we address their concerns about the validity of the ESFT and conclude that it is indeed a useful model that provides a parsimonious explanation for many diverse patterns of deficits.
Garrett (1982) developed a model of normal sentence production which has been used in the description of aphasic language (Schwartz, 1987). This study investigated the effects of the thematic representation specified at the functional level on the complexity of the phrases produced at the positional level. A group of 14 nonfluent, agrammatic subjects were compared to 20 normal controls in their production of the story of Cinderella. The agrammatic subjects produced fewer argument structures than the normal control subjects. Their phrasal realization of the arguments, however, was not qualitatively different from that of the normal subjects. In both cases, with an increase in the number of arguments, there was a concurrent increase in the mean complexity of the phrases used to realize those arguments and in the total phrasal complexity of the utterances. The complexity of noun phrases differed according to the thematic roles expressed; this seemed to be a consequence of their different locations in the sentence. Preverbal noun phrases were much less complex than postverbal noun phrases. There was no evidence to suggest that there was a trade-off between the production of thematic structure and subsequent phrasal production. Neither was there evidence to suggest that production differed according to whether the phrase was an argument of the verb or a nonargument. The complexity of a phrase was determined by the type of information it conveyed.
Age of acquisition and imageability ratings were collected for 2,645 words, including 892 verbs and 213 function words. Words that were ambiguous as to grammatical category were disambiguated: Verbs were shown in their infinitival form, and nouns (where appropriate) were preceded by the indefinite article (such as to crack and a crack). Subjects were speakers of British English selected from a wide age range, so that differences in the responses across age groups could be compared. Within the subset of early acquired noun/verb homonyms, the verb forms were rated as later acquired than the nouns, and the verb homonyms of high-imageability nouns were rated as significantly less imageable than their noun counterparts. A small number of words received significantly earlier or later age of acquisition ratings when the 20-40 years and 50-80 years age groups were compared. These tend to comprise words that have come to be used more frequently in recent years (either through technological advances or social change), or those that have fallen out of common usage. Regression analyses showed that although word length, familiarity, and concreteness make independent contributions to the age of acquisition measure, frequency and imageability are the most important predictors of rated age of acquisition.
BACKGROUND: Reboxetine is a potent antidepressant, with efficacy comparable to that of imipramine, desipramine, and fluoxetine, and has improved side-effect profile. The basis of its efficacy and improved tolerability is sought through studies of reboxetine in a number of pharmacological models of depression. METHODS: Pharmacological selectivity for uptake systems was defined by uptake and binding assays for the three monoamine uptake sites. Specificity was determined in 39 different receptor and 6 enzyme assays. In vivo selectivity was defined by measurement of neuronal firing rates in the locus coeruleus, dorsal raphe, and substantia nigra. Reserpine-induced blepharospasm and hypothermia, clonidine-induced hypothermia, defined reboxetine's in vivo pharmacology. Reboxetine's antidepressant potential was evaluated behaviorally by the tail-suspension test, forced swimming, and the DRL72 operant responding test. RESULTS: Reboxetine is a potent, selective, and specific norepinephrine reuptake inhibitor (selective NRI) as determined by both in vitro and in vivo measurements. Unlike desipramine or imipramine, reboxetine has weak affinity (Ki > 1,000 nmol/L)for muscarinic, histaminergic H1, adrenergic alpha1, and dopaminergic D2 receptors. In vivo action of reboxetine is entirely consistent with the pharmacological action of an antidepressant with preferential action at the norepinephrine reuptake site. Reboxetine showed an antidepressant profile in all tests of antidepressant activity used. Significant decreases in immobility were observed in the tail suspension test and behavioral despair test. Increased efficiency in responding was observed in the DRL72 test. CONCLUSIONS: Reboxetine is a potent, selective, and specific noradrenergic reuptake inhibitor. It has a superior pharmacological selectivity to existing tricyclic antidepressants and selective serotonin reuptake inhibitors when tested in a large number of in vitro and in vivo systems. Given the pharmacological profile, reboxetine is expected to be a selective and potent tool for psychopharmacological research. The use of reboxetine in the clinic will also help clarify the role norepinephrine plays in depression.
An isocratic method for the identification and quantitation of erythromycin and related substances in enteric-coated tablet formulations using high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection at 205 nm is described. A novel method for sample preparation using a molecular weight centrifuge filter to reduce the interferences observed from polymeric tablet coating material is also presented. Erythromycin HPLC assays are best run at high pH; therefore, various polymer columns were evaluated. The resulting HPLC method that was developed has several advantages over current pharmacopeial assay methods for enteric-coated erythromycin tablets. Comparative data from both methods for the same batch of EryTab tablets are presented. The method can also be applied to various other erythromycin formulations, including particle-coated tablets, erythromycin stearate tablets, and erythromycin ethylsuccinate suspensions and fermentation broths. A C18 Polymeric column is used with a mobile phase composition of 0.02 M potassium phosphate dibasic buffer (pH 9): acetonitrile (60:40) and flow rate of 1 mL/min. This method is more sensitive, specific, and rugged than the pharmacopeial method.
Semantic category effects, such as difficulties in naming animate things relative to inanimate objects, have been explained in terms of the relative weightings of perceptual and functional features within the semantic representations of these concepts. We argue that grammatical category deficits, such as difficulties in naming nouns relative to verbs, can be explained within the same framework. We hypothesize that verb concepts are richer in functional than sensory features and present a model of the semantic representations of animate nouns, inanimate nouns, and verbs. The model demonstrates that sensory feature damage results in a deficit for naming living things but spares verb naming, and functional feature damage results in a deficit for naming inanimate objects and verbs. We then report the assessment results of two patient groups. In accordance with the model's predictions, the "verb spared" patients were consistently worse at naming living things than inanimate objects, and their definitions of both living and nonliving items were lacking in sensory information. We conclude that damage to sensory features in semantic representations causes difficulties in naming concrete nouns relative to action verbs, and within the grammatical category of nouns, animate items will be more severely affected. Imageability was shown to be a strong predictor of naming performance in the "verb deficit" patients, and when this variable was controlled no class effect remained. Production of definitions revealed no differential damage to sensory or functional features, and no consistent effect of animacy in naming was shown. While the model suggests that verb deficits might occur in patients for whom functional features are damaged relative to sensory features, we conclude that the "verb deficit" shown in our patients (and potentially in many previously reported cases) was an artifact of the lower imageability of verbs in confrontation naming tasks.
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BACKGROUND: The proto-oncogene eIF4E has been found to be elevated in head and neck squamous cell carcinomas. In an earlier prospective study overexpression of eIF4E, detected by Western blot analysis, in histologically normal surgical margins correlated with an increased local-regional recurrence rate during a 1-year follow-up. OBJECTIVE: To test the reverse hypothesis that absence of overexpression of eIF4E in the surgical margins is a predictor for long-term survival in patients with squamous cell carcinoma of the head and neck. DESIGN: A retrospective analysis was performed on 31 patients who underwent surgery for squamous cell carcinoma of the larynx or hypopharynx. Immunohistochemical analysis was used to detect eIF4E on paraffin embedded sections of the tumor and the histologically negative surgical margins. RESULTS: All 31 patients overexpressed eIF4E in the tumors. Thirteen patients had no detectable level of eIF4E in the margins, and only 1 had a local-regional recurrence. The average disease-free interval in this group of patients was 82.08 months. The remaining 18 patients all overexpressed eIF4E in the surgical margins (eIF4E score range, 5-80). Twelve (67%) of these patients developed a recurrence; the average disease-free interval was 31.95 months. Cox regression analysis showed that eIF4E in the margin (P= .01), nodes (P= .06), site (P= .02), and age (P= .02) had significant effects on the disease-free interval. The Kaplan-Meier survival curves were significantly different for eIF4E-positive and eIF4E-negative margins (P = .002). CONCLUSIONS: eIF4E in the surgical margins is an independent prognostic factor and its absence in surgical margins may predict long-term survival. Detecting eIF4E in the margins may improve survival by determining which patients would benefit from further resection or adjuvant therapy.
Baars (1988, 1997) has proposed a psychological theory of consciousness, called global workspace theory. The present study describes a software agent implementation of that theory, called "Conscious" Mattie (CMattie). CMattie operates in a clerical domain from within a UNIX operating system, sending messages and interpreting messages in natural language that organize seminars at a university. CMattie fleshes out global workspace theory with a detailed computational model that integrates contemporary architectures in cognitive science and artificial intelligence. Baars (1997) lists the psychological "facts that any complete theory of consciousness must explain" in his appendix to In the Theater of Consciousness; global workspace theory was designed to explain these "facts." The present article discusses how the design of CMattie accounts for these facts and thereby the extent to which it implements global workspace theory.
OBJECTIVE: The translation initiation factor eIF4E (4E) when overexpressed in mammalian cells results in their oncogenic transformation. 4E facilitates the synthesis of two powerful tumor angiogenic factors (VEGF and FGF-2) by selectively enhancing their translation. 4E is overexpressed not only in all head and neck squamous cell cancers but also in some dysplastic margins. Tumorigenesis in the head and neck is proposed to be a multistep process preceded by clinically evident precancerous lesions. Molecular events underlie the histological changes that herald transformation. We wanted to study the role of 4E in tumorigenesis and further elucidate its causal role in angiogenesis. METHODS: An immunohistochemical analysis with antibodies to 4E, VEGF, and basic (b)-FGF was performed on 115 specimens of the head and neck representing various stages of histological progression of malignancy. This was correlated with mean vessel density (MVD) using factor VIII. RESULTS: There were 41 cases of hyperplasia and low-grade dysplasia, 40 cases of high-grade dysplasia and 34 cases of cancer. There was a significant increase in the percent of cases expressing 4E from low-grade dysplasia through tumor. However, for VEGF and b-FGF the significant increase was only seen between the tumor group and dysplastic groups and no significant increase was noted between low-grade and high-grade dysplasia There was a significant increase in MVD from low- (10.7+/-1) to high-grade grade dysplasia (18.0+/-2.3). This increase was even more striking for the 4E positive cases. CONCLUSION: 4E elevation is correlated with progressive cell transformation in the head and neck. Its correlation with VEGF, b-FGF, and MVD potentiates its possible role in angiogenesis.
PURPOSE: Complete excision of cancer is guided by histologic assessment of surgical margins. Molecular markers may be more sensitive in identifying malignant cells. eIF4E, a eukaryotic protein synthesis initiation factor, is found elevated in all head and neck squamous cell cancers (HNSCC). In a preliminary study using Western blots and a retrospective study using immunohistochemistry, eIF4E elevation in histologically tumor-free surgical margins correlated with a higher local-regional recurrence. We wanted to confirm this hypothesis in a prospective study. PATIENTS AND METHODS: Immunohistochemical analysis of surgical margins and tumors with an antibody to eIF4E was performed on all newly diagnosed HNSCC patients who underwent surgical resection for their disease between January 1996 and December 1997. RESULTS: All 65 patients had elevated levels of eIF4E in the tumors. Thirty-six patients (55%) had elevated eIF4E in histologically tumor-free margins, and 20 of these patients (56%) have had local-regional recu rrences. Twenty-nine patients (45%) had no elevation of eIF4E in the margins, and only two of these patients (6.9%) have had recurrences. Cox regression analysis showed that elevated eIF4E in the margins was an independent prognostic factor (P =.009) for recurrence. The Kaplan-Meier curves for the probability of nonrecurrence were significantly different for positive and negative eIF4E margins (P =. 0001, log-rank test). CONCLUSION: In histologically tumor-free surgical margins, elevated levels of eIF4E predict a significantly increased risk of recurrence. Elevated levels of eIF4E in tumor margins may identify patients who could benefit from additional therapy.
1. Diseases transmitted from animals to humans, referred to as zoonoses, pose risks for persons occupationally exposed to animals. 2. Occupational health nurses should be proactive in identifying potential occupational health risks and educating employees to protect themselves from animal exposure risks. 3. Exposure history should include exposure to birds and animals during occupational and recreational activities. 4. Primary prevention is critical, as immunizations and treatments are limited and include many associated risks.
A client with dysphasia was treated during the first six months following onset. A cognitive neuropsychological model of language processing was used to establish the levels of impairment in auditory comprehension. Three separate phases of therapy were administered: a semantic therapy; a period of therapy where both semantics and auditory processing were treated; and therapy designed to enhance the processing of words in a sentence. Four assessments were used to measure changes between each therapy phase and the results demonstrate that improvement occurred in a pattern which suggests specific effects of treatment.
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In these experiments, the effect of the irreversible mu-opioid receptor antagonist clocinnamox on the potency of morphine, opioid receptor binding and mu-opioid receptor mRNA was examined. Mice were injected with clocinnamox (0.32-12.8 mg/kg) and the analgesic potency of morphine was examined 24 h later. Clocinnamox produced a dose-dependent decrease in the potency of morphine; and at the higher dose of clocinnamox the maximal analgesic effect was not observed following doses of morphine in excess of 500 mg/kg s.c. In saturation binding studies in brain, clocinnamox (0.32-25.6 mg/kg) dose-dependently decreased mu-opioid ([3H][D-Ala2,MePhe4,Gly-ol5]enkephalin; DAMGO) receptor Bmax with relatively minimal effects on Kd. Binding to delta-opioid receptor ([3H][D-Pen2,D-Pen5]enkephalin; DPDPE) and kappa-opioid receptor ([3H](5,7,8)-(-)-N-methyl-N-(7-(1-pyrrolidinyl)-1-oxaspiro(4,5)dec -8-yl) benzeneacetamide; U69,593) was not affected by clocinnamox. The effect of clocinnamox was time-dependent in that the greatest changes in morphine potency and mu-opioid receptor density were observed within 24 h of administration and decreased with time (336 h). Although mu-opioid receptor density was decreased to less than 30% of control 24 h following clocinnamox (12.8 mg/kg) and had increased to 80% by 5 days, a solution hybridization assay for mu-opioid receptor mRNA transcript revealed no changes in the steady-state levels of this mRNA. These studies indicate that clocinnamox is an irreversible antagonist at the mu-opioid receptor since it appears to selectively affect receptor density with minimal effects on affinity. Furthermore, clocinnamox produces time- and dose-dependent changes in Bmax and these changes appear to be unrelated to changes in mu-opioid receptor mRNA. It is possible that the repopulation of brain by mu-opioid receptors following clocinnamox is mediated by an existing pool of receptors that are activated following treatment.
The baculovirus antiapoptotic protein p35 inhibited the proteolytic activity of human interleukin-1 beta converting enzyme (ICE) and three of its homologs in enzymatic assays. Coexpression of p35 prevented the autoproteolytic activation of ICE from its precursor form and blocked ICE-induced apoptosis. Inhibition of enzymatic activity correlated with the cleavage of p35 and the formation of a stable ICE-p35 complex. The ability of p35 to block apoptosis in different pathways and in distantly related organisms suggests a central and conserved role for ICE-like proteases in the induction of apoptosis.