Ankle osteoarthritis scale

Although there is a wide array of outcome tools for assessing patients with symptomatic ankle arthritis, no disease-specific instrument for ankle arthritis has been shown to be reliable and valid. The purpose of this study was to develop a simple, reliable, and validated outcome measure for the clinical assessment of ankle osteoarthritis. We modified the Foot Function Index, a visual analog-based scale used to assess rheumatoid foot problems, to measure patient symptoms and functional limitations stemming from osteoarthritis of the ankle joint. Test-retest reliability and criterion and construct validity were determined for the overall Ankle Osteoarthritis Scale and its two subscales (pain and disability). Overall reliability (r=0.97; 95% confidence interval [CI], 0.94-0.99), pain subscale reliability (r=0.95; 95% CI, 0.90-0.98), and disability subscale reliability (r=0.94; 95% CI, 0.88-0.97) were excellent. Criterion validity testing of the instrument with the WOMAC (a disease-specific scale for osteoarthritis) and the SF-36 (a general health survey) showed a high degree of concordance for related subscales. Construct validity using a physical measure of ankle function demonstrated sensitivity of the instrument to the degree of joint dysfunction. Normative data were obtained from 562 individuals who were not patients (264 men and 298 women). The responses were analyzed for trends in gender, body mass index, presence of arthritis, history of fracture in relation to the response levels, and age. A small but statistically significant main effect for gender was found, with women consistently reporting higher pain, disability, and total index scores. Body mass index and arthritis were also found to correlate with response answers across the subscale and total index scores; however, these factors only accounted for 12% of the variation. The Ankle Osteoarthritis Scale is a reliable and valid self-assessment instrument that specifically measures patient symptoms and disabilities related to ankle arthritis.     

The malonyl-CoA-sensitive form of carnitine palmitoyltransferase is not localized exclusively in the outer membrane of rat liver mitochondria

The data used to support the idea that malonyl-coenzyme A (CoA)-sensitive carnitine palmitoyltransferase (CPT-I) is localized on the outer mitochondrial membrane are based on harsh techniques that disrupt mitochondrial physiology. We have turned to the use of the French press, which produces a shearing force that denudes mitochondria of their outer membrane without the physiologically disruptive effects characteristic of phosphate swelling. Our results indicate that the mitoplasts contain just 15-19% of the outer membrane marker enzyme activity while retaining 85% of the total CPT activity and 50% of both CPT-I, as well as long-chain acyl-CoA synthase activity, the latter two supposed outer membrane enzymes. These mitoplasts were shown by electron microscopy to have the configuration of mitochondria that merely have been divested of their outer membranes. Carnitine-dependent fatty acid oxidation was retained in the mitoplasts, showing that they were physiologically intact. Moreover, protein immunoblotting analysis showed that CPT-I, as well as the inner CPT-II, was localized in the mitoplast fraction. The outer membrane fraction, which consisted of membrane "ghosts," contained most (50-60%) of marker enzyme activity, monoamine oxidase-B and porin proteins, but only about 27-29% CPT-I activity. Because CPT-I and long-chain acyl-CoA synthetase appear to be associated with both inner and outer membranes, we postulate that these enzymes reside in contact sites, which represent a melding of both limiting membranes.     

A clinicopathologic analysis of AIDS-related cryptosporidiosis

OBJECTIVE: To characterize the histology of AIDS-associated cryptosporidiosis and identify features that explain the clinical variability. DESIGN: A retrospective analysis of HIV-positive individuals with cryptosporidiosis who underwent endoscopy at the Johns Hopkins Hospital between 1985 and 1996. METHODS: The histologic features (intensity of Cryptosporidium infection, inflammation, mucosal damage, copathogens) of gastrointestinal biopsies from 37 HIV-positive individuals with cryptosporidiosis were systematically graded. These histologic features were correlated with the severity of the diarrheal illness obtained from a patient chart review. RESULTS: Histologic features associated with Cryptosporidium infection include a neutrophilic infiltrate in the stomach, villus blunting in the duodenum, cryptitis and epithelial apoptosis in the colon, and reactive epithelial changes in the stomach and duodenum. The nature and intensity of the inflammatory response varied widely; however, duodenal biopsies from a subset of patients (37%) revealed marked acute inflammation that was associated with concomitant cytomegalovirus infection. Although duodenal infection was common (93% of individuals), infection of other sites was variable (gastric cryptosporidiosis in 40% and colonic cryptosporidiosis in 74%). Widespread infection of the intestinal tract, which included both the large and small intestine, was associated with the most severe diarrheal illness. CONCLUSIONS: Cryptosporidium infection produces histologic evidence of gastrointestinal mucosal injury. The inflammatory response to the infection is variable, and may be modified by copathogens such as cytomegalovirus. The clinical manifestations are influenced, in part, by the anatomic distribution of the infection, with extensive infections involving both small and large intestines producing the most severe illness.     

Responding for rewarding brain stimulation: cocaine and isradipine plus naltrexone

We recently identified a gene which shows high similarity to the beta-spectrin gene but with a different chromosomal location from either of the two known beta-spectrin genes [T. Nagase, K.-I. Ishikawa, D. Nakajima, M. Ohira, N. Seki, N. Miyajima, A. Tanaka, H. Kotani, N. Nomura, O. Ohara, Prediction of the coding sequences of unidentified human genes: VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro, DNA Res. 4 (1997) 141-150]. In order to further characterize this new spectrin gene and its product, we isolated the rat counterpart of this gene and analyzed it in terms of its protein coding sequence, the tissue distribution of its mRNA and the product, and the regional distribution of the mRNA and the product in the brain. The results indicated that this gene was most abundantly transcribed in the brain and neurons were the predominant cell-type to express this gene. In particular, Purkinje cells were the richest in this gene product, and this new form of beta-spectrin was found more prominently in the dendrites than in the cell bodies. Since the expression pattern and the subcellular localization of this gene product were quiet distinct from those of the two beta-spectrin isoforms already characterized, this beta-spectrin gene would play an important role in neuronal membrane skeleton although it has been overlooked to date.     

Molecular cloning and characterization of fengycin synthetase gene fenB from Bacillus subtilis

A fengycin synthetase gene, fenB, has been cloned and sequenced. The protein (FenB) encoded by this gene has a predicted molecular mass of 143.6 kDa. This protein was overexpressed in Escherichia coli and was purified to near homogeneity by affinity chromatography. Experimental results indicated that the recombinant FenB has a substrate specificity toward isoleucine with an optimum temperature of 25 degrees C, an optimum pH of 4.5, a Km value of 922 microM, and a turnover number of 236 s(-1). FenB also consists of a thioesterase domain, suggesting that this protein may be involved in the activation of the last amino acid of fengycin.     

Hypopharyngeal carcinoma with clinical peritoneal carcinomatosis: a report of two patients

An inbred Arab family with three neonates affected by microlissencephaly syndrome is reported. Brain magnetic resonance imaging in the index case revealed very thin brain mantle with agyria-pachygyria, agenesis of the corpus callosum, and hypoplasia of the brainstem and cerebellum. All three neonates had microcephaly, arthrogryposis multiplex congenita, and micropenis. The presence of three affected newborn infants in a consanguineous family suggests an autosomal-recessive mode of inheritance of this syndrome. The spectrum of microlissencephaly syndrome is reviewed.     

Specific requirement for CD3epsilon in T cell development

T cell antigen receptor (TCR) and pre-TCR complexes are composed of clonotypic heterodimers in association with dimers of signal transducing invariant subunits (CD3gamma, -delta, -epsilon, and zeta). The role of individual invariant subunits in T cell development has been investigated by generating gene-specific mutations in mice. Mutation of CD3gamma, -delta, or zeta results in an incomplete block in development, characterized by reduced numbers of mature T cells that express low levels of TCR. In contrast, mature T cells are absent from CD3epsilon-/- mice, and thymocyte development is arrested at the early CD4(-)CD8(-) stage. Although these results suggest that CD3epsilon is essential for pre-TCR and TCR expression/function, their interpretation is complicated by the fact that expression of the CD3gamma and CD3delta genes also is reduced in CD3epsilon-/- mice. Thus, it is unclear whether the phenotype of CD3epsilon-/- mice reflects the collective effects of CD3gamma, -delta, and -epsilon deficiency. By removing the selectable marker (PGK-NEO) from the targeted CD3epsilon gene via Cre/loxP-mediated recombination, we generated mice that lack CD3epsilon yet retain normal expression of the closely linked CD3gamma and CD3delta genes. These (CD3epsilonDelta/Delta) mice exhibited an early arrest in T cell development, similar to that of CD3epsilon-/- mice. Moreover, the developmental defect could be rescued by expression of a CD3epsilon transgene. These results identify an essential role for CD3epsilon in T cell development not shared by the CD3gamma, CD3delta, or zeta-family proteins and provide further evidence that PGK-NEO can influence the expression of genes in its proximity.     

Low doses of ethanol reduce evidence for nonlinear structure in brain activity

Recent theories of the effects of ethanol on the brain have focused on its direct actions on neuronal membrane proteins. However, neuromolecular mechanisms whereby ethanol produces its CNS effects in low doses typically used by social drinkers (e.g., 2-3 drinks, 10-25 mM, 0.05-0.125 gm/dl) remain less well understood. We propose the hypothesis that ethanol may act by introducing a level of randomness or "noise" in brain electrical activity. We investigated the hypothesis by applying a battery of tests originally developed for nonlinear time series analysis and chaos theory to EEG data collected from 32 men who had participated in an ethanol/placebo challenge protocol. Because nonlinearity is a prerequisite for chaos and because we can detect nonlinearity more reliably than chaos, we concentrated on a series of measures that quantitated different aspects of nonlinearity. For each of these measures the method of surrogate data was used to assess the significance of evidence for nonlinear structure. Significant nonlinear structure was found in the EEG as evidenced by the measures of time asymmetry, determinism, and redundancy. In addition, the evidence for nonlinear structure in the placebo condition was found to be significantly greater than that for ethanol. Nonlinear measures, but not spectral measures, were found to correlate with a subject's overall feeling of intoxication. These findings are consistent with the notion that ethanol may act by introducing a level of randomness in neuronal processing as assessed by EEG nonlinear structure.     

Evolution on a volcanic conveyor belt: using phylogeographic reconstructions and K-Ar-based ages of the Hawaiian Islands to estimate molecular evolutionary rates

This article reports dissociations between verbal span and the recency portion of the serial position curve in immediate free recall, in 2 neuropsychological case studies and in 3 experiments with normal participants. Patient A. N. presented with an impaired serial verbal span while showing an intact recency effect. The opposite pattern was observed in patient G. C., who despite a poor recency showed normal span in verbal serial recall tasks. Experiments 1 and 2 showed a recency effect with visually and auditory presented lists and written recall was resistant to the effects of articulatory suppression and of irrelevant speech, but was disrupted by the suffix effect. Experiment 3 showed that in contrast with recency, memory span was affected by articulatory suppression and irrelevant speech during presentation but not by a suffix. These findings are not consistent with the idea that span and recency measure aspects of the same memory system. Moreover, in clinical practice, they should not be used as equivalent alternatives.