Field evaluation of two bait delivery systems for the oral immunization of dogs against rabies in Tunisia

In a study of the relation between foot pain and disability, a cross-sectional analysis was performed using baseline data (1992-1995) from the Women's Health and Aging Study, a population-based study of 1,002 disabled women aged 65 years and older living in Baltimore, Maryland. Chronic and severe foot pain, defined as pain lasting 1 month or longer in the previous year, plus pain in the previous month rated severe (7-10 on a scale of 0 to 10), was reported by 14% of the women. Severe foot pain was more common in women who were younger (aged 65-74 years), obese, or had hand or knee osteoarthritis. Walking speed and five repeated chair stands were slower in women with foot pain. After adjustment for age, body mass index, race, education, self-rated health, smoking status, comorbidities, and number of other pain sites, severe foot pain was independently associated with increased risk for walking difficulty (adjusted odds ratio = 1.69, 95% confidence interval 1.10-2.59) and disability in activities of daily living (adjusted odds ratio = 1.91, 95% confidence interval 1.21-3.01). These findings suggest that severe foot pain may play a key role in disability in older women. Further studies are warranted to confirm these results longitudinally and to determine whether interventions to alleviate foot pain could reduce or prevent disability in older women.     

Unusual case of disseminated sarcoidosis with prominent gastrointestinal symptoms

HISTORY AND ADMISSION FINDINGS: A 63-year-old man had for 10 months suffered from marked weight loss, night sweats, diffuse abdominal pain and increased stool frequency. He was admitted to evaluate an ultrasonically abnormal focus in the liver parenchyma and elevated liver function parameters. His sclerae were obviously icteric and he looked under-weight. INVESTIGATIONS: He had a hypochromic microcytic anemia and abnormal liver and pancreatic function tests: total bilirubin 3.11 mg/dl, direct bilirubin 2.21 mg/dl, GOT21U/l, gamma-GT 422 U/l, alkaline phosphatase 1449 U/l, alpha-amylase 481 U/l, lipase 2827 U/l. The serum creatinine level was elevated to 1.47 mg/dl. Computed tomography revealed enlarged liver and spleen as well as an enlargement of intraabdominal lymph nodes, chest radiogram and endoscopic cholangio-pancreatography were unremarkable. Biopsies from the lower duodenum, large intestine, bone marrow and liver showed inflammatory changes with Langhans-type mononuclear granulomas. Together with these findings an increased activity of the angiotensin-converting-enzyme (ACE) indicated sarcoidosis, other causes having been excluded. TREATMENT AND COURSE: All signs and symptoms rapidly improved under prednisolone, and 4 weeks after begin of treatment the biochemical abnormalities had clearly regressed. The raised serum levels of soluble IL-2 receptors and of neopterin, measures of sarcoidosis activity, had decreased. Activity of ACE had fallen. CONCLUSION: Sarcoidosis can present with diverse clinical signs and symptoms. In a case of multi-system disease that cannot be readily classified, sarcoidosis should be included in the differential diagnosis.     

The three-dimensional structure of human RNase 4, unliganded and complexed with d(Up), reveals the basis for its uridine selectivity

The RNase 4 family is unique among RNase enzymes, displaying the highest level of sequence similarity and encompassing the shortest polypeptide chain. It is the only one showing high specificity. The human representative is an intracellular and plasma enzyme, first isolated from colon adenocarcinoma cell line HT-29. The crystal structures of human recombinant RNase 4, unliganded and in complex with d(Up), have been determined, revealing in the unique active site an explanation for the uridine specificity. Arg101, at a position not involved in catalysis in the other RNase enzymes, penetrates the enzyme moiety shaping the recognition pocket, a flip that is mediated by the interaction with the (shorter chain) C-terminal carboxylate group, providing an anchoring point for the O4 atom of the substrate uridine. The bulky Phe42 side-chain forces Asp80 to be in the chi1=-72.49 degrees rotamer, accepting a hydrogen bond from Thr44, further converting the latter into a hydrogen bond acceptor. This favours an interaction with the -NH-donor group of uridine at position 3 over that with the =N-acceptor of cytidine. The two chemical groups that distinguish uracyl from cytosine are used by the enzyme to discriminate between these two bases.     

Optimal control of production and remanufacturing in a simple recovery model with linear cost functions

One aspect in reverse logistics concerns returns of used products and recovery for another life cycle. Remanufactured parts can be used for assembly of new products or the entire (upgraded) product can be sold again. Limitations and enormous waste disposal cost, the duty for manufacturers to take back used products from customers, and the fact that returned products can be regarded as a resource for material requirements are reasons for a consideration of product recovery. In this paper, we present an optimal control approach to optimize the production, remanufacturing, and disposal strategy with respect to dynamic demand and returns.     

Cerebrospinal fluid cytokines in pediatric neuropsychiatric disease

This study examines cerebrospinal fluid from patients with three neuropsychiatric diseases of childhood for the presence and levels of several cytokines relevant to cell-mediated (type 1) and humoral (type 2) immunity. The patient groups include childhood-onset schizophrenia (n = 22), obsessive-compulsive disorder (OCD) (n = 24), and attention deficit hyperactivity disorder (n = 42). The cytokines examined include IL-2, IFN-gamma, TNF-beta/LT, IL-4, IL-5, IL-10, and TNF-alpha. Patients with OCD had a preponderance of type 1 cytokines. IL-4 was detectable only in samples from patients with schizophrenia. IL-10 was rarely detected and never in patients with OCD. Few patients with schizophrenia had detectable amounts of IFN-gamma in CSFL. We conclude that there is a relative skewing of CSFL profiles toward type 1 cytokines in patients with OCD, whereas in schizophrenia the relative preponderance is toward type 2 mediators. Patients with attention deficit hyperactivity disorder exhibited profiles intermediate between OCD and schizophrenia. We infer that cell-mediated immunity may be involved in the etiopathogenesis of OCD, whereas a relative lack of cell-mediated immunity and involvement of humoral immunity may be present in schizophrenia. These data provide a rationale for immune-based strategies of study and therapeutics in childhood neuropsychiatric disease.     

Expertise and the regulation of gait in the approach phase of the long jump

In the approach phase of the long jump, athletes attempt to strike the take-off board accurately with minimum loss of speed, and in an optimum body position for take-off. Previous research has shown that skilled long jumpers demonstrate an ascending-descending trend of variability rather than a consistent pattern of foot placement over trials. The present study examined whether non-long jumpers showed a similar pattern of variability in footfall placement between trials to skilled long jumpers. Consistency of foot placement over trials for non-long jumpers (n = 11) was determined using a panned video camera. Digitization of the foot position provided toe-board distances during the run-up phase. Our results showed that non-long jumpers have a similar pattern of descending variability near to the take-off board to expert long jumpers, suggesting the use of visual regulation. However, in comparison to more skilled subjects, non-long jumpers accumulated a considerably larger maximum mean standard deviation in footfall placement between trials (58 cm). Since non-long jumpers had no previous task-specific training, these data extend our current understanding of the regulation of goal-directed gait.     

Amino-terminal dimerization of an erythropoietin mimetic peptide results in increased erythropoietic activity

BACKGROUND: Erythropoietin (EPO), the hormone involved in red blood cell production, activates its receptor by binding to the receptor's extracellular domain and presumably dimerizing two receptor monomers to initiate signal transduction. EPO-mimetic peptides, such as EMP1, also bind and activate the receptor by dimerization. These mimetic peptides are not as potent as EPO, however. The crystal structure of the EPO receptor (EBP) bound to EMP1 reveals the formation of a complex consisting of two peptides bound to two receptors, so we sought to improve the biological activity of EPO-mimetic peptides by constructing covalent dimers of EMP1 and other peptide mimetics linked by polyethylene glycol (PEG). RESULTS: The potency of the PEG-dimerized EPO peptide mimetics both in vitro and in vivo was improved up to 1,000-fold compared to the corresponding peptide monomers. The dimers were constructed using peptide monomers which have only one reactive amine per molecule, allowing us to conclude that the increase in potency can be attributed to a structure in which two peptides are linked through their respective amino termini to the difunctional PEG molecule. In addition, an inactive peptide was converted into a weak agonist by PEG-induced dimerization. CONCLUSIONS: The potency of previously isolated peptides that are modest agonists of the EPO receptor was dramatically increased by PEG-induced dimerization. The EPO receptor is thought to be dimerized during activation, so our results are consistent with the proposed 2:2 receptor : peptide stoichiometry. The conversion of an inactive peptide into an agonist further supports the idea that dimerization can mediate receptor activation.     

Cyclophilin and trigger factor from Bacillus subtilis catalyze in vitro protein folding and are necessary for viability under starvation conditions

Cyclophilin (the product of the ppiB gene) and the trigger factor (the product of the tig gene) are the only cytosolic peptidyl-prolyl cis-trans isomerases that are known in Bacillus subtilis. Both enzymes catalyze the in vitro refolding of ribonuclease T1, a reaction that is limited in rate by a prolyl cis/trans isomerization. The efficiency of cyclophilin as a folding catalyst is only modest with a kcat/KM value of 3.8 x 10(4) M-1 s-1, but the trigger factor shows an almost 40-fold higher specific activity with a kcat/KM value of 1.4 x 10(6) M-1 s-1. This high catalytic activity originates from the tight binding to the protein substrate as reflected in both the low KM value of 0.5 microM and in the strong inhibition of the trigger factor by unfolded proteins. By use of a protein-folding assay, the concentrations of cyclophilin and the trigger factor in the cytosol of B. subtilis could be determined as 26 and 35 microM, respectively. Together they account for the entire folding activity that is detectable in crude extracts of wild-type B. subtilis cells. The genes encoding cyclophilin and the trigger factor in the B. subtilis chromosome were disrupted individually and simultaneously. Even in combination, these disruptions had no effect on cell viability in rich medium or under several stress conditions, such as heat, osmotic, or oxidative stress. However, in poor medium and, in particular, in the absence of amino acids, the growth of the double mutant strain was strongly decelerated, indicating that the prolyl isomerases become essential for growth under starvation conditions. It is not yet known whether this function relates to the catalysis of the proline-limited folding of essential proteins.