Probing the specificity of the S1 binding site of subtilisin Carlsberg with boronic acids.
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Allosteric Site↗
Biomedical subjects
R Martin
Publications and source records attributed to R Martin.
Specificity in social support: perceptions of helpful and unhelpful provider behaviors among irritable bowel syndrome, headache, and cancer patients.
Perceived social support was assessed among 53 patients suffering from non-life-threatening chronic illnesses (i.e., irritable bowel syndrome or recurrent headache). Subjects recalled predominantly helpful support interactions and reported the three major types of social support as equally helpful. In addition, irritable bowel syndrome patients, who experience embarrassing physical symptoms, reported fewer instances of tangible assistance than chronic headache patients. Comparisons to cancer patients studied by Dakof and Taylor (1990) revealed differences in perceived social support as a function of diagnosis. These results offer insight into the needs of patients with noncatastrophic illnesses and suggest that the challenges and tasks confronting these individuals are unique from those encountered by patients with catastrophic diseases.
Adaptation, Psychological↗
Using mug shots to find suspects.
The authors examined the use of mug shots as an investigative tool. Data are reported from 3 staged-crime experiments (N = 365) exploring the effects on mug-shot selections of number of faces seen before the confederate criminal's, of biased procedures, and of sorting pictures to fit the description of the criminal. The confederate was frequently selected from mug shots, and few innocent people were selected. Selections of faces declined with number of pictures viewed before the confederate's. Biased instructions and clothing bias increased choices of innocent people but not of guilty people. More innocent faces were selected when the pictures matched the confederate's description than when the pictures were not sorted to match the confederate's description. Viewing mug shots had no effect on subsequent identifications in lineups. Implications for police use of mug shots are discussed.
Adult↗
Volatile anesthetics and agonist-induced contractions in porcine coronary artery smooth muscle and Ca2+ mobilization in cultured immortalized vascular smooth muscle cells.
BACKGROUND: These experiments addressed four specific questions. Do isoflurane and halothane (0.5-3.0% in the gas phase) inhibit contractions evoked in isolated porcine coronary artery rings (without endothelium) by the specific Ca2+ mobilizing agonists serotonin, endothelin-1, and F-? Are contractions evoked by phorbol-activated protein kinase C inhibited by the anesthetics? In a well-characterized vascular smooth muscle cell culture model (A7r5 and A10), do the anesthetics attenuate serotonin- and endothelin-induced Ca2+ mobilization? Do the anesthetics inhibit intracellular Ca2+ mobilization via facilitated cAMP formation? METHODS: Tension was measured in rings suspended in organ chambers. Apparent intracellular Ca2+ was estimated in cells using indo-1 and flow cytometry. Cyclic AMP was measured by radioimmunoassay. RESULTS: At the anesthetic concentrations examined, isoflurane attenuated contractions evoked by serotonin and F- but not those induced by endothelin-1 or phorbol dibutyrate. In cells, isoflurane 2% attenuated 3 x 10(-5) M serotonin-induced Ca2+ mobilization by about 26%, whereas Ca2+ responses evoked by endothelin 10(-8) M were more resistant to anesthetic inhibitory effect. Halothane attenuated contractions in rings evoked by serotonin, endothelin, and F- but lacked effect on phorbol-induced responses. In cells, halothane 2% inhibited Ca2+ mobilization induced by serotonin by about 43% and that induced by endothelin by about 31%. Neither anesthetic facilitated cAMP formation. CONCLUSIONS: Isoflurane and halothane variably attenuated contractions evoked by Ca2+ mobilizing agonists--by a cellular action beyond the receptor level--but did not inhibit phorbol activated protein kinase C. Serotonin- and endothelin-induced Ca2+ mobilization was inhibited by isoflurane and halothane--but the mechanism does not depend upon increased cAMP.
Aluminum Compounds↗
Characteristics of somatotopic organization and spontaneous neuronal activity in the region of the thalamic principal sensory nucleus in patients with spinal cord transection.
1. We explored the region of the principal sensory nucleus of thalamus (Vc) during stereotactic surgical procedures for treatment of patients with pain after spinal cord transection (n = 23). Receptive fields (RFs) of thalamic single neurons and locations of sensations evoked by stimulation (projected field, PF) were determined by standard methods. The cellular thalamic region where sensations were evoked at < 25 microA was termed the "region of Vc." The region of Vc in spinal patients was subdivided into different areas according to RF and PF locations. Areas that were distant from the representation of the anesthetic part of the body were termed "spinal control" areas, whereas those that were adjacent to or included in the representation of the area of absolute sensory loss were termed "border zone/anesthetic" areas. The region of Vc in movement disorder patients were termed the "control" area. 2. Border zone/anesthetic areas of thalamus often exhibited increased representations of the border of the anesthetic part of the body in comparison with the representation of the same parts of the body in control and spinal control areas. 3. In control and spinal control areas the locations of RFs and PFs were usually well matched. However, in border zone/anesthetic areas of the thalamus there was frequently a mismatch between the location of RFs and PFs (RF/PF mismatch). In border zone/anesthetic areas, RFs were often located on the border of the anesthetic part of the body whereas PFs were referred to anesthetic parts of the body. 4. Analysis of first- and higher-order properties of spontaneous neuronal activity revealed that spike trains could be classified into two groups with distinct patterns of activity. The R group (n = 49) was characterized by independence of sequential interspike intervals (ISIs), a Poisson distribution of ISIs, initially inhibitory or flat autocovariance function (acvf), and low level of high-frequency bursting. The O group (n = 26) was characterized by correlation of sequential ISIs, large sustained postspike facilitation on the acvf, and high prevalence of high-frequency bursting--all consistent with a bursting pattern of activity. A third group of spike trains (n = 17) had an initially inhibitory or flat acvf and a unimodal, positively shifted, ISI distribution that did not meet criteria for a Poisson distribution. 5. Spike trains in the R group were much more common in control and control spinal areas, whereas those in the O group were more common in border zone/anesthetic areas.(ABSTRACT TRUNCATED AT 400 WORDS)
Brain Mapping↗
Occurrence of transient ischemic attacks in Alcoi: descriptive epidemiology.
A door-to-door survey of transient ischemic attack (TIA) and stroke was conducted in 3 towns of the Alcoi health area. The prevalence ratios found for TIA and stroke were 13/1,000 people (95% CI 8.8-17.9) and 21.5/1,000 (95% CI 15.8-27.2), respectively. The crude incidence rates for both TIA and stroke were 2.8/1,000 (95% CI 0.7-4.9). Methodological differences in the ascertainment of the cases may explain the variations in the rates between the present work and other studies in the literature.
Adult↗
Birth order in multiple sclerosis: a population-based case-control study in Alcoi, Spain.
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Birth Order↗
Homologies between T cell receptor junctional sequences unique to multiple sclerosis and T cells mediating experimental allergic encephalomyelitis.
The selection of T cell clones with mutations in the hypoxanthine guanine phosphoribosyltransferase (hprt) gene has been used to isolate T cells reactive to myelin basic protein (MBP) in patients with multiple sclerosis (MS). These T cell clones are activated in vivo, and are not found in healthy individuals. The third complementarity determining regions (CDR3) of the T cell receptor (TCR) alpha and beta chains are the putative contact sites for peptide fragments of MBP bound in the groove of the HLA molecule. The TCR V gene usage and CDR3s of these MBP-reactive hprt-T cell clones are homologous to TCRs from other T cells relevant to MS, including T cells causing experimental allergic encephalomyelitis (EAE) and T cells found in brain lesions and in the cerebrospinal fluid (CSF) of MS patients. In vivo activated MBP-reactive T cells in MS patients may be critical in the pathogenesis of MS.
Amino Acid Sequence↗
Citrulline-containing myelin basic protein is recognized by T-cell lines derived from multiple sclerosis patients and healthy individuals.
The cause of MS is uncertain, but an autoimmune disorder of the CNS is likely, and myelin basic protein (MBP) is a candidate antigen. MBP exists in different isoforms, generated by differential splicing of exons, and in charge isomers, generated by posttranslational modifications. Different isoforms and charge isomers presumably subserve different functions, and they vary in abundance in immature myelin found during myelinogenesis and remyelination compared with mature myelin. The 18.5-kd isomer is most abundant in normal human adults and consequently has been used almost exclusively for immunologic studies in MS. In the present study, we examined a different but abundant charge isomer of MBP, termed MBP-C8, to determine whether it could be recognized by MBP-specific cytotoxic and proliferative T-cell lines (TCL) and whether a T-cell response directed exclusively against citrulline-containing residues of MBP-C8 exists in MS patients and healthy controls. We showed that citrulline affects antigen recognition by some TCL that are specific for areas of MBP that contain the citrulline residues. Following stimulation with MBP-C8, MBP-C8-specific TCL could be generated from both MS patients and controls. T-cell responses against antigens that appear during myelinogenesis and during remyelination may be important in inducing and perpetuating an autoimmune response involved in the pathogenesis of MS.
Adult↗
A study of 500 cases of acute renal failure (1978-1991).
A retrospective study of 500 consecutive cases of acute renal failure (ARF) in a period covering 1978 through 1991 is presented. A total of 316 females and 182 males with an average age of 46.4 years (14 to 84) had a global survival rate of 68%. Oligoanuric ARF was present in 77% of the patients and, except in 13 cases, all were dialyzed with varied techniques. The treatment plan consisted of early and repetitive dialysis, rational use of antibiotics, and parenteral and/or oral nutritional support. The patients have been divided into three main categories according to etiology: gyneco-obstetric, medical, and postsurgical cases, the latter having the poorest survival rate. With regard to ARF post-septic abortion, we strongly believe that a hysterectomy should not be carried out except in the presence of gangrene or proven uterine perforation, as surgery increases the morbomortality rate in these septic patients.
Abortion, Septic↗
Health care reform and long-term care pharmacy.
"Waiting and preparing" describes the health care reform activity of most of the larger long-term care pharmacy providers. The complexity of this service sector, in combination with the potentially enormous cost and actuarial uncertainty, seems to have averted major federal action at this time. The frenzy caused by the reform debate, however, has precipitated several changes at the state level that may not be as prudent.
Contract Services↗
Opioid peptides in the pituitary: a hormone, a paracrine modulator and a peptide in search of a function.
Endogenous opioid peptides derived from all three opioid precursors have been isolated from the pituitary of mammalian species. While beta-endorphin of the anterior lobe was soon shown to be secreted into the circulation as a hormone, the dynorphins and the enkephalins were found to occur in relative small quantities too low for export and effects in the periphery. With respect to the prodynorphin family in the neural lobe convincing evidence has been accumulated for a role of dynorphin A(1-8) in the local control of the release of the hormone oxytocin. The function of the enkephalins in the anterior and neural lobes, in spite of many efforts with in situ hybridization, immunocytochemistry, receptor autoradiography and receptor binding and bioassays, is still elusive. Research should be directed into the role of enkephalins in different physiological states, developmental stages and in non-mammalian vertebrate species.
Animals↗
Association of HLA and multiple sclerosis.
Multiple Sclerosis (MS) is a demyelinating disease of the central nervous system. Although the cause of MS is still unknown, it is considered an autoimmune disease based on the composition of inflammatory infiltrates in the brain and on parallels with a T-cell-mediated animal model of demyelinating diseases called experimental allergic encephalomyelitis (EAE). Similar to other autoimmune diseases, the immunogenetic background, in particular the MHC/HLA type, contributes to susceptibility. This review summarizes the current knowledge about the association between HLA background and MS as well as immunological findings in EAE and MS. Finally, an attempt is made to explain how structural interactions between disease-associated HLA type and binding of an autoantigenic peptide could relate to disease.
Alleles↗
An innovative model of system-linked community care: home-based traction as an alternative to institutional treatment.
Home-based traction is an alternative treatment to conventional hospital-based traction for children with orthopedic conditions such as congenital dislocated hip and Legg-Perthes disease. The application of a proposed theoretical model is used to describe the process of the home-based traction innovation. Creativity and innovation occasions a reconceptualization of stresses. The reconceptualization of stress, plus the operational support of coordinated in-home services, can help families and nurses in the community and in the hospital develop, implement, and evaluate this kind of innovative care. In applying the home-based traction professionals empower and legitimize parents as resourceful co-providers of care. The legitimizing of the alternative in-home service affords parents a more optimistic appraisal of their situation as manageable. Parents are free to develop a coordinated response to their overall circumstance, including the treatment of their one child's illness. The evaluation of this home-based traction example found the alternative to be acceptable, safe, effective in accomplishing treatment goals, and less expensive than conventional hospital-based traction.
Adult↗
The 3' codon context effect on UAG suppressor tRNA is different in Escherichia coli and human cells.
We have compared the effect of 3' context on the efficiency of nonsense suppressor tRNAs in Escherichia coli and human cells. Plasmids containing amber (UAG) termination codons were constructed in the vector pRSV beta gal by oligonucleotide insertion at an N-terminal location in a lacZ fusion. A family of identical vectors was prepared with either A, C, G or U as the first 3' base following the stop codon. These derivatives of pRSV beta gal were expressed in E. coli as stable plasmids, or transiently in human 293 cell tissue culture. Nonsense suppression was monitored using enzyme assays for beta-galactosidase. In E. coli the efficiency of a plasmid-borne bacterial tRNA(trp) UAG suppressor varied A > G > C = U. When the same lacZ reporter vectors were cotransfected with a human tRNA(ser) UAG suppressor plasmid into human cells, context effects of a different nature were detected. Double reciprocal analysis of dose-response experiments were used to show that the efficiency of suppression varied C > G > U = A. The discovery of different codon context effects on nonsense suppression in human cells suggest that the interaction between mammalian tRNAs or release factors and their target codons may have different characteristics from those in bacteria.
Base Sequence↗
Skewed T-cell receptor repertoire in genetically identical twins correlates with multiple sclerosis.
Although the cause of multiple sclerosis (MS) is unknown, it is thought to involve a T cell-mediated autoimmune mechanism. Susceptibility to the disease is influenced by genetic factors such as genes of the HLA and T-cell receptor (TCR) complex. Other evidence for a genetic influence includes the low incidence in certain ethnic groups, the increased risk if there are affected family members and the increased concordance rate for disease in monozygotic twin pairs (26%), compared to dizygotic twins. Epidemiological studies indicate that there may be an additional role for environmental factors. Although the target antigen(s) are not yet identified, several myelin or myelin-associated proteins have been suspected, among them myelin basic protein. A lack of genetically comparable controls has impaired the analysis of the T-cell response in MS patients and caused disagreement on TCR usage in the disease. Here we analyse the role of TCR genes in MS by comparing TCR usage in discordant versus concordant monozygotic twins in response to self and foreign antigens. We find that after stimulation with myelin basic protein or tetanus toxoid, control twin sets as well as concordant twin sets select similar V alpha chains. Only the discordant twin sets select different TCRs after stimulation with antigens. Thus exogenous factors or the disease shape the TCR repertoire in MS patients, as seen by comparison with unaffected genetically identical individuals. This skewing of the TCR repertoire could contribute to the pathogenesis of MS and other T-cell-mediated diseases.
Adult↗
Cephalosporins as risk factor for nosocomial Enterococcus faecalis bacteremia. A matched case-control study.
BACKGROUND: Nosocomial enterococcal infections have increased in various institutions, and patients with these infections had often been treated with cephalosporins during the previous weeks. The objective of this study was to determine whether the use of second- and third-generation cephalosporins is a risk factor for nosocomial enterococcal bacteremia (NEB), by means of a matched case-control study design. METHODS: Two hundred seven cases of NEB were studied. A control was matched to each case by sex, age (+/- 10 years), date of admission (+/- 2 years), hospital service, days of hospitalization, primary diagnosis, and operative procedures. RESULTS: One hundred fifty-six cases had an appropriate matched control. The univariate analysis of unmatched variables showed that the presence of a urinary catheter (odds ratio [OR], 3.8), mechanical ventilation (OR = 2.6), and cephalosporin use (OR = 5.1) were associated with NEB. Using a conditional logistic regression model, cephalosporin use (adjusted OR = 4.8, 95% confidence interval, 2.3 to 9.8) and urinary catheter use (adjusted OR = 3.6, 95% confidence interval, 1.7 to 7.4) remained significantly associated with NEB after controlling for other unmatched variables. CONCLUSIONS: These data show that the use of second- and third-generation cephalosporins may be a major risk factor for NEB. It may explain, at least partially, the steadily increasing number of enterococcal infections observed in some hospitals.
Adult↗
Clinical worsening in multiple sclerosis is associated with increased frequency and area of gadopentetate dimeglumine-enhancing magnetic resonance imaging lesions.
It is now well established that clinically stable patients with relapsing-remitting multiple sclerosis have ongoing disease activity when evaluated by serial gadolinium-enhanced (Gd-DTPA) magnetic resonance imaging (MRI) scans. Despite this, the relationship between clinical disease and MRI lesions, though suspected, has not been extensively documented. The relationship between Gd-DTPA MRI lesions and clinical disease was examined in this study of 9 patients with mild relapsing-remitting multiple sclerosis (Expanded Disability Status Scale [EDSS] < 3.5) who had 24 to 37 monthly Gd-DTPA MRI scans, neurological examinations, and EDSS score assignments. The area and frequency of Gd-DTPA lesions were examined during months with and without clinical worsening as measured by EDSS. Forty-one episodes of clinical worsening were noted during the study. A significant association was observed between these periods of clinical worsening and MRI parameters, including increases in total number, number of new lesions, and the total area of enhancement. Logistic regression analysis showed a significant effect of the number and area of Gd-DTPA MRI lesions on both the onset and continuation of clinical worsening, confirming an important relationship between clinical disease and an increase in cerebral Gd-DTPA MRI activity. A relationship with long-term disability was suggested, but cannot be confirmed without longer follow-up of these patients.
Adult↗