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Biomedical subjects

C Adams

Publications and source records attributed to C Adams.

At least 55 records · Page 3Linked to original sources
PubMed2000

Smoking and schizophrenia: abnormal nicotinic receptor expression.

Biological and genetic evidence suggests a role for the neuronal nicotinic receptors in the neuropathophysiology of schizophrenia. Nicotine normalizes an auditory evoked potential deficit seen in subjects who suffer from the disease. Nicotinic receptors with both high and low affinity for nicotine are decreased in postmortem brain of schizophrenics compared to control subjects. The chromosomal locus of the human alpha-7 gene (15q14) is linked to the gating deficit with a lod of 5.3, and antagonists of the alpha-7 receptor (alpha-bungarotoxin and methyllycaconitine) induce a loss of gating in rodents. We have cloned the human alpha-7 gene and found it to be partially duplicated proximal to the full-length gene. The duplication is expressed in both the brain and in peripheral blood cells of normal subjects, but is missing in some schizophrenic subjects. The results of these studies suggest the presence of abnormal expression and function of the neuronal nicotinic receptor gene family in schizophrenia.

Animals↗
PubMed2000

Sleep-disordered breathing in Duchenne muscular dystrophy: a preliminary study of the role of portable monitoring.

Although Duchenne muscular dystrophy (DMD) is often associated with sleep disordered breathing (SDB), it is not standard clinical practice to routinely test this population for SDB, and the optimal timing and methodology for such testing has not been established. Our objectives were: 1) to examine the concordance between laboratory polysomnography (PSG) and two portable monitoring systems, and 2) to identify clinical factors associated with the onset of SDB. We performed a cross-sectional pilot study of patients with DMD who were 6 years of age or older, and who were registered at the Alberta Children's and Calgary General Hospitals. Patient symptom and functional rating scores were calculated, and pulmonary function tests, awake oxygen saturation, and capillary blood gases were obtained. PSG was performed according to standard methods, and results were compared with Snoresat(R) (Saga Tech Electronics, Inc.) and EdenTec(R) (Nellcor Puritan Bennett) portable home monitors. Eleven boys were studied. Ten of 11 subjects had normal awake oxygen saturation and capillary blood gases. Median forced vital capacity (FVC) was 70% of predicted values (15-104%). PSG identified 3 boys with severe hypoventilation occurring throughout REM sleep. Reported symptom severity did not predict the patients with significant SDB. All 3 boys with SDB had a severe functional disability and severely reduced FVCs. Portable monitoring in the home identified all patients with abnormal PSG. One additional patient was falsely identified by the EdenTec(R) monitor. We conclude that initial results using Snoresat(R) or EdenTec(R) monitoring equipment for the identification of SDB are promising, but further validation of portable home monitoring is required in this group of patients.

Adolescent↗
PubMed2000

Preservation of the brainstem auditory evoked potential in non-convulsive status epilepticus.

Brainstem auditory evoked potentials (BAEPs) were recorded from a patient simultaneously experiencing non-convulsive generalized status epilepticus (NGSE). Waves I, III and V were normal but all subsequent waves were absent. This finding indicates that structures within the brainstem adjacent to the generators for the BAEP are likely not affected by NGSE and also illustrates the resilient nature of the BAEP. This is the first report of the recording of an evoked potential during a naturally occurring generalized seizure.

Aged↗
PubMed2000

Autoantibodies in childhood post-varicella acute cerebellar ataxia.

BACKGROUND: Anti-Purkinje cell antibodies have been reported in cerebellar ataxia following Epstein-Barr virus (EBV) infection. We investigated autoantibody responses, including anti-Purkinje cell antibodies, and the clinical course in eight children who developed post-varicella ataxia, five of their siblings with uncomplicated varicella, one child with post-EBV ataxia, two children with acute disseminated encephalomyelitis (ADEM) and one with neuroblastoma associated ataxia, and in age and gender matched controls. METHODS: Autoantibodies were tested by indirect immunofluorescence (IIF) on cryopreserved cerebrum and cerebellum sections. Other autoantibodies were measured by conventional IIF protocols using HEp-2 cells as a substrate. Antibodies to myelin associated glycoprotein (MAG), asialo-GM1, beta2 glycoprotein 1, cardiolipin and myelin basic protein (MBP) were measured by ELISA. RESULTS: Three of eight children with acute post-varicella ataxia, one child with post-EBV ataxia, one child with ADEM and one child with uncomplicated varicella, had high titer autoantibodies (>1/160) that reacted with cerebrum and cerebellar tissue. This reactivity was not seen in one child with ADEM, in one with neuroblastoma and ataxia, in the remainder of the children with uncomplicated varicella or age and gender matched controls. Autoantibodies were not seen in CSF from two children with post-varicella ataxia. The punctate staining seen on cerebrum and cerebellum sections co-localized with rabbit antibodies to the centrosome protein pericentrin. All patients with strong reactivity with cerebrum and cerebellar tissue by IIF had elevated levels of anti-MAG that was not confirmed by absorption assay. No reactivity was seen with asialo-GM1, MBP, beta2 glycoprotein 1 or cardiolipin. None of the sera had autoantibodies directed against endosomes, the Golgi complex, or the paraneoplastic autoantigens Hu and Yo. CONCLUSION: Some children with post-viral ataxia develop antibodies that have strong reactivity with cerebral and cerebellar tissue. Some of the antigenic reactivity co-localized with the centrosome protein pericentrin.

Animals↗
PubMed2000

Conversational responsiveness in specific language impairment: evidence of disproportionate pragmatic difficulties in a subset of children.

Eighteen children with specific language impairment (SLI), from 6 to 8 years of age, were compared with 9 control children matched on age and nonverbal ability (CA controls) and with 9 younger control children of comparable language level (LA controls). Half of the SLI group were rated on a teacher checklist as having pragmatic difficulties: these were referred to as the pragmatic language impairment (PLI) group; the remainder were the typical (SLI-T) group. Children's responses to adult soliciting utterances were compared. All children usually responded to conversational solicitations, but children in the PLI group were more likely than control children to give no response, and they also made very little use of nonverbal responses, such as nodding. Nonverbal responding was closely related to the quality of children's responses. Children who failed to use nonverbal responses also had a relatively high level of pragmatically inappropriate responses that were not readily accounted for in terms of limited grammar or vocabulary. This study lends support to the notion that there is a subset of the language-impaired population who have broader communicative impairments, extending beyond basic difficulties in mastering language form, reflecting difficulty in responding to and expressing communicative intents. The analytic methods developed for this project have promise for the study of pragmatic difficulties in other clinical groups.

Adult↗
PubMed2000

Update on family psychoeducation for schizophrenia.

The Schizophrenia Patient Outcomes Research Team and others have previously included family psychoeducation and family support in best practices guidelines and treatment recommendations for persons with schizophrenia. In this article we review in detail 15 new studies on family interventions to consider issues around the implementation of family interventions in current practice. The data supporting the efficacy of family psychoeducation remain compelling. Such programs should remain as part of best practices guidelines and treatment recommendations. However, assessment of the appropriateness of family psychoeducation for a particular patient and family should consider (1) the interest of the family and patient; (2) the extent and quality of family and patient involvement; (3) the presence of patient outcomes that clinicians, family members, and patients can identify as goals; and (4) whether the patient and family would choose family psychoeducation instead of alternatives available in the agency to achieve outcomes identified.

Cognitive Behavioral Therapy↗
PubMed2000

Evaluation of a single seizure: guidelines for advance practice nurses.

Deciding whether or not to treat a client after a single seizure can be challenging for the clinician. The risk of seizure recurrence is greatest in the first six months after the initial episode. The decision to treat a single seizure should be based on diagnostic and clinical findings that assess the client's risk for recurrence. When making treatment decisions, the clinician must consider the benefits and risks of single-seizure therapy. Careful consideration should be given to differential diagnosis, factors that induce symptomatic seizures and risk factors for epilepsy.

Adult↗
PubMed2000

R1 region of P97 mediates adherence of Mycoplasma hyopneumoniae to swine cilia.

Adherence of Mycoplasma hyopneumoniae to the swine respiratory tract is mediated by the membrane protein P97. This protein is located on the outer membrane surface, and its role in adherence has been firmly established. The general region of P97 that mediates adherence to swine cilia is thought to be the R1 region near the carboxy terminus of the protein, but it was not clear if this region could mediate adherence to swine cilia independently of other P97 sequences. To examine this in more detail, a series of R1 repeat sequences containing different numbers of repeating units cloned in frame with lacZ was used to produce R1-beta-galactosidase fusion proteins. These proteins were then tested for adherence to swine cilia and for reactivity to the adherence-blocking monoclonal antibody F2G5 and convalescent-phase swine sera. In this way it was possible to accurately define the cilium binding epitope of P97 and the minimal epitope recognized by antibody. Our results indicate that eight R1 repeating units are required for cilium binding and that three repeating units are needed for antibody recognition. These results could lead to more effective therapeutic measures against this important swine pathogen.

Adhesins, Bacterial↗
PubMed2000

A regulatory RNA (PrrB RNA) modulates expression of secondary metabolite genes in Pseudomonas fluorescens F113.

The GacS-GacA two-component signal transduction system, which is highly conserved in gram-negative bacteria, is required for the production of exoenzymes and secondary metabolites in Pseudomonas spp. Screening of a Pseudomonas fluorescens F113 gene bank led to the isolation of a previously undefined locus which could restore secondary metabolite production to both gacS and gacA mutants of F113. Sequence analysis of this locus demonstrated that it did not contain any obvious Pseudomonas protein-coding open reading frames or homologues within available databases. Northern analysis indicated that the locus encodes an RNA (PrrB RNA) which is able to phenotypically complement gacS and gacA mutants and is itself regulated by the GacS-GacA two-component signal transduction system. Primer extension analysis of the 132-base transcript identified the transcription start site located downstream of a sigma(70) promoter sequence from positions -10 to -35. Inactivation of the prrB gene in F113 resulted in a significant reduction of 2, 4-diacetylphloroglucinol (Phl) and hydrogen cyanide (HCN) production, while increased metabolite production was observed when prrB was overexpressed. The prrB gene sequence contains a number of imperfect repeats of the consensus sequence 5'-AGGA-3', and sequence analysis predicted a complex secondary structure featuring multiple putative stem-loops with the consensus sequences predominantly positioned at the single-stranded regions at the ends of the stem-loops. This structure is similar to the CsrB and RsmB regulatory RNAs in Escherichia coli and Erwinia carotovora, respectively. Results suggest that a regulatory RNA molecule is involved in GacA-GacS-mediated regulation of Phl and HCN production in P. fluorescens F113.

Bacterial Proteins↗
PubMed2000

The MN1-TEL fusion protein, encoded by the translocation (12;22)(p13;q11) in myeloid leukemia, is a transcription factor with transforming activity.

The Tel gene (or ETV6) is the target of the translocation (12;22)(p13;q11) in myeloid leukemia. TEL is a member of the ETS family of transcription factors and contains the pointed protein interaction (PNT) domain and an ETS DNA binding domain (DBD). By contrast to other chimeric proteins that contain TEL's PNT domain, such as TEL-platelet-derived growth factor beta receptor in t(5;12)(q33;p13), MN1-TEL contains the DBD of TEL. The N-terminal MN1 moiety is rich in proline residues and contains two polyglutamine stretches, suggesting that MN1-TEL may act as a deregulated transcription factor. We now show that MN1-TEL type I, unlike TEL and MN1, transforms NIH 3T3 cells. The transforming potential depends on both N-terminal MN1 sequences and a functional TEL DBD. Furthermore, we demonstrate that MN1 has transcription activity and that MN1-TEL acts as a chimeric transcription factor on the Moloney sarcoma virus long terminal repeat and a synthetic promoter containing TEL binding sites. The transactivating capacity of MN1-TEL depended on both the DBD of TEL and sequences in MN1. MN1-TEL contributes to leukemogenesis by a mechanism distinct from that of other chimeric proteins containing TEL.

Animals↗
PubMed2000

Unpublished rating scales: a major source of bias in randomised controlled trials of treatments for schizophrenia.

BACKGROUND: A recent review suggested an association between using unpublished scales in clinical trials and finding significant results. AIMS: To determine whether such an association existed in schizophrenia trials. METHOD: Three hundred trials were randomly selected from the Cochrane Schizophrenia Group's Register. All comparisons between treatment groups and control groups using rating scales were identified. The publication status of each scale was determined and claims of a significant treatment effect were recorded. RESULTS: Trials were more likely to report that a treatment was superior to control when an unpublished scale was used to make the comparison (relative risk 1.37 (95% CI 1.12-1.68)). This effect increased when a 'gold-standard' definition of treatment superiority was applied (RR 1.94 (95% CI 1.35-2.79)). In non-pharmacological trials, one-third of 'gold-standard' claims of treatment superiority would not have been made if published scales had been used. CONCLUSIONS: Unpublished scales are a source of bias in schizophrenia trials.

Humans↗
PubMed2000

Use of phage display for the generation of human antibodies that neutralize factor IXa function.

The use of libraries of phage-displayed human single-chain antibody fragments (scFv) has become a new, powerful tool in rapidly obtaining therapeutically useful antibodies. Here, we describe the generation of human scFv and F(ab')2 directed against the gamma-carboxyglutamic acid (Gla) domain of coagulation factor IX. A large library of human scFv, displayed either on M13 phage or expressed as soluble proteins, was screened for binding to human Gla-domain peptide (Tyr1-Lys43). Among a panel of scFv that bound to the factor IX-Gla domain, six scFv clones recognized full-length factor IX and exhibited strong inhibitory activity of factor IX in vitro. After reformatting as F(ab')2, the affinity for factor IX of three selected clones was determined: 10C12 Kd = 1.6 nmol/l, 13D1 Kd = 2.9 nmol/l, and 13H6 Kd = 0.46 nmol/l. The antibodies specifically bound to factor IX and not to other coagulation factors, as assessed by enzyme-linked immunosorbent-type and human plasma clotting assays. The complementarity determining region amino acid sequences of clones 10C12 and 13D1 only differed at a single residue, whereas 13H6 showed little homology, suggesting that 13H6 binds to a different epitope within the factor IX-Gla domain. Despite the slightly lower affinity of 10C12 F(ab')2 versus 13H6 F(ab')2, 10C12 was consistently more potent than 13H6 in prolonging the activated partial thromboplastin time (APTT), in inhibiting platelet-mediated plasma clotting, and in inhibiting factor X activation by the intrinsic Xase complex. Finally, 10C12 F(ab')2 also recognized and neutralized factor IX/factor IXa of different species, as demonstrated by the specific APTT prolongation of dog, mouse, baboon and rabbit plasma. In summary, the results validate the usefulness of scFv phage-displayed libraries to rapidly generate fully human antibodies as potential new therapeutics for thrombotic disorders.

Amino Acid Sequence↗
PubMed2000

Frequent codon 12 Ki-ras mutations in mouse skin tumors initiated by N-methyl-N'-nitro-N-nitrosoguanidine and promoted by mezerein.

The skin tumor initiators N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 7,12-dimethylbenz[a]anthracene (DMBA) differ in effectiveness when tumor formation is promoted by 12-O-tetradecanoylphorbol-13-acetate (TPA). Even at high doses, MNNG is less effective, producing fewer benign and malignant tumors with a longer latent period. In DMBA-initiated skin, 10 wk of TPA promotion produced a maximal tumor response. With MNNG, 20 wk of TPA promotion was required, producing nearly four times as many papillomas as 10 wk of promotion. Promotion of MNNG-initiated skin with mezerein induced the appearance of very rapidly-growing papillomas within 5 wk, 3 wk earlier than the first TPA-promoted papillomas. Thus, MNNG may induce a novel mutation resulting in a population of initiated cells that respond especially well to mezerein. Since ras mutations are common in experimental tumors in many tissues, we determined the frequency of activating mutations in the Ha-ras, Ki-ras, and N-ras oncogenes. Activating Ha-ras mutations were present in essentially all DMBA-initiated tumors and about 70% of MNNG-initiated tumors. No N-ras mutations were found in tumors lacking other ras mutations. Surprisingly, 41% of the papillomas arising in the first 11 wk in MNNG-initiated, mezerein-promoted mice bore mutations in codon 12 of the Ki-ras oncogene. Activating Ki-ras mutations were also found in more than 60% of squamous cell carcinomas and 40% of keratoacanthomas. Although mutations in Ha-ras are frequently detected in mouse skin tumors, mutations in Ki-ras are rare. This is the first report of mutated Ki-ras in skin tumors from mice initiated by MNNG.

Animals↗
PubMed1999

Acute melioidosis outbreak in Western Australia.

A cluster of acute melioidosis cases occurred in a remote, coastal community in tropical Western Australia. Molecular typing of Burkholderia pseudomallei isolates from culture-confirmed cases and suspected environmental sources by pulsed-field gel electrophoresis (PFGE) of XbaI chromosomal DNA digests showed that a single PFGE type was responsible for five cases of acute infection in a community of around 300 during a 5 week period. This temporal and geographical clustering of acute melioidosis cases provided a unique opportunity to investigate the environmental factors contributing to this disease. B. pseudomallei isolated from a domestic tap at the home of an asymptomatic seroconverter was indistinguishable by PFGE. Possible contributing environmental factors included an unusually acid communal water supply, unrecordable chlorine levels during the probable exposure period, a nearby earth tremor, and gusting winds during the installation of new water and electricity supplies. The possible role of the potable water supply as a source of B. pseudomallei was investigated further.

Acute Disease↗