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Biomedical subjects

J Patrick

Publications and source records attributed to J Patrick.

At least 19 recordsLinked to original sources
PubMed1998

A study of the effect of cyproheptadine on gait in hemiplegic children.

The properties of cyproheptadine as an anti-spastic agent have been reported since 1980. In this study we sought to investigate whether gait function, as specified by stride length, cadence, heart rate, and also by questionnaire, correlated with cyproheptadine medication during a double-blind matched-placebo cross-over trial, undertaken on a group of 16 hemiplegic spastic patients aged 4-18 years. We found that neither qualitative nor quantitative analyses suggested any systematic change in gait parameters dependent on cyproheptadine medication. We conclude that our study on 16 patients showed no statistical evidence of improvement in spasticity due to the action of cyproheptadine. An effect was, however, found in the case of mean patient heart rate, which was 10% higher (P<0.003) at the end of the cyproheptadine medication period. Copyright 1998 Elsevier Science B.V.

Journal Article↗
PubMed1997

Peptidyl prolyl cis-trans isomerase activity of cyclophilin A in functional homo-oligomeric receptor expression.

The functional expression of homo-oligomeric alpha7 neuronal nicotinic and type 3 serotonin receptors is dependent on the activity of a cyclophilin. In this paper we demonstrate that the mechanism of cyclophilin action during functional homo-oligomeric receptor expression in Xenopus oocytes is distinct from the calcineurin-dependent immunosuppressive mechanism by showing that a nonimmunosuppressive analog of cyclosporin A (CsA), SDZ 211-811, reduces functional receptor expression to the same extent as CsA. The cytoplasmic subtype of cyclophilin, cyclophilin A (CyPA), appears to be required for functional receptor expression. This is because overexpression of CyPA and a CyPA mutant that is deficient in CsA binding activity reverses CsA-induced reduction in functional receptor expression. The mechanism of action of CyPA is likely to involve its prolyl isomerase activity because a mutant CyPA with a single amino acid substitution (arginine 55 to alanine) that is predicted to produce a 1000-fold attenuation in isomerase activity fails to reverse the cyclosporin A effect. Our data also suggest that CyPA does not form a stable complex with receptor subunits.

Amino Acid Isomerases↗
PubMed1997

Paraplegia: prolonged closed-loop standing with implanted nucleus FES-22 stimulator and Andrews' foot-ankle orthosis.

Our object is to develop a reliable, implantable and closed-loop functional electrical stimulator (FES) hybrid system for safe prolonged standing in paraplegic individuals. Open-loop FES systems rapidly induce muscle fatigue that limits paraplegic standing to less than 20 and typically 10 min. Since December 1991, a paraplegic male (CS: 23 years old, T10 level, Asia: A) has been implanted with the first Nucleus FES-22 channel stimulating system (Cochlear Ltd., Lane Cove, N.S.W., Australia). Epineural platinum disc electrodes (2.5 mm) were placed on branches of the femoral, gluteal and sciatic nerves, which can be activated to produce controlled lower extremity movements for exercise and standing. No medical complications have occurred during these 5 1/2 years of implantation. The ankles are stabilized with Andrews' ankle-foot braces, the knees are free to flex. With bilateral knee goniometers fitted to sense a 10 degrees angle flexion, this hybrid closed-loop stimulation system allows the patient to achieve safe uninterrupted standing for over 60 min. The stimulator has needed to be activated 'on' for 8% (range: 3-17%) of the standing times, preventing muscle fatigue, with little or no changes found in the vital signs. The patient can manipulate and transfer objects at arm length up to 2.2 kg with good stability. New, less obstrusive sensors are currently being tested for a safer and more reliable closed-loop system.

Adult↗
PubMed1996

Impulsivity, defensive functioning, and borderline personality disorder.

OBJECTIVE: To replicate previous research suggesting that impulsivity highly predicts current DIB(R) score and social functioning, with the additional inclusion of other measures, including defensive functioning. METHOD: Correlational analyses between impulsivity and other measures, and regression analyses with DIB(R) and SAS-SR as outcome measures, and impulsivity and other measures as predictor variables, were performed on data derived from n = 57 initially borderline personality disorder (BPD) subjects recruited as part of a 7-year follow-up study of BPD. RESULTS: Data showed strong correlations between the elements of impulsivity described previously and defensive functioning. The initial study results were repeated, and only a minor contribution from defensive functioning additionally contributed to the regression models. No other variables entered the model, unless anger was dropped from the variables entered into the analysis. CONCLUSIONS: The results may contribute to a better definition of the term "impulsivity" as related to BPD, and may lead to further, improved research into the cause, treatment, and prognosis of BPD.

Borderline Personality Disorder↗
PubMed1996

A controlled trial of general practitioners' attitudes to patients with schizophrenia.

OBJECTIVE: To examine general practitioners' attitudes to patients with schizophrenia. DESIGN: A random sample of primary care physicians were alternately sent a case vignette of a patient with or without schizophrenia, in an otherwise identical clinical abstract, and asked to indicate their level of agreement with fifteen statements based on it. SUBJECTS AND SETTING: A one-in-five sample of general practitioners who were identified from the Primary Care Services Register of Lothian Health Board. RESULTS: The median score for each statement was compared by the two-tailed Wilcoxon rank sum test. Doctors responding to the vignette of the patient with schizophrenia were significantly less willing to have the patient on their practice list, more likely to refer them to a specialist and more likely to think that they would be violent; whereas they did not think that they would take up any more time than the other patient. These impressions were no different between those who had or had not received work training in psychiatry. CONCLUSIONS: This controlled trial of primary care physicians' attitudes towards patients with schizophrenia amounts to an empirical demonstration of medical discrimination against the sufferers of this and potentially of other long term psychiatric disorders. Psychiatrists and general practitioners should share care in the management of schizophrenia and try to overcome the prejudices against such patients in an attempt to improve their overall clinical care.

Attitude of Health Personnel↗
PubMed1996

Detection of genomic alterations in human cervical cancer by two-dimensional gel electrophoresis.

Two-dimensional gel electrophoresis was used to comprehensively scan the whole genome of 6 cervical intraepithelial neoplasia (CIN) lesions, 7 cervical squamous cell carcinomas, 1 cervical adenosquamous cell carcinoma, and 2 cervical adenocarcinomas for multiple genetic alterations, such as DNA amplification, chromosome deletion, loss of heterozygosity, and chromosome translocation, as compared with the paired normal tissues. DNA spot analysis of the genomic 2-dimensional gels was performed by a computer color overlay system and by spot recognition software allowing for objective spot comparison and quantitation. Nine spots were found to be amplified in the cervical carcinomas while two amplified spots were detected in the CIN III lesions. Fourteen DNA spots were either reduced in their intensity or absent in cervical carcinomas as compared to their normal paired tissues. Reduction of intensity in 6 spots was observed in the 5 CIN III lesions. These genetic alterations may represent changes in cancer genes that are associated with human cervical carcinogenesis. Further characterization of these alterations may be significant to the understanding of cervical tumorigenesis and to the development of biomarkers for clinical trials in cancer chemoprevention.

Adenocarcinoma↗
PubMed1995

Production of polyclonal antisera that recognize and distinguish between the extracellular domains of neuronal nicotinic acetylcholine receptor subunits.

Ligand-gated ion channels are oligomeric transmembrane proteins that usually contain more than one kind of monomer. The variety of monomers available to participate in oligomer formation and the apparent latitude in acceptable monomer combinations allows considerable diversity. Mechanisms for identifying the monomers comprising specific receptors are needed. We have generated affinity-purified polyclonal antisera that recognize the extracellular domain of nine neuronal nicotinic acetylcholine receptor (nAChR) subunits and distinguish between them. We prepared these antisera by immunizing rabbits with bacterially expressed recombinant protein representing the N-terminal extracellular domain of each neuronal nAChR subunit followed by affinity purification of antibodies against synthetic peptides corresponding to residues 68-81 of the alpha 1 subunit. We demonstrate subunit specificity of each affinity-purified antisera by western blots of the bacterially expressed protein and immunoblot against peptide. We further used these antibodies to demonstrate expression of neuronal nAChR subunits on the surface of transiently transfected simian kidney (COS-7) cells.

Amino Acid Sequence↗
PubMed1995

Borderline psychopathology and recurrences of clinical disorders.

This prospective cohort study of patients with borderline psychopathology reports on the clinical disorders occurring during the course and at 7-year follow-up. Subjects with persistent versus remitted borderline personality disorder (BPD) are compared. The relationship between the initial levels of borderline psychopathology and the occurrence of clinical disorders on follow-up is examined. Consecutive admissions to inpatient units were screened for borderline characteristics. This resulted in a sample of 130 subjects, 88 of whom were positive for BPD based on the Diagnostic Interview for Borderlines. At 7-year follow-up, 81 (62.3%) subjects were reinterviewed in person, 6 (4.6%) suicided, 2 (1.6%) were decreased, 36 (27.7%) refused to participate, and 5 (3.8%) could not be located. Twenty-seven of 57 (47.4%) who initially were positive for BPD were rediagnosed at 7-year follow-up (the persistent group) and 30 (52.6%) were no longer diagnosed as BPD (the remitted group). The persistent individuals were significantly more likely to be diagnosed as having major depression, dysthymia, and other psychiatric disorders than the remitted group. The persistent group had significantly more episodes of substance abuse over the follow-up period compared with the remitted group. Individuals with persistent BPD suffered more episodes of clinical disorders over the follow-up period and the initial level of borderline psychopathology predicted the recurrence of major depression.

Adolescent↗
PubMed1995

Borderline personality disorder and substance abuse: consequences of comorbidity.

The objective of this paper was to examine the prognostic significance of borderline personality disorder (BPD) and substance abuse in a cohort of former inpatients screened for BPD and followed up prospectively seven years after the index admission. The impact of comorbidity on borderline psychopathology, impulsivity and psychosocial functioning was examined. The original cohort was assembled between April 1983 and December 1985. Admissions were screened for borderline characteristics which resulted in a sample of 130 subjects, 88 of whom were positive for BPD based on the Diagnostic Interview for Borderlines. At seven years follow-up, 81 out of 130 (62.3%) subjects were re-interviewed. Six (4.6%) had committed suicide, two (1.5%) were deceased and 41 (31.6%) were lost to follow-up. The subjects with BPD and substance abuse were significantly differentiated from subjects with BPD only, substance abuse only and neither disorder on the basis of demonstrating more borderline psychopathology and more self-destructive and suicidal thoughts and behaviours. Probands with initial diagnoses of BPD and substance abuse were twice as likely to be diagnosed BPD on follow-up as probands with initial diagnosis of BPD only (relative risk = 2.19, 95% CI, 1.21 to 3.97). These findings and other research suggest that patients with comorbid BPD and substance abuse should be encouraged to focus on their abuse problems as a priority.

Adolescent↗
PubMed1994

Transgenic engineering of neuromuscular junctions in Xenopus laevis embryos transiently overexpressing key cholinergic proteins.

To examine the role of key cholinergic proteins in the formation of neuromuscular junctions (NMJs), we expressed DNAs encoding the mouse muscle nicotinic acetylcholine receptor (nAChR) or human brain and muscle acetylcholinesterase (hAChE) in developing Xenopus laevis embryos. Acetylthiocholine hydrolysis and alpha-bungarotoxin binding in homogenates of transgenic embryos revealed transient overexpression of the respective proteins for at least 4 days postfertilization. Moreover, hAChE injection induced an approximately 2-fold increase in endogenous Xenopus nAChR. Electron microscopy coupled with cytochemical staining for AChE activity revealed that AChE-stained areas, which reached 0.17 microns2 in NMJs of control embryos raised at 21 degrees C, increased up to 0.53 and 0.60 microns2 in nAChR and hAChE transgenics, respectively. These increases coincided with the appearance of a class of large NMJs with average postsynaptic lengths up to 1.8-fold greater than controls. As much as 57% and 34% of the NMJs in animals transgenic for nAChR and hAChE, respectively, displayed AChE activity in nerve terminals in addition to muscle labeling, as compared with 10% nerve-labeled NMJs in control animals. Moreover, area, but not length values, were > 2-fold larger in hAChE-expressing NMJs labeled in their nerve terminals than in those labeled in muscle alone, reflecting a hAChE-induced increase in synaptic cleft width. These findings indicate that modulation of cholinergic neurotransmission in NMJs modifies the features of nerve-muscle connections.

Acetylcholinesterase↗
PubMed1994

alpha-Bungarotoxin blocks the nicotinic receptor mediated increase in cell number in a neuroendocrine cell line.

Exposure of H69 small cell lung carcinoma cells to nicotinic agonists resulted in a significant increase (up to 100%) in cell number after 6 to 12 days. The effect of nicotine (10(-8) M to 10(-4) M) was both dose and time dependent as was that of another nicotinic agonist cytisine (10(-6) M to 10(-4) M). Interestingly, both the nicotine and cytisine induced increases in H69 cell number were blocked by alpha-bungarotoxin, as well as d-tubocurarine a nicotinic blocker which appears to interact with most nicotinic receptors. These results suggest that the nicotine induced increase in cell number is mediated through an interaction at the nicotinic alpha-bungarotoxin receptor. This idea is further supported by experiments which show (1) that H69 cells possess high affinity alpha-bungarotoxin sites (Kd = 25 nM, Bmax = 10.4 fmol/10(6) cells) with the characteristics of a nicotinic alpha-bungarotoxin receptor and (2) that the potencies of nicotinic receptor ligands in the alpha-bungarotoxin binding assay were similar to those observed in the functional studies. Northern analysis showed that mRNA for alpha 7, a putative nicotinic alpha-bungarotoxin binding subunit, and for alpha 5 were present in H69 cells. The present data provide further evidence that nicotine increases cell number in small cell lung carcinoma and are the first to show that this effect is mediated through an interaction at the nicotinic alpha-bungarotoxin receptor population. These results suggest that the alpha-bungarotoxin site may be involved in modulating proliferative responses in neuroendocrine derived SCLC cells.

Alkaloids↗
PubMed1994

Prolyl isomerase requirement for the expression of functional homo-oligomeric ligand-gated ion channels.

Ligand-gated ion channel subunits show a striking abundance of highly conserved proline residues. We, therefore, tested the hypothesis that peptidyl-prolyl isomerases may be involved in the maturation of these channels. Cyclosporin A, a selective blocker of a ubiquitous isomerase cyclophilin, reduced the surface expression in Xenopus oocytes of functional homo-oligomeric receptors containing nicotinic acetylcholine receptor subunit alpha 7 without blocking alpha 7 polypeptide synthesis. This effect could be generalized to the homo-oligomeric 5-hydroxytryptamine type 3 receptor but not to the hetero-oligomeric muscle nicotinic receptor. An alpha 7 receptor could be rescued from cyclosporin A blockade by coexpressed muscle non-alpha subunits. The effect of cyclosporin A was reversed by overexpression of exogenous rat brain cyclophilin. These findings indicate that cyclophilins may play a critical role in the maturation of homo-oligomeric receptors, acting directly or indirectly as prolyl isomerases or as molecular chaperones.

Amino Acid Isomerases↗
PubMed1994

Neuropathology of the near-term and midgestation ovine fetal brain after sustained in utero hypoxemia.

OBJECTIVE: The neuropathologic mechanisms of the ovine fetal brain in response to several hours of sustained hypoxemia with variable degrees of metabolic acidemia was investigated in both the preterm and near-term ovine fetus. STUDY DESIGN: Three groups of fetuses were studied in each of the near-term and midgestation groups: a hypoxic group, a control group, and an uninstrumented control group. Histopathologic studies were performed after a 40-hour recovery period after experimentation. RESULTS: Pathologic findings consisted of predominately white matter damage with some adjacent cortical necrosis but no selective neuronal injury. In the near-term group the hypoxia group fetuses demonstrated significantly higher white matter injury scores than did control group fetuses (p < 0.05). Periventricular white matter injury was the predominant pattern seen in the midgestation group. CONCLUSIONS: In spite of normalization of biophysical and biochemical parameters after hypoxemia both midgestation and near-term fetuses sustained pathologic changes. Presence or extent of injury did not correlate with the degree of hypoxemia or metabolic acidosis achieved.

Acidosis↗