PubMed Health⌕ Search

Biomedical subjects

J Patrick

Publications and source records attributed to J Patrick.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1994

Recovery of the ovine fetus from sustained hypoxia: effects on endocrine, cardiovascular, and biophysical activity.

OBJECTIVE: The purpose of this study was (1) to determine the ability of the ovine fetus to recover from a self-limiting asphyxial insult and (2) to monitor cardiovascular and biophysical activity as potential markers of such an insult or underlying neurologic impairment. STUDY DESIGN: Nineteen fetal sheep were studied (12 hypoxia and 7 control) at 0.9 of gestation during a 24-hour control period, up to 8 hours of either sustained hypoxemia or room air, and for a 40-hour recovery period. Fetal heart rate, blood pressure, electrocortical activity, electroocular activity, and breathing movements were monitored continuously. Fetal arterial blood was sampled at set times for blood gases, pH, lactate, and catecholamine levels. RESULT: Induced fetal hypoxemia resulted in a lactic metabolic acidosis that progressively worsened, with death occurring in three of the animals during the early recovery period. The remaining animals showed a rapid metabolic and endocrine normalization of values by 24 hours. Fetal cardiovascular and biophysical measurements likewise returned to control values during the early recovery period, although three animals had seizure-like activity. CONCLUSION: The near-term ovine fetus surviving a sustained asphyxial insult sufficient to induce neuropathologic change within the brain demonstrates a normalization of biophysical activity during the early period of recovery, although seizure-like activity may subsequently be evident.

Animals↗
PubMed1993

Validation of the MCMI-I Borderline Personality Disorder Scale with a well-defined criterion sample.

This study examined the MCMI-I BPD scale's accuracy in assigning borderline personality disorder as a primary diagnosis. Clinicians with particular expertise in Axis II pathology diagnosed borderline patients in two groups in this sample. Results indicate that the MCMI-I BPD scale has very limited utility as a screening instrument for individual diagnoses when a well-defined borderline sample is-used as a criterion. This study further suggests that at present only clinicians with particular expertise in the diagnosis of personality disorders can assess the degree and type of Axis II pathology present in a given patient. Because most structured interview and self-report validation studies have not included well-defined criterion groups, diagnostic validity of particular measures generally has not been established beyond the level of concordance.

Adult↗
PubMed1993

Altered brown adipose tissue and Na,K pump activities during diet-induced obesity and weight loss in rats.

Brown adipose tissue (BAT) thermogenesis is an uncoupled ATPase-independent thermogenic mechanism. Ion transport by the Na,K pump is an ATPase-dependent thermogenic mechanism. Both have been proposed as mechanisms of altered energy expenditure during states of dietary energy surfeit and deficit. Our aim was to study these mechanisms during diet-induced obesity and weight loss. Over 36 weeks rats were fed lard- or tallow-based diets (63% energy as fat), or a control diet (12% energy as fat). During periods of restriction rats were fed 50% of the energy intake of controls in the form of a control diet. Several components of thermogenic response increased in rats eating high fat diets and decreased following dietary restriction. BAT activation occurred, particularly with a lard-based diet, as indicated by increased GDP binding and uncoupling protein (UCP) content. Na,K pump activity in thymocytes increased with the feeding of both high fat diets at some time points. Plasma T3 level increased in rats eating the lard-based diet and decreased with dietary restriction regardless of previous diet. Resting metabolic rate (RMR) of the animals was unchanged despite increases in these thermogenic components and was decreased in all groups following dietary restriction. Our results indicate a lack of any major role for activated BAT thermogenesis in mitigating the extent of the obesity induced by the high fat diets. The reasons for the differences in response to the two different sources of saturated fat, lard, and tallow, are not clear.

Adenosine Triphosphatases↗
PubMed1993

Management of lentigo maligna and lentigo maligna melanoma with paraffin-embedded tangential sections: utility of immunoperoxidase staining and supplemental vertical sections.

BACKGROUND: The use of frozen sections in the management of lentigo maligna and lentigo maligna melanoma has been the focus of some controversy. OBJECTIVE: Our purpose was to utilize paraffin-embedded tangential sections in the management of two cases of lentigo maligna and three cases of lentigo maligna melanoma. METHODS: A modification of Mohs micrographic surgery using rush paraffin-embedded sections with adjunctive immunoperoxidase staining (HMB-45) and supplemental vertical sections was employed. RESULTS: This method resulted in enhanced histologic evaluation of section margins and did not compromise the diagnosis of the primary invasive melanoma or Breslow measurements. CONCLUSION: Mohs micrographic surgery modified by the use of rush paraffin-embedded sections allows adjunctive immunoperoxidase staining and supplemental vertical sections that may be helpful in the management of lentigo maligna and lentigo maligna melanoma.

Aged↗
PubMed1993

Mapping of ligand binding sites of neuronal nicotinic acetylcholine receptors using chimeric alpha subunits.

We constructed a series of chimeric neuronal nicotinic acetylcholine (ACh) receptor (nAChR) alpha subunits to map the location of amino acid residues that determine the pharmacological properties of these receptors. The alpha 2 and alpha 3 subunits form pharmacologically distinct nAChRs upon expression, in combination with the beta 2 subunit, in Xenopus oocytes. The alpha 2 beta 2 subunit combination is insensitive to the nicotinic antagonist neuronal bungarotoxin (NBT) and is much more sensitive to nicotine than to ACh. In contrast, the alpha 3 beta 2 subunit combination is potently inhibited by NBT and is much less sensitive to nicotine than to ACh. Chimeric subunits were constructed by replacing portions of alpha 2 or alpha 3 with the analogous portion of the other alpha subunit. Pharmacological analysis of receptors formed by these chimeric subunits, in combination with beta 2, revealed that amino acid residues involved in determining NBT sensitivity were located within sequence segments 84-121, 121-181, and 195-215. Amino acid residues that determine agonist sensitivity were located within sequence segments 1-84 and 195-215. Within region 195-215, we used site-directed mutagenesis to demonstrate the importance of Gln-198 of alpha 3 (proline in alpha 2) in determining both the antagonist sensitivity and the agonist sensitivity of neuronal nAChRs.

Acetylcholine↗
PubMed1993

Borderline disorder and attachment pathology.

In this paper, the authors investigate the theoretical and empirical association between dysfunctions of the attachment system and borderline personality disorder. Attachment theory focuses on the maintenance of a sense of safety and security through a close personal relationship with a particular person. Based on a biological behavioural system, functional attachment relationships in adulthood rely on experiences and expectations of security within the relationship. These issues are also important to the definition and dynamics of borderline personality disorder. The dimensions and patterns of reciprocal attachment were compared with other scales measuring components of psychopathology and interpersonal relationships. In a sample of 85 female outpatients, only four of the attachment scales--feared loss, secure base, compulsive care-seeking and angry withdrawal--identified patients with high scores on a measure of borderline disorder. Of these four scales, feared loss had the predominant effect. These empirical results support the hypothesized relationship between dysfunctions of the attachment system and borderline disorder.

Adult↗