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Biomedical subjects

J Sheridan

Publications and source records attributed to J Sheridan.

At least 37 records · Page 2Linked to original sources
PubMed1996

Chronic stress alters the immune response to influenza virus vaccine in older adults.

To determine whether a chronic stressor (caregiving for a spouse with a progressive dementia) is associated with an impaired immune response to influenza virus vaccination, we compared 32 caregivers' vaccine responses with those of 32 sex-, age-, and socioeconomically matched control subjects. Caregivers showed a poorer antibody response following vaccination relative to control subjects as assessed by two independent methods, ELISA and hemagglutination inhibition. Caregivers also had lower levels of in vitro virus-specific-induced interleukin 2 levels and interleukin 1beta; interleukin 6 did not differ between groups. These data demonstrate that down-regulation of the immune response to influenza virus vaccination is associated with a chronic stressor in the elderly. These results could have implications for vulnerability to infection among older adults.

Aged↗
PubMed1995

Mechanisms of VCAM-1 and fibronectin binding to integrin alpha 4 beta 1: implications for integrin function and rational drug design.

Integrin alpha 4 beta 1 can mediate both cell-cell and cell-extracellular matrix adhesion by binding to either fibronectin or vascular cell adhesion molecule 1 (VCAM-1). Both interactions are important for extravasation of leukocytes from the blood implying that rationally designed inhibitors of alpha 4 beta 1 function may be useful for treating a various inflammatory conditions. The mechanisms of ligand binding by alpha 4 beta 1 are complicated by the fact that alternative splicing can generate different isoforms of the receptor-binding domains in both fibronectin and VCAM-1. Therefore, in addition to developing alpha 4 beta 1 antagonists, we have also been interested in identifying isoform-specific functions. Recombinant ligand variants have been tested in adhesion and direct receptor-binding assays and each molecule was found to have a different inherent affinity for alpha 4 beta 1 that endows them with different adhesive activities. This suggests that alternative splicing may regulate alpha 4 beta 1-dependent motility in vivo. The initial strategy that we have adopted to develop alpha 4 beta 1 inhibitors has been to identify key amino acid residues and peptide sequences participating in the receptor-ligand binding event and to use this information to generate synthetic mimetics. Three active sites have been identified in fibronectin by testing truncated proteins, expressing recombinant fragments and screening synthetic peptides. Two of these sites employ versions of a novel integrin-binding motif, LDVP/IDAP. A key active site in VCAM-1 has been identified by similar approaches as the related sequence IDSP. Since IDSP-like sequences are probably used by other integrin-binding immunoglobulins, derivatives of these peptides may turn out to be the forerunners of a new generation of therapeutic agents with multiple applications.

Amino Acid Sequence↗
PubMed1995

Transneuronal labeling in hamster brainstem following lingual injections with herpes simplex virus-1.

Brainstem projections to hypoglossal motoneurons innervating the intrinsic and extrinsic muscles of the tongue were determined using the transneuronal transfer of Herpes simplex virus-1. Injections of Herpes simplex virus-1 into the intrinsic muscles of the anterior tongue, the geniohyoid and styloglossus muscles each produced specific patterns of label within the hypoglossal nucleus that corresponded closely to the distributions of retrogradely labeled neurons produced by similar injections of horseradish peroxidase. With relatively short survival times, Herpes simplex virus-1 injections further labeled neurons in both the brainstem reticular formation lateral to the hypoglossal nucleus and in the nucleus of the solitary tract. Intrinsic lingual muscles injections of Herpes simplex virus-1 labeled reticular formation neurons distributed laterally along the entire anterior-posterior length of hypoglossal nucleus. In contrast, labeled reticular formation neurons in the immediate vicinity of the hypoglossal nucleus following extrinsic muscles injections, were located lateral to intermediate and anterior levels of hypoglossal nucleus. Thus, despite extensive areas of overlap, there was evidence for a differential distribution of pre-hypoglossal reticular formation neurons along the anterior-posterior axis associated with different lingual injections. Most of the overlap occurred anteriorly, at a level where the nucleus of the solitary tract abuts the fourth ventricle. The potential importance of this area is lingual integrative function was further suggested by camera lucida reconstructions that showed overlapping dendritic fields of labeled neurons in the reticular formation and nucleus of the solitary tract. The dendritic fields of other labeled neurons located more rostral and lateral in the reticular formation sometimes extended into the rostral (gustatory) nucleus of the solitary tract and spinal trigeminal nuclei, suggesting possible multisynaptic pathways through which tactile and gustatory information might influence hypoglossal nucleus. Not all injections of Herpes simplex virus-1 produced label in the hypoglossal nucleus. Some injections into the anterior tongue labeled neurons in the reticular formation near the exiting facial nerve, a region containing populations of preganglionic parasympathetic neurons. Other injections, particularly into the extrinsic lingual muscles, labeled brainstem neurons associated with the sympathetic nervous system, e.g. nuclei raphe magnus and pallidus, the rostral ventrolateral reticular formation, and neurons in the A5 region. These patterns of labeled neurons within the brainstem are suggestive of a differential autonomic innervation of the intrinsic and extrinsic muscles of the tongue.

Animals↗
PubMed1995

Duplex ultrasound scanning for diagnosing lower limb deep vein thrombosis.

BACKGROUND: Traditionally, venography is used to investigate deep vein thrombosis (DVT), though duplex ultrasound offers a challenging, noninvasive alternative method and previous reports have described the use of duplex ultrasound for detecting proximal lesions. OBJECTIVE: To compare duplex ultrasound imaging with venography for both proximal and distal lesions using the probe compression technique and a different protocol. METHODS: Duplex scans were done by the same operator prior and blind to venography, which was performed using a standard protocol with the films being reviewed blindly by a second radiologist at a later date. RESULTS: In 74 patients, 21 of 22 above-knee lesions present on venography were detected by duplex scanning and there was complete agreement in the 52 of 52 venogram negatives. For lesions below the knee, duplex detected 26 of 27 lesions also present on venography and agreed on 37 of 43 venogram negatives. These figures give duplex ultrasound overall accuracies of 99% and 90% (Kappa 98% and 89%) for above- and below-knee lesions, respectively. CONCLUSION: These figures suggest duplex ultrasound technique compares favorably with venography for diagnosing both proximal and distal lesions.

Female↗
PubMed1994

Life, death and genomic change in perturbed cell cycles.

HeLaS3 cells undergo apoptosis after 18-24 h of cell cycle stasis irrespective of the agent employed (colcemid, aphidicolin, cis-platin). At high drug concentrations apoptosis occurs in cells arrested in the cell cycle in which the drug is applied and at a cell cycle position dependent on the mechanism of drug action. At low concentrations (or short exposure times) cells undergo apoptosis after progressing through an aberrant mitosis and only after 18 h of cell cycle stasis in a 'pseudo G1/S' cell cycle position. Aberrent mitoses result in multipolar mitoses, chromosomal breakage and interchromosomal concatenation events. We propose that the ability of cells to delay progression into aberrent mitosis, as well as their propensity to undergo apoptosis, are important determinants of clinical cytotoxicity. We also suggest that apoptosis plays an important role in preventing the generation of aneuploidy and recombination and rearrangement events commonly associated with cancer.

Animals↗
PubMed1994

Educational intervention in pharmacy students' attitudes to HIV/AIDS and drug misuse.

By providing injecting equipment to drug misusers, community pharmacists in the UK may become involved in preventing the spread of HIV via the intravenous route. Over 60% of pharmacy graduates from the School of Pharmacy enter community pharmacy and, as part of their undergraduate course, attend a series of lectures and seminars on HIV/AIDS and drug misuse. The aim of this research was to: (1) investigate students' attitudes to these subjects; (2) assess the students' knowledge of HIV/AIDS; (3) evaluate any change in level of knowledge or of attitude after attending the course; and (4) investigate students' attitudes towards the teaching of these subjects. A questionnaire was administered to students before and after their undergraduate course. The level of knowledge increased significantly after attending the course. Students were asked their opinion on the teaching of HIV/AIDS and drug misuse at the School of Pharmacy. After the course, significantly more responded 'good' or 'very good' with regard to teaching on social issues in drug misuse, rehabilitation and treatment of drug misusers, and health education on HIV/AIDS. There was no significant change in attitude, after the course. Attitude to HIV/AIDS and drug misuse was found to be unassociated with previous experience of working in pharmacies supplying injecting equipment and prescribed methadone. Both attitude and pre-course assessed knowledge were significantly associated with race and religion. These results indicate that attending the course had the effect of increasing knowledge of HIV/AIDS and increasing confidence in counselling clients. The perception of the teaching was also seen to be more positive.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Human blink startle during aversive and nonaversive Pavlovian conditioning.

Potentiation of blink startle during aversive and nonaversive Pavlovian single-cue conditioning was assessed in human Ss. In Experiment 1 (N = 89), the conditioning group received paired presentations of a visual conditioned stimulus (CS) and an unconditioned stimulus (US), whereas the control group was presented with a random sequence. The US was an electric shock for half the Ss and a nonaversive reaction time task for the other half. Electrodermal conditioning was evident regardless of the nature of the US, but blink potentiation was found only in the conditioning group that had been trained with the aversive US. These results were replicated in Experiment 2 (N = 65), in which a nonaversive US of increased motivational significance was used. Thus, only aversive conditioning seems to affect the affective valence of the CS, at least as reflected by changes in a skeletal reflex.

Adolescent↗
PubMed1993

The effect of adrenalectomy on the restraint stressed induced suppression of MHC class II expression by murine peritoneal macrophages.

Restraint stress suppresses the expression of MHC class II (I-A) glycoproteins by murine peritoneal macrophages. In order to evaluate the role of the pituitary adrenal axis, the effect of restraint stress on I-A expression by macrophages from adrenalectomized mice was evaluated. Adrenalectomy resulted in elevated levels of ACTH but abrogated the increase in corticosterone that results from restraint stress. The expression of I-A by macrophages from adrenalectomized mice was similar to that of sham operated mice or untreated mice. Adrenalectomy ameliorated the suppressive effects of restraint but the expression of I-A was below that of macrophages from adrenalectomized control mice. These results suggest that other factors in addition to corticosterone may effect I-A expression by murine peritoneal macrophages. A survey of other neuropeptides and catecholamines indicated that the addition of ACTH or epinephrine to macrophage cultures resulted in a suppression of I-A expression.

Adrenalectomy↗
PubMed1993

Regulation of mycobacterial growth by the hypothalamus-pituitary-adrenal axis: differential responses of Mycobacterium bovis BCG-resistant and -susceptible mice.

The role of the hypothalamus-pituitary-adrenal (HPA) axis in regulating the growth of Mycobacterium avium in Mycobacterium bovis BCG-resistant and -susceptible congenic mice was evaluated. Restraint was used to activate the HPA axis, which resulted in an increase in the level of corticosterone in the plasma. Activation of the HPA axis increased the susceptibility of BALB/c.Bcgs mice to the growth of M. avium. In contrast, the growth of M. avium was not altered in BALB/c.Bcgr mice as a result of HPA activation. Adrenalectomy abolished the effect of HPA activation on mycobacterial growth, as did treatment of the mice with a glucocorticoid receptor antagonist, RU 486. Activation of the HPA axis also resulted in the increased susceptibility of splenic macrophages from Bcgs mice but not from Bcgr mice to M. avium growth in vitro. The production of tumor necrosis factor alpha and of reactive nitrogen intermediates by splenic macrophages from both strains of mice was suppressed as a result of HPA activation. The implications of these findings for resistance controlled by Bcg and for susceptibility to mycobacterial growth are discussed.

Adrenalectomy↗
PubMed1992

Iron deficiency.

Explore the source record for details and available documents.

Child↗
PubMed1992

Purification and characterization of a novel growth factor from human breast cancer cells.

We have purified and characterized a novel 30-kDa glycoprotein (gp30) with TGF alpha-like properties secreted from the estrogen receptor negative breast cancer cell line MDA-MB-231. This factor was immunoprecipitated by an anti-TGF alpha polyclonal antibody and also had TGF alpha-like biological activity, as assayed by EGF radioreceptor assay and anchorage-independent assays. In addition, the novel growth factor stimulated phosphorylation of the EGF receptor and erbB-2 receptor. However, the novel growth factor, unlike EGF and TGF alpha, bound to heparin-Sepharose. Purification of gp30 was obtained to apparent homogeneity by heparin affinity chromatography and subsequent reversed-phase chromatography. Tunicamycin treatment in vivo or N-glycanase deglycosylation in vitro revealed a putative precursor of approximately 22 kDa molecular mass in contrast to the "normal" 16-kDa precursor species for TGF alpha. In vitro translation of total mRNA from MDA-MB-231 cells confirmed the size of the putative precursor. Biochemical characterization of gp30 was begun by V8 protease digestion of the deglycosylated polypeptide and the translated products. Peptide mapping of V8-digested, immunoprecipitated material suggests that the amino acid sequence of this unique protein is distinct from mature TGF alpha and not the result of a posttranslational modification of the precursor. We conclude that this TGF alpha-like (gp30) polypeptide is a novel growth factor with agonistic activity for both EGF and erbB-2 receptors.

Animals↗
PubMed1991

The effects of age on platelet intracellular free calcium concentrations in normotensives and hypertensives.

We have investigated relationships between age, blood pressure and intracellular calcium concentration in platelets from normotensives and hypertensives. In normotensives, there were positive correlations between age and platelet intracellular calcium concentration (r = 0.76, P less than 0.001), age and mean arterial pressure (MAP; r = 0.55, P less than 0.01) and MAP and platelet intracellular calcium concentration (r = 0.45, P less than 0.01). Multiple regression analysis revealed that age was the primary determinant of platelet intracellular calcium concentration in normotensives. The effect of MAP on platelet intracellular calcium concentration when adjusted for age was not significant (P = 0.73). In hypertensives, there was no significant relationship between age and platelet intracellular calcium concentration (r = 0.15, P = 0.43), age and MAP (r = 0.17, P = 0.37) or MAP and platelet intracellular calcium concentration (r = -0.27, P = 0.15). Overall, platelet intracellular calcium concentration was significantly higher in hypertensives than in age-matched normotensives (P less than 0.05). Within the age groups examined, platelet intracellular calcium concentration was significantly higher only in younger hypertensives when compared with controls of a similar mean age (P less than 0.001). Thus, age, in addition to hypertension, is an important determinant of platelet intracellular calcium concentration.

Adult↗
PubMed1990

Oesophageal stenosis distal to oesophageal atresia.

Oesophageal atresia with or without tracheo-oesophageal fistula is often associated with a functionally abnormal distal oesophagus. The association of oesophageal atresia and a distal oesophageal stenosis is less well recognized and is usually regarded as a rarity. We describe four cases of oesophageal stenosis distal to oesophageal atresia and review the literature relating to this condition.

Esophageal Atresia↗