Search PubMed⌕ Search

Biomedical subjects

R Sheridan

Publications and source records attributed to R Sheridan.

At least 19 recordsLinked to original sources
PubMed2001

Heterogeneity of genetic alterations in prostate cancer: evidence of the complex nature of the disease.

Prostate cancer is a complex, multifactorial disease with genetic and environmental factors involved in its etiology. The search for genetic determinants involved in the disease has proven to be challenging, in part because such complex diseases are often not amenable to characterization by linkage analysis and positional cloning as is the case for diseases with simple Mendelian genetic inheritance. Prostate cancer susceptibility loci that have been reported so far include HPC1 (1q24-q25), PCAP (1q42-q43), HPCX (Xq27-q28), CAPB (1p36), HPC20 (20q13), HPC2/ELAC2 (17p11) and 16q23. Prostate cancer aggressiveness loci have also been reported (5q31-q33, 7q32 and 19q12). Further complicating the process is the existence of polymorphisms in several genes associated with prostate cancer including, AR, PSA, SRD5A2, VDR and CYP isoforms. These polymorphisms, however, are not thought to be highly penetrant alleles in families at high risk for prostate cancer. It is clear that prostate cancer etiology involves several genetic loci with no major gene accounting for a large proportion of susceptibility to the disease.

Genetic Heterogeneity↗
PubMed2001

Relationship between acute morphine and the course of PTSD in children with burns.

OBJECTIVE: To investigate the relationship between the dose of morphine administered during a child's hospitalization for an acute burn and the course of posttraumatic stress disorder (PTSD) symptoms over the 6-month period following discharge from the hospital. METHOD: Twenty-four children admitted to the hospital for an acute burn were assessed twice with the Child PTSD Reaction Index: while in the hospital and 6 months after discharge. The Colored Analogue Pain Scale was also administered during the hospitalization. All patients received morphine while in the hospital. The mean dose of morphine (mg/kg/day) was calculated for each subject through chart review. RESULTS: The Pearson product moment correlation revealed a significant association between the dose of morphine received while in the hospital and a 6-month reduction in PTSD symptoms. Children receiving higher doses of morphine had a greater reduction in PTSD symptoms over 6 months. CONCLUSIONS: This study suggests the possibility that acute treatment with morphine can secondarily prevent PTSD. This result is discussed in terms of the possible effect of morphine on fear conditioning and the consolidation of traumatic memory.

Adolescent↗
PubMed2000

SB-253514 and analogues; novel inhibitors of lipoprotein-associated phospholipase A2 produced by Pseudomonas fluorescens DSM 11579. I. Fermentation of producing strain, isolation and biological activity.

Two new classes of inhibitors of LpPLA2 have been identified in fermentations of Pseudomonas fluorescens. The two structurally isomeric series differ in the geometry of closure of the bicyclic carbamate and comprise a range of compounds varying only in length of their lipophilic sidechain. The most abundant species were extracted from the cells and purified by silica and C18 chromatography. Members of the more stable class were shown to be potent and selective competitive inhibitors of LpPLA2.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1999

Percutaneous endoscopic gastrostomy in burn patients.

BACKGROUND: Prolonged enteral feedings are required occasionally in seriously burned individuals. We have employed percutaneous endoscopic gastrostomy (PEG) in selected patients who require particularly prolonged access, thus prompting this review. METHODS: The PEG procedure was performed under general anesthesia in combination with another surgical procedure using a variety of commercially available needle and guidewire kits in 14 patients. RESULTS: These 14 patients had an average age of 55.2 +/- 6.6 years and a burn involving 38 +/- 8% of the body surface. Eleven of these patients had suffered an inhalation injury. The tubes were placed an average of 57 +/- 10.5 days after injury through unburned and unharvested skin in four patients (28%), healed donor sites in five patients (35%), healed burn in one patient (1%), and grafted burn in four patients (28%). One patient, whose catheter was placed through a grafted fascial excision, developed moderate local wound erosion. Tubes were known to have been left in place as long as 155 days. However, most were removed in rehabilitation hospitals, and we were unable to determine how long most were left in place. We are unaware of any problems with the tubes occurring after discharge from the acute care setting. CONCLUSIONS: In selected patients, PEG can provide more comfortable access for prolonged enteral feedings than nasogastric tubes and can be placed with minimal morbidity.

Adult↗
PubMed1999

Infradiaphragmatic central venous pressures reflect supradiaphragmatic pressures in stable burn patients.

OBJECTIVE: Because the skin of the groin is often spared, femoral central venous catheters are sometimes used in patients with extensive burns. The accuracy of central venous pressures obtained from the infradiaphragmatic location relative to the traditional supradiaphragmatic value is not known in this population. METHODS: Seventeen seriously injured but hemodynamically stable burn patients were enrolled in a protocol approved by the human studies committee in which, during scheduled central venous line rotations, supradiaphragmatic and infradiaphragmatic central venous pressures were determined simultaneously. RESULTS: These 17 patients were an average of 21.8+/-20.1 years old (range, 6 months to 61 years), and the average burn size was 60.8+/-22.6% (range, 20 to 90%). Supradiaphragmatic and infradiaphragmatic pressures correlated well, with an r value of 0.903, p less than 0.01. CONCLUSION: In the absence of clinically significant abdominal distention, infradiaphragmatic central venous pressure is an accurate reflection of supradiaphragmatic pressure, and indirectly, circulating blood volume.

Adolescent↗
PubMed1998

Rational engineering of the TOL meta-cleavage pathway

The meta-cleavage pathway of Pseudomonas putida mt-2 was simulated using a biochemical systems simulation developed by Regan (1996). A non-competitive inhibition term for catechol-2,3-dioxygenase (C23O) by 2-OH-pent-2,4-dienoate (Ki = 150 μM) was incorporated into the model. The simulation predicted steady state accumulation levels in the μM range for metabolites pre-meta-cleavage, and in the mM range for metabolites post-meta-cleavage. The logarithmic gains L[V-i, Xj] and L[X-i, Xj] clearly indicated that the pathway was most sensitive to the concentration of the starting substrate, benzoate, and the first enzyme of the pathway, toluate-1, 2-dioxygenase (TO). The simulation was validated experimentally; it was found that the amplification of TO increased the steady state flux from 0.024 to 0.091 (mmol/g cell dwt)/h. This resulted in an increased accumulation of a number of the pathway metabolites (intra- and extracellularly), especially cis-diol, 4-OH-2-oxovalerate, and 4-oxalocrotonate. Metabolic control analysis indicated that C23O was, in fact, the major controling enzymic step of the pathway with a scaled control coefficient of 0.83. The amplification of TO resulted in a shift of some of the control away from C23O. Catechol-2,3-dioxygenase, however, remained as the major controling element of the pathway. Copyright 1998 John Wiley & Sons, Inc.

Journal Article↗
PubMed1998

Autologous skin banking.

Small amounts of excess autograft are commonly harvested during burn procedures, and typically these are discarded. However, the resources of a local skin bank may be used to preserve this tissue for a later autologous use. This has been a routine practice in our institution and we feel that it has impacted favorably on patient care. In this paper we report 42 consecutive applications of autologous frozen skin and illustrate the technique with a case report.

Adolescent↗
PubMed1997

The index of deep burn injury: an analysis of 66 extremity sites in 15 children.

The group of burn injuries generally classified as 'fourth degree' vary enormously in extent and severity. This fact, and the absence of a widely accepted grading system for these relatively uncommon injuries, has hindered our ability to learn from the experiences of others as reported in the literature. Based on a series of cadaver dissections, the Index of Deep Burn Injury (IDBI) was developed to provide such a classification scheme. The initial experience with the IDBI in a group of locally destructive "fourth degree' wounds is presented. It is believed that this index has the potential to improve our ability to describe highly destructive wounds.

Adolescent↗
PubMed1997

Electrical injury from subway third rails: serious injury associated with intermediate voltage contact.

BACKGROUND: Railway and subway-associated electrical trauma is rare and typically involves high voltage (> 20,000) arc injuries. Not all rail systems utilize such high voltage. We report 16 cases of electrical trauma due to 600 V direct contact with subway 'third' rails. METHODS: A case series of injured patients presenting to Shriners Burns Institute, Boston or Massachusetts General Hospital between 1970 and 1995 was retrospectively analyzed. RESULTS: A total of 16 cases was identified. Among seven subway workers, the mechanism of rail contact was unintentional by a tool, a hand or by falling; no deaths occurred. Among nine non-occupational victims, injuries involved suicide attempts, unintentional falls, or risk-taking behavior. This group suffered greater burn severity, operative procedures, and complications; three deaths occurred. CONCLUSIONS: This is the largest report series of direct electrical trauma from a subway third rail. The high morbidity and mortality from this 600 V contact suggests that the traditional classification of low voltage (< 1000 V) exposure can be subdivided to reflect the serious and lethal potential of intermediate range exposures compared to household range exposures (0-220 V).

Accidents↗
PubMed1997

Molecular characterization of murine humoral immune response to botulinum neurotoxin type A binding domain as assessed by using phage antibody libraries.

To produce antibodies capable of neutralizing botulinum neurotoxin type A (BoNT/A), the murine humoral immune response to BoNT/A binding domain (H(C)) was characterized at the molecular level by using phage antibody libraries. Mice were immunized with BoNT/A H(C), the spleens were harvested, and single-chain Fv (scFv) phage antibody libraries were constructed from the immunoglobulin heavy and light chain variable region genes. Phage expressing BoNT/A binding scFv were isolated by selection on immobilized BoNT/A and BoNT/A H(C). Twenty-eight unique BoNT/A H(C) binding scFv were identified by enzyme-linked immunosorbent assay and DNA sequencing. Epitope mapping using surface plasmon resonance in a BIAcore revealed that the 28 scFv bound to only 4 nonoverlapping epitopes with equilibrium constants (Kd) ranging from 7.3 x 10(-8) to 1.1 x 10(-9) M. In a mouse hemidiaphragm assay, scFv binding epitopes 1 and 2 significantly prolonged the time to neuroparalysis, 1.5- and 2.7-fold, respectively, compared to toxin control. scFv binding to epitopes 3 and 4 showed no protection against neuroparalysis. A combination of scFv binding epitopes 1 and 2 had an additive effect on time to neuroparalysis, which increased to 3.9-fold compared to the control. The results suggest that there are two "productive" receptor binding sites on H(C) which lead to toxin internalization and toxicity. Blockade of these two epitopes with monoclonal antibodies may provide effective immunoprophylaxis or therapy against BoNT/A intoxication.

Amino Acid Sequence↗
PubMed1996

Changes in cell morphology and carnitine acetyltransferase activity in Candida albicans following growth on lipids and serum and after in vivo incubation in mice.

Candida albicans C316, maintained in the yeast form, showed a proliferation of peroxisomes when grown on triolein or serum as sole carbon source but these structures were absent from glucose-grown cells. Peroxisomes were also apparent in C. albicans obtained after injection into mice and recovery from intraperitoneal washings and kidneys; they may therefore be useful markers to assess a potential in vivo response in cells that are growing in vitro. Transcell-wall structures also occurred in C. albicans grown on triolein or serum, and in cells cultured in vivo, but were not seen in cells grown on glucose. These structures consisted of electron-dense fibrillar material penetrating through the cell wall from the plasmalemma side and protruded out to the exterior of the cell. Endoplasmic reticulum, located at the periphery of the cell, was found to be in close proximity with these cell wall structures. Carnitine acetyltransferase (CAT; EC 2.3.1.7), the key enzyme for the translocation of acetyl units between intracellular compartments, was present in low activities in glucose-grown cells; its activity was increased some 100-fold in triolein-grown cells but only 4-fold in serum-grown cells. It was not possible to assess this activity in the in vivo-cultured cells. Two separate CAT proteins, partially purifed from isolated microchondria and peroxisomes, respectively, were identified, with different specificities and kinetic properties.

Acetic Acid↗
PubMed1994

Monoclonal antibodies to high-incidence Kell epitopes: characterization and application in automated screening of donor samples.

Monoclonal antibodies, LM313/706 and LM357/828, recognize high-frequency epitopes which are absent on red cells of Ko phenotype. Both antibodies have proved suitable for automated screening of blood donor samples, with 5 ml of each culture supernatant sufficient to screen 3,000 donor samples. In a screen of 45,545 samples, LM313/706 revealed 11 samples (1:3686) of Kp(a+b-) phenotype. Thirty-seven samples of K+k- phenotype were identified in 15,235 samples screened with LM357/828 antibody (0.24%). The epitope recognized by LM313/706 was inactivated by 2 mM DTT suggesting a possible association with the Jsa/Jsb antigen structure. The expression of the k-like epitope detected by LM357/828 antibody was found to be influenced by pH change.

Antibodies, Monoclonal↗
PubMed1992

Diagnosis of the acute abdomen in the neurologically stable spinal cord-injured patient. A case study.

The diagnosis of the acute abdomen in the spinal cord injured patient is difficult. Diagnoses are often so delayed that approximately 10% of these patients die of acute abdominal problems. The presentation also varies with the level and duration of injury. An understanding of the functional neuroanatomy of the abdominal wall and viscera aids in timely diagnosis. I present an illustrative case and describe the pertinent functional neuroanatomy.

Abdomen, Acute↗
PubMed1990

Pathways to acetyl-CoA formation in Candida albicans.

The supply of acetyl units from the mitochondrion to the cytosol of Candida albicans appears to be dependent only upon the activity of carnitine acetyltransferase (CAT). The enzyme ATP:citrate lyase (ACL), the major source of acetyl units in oleaginous yeasts, is absent from C. albicans in both the mycelial and yeast forms. There appears to be no other active translocation of acetate or acetyl groups except via the action of carnitine acetyltransferase.

ATP Citrate (pro-S)-Lyase↗