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Biomedical subjects

J Barrett

Publications and source records attributed to J Barrett.

At least 163 records · Page 9Linked to original sources

Syngeneic bone marrow transplantation eliminates V beta 8.2 T lymphocytes from the spinal cord of Lewis rats with experimental allergic encephalomyelitis.

Experimental allergic encephalomyelitis (EAE), an animal model for multiple sclerosis (MS), is a paralytic disease of the central nervous system (CNS) mediated by T-lymphocytes reactive to myelin basic protein (MBP). Lewis rats actively immunized with fragment 68 to 82 of guinea pig MBP develop a monophasic disease with spontaneous recovery. Lymphocyte recognition of the primary encephalitogenic sequence of MBP (fragment 68 to 82) is V beta 8.2 T cell receptor (TCR) skewed [1-3]. Lewis rats in clinical remission at 1 month and 3 months after spontaneous resolution of EAE retain V beta 8.2 T-lymphocytes in the CNS when analyzed by reverse transcriptase polymerase chain reaction or in situ hybridization. In contrast, 1 and 3 months after clinical remission from syngeneic bone marrow transplantation, V beta 8.2 T lymphocytes are absent from the CNS. During clinically active EAE and inflammatory breakdown of the blood-brain barrier, immune ablation and reconstitution with syngeneic bone marrow results in clinical tolerance of the new immune system to myelin.

Animals↗

In vitro control analysis of an enzyme system: experimental and analytical developments.

In this paper we describe a flow-through system for reconstituting parts of metabolism from purified enzymes. This involves pumping continuously into a reaction chamber, fresh enzymes and reagents so that metabolic reactions occur in the chamber. The waste products leave the chamber via the outflow so that a steady state can be setup. The system we chose consisted of a single enzyme, lactate dehydrogenase. This enzyme was chosen because it consumes NADH in the chamber which could be monitored spectrophotometrically. The aim of the work was to investigate whether a steady state could be achieved in the flow system and whether a metabolic control analysis could be done. We measured two control coefficients, CLDH and Cpump for the enzyme flux and NADH concentration and confirmed that the summation theorem applied to this system. The advantage of a flow-through system is that the titrations necessary to estimate the control coefficients can be easily and precisely controlled; this means that accurate estimates for the control coefficients can be obtained. In the paper, we discuss some statistical aspects of the data analysis and some possible applications of the technique, including a method to determine the presence of metabolic channelling between two different enzymes.

Kinetics↗

Vasoproliferative tumors of the ocular fundus. Classification and clinical manifestations in 103 patients.

OBJECTIVE: To describe the clinical features of vasoproliferative tumors of the ocular fundus and to propose a comprehensive classification of these tumors. METHODS: A retrospective review of all cases that were diagnosed as acquired retinal hemangioma or vasoproliferative retinal tumor was conducted on the Ocular Oncology Service at Wills Eye Hospital, Philadelphia, Pa. RESULTS: There were 129 vasoproliferative tumors in 113 eyes of 103 patients. The tumors were classified as idiopathic in 84 eyes (74%) and secondary to preexisting ocular disease in 29 (26%). Subclassification into solitary (88 eyes), multiple (17 eyes), and diffuse (eight eyes) involvement was made. Of the 84 eyes with idiopathic tumors, 73 (87%) had solitary tumors, five (6%) had multiple tumors, and six (7%) had diffuse tumors. The lesion was located in the inferior, inferotemporal, or temporal region of the fundus in 78% and developed within 6 mm of the ora serrata retinae in 88%. Associated vitreoretinal findings included intraretinal exudation (82%), secondary exudative retinal detachment (48%), vitreous cells (46%), vitreous hemorrhage (21%), preretinal macular fibrosis (31%), and macular edema (18%). Of the 29 eyes with secondary tumors, the tumor was solitary in 15 (52%), multiple in 12 (41%), and diffuse in two (7%). The most common preexisting ocular disease included intermediate uveitis (pars planitis) in eight eyes (28%), retinitis pigmentosa in six (21%), toxoplasmic retinitis in two (7%), toxocariasis in two (7%), retinochoroidal coloboma in two (7%), and traumatic chorioretinopathy in two (7%). Retinal pigment epithelial hyperplasia was a prominent feature that was adjacent to 58% of the secondary tumors. Overall, management of the 129 tumors consisted of observation in 63 (49%), cryotherapy in 54 (42%), laser photocoagulation in seven (5%), plaque radiotherapy in three (2%), and other modes of treatment in two (2%). CONCLUSIONS: Vasoproliferative retinal tumors can be idiopathic, or they can develop secondary to congenital, inflammatory, vascular, traumatic, dystrophic, and degenerative ocular diseases. They can produce a variety of complications. Awareness and recognition of these tumors and differentiation from other retinal vascular tumors are important.

Adolescent↗

Chemical modification of a cloned glutathione S-transferase from Schistosoma japonicum: evidence for an essential histidine residue.

Diethylpyrocarbonate (DEP) inhibits the catalytic activity of a cloned glutathione S-transferase from Schistosoma japonicum (Sj26GST) with a second-order rate constant of 474 M-1 min-1 at pH 7.0 and 25 degrees C. There is an accompanying increase in absorbance at 242 nm due to the formation of N-carbethoxyhistidyl derivatives. There was no evidence that tyrosine or cysteine residues were modified by DEP treatment nor did the enzyme undergo any major conformational change. Activity can be restored by treating the DEP-modified enzyme with hydroxylamine and the pH curve for inactivation indicates involvement of a residue with a pKa of 7.3. Complete inactivation of Sj26GST requires the modification of six histidine residues per subunit. Statistical analysis of residual enzyme activity versus number of groups modified showed that of the six modifiable groups, only one is critical for activity. Substrate protection suggests that this essential histidine residue is at or near the active site.

Animals↗

The relationship between hospital per diem billing and DRG reimbursement for urban trauma patients.

STUDY OBJECTIVE: To study the relationship between a trauma center per diem charges and medicare DRG reimbursement. DESIGN: Retrospective comparison of charges ($630/day, $1500/ICU day) and hypothetical DRG reimbursement using medical records ICD-9 N and P codes and version 5.0 of grouper. SETTING: An urban level I trauma center that participates in a trauma system that serves a population of three million people. PATIENT POPULATION: Trauma patients > or = 16 years old (mean age of 32 years) admitted and discharged between 1/1/88 and 9/30/88. The group was 86% male, 75% black, with a blunt mechanism of injury in 64%. The mean ICU stay was 0.9 days, and the mean total length of stay was 5.0 days. RESULTS: Total per diem charges were $8,652,159, and DRG reimbursement was $8,636,505, causing a net loss of $15,654, or 0.2% of charges. Mean charges and reimbursement did not differ for the entire group. The mean loss per patient was $8. Mean charges and reimbursement differed in penetrating trauma patients (mean loss = $138), as well as those with different lengths of stay. The correlation between charges and reimbursement was 0.42; for penetrating trauma patients, the correlation was 0.58. (p < .001) CONCLUSION: If DRG reimbursement were provided for all admitted trauma patients, the amount would equal per diem rates. Trauma centers with similar patients and lengths of stay can use these per diem rates to estimate DRG reimbursement.

Adolescent↗

The relationship between hospital per diem billing and DRG reimbursement for urban trauma patients.

STUDY OBJECTIVE: To study the relationship between a trauma center per diem charges and medicare DRG reimbursement. DESIGN: Retrospective comparison of charges ($630/day, $1500/ICU day) and hypothetical DRG reimbursement using medical records ICD-9 N and P codes and version 5.0 of grouper. SETTING: An urban level I trauma center that participates in a trauma system that serves a population of 3 million people. PATIENT POPULATION: Trauma patients > or = 16 years old (mean age of 32 years) admitted and discharged between 1/1/88 and 9/30/88. The group was 85% male, 75% black, with a blunt mechanism of injury in 64%. The mean ICU stay was 0.9 days, and the mean total length of stay was 5.0 days. RESULTS: Total per diem charges were $8,652.159, and DRG reimbursement was $8,636,505, causing a net loss of $15,654, or 0.2% of charges. Mean charges and reimbursement did not differ for the entire group. The mean loss per patient was "8. Mean charges and reimbursement differed in penetrating trauma patients (mean loss = $138), as well as those with different lengths of stay. The correlation between charges and reimbursement was 0.42; for penetrating trauma patients, the correlation was 0.58 (p < .001). CONCLUSION: If DRG reimbursement were provided for all admitted trauma patients, the amount would equal per diem rates. Trauma centers with similar patients and lengths of stay can use these per diem rates to estimate DRG reimbursement.

Adolescent↗

Application of metabolic control analysis to the pathways of carbohydrate breakdown in Hymenolepis diminuta.

The application of metabolic control theory to carbohydrate breakdown in the tapeworm Hymenolepis diminuta shows that it is not necessary for both phosphoenolpyruvate carboxykinase and pyruvate kinase to be modulated in order to control the relative fluxes through the two arms of the phosphoenolpyruvate branchpoint. Changes in activity of enzymes outside of the two branches also influence the flux ratio. Control coefficients of individual enzymes for the fluxes through phosphoenolpyruvate carboxykinase and pyruvate kinase are not fixed, but vary as the flux ratio between the two arms of the branchpoint changes. The metabolic model can also be used to evaluate the role of the fructose-1,6-bisphosphate loop and to calculate metabolite transition time control coefficients.

Acetates↗

Biochemical analyses on single amphidial glands, excretory-secretory gland cells, pharyngeal glands and their secretions from the avian nematode Syngamus trachea.

The gape nematode, Syngamus trachea, has been used as a model to study nematode secretions. Individual and intact pairs of amphidial glands, pharyngeal glands and pairs of excretory-secretory gland cells have been dissected and their secretory products analysed. The protein profiles of each gland and the total nematode secretions were analysed on 12.5% homogeneous SDS-PAGE minigels. The protein analyses revealed that the structural protein profile of each gland is different. The amphidial gland secretes two major proteins of 36.0 and 41.5 kDa, the excretory-secretory gland cell secretes a protein of 28.2 kDa and a protein of 14.3 kDa, and the pharyngeal gland secretes proteins of 41.5 and 14.6 kDa. Analysis of the total nematode secretions revealed all of the above major secretory proteins and an additional protein of 49.3 kDa. Syngamus trachea secretes acetylcholinesterases and its secretions contain multiple proteases.

Animals↗

The purification and properties of glutathione reductase from the cestode Moniezia expansa.

Glutathione reductase has a central role in glutathione metabolism and as such is a potential target for chemotherapy. The aim of the work was to purify and characterise glutathione reductase from the cestode Moniezia expansa and to compare the properties of the helminth enzyme with its mammalian counterpart. The enzyme was purified by a combination of anion exchange and affinity chromatography and further characterized by chromatofocusing and gel electrophoresis. Analysis revealed a single isoenzyme of glutathione reductase in Moniezia expansa, with a pI of 5.8. The enzyme was a homodimer of native molecular weight 114 kDa, subunit weight 63 kDa. Enzyme activity was affected by buffer concentration and the presence of monovalent sodium salts. The pH optimum was 7.4 with NADPH as cofactor and 5 with NADH. The Kma for oxidized glutathione was 76 microM and for NADPH and NADH, 21 and 350 microM respectively. In addition to oxidized glutathione only the mixed disulphide between CoA and glutathione (CoASSG) showed any significant activity as substrate. The cestode enzyme was inhibited by a variety of compounds including arsonic derivatives, 2,4,6 trinitrobenzene sulfonate 1,3-bis (2-chlorethyl)-1-nitrosourea and oxidized glutathione. In conclusion the glutathione reductase of M. expansa resembles the mammalian enzyme in its general physical properties and its substrate and inhibitor profile. However, the parasite enzyme shows an unusually high activity with the mixed disulphide of coenzyme A and glutathione (CoASSG) and appears to be more sensitive to inhibition by sodium ions.

Animals↗

Investigation of the chemosensory function of amphids of Syngamus trachea using electrophysiological techniques.

Syngamus trachea, the gape nematode, has been used as a model to study the chemosensory function of amphids. Extracellular electrophysiological recordings were performed directly on amphids. The amphids were stimulated by blood serum from a host bird and by D-tryptophan. The spike frequency produced by the amphid increased significantly after the application of the serum and the application of D-tryptophan. Two types of amphidial neurones responded to the presence of the stimuli. These extracellular recordings have verified the chemosensory function of the amphids.

Action Potentials↗

Human immunodeficiency virus and hepatitis B virus seroprevalence in an urban trauma population.

OBJECTIVE: To determine the seroprevalence of the human immunodeficiency virus (HIV) and the hepatitis B virus (HBV) in patients of an urban level I trauma center. DESIGN: Prospective, blinded point prevalence study of serum HIV and HBV antibody and antigen. SETTING: An urban level I trauma center that participates in a trauma system serving three million people. PATIENTS: The study included 994 (94.8%) of 1049 consecutive trauma service patients treated between June 6, 1988 and September 22, 1988. The patients were 82.2% male and 73.1% black, with a mean age of 28.8 +/- 12.3 years. Blunt trauma was seen in 65.4% of patients, 5.2% were in shock, and 96.2% survived their trauma. MAIN OUTCOME MEASURES: HIV and HBV seroprevalence, using both antibody and antigen testing. RESULTS: HIV infection was seen in 43 patients (4.3%); 41 (95.3%) were HIV Ab+ and two (4.7%) were HIV Ab-/HIV Ag+. Infection with the HBsAg was seen in 31 patients (3.1%). Infection with either virus was seen in 70 patients (7%); four patients (0.4%) were infectious for both viruses. Infection was related to age 20 to 49 years, i.v. drug use, a hepatitis or sexually transmitted disease history, prior HIV testing, shock, and death (p < 0.05). Penetrating trauma was not predictive of infection. In a logistic regression model, IV drug use was the single significant predictor of infection (p < 0.05). CONCLUSIONS: Young urban trauma patients, because of drug-related intentional violence, are 15.3 to 17.6 times more likely to be HIV infected and 3.9 to 7.9 times more likely to be infectious for HIV or HBV than the trauma population overall. The 12 to 21% infection rates in critically injured patients who require shock resuscitation and/or die reinforces the need for mandated universal precautions and for clear policies which govern the performance of procedures by physicians in training. Primary HIV infection in critically injured patients may worsen their outcome and may adversely affect the exposed health care worker. Emergency departments and trauma units should develop a referral system to HIV primary care services (HIV counselling and testing) for high risk patients and for adversely exposed health care workers.

AIDS Serodiagnosis↗

Role of echocardiography in the diagnosis of occult penetrating cardiac injury.

OBJECTIVE: To determine the usefulness of early echocardiography in stable patients with penetrating wounds in proximity to the heart. DESIGN: Retrospective chart review over a 1-year period. SETTING: Urban level I trauma center. PATIENTS: 121 clinically stable patients with penetrating wounds in proximity to the heart underwent immediate echocardiography (ECHO). Those with evidence of pericardial effusion then underwent subxiphoid pericardial window (SPW), followed by a median sternotomy if blood was found. RESULTS: Thirty patients had an ECHO that was positive and underwent immediate SPW. One patient with an initially negative ECHO deteriorated 5 hours after admission; a repeat ECHO was positive, and he also underwent SPW. In 16 of the 31 SPW performed, blood in the pericardial sac was confirmed. Of these 16, four had pericardial blood that cleared with irrigation and required no further intervention. The remaining 12 patients underwent exploration: 3 had injury to the pericardium only, 4 had injury to the right atrium, 3 had injury to the right ventricle, and 2 had injury to the left ventricle. All nine myocardial injuries required operative repair; all survived. CONCLUSIONS: Using the protocol of early ECHO and selective pericardial window, no clinically significant injuries were missed. In all, 12 penetrating cardiac injuries were identified and repaired successfully. We have found early and aggressive work-up, as outlined herein, to be helpful in the successful treatment of occult cardiac injuries.

Adolescent↗

Factor V Leiden gene mutation and thrombin generation in relation to the development of acute stroke.

To determine the prevalence of the factor V Leiden gene mutation in relation to the phenotypes of cerebral infarction and cerebral hemorrhage, we studied 386 randomly selected cases of acute stroke and 247 control subjects. Factor V genotype was determined by amplification of a 267-bp sequence of exon/intron 10 of the factor V gene. Levels of prothrombin fragment F(1 + 2), a marker of thrombin generation, were determined in both acute and convalescent stroke and related to factor V genotype. Prothrombin fragment F(1 + 2) was assessed by using an enzyme-linked immunosorbent assay. Sixteen stroke cases (4.1%) were identified as having the mutation compared with 14 (5.6%) control subjects. Prothrombin fragment F(1 + 2) levels were estimated in 191 cases and found to be elevated both acutely and after 3 months, but they were not related to factor V genotype. Prothrombin fragment F(1 + 2) is elevated in acute stroke and requires further evaluation in relation to cerebrovascular disease. These results suggest that the factor V Leiden gene mutation is not a risk factor for arterial thrombosis causing stroke.

Base Sequence↗

The role of the immune system in anti-tumour responses. Potential for drug therapy.

In the last 5 years significant progress has been made in our understanding of the molecular nature of anti-tumour T cell-mediated responses. This review describes the involvement of the cellular immune system in the recognition and destruction of cancer cells. Four aspects are discussed: (i) the generalized immune activation induced by the systemic administration of cytokines, in particular, interleukin-2; (ii) the specific T cell-mediated reactions against tumour cells through the recognition of tumour-associated molecules, 1) and tyrosinase proteins described in melanomas, and minor histocompatibility antigens in the setting of allogenic bone marrow transplantation for leukaemia; (iii) the potentially significant but still hypothetical immune-mediated recognition of molecules either tumour-associated or transformation-related (including altered oncogenic proteins); and (iv) the role of co-stimulatory molecules in the induction of tumour-specific immunity. The current and future therapeutic applications in cancer treatment and potential limitations in this approach are discussed.

Animals↗

The role of shoes in the prevention of ankle sprains.

Ankle sprains are a common sports injury that can cause significant, chronic disability. Studies aimed at prevention through the use of footwear have focused on the biomechanical aspects of foot and ankle anatomy, proprioceptive input of the foot/ankle complex, external stresses applied to the joint, and shoe traction. These studies support the use of high top shoes for ankle sprain prevention because of their ability to limit extreme ranges of motion, provide additional proprioceptive input and decrease external joint stress. Despite this biomechanical evidence, clinical trials are inconclusive as to the clinical benefit of high top shoes in the prevention of ankle sprains. Further study is necessary to delineate the benefits of shoe designs for ankle sprain prevention.

Ankle Injuries↗

Endogenous endophthalmitis simulating retinoblastoma. The 1993 David and Mary Seslen Endowment Lecture.

BACKGROUND: Among conditions that can simulate retinoblastoma, endogenous endophthalmitis is quite rare. METHODS: Case records of six children with unusual forms of endogenous endophthalmitis, all of whom were referred to the authors because retinoblastoma was a strong diagnostic consideration, were reviewed. The clinical features that may help differentiate atypical endophthalmitis from retinoblastoma were investigated. RESULTS: The final diagnosis in these cases included idiopathic subretinal abscess, streptococcal endophthalmitis, idiopathic retinovitreal abscess, cytomegalovirus endophthalmitis, Candida endophthalmitis, and meningococcal endophthalmitis. All of the affected children presented primarily with ocular findings without serious systemic infection. Although these conditions closely simulated retinoblastoma, they were more likely to have signs of concurrent or prior inflammation. CONCLUSION: Differentiation between infectious conditions and retinoblastoma can sometimes be difficult, but clues as to the diagnosis can be obtained from careful clinical examination.

Abscess↗