Biomedical subjects
T A O'Brien
Publications and source records attributed to T A O'Brien.
Ischemia induces a selective biphasic response in brain mitochondrial mRNA levels.
We determined the independent effects of hypoxia, glucose deprivation and ischemia (hypoxia plus glucose deprivation) on steady-state levels of mRNA coding for specific nuclear and mitochondrially encoded enzymes of oxidative metabolism in cultured rat neurons and glia. Neither hypoxia nor low glucose alone changed steady-state message levels for any transcript. However, ischemia induced a biphasic effect on mitochondrially encoded transcripts for cytochrome oxidase subunit two (CO2) and the subunits 8 and 6 of ATPase (A 8/6), initially decreasing and then increasing mRNA levels to or above the levels recorded prior to ischemia. In contrast, three nuclear encoded transcripts for mitochondrial proteins were decreased by ischemia. These data demonstrate a lack of coordination between the expression of nuclear and mitochondrial genes in the initial response to ischemia and suggest that a selective, primary reaction to brain cell insults exists within the mitochondrion.
Liver function in early Lyme disease.
To evaluate the frequency, pattern, and severity of liver function test abnormalities in patients with Lyme disease associated with erythema migrans (EM), 115 individuals with no other identifiable cause for liver function test abnormalities who presented with EM between July 1990 and September 1993 were prospectively evaluated. For individuals with abnormal liver function tests, common causes of hepatitis, including hepatitis A, B, and C, were excluded. A local control group was used for comparison. Forty-six (40%) patients had at least one liver test abnormality, and 31 (27%) had more than 1 abnormality compared with 19 (19%) and 4 (4%) of controls, respectively (P < .01 for each comparison). gamma-Glutamyl transpeptidase (28%) and alanine transaminase (ALT) (27%) were the most frequently elevated liver function tests among Lyme disease patients. Anorexia, nausea, or vomiting was reported by 30% of patients, but did not occur more frequently in patients with elevated liver function tests compared with those with normal values. Patients with early disseminated Lyme disease were more likely to have elevated liver function studies (66%) compared with patients with localized disease (34%) (P = .002). After antibiotic treatment, elevated liver function tests improved or resolved in most patients. Liver function test abnormalities are common in patients with EM but were mild, most often not associated with symptoms, and improved or resolved by 3 weeks after the onset of antibiotic therapy in most patients.
Seroprevalence of human immunodeficiency virus-1, hepatitis B virus, and hepatitis C virus in patients having major surgery.
OBJECTIVE: To determine the proportion of major surgical procedures that involve patients having serologic evidence of infection with human immunodeficiency virus-1 (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) in a single center in Westchester County, New York. METHODS: Blood samples sent for transfusion screening or cross-match were tested blindly for HIV antibody (anti-HIV), HBV core antibody, HBV surface antigen (HBsAg), and HCV antibody (anti-HCV). Demographic characteristics and operation category were correlated with serologic results by univariate and regression analyses. RESULTS: Of 1,062 operations evaluated, 71 (6.7%, 95% confidence interval [CI95], 5.2% to 8.4%) were performed on patients with either anti-HIV, HBsAg, or anti-HCV. In 17 (1.6%, CI95, .93% to 2.5%) of these operations, the patient evidenced anti-HIV; in 15 (1.4%; CI95, .79% to 2.3%), HBsAg; and in 55 (5.2%, CI95, 3.9% to 6.7%), anti-HCV. Anti-HCV was detected significantly more often than anti-HIV (5.2% versus 1.6%, P < .001) or HBsAg (5.2% versus 1.4%, P < .001). Operations involving women aged 25 to 44 years had the highest proportion with serologic evidence of at least one of the three viruses (17.2%); of anti-HCV (15.3%); and of anti-HIV (6.7%). Logistic regression analysis found that being in the 25- to 44-year age group was associated significantly with infection with any virus (P < .001) and with anti-HCV (P < .001). The strongest logistic predictors of anti-HIV seropositivity were having anti-HCV seropositivity (P < .001), being age 25 to 44 years (P < .001), and having a general surgery operation (P = .002). CONCLUSION: The prevalences of serologic evidence of at least one of the three viruses (16.7%), of anti-HCV (14.5%), and of anti-HIV (5.6%) are high in patients aged 25 to 44 years undergoing major surgery at a tertiary-care medical center located in Westchester County, New York. Anti-HCV is more prevalent than anti-HIV or HBsAg and is predictive of anti-HIV seropositivity. Testing for anti-HIV alone would have detected only 24% of patients infected with a bloodborne pathogen. These data strongly underscore the importance of universal precautions.
A one year analysis of appeals made to mental health review tribunals in New Zealand.
OBJECTIVES: The aim of the paper is to present data on the first year of all appeals lodged with a Mental Health Review Tribunal against compulsory treatment orders of psychiatric inpatients. METHOD: Two tribunals have been in operation in New Zealand since the introduction of a new Mental Health (Compulsory Assessment and Treatment) Act in 1992. The case records of all patients who had appeals heard by either the Northern or Southern regional tribunal from 16/12/92 to 7/12/93 inclusive were examined. RESULTS: 145 appeals were heard by the tribunals: 14.5% of appeal hearings resulted in the discharge of a patient from their compulsory treatment status. Discharge rates for the Southern Tribunal were found to be significantly higher at 22%, compared with 10% for the Northern Tribunal (p < 0.05). Application for appeal was initiated by the patient in 72% of cases; District Inspectors initiated the remaining cases. District Inspectors were found to initiate significantly more female review applications (47%) than male applications (22%) (p < 0.05). Of the appeals heard, 126 were lodged under s.79 of the Mental Health Act. The remaining cases were s.80 (special) cases: in no case was discharge from compulsory treatment recommended. Overall, 69% of appellants were represented by a lawyer. It was found however that engaging legal representation did not significantly increase patients' chances of successful discharge but did delay the hearings. Also considered in the study were the presence or absence of witnesses at hearings and the relationship this had to the outcome of the tribunal hearing. CONCLUSIONS: Ambiguities within the Act need to be addressed in order that criteria used to judge a patient's fitness for discharge may be standardised. In addition, the Act stipulates a maximum delay of 14 days in reviewing a patient's case; however in practice a mean of 22 days elapses, indicating that this stipulation requires review.
Hepatitis C in the health care setting. II. Seroprevalence among hemodialysis staff and patients in suburban New York City.
BACKGROUND: Hepatitis C virus (HCV) is a newly identified blood-borne virus that may pose an occupational hazard for health care workers. Hemodialysis nurses could be anticipated to be at high risk for HCV infection because this group of health care workers frequently comes into contact with blood of a patient population with a seroprevalence rate of at least 10%. METHODS: To assess the risk of HCV infection for hemodialysis nurses, serum samples from all of the nurses (22/22, 100%) and patients (125/125, 100%) in one hemodialysis unit (unit A) and 85% (29/34) of nurses from a second unit (unit B), both units in suburban New York City, were tested for HCV antibodies. Samples with positive results of enzyme-linked immunosorbent assay underwent supplemental testing by a first-generation recombinant immunoblot assay. RESULTS: Twenty-four (19%) of the hemodialysis patients in unit A were HCV seropositive. Despite an average of 4.7 years spent working in hemodialysis unit A, none of the nurses tested seropositive for HCV antibody. In unit B, despite an average of 6.4 years working in the unit studied, only one nurse tested seropositive for HCV antibody. This nurse reported a long history of elevated liver function values and a negative HBV core antibody status that predated her hemodialysis nursing career. CONCLUSIONS: In contrast to the experience with hepatitis B virus infection, hemodialysis nurses appear to be at low risk for occupationally acquired HCV infection.
Hepatitis C virus seroprevalence in the developmentally disabled.
BACKGROUND: Hepatitis C virus (HCV) is the principal cause of nonenteric non-A, non-B hepatitis worldwide. While it has been well documented that people with developmental disabilities are at an increased risk for infections with hepatitis B virus, little is known of the prevalence of HCV infection among this population. METHODS: Serum samples obtained from 113 evaluable outpatients with developmental disabilities at one center in suburban New York City (NY) were tested for antibodies to HCV and hepatitis B core antibody. RESULTS: None of the 113 samples tested positive for HCV antibody by enzyme-linked immunosorbent assay, whereas 24 (21%) showed serologic evidence of past hepatitis B virus infection on the basis of hepatitis B core antibody positivity. Three (2.7%) were also positive for hepatitis B surface antigen. CONCLUSIONS: In contrast to hepatitis B virus, HCV infection is uncommon among outpatients with developmental disabilities in suburban New York City. Further testing for HCV is indicated to determine if these results can be generalized to individuals within institutions, or to individuals in other geographic locations.
Hepatitis C in HIV-infected intravenous drug users and homosexual men in suburban New York City.
Explore the source record for details and available documents.
Hepatitis C infection in the health care setting. I. Low risk from parenteral exposure to blood of human immunodeficiency virus-infected patients.
Many patients with human immunodeficiency virus (HIV) infection have also been infected with hepatitis C virus (HCV). To understand better the epidemiology of HCV infection in the health care setting, HCV antibody testing was done for 125 health care workers who had experienced parenteral exposures to blood of HIV-infected patients and for 33 control health care workers without such exposures. Of the 158 health care workers studied, two (1.3%) had positive tests for HCV, both on the baseline serum sample obtained at parenteral exposure. For the 98 exposed, seronegative health care workers who were prospectively followed, no HCV seroconversions were observed over a time of 17.6 +/- 16.9 months. At least 64 of these 98 health care workers were exposed to blood of HIV-infected intravenous drug users, a group with an HCV seroprevalence rate in excess of 50% at our center in suburban New York City. We conclude that parenteral exposure to blood of HIV-infected patients in the health care setting is rarely associated with the development of hepatitis C infection.
Human immunodeficiency virus type 1 reference materials.
Since licensure of the first human immunodeficiency virus type 1 screening assay in March 1985, there has been a need for well-characterized human immunodeficiency virus type 1 reference sera. These sera would be used in an effort to ensure uniformity of human immunodeficiency virus type 1 test results worldwide. Three major organizations--the World Health Organization, the Pan American Health Organization, and the National Committee for Clinical Laboratory Standards working with the College of American Pathologists--have ongoing programs aimed at the preparation of these reference sera. All three organizations are preparing both negative and human immunodeficiency virus type 1 seropositive sera. In addition, one organization is preparing early sero-converter and late acquired immunodeficiency syndrome samples. The status of these efforts and the serologic characteristics of the sera were reviewed.
HIV testing: an overview of current technology.
Explore the source record for details and available documents.
Prognostic importance of antibodies to human immunodeficiency virus by recombinant immunoassay and Western blot techniques in HIV antibody-positive hemophiliacs.
Antibodies to specific HIV viral antigens were measured by ELISA recombinant proteins representing gag and env amino acid sequences of human immunodeficiency virus (HIV) (E. I. du Pont de Nemours, Wilmington, DE) and by a Western blot system using biotinavidin detection (Biotech Research Labs, Rockville, MD) on 36 HIV antibody-positive hemophiliacs (HTLV-III ELISA, du Pont) on whom date of seroconversion was known and on whom serial samples where available between 1977 and 1986, representing 2-8 years following seroconversion. The 36 included 9 acquired immunodeficiency syndrome (AIDS) and 27 non-AIDS (7 AIDS-related complex (ARC); 4 other HIV class IV, 16 asymptomatic) patients. The development of AIDS was preceded 1-4 years by loss or lack of antibody to gag (p15, 24, or 55) and/or to pol (p31, 53, or 64), each p less than 0.001, compared with non-AIDS patients. Correlation between Western blot and recombinant assays was good except in one Western blot p24 (gag) only seroconverter who showed strong reactivity to env by recombinant assay. In conclusion, HIV antibody patterns appear to show prognostic significance in HIV-infected hemophiliacs.
Course, prognosis and complications of childhood-onset myotonic dystrophy.
The outcome for 71 patients with childhood-onset myotonic dystrophy was examined. In addition to 18 patients with later onset, but presenting in childhood, and 46 with the congenital form, seven patients from congenital sibships who did not present in the neonatal period were found to have myotonic dystrophy of intermediate severity. The incidence of the congenital form in South Wales was six per 100,000. In all groups the mortality rate was low after the perinatal period. The prognosis for normal family life and ultimate gainful employment was poor. Testicular atrophy in congenitally affected males was evident at puberty, and there was a high incidence of gastro-intestinal problems. The contributions of deafness as a result of recurrent otitis, and of severe articulation defects, should be considered when assessing the degree of mental handicap.
Role of the divalent metal cation in the pyruvate oxidase reaction.
Purified pyruvate oxidase requires a divalent metal cation for enzymatic activity. The function of the divalent metal cation was studied for unactivated, dodecyl sulfate-activated, and phosphatidylglycerol-activated oxidase. Assays performed in the presence of Mg2+, CA2+, Zn2+, Mn2+, Ba2+, Ni2+, Co2+, Cu2+, and Cr3+ in each of four different buffers, phosphate, 1,4-piperazinediethanesulfonic acid, imidazole, and citrate, indicate that any of these metal cations will fulfill the pyruvate oxidase requirement. Extensive steady state kinetics data were obtained with both Mg2+ and Mn2+. All the data are consistent with the proposition that the only role of the metal is to bind to the cofactor thiamin pyrophosphate (TPP) and that it is the Me2+-TPP complex which is the true cofactor. Values of the Mg2+ and Mn2+ dissociation constants with TPP were determined by EPR spectroscopy and these data were used to calculate the Michaelis constant for the Me2+-TPP complexes. The results show that the Michaelis constants for the Me2+-TPP complexes are independent of the metal cation in the complex. Fluorescence quenching experiments show that the Michaelis constant is equal to the dissociation constant of the Mn2+-TPP complex with the enzyme. It was also shown that Mn2+ will only bind to the enzyme in the presence of TPP and that one Mn2+ binds per subunit. Steady state kinetics experiments with Mn2+ were more complicated than those obtained with Mg2+ because of the formation of an abortive Mn2+-pyruvate complex. Both EPR and steady state kinetics data indicated complex formation with a dissociation constant of about 70 mM.
Conformational studies of Escherichia coli pyruvate oxidase.
Pyruvate oxidase (pyruvate:oxygen oxidoreductase (phosphorylating), EC 1.2.3.3) is a peripheral membrane enzyme from Escherichia coli which utilizes the cofactors thiamin pyrophosphate (TPP) and flavin-adenine dinucleotide (FAD) to catalyze the decarboxylation of pyruvate to acetic acid and carbon dioxide. The specific activity of the oxidase is enhanced 25-fold when assayed in the presence of certain lipids and detergents. Previous studies have demonstrated that the affinity of pyruvate oxidase for phospholipids and detergents is substantially increased when the flavin is reduced. In this paper, several techniques are utilized to probe both the nature of the active site and the conformational changes in the protein which are concomitant with flavin reduction and with the binding of lipids to the enzyme. Analysis of the circular dichroism spectrum in the far ultraviolet region indicates that neither the binding of lipid activators to the oxidase nor reduction of the enzyme-bound flavin by pyruvate has a significant effect on the average secondary structure of the enzyme. High-resolution electron microscopy demonstrates that at low enzyme concentrations, i.e., assay conditions, incubation of the reduced flavoprotein in the presence of an amphiphilic activator does not alter the quaternary structure of pyruvate oxidase. The results indicate that the conformational changes in the protein due either to reduction of the flavin or to the binding of lipid activators are localized.
Role of arginine in the binding of thiamin pyrophosphate to Escherichia coli pyruvate oxidase.
The mode of interaction between Escherichia coli pyruvate oxidase and its cofactor, thiamin pyrophosphate (TPP), was studied with the aid of arginine-directed reagents. The enzyme is rapidly inactivated by either phenylglyoxal or 2,3-butanedione, with the cofactor, TPP, offering partial protection against these reagents. The inactivation by phenylglyoxal was found to be reversible. Experiments with [7-14C]phenylglyoxal showed that while several arginine residues react with this reagent, TPP can prevent the labeling of one such residue. Furthermore, inactivation by 2,3-butanedione is attended by at least a 100-fold decrease in affinity of the enzyme for TPP. These results suggest a direct role for arginine in the binding of the cofactor.
Penicillin is an active-site inhibitor for four genera of bacteria.
The hypothesis that penicillin acts as an active-site inhibitor cell wall biosynthesis was tested by a method of partial proteolytic mapping of penicillin-binding sites versus substrate-binding sites in cell wall D-alanine carboxypeptidases. This enzyme was obtained from four genera of bacteria, purified, and tested.
The changing face of Reye's Syndrome.
Explore the source record for details and available documents.