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Biomedical subjects

J O'Connor

Publications and source records attributed to J O'Connor.

At least 19 recordsLinked to original sources
PubMed1992

Proton magnetic resonance spectroscopic imaging for metabolic characterization of demyelinating plaques.

We used proton magnetic resonance (MR) spectroscopic imaging to determine the serial changes in MR signals from choline, creatine, lactate, and N-acetylaspartate in and around a large demyelinating lesion followed over a period of 8 months. Elevated lactate and choline signals were observed at the first examination 3 days after the onset of symptoms. Reduced N-acetylaspartate signals were observed a few days afterward. The abnormal metabolite signals varied in different regions of the lesion and extended beyond the borders of abnormal signal intensity seen on conventional MR imaging (MRI). On the last examination at 8 months when the lesion appeared much smaller on MRI, choline signals from the center of the lesion were still high, but were falling. Choline signals outside the lesion on MRI had returned to normal as had lactate signals everywhere. Importantly, there was no recovery of N-acetylaspartate signals in or adjacent to the lesion on MRI. This serial study demonstrates the potential of MR spectroscopic imaging for characterizing the chemical pathological evolution of demyelinating lesions in ways that conventional MRI cannot. We propose that abnormal signals from choline can indicate recent regional demyelination, while persistent abnormal signals from N-acetylaspartate can provide an index of irreversible damage in the nervous system.

Acute Disease↗
PubMed1992

Sequence homology and absence of mRNA defines a possible pseudogene member of the Trypanosoma cruzi gp85/sialidase multigene family.

A genomic clone, pTt21, containing DNA apparently transcribed specifically in Trypanosoma cruzi trypomastigotes, was obtained by differentially screening a genomic library with trypomastigote and epimastigote cDNA. This 3444-bp clone contained open reading frames at each end, separated by a 1.8-kb non-coding region. The translated polypeptide from the 3' open reading frame (ORF2) of 1037 bp had 25-30% identity with 5 recently published T. cruzi gp85/sialidase sequences, and 20-25% identity with bacterial sialidases. Rabbit antiserum raised against an Escherichia coli fusion protein derived from the 5' open reading frame (ORF1) identified a surface antigen of 160 kDa, specifically expressed in trypomastigotes. A probe containing the first 211 bp from ORF1 was used to obtain a complete copy (c1821) of a gene that was closely related to ORF1, and encoded another member of the gp85/sialidase family. c1821 encodes a protein of 897 amino acids, but assignment of the N-terminus of the polypeptide was not possible. The 5'-most start codon is an unfavourable context to act as a translation initiator, it does not align with the initiator methionines of other gp85/sialidase sequences, nor is it followed by a signal peptide sequence characteristically found in other gp85/sialidase sequences. Although homology with the 5' ends of other gp85/sialidase sequences decays towards the 5' end of c1821, alignment of c1821 with 4 other gp85/sialidases indicated that the coding sequence should extend upstream at least 160 amino acids. In this region of c1821 there are multiple stop codons in each frame. The presence of the stop codons, the alignment data and our inability to amplify reverse transcribed mRNA using four internal primers, suggest that c1821 may not be present as a mature mRNA and is a pseudogene. Comparison of the apparently non-repetitive 3' coding domain of c1821 with the corresponding repetitive domains of two other members of the gp85/sialidase family revealed a high degree of similarity in nucleotide but not in amino acid sequence, and c1821 may thus represent an evolutionary intermediate between sub-families of the gp85/sialidase superfamily.

Amino Acid Sequence↗
PubMed1992

Drug education: an appraisal of a popular preventive.

Drug education is a popular preventive. In this paper, school-based drug education programs as currently conceived and implemented are critically appraised. The evidence indicates that while such education influences knowledge and attitudes, it has little impact on behavior. It is contended that in most drug education programs the value and meaning of being a drug user is misunderstood and the benefits of drug use underestimated. It is argued that existing health promotion models have in the main failed to adopt a systemic approach to drug use and have focused too much attention on individual change at the expense of a broader social understanding of behavior. It is proposed that with regard to illicit drugs, future educational endeavors should take the form of training in "low(er) risk" drug use within a harm-reduction paradigm, and that with regard to alcohol, such strategies need to be augmented by social and legislative changes. It is concluded that if a harm-reduction and systemic approach is adopted, then education will lose some of its popularity, since such an endeavor will be a more challenging, politically difficult, and socially complex enterprise.

Adolescent↗
PubMed1992

The anterior cruciate ligament in knee arthroplasty. A risk-factor with unconstrained meniscal prostheses.

Three hundred one unconstrained meniscal arthroplasties were observed for as long as nine years, during which time 25 (8.3%) failed. Risk factors were sought by comparing the distributions of several preoperative variables in the group that failed with the group that was successful. Age, weight, the magnitude or direction of preoperative deformity, and the presence of postoperative malalignment were all without effect on the outcome of the operations. Knees with rheumatoid arthritis had a 95% survival rate at six years. Knees with osteoarthrosis had an equivalent survival rate of 83%. Knees in which the anterior cruciate ligament (ACL) was normal had a survival rate of 95% at six years; those in which the ligament was damaged or absent had an equivalent survival rate of 81%. Successful reconstruction of a knee with an unconstrained meniscal implant requires the presence and the preservation of an intact ACL.

Actuarial Analysis↗
PubMed1991

Aluminum alters calcium influx and efflux from bone in vitro.

Aluminum retention can cause osteomalacia and adynamic lesions of bone in patients undergoing long-term dialysis. It is not known, however, whether aluminum inhibits the mineralization of bone directly or whether alterations in osteoblastic function mediate this response. To examine this issue, the uptake of 45Ca by 14-day embryonic chick calvaria was measured in vitro. Comparative studies were done in living and devitalized tissues to evaluate the role of bone cells in aluminum-related changes in 45Ca uptake. Aluminum was added to serum-free media as the citrate complex, and paired hemicalvaria maintained in equimolar sodium citrate served as controls. Aluminum citrate decreased the uptake of 45Ca into bone during 24 hour incubations to 76 +/- 3% and 38 +/- 2% (x +/- SD) of control values at 10 microM and 100 microM aluminum, respectively. No change in 45Ca uptake was observed at the end of four hour incubations with 100 microM aluminum citrate, whereas 45Ca uptake decreased from 356 +/- 48 to 266 +/- 36 cpm/micrograms bone, P less than 0.05, at eight hours and from 327 +/- 22 to 269 +/- 41 cpm/micrograms bone, P less than 0.05, at 24 hours. The inhibitory effects of 10 microM and 100 microM aluminum on 45Ca uptake were eliminated, however, in devitalized tissues, and reductions in 45Ca uptake during incubations with aluminum were markedly attenuated by lowering the media phosphorus level from 4.0 mM to 2.0 mM.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗
PubMed1991

Development and characterization of a new, highly specific antibody to the human chorionic gonadotropin-beta fragment.

In addition to high concentrations of hCG, pregnancy urine contains even higher concentrations of a fragment of the hCG beta-subunit. This biologically inactive material complicates immunological measurement of hCG, since it cross-reacts with many polyclonal and monoclonal antibodies to the hCG beta-subunit that are employed for assays of hCG in urine. Although we and others have developed antibodies to this fragment, specific measurement of the fragment in the presence of free hCG beta has remained difficult due to intrinsic cross-reactivity of these antibodies with the intact hCG beta. Rather than attempt to increase specificity by assay optimization, we developed a new, highly specific monoclonal antibody, designated B210, which cross-reacts less than 0.1% with the free hCG beta-subunit in both liquid and solid phase immunoassay formats. We have used this new monoclonal antibody in immunoradiometric assays to measure specifically the hCG beta fragment in urine throughout pregnancy as well as in the sera of two individuals with cancers producing the hCG beta-subunit. We discovered that the hCG beta fragment can bind three monoclonal antibodies simultaneously, indicating that although the epitope for antibody B210 is a new determinant exposed on the hCG beta fragment and not on intact hCG or on free hCG beta-subunit, the hCG beta fragment retains at least two other hCG beta-related epitopes intact, i.e. those that bind monoclonal antibodies B108 and B201.

Antibodies, Monoclonal↗
PubMed1991

The heterogeneity of human chorionic gonadotropin (hCG). III. The occurrence and biological and immunological activities of nicked hCG.

Nicks, or missing peptide linkages, have been found in hCG beta-subunit between residues 44 and 45 and between residues 47 and 48. We examined the occurrence and biological and immunological activities of nicked hCG. As shown by sequence analysis, CR127 standard hCG is approximately 20% nicked, half at beta 44-45 and half at beta 47-48. Treatment with human leukocyte elastase increased the extent of nicking of CR127 standard hCG. The longer the incubation of CR127 standard with human leukocyte elastase (0, 2, and 21 h), the greater the extent of nicked hCG (20%, 46%, and 89%). As the extent of nicking increased, the receptor-binding ability diminished, as did the ability to stimulate progesterone production by rat corpus luteal cells in vitro (0.9, 0.74, and 0.29 microgram/microgram hCG, respectively). In a regression analysis, a linear relationship was indicated between the extent of nicking and receptor binding values (97% correlation) and between the extent of nicking and steroidogenic activity in vitro (99% correlation). From the intercepts of the regression lines, it was estimated that nicks reduced receptor binding by 11-fold and reduced the steroidogenic activity of hCG by 5-fold. We examined eight individual hCG preparations, three purified from pregnancy urine, three from urine from patients with hydatidiform mole, and two from urine from women with choriocarcinoma. In descending order, the eight individual hCG preparations were 100%, 100%, 85%, 76%, 42%, 41%, 0%, and 0% intact. Although no correlation was observed between the percent intact and the ability of the eight individual samples to displace 50% [125I]hCG in binding CG/LH receptor (r less than 0.5), a close correlation was noted between the percent intact and the steroidogenic activity in vitro (98% correlation). This separated the effects of nicking on receptor binding and steroidogenic activities and indicated that while multiple factors influence receptor binding, only nicking suppresses the steroidogenic activity of bound hCG. We examined the recognition of nicked hCG molecules by different hCG immunoassays. The Hybritech Tandem assay measured total hCG and did not distinguish nicked and intact hCG molecules (in a regression analysis, immunoactivity vs. percent intact hCG, r less than 0.5). In contrast, the immunometric assay using B109 hCG dimer-specific monoclonal antibody and anti-beta-peroxidase only detected the intact component of hCG (in a regression analysis, immunoreactivity vs. percent intact hCG, 98% correlation). We used these assays together to estimate the percentage of intact hCG and to deduce the extent of nicking.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1991

Soldier performance and mood states following a strenuous road march.

Eighty-nine soldiers performed a maximal effort 20-km road march, carrying a total load of 46 kg. Compared to pre-march values, post-march marksmanship accuracy decreased 26% for number of target hits and 33% for distance from the centroid of the target. Maximal grenade throw distance decreased 9%, but there was no change in maximal vertical jump height. The Profile of Mood States questionnaire revealed an 82% increase in self-reported fatigue and 38% decrease in vigor. Significant decrements in some aspects of military performance occur when soldiers march rapidly with heavy loads over long distances.

Affect↗
PubMed1990

Bacteraemia--a New York perception.

Positive blood cultures (in total 7541) obtained from patients of varied social background in a New York medical centre between 1984 and 1989 are reviewed. Streptococcus pneumoniae predominated in community-acquired infections, and coagulase-negative staphylococci and Staphylococcus aureus in nosocomial infections, the latter often arising from intravenous lines. The reported trend towards Gram-positive isolates is confirmed in this series.

Cross Infection↗
PubMed1990

The use of D-Dimer assay by enzyme immunoassay and latex agglutination techniques in the diagnosis of deep vein thrombosis.

The blood of 107 patients undergoing venography for suspected deep vein thrombosis (DVT) was tested for D-Dimers using enzyme immunoassay (EIA) and two latex agglutination techniques. D-Dimer levels by EIA were raised in 88% of patients with proven DVT. However, levels detected with the two agglutination tests were much less sensitive, being raised in only 43% patients with DVT. A more sensitive rapid screening test is needed to provide a useful non-invasive test for the exclusion of DVT.

Adolescent↗
PubMed1990

Narcotic addiction: the expectant mother and her baby.

In a retrospective study of the period 1982-1985, the records of 29 narcotic-addicted mothers and their 42 babies were reviewed. All mothers were from socially deprived backgrounds, had a poor record of ante-natal attendance and had frequent admissions to hospital. Thirteen mothers had a past history of hepatitis B and four were HBsAg positive. The babies had significantly lower mean gestational age and mean birth weight than the control group. Features of withdrawal were recorded in 84% of babies where a history was available. A high incidence of twins (10.5%) was also observed. Testing for HIV antibody in more recent cases has revealed positive results in seven mothers and three babies; one infant has since died from acquired immune deficiency syndrome.

Adolescent↗
PubMed1989

Second opinions.

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Referral and Consultation↗
PubMed1989

Reliability of the Cobb angle index derived by traditional and computer assisted methods.

The reliability of the traditional Cobb angle index, which at present exhibits a wide range of reported values, was determined in this study and amounted to a within subject error of +/-4.3 degrees and a between subject error of +/-4.9 degrees. An attempt to pinpoint the source of this variability by investigating the influence of choice of end vertebrae proved inconclusive. The reliability of a computer assisted Cobb angle index, developed to improve measurement accuracy, was also examined and an estimated within subject error of +/-1.5 degrees and a between subject error of +/-1.6 degrees obtained. A comparison of the traditional and computer assisted methods indicates a high correlation between the Cobb angle derived using the two methods when measuring like curves and an improved reliability obtained by the computer method. Such an improvement is worth implementing clinically but of course the availability of a computer and digitizer and a little extra time for an operator to input the X-ray coordinates may be a barrier to its general use.

Diagnostic Errors↗
PubMed1989

Children's ability to make probability estimates: skills revealed through application of Anderson's functional measurement methodology.

Functional measurement methodology was used to assess children's attention to the total number of alternative outcomes as well as the number of target outcomes when making probability estimates. In Study 1, first-, third-, and fifth-grade children were given the task of estimating on a simple, continuous but nonnumeric scale the probability of drawing a particular color of jelly bean from a bag containing either 1, 2, or 3 jelly beans of that color, and either 6, 8, or 10 jelly beans total. In Study 2, first- through fifth-grade children were given the task of estimating the likelihood that a bug would fall on a pot containing a flower when presented displays of planters containing either 2, 3, 4, or 5 pots with flowers, and 6, 8, or 10 pots total. In both studies, the children were exposed to each of the combinations of numerator and denominator across 3 replications. The results indicate that all age groups attend to variations in the denominator as well as to variations in the numerator, and, furthermore, that they attend to the interaction between these variables. This finding contrasts sharply with research that requires children to choose which of 2 containers offers the greater chance of yielding a target item in a blind draw. It is suggested that children possess the skill to make accurate probability estimates, but they are unaware that these estimates should always be made and used when comparing the probability of an event across trials. The findings are discussed in relation to the broader issue of the limitations of the choice paradigm as a means of investigating children's thinking.

Attention↗
PubMed1988

Prospective comparison of double contrast barium enema plus flexible sigmoidoscopy v colonoscopy in rectal bleeding: barium enema v colonoscopy in rectal bleeding.

Rectal bleeding often heralds serious colonic disease. The literature suggests that colonoscopy is superior to barium enema plus sigmoidoscopy, although no good comparative studies exist. Seventy one patients with overt rectal bleeding had prospectively flexible sigmoidoscopy, double contrast barium enema and colonoscopy completed independently. Against the gold standard, the sensitivity and specificity of colonoscopy were 0.69 and 0.78 respectively for a spectrum of colonic lesions, while for combined flexible sigmoidoscopy and double contrast barium enema these values were 0.80 and 0.56, respectively. When assessing adenoma or carcinoma, colonoscopy was more sensitive at 0.82 v 0.73, while flexible sigmoidoscopy plus double contrast barium enema was superior for detecting diverticular disease. The positive predictive value for colonoscopy was 0.87 against 0.81 for flexible sigmoidoscopy and double contrast barium enema. This study confirms that colonoscopy should be a first line investigation in subjects likely to require biopsy or therapeutic intervention.

Barium Sulfate↗
PubMed1988

Preparation and characterization of antibodies to the urinary fragment of the human chorionic gonadotropin beta-subunit.

hCG is a glycoprotein hormone composed of two dissimilar subunits (alpha and beta) and is normally synthesized by trophoblastic tissue. Its measurement by immunoassay is widely employed as a test for pregnancy, but can be complicated by cross-reactivity with human (h) LH. Immunoassays based on the beta-subunit of hCG have been employed to decrease this cross-reactivity with hLH, but when these assays are used with urine specimens, the antibodies employed also detect a fragment of hCG beta, which can lead to significant differences in measurement. To overcome these problems, we have developed a series of monoclonal antibodies to the beta fragment of hCG recovered from pregnancy urine. Some of the antibodies that bind to this beta fragment are directed to a region of hCG beta that is different from the epitopes recognized by antibodies raised against the intact beta-subunit. The new epitopes available in the hCG beta fragment form the basis for novel immunoassays. These beta fragment antibodies are used in conjunction with other antibodies, directed to different epitopes of the hormone, to produce a series of immunoradiometric assays that can discriminate among intact hormone, free hCG beta, and hCG beta fragment. The hCG beta fragment antibodies described herein have affinities between 10(9) and 10(11) M-1 for the beta fragment and exhibit varying degrees of discrimination between the hCG beta fragment, the beta-subunits of hCG and hLH, and intact hCG and hLH.

Animals↗