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J O'Connor

Publications and source records attributed to J O'Connor.

At least 55 records · Page 3Linked to original sources
PubMed1999

Development and characterization of antibodies to a nicked and hyperglycosylated form of hCG from a choriocarcinoma patient: generation of antibodies that differentiate between pregnancy hCG and choriocarcinoma hCG.

Human chorionic gonadotropin (hCG) exists in blood and urine as a variety of isoforms one of which contains peptide bond cleavages within its beta-subunit loop 2 and is referred to as nicked hCG (hCGn). This hCG isoform appears to be more prevalent in the urine of patients with certain malignancies and possibly in some disorders of pregnancy. Until now, only indirect immunoassays could be used to quantify hCGn. We report the development of two monoclonal antibodies (MAbs) to a form of hCGn isolated from a choriocarcinoma patient. This hCG isoform was not only 100% nicked, but also contained 100% tetrasaccharide-core O-linked carbohydrate moieties in its beta COOH-terminal region. Two-site immunometric assays have been developed using these new antibodies, B151 and B152. The former exhibits good specificity for hCGn independent of the source of the hCGn, the form excreted by choriocarcinoma patients or the form of hCGn from normal pregnancies. The latter antibody, B152, is sensitive to the carbohydrate moieties and possibly other differences in hCG isoforms, but is not for nicking of the beta-subunit. These two immunometric assays provide potential novel diagnostic tools for direct measurement of hCG isoforms which could not be accurately quantified earlier before development of the assays using these newly generated antibodies.

Animals↗
PubMed1999

Relationships between maternal risk of insulin resistance and the child's muscle membrane fatty acid composition.

In adult humans, insulin resistance is associated with relatively low proportions of polyunsaturated fatty acids (PUFAs) in muscle membrane structural lipid. The aim of the present study was to determine the relationship between young children's muscle membrane fatty acid (FA) composition and indices of insulin resistance in their mothers. Muscle biopsy specimens obtained at the time of elective surgery from 83 children (54 boys), aged 0.78 +/- 0.05 year (mean +/- SE), were analyzed for phospholipid FA composition. Fasting blood samples were collected from the mothers of the children, and maternal BMIs were calculated. Stepwise multiple regression analysis showed that after accounting for the effect of breast-feeding, log maternal insulin levels were inversely associated with the child's muscle membrane docosahexaenoic acid (22:6 n-3; R2 = 0.29, P = 0.0006) and the sum of the n-3 PUFAs (R2 = 0.23, P = 0.0016) but positively associated with the sum of the n-6 PUFAs (R2 = 0.05, P = 0.03) and the n-6/n-3 PUFA ratio (R2 = 0.20, P = 0.007). Independent of breast-feeding, log maternal triglyceride levels were inversely associated with the child's muscle membrane unsaturation index (a measure of unsaturation) (R2 = 0.08, P = 0.005). Maternal BMI; total, LDL, and HDL cholesterol; and the child's age, sex, and birth weight were not significant predictors of the child's muscle membrane FA composition. Thus, maternal fasting insulin and triglyceride levels are significant predictors of the FA composition of the child's muscle membrane. The less unsaturated muscle membranes in children whose mothers have higher fasting insulin and triglyceride levels may reflect a genetic reluctance to incorporate PUFAs into membranes, thus predisposing them to insulin resistance syndromes.

Adult↗
PubMed1999

Phase I/II studies of docetaxel (Taxotere) combined with estramustine in men with hormone-refractory prostate cancer.

Evaluation of the combined regimen of estramustine and docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA) in men with hormone-refractory prostate cancer is in its early stages. While this combination is promising in terms of efficacy, adverse events associated with estramustine are a concern. Estramustine has been associated with side effects such as nausea, vomiting, edema, and serious vascular events. Reported here are the results of phase I and phase II trials in which 280 mg estramustine was given three times daily on days I to 5 in 21-day treatment cycles with docetaxel at varying doses. Data from patients evaluable thus far support the efficacy of this combination, both in chemotherapeutically naive patients and in those who have had prior therapy. A survival benefit from this combination appears achievable from these early studies. As significant antitumor activity can be achieved with docetaxel alone, future studies need to define the minimal dose of estramustine for this combination.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

A versatile set of vectors for constitutive and regulated gene expression in Pichia pastoris.

The budding yeast Pichia pastoris is an attractive system for exploring certain questions in cell biology, but experimental use of this organism has been limited by a lack of convenient expression vectors. Here we describe a set of compact vectors that should allow for the expression of a wide range of endogenous or foreign genes in P. pastoris. A gene of interest is inserted into a modified pUC19 polylinker; targeted integration into the genome then results in stable and uniform expression of this gene. The utility of these vectors was illustrated by expressing the bacterial beta-glucuronidase (GUS) gene. Constitutive GUS expression was obtained with the strong GAP promoter or the moderate YPT1 promoter. The regulatable AOX1 promoter yielded very strong GUS expression in methanol-grown cells, negligible expression in glucose-grown cells, and intermediate expression in mannitol-grown cells. GenBank Accession Numbers are: pIB1, AF027958; pIB2, AF0279959; pIB3, AF027960; pIB4, AF027961.

Alcohol Oxidoreductases↗
PubMed1998

Clinical case-based multimedia tutorials as a solution to some problems facing medical education.

Medical education faces many challenges as curricula become crowded and teacher numbers fall. In addition, there are moves to reduce factual overload and to concentrate more on pathophysiological principles illustrated by relevant clinical cases. We describe one means of addressing these problems, using computer-aided learning programs which are based on clinical cases, are interactive and which incorporate multimedia elements. These CD-ROM programs include student assessments, a resource of background material and support self-managed and distance learning.

CD-ROM↗
PubMed1998

The fatty acid composition of skeletal muscle membrane phospholipid: its relationship with the type of feeding and plasma glucose levels in young children.

Long-chain polyunsaturated fatty acids (LCPUFAs), including docosahexaenoic acid ([DHA] 22:6 n-3), are important components of cell membranes. Low levels of DHA and other LCPUFAs in skeletal muscle membrane phospholipid are associated with insulin resistance and obesity in adults. These findings may be influenced by both dietary and genetic factors. This study aimed to investigate the interrelationships between the type of infant feeding, skeletal muscle phospholipid fatty acid (FA) composition, and glucoregulation in young children. Skeletal muscle biopsies and fasting blood samples were obtained from 56 normally nourished young children (35 males and 21 females) aged less than 2 years (mean +/- SE, 0.76 +/- 0.06) undergoing elective surgery. The dietary history was taken, and muscle phospholipid FA composition was analyzed. Subgroups of totally breast-fed and age-matched formula-fed infants were compared. Breast-fed infants (n = 13; age, 0.54 +/- 0.06 years) had a significantly higher percentage of DHA (3.63% +/- 0.22% v 1.84% +/- 0.11%, P < .0001) and total percentage of LCPUFAs (30.24 +/- 0.87% v 25.17% +/- 0.86, P < .0001) in muscle phospholipids compared with the formula-fed group (n = 12; age, 0.59 +/- 0.08 years). The totally breast-fed group had lower plasma glucose levels than the formula-fed group (4.7 +/- 0.2 v 5.4 +/- 0.2 mmol/L, P < .02). Consistent with these findings, further analysis of a group of 39 children who had either never or not recently been breast-fed showed significant inverse correlations between fasting plasma glucose and the percentage of both DHA (r = -.47, P < .003) and total LCPUFAs (r = -.38, P < .05). The results of this study show that (1) breast-feeding increases LCPUFA levels in skeletal muscle membrane and (2) early development of relatively higher levels of LCPUFAs in the phospholipid of skeletal muscle, influenced both by type of feeding and by genetic predisposition, is associated with lower fasting plasma glucose. Early changes in skeletal muscle membrane phospholipid FA saturation may play a role in the subsequent development of diseases associated with insulin resistance.

Biopsy↗
PubMed1998

Latex allergy and latex sensitization in children and adolescents with meningomyelocele.

BACKGROUND: The high prevalence of clinical latex allergy and latex sensitization in children with meningomyelocele has been widely reported. It has also been noted that these same children have a higher than expected prevalence of atopic disease. It would be useful to have a safe, sensitive, and specific skin test to detect latex sensitivity and to know how well this test compares with available in vitro tests. It would likewise be helpful to know as fully as possible the characteristics of the individual and to evaluate the relative importance of factors suspected to contribute to clinical latex allergy and latex sensitization in this population. METHODS: A group of 116 children and adolescents 1 to 20 years of age were recruited for the study. An extensive history of latex allergy, atopic diseases, and surgical procedures was taken on all subjects. Each subject had either a latex skin test or an in vitro study for latex-specific IgE, and 67 subjects had both tests simultaneously. Eighty-five subjects had epicutaneous skin tests to a panel of environmental allergens. RESULTS: Overall, 25 of 116 (21.5%) subjects had a history of clinical latex allergy, and 51 of 116 (44%) were sensitized to latex. The sensitivity and specificity of skin tests for clinical latex allergy were slightly greater than for the in vitro test (100% vs 95.8% and 82.3% vs 68.9%, respectively). The positive predictive value and negative predictive value of skin testing for clinical latex allergy were also greater (67.6% vs 50% and 100% vs 98.1%, respectively). Age was found to be a significant variable for both latex allergy and latex sensitization. The number of surgical procedures undergone and the presence of positive skin test responses to environmental allergens were significantly correlated with latex sensitization but not with clinical allergy to latex. CONCLUSIONS: A sensitive, specific, and safe skin test for latex sensitivity appears superior to in vitro testing for latex allergy. Age, number of surgical procedures, and the presence of positive allergen skin test responses are significantly correlated with latex sensitization. Age alone is significantly correlated with clinical allergy to latex.

Adolescent↗
PubMed1998

Oxidative damage to DNA in plaques of MS brains.

A major cause of clinical disability in multiple sclerosis (MS) is related to a degenerative process in the central nervous system (CNS) which ultimately develops from a potentially reversible inflammation and demyelination. The mechanism of this degenerative process within MS lesions is not completely understood. We hypothesize that oxidative damage to DNA secondary to inflammation may contribute to irreversible tissue alterations in a plaque. To test this assumption, we determined the level of a DNA oxidative marker, 8-hydroxy-deoxy-guanosine (8-OH-dG) in the normal appearing white matter (NAWM), plaque and cortical regions of cerebella from MS patients who suffered from severe cerebellar symptoms during the course of the disease, and in NAWM and cortical regions of cerebella from non-neurological controls. We found a significant increase in DNA oxidation within plaques compared to NAWM specimens in MS cerebella. A tendency for increase of oxidative markers in normal appearing cortical tissues located in the proximity of MS plaques was also observed when compared to those in control cortical specimens. Oxidative damage to DNA in MS lesions, and in neuron rich areas located in the proximity of these lesions is likely related to the release of reactive oxygen species (ROS) and nitric oxide (NO) during inflammation in the brain. This biochemical impairment of DNA and of other macromolecules may contribute to the development of severe clinical disability through the induction of degenerative changes within and outside of plaques in MS brains.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1998

Short-interval follow-up mammography versus immediate core biopsy of benign breast lesions: assessment of patient stress.

OBJECTIVE: The stress experienced by women undergoing surveillance mammography for benign lesions was compared with that experienced by women undergoing core biopsy of benign lesions. MATERIALS AND METHODS: A retrospective survey was mailed to women in whom were diagnosed breast abnormalities that were likely to be benign and that were stable at short-interval follow-up mammography (n = 174) or in whom a core biopsy of the breast was performed, with benign findings (n = 116). The survey included questions about stress related to the diagnostic experience as well as questions about who advised the women of the results of their breast imaging studies and about the information provided. RESULTS: Eighty eligible surveys were received from the women who underwent short-interval follow-up mammography, and 58 surveys were received from the women who underwent biopsies. The self-reported overall stress experienced by the women who underwent core biopsies was significantly greater (p < .001) than that reported by the group who were followed up with mammography. The level of anxiety was not affected by the patient's perception of the probability that the lesion represented carcinoma. We found no significant differences in stress between women who discussed their mammogram results with a radiologist and women who were notified by their primary care provider. CONCLUSION: Short-interval follow-up mammography continues to be acceptable for the evaluation of lesions that are probably benign, even when patient anxiety is considered.

Anxiety↗
PubMed1997

Multiple idiopathic arterial aneurysms in children: a case report and review of the literature.

A 6-year-old boy from China presented initially at 2 years of age with a pulsatile mass in his right antecubital fossa. He was not fully evaluated until the age of six years, when pan-angiography and computed axial tomography scan revealed multiple aneurysms of his right brachial artery, right radial artery aneurysms, an infrarenal aortic aneurysm, and a right internal carotid artery aneurysm in the region of the cavernous sinus. The patient underwent uneventful repairs of both the abdominal aortic aneurysm and the multiple aneurysms of the right arm. Pathologic evaluation was significant for medial fibrosis of the arterial wall with decreased and disordered elastin fibers. Review of the previously reported cases in children indicate the upper extremity arteries are involved in 92% of patients, the aortoiliac region in 92% of patients, and the renal/mesenteric vessels in 77% of cases. Lower extremity and cerebrovascular arteries are involved to a lesser extent. Children with peripheral aneurysms should have pan-angiography performed before treatment is begun. Surgical repair in these cases has been excellent.

Aneurysm↗
PubMed1997

Plasma leptin is partly cleared by the kidney and is elevated in hemodialysis patients.

Leptin, the gene product of the ob gene, is important in the control of appetite in rodents and may have an important role in humans. The clearance of leptin from the circulation is unknown. As the leptin receptor is present in the kidney, we evaluated the role of the kidney in removing circulating leptin in humans. We measured leptin in aortic and renal vein plasma in 8 patients with intact renal function and 6 patients with impaired renal function who were undergoing elective cardiac catheterization. Renal blood flow was measured in all patients to calculate net mass balance across the kidney. In patients with intact renal function there is net renal uptake of 12% of circulating leptin, whereas in patients with renal insufficiency there is no renal uptake of leptin. In a separate cohort of 36 patients with end-stage renal failure on hemodialysis, peripheral leptin levels factored for body mass index was increased by > fourfold as compared to a group of healthy controls (N = 338). In addition, plasma leptin is not cleared by hemodialysis with a modified cellulose membrane. Additional studies are required to evaluate the role of leptin in mediating the anorexia of uremia.

Aged↗
PubMed1997

Muscle fibre type composition in infant and adult populations and relationships with obesity.

OBJECTIVES: To investigate the fibre type composition of skeletal muscle in infants and young children and to compare the findings to an adult population. To relate the fibre type profile of skeletal muscle in adults to measures of adiposity. DESIGN: Cross-sectional studies of skeletal muscle fibre composition in infants and adults with measures of adiposity in the adults. SUBJECTS: 21 healthy infants and young children (age: 3-21 months) and 40 healthy adult Australian Caucasians (age: 26-62 y; BMI: 18-48 kg/m2). MEASUREMENTS: Skeletal muscle fibre type composition (by myosin ATPase method) and relative body fatness (BMI, waist circumference and waist/hip ratio (WHR)). RESULTS: Infants and young children had significantly lesser proportions of glycolytic Type 2b fibres (6.2 +/- 1.1%; range 0.3-18.9%) compared with adults (20.5 +/- 1.6%; range 4.9-36.0%) (p < 0.0001). The percentage of Type 2b fibres was directly related to BMI (r = 0.44, p = 0.02), waist circumference (r = 0.49, p = 0.009) and WHR (r = 0.44, p = 0.02) in adults. A significant, direct relationship was also found between the proportion of glycolytic Type 2b fibres and age in the adults (r = 0.45, p = 0.01). CONCLUSION: Skeletal muscle fibre type composition is different in infants and adults and there is an age-dependent increase in Type 2b fibres over the lifespan. An increased proportion of glycolytic Type 2b fibres is associated with obesity in adults. Results support a gene-environment interaction on fibre type composition in human skeletal muscle.

Adult↗
PubMed1996

Metabolism of hCG and hLH to multiple urinary forms.

Human chorionic gonadotropin (hCG) is synthesized primarily in the placenta while human luteinizing hormone (hLH) is produced in the pituitary. Both hormones are highly homologous in structure and both appear to be altered to analogous molecular forms as the hormones are proteolytically processed, or metabolized, from tissue of origin, through the circulation, and finally to the urine. Placental hCG is excreted into urine as heterodimeric hormone, heterodimeric nicked hCG, free subunits (some nicked), and predominantly as the hCG beta core fragment. A pituitary form of heterodimeric hCG, which is partly sulfated as is pituitary hLH, was recently isolated and is likely the form of hCG observed in the urine of healthy postmenopausal women and nonpregnant premenopausal women as well. A pituitary form of the hLH beta core fragment, highly analogous in structure to that of urinary hCG beta core fragment, has been used to develop specific monoclonal antibody assays to measure urinary hLH beta core fragment which is excreted at significantly higher molar concentrations than is hLH in the urine of ovulating women 1 or 2 days after the LH surge. This fragment of LH appears in the urine of postmenopausal women as well. The development of the capability to distinguish the hCG beta core fragment from the hLH beta core fragment in urine may have useful applications in tumor marker assays, pregnancy tests, and menopause. While hCG urinary assays have been widely employed, urinary assays for hCG and hLH metabolites are much less used since the urinary molecular forms are only partly known. Our studies of hCG and hLH urinary metabolites are directed towards improvement of the utility of urinary measurements of molecules derived from these hormones. Since many of the molecular forms of these two hormones in urine differ from their forms in blood, it may be necessary to produce new immunoassays as well as novel urinary reference preparations to accurately measure these molecules within their urinary matrix.

Chorionic Gonadotropin↗
PubMed1996

Expression, purification and initial characterization of the recombinant storage protein precursor of Theobroma cacao.

The gene encoding the 67-kDa cocoa storage protein precursor has been cloned from Theobroma cacao and expressed in Escherichia coli using the pET expression system. The recombinant storage protein has been renatured from inclusion bodies at 30 degrees C using 20 mM glycine-NaOH buffer, pH 10.0, containing 1 mM oxidized glutathione and 0.1% Brij. The renatured protein was purified and demonstrated to adopt a stable native conformation by optical spectroscopy. Secondary structure analysis from circular dichroism indicated the protein to be 23% alpha-helix and 38% beta-sheet, in close agreement with values obtained using a secondary structure prediction program.

Cacao↗
PubMed1996

Skeletal muscle membrane lipids and insulin resistance.

Skeletal muscle plays a major role in insulin-stimulated glucose disposal. This paper reviews the range of evidence in humans and experimental animals demonstrating close associations between insulin action and two major aspects of muscle morphology: fatty acid composition of the major structural lipid (phospholipid) in muscle cell membranes and relative proportions of major muscle fiber types. Work in vitro and in vivo in both rats and humans has shown that incorporation of more unsaturated fatty acids into muscle membrane phospholipid is associated with improved insulin action. As the corollary, a higher proportion of saturated fats is linked to impairment of insulin action (insulin resistance). Studies in vitro suggest a causal relationship. Among polyunsaturated fatty acids (PUFA) there is some, but not conclusive, evidence that omega-3 (n-3) PUFA may play a particular role in improving insulin action; certainly a high n-6/n-3 ratio appears deleterious. In relation to fiber type, the more highly oxidative, insulin-sensitive type 1 and type 2a fibers have a higher percentage of unsaturated fatty acids, particularly n-3, in their membrane phospholipid, compared to the insulin-resistant, glycolytic, type 2b fibers. These variables, however, can be separated and may act in synergy to modulate insulin action. It remains to establish whether lifestyle (e.g., dietary fatty acid profile and physical activity), genetic predisposition, or a combination are the prime determinants of muscle morphology (particularly membrane lipid profile) and hence insulin action.

Animals↗