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Biomedical subjects

M Mahoney

Publications and source records attributed to M Mahoney.

At least 37 records · Page 2Linked to original sources
PubMed1992

The relation between multiple births and maternal risk of breast cancer.

Data from two case-control studies conducted in New York State during 1982-1986 were used to examine the relation between multiple births and the maternal risk of breast cancer. The cases were 2,561 women between 20 and 79 years of age with a diagnosis of primary breast cancer. Controls (n = 2,616) were selected from driver's license files and matched to cases by year of birth and county of residence. The odds ratio for any multiple birth was 0.94 (95% confidence interval (CI) 0.56-1.56) in women less than 55 years of age and 0.95 (95% CI 0.62-1.46) in women aged 55-79 years. A previous study had shown a multiple last birth to be protective against breast cancer in women less than 55 years of age (odds ratio (OR) = 0.60, 95% CI 0.43-0.85). A decreased risk of breast cancer was also observed for this age group in the present study, but the magnitude of the effect was not as strong and the confidence interval included unity (OR = 0.85, 95% CI 0.43-1.68). A logistic model that controlled for age at first pregnancy, number of live births, age, and county of residence increased the odds ratio to 0.97 for a multiple last birth. The current study does not support an association between multiple births and maternal risk of breast cancer.

Adult↗
PubMed1992

Testicular epidermoid cyst--is pre-operative diagnosis possible?

A case of testicular epidermoid cyst which had initially been misdiagnosed as a malignant testicular tumour is presented. The role of clinical and ultrasound examination in the pre-operative assessment is discussed. Although the benign nature of this condition must be demonstrated histologically before conservative surgery is contemplated, it is equally important that the patient should not be told that the tumour is malignant without adequate evidence.

Adult↗
PubMed1991

The impact of injury severity and prehospital procedures on scene time in victims of major trauma.

STUDY OBJECTIVE: To evaluate the relationship among injury severity, prehospital procedures, and time spent at the scene by paramedics for victims of major trauma. DESIGN: Retrospective study of 98 consecutive patients with an Injury Severity Score of more than 15 who were brought to a trauma center by fire department paramedics. SETTING: A medium-sized metropolitan emergency medical services (EMS) system and a Level I trauma center. RESULTS: There were 66 male and 32 female patients with a mean age of 34 years. Thirty-two patients (32.6%) died. Blunt and penetrating trauma accounted for 68.4% and 31.6% of cases, respectively. Thirty-three patients (33.7%) had successful advanced airway procedures, and 81 (82.7%) had at least one IV line started in the field. Analysis of scene time, prehospital procedures, and injury severity parameters revealed that more procedures were performed in the field on the more severely injured cases; that despite this, there was a trend toward shorter scene time for more severely injured patients; and that there was a mean scene time of 8.1 minutes. This is the shortest scene time reported to date for prehospital trauma care in an EMS system. CONCLUSION: Extremely short scene times can be attained without foregoing potentially life-saving advanced life support interventions in an urban EMS system with strong medical control. In such a system, the most severely injured victims may spend less time at the scene although more procedures are performed on them.

Adolescent↗
PubMed1991

The role of the OOP antisense RNA in coliphage lambda development.

We have made a derivative of bacteriophage lambda that makes no OOP antisense RNA. The mutant phage carries a point mutation that inactivates the OOP promoter, po. The phages lambda + and lambda po- have identical plaque morphologies, one-step growth curves, and frequencies of lysogenization of a sensitive host. OOP RNA synthesis is weakly repressed by the Escherichia coli LexA protein. Consonant with this inducibility of OOP RNA synthesis by ultraviolet light, we find a two-fold greater phage burst following ultraviolet induction of a lambda + than of a lambda po- prophage. In lambda + infections, OOP RNA causes two cleavage events in cll mRNA: one is in the 3'-end of the coding region, and the second is in the intercistronic region between the cll and O genes. The cll gene fragments are subject to additional hydrolytic events, and cll mRNA levels are several-fold lower in lambda + than in lambda po- infections late in the infection cycle. However, O mRNA levels are almost unaffected by the po- mutation.

Bacterial Proteins↗
PubMed1990

Enhanced prostaglandin synthesis after ultraviolet injury is mediated by endogenous histamine stimulation. A mechanism for irradiation erythema.

Acute ultraviolet light B (UVB) injury is associated with dermal mast cell histamine release. The possibility that histamine-stimulated prostaglandin (PG) synthesis could be a mechanism for irradiation erythema was therefore examined using human skin explants. Explants responded to UV irradiation (120 mJ/cm2) with a fivefold increase in synthesis of prostaglandins E2, F2 alpha and 6-keto PGF1 alpha. Incubating explants with the H1 antihistamines brompheniramine (50 microM) or pyrilamine (30 microM) inhibited PG release from irradiated explants 63 +/- 4.9% (mean +/- SEM) 6 h after UV exposure. Antihistamines did not affect PG synthesis in control explants. Irradiation increased the histamine concentration in explant conditioned medium only 50% over basal values, suggesting that irradiation enhanced histamine responsiveness. Explants were therefore incubated with exogenous histamine. In irradiated explants, PG synthesis was stimulated threefold by 3 microM histamine. Unirradiated explants' PG synthesis was unaffected by histamine. Enhanced histamine sensitivity was also examined in epidermal cell cultures. In irradiated cultures, histamine sensitivity was again markedly potentiated: as little as 1 microM histamine stimulated significant PGE2 release and the response to 10-30 microM histamine was increased six to eight times compared with that of unirradiated cultures. These studies demonstrate that endogenous histamine stimulates PG synthesis in human skin after UV injury by potentiation of histamine-induced prostaglandin release. Potentiated agonist responses induced by UV exposure may contribute to the effects of UVB irradiation injury and in particular to irradiation erythema.

Animals↗
PubMed1987

A sonographic screening method for Down syndrome.

We describe a potential screening method for the second trimester detection of the fetus with Down syndrome by the use of standard sonographic biometry. Retrospective assessment of the biparietal diameter, femur length, and biparietal diameter/femur length ratio in 55 fetuses with Down syndrome and 544 control fetuses was performed at two medical centers. Adequate numbers of cases and controls were available to permit statistically significant comparisons between the groups at 15 to 23 weeks' gestation. Fetuses with Down syndrome displayed no statistically significant differences in the cephalic index or the biparietal diameter compared with controls at a given gestational age. Significant femur length shortening was observed, but the greatest statistical difference was noted for the biparietal diameter/femur length ratio. This ratio was found to decrease with gestational age in the normal population and was consistently elevated in the Down syndrome population (compared with control) throughout the second trimester. With a cutoff value of 1.5 SD above the normal population mean for the biparietal diameter/femur length ratio, 50% to 70% of fetuses with Down syndrome could be identified in 6% of the total population (p less than 0.0001). This preliminary study suggests that the biparietal diameter/femur length ratio may prove superior to current Down syndrome screening methods and, as a third independent variable, may significantly enhance the sensitivity and specificity of combined maternal age/maternal serum alpha-fetoprotein screening modalities.

Down Syndrome↗
PubMed1986

Polyomavirus small t antigen: overproduction in bacteria, purification, and utilization for monoclonal and polyclonal antibody production.

Polyomavirus small t antigen was purified from genetically engineered Escherichia coli and used as the immunogen for the production of polyclonal and monoclonal antibodies. A new series of plasmids for increased expression of polyomavirus T antigens or a T antigen-beta-galactosidase fusion protein was constructed by replacing sequences coding for the ribosome-binding site of previously published plasmids with a chemically synthesized sequence that has a higher degree of complementarity to the 3' end of the 16S rRNA. Cells expressing the fusion protein from the plasmid with the synthetic sequence contained 5- to 10-fold more fusion protein after a 3-h induction than did control cells. Pulse-labeling of cells bearing the new plasmids revealed that the T antigens were synthesized at high levels after induction: 10% of total synthesis for small t; 15% for Py-1387T middle T, a truncated mutant of middle T; and probably 1 to 5% for middle T. Small t and Py-1387T middle T, but not wild-type middle T, were seen as minor bands in total cell protein analyzed on sodium dodecyl sulfate-polyacrylamide gels stained with Coomassie blue. A simple, rapid procedure for purification of bacterial small t from the pellet of sonicated bacteria yielded 1 to 2 mg of small t per liter of bacterial culture at 80 to 90% homogeneity. High-titer polyclonal rabbit antisera raised against purified small t recognized all three T antigens and were suitable for immunoaffinity purification of middle T. Mouse monoclonal antibodies raised against bacterial small t were of four classes, immunoprecipitating either all three polyomavirus T antigens, small t and middle T only, primarily small t, or middle T and large T in preference to small t. One of the latter monoclonal antibodies also immunoprecipitated large T but not small t of simian virus 40, suggesting that the site recognized by this antibody may be functionally important. None of the monoclonal antibodies yielded an immunoprecipitate active in phosphorylating middle T in vitro.

Antibodies, Monoclonal↗
PubMed1985

Calcium ionophore enables soluble agonists to stimulate macrophage 5-lipoxygenase.

The regulation of arachidonic acid conversion by the 5-lipoxygenase and the cyclooxygenase pathways in mouse peritoneal macrophages has been studied using particulate and soluble agonists. Particulate agonists, zymosan and latex, stimulated the production of cyclooxygenase metabolites as well as the 5-lipoxygenase product, leukotriene C4. In contrast, incubation with the soluble agonist phorbol myristate acetate or exogenous arachidonic acid led to the production of cyclooxygenase metabolites but not leukotriene C4. We tested the hypothesis that the 5-lipoxygenase, unlike the cyclooxygenase, requires activation by calcium before arachidonic acid can be utilized as a substrate. Addition of phorbol myristate acetate to macrophages in the presence of calcium ionophore (A23187) at a concentration which alone did not stimulate arachidonate metabolism resulted in a synergistic increase (50-fold) in leukotriene C4 synthesis compared to phorbol ester or A23187 alone. No such effect on the cyclooxygenase pathway metabolism was observed. Exogenous arachidonic acid in the presence of A23187 produced similar results yielding a 10-fold greater synthesis of leukotriene C4 over either substance alone without any effects on the cyclooxygenase metabolites. Presumably, calcium ionophore unmasked the synthesis of leukotriene C4 from phorbol myristate acetate-released and exogenous arachidonate by elevating intracellular calcium levels enough for 5-lipoxygenase activation. These data indicate that once arachidonic acid is released from phospholipid by an agonist, it is available for conversion by both enzymatic pathways. However, leukotriene synthesis may not occur unless intracellular calcium levels are elevated either by phagocytosis of particulate agonists or with calcium ionophore.

Animals↗
PubMed1985

Cyclic melanotropins. 9. 7-D-Phenylalanine analogues of the active-site sequence.

The cyclic melanotropin Ac-Ser1-Tyr2-Ser3-Cys4-Glu5-His6-Phe7-Arg8 -Trp9-Cys10-Lys11-Pro12-Val13-NH is a highly potent agonist as determined in several melanocyte bioassays. In linear melanotropins, a D-Phe7 substitution leads to increased potency and often prolonged biological activity. In order to determine if this substitution would have the same effect in cyclic melanotropins, we have prepared a series of these analogues. The D-Phe7-substituted cyclic melanotropins Ac-[Cys4,D-Phe7,Cys10]-alpha-MSH4-10-NH2 and Ac-[Cys4,D-Phe7,Cys10]-alpha-MSH4-11-NH2 were both more potent than their cyclic L-Phe7-containing counterparts in either the frog or lizard skin bioassay by more than a factor of 10. Neither peptide, however, exhibited prolongation of biological activity in either assay. Substitution of D-Phe7 into the cyclic 4-12 and 4-13 sequences led to a slight or no increase in potency in both assays relative to the L-Phe7 counterparts, but the activity of the melanotropins was ultraprolonged in each assay. Ac-[Cys4,D-Phe7,Cys10]-alpha-MSH4-12-NH2 was about equipotent to Ac-[Cys4,D-Phe7,Cys10]-alpha-MSH4-13-NH2, again demonstrating, as with certain linear and cyclic L-Phe7-containing melanotropins, that the C-terminal amino acid valine is not required for biological activity or for superpotency. Similar to the linear D-Phe7 analogues that possessed ultraprolonged melanotropic activity, the 4-12 and 4-13 cyclic D-Phe7 analogues also displayed the phenomenon of superagonism, which is a time-dependent increase in efficacy over that produced by an equipotent concentration of the native hormone. Cyclization of certain linear melanotropins resulted in analogues with increased resistance to biological degradation by serum enzymes or purified proteolytic enzymes. Further, incorporation of a D-Phe7 into in the cyclic analogues led to melanotropins that were totally resistant to enzymatic inactivation by trypsin.

Animals↗
PubMed1984

Antenatal diagnosis of renal anomalies with ultrasound. I. Obstructive uropathy.

During a 5-year period, a diagnosis of obstructive uropathy was made in 25 fetuses. Eight of them had unilateral obstruction and 17 were affected bilaterally. The most common condition encountered was urethral obstruction by posterior valves. The site and nature of the obstruction were correctly identified in 22 of the 25 fetuses. Among the 17 who had bilateral obstruction, only three survived. In contrast, only one infant with unilateral obstruction died (of unrelated causes). Oligohydramnios in low-level (urethral) obstruction was a uniformly lethal finding. Relief of urethral obstruction in two fetuses after 20 weeks of gestation did not result in survival of the infant, whereas shunting prior to 20 weeks in one fetus seemed to have a beneficial effect. On the basis of this experience, we suggest that unilateral obstruction would be treated best by conservative management, while in bilateral obstruction invasive treatment may be effective if initiated early in gestation, before significant oligohydramnios occurs.

Female↗
PubMed1984

Mutational analysis of a regulatory region in bacteriophage lambda that has overlapping signals for the initiation of transcription and translation.

The positively regulated PRE promoter of phage lambda structurally overlaps with the ribosome-binding and NH2-terminal coding region of the regulatory protein (cII) that activates PRE transcription. We have isolated and characterized 27 different point mutations that occur within the 36-base-pair overlapping region. A comparison of genetic crossover data with nucleotide separations as determined by DNA sequence analysis reveals that recombination frequencies are greatly depressed at very short distances. Moreover, recombination frequency is critically dependent upon the precise nucleotide sequence of the crossover region for distances of five nucleotides or less. The mutations define precise positions and sequences that are important to (i) PRE promoter function, (ii) translation of the cII gene, and (iii) cII gene function. Mutational changes that affect the function of one element in this region concomitantly define phenotypically silent alterations in the other two elements. Mutations deficient in promoter function (P-RE or cy) are clustered in two regions that lie approximately equal to 10 and approximately equal to 35 nucleotides before the initial base of PRE mRNA, analogous to mutations in other promoters. P-RE mutations in the -10 region alter bases that are conserved in prokaryotic promoters, but P-RE mutations in the -35 region do not affect bases that are normally conserved in other promoters. Several mutations deficient in cII gene activity affect the initiation of cII protein synthesis, including an A leads to G change four bases outside the cII coding region, and AUG leads to GUG, AUG leads to ACG, and AUG leads to AUA mutations in the initiation codon. In the region of overlap between the PRE promoter and the NH2-terminal region of the cII gene, most amino acid substitutions in the cII protein do not result in a loss of cII function, indicating that this region of the gene does not contain essential information for cII function. We suggest that the overlap itself is an evolutionarily conserved structure and that it somehow coordinates the bidirectional transcriptional and translational events that occur in this region.

Bacteriophage lambda↗
PubMed1976

Inhalation of fenoterol (Berotec) by asthmatic children: A clinical comparison with salbutamol, orciprenaline and isoprenaline.

Fenoterol (Berotec) has been administered by inhalation, via a Bennett nebulizer, to symptom-free asthmatic children aged 6 to 14 years. The effects of treatment on the results of respiratory function tests, pulse rate and blood pressure were followed. The effects of fenoterol have been compared with those of placebo, salbutamol, orciprenaline and isoprenaline. Inhalation of 1 mg of fenoterol produced effective bronchodilatation, which was more than a placebo effect and was comparable with the responses achieved with other known effective bronchodilators given by inhalation. It produced only a minor increase in heart rate at this dose level.

Adolescent↗