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Biomedical subjects

M Mahoney

Publications and source records attributed to M Mahoney.

At least 19 recordsLinked to original sources

The effect of processed meat and meat starter cultures on gastrointestinal colonization and virulence of Listeria monocytogenes in mice.

Listeria monocytogenes is a foodborne pathogen of major concern to the food industry in general and the meat industry in particular. The aim of this study was firstly to identify a strain of Listeria that was virulent in SPF BALB/c mice. Secondly, to investigate if a traditional meat starter culture (FloraCarn) and nontraditional meat starter (NTMS) cultures of dairy product and human origin (Lactobacillus and bifidobacteria) inhibit this pathogen in vivo. In addition, the inhibition of Listeria was investigated in vitro. In vitro inhibition was investigated using an agar inhibition assay, where soft agar containing the pathogen was laid over colonies of NTMS cultures, and inhibition expressed as the zones of inhibition developing around the colonies. For assessment of virulence, mice were intragastrically challenged with broth cultures of five strains of Listeria. For assessment of anti-listeria effect in vivo, the Listeria strain proven to be most pathogenic (LM3) was given to mice in salami batter containing no other added cultures (control) or batter inoculated with either (1) FloraCarn, (2) a NTMS culture, or (3) a combination of FloraCarn and a NTMS culture. The batter was given to mice after a 3-day fermentation and faecal levels of pathogen and body weight were monitored. Intragastric challenge with LM3, but no other strains, resulted in a significant weight loss (p<0.05) and up to 10(6) colony forming units (cfu) of LM3 per gram faeces. No weight loss was observed in animals fed with salami batter containing LM3. Consumption of salami batter fermented by a combination of NTMS culture (Lactobacillus acidophilus LAFTI(R) L10) and FloraCarn reduced faecal levels of the pathogen by 2.5 log units compared to the control. Consumption of salami batter fermented with FloraCarn and LAFTI(R) L10 (L10) alone reduced faecal levels by 0.5-1 and 1.5 log units, respectively. Of the NTMS cultures investigated here, L10 displayed the greatest inhibition of LM3 in vitro. These results indicate that the ability of pathogenic Listeria to cause listeriosis is dependent on the nature of the food in which the pathogen is present, and that a traditional meat starter culture (FloraCarn) and some NTMS cultures, particularly L10, inhibit growth of the pathogen during passage through the gastrointestinal tract.

Animals↗

Microanatomical changes in alveolar type II cells in juvenile mice intratracheally exposed to Stachybotrys chartarum spores and toxin.

Stachybotrys chartarum is an important environmental fungus. We have shown recently that alveolar type II cells are sensitive to exposure to Stachybotrys chartarum spores and to the trichothecene, isosatratoxin-F, both in vitro and in vivo, in a juvenile mouse model. This sensitivity is manifest as significant changes in the composition and normal metabolic processing of pulmonary surfactant. This study evaluated the effects of a single intratracheal exposure of S. chartarum spores and toxin on ultrastructure and dimensions of alveolar type II cells from juvenile mice. This was to determine whether there are concurrent morphological and dimensional changes in the alveolar type II cell that reflect the metabolic alterations in pulmonary surfactant that we observed in the treated mice. Marked ultrastructural changes were associated with alveolar type II cells in both S. chartarum and isosatratoxin-F treated animals compared to untreated, saline, and Cladosporium cladosporioides spore treated animals. These ultrastructural changes included condensed mitochondria with separated cristae, scattered chromatin and poorly defined nucleolus, cytoplasmic rarefaction, and distended lamellar bodies with irregularly arranged lamellae. Point count stereological analysis revealed a significant increase (p < 0.05) in lamellar body volume density in S. chartarum and isosatratoxin-treated animals after 48 h exposure. Mitochondria volume density was significantly lower in the isosatratoxin-F (48 h exposure) and S. chartarum treated (24 and 48 h exposure) animals compared to those in the other treatment groups. These results reveal that exposure to S. chartarum spores and toxin elicit cellular responses in vivo differently from those associated with exposure to spores of a nontoxigenic mold species. They also indicate that accumulation of newly secreted pulmonary surfactant in the alveolar space of S. chartarum and isosatratoxin-F treated animals might be a consequence of cellular trauma resulting in lamellar body volume density changes leading to increased release of pulmonary surfactant into the alveolar space.

Animals↗

Phase response curve and light-induced fos expression in the suprachiasmatic nucleus and adjacent hypothalamus of Arvicanthis niloticus.

This article describes the phase response curve (PRC), the effect of light on Fos immunoreactivity (Fos-IR) in the suprachiasmatic nucleus (SCN), and the effect of SCN lesions on circadian rhythms in the murid rodent, Arvicanthis niloticus. In this species, all individuals are diurnal when housed without a running wheel, but running in a wheel induces a nocturnal pattern in some individuals. First, the authors characterized the PRC in animals with either the nocturnal or diurnal pattern. Both groups of animals were less affected by light during the middle of the subjective day than during the night and were phase delayed and phase advanced by pulses in the early and late subjective night, respectively. Second, the authors characterized the Fos response to light at circadian times 5, 14, or 22. Light induced an increase in Fos-IR within the SCN during the subjective night but not subjective day; this effect was especially pronounced in the ventral SCN, where retinal inputs are most concentrated, but was also evident in other regions. Both light and time influenced Fos-IR within the lower subparaventricular area. Third, SCN lesions caused animals to become arrhythmic when housed in a light-dark cycle as well as constant darkness. In summary, Arvicanthis appear to be very similar to nocturnal rodents with respect to their PRC, temporal patterns of light-induced Fos expression in the SCN, and the effects of SCN lesions on activity rhythms.

Animals↗

Outcome of pediatric thromboembolic disease: a report from the Canadian Childhood Thrombophilia Registry.

The outcome for children with deep vein thrombosis (DVT) and pulmonary embolism (PE) is unknown. An understanding of morbidity and mortality of DVT/PE is crucial to the development of rational treatment protocols. The Canadian Childhood Thrombophilia Registry has followed 405 children aged 1 mo to 18 y with DVT/PE for a mean of 2.86 y (range, 2 wk to 6 y) to assess outcome. The all-cause mortality was 65 of 405 children (16%). Mortality directly attributable to DVT/PE occurred in nine children (2.2%), all of whom had central venous line-associated thrombosis. Morbidity was substantial, with 33 children (8.1%) having recurrent thrombosis, and 50 children (12.4%) having postphlebitic syndrome. Recurrent thrombosis and postphlebitic syndrome were more common in older children, although deaths occurred equally in all age groups. The incidence of recurrent thrombosis and postphlebitic syndrome are likely underestimated because of difficulties in diagnosis, especially in younger children. The significant mortality and morbidity found in our study supports the need for international multicenter randomized clinical trials to determine optimal prophylactic and therapeutic treatment for children with DVT/PE.

Adolescent↗

Urine hyperglycosylated hCG plus ultrasound biometry for detection of down syndrome in the second trimester in a high-risk population.

OBJECTIVE: To evaluate measurement of levels of urine hyperglycosylated hCG, a form of hCG with abnormally branched oligosaccharide side chains, in conjunction with ultrasound biometry for Down syndrome risk prediction in an at-risk group. METHOD: We prospectively measured urine hyperglycosylated hCG levels, humeral length, and nuchal thickness in women who had second-trimester amniocentesis. Urine hyperglycosylated hCG levels were measured by a two-step enzyme-immunometric assay using monoclonal antibody beta152. Humeral length, nuchal thickness, and hyperglycosylated hCG values were expressed as multiples of the median, and the Down syndrome screening efficiency of the three analytes plus age was determined. A receiver operating characteristic (ROC) curve was generated, and the area under the curve was used to assess the Down syndrome screening performance of the algorithm. RESULTS: There were 23 cases of Down syndrome among 1016 singleton pregnancies. Mean gestational age (+/- standard deviation) was 16.1 +/- 1.2 weeks at the time of amniocentesis. Mean maternal age was 37.1 +/- 3.2 years. Biometry and measurement of hyperglycosylated hCG levels had a 91.3% detection rate at a 3.2% false-positive rate and a 100% detection rate at a 10.7% false-positive rate. The area under the ROC curve was 0.986 (P <.001), and that for measurement of hyperglycosylated hCG levels plus age was 0.941 (P <.001). The area under the curve was significantly larger with combined biochemical and biometry markers compared with measurement of hyperglycosylated hCG levels plus age alone (P <.02), proving that the former was superior to the latter. CONCLUSION: A new Down syndrome biochemical marker combined with ultrasound biometry had a high screening efficiency in a high-risk group. All cases of Down syndrome in this study population would have been detected at an amniocentesis rate of less than 10.7%. Our results appear superior to those found with other second-trimester algorithms. The combination is promising as an alternative to "automatic" genetic amniocentesis in women of advanced maternal age and other high-risk groups.

Adult↗

Repression and activation of promoter-bound RNA polymerase activity by Gal repressor.

By binding to the DNA site OE at position -60.5 in the gal operon, the GalR protein activates transcription from the P2 promoter located on the opposite face of DNA (position -5) and represses transcription from the P1 promoter located on the same face (position +1). GalR increases RNA polymerase binding at P2 and inhibits isomerization at P1 by forming a GalR-DNA-RNA polymerase ternary complex in each case. The specific effect of GalR at one promoter is independent of the presence of the other promoter. The enhancement or repression is also not the intrinsic property of a promoter; the regulation can be reversed by switching the angular orientation of the promoters relative to OE. Both enhancement and repression appear to require the same interaction between RNA polymerase alpha-subunit and GalR and/or the same interaction between RNA polymerase alpha-subunit and DNA in the ternary complexes. We have discussed how GalR might exert opposite effects in the steps involved in the formation of the open complex from free RNA polymerase and DNA.

Binding Sites↗

Bloodstream infections associated with a needleless intravenous infusion system in patients receiving home infusion therapy.

OBJECTIVE: To determine risk factors for bloodstream infections (BSIs) in an outbreak among patients receiving home intravenous infusion therapy. DESIGN: Case-control and retrospective cohort studies. SETTING: Home health agency. PATIENTS: Patients receiving home intravenous infusion therapy from Rhode Island Home Therapeutics (RIHT) from January through December 1993. MAIN OUTCOME MEASURE: Development of primary BSI. METHODS: We compared patients with BSI (ie, case patients) with randomly selected noninfected RIHT patients receiving intravenous therapy, conducted a cohort study of all RIHT patients receiving intravenous therapy via a central venous catheter (CVC), and conducted a culture survey of injection cap luminal fluid. RESULTS: Case patients were more likely than controls to have had therapy via a CVC (11/11 vs 14/32; odds ratio [OR] undefined; P < .001) or total parenteral nutrition and intralipid therapy (TPN/IL) (9/11 vs 3/32; OR, 43.5; 95% confidence interval [CI], 4.9 to 510.0). Among RIHT patients with CVCs, risk factors for BSI were receipt of TPN/IL (9/35 vs 2/67; rate ratio [RR], 8.6; 95% CI, 2.0 to 37.7) or use of a needleless infusion system (10/41 vs 1/61; RR, 14.9; 95% CI, 2.0 to 111.8). Only the combination of both exposures was significantly associated with development of a BSI (P < .001). Luminal fluid from injection caps of needleless devices was significantly more likely to be culture positive than fluid from protected-needle devices (5/23 vs 0/18; RR undefined; P = .04). CONCLUSIONS: Our data suggest that a needleless device used for TPN/IL was associated with increased risk of BSI when injection caps were changed every 7 days.

Case-Control Studies↗

Hippocampal volumetrics differentiate patients with temporal lobe epilepsy and extratemporal lobe epilepsy.

OBJECTIVE: To determine whether the occurrence of hippocampal formation (HF) volumetric asymmetry can reliably discriminate between complex partial seizures (CPSs) of a temporal lobe origin and CPSs of an extra-temporal lobe origin in a prospective study of patients with intractable CPSs (approximately 70% of patients have electrographic foci in the temporal lobe [HF volumetric asymmetry on magnetic resonance imaging scans has been shown to lateralize such foci reliably)]. DESIGN: We examined HF volumetrics on magnetic resonance imaging scans that were acquired with a 1-T magnetic resonance imaging scanner (Siemens Magnetom, Siemens Medical Systems, Iselin, NJ) by using magnetization-prepared rapid gradient echo three-dimensional sequences (producing a gapless series of high-contrast 1.25-mm images). These data were compared with ictal, interictal, invasive, and noninvasive videoelectroencephalographic monitoring data, functional imaging data, and outcome data to define each patient's type of epilepsy. SETTING AND PATIENTS: Forty-one patients were recruited from a tertiary university comprehensive epilepsy program, and 22 control subjects were recruited from the neurologically normal university community. RESULTS: Among the control subjects, the difference in HF volumetrics (right-left HF volumetrics) was + 0.085 +/- 0.253 cm3. Of the 41 patients, 25 had temporal lobe epilepsy. When we set the upper limit of normal at the mean +/- 3 SDs, all patients beyond the upper limit had CPSs of a temporal lobe origin. Of the patients with temporal lobe epilepsy, only three fell within normal limits. No patient with CPSs of an extratemporal lobe origin fell beyond the upper limit. CONCLUSION: The presence of significant HF volumetric asymmetry makes it highly unlikely that a patient's CPSs are of an extratemporal lobe origin.

Adolescent↗

The incidence of testicular cancer in Royal Air Force personnel.

OBJECTIVES: To review the incidence of testicular cancer within the Royal Air Force (RAF) compared with the national incidence. METHODS: The medical statistics for RAF personnel (supplied by the Central Statistics Office, categorized by occupation) were reviewed for the incidence of testicular cancer and compared to the national rate. RESULTS: A significantly elevated incidence of testicular neoplasm was detected in RAF personnel, which was well above the national rate. The increased incidence appeared most marked in those personnel working directly with aircraft. CONCLUSION: The only cause of the significantly higher incidence of testicular cancer in RAF personnel is probably related to working with aircraft. This concurs with a finding that aircraft technicians in the US Navy had an increased incidence of testicular cancer, and the exposure to hydrocarbon carcinogens in the workplace was implicated.

Adult↗

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↗

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↗

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↗

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↗

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↗