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Biomedical subjects

C Hill

Publications and source records attributed to C Hill.

At least 127 records · Page 7Linked to original sources
PubMed1999

Characterization and heterologous expression of the genes encoding enterocin a production, immunity, and regulation in Enterococcus faecium DPC1146.

Enterocin A is a small, heat-stable, antilisterial bacteriocin produced by Enterococcus faecium DPC1146. The sequence of a 10, 879-bp chromosomal region containing at least 12 open reading frames (ORFs), 7 of which are predicted to play a role in enterocin biosynthesis, is presented. The genes entA, entI, and entF encode the enterocin A prepeptide, the putative immunity protein, and the induction factor prepeptide, respectively. The deduced proteins EntK and EntR resemble the histidine kinase and response regulator proteins of two-component signal transducing systems of the AgrC-AgrA type. The predicted proteins EntT and EntD are homologous to ABC (ATP-binding cassette) transporters and accessory factors, respectively, of several other bacteriocin systems and to proteins implicated in the signal-sequence-independent export of Escherichia coli hemolysin A. Immediately downstream of the entT and entD genes are two ORFs, the product of one of which, ORF4, is very similar to the product of the yteI gene of Bacillus subtilis and to E. coli protease IV, a signal peptide peptidase known to be involved in outer membrane lipoprotein export. Another potential bacteriocin is encoded in the opposite direction to the other genes in the enterocin cluster. This putative bacteriocin-like peptide is similar to LafX, one of the components of the lactacin F complex. A deletion which included one of two direct repeats upstream of the entA gene abolished enterocin A activity, immunity, and ability to induce bacteriocin production. Transposon insertion upstream of the entF gene also had the same effect, but this mutant could be complemented by exogenously supplied induction factor. The putative EntI peptide was shown to be involved in the immunity to enterocin A. Cloning of a 10.5-kb amplicon comprising all predicted ORFs and regulatory regions resulted in heterologous production of enterocin A and induction factor in Enterococcus faecalis, while a four-gene construct (entAITD) under the control of a constitutive promoter resulted in heterologous enterocin A production in both E. faecalis and Lactococcus lactis.

Amino Acid Sequence↗
PubMed1999

Identification and disruption of BetL, a secondary glycine betaine transport system linked to the salt tolerance of Listeria monocytogenes LO28.

The trimethylammonium compound glycine betaine (N,N, N-trimethylglycine) can be accumulated to high intracellular concentrations, conferring enhanced osmo- and cryotolerance upon Listeria monocytogenes. We report the identification of betL, a gene encoding a glycine betaine uptake system in L. monocytogenes, isolated by functional complementation of the betaine uptake mutant Escherichia coli MKH13. The betL gene is preceded by a consensus sigmaB-dependent promoter and is predicted to encode a 55-kDa protein (507 amino acid residues) with 12 transmembrane regions. BetL exhibits significant sequence homologies to other glycine betaine transporters, including OpuD from Bacillus subtilis (57% identity) and BetP from Corynebacterium glutamicum (41% identity). These high-affinity secondary transporters form a subset of the trimethylammonium transporter family specific for glycine betaine, whose substrates possess a fully methylated quaternary ammonium group. The observed Km value of 7.9 microM for glycine betaine uptake after heterologous expression of betL in E. coli MKH13 is consistent with values obtained for L. monocytogenes in other studies. In addition, a betL knockout mutant which is significantly affected in its ability to accumulate glycine betaine in the presence or absence of NaCl has been constructed in L. monocytogenes. This mutant is also unable to withstand concentrations of salt as high as can the BetL+ parent, signifying the role of the transporter in Listeria osmotolerance.

Amino Acid Sequence↗
PubMed1999

Identification and disruption of lisRK, a genetic locus encoding a two-component signal transduction system involved in stress tolerance and virulence in Listeria monocytogenes.

lisRK encodes a two-component regulatory system in the food pathogen Listeria monocytogenes LO28. Following identification of the operon in an acid-tolerant Tn917 mutant, a deletion in the histidine kinase component was shown to result in a growth phase variation in acid tolerance, an ability to grow in high ethanol concentrations, and a significant reduction in virulence.

Animals↗
PubMed1999

VP4 and VP7 genotyping of rotavirus samples recovered from infected children in Ireland over a 3-year period.

Between September 1995 and August 1998, the incidence and diversity of the main human rotavirus genotypes (G1, G2, G3, and G4 and P[8], P[4], P[6], and P[9]) among Irish children were determined by using established and adapted reverse transcriptase PCR-based genotyping methods. From a total of 193 rotavirus-positive specimens collected from nine hospitals we successfully identified the P type in 182 (94%) of the samples and the G type in 165 (85.5%) of the samples. Only four samples could not be assigned a G or P type. Two P types existed in Ireland, P[8] (78%) and P[4] (16%), and their relative incidence varied over the 3 years of this study. No P[6] or P[9] types were detected. G1 was the most predominant G type (55%), and the incidences of G2, G3, and G4 isolates were 15.5, 1, and 11%, respectively. Three percent of the samples tested had a mixed G type. A P and G type was assigned to 158 (81.8%) of samples. Of the typeable samples, G1 P[8] was the most prevalent (65%), whereas G2 P[4] (17%), G3 P[8] (1%), G4 P[8] (12%), and mixed types (all G1/ G4 P[8]) (4%) were detected less frequently. In the third year a significant genotypic shift from G1 P[8] to G2 P[4] and G4 P[8] was observed. During the study, we noticed that the inclusion of random primers during cDNA synthesis greatly increased the specificity of the PCR typing assays. No correlation was seen between the contributing hospitals and a specific genotype. In conclusion, the coverage of infection given by the recently licensed tetravalent vaccine would be significantly high in Ireland, although future monitoring of genotypic changes among Irish isolates should be encouraged.

Antigens, Viral↗
PubMed1999

Energy cost of sport rock climbing in elite performers.

OBJECTIVES: To assess oxygen uptake (VO2), blood lactate concentration ([La(b)]), and heart rate (HR) response during indoor and outdoor sport climbing. METHODS: Seven climbers aged 25 (SE 1) years, with a personal best ascent without preview or fall (on sight) ranging from 6b to 7a were assessed using an indoor vertical treadmill with artificial rock hand/foot holds and a discontinuous protocol with climbing velocity incremented until voluntary fatigue. On a separate occasion the subjects performed a 23.4 m outdoor rock climb graded 5c and taking 7 min 36 s (SE 33 s) to complete. Cardiorespiratory parameters were measured using a telemetry system and [La(b)] collected at rest and after climbing. RESULTS: Indoor climbing elicited a peak oxygen uptake (VO2climb-peak) and peak HR (HRpeak) of 43.8 (SE 2.2) ml/kg/min and 190 (SE 4) bpm, respectively and increased blood lactate concentration [La(b)] from 1.4 (0.1) to 10.2 (0.6) mmol/l (p < 0.05). During outdoor climbing VO2 and HR increased to about 75% and 83% of VO2climb-peak and HRpeak, respectively. [La(b)] increased from 1.3 (0.1) at rest to 4.5 mmol/l (p < 0.05) at 2 min 32 s (8 s) after completion of the climb. CONCLUSIONS: The results suggest that for elite climbers outdoor sport rock climbs of five to 10 minutes' duration and moderate difficulty require a significant portion of the VO2climb-peak. The higher HR and VO2 for outdoor climbing and the increased [La(b)] could be the result of repeated isometric contractions, particularly from the arm and forearm muscles.

Adult↗
PubMed1999

The natural food grade inhibitor, lacticin 3147, reduced the incidence of mastitis after experimental challenge with Streptococcus dysgalactiae in nonlactating dairy cows.

Lacticin 3147 is a broad-spectrum bacteriocin produced by the food-grade organism Lactococcus lactis. Lacticin 3147 is active at a neutral pH and has been shown to be bactericidal to streptococci and staphylococci in vitro. The effectiveness of an intramammary teat seal formulation, and a teat seal containing lacticin 3147 was evaluated at drying off in 68 uninfected quarters of 18 cows. Following infusion of either teat seal or lacticin 3147 combined with teat seal, a deliberate infection challenge of Streptococcus dysgalactiae (approximately equal to 1.5 x 10(4) cfu per teat) was administered by direct inoculation into the teat sinus. During an 8-d experimental period following inoculation, 61% of control quarters and 6% of the treatment quarters either developed clinical mastitis or were shedding the challenge organism. Randomly amplified polymorphic DNA polymerase chain reaction genetic typing was used to confirm that both the new infections and the bacteria surviving in the teats at the end of the experiment were the challenge strain. The combination of teat seal and lacticin 3147 was well tolerated within the udder and elicited only a temporary increase in somatic cell count to 5.7 x 10(5)/ml (88 h after infusion) in a previously uninfected lactating udder quarter. Therefore, we concluded that this nonantibiotic approach to mastitis prevention may contribute to a reduction in the routine application of antibiotics at drying off in the future.

Animals↗
PubMed1999

The natural food grade inhibitor, lacticin 3147, reduced the incidence of mastitis after experimental challenge with Streptococcus dysgalactiae in nonlactating dairy cows.

Lacticin 3147 is a broad-spectrum bacteriocin produced by the food-grade organism Lactococcus lactis. Lacticin 3147 is active at a neutral pH and has been shown to be bactericidal to streptococci and staphylococci in vitro. The effectiveness of an intramammary teat seal formulation, and a teat seal containing lacticin 3147 was evaluated at drying off in 68 uninfected quarters of 18 cows. Following infusion of either teat seal or lacticin 3147 combined with teat seal, a deliberate infection challenge of Streptococcus dysgalactiae (approximately equal to 1.5 x 10(4) cfu per teat) was administered by direct inoculation into the teat sinus. During an 8-d experimental period following inoculation, 61% of control quarters and 6% of the treatment quarters either developed clinical mastitis or were shedding the challenge organism. Randomly amplified polymorphic DNA polymerase chain reaction genetic typing was used to confirm that both the new infections and the bacteria surviving in the teats at the end of the experiment were the challenge strain. The combination of teat seal and lacticin 3147 was well tolerated within the udder and elicited only a temporary increase in somatic cell count to 5.7 x 10(5)/ml (88 h after infusion) in a previously uninfected lactating udder quarter. Therefore, we concluded that this nonantibiotic approach to mastitis prevention may contribute to a reduction in the routine application of antibiotics at drying off in the future.

Animals↗
PubMed1999

Acid-adapted Listeria monocytogenes displays enhanced tolerance against the lantibiotics nisin and lacticin 3147.

Log-phase Listeria monocytogenes cells become tolerant to a variety of environmental stresses following acid adaptation at pH 5.5. We demonstrated that adapted cells also exhibit increased tolerance to nisin and, to a lesser extent, lacticin 3147. At nisin concentrations of 100 and 200 IU/ml the survival of acid-adapted cells was approximately 10-fold greater than nonadapted cells. However, acid adaptation had only a moderate effect on the tolerance of L. monocytogenes to lacticin 3147, a phenomenon that possibly reflects the distinct mode of action of this bacteriocin. Analysis of the fatty acid composition of the bacterial membrane indicated that straight-chain fatty acids C14:0 and C16:0 were significantly increased in acid-adapted cells while levels of C18:0 decreased. The results indicate that stress mechanisms that are induced in mildly acidic conditions provide protection against the antimicrobial action of bacteriocins. This increased resistance of acid-adapted L. monocytogenes could cause increased survival of this pathogen in food products in which nisin or other bacteriocins are used as preservatives.

Adaptation, Physiological↗
PubMed1999

Development of a lacticin 3147-enriched whey powder with inhibitory activity against foodborne pathogens.

The broad-spectrum bacteriocin lacticin 3147, produced by Lactococcus lactis DPC3147, is inhibitory to a wide range of gram-positive food spoilage and pathogenic organisms. A 10% solution of demineralized whey powder was fermented with DPC3147 at a constant pH of 6.5. The fermentate was spray dried, and the resulting powder exhibited inhibitory activity. The ability of the lacticin 3147-enriched powder to inhibit Listeria monocytogenes Scott A and Staphylococcus aureus 10 was assessed in buffer at both acidic (pH 5) and neutral (pH 7) pH. In addition, the ability of the powder to inhibit L. monocytogenes Scott A in an infant milk formulation was assessed. Resuspension of approximately 10(8) midexponential phase L. monocytogenes Scott A cells in a 10% solution of the lacticin 3147-enriched powder resulted in a 1,000-fold reduction in viable cells at pH 5 and pH 7 after 3 h at 30 degrees C. In the case of S. aureus 10, resuspension of 2.5 x 10(7) midexponential phase cells in a 15% solution of the lacticin 3147-enriched powder at pH 5 resulted in only a 10-fold reduction in viable cell counts, compared with a 1,000-fold reduction at pH 7, following incubation for 3 h at 30 degrees C. The use of the lacticin 3147 powder in an infant milk formulation resulted in greater than a 99% kill of L. monocytogenes within 3 h at 30 degrees C. These results suggest that this bioactive lacticin 3147 food ingredient may find applications in many different foods, including those with pH close to neutrality.

Animals↗
PubMed1999

[Meta-analyses of randomized trials in oncology: pros and cons].

A meta-analysis of trials is a quantitative synthesis of the results of trials addressing the same question. Such a synthesis is useful when the consideration of the results of the trials does not produce a clear answer. To perform a meta-analysis, one must identify all the randomized trials addressing the question, whether their results have been published or not. A meta-analysis can be based on summary data, or it can be based on individual patient data which allows extensive data checking, corrections, and an intent to treat analysis. A meta-analysis provides a test for the efficacy of the treatment under study, and an estimation of this efficacy. It allows also the study of the heterogeneity in efficacy between trials according to their characteristics or between sub-population of patients. Lastly, the results of a meta-analysis may be of help in the design of future trials. The quality of a meta-analysis depends essentially on the completeness of the collection of trials. Apart from this problem, the limits of a meta-analysis are the limits of the trials it includes, the addition of ill designed and ill conducted trials can only lead to a bad meta-analysis. The moderate effect of the treatments available for solid tumours in adults explains the widespread use of meta-analysis in oncology.

Humans↗
PubMed1999

[Smoking in women in France].

Surveillance of smoking behavior and study of consequences of smoking on the health of the French population, and particularly the female population, is a public health priority. The amount of tobacco consumed can be determined from sales figures and from surveys. Globally, tobacco sales increased through 1985. According to the available surveys, the proportion of regular smokers has varied little as smoking rate has decreased in men and increased in women. The decrease occurred in all age groups for men and increased only in the 25-49 year age group for women. Smoking is the cause of 60,000 deaths per year in France, 57,000 in the male population and 3,000 in the female population. Despite reinforced legislation (The Veil and Evin laws) which is unfortunately poorly applied, tobacco consumption has not decreased greatly. Funding levels for anti-smoking campaigns are totally insignificant compared with the efforts of the tobacco industry to promote their products. However, the beneficial health effect of stopping smoking is truly great since the risk depends much more on the duration of smoking than on the number of daily cigarettes. In addition, the delay between the cause and consequence is long, the consequences of the increase in tobacco smoking among young women over the last 20 years will not become visible until 20 to 40 years from now. One could wonder why so little effort has been put into anti-smoking campaigns despite the readily available data clearly warranting their promotion.

Adolescent↗
PubMed1998

Use of a broad-host-range bacteriocin-producing Lactococcus lactis transconjugant as an alternative starter for salami manufacture.

Lactococcus lactis DPC4268 is widely used for Cheddar cheese manufacture in Ireland where it is recognised for its reliable fast acid producing ability in dairy environments. A transconjugant of this strain, L. lactis DPC4275, was generated which produces the broad spectrum, two-component bacteriocin lacticin 3147, which is inhibitory to a variety of undesirable gram-positive bacteria including Clostridium, Bacillus, Enterococcus, Listeria, Staphylococcus and Streptococcus. Both DPC4268 and DPC4275 were used as single strain starters for manufacture of salamis. These products were compared with a salami manufactured with a conventional starter (Lactobacillus sake and Staphylococcus carnosus) in terms of pH development, a(w)-value, weight loss, colour development and sensory characteristics. Salamis produced with either lactococcal culture exhibited pH values below 5.1 and a(w)-values below 0.90 which is favourable for preservation and hygienic stability. In addition, these salamis had good sensory and colorimetric qualities. A minimum lacticin 3147 concentration of 640 AU/g was detected in the salamis which were produced with L. lactis DPC4275.

Animals↗
PubMed1998

Effects of antisense-based folypoly-gamma-glutamate synthetase down-regulation on reduced folates and cellular proliferation in CCRF-CEM cells.

The effect of down-regulation of folylpoly-gamma-glutamate synthetase (FPGS) activity on intracellular reduced folate accumulation and cellular proliferation was examined, using an inducible antisense expression system in the human T-lymphoblastic leukemia cell line CCRF-CEM. FPGS catalyzes the addition of gamma-glutamyl residues to natural folates and classical antifolates, which results in their enhanced cellular retention and increased cytotoxicity. As such, this enzyme has become a focus as a potential anticancer drug target. However, direct evidence to support this concept has been elusive. Hence, a study was undertaken using an antisense-based expression system to down-regulate FPGS activity. This inducible expression system was used to demonstrate that lower FPGS activity can lead to substantially lower intracellular folate content, which coincides with suppression of thymidylate synthesis and inhibition of cellular proliferation.

DNA Primers↗
PubMed1998

Iatrogenic risks of endometrial carcinoma after treatment for breast cancer in a large French case-control study. Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC).

Since tamoxifen is widely used in breast cancer treatment and has been proposed for the prevention of breast cancer, its endometrial iatrogenic effects must be carefully examined. We have investigated the association between endometrial cancer and tamoxifen use or other treatments in women treated for breast cancer in a case-control study. Cases of endometrial cancer diagnosed after breast cancer (n = 135) and 467 controls matched for age, year of diagnosis of breast cancer and hospital and survival time with an intact uterus were included. Women who had received tamoxifen were significantly more likely to have endometrial cancer diagnosed than those who had not (crude relative risk = 4.9, p = 0.0001). Univariate and adjusted analyses showed that the risk increased with the length of treatment (p = 0.0001) or the cumulative dose of tamoxifen received (p = 0.0001), irrespective of the daily dose. Women who had undergone pelvic radiotherapy also had a higher risk (crude relative risk = 7.8, p = 0.0001). After adjusting for confounding factors, the risk was higher for tamoxifen users (p = 0.0012), treatment for more than 3 years (all p < 0.03) and pelvic radiotherapy (p = 0.012). Women who had endometrial cancer and had received tamoxifen had more advanced disease and poorer prognosis than those with endometrial cancer who had not received this treatment. Our results suggest a causal role of tamoxifen in endometrial cancer, particularly when used as currently proposed for breast cancer prevention. Pelvic radiotherapy may be an additional iatrogenic factor for women with breast cancer. Endometrial cancers diagnosed in women treated with tamoxifen have poorer prognosis. Women who receive tamoxifen for breast cancer should be offered gynaecological surveillance during and after treatment. A long-term evaluation of the risk-benefit ratio of tamoxifen as a preventive treatment for breast cancer is clearly warranted.

Adenocarcinoma↗
PubMed1998

Nursery practices and detection of jaundice after newborn discharge.

OBJECTIVE: To investigate nursery practices regarding outpatient recognition of neonatal jaundice. DESIGN: Descriptive survey. PARTICIPANTS: Random sample of nursery head nurses and pediatricians from national lists. SETTING: Nurseries with more than 100 births per year and pediatricians responsible for newborn discharges. RESULTS: Head nurses from 204 nurseries and 200 pediatricians were surveyed, with 62% of head nurses and 55% of pediatricians responding. Almost half of the head nurses (45%) reported lack of a written neonatal jaundice protocol. Twenty-seven percent of head nurses and pediatricians reported that no system is in place to track jaundiced newborns after discharge. Forty percent of head nurses and 26% of pediatricians reported from higher-risk nurseries, defined as nurseries where more than 25% of mothers did not have a high school diploma or more than 50% of infants were born to single-parent families. These nurseries were no more likely to have a protocol for jaundice management or to use a system to track newborns after discharge. Discharge of most newborns before 36 hours of age was common (70% of head nurses, 62% of pediatricians) and some respondents discharged most newborns before 24 hours of age (16% of head nurses, 12% of pediatricians). For newborns discharged before 24 hours of age, more than half of the nurseries surveyed scheduled follow-up within 2 to 3 days (53% of head nurses, 62% of pediatricians). The likelihood of such follow-up did not differ by type of health care insurance, level of maternal education, percentage of single-parent families, predominance of minority patients, or higher risk as defined above. CONCLUSIONS: In our sample, many nurseries lack parent education, neonatal jaundice protocols, and neonatal jaundice tracking systems. Newborns discharged before 48 hours of age are often not scheduled to be seen by a health care provider within 2 to 3 days, despite American Academy of Pediatrics guidelines recommending such follow-up.

Continuity of Patient Care↗
PubMed1998

A regional audit of hand and wrist injuries. A study of 4873 injuries.

This study reports the characteristics, causes and disposal of isolated injuries to the hand and wrist presenting to six accident and emergency departments over a period of 4 months. The rate of isolated injury to the hand or wrist was 6.6%. The male: female ratio was 2.2: 1, with the mean age for injury being 26.4 years in men and 29.2 years in women. The modal age group for injury was 21-25 years in men and 11-15 years in women. The right and left hand were injured almost equally. The dominant hand was more commonly injured although this was influenced by the cause of injury: 16.3% were caused by a fall; 15% by sport; and 7% were work/machinery related. 13.3% were referred to specialities for further treatment.

Adolescent↗
PubMed1998

Randomized trial of induction chemotherapy in larynx carcinoma.

We conducted a randomized study in patients with previously untreated advanced (T3) larynx carcinoma to compare total laryngectomy followed by radiotherapy to induction chemotherapy, followed by radiotherapy in good responders, and by total laryngectomy plus radiotherapy in poor responders. A total of 68 patients were included in the study, 36 in the induction chemotherapy group and 32 in the no chemotherapy group. 15 of the 36 patients in the induction chemotherapy group did not have a laryngectomy. Survival and disease-free survival were significantly worse in the induction chemotherapy group than in the no chemotherapy group (P = 0.006 and P = 0.02, respectively). The 2-year survival rates were 69% in the induction chemotherapy group and 84% in the no chemotherapy group. Larynx preservation for patients, selected on the basis of having responded to induction chemotherapy, cannot be considered a standard treatment at the present time.

Aged↗