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Biomedical subjects

M Lynch

Publications and source records attributed to M Lynch.

At least 109 records · Page 6Linked to original sources
PubMed1997

Inherited susceptibility to several cancers but absence of linkage between dysplastic nevus syndrome and CDKN2A in a melanoma family with a mutation in the CDKN2A (P16INK4A) gene.

Genetic predisposition plays an important role in the development of nearly 10% of cases of cutaneous malignant melanoma (CMM). The CDKN2A gene has been described as responsible for melanoma susceptibility in a proportion of families with CMM linked to 9p. CDKN2A encodes a cyclin-dependent kinase inhibitor also implicated in the carcinogenesis of several sporadic tumors. Even though the incidence of other cancers is higher in CMM families, pancreatic adenocarcinoma is the only other well demonstrated cancer associated with CDKN2A mutations in some CMM pedigrees. We describe a family with four cases of CMM, eight patients affected by other cancers, and nine patients affected by dysplastic nevus (DN) syndrome. A CDKN2A frameshift mutation (358delG) was present in all the CMM patients, in at least three of the patients with other cancers (CDKN2A status is unknown in four patients), and in only two of the DN patients (CDKN2A status is unknown in one patient). An absence of linkage between chromosome 9p markers and the 358delG CDKN2A mutation and DN was detected, indicating genetic heterogeneity for DN and CMM in this family. The study strongly suggests that CDKN2A mutations are involved not only in the predisposition to CMM but also to several other types of cancer.

Adult↗
PubMed1997

Recanalization of the left atrial appendage demonstrated by transesophageal echocardiography.

Closure of the fibrillating left atrial appendage has been recommended during mitral valve operations to help prevent thrombus formation and systemic embolization postoperatively. We report recanalization of the appendage orifice in 6 patients after surgical closure by pursestring suturing at the time of mitral valve replacement. Transesophageal echocardiography demonstrated disruption of the closure line and partial recanalization of the sutured orifice with relatively high velocity flow between the left atrial body and the appendage.

Diagnosis, Differential↗
PubMed1997

The ureteric jet index: a novel measure of divided renal function.

The aim of this study was to evaluate an index of divided renal function based on the quantification of the ureteric jets seen on colour Doppler ultrasound of the bladder. Thirty-one patients attending for scintigraphic renography underwent colour Doppler ultrasound with video recording for 5 min. Divided renal function was calculated as the proportion of jets from the right-sided orifice ('jet index'). This was compared with the corresponding 'scintigraphic index' found using Patlak-Rutland graphical analysis. Absolute discrepancies were calculated. Twenty-eight of thirty-one (90%) of studies were diagnostic for the calculation of jet indices. The mean jet index was 52% (n=28, SEM=5.8%) compared to a mean scintigraphic index of 54% (n = 28, SEM = 4.0%). The two scores were correlated, with a correlation coefficient of 0.72 and the median absolute difference between the two scores was 7.7%. Forty-three per cent (12/28) of subjects had discrepancies in the two scores of 5% or less. The score differences, however, showed a highly skewed distribution with 32% (9/28) subjects showing discrepancies over 20%. This discordant group (> 20% difference) included three patients with functional pelviureteric obstruction, one with a pelvic mass and one with an underfilled bladder. Two patients with very poor quality jets had impaired renal function. In one case, the index improved after angioplasty for renal artery stenosis. This simple test is a useful adjunct to urinary tract ultrasound but should be interpreted alongside evidence of renal obstruction, and complements rather than replaces existing tests.

Adolescent↗
PubMed1997

Investigation of a methicillin-resistant Staphylococcus aureus (MRSA) outbreak in an Irish hospital: triplex PCR and DNA amplification fingerprinting.

Methicillin-resistant Staphylococcus aureus (MRSA) is becoming a problematic nosocomial pathogen. A continuing increase in numbers of isolates is reported from Irish hospitals each year. Preventing cross-infection and the further spread of endemic strains requires effective control measures. This necessitates the development of sensitive methods for both detection and genetic identification of MRSA isolates. In this study, 48 MRSA strains isolated in the Cork University Hospital were analysed between January and July 1995 using a one-tube triplex-polymerase chain reaction (PCR), wherein three genes, the methicillin-resistance gene (mecA), femA and the extracellular thermonuclease gene, nuc, were simultaneously amplified. Methicillin-sensitive S. aureus (MSSA) and coagulase-negative staphylococci (CNS) were also tested and the assay was found to be MRSA specific. The genetic relationship among this collection of MRSA isolates was also investigated. A single primer, RW3A, derived from a well-characterized, repetitive sequence found in Mycoplasma pneumoniae produced discriminating DNA fragment arrays with all the study organisms. The patterns were reproducible, even after several passages of the isolates. Quantitative analysis of the patterns divided the collection into two main groups, DAF group I representing 48% of the collection and DAF group II a further 19%. The remaining strains showed unrelated patterns. To fully outline the distribution of MRSA in this area a larger study will be necessary. This paper outlines the applicability of both the identification and fingerprinting techniques to local strains.

Cross Infection↗
PubMed1997

Diagnosis of esophageal varices by transesophageal echocardiography: a mimicker of aortic disease.

The use of transesophageal echocardiography is well established in the emergency department diagnosis of traumatic aortic diseases. It has very high sensitivity and specificity compared with those of other tests. The physician performing transesophageal echocardiography should be aware of conditions that can mimic aortic pathologic conditions, thus leading to an incorrect diagnosis. We report a case in which the presence of previously undiagnosed esophageal varices mimicked traumatic aortic disease.

Aged↗
PubMed1997

Inbreeding depression and inferred deleterious-mutation parameters in Daphnia.

DENG and LYNCH recently proposed a method for estimating deleterious genomic mutation parameters from changes in the mean and genetic variance of fitness traits upon inbreeding in outcrossing populations. Such observations are readily acquired in cyclical parthenogens. Selfing and life-table experiments were performed for two such Daphnia populations. We observed a significant inbreeding depression and an increase of genetic variance for all traits analyzed. DENG and LYNCH's original procedures were extended to estimate genomic mutation rate (U), mean dominance coefficient (h), mean selection coefficient (s), and scaled genomic mutational variance (Vm/Ve). On average, U, h, s and Vm/Ve (indicates an estimate) are 0.84 [corrected], 0.30, 0.14 and 4.6E-4, respectively. For the true values, the U and h are lower bounds, and s and Vm/Ve upper bounds. The present U, h and Vm/Ve are in general concordance with earlier results. The discrepancy between the present s and that from mutation-accumulation experiments in Drosophila (approximately 0.04) is discussed. It is shown that different reproductive modes do not affect gene frequency at mutation-selection equilibrium if mutational effects on fitness are multiplicative and not completely recessive.

Animals↗
PubMed1997

Mutation accumulation in nuclear, organelle, and prokaryotic transfer RNA genes.

A comparative analysis of the transfer RNA genes in the genomes of the major kingdoms of eukaryotes and prokaryotes leads to the general conclusion that the rate of evolution of organelle tRNA genes is typically equal to of greater than that of their nuclear counterparts. Situations where this is not the case, most notably in vascular plants, are attributable to an elevated mutation rate in the nuclear genome. Through a comparison of rates of mutation with rates of nucleotide substitution, it is shown that there is a reduction in the efficiency of selection on new mutations in organelle genes. Numerous lines of evidence, including observed reductions in stem duplex stability and changes in loop sizes, suggest that the excess changes observed in the organelle genes are mildly deleterious. Uniparental inheritance of organelles causes a reduction in the efficiency of selection through the joint effects of an increase in linkage disequilibrium and a decrease in effective population size. These results provide molecular support for the idea that asexually propagating genomes are subject to long-term, gradual fitness loss and raise questions about the role of organelle mutations in the long-term survival of major phylogenetic lineages.

Animal Population Groups↗
PubMed1997

In vitro activity of a new pneumocandin antifungal, L-743,872, against azole-susceptible and -resistant Candida species.

The in vitro activity of a new pneumocandin, L-743,872, was evaluated with 108 strains of Candida and compared with the activities of various antifungals. L-743,872 demonstrated the best activity against azole-susceptible and -resistant strains of C. albicans, C. glabrata, C. tropicalis, C. parapsilosis, and C. kefyr and less activity against C. krusei, C. lusitaniae, and C. guilliermondii.

Anti-Bacterial Agents↗
PubMed1997

Impacts of the proposed restructuring of Medicare and Medicaid on the elderly: a conceptual framework and analysis.

The article examines the proposed transformations in U.S. Medicare and Medicaid as these are likely to affect the nation's elderly population. Drawing on political economy, moral economy, and notions of the deserving versus the undeserving poor, the authors develop a broad conceptual framework within which to better understand the current upheavals. Both Republican and Democratic proposals for restructuring Medicare and Medicaid are described and analyzed, and common themes within the various proposals highlighted. After exploring the differential impacts of the restructuring on subgroups within the elderly population, including low-income seniors, the disabled, women, and elders of color, the authors conclude with a discussion of the symbolic importance of the proposed transformations. The latter reflect both accelerated government movement away from its legitimation functions and toward increased capital accumulation, and continuing government attempts to reshape our perceptions of the state economy in ways that permit more radical cutbacks and austerity measures.

Aged↗
PubMed1997

Rotavirus in Ireland.

Acute diarrhoeal disease is the commonest single cause of morbidity and mortality worldwide. Infectious diarrhoea has been estimated to cause at least 5 million deaths each year in the developing world. Very young children are particularly susceptible to

Journal Article↗
PubMed1996

Estimate of the genomic mutation rate deleterious to overall fitness in E. coli.

Mutations are a double-edged sword: they are the ultimate source of genetic variation upon which evolution depends, yet most mutations affecting fitness (viability and reproductive success) appear to be harmful. Deleterious mutations of small effect can escape natural selection, and should accumulate in small population. Reduced fitness from deleterious-mutation accumulation may be important in the evolution of sex, mate choice, and diploid life-cycles, and in the extinction of small populations. Few empirical data exist, however. Minimum estimates of the genomic deleterious-mutation rate for viability in Drosophila melanogaster are surprisingly high, leading to the conjecture that the rate for total fitness could exceed 1.0 mutation per individual per generation. Here we use Escherichia coli to provide an estimate of the genomic deleterious-mutation rate for total fitness in a microbe. We estimate that the per-microbe rate of deleterious mutations is in excess of 0.0002.

Animals↗
PubMed1996

Risk factors for constant, severe trachoma among preschool children in Kongwa, Tanzania.

Trachoma, an ocular infection caused by Chlamydia trachomatis, is the second leading cause of blindness worldwide. The blinding sequelae, which occur in middle age, are felt to be the result of numerous or lengthy episodes of severe inflammatory trachoma in childhood. Risk factors for constant, severe trachoma were identified in a group of children enrolled in a longitudinal study in Kongwa, Tanzania, where villages were randomized in a clinical trial of mass treatment and a behavior modification campaign. In 1989, each of 1,417 randomly selected children had photographs taken of an upper eyelid for determination of their trachoma status. The photographs were graded by a reader who was masked as to the village and date of each photograph. Risk factor data on the family's socioeconomic status, distance to water, and hygiene practices were obtained at baseline. Follow-up examinations occurred 2, 6, and 12 months from baseline. Data from all four time points were available for 82% of the children enrolled. Overall, 10% of the children had constant, severe trachoma, defined as severe trachoma at three or four examinations. The odds ratio for severe trachoma was 1.9 for female children (95% confidence interval 1.3-2.7). Familial cattle ownership and having one or more siblings with trachoma at baseline were also significantly related to the odds of having severe trachoma. Children with a sustainably clean face had lower odds (odds ratio = 0.4, 95% confidence interval 0.3-0.7). A subgroup of 10% of children in these hyperendemic communities always seemed to have severe trachoma, despite enrollment in a mass treatment campaign. Improved face-washing plus antibiotic treatment may decrease the likelihood that these children will be at risk for blinding complications in adulthood.

Animals↗
PubMed1996

Limb-sparing procedures: postoperative planar bone scan appearance.

OBJECTIVE: The objective of this study was to evaluate the postoperative technetium-99m-labeled methylene diphosphonate (99mTc-MDP) scintigraphic appearance of limb-sparing procedures in patients treated for bone tumors. MATERIALS AND METHODS: We retrospectively reviewed the medical records and assessed planar bone scans, subjectively and semiquantitatively, of all patients treated with limb-sparing procedures at our institution who survived at least 1 year following resection of the primary lesion. RESULTS: The operative sites of 20 of the evaluable 45 patients (44%) demonstrated normal tracer avidity during follow-up (median 12 months). Nine patients (20%) demonstrated normal avidity on their first follow-up bone scans (median 6 months). Coincident 99mTc-MDP bone scans were obtained on 11 patients who developed 12 postoperative complications or injury during the study and accurately identified the lesion in eight (67%). CONCLUSION: Although many patients have abnormal 99mTc-MDP avidity in the operative site after limb-sparing surgery, almost half eventually have normalization of uptake. However, planar bone scans have limited use for assessing the primary tumor site postoperatively as persistent abnormal avidity may preclude detection of changes associated with development of postoperative complications.

Adolescent↗
PubMed1996

Acquired supravalvular pulmonary stenosis due to extrinsic compression by a metastatic thymic carcinoid tumor.

Acquired pulmonary artery stenosis is rare. There are two main types, firstly intrinsic disease of the pulmonary valve itself, such as carcinoid heart disease. Secondly, extrinsic compression of the pulmonary artery from a mediastinal structure. We report a case of acquired pulmonary supravalvular stenosis due to extrinsic compression by carcinoid mediastinal tumor, confirmed by echocardiographic imaging/Doppler interrogation and computerized tomography.

Carcinoid Tumor↗
PubMed1996

Expression of receptors for epidermal growth factor and insulin-like growth factor I by ZR-75-1 human breast cancer cell variants is inversely related: the effect of steroid hormones on insulin-like growth factor I receptor expression.

We have investigated the expression of insulin-like growth factor I receptors (IGFR) by the ZR-75-1 human breast cancer cell line and tamoxifen-resistant (ZR-75-9a1) and oestrogen-independent (ZR-PR-LT) variants. ZR-75-1 cells expressed 6633+/-953 receptors per cell,(K(d) 0.24+/-0.06 nM). IGFR expression was reduced in ZR-75-9a1 cells (1180+/-614 receptors per cell, K(d) 0.13+/-0.05) and increased in the ZR-PR-LT cell line (18 430+/-3210 receptors per cell, K(d) 0.24+/-17). A comparison of these data with previously published findings for epidermal growth factor receptor (EGFR) expression by these cell lines revealed that IGFR and EGFR expression are inversely related in the variant lines whereas ZR-75-1 cells express similar numbers of both receptors. Since the changes in IGFR expression observed are associated with changes in steroid hormone receptor status, we also investigated the effects of oestradiol, the synthetic progestin ORG 2058 and dexamethasone on IGFR expression. Oestradiol increased IGFR expression only in the ZR-75-1 cell line. Low concentrations of ORG 2058 increased IGFR levels in the two cell lines positive for progesterone receptor (ZR-75-1 and ZR-PR-LT). High concentrations of ORG 2058 increased IGFR expression in all cell lines, as did dexamethasone. These data suggest that EGFR and IGFR expression may be linked in breast cancer, and that EGFR/IGFR ratios in breast cancer may be a more sensitive prognostic indicator than EGFR expression alone. Regardless of basal IGFR expression by the cell studied, ORG 2058 increased IGFR expression, possibly via both the progesterone and glucocorticoid receptors.

Breast Neoplasms↗
PubMed1996

Change of genetic architecture in response to sex.

A traditional view is that sexual reproduction increases the potential for phenotypic evolution by expanding the range of genetic variation upon which natural selection can act. However, when nonadditive genetic effects and genetic disequilibria underlie a genetic system, genetic slippage (a change in the mean genotypic value contrary to that promoted by selection) in response to sex may occur. Additionally, depending on whether natural selection is predominantly stabilizing or disruptive, recombination may either enhance or reduce the level of expressed genetic variance. Thus, the role of sexual reproduction in the dynamics of phenotypic evolution depends heavily upon the nature of natural selection and the genetic system of the study population. In the present study, on a permanent lake Daphnia pulicaria population, sexual reproduction results in significant genetic slippage and a significant increase in expressed genetic variance for several traits. These observations provide evidence for substantial genetic disequilibria and nonadditive genetic effects underlying the genetic system of the study population. From these results, the fitness function of the previous clonal selection phase is inferred to be directional and/or stabilizing. The data are also used to infer the effects of natural selection on the mean and the genetic variance of the population.

Analysis of Variance↗
PubMed1996

Comparing mutational variabilities.

We have reviewed the available data on VM, the amount of genetic variation in phenotypic traits produced each generation by mutation. We use these data to make several qualitative tests of the mutation-selection balance hypothesis for the maintenance of genetic variance (MSB). To compare VM values, we use three dimensionless quantities: mutational heritability, VM/VE, the mutational coefficient of variation, CVM; and the ratio of the standing genetic variance to VM, VC/VM. Since genetic coefficients of variation for life history traits are larger than those for morphological traits, we predict that under MSB, life history traits should also have larger CVM. This is confirmed; life history traits have a median CVM value more than six times higher than that for morphological traits. VC/VM approximates the persistence time of mutations under MSB in an infinite population. In order for MSB to hold, VC/VM must be small, substantially less than 1000, and life history traits should have smaller values than morphological traits. VC/VM averages about 50 generations for life history traits and 100 generations for morphological traits. These observations are all consistent with the predictions of a mutation-selection balance model.

Analysis of Variance↗