Biomedical subjects

A Collins

Publications and source records attributed to A Collins.

At least 91 records · Page 5Linked to original sources

PubMed1999

Gender differences in psychological reactions to infertility among couples seeking IVF- and ICSI-treatment.

BACKGROUND: Gender differences and similarities in psychological reactions related to infertility, perception of social support, the effect of infertility on the marital relationship and coping-style were investigated among Swedish couples seeking in vitro fertilization -- or intracytoplasmic sperm injection - treatment. METHODS: Ninety-one couples entering treatment completed the Infertility Reaction Scale, a self-report questionnaire with structured and open-ended questions and the Miller Behavioral Style Scale. RESULTS: The women reacted more strongly to their infertility than the men as measured by the Infertility Reaction Scale (p<0.05). Factor analysis of the Infertility Reaction Scale produced three factors for men and women respectively. The first factor that emerged for the men was 'The male role and social pressure' and the second factor was 'The major focus of life'. For the women the two first factors were reversed compared to those of the men. The third factor 'Effect on sexual life' was similar for men and women. Significantly more men than women had not confided in anyone about their infertility problem (p<0.001). The information-seeking coping style was significantly correlated with infertility distress only among men (p<O.05). CONCLUSION: The women reacted more strongly to their infertility than the men and they felt an intense desire to have a child. They received more social support than their partners, who experienced the fulfillment of the male role as well as the social role to become a parent as the most central aspects of infertility. The information-seeking coping style was significantly correlated with infertility distress only among men.

Adult↗

PubMed1998

Linkage of asthma to markers on chromosome 12 in a sample of 240 families using quantitative phenotype scores.

We present evidence of linkage between markers on chromosome 12 and asthma using the BETA program for nonparametric single- and multipoint linkage analysis. We have used quantitative scores as our phenotypic variables, combining data into indices for asthma and atopy and maximizing heritability. The largest single-locus LODs were achieved for asthma: D12S342 and asthma score (LOD 2.255), D12S324 and asthma affection (LOD 2.214), and D12S366 and wheeze (LOD 3.307). The region of interest identified using multipoint analysis, with a maximum LOD of 2.29, centers around D12S97 at location 173.5 cM with a standard error of 6.5 for the asthma score and close agreement for asthma affection and wheeze. Such evidence merits further investigation of this area in an attempt to define the region with greater precision with a view to identifying candidate genes. We hope that the methods presented will encourage researchers to use phenotypic information in a way that encourages meta-analysis.

Adolescent↗

PubMed1998

Allelic association under map error and recombinational heterogeneity: a tale of two sites.

Recombination acts on the genetic map, not on the physical map. On the other hand, the physical map is usually more accurate. Choice of the genetic or physical map for positional cloning by allelic association depends on the goodness of fit of data to each map under an established model. Huntington disease illustrates the usual case in which the greater reliability of physical data outweighs recombinational heterogeneity. Hemochromatosis represents an exceptional case in which unrecognized recombinational heterogeneity retarded positional cloning for a decade. The Malecot model performs well for major genes, but no approach assuming either equilibrium or disequilibrium has been validated for oligogenes contributing to common disease. In this case of greatest interest, the power of allelic association relative to linkage is less clear than for major genes.

Alleles↗

PubMed1998

Tests and estimates of allelic association in complex inheritance.

Family-based procedures such as the transmission disequilibrium test (TDT) were motivated by concern that sample-based methods to map disease genes by allelic association are not robust to population stratification, migration, and admixture. Other factors to consider in designing a study of allelic association are specification of gene action in a weakly parametric model, efficiency, diagnostic reliability for hypernormal individuals, interest in linkage and imprinting, and sibship composition. Family-based samples lend themselves to the TDT despite its inefficiency compared with cases and unrelated normal controls. The TDT has an efficiency of 1/2 for parent-offspring pairs and 2/3 for father-mother-child trios. Against cases and hypernormal controls, the efficiency is only 1/6 on the null hypothesis. Although dependent on marker gene frequency and other factors, efficiency for hypernormal controls is always greater than for random controls. Efficiency of the TDT is increased in multiplex families and by inclusion of normal sibs, approaching a case-control design with normal but not hypernormal controls. Isolated cases favor unrelated controls, and only in exceptional populations would avoidance of stratification justify a family-based design to map disease genes by allelic association.

Alleles↗

PubMed1998

High-density perfusion culture of insect cells with a biosep ultrasonic filter.

The baculovirus/insect cell expression system has provided a vital tool to produce a high level of active proteins for many applications. We have developed a very high-density insect cell perfusion process with an ultrasonic filter as a cell retention device. The separation efficiency of the filter was studied under various operating conditions. A cell density of over 30 million cells/mL was achieved in a controlled perfusion bioreactor and cell viability remained greater than 90%. Sf9 cells from a high-density culture and a spinner culture were infected with two recombinant baculoviruses expressing genes for the production of human chitinase and monocyte-colony inhibition factor. The protein yield on a cell basis from infecting high-density Sf9 cells was the same as or higher than that from the spinner Sf9 culture. Virus production from the high-density culture was similar to that from the spinner culture. The results show that the ultrasonic filter did not affect insect cells' ability to support protein expression and virus production following infection with baculovirus. The potential applications of the high-density perfusion culture for large-scale protein expression from Sf9 cells are also highlighted.

Animals↗

PubMed1998

Reproductive cessation in female mammals.

In female mammals, fertility declines abruptly at an advanced age. The human menopause is one example, but reproductive cessation has also been documented in non-human primates, rodents, whales, dogs, rabbits, elephants and domestic livestock. The human menopause has been considered an evolutionary adaptation, assuming that elderly women avoid the increasing complications of continued childbirth to better nurture their current children and grandchildren. But an abrupt reproductive decline might be only a non-adaptive by-product of life-history patterns. Because so many individuals die from starvation, disease and predation, detrimental genetic traits can persist (or even be favoured) as long as their deleterious effects are delayed until an advanced age is reached, and, for a given pattern of mortality, there should be an age by which selection would be too weak to prevent the onset of reproductive senescence. We provide a systematic test of these alternatives using field data from two species in which grandmothers frequently engage in kin-directed behaviour. Both species show abrupt age-specific changes in reproductive performance that are characteristic of menopause. But elderly females do not suffer increased mortality costs of reproduction, nor do post-reproductive females enhance the fitness of grandchildren or older children. Instead, reproductive cessation appears to result from senescence.

Adaptation, Physiological↗

PubMed1998

Mapping a disease locus by allelic association.

Allelic association provides a means to map disease genes that, in a dense map of polymorphic markers, has considerably higher resolution than linkage methods. We describe here a composite likelihood estimate of location for a disease gene against a high-resolution marker map by using allele frequencies at linked loci. Data may be family-based, as in the transmission disequilibrium test, or from a case-control study. chi2 tests, logarithm of odds, standard errors, and information weights are provided. The method is illustrated by analysis of published cystic fibrosis haplotypes, in which DeltaF508 is more accurately localized than by other association studies. This differs from current approaches by adopting a more general Malecot model for isolation by distance, where distance here is between marker and disease locus, allowance for errors in the map and model, and freedom from assumptions about demography, systematic pressures, and the ratio of physical to genetic distance. When these assumptions are introduced the number of generations since the original mutation may be estimated, but this is not required to determine location and its standard error, so that evidence from allelic association may be efficiently combined with linkage evidence to identify a region for positional cloning of a disease gene.

Alleles↗

PubMed1998

Preculturing of Chinese hamster V79 cells with sublethal concentration of theophylline sensitizes cells to cytotoxic effects of MNNG.

In our previous work concerning the biologic effects of theophylline, we found that cells incubated during 48 h at low concentrations of theophylline (0.3 mg/ml of medium) manifested short-term deviations in the rate of DNA replication; however, this short-term inhibition of DNA replication did not reduce either the growth rate or the colony-forming ability of cells. In the present study, we concentrated on cytotoxic and DNA-damaging effects of MNNG on V79 cells precultured with sublethal concentration of methylxanthine theophylline. Cytotoxicity was evaluated on the basis of growth rate of treated cells as well as by colony-forming ability (plating efficiency) test and by trypan blue exclusion test. The level of DNA lesions (strand breaks) induced by MNNG was measured by alkaline DNA unwinding and by the comet assay. In an effort to explain higher cytotoxic effects of MNNG on precultured cells, we studied rejoining of damaged parental DNA after 4 h incubation post-MNNG-treatment as well. We found differences as against the controls in theophylline-precultured cells after treatment with the mutagen and carcinogen MNNG. The higher cytotoxic effect of MNNG in precultured cells was accompanied by a higher level of ss breaks of DNA and by more unrepaired lesions which remained after 4 h in parental DNA. Our results demonstrate that theophylline belongs to the group of agents inhibiting repair of potentially lethal DNA lesions.

Animals↗

PubMed1998

Responses of alveolar macrophages and epithelial type II cells to oxidative DNA damage caused by paraquat.

Because lung cells are inevitably exposed to chemicals, drugs and mineral particles, they are appropriate target cells for investigating effects of environmental toxins. We have studied alveolar macrophages and epithelial type II pneumocytes freshly isolated from the rat lung, using the comet assay to detect DNA damage (strand breaks and oxidized bases) in individual cells after treatment with the pesticide paraquat. The background level of strand breaks is five times higher in freshly isolated pneumocytes than in alveolar macrophages. This difference remains even after 48 h of in vitro culture and therefore probably does not reflect trauma suffered during isolation. In contrast, endogenous formamidopyrimidine glycosylase- and endonuclease III-sensitive sites, which are specific indicators of oxidative damage, are present in freshly isolated alveolar macrophages but not in pneumocytes, reflecting the high metabolic activity of macrophages and their defensive role. Both cell types are exquisitely sensitive to strand breakage by paraquat. In addition, specific base oxidation is detected after 24 h of treatment with paraquat, especially in alveolar macrophages. Susceptibility to DNA damage, rather than lipid peroxidation, is likely to be the cause of paraquat-induced death in these cells. The relatively high level of endogenous damage in pneumocytes suggests that these cells are inefficient at DNA repair, which would be consistent with their probable role as the principal progenitors of lung cancer.

Animals↗

PubMed1998

Non-disjunction of chromosome 18.

A sample of 100 trisomy 18 conceptuses analysed separately and together with a published sample of 61 conceptuses confirms that an error in maternal meiosis II (MII) is the most frequent cause of non-disjunction for chromosome 18. This is unlike all other human trisomies that have been studied, which show a higher frequency in maternal meiosis I (MI). Maternal MI trisomy 18 shows a low frequency of recombination in proximal p and medial q, but not the reduction in proximal q observed in chromosome 21 MI non-disjunction. Maternal MII non-disjunction does not fit the entanglement model that predicts increased recombination, especially near the centromere. Whereas recent data on MII trisomy 21 show the predicted increase in recombination proximally, maternal MII trisomy 18 has non-significantly reduced recombination. Therefore, chromosome-specific factors must complicate the simple model of susceptible chiasma distributions interacting with age-dependent deterioration of the meiotic mechanism. For chromosome 18, 30% of tetrads are nullichiasmate in maternal MI non-disjunction, but nullichiasmates are not observed in maternal MII non-disjunction. Chiasma distributions from normal chromosome 18 meioses provide no evidence for normal disjunction from nullichiasmate tetrads. We extend this study to examine the remaining autosomes and find no evidence for normal disjunction from nullichiasmate tetrads generally.

Age Factors↗

PubMed1998

Psychological reactions during in-vitro fertilization: similar response pattern in husbands and wives.

The purpose of this study was to examine differences in daily emotional, physical and social reactions among husbands and wives during in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Forty couples about to undergo ICSI or IVF at a private infertility clinic monitored their emotional, physical and social reactions daily for one complete treatment cycle from the first day of stimulation until the outcome of treatment was known (approximately 35 days). The results showed that men and women had a similar response pattern to oocyte retrieval, fertilization, embryo transfer and the pregnancy test. These stages were associated with the most significant changes in reactions for both spouses. The pattern of results suggested that the most important psychological determinant of reactions during IVF was the uncertainty of treatment procedures. Spouses appeared to be equally sensitive to this uncertainty and both appeared to respond to it with ambivalent feelings involving emotional distress and positive feelings of hope and intimacy.

Adult↗

PubMed1998

Distress level in men undergoing intracytoplasmic sperm injection versus in-vitro fertilization.

The purpose of this study was to compare the psychological reactions of men undergoing intracytoplasmic sperm injection (ICSI) (n=18) or in-vitro fertilization (IVF) (n=22). Men monitored their psychological reactions daily for one complete treatment cycle from the first day of down-regulation until the outcome of treatment was known (approximately 52 days). The results showed that ICSI patients reported marginally more distress on the days prior to retrieval than the IVF patients. Other than this difference the pattern of results indicated that the psychological reactions of men undergoing ICSI or IVF were similar and that there was no need to manage these patients differently during treatment. However, ICSI patients may benefit from some reassuring comments on the days prior to retrieval when they showed more anticipatory anxiety.

Adult↗

PubMed1998

A review of myeloproliferative disease with presentation in the head and neck region.

The diagnosis of an essential thrombocytosis is demonstrated in this presentation of a well-looking 53 year old man who had a five-year history of increasing facial asymmetry as evidenced by deviation of his mandible to the right and malocclusion. The enlarged mandibular condyle was the first manifestation of his underlying myeloproliferative disorder. His management will be discussed. Neoplastic diseases of the multipotent haematopoietic stem cells result in four major diseases: chronic myelogenous leukaemia (CML); polycythaemia vera (PV); agnogenic myeloid metaplasia with myelofibrosis (AMM/MF); essential thrombocytosis (ET). CML: demonstrates increased production of neutrophils and marked splenomegaly. It is divided into a chronic phrase typified by hyperplasia of mature bone marrow elements and a blastic or acute phase which evolves into a proliferation of immature marrow elements and can develop into acute myelogenous leukaemia. PV: associated with increased production of all myeloid cells but dominated by increased red blood cells with splenomegaly. AMM/MF: allows the neoplastic stem cells to proliferate and lodge in multiple sites outside the bone marrow. Splenomegaly and fibrosis of marrow spaces also occurs. ET: resulting in a markedly elevated platelet count in the absence of a recognizable stimulus. Treatment revolves around measures to maintain hydration, to relieve arthralgias, to prevent thrombotic episodes, and to prevent infections.

Diagnosis, Differential↗

PubMed1998

Beta-carotene enhances the recovery of lymphocytes from oxidative DNA damage.

Epidemiological studies have revealed a strong correlation between high intake of fruit and vegetables and low incidence of certain cancers. Micronutrients present in these foods are thought to decrease free radical attack on DNA and hence protect against mutations that cause cancer, but the fine details of the causal mechanism have still to be elucidated. Whether dietary factors can modulate DNA repair--a crucial element in the avoidance of carcinogenesis--is an intriguing question that has not yet been satisfactorily answered. In order to investigate the effects of beta-carotene on oxidative damage and its repair, volunteers were given a single 45 mg dose and lymphocytes taken before and after the supplement were treated in vitro with H2O2. DNA strand breaks and oxidised pyrimidines were measured at intervals, to monitor the removal of oxidative DNA damage. We found inter-individual variations in response. In cases where the baseline plasma beta-carotene concentration was high, or where supplementation increased the plasma concentration, recovery from oxidative damage (i.e. removal of both oxidised pyrimidines and strand breaks) was relatively rapid. However, what seems to be an enhancement of repair might in fact represent an amelioration of the continuing oxidative stress encountered by the lymphocytes under in vitro culture conditions. We found that culture in a 5% oxygen atmosphere enhanced recovery of lymphocytes from H2O2 damage.

Adult↗

PubMed1997

Urogenital and vasomotor symptoms in relation to menopausal status and the use of hormone replacement therapy (HRT) in healthy women during transition to menopause.

OBJECTIVE: To investigate the relationship between climacteric status, hormonal levels, vasomotor symptoms, vaginal dryness and urinary incontinence in a cohort of healthy women during transition to menopause, and further to evaluate the effects of hormone replacement therapy on these symptoms. METHODS: A total of 147 women were followed for 4 years during transition to menopause. They were all 49 years old when entering the study. Each annual visit included a general health screening, gynecological examination and blood sampling. The subjects were questioned about sociodemographic background, obstetric and gynecological history and they kept bleeding diary cards. RESULTS: Urinary incontinence was reported by 57% at the first visit and decreased to 34% at the last visit. No correlation to hormonal levels or to the use of HRT (hormone replacement therapy) was seen, but parity was significantly (P = 0.05) correlated to urinary incontinence. Vaginal dryness occurred in 37% at the first visit. Vaginal dryness was experienced by 1/3 of the premenopausal women. Vasomotor symptoms were reported by 56% at the first visit and were associated with high levels of FSH and LH (P < 0.001 and P = 0.002, respectively). One third of premenopausal women reported on vasomotor symptoms. Hormone replacement therapy did not relieve hot flushes in these women. CONCLUSIONS: Urogenital and vasomotor symptoms experienced by premenopausal women do not seem to be relieved by hormone replacement therapy.

Cohort Studies↗

PubMed1997

Immunogenetics of leishmanial and mycobacterial infections: the Belem Family Study.

In the 1970s and 1980s, analysis of recombinant inbred, congenic and recombinant haplotype mouse strains permitted us to effectively 'scan' the murine genome for genes controlling resistance and susceptibility to leishmanial infections. Five major regions of the genome were implicated in the control of infections caused by different Leishmania species which, because they show conserved synteny with regions of the human genome, immediately provides candidate gene regions for human disease susceptibility genes. A common intramacrophage niche for leishmanial and mycobacterial pathogens, and a similar spectrum of immune response and disease phenotypes, also led to the prediction that the same genes/candidate gene regions might be responsible for genetic susceptibility to mycobacterial infections such as leprosy and tuberculosis. Indeed, one of the murine genes (Nramp1) was identified for its role in controlling a range of intramacrophage pathogens including leishmania, salmonella and mycobacterium infections. In recent studies, multicase family data on visceral leishmaniasis and the mycobacterial diseases, tuberculosis and leprosy, have been collected from north-eastern Brazil and analysed to determine the role of these candidate genes/regions in determining disease susceptibility. Complex segregation analysis provides evidence for one or two major genes controlling susceptibility to tuberculosis in this population. Family-based linkage analyses (combined segregation and linkage analysis; sib-pair analysis), which have the power to detect linkage between marker loci in candidate gene regions and the putative disease susceptibility genes over 10-20 centimorgans, and transmission disequilibrium testing, which detects allelic associations over 1 centimorgan (ca. 1 megabase), have been used to examine the role of four regions in determining disease susceptibility and/or immune response phenotype. Our results demonstrate: (i) the major histocompatibility complex (MHC: H-2 in mouse, HLA in man: mouse chromosome 17/human 6p; candidates class II and class III including TNF alpha/beta genes) shows both linkage to, and allelic association with, leprosy per se, but is only weakly associated with visceral leishmaniasis and shows neither linkage to nor allelic association with tuberculosis; (ii) no evidence for linkage between NRAMP1, the positionally cloned candidate for the murine macrophage resistance gene Ity/Lsh/Bcg (mouse chromosome 1/human 2q35), and susceptibility to tuberculosis or visceral leishmaniasis could be demonstrated in this Brazilian population; (iii) the region of human chromosome 17q (candidates NOS2A, SCYA2-5) homologous with distal mouse chromosome 11, originally identified as carrying the Scl1 gene controlling healing versus nonhealing responses to Leishmania major, is linked to tuberculosis susceptibility; and (iv) the 'T helper 2' cytokine gene cluster (proximal murine chromosome 11/human 5q; candidates IL4, IL5, IL9, IRF1, CD14) controlling later phases of murine L. major infection, is not linked to human disease susceptibility for any of the three infections, but shows linkage to and highly significant allelic association with ability to mount an immune response to mycobacterial antigens. These studies demonstrate that the 'mouse-to-man' strategy, refined by our knowledge of the human immune response to infection, can lead to the identification of important candidate gene regions in man.

Animals↗

PubMed1997

Molecular cloning and expression of 56-58 KD antigen associated with transplant coronary artery disease.

High circulating levels of anti-endothelial antibodies have been reported in patients with accelerated transplant coronary artery disease (TxCAD); however, the nature or characteristics of the antigen to which these antibodies bind in vivo remain unclear. To identify the antigen, a human endothelial cell cDNA expression library was constructed in lambdaZAP and immuno-screened with serum containing a high titre of anti-endothelial antibodies. Nucleotide sequence of cloned cDNA inserts and GenBank database searches revealed a 94% identity in a 35 bp overlap to the human vimentin gene. The cloned antigen fusion protein co-migrated with human vimentin of molecular mass 56-58 KD in SDS-PAGE and exhibited immunoreactivity towards monoclonal and polyclonal anti-human vimentin antibodies. These results suggest that the 56-58 KD antigen associated with accelerated TxCAD is vimentin (or a vimentin-like protein), a cytoskeletal protein present in cells of the blood vessel walls.

Antibodies, Monoclonal↗

PubMed1997

Scanning mutagenesis of the putative transmembrane segments of Kir2.1, an inward rectifier potassium channel.

Structural models of inward rectifier K+ channels incorporate four identical or homologous subunits, each of which has two hydrophobic segments (M1 and M2) which are predicted to span the membrane as alpha helices. Since hydrophobic interactions between proteins and membrane lipids are thought to be generally of a nonspecific nature, we attempted to identify lipid-contacting residues in Kir2.1 as those which tolerate mutation to tryptophan, which has a large hydrophobic side chain. Tolerated mutations were defined as those which produced measurable inwardly rectifying currents in Xenopus oocytes. To distinguish between water-accessible positions and positions adjacent to membrane lipids or within the protein interior we also mutated residues in M1 and M2 individually to aspartate, since an amino acid with a charged side chain should not be tolerated at lipid-facing or interior positions, due to the energy cost of burying a charge in a hydrophobic environment. Surprisingly, 17 out of 20 and 17 out of 22 non-tryptophan residues in M1 and M2, respectively, tolerated being mutated to tryptophan. Moreover, aspartate was tolerated at 15 out of 22 and 15 out of 21 non-aspartate M1 and M2 positions respectively. Periodicity in the pattern of tolerated vs. nontolerated mutations consistent with alpha helices or beta strands did not emerge convincingly from these data. We consider the possibility that parts of M1 and M2 may be in contact with water.

Alanine↗