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Biomedical subjects

L Clarke

Publications and source records attributed to L Clarke.

At least 19 recordsLinked to original sources
PubMed2001

Functional redundancies, distinct localizations and interactions among three fission yeast homologs of centromere protein-B.

Several members of protein families that are conserved in higher eukaryotes are known to play a role in centromere function in the fission yeast Schizosaccharomyces pombe, including two homologs of the mammalian centromere protein CENP-B, Abp1p and Cbh1p. Here we characterize a third S. pombe CENP-B homolog, Cbh2p (CENP-B homolog 2). cbh2Delta strains exhibited a modest elevation in minichromosome loss, similar to cbh1Delta or abp1Delta strains. cbh2Delta cbh1Delta strains showed little difference in growth or minichromosome loss rate when compared to single deletion strains. In contrast, cbh2Delta abp1Delta strains displayed dramatic morphological and chromosome segregation defects, as well as enhancement of the slow-growth phenotype of abp1Delta strains, indicating partial functional redundancy between these proteins. Both cbh2Delta abp1Delta and cbh1Delta abp1Delta strains also showed strongly enhanced sensitivity to a microtubule-destabilizing drug, consistent with a mitotic function for these proteins. Cbh2p was localized to the central core and core-associated repeat regions of centromeric heterochromatin, but not at several other centromeric and arm locations tested. Thus, like its mammalian counterpart, Cbh2p appeared to be localized exclusively to a portion of centromeric heterochromatin. In contrast, Abp1p was detected in both centromeric heterochromatin and in chromatin at two of three replication origins tested. Cbh2p and Abp1p homodimerized in the budding yeast two-hybrid assay, but did not interact with each other. These results suggest that indirect cooperation between different CENP-B-like DNA binding proteins with partially overlapping chromatin distributions helps to establish a functional centromere.

Amino Acid Sequence↗
PubMed2001

Gingko biloba: a case report of herbal medicine and bleeding postoperatively from a laparoscopic cholecystectomy.

An increasing variety of alternative health care products (defined as "over-the-counter," nonprescribed herbal medicines) are taken by patients for a plethora of reasons. Unfortunately these self-prescribed remedies are seldom considered by the patient to be medications and as a result it has been noted that 70 per cent of patients do not reveal herbal use to their allopathic practitioners or hospital personnel. The rapid growth of this herbal self-therapy has important implications for the practice of surgery. A case of post-laparoscopic cholecystectomy bleeding in a patient taking Gingko biloba is reported. This preparation has been reported to cause spontaneous bleeding and may interact with anticoagulants and antiplatelet agents. Other herbal medicines have also been associated with potential increased bleeding including garlic, feverfew, ginger, and ginseng. It is vital for surgeons to be apprised of all substances ingested by patients, to be cognizant of their potential adverse effects and drug interactions, and to be familiar with their therapeutic modality, all of which will help to optimize therapeutic approaches and improve patient outcome.

Adult↗
PubMed2000

A novel member of the Swi6p family of fission yeast chromo domain-containing proteins associates with the centromere in vivo and affects chromosome segregation.

We previously used a genetic approach to identify a new class of Schizosaccharomyces pombe genes (chromosome loss when overexpressed; clo genes) that, when present in elevated dosage, cause the loss of an otherwise stable cen1 linear minichromosome at high rates. Here we report the identities of two clo genes; one encodes histone H3.3 and the other, designated clo2, encodes a novel protein with significant homology to fission yeast Swi6p, human and Drosophila HP1 heterochromatin proteins, and other chromo domain-containing proteins. Members of this group have been shown to localize to heterochromatic DNA, including centromeres, and to play roles in chromatin formation and organization. The S. pombe Clo2 protein localizes to centromere DNA in vivo, and overexpression of clo2 leads to a dramatic increase in the rate of mitotic loss of an artificial chromosome. Clo2p is not essential for mitotic growth, however, even in cells that also lack Swi6p. Thus, fission yeast appears to utilize multiple, functionally redundant, HP1-related proteins for heterochromatin-associated activities at centromeres and perhaps elsewhere in the genome.

Amino Acid Sequence↗
PubMed2000

Influence of thyrotropin-releasing hormone administration at birth on thermoregulation in lambs delivered by cesarean.

OBJECTIVE: We examined the hypothesis that exogenous stimulation with thyrotropin-releasing hormone immediately before umbilical cord clamping can improve thermoregulation in near-term lambs delivered by cesarean. STUDY DESIGN: Twin lambs were injected with either saline solution alone (control, n = 12) or thyrotropin-releasing hormone in saline solution (n = 16) and were immediately placed in a warm (30 degrees C; n = 14) or cool (15 degrees C; n = 14) ambient temperature. In vivo measurements of temperature control (colonic temperature, oxygen consumption, and incidence of shivering) were then performed during the first 6 hours after birth, in conjunction with plasma thyroid hormone measurements. Brown adipose tissue was then sampled for measurement of uncoupling protein 1 abundance. RESULTS: Plasma triiodothyronine concentrations were significantly higher in lambs treated with thyrotropin-releasing hormone than in control lambs between 3 and 6 hours after birth, as were plasma thyroxine concentrations 1 and 5 hours after birth. Delivery temperature had no effect on plasma thyroid hormone concentrations. At 6 hours after birth the abundance of uncoupling protein 1 was higher in lambs treated with thyrotropin-releasing hormone than in control lambs. Lambs treated with thyrotropin-releasing hormone exhibited a lower incidence of shivering than did control lambs between 5 and 6 hours after birth, and an effect of ambient temperature on the incidence of shivering was observed only in the control group. From 3 to 6 hours after birth colonic temperature was significantly higher in cool-delivered lambs treated with thyrotropin-releasing hormone than in the control group. Oxygen consumption was higher in cool-delivered lambs than warm-delivered lambs, but this was not influenced by thyrotropin-releasing hormone. Irrespective of delivery temperature, lambs treated with thyrotropin-releasing hormone possessed more pericardial adipose tissue and hepatic glycogen than did control lambs. CONCLUSION: Thyrotropin-releasing hormone treatment stimulated thyroid hormone secretion in the neonatal lamb and improved thermoregulation during the first 6 hours after birth in near-term lambs delivered by cesarean under cool conditions.

Adipose Tissue, Brown↗
PubMed2000

Influence of relative size at birth on growth and glucose homeostasis in twin lambs during juvenile life.

The effect of differences in size at birth on growth and glucose homeostasis between female twin lambs during juvenile life was examined. Twenty-six sets of twins were entered into the study, of which ten were used for organ sampling at birth and 16 were studied over the first year of life. Eleven sets were defined as being mismatched for birthweight as the weight difference between twins was >25%, with light lambs weighing 4.1 +/- 0.3 kg and heavy lambs weighing 5.1 +/- 0.1 kg. All remaining twins were matched in bodyweight, weighing 4.6 +/- 0.5 kg. During the rapid period of juvenile growth (i.e. one, three and six months of age) and following stabilization of bodyweight (i.e. 12 months of age) glucose tolerance tests were performed by intravenously injecting 0.8 mg kg(-1) bodyweight glucose. This was followed the next day with an insulin tolerance test, performed by intravenously injecting 0.08 units kg(-1) bodyweight insulin. At birth there were no differences in organ weight as a fraction of total bodyweight between matched and mismatched twins, but the ratio of liver to brain weight was lower in light compared with heavy twins. Light lambs remained lighter than their twins up to six months of age, and crown-rump length was also shorter. At one and three months of age there were no differences in basal plasma glucose concentrations between the groups, but glucose tolerance was greater in light compared with heavy lambs at one and six months of age. Insulin tolerance was greater in light compared with matched lambs at one and six months of age. In conclusion, it has been shown that size at birth of one twin in relation to its co-twin is one factor determining glucose regulation during postnatal life. This not only affects glucose and insulin tolerance but also growth over the first six months of age.

Abdomen↗
PubMed2000

HIV infection with negative serological tests: development of seropositivity in association with highly active antiretroviral therapy.

A 19-year-old woman with well-documented HIV-1 infection had persistently negative enzyme immunoassay (EIA) and Western blot serological tests. She has plasma HIV-1 RNA levels of > 480,000 copies/mL and T-helper cell counts of approximately 100/mm3. When treated with highly active antiretroviral therapy (HAART), the viral load became undetectable (< 400 copies/mL), the T-helper cell count increased to > 500/mm3 and EIA and Western blot tests became positive.

Adult↗
PubMed2000

Fission yeast homologs of human CENP-B have redundant functions affecting cell growth and chromosome segregation.

Two functionally important DNA sequence elements in centromeres of the fission yeast Schizosaccharomyces pombe are the centromeric central core and the K-type repeat. Both of these DNA elements show internal functional redundancy that is not correlated with a conserved DNA sequence. Specific, but degenerate, sequences in these elements are bound in vitro by the S. pombe DNA-binding proteins Abp1p (also called Cbp1p) and Cbhp, which are related to the mammalian centromere DNA-binding protein CENP-B. In this study, we determined that Abp1p binds to at least one of its target sequences within S. pombe centromere II central core (cc2) DNA with an affinity (K(s) = 7 x 10(9) M(-1)) higher than those of other known centromere DNA-binding proteins for their cognate targets. In vivo, epitope-tagged Cbhp associated with centromeric K repeat chromatin, as well as with noncentromeric regions. Like abp1(+)/cbp1(+), we found that cbh(+) is not essential in fission yeast, but a strain carrying deletions of both genes (Deltaabp1 Deltacbh) is extremely compromised in growth rate and morphology and missegregates chromosomes at very high frequency. The synergism between the two null mutations suggests that these proteins perform redundant functions in S. pombe chromosome segregation. In vitro assays with cell extracts with these proteins depleted allowed the specific assignments of several binding sites for them within cc2 and the K-type repeat. Redundancy observed at the centromere DNA level appears to be reflected at the protein level, as no single member of the CENP-B-related protein family is essential for proper chromosome segregation in fission yeast. The relevance of these findings to mammalian centromeres is discussed.

Autoantigens↗
PubMed2000

Effect of maternal nutrient restriction in early to mid gestation and thyrotrophin-releasing hormone on lamb survival following Caesarean section delivery near to term.

We investigated the influence of restricted maternal nutrition between 28 and 77 days gestation on survival and thermoregulatory adaptation following Caesarean section delivery near to term. This study was designed to examine the hypothesis that adaptation after birth would be compromised in those lambs born to nutrient restricted ewes. We further hypothesised that this would be due in part to inadequate hypothalamic-pituitary-thyroidal function. Lambs born to nutrient restricted ewes were untreated (RU) or treated with thyrotrophin-releasing hormone (TRH; RT) immediately prior to umbilical cord clamping. Single bearing ewes consumed either 6.60 MJ x day(-1) (controls, n = 4) or 3.00 MJ x day(-1) (nutrient restricted, n = 15) from 28-77 days gestation, after which all ewes consumed 7.20 MJ x day(-1). All lambs born to control ewes commenced continuous breathing and began to shiver following Caesarean section delivery and survived to 6 h after birth. Only 4 out of 9 RU lambs established continuous breathing and survived to 6 h after birth compared with all RT lambs. Six hours after birth, RT lambs possessed perirenal brown adipose tissue with a higher thermogenic activity than 6 h old RU or control lambs. Lamb birth weight was similar in all groups. In conclusion, near-term lambs born to ewes nutrient restricted in early to mid gestation are at increased risk of death following Caesarean section delivery. Survival after birth can be significantly enhanced if TRH is administered to the lambs immediately before delivery.

Adaptation, Physiological↗
PubMed2000

Effect of delivery temperature on endocrine stimulation of thermoregulation in lambs born by cesarean section.

We examined the hypothesis that exogenous stimulation with physiological doses of 3,5,3'-triiodothyronine (T(3)) and/or norepinephrine at birth can improve thermoregulation in near-term lambs delivered by cesarean section. This was achieved by investigating the effect of delivery temperature [i.e., warm (30( degrees )C) vs. cool (15( degrees )C) ambient temperatures] on hormonal stimulation on uncoupling protein-1 (UCP1) abundance in brown adipose tissue. In vivo measurements of temperature control (i. e., colonic temperature, oxygen consumption, and incidence of shivering) were made over the first 2.5 h after birth. Each lamb was injected with saline with or without T(3), norepinephrine, or T(3) plus norepinephrine. Irrespective of delivery temperature, abundance of UCP1 increased and incidence of shivering decreased by all hormonal treatments, but this only reduced the rate of decline in colonic temperature of cool-delivered lambs. Oxygen consumption was higher in cool-delivered lambs that were able to fully restore body temperature, an adaptation not observed in controls or any warm-delivered groups. Exogenous administration of endocrine stimulatory factors can enhance the abundance of UCP1 in cesarean-section-delivered lambs with the magnitude of thermoregulatory response being greater at cool than warm delivery temperatures.

Adipose Tissue↗
PubMed2000

Effect of feeding level and thyroxine on adipose tissue development and growth in postnatal lambs.

We investigated the influence of exogenous thyroxine (T4) administration in conjunction with level of feeding on adipose tissue and liver growth in postnatal lambs. Pairs of lambs were fed either 100 g (i.e. low fed) or 200 g (i.e. high fed) of milk powder per litre of reconstituted milk replacer over the first month of life. Half of the pairs of lambs were fed a bolus dose of T4 (15 mg (kg body weight)-1) daily until 8 days of age. Perirenal adipose tissue and hepatic tissue were sampled at either 8 or 35 days of age. High fed lambs grew faster, possessed more adipose tissue and had larger livers than low fed lambs at 8 and 35 days of age. T4 administration resulted in a lower thermogenic activity (i.e. GDP binding) in adipose tissue at 8 days of age in low, but not high fed lambs. There was no difference between groups in colonic temperature or oxygen consumption. Between 17 and 35 days of age high fed lambs previously treated with T4 had lower daily milk consumption than untreated siblings, but still attained the same growth rate. Plasma insulin-like growth factor-I concentrations were greater in high than low fed lambs, a relationship that was not influenced by T4 treatment. In adipose tissue, iodothyronine 5' deiodinase activity was not influenced by T4 administration and was greater in high than low fed lambs. Hepatic iodothyronine 5' deiodinase activity was not influenced by T4 administration in low fed lambs, but was reduced by T4 in high fed lambs. In conclusion, T4 administration over the first 8 days of life can accelerate the rate of decline in thermogenic activity of uncoupling protein-1. This effect is not observed when the level of feeding is increased. Following withdrawal of T4 treatment, high fed T4-treated lambs were able to maintain the same growth rate as untreated lambs despite having a lower food intake.

Adipose Tissue↗
PubMed2000

Children's family change: reports and records of mothers, fathers and children compared.

Family change, when adults depart or arrive around children, raises policy issues. Its measurement depends upon the evidence collected and from whom. This paper compares British children's histories obtained from fathers and mothers. The evidence, on one birth cohort of parents, comes from two sources: the National Child Development Study and the ONS Longitudinal Study. The resulting account of family change is not substantially different between parents. There is some under-reporting of children not living with their fathers. This is due to under-reporting by those included in the studies and to under-representation in them of absent fathers and lone parents.

Adolescent↗
PubMed1999

Attenuation of the euphoric effects of cocaine by the dopamine D1/D5 antagonist ecopipam (SCH 39166)

BACKGROUND: The subjective and reinforcing effects of cocaine in humans are associated with the enhancement of endogenous dopamine function in the mesolimbic system. This study examined the role of dopamine D1-like receptors in the behavioral and mood effects of cocaine by evaluating the effects of the selective D1/D5 antagonist ecopipam (SCH 39166) on subjective responses to intravenous cocaine in 11 subjects with cocaine dependence as defined by DSM-IV. METHODS: Subjects were pretreated in a randomized double-blind fashion with either placebo or 10 mg, 25 mg, or 100 mg of ecopipam orally on 4 separate occasions. Two hours later a single intravenous injection of 30 mg of cocaine was administered. Subjective and cardiovascular responses were measured and blood samples for pharmacokinetic evaluation were obtained prior to cocaine dosing and at various times after dosing. RESULTS: The euphoric (P = .004) and stimulating (P = .03) effects of cocaine were attenuated in a dose-dependent manner by ecopipam, while ratings of desire to take cocaine were diminished (P = .02). Ecopipam in combination with cocaine was safe and well tolerated. CONCLUSION: These data indicate a potentially important role for D1-like receptors in the acute mood-altering and rewarding effects of cocaine in humans.

Adult↗
PubMed1999

Prevalence and incidence of gynecologic disorders among women infected with human immunodeficiency virus.

OBJECTIVE: Our purpose was to ascertain the prevalence, incidence, and predictors of gynecologic disorders among women infected with human immunodeficiency virus. STUDY DESIGN: We serially assessed 292 women infected with human immunodeficiency virus and 681 uninfected women. Outcomes were incidence and prevalence of sexually transmitted diseases, viral shedding, findings of Papanicolaou smears, fungal infections, and menstrual disorders. RESULTS: Women infected with the virus were more likely to have prevalent vulvovaginal candidiasis (odds ratio 1.80, 95% confidence interval 1. 0-3.25, P =.05), oncogenic human papillomavirus (odds ratio 3.79, 95% confidence interval 2.43-5.91, P =.001), abnormal Papanicolaou smears (odds ratio 5.40, 95% confidence interval 3.35-8.78, P =.001), amenorrhea (4.8% vs 0%, P =.05), positive results on Treponema pallidum hemagglutination assay (odds ratio 1.83, 95% confidence interval 1.16-2.88, P =.01), infection with cytomegalovirus (odds ratio 4.2, 95% confidence interval 1.82-10.62, P =.001), and genital warts (odds ratio 6.93, 95% confidence interval 3.16-16.30, P =.001) but were less likely to have Chlamydia trachomatis infection (odds ratio 0.28, 95% confidence interval 0.10-0.66, P =.01). Annual incidence rates among women infected with human immunodeficiency virus were 4.0% for candidiasis, 22.0% for oncogenic human papillomavirus, 11.4% for genital warts, 1.7% for infection with C trachomatis, 1.7% for infection with Neisseria gonorrhoeae, 10.3% for Trichomonas vaginalis, 1.1% for positive results on T pallidum hemagglutination assay, 7.4% for an abnormal Papanicolaou smear, and 10.9% for infection with herpes simplex virus. Overall, 46.9% had at least 1 incident condition. Women infected with human immunodeficiency virus were more likely to have incident oncogenic human papillomavirus infection (odds ratio 2.0, 95% confidence interval 1.01-3.8), abnormal Papanicolaou smears (odds ratio 7.76, 95% confidence interval 2.08-42.8), and genital warts (odds ratio 9. 32, 95% confidence interval 3.04-38.0). Incidence and prevalence of sexually transmitted diseases and oncogenic human papillomavirus infection increased with increased CD4(+) cell counts. CONCLUSIONS: Women infected with the human immunodeficiency virus are significantly more likely to have prevalent and incident gynecologic disorders but not disorders related to risk taking (eg, incident sexually transmitted diseases). The latter disorders increased in women with CD4(+) cell counts >500 cells/mm3. Clinicians should be aware of these patterns so that they can provide appropriate evaluation and treatment of gynecologic disorders.

Adult↗
PubMed1999

Effects of single intravenous doses of recombinant human interleukin-10 on subsets of circulating leukocytes in humans.

Recombinant human interleukin-10 (rhIL-10) is a potent and specific immunomodulatory agent which inhibits endotoxin-stimulated pro-inflammatory cytokine production by monocytes, blocks T-lymphocyte activation by antigen presenting cells, and modulates T(H)1/T(H)2 balance in immune responses. In previous clinical trials, rhIL-10 administered to healthy volunteers induced rapid and transient elevations of neutrophil and monocyte counts and reductions of lymphocyte counts in addition to suppression of endotoxin-stimulated whole blood cytokine synthesis. We sought to better characterize the effects of rhIL-10 on immunophenotypically defined subsets of circulating leukocytes that could be relevant to its immunomodulatory effects. Healthy volunteers were given single doses of 10 microg/kg rhIL-10 (n = 8) or equivalent placebo (n = 4) by intravenous injection. Significant changes of circulating leukocytes included transiently increased neutrophils and monocytes with parallel increases of CD33+ and CD14+ cells. Total lymphocytes as well as total CD3+, CD3+/CD4+ and CD3+/CD8+ cells transiently decreased. Mean fluorescence intensity of CD11a (integrin alpha-chain subunit of lymphocyte function antigen-1, LFA-1) on lymphocytes transiently but significantly decreased, suggesting a mechanism for transient alteration of lymphocyte trafficking. In addition, mean fluorescence intensity of HLA-DR (major histocompatibility class II) on CD14+ cells (predominantly monocytes) transiently but significantly decreased, implying a possible alteration of antigen presenting function. Further study will be required to elucidate the immunomodulatory roles and potential clinical significance of these hematologic changes in therapeutic trials of rhIL-10 in patients with chronic inflammatory and autoimmune diseases.

Adult↗
PubMed1999

Digital mammography: comparison of adaptive and nonadaptive CAD methods for mass detection.

RATIONALE AND OBJECTIVES: The authors compared the performance of adaptive and nonadaptive computer-aided diagnostic (CAD) methods for breast mass detection with digital mammography. MATERIALS AND METHODS: Both adaptive and nonadaptive modular CAD methods employed recent advances in multiresolution and mutiorientation wavelet transforms for improved feature extraction. The nonadaptive method uses fixed parameters for the image preprocessing modules. The adaptive method, a new class of algorithms, adapts to image content by selecting parameters for the image preprocessing modules within a parameter range. Comparison of the two methods was performed for each individual CAD module with a region-of-interest (ROI) database containing all mass types and normal tissue. RESULTS: Receiver operating characteristic (ROC) analysis clearly demonstrated an improvement in performance for the three adaptive modules and a significant overall difference between the two methods. The average ROC area index (Az) values were 0.86 and 0.95 for the nonadaptive and adaptive methods, respectively. The corresponding P value is .0145. For a previously reported database of full mammographic images containing 50 abnormal cases with all mass types and 50 normal images, the adaptive CAD method had a sensitivity of 96% (1.71 false-positive results per image) compared with 89% (1.91 false-positive results per image) for the nonadaptive CAD method. CONCLUSION: The adaptive CAD method demonstrated better performance. A study is in progress to determine the generalizability of the adaptive CAD method by applying it to larger retrospective image databases with different film digitizers.

Algorithms↗