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Biomedical subjects

A Perkins

Publications and source records attributed to A Perkins.

At least 19 recordsLinked to original sources
PubMed2004

Cholesterol and APOE genotype interact to influence Alzheimer disease progression.

In this retrospective analysis of 443 Alzheimer disease (AD) patients from a 30-week tacrine trial, change in Alzheimer's Disease Assessment Scale score from baseline to final value was significantly associated with a total serum cholesterol/APOE genotype interaction. Disease progression in the no-APOE epsilon4 allele/high-cholesterol subgroup was greater than in the normal-cholesterol subgroups with or without epsilon4. Cholesterol levels and APOE genotype may interact to affect AD progression. The results are consistent with preclinical data on cholesterol's effects in AD.

Aged↗
PubMed2004

Comparison of measured and calculated radiotherapy doses in the chest region of an inhomogeneous humanoid phantom.

Errors in dose calculation by treatment planning computers are known to arise when calculation algorithms do not account for electron disequilibrium near interfaces between tissues of different density. The accuracy of a treatment planning system (Plato, Nucletron International BV) was investigated for two treatments in the chest region: tangential 6 MV photons to the chest wall and opposed AP-PA 18 MV photon fields to the mediastinum. Thermo-luminescent dosimeters were used to measure dose at 40 sites in the chest of a humanoid phantom (Rando, Alderson Associates). Measurements were compared with point doses calculated using two different versions of the Plato external beam calculation software: RTS 1.8 and the newer RTS 2.2. Measured and calculated doses differed by 3% or more at more than one quarter of all sites. The greatest discrepancies occurred for points located in lung, which were generally overestimated. The maximum discrepancies for the 6 MV tangential breast irradiation were 8.5% for RTS 1.8 and 3.5% for RTS 2.2. For the 18 MV opposed field irradiation, the maximum discrepancies were 11.4% and 8.1% respectively. RTS 2.2 was more accurate than RTS 1.8, with smaller mean and maximum discrepancies.

Anisotropy↗
PubMed2004

Testosterone and luteinizing hormone responses to naloxone help predict sexual performance in rams.

The first objective of this study was to determine whether LH and testosterone respond differently to a naloxone injection in relation to varying sexual performance in rams. If differences occurred, the second objective was to determine whether differences would predict variation in sexual performance. From a group of 1.5- to 3-yr-old rams, 20 sexually active and 39 sexually inactive rams were selected based on previously observed sexual behavior with estrual ewes. Each ram was exposed to three estrual ewes for 18 30-min sexual performance tests, and those found to be inactive were given two 30-min sexual partner preference tests. The final distribution was 28 sexually active, 22 inactive, and nine male-oriented rams. Rams were treated with 1.5 mg of naloxone/kg BW in December of Year 1 and again with either 0.75 or 1.5 mg of naloxone/kg BW in November of Year 2. Plasma concentrations of LH and testosterone were evaluated with mixed model analyses for repeated measures separately for each year to coincide with logistic procedures for modeling the probability that rams were sexually active. For Year 1, a sexual activity x age x time interaction for LH after naloxone was observed (P < 0.03). For testosterone, there was a sexual activity x time interaction (P < 0.03), with a similar, early increase for sexually active female-and male-oriented rams compared with a delayed, minimal increase for inactive rams. For Year 2, when all rams were over 2.5 yr of age, a sexual activity x time interaction for both LH and testosterone (P < 0.02) seemed more related to an earlier increase of both hormones for sexually active rams than the increase observed for inactive rams. In addition, sexually active rams had a greater increase in testosterone than inactive rams. No significant difference was observed between 0.75 and 1.50 mg of naloxone/kg BW. Testosterone and LH were used as explanatory variables and sexual activity was used as the response variable in logistic procedures. In Year 1, greatest prediction accuracy was 73.5% using testosterone at 60 min after naloxone injection. In Year 2, the greatest prediction accuracy was 85% using LH at 15 min multiplied by testosterone at 60 min after naloxone. Test repeatability for both years on the same rams was 76%. In conclusion, pattern and magnitude of naloxone-induced changes in endocrine function may facilitate identification of sexually active and inactive rams during the breeding season. Prediction accuracy of the naloxone-based test was 69 to 85%.

Animals↗
PubMed2002

Comparison of three heart disease specific health-related quality of life instruments.

BACKGROUND: We were interested in the feasibility of existing valid specific health-related quality of life [HRQL] instruments, designed for patients with heart failure, angina pectoris, or myocardial infarction [MI], being used to make outcome comparisons among pure or mixed populations of patients with these heart disease diagnoses. METHODS: A battery of specific HRQL questionnaires, including the Minnesota Living with Heart Failure questionnaire, the Seattle Angina Questionnaire, the MacNew Heart Disease questionnaire, the generic SF-36 health status survey, and the Hospital Anxiety and Depression Scale, was mailed to the 205 patients with current mailing addresses and returned by 161 patients [78.5%]. RESULTS: None of the 22 specific and generic HRQL scales differed by diagnostic category. There were significant correlations between all corresponding HRQL scales in the MLHF, SAQ, and MacNew instruments as well as between each of the corresponding specific and generic SF-36 scales. In all cases, the correlations between the specific HRQL scales were numerically greater than those between the specific instruments and the generic SF-36 scales. Patients with and without either anxiety or depression differed significantly on each of the specific HRQL instruments and on the majority of the SF-36 scales. CONCLUSION: The results of this investigation suggest that a common HRQL instrument for patients with heart failure, angina, and MI may prove to be useful when there is an interest in comparing outcomes among pure or mixed populations of patients with heart disease.

Aged↗
PubMed2001

Prevalence of cognitive impairment: data from the Indianapolis Study of Health and Aging.

BACKGROUND: The epidemiology and natural history of cognitive impairment that is not dementia is important to the understanding of normal aging and dementia. OBJECTIVE: To determine the prevalence and outcome of cognitive impairment that is not dementia in an elderly African American population. METHOD: A two-phase, longitudinal study of aging and dementia. A total of 2212 community-dwelling African American residents of Indianapolis, IN, aged 65 and older were screened, and a subset (n = 351) received full clinical assessment and diagnosis. Subsets of the clinically assessed were seen again for clinical assessment and rediagnosis at 18 and 48 months. Weighted logistic regression was used to generate age-specific prevalence estimates. RESULTS: The overall rate of cognitive impairment among community-dwelling elderly was 23.4%. Age-specific rates indicate increasing prevalence with increasing age: 19.2% for ages 65 to 74 years, 27.6% for ages 75 to 84 years, and 38.0% for ages 85+ years. The most frequent cause of cognitive impairment was medically unexplained memory loss with a community prevalence of 12.5%, followed by medical illness-associated cognitive impairment (4.0% prevalence), stroke (3.6% prevalence), and alcohol abuse (1.5% prevalence). At 18-month follow-up, 26% (17/66) of the subjects had become demented. CONCLUSIONS: Cognitive impairment short of dementia affects nearly one in four community-dwelling elders and is a major risk factor for later development of dementia.

Age Distribution↗
PubMed2001

Erythroid Kruppel-like factor (EKLF) coordinates erythroid cell proliferation and hemoglobinization in cell lines derived from EKLF null mice.

Erythroid Kruppel-like factor (EKLF) is a transcription factor of the C2H2 zinc-finger class that is essential for definitive erythropoiesis. We generated immortal erythroid cell lines from EKLF(-/-) fetal liver progenitor cells that harbor a single copy of the entire human beta-globin locus and then reintroduced EKLF as a tamoxifen-inducible, EKLF-mutant estrogen receptor (EKLF-ER) fusion protein. Addition of tamoxifen resulted in enhanced differentiation and hemoglobinization, coupled with reduced proliferation. Human beta-globin gene expression increased significantly, whereas gamma-globin transcripts remained elevated at levels close to endogenous mouse alpha-globin transcript levels. We conclude that EKLF plays a role in regulation of the cell cycle and hemoglobinization in addition to its role in beta-globin gene expression. The cell lines we used will facilitate structural and functional analyses of EKLF in these processes and provide useful tools for the elucidation of nonglobin EKLF target genes.

Active Transport, Cell Nucleus↗
PubMed2001

Assessment of clonality in melanocytic nevi.

BACKGROUND: Melanocytic nevi are among the most common lesions in man; however; their pathogenesis remains largely unknown. While often held to be neoplastic, this hypothesis has not been conclusively verified. Alternatively, some authorities have held that melanocytic nevi are hamartomas. More practically, difficulty may be encountered in the histologic discrimination of melanocytic nevi from melanoma. It was reported that nevi may be differentiated from melanoma in females by polymerase chain reaction (PCR) analysis of loci of human androgen receptor gene on the X-chromosome. However, contradictory findings have also been reported, suggesting that both acquired nevi and melanoma are clonal. METHODS: Fifteen examples of melanocytic nevus were analyzed via PCR for pattern of X-chromosome inactivation as indicated by the methylation status of the human androgen receptor gene. RESULTS: Among 15 nevi analyzed, 11 cases provided informative polymorphism at the androgen receptor loci. Nine of these 11 cases revealed a non-random pattern of X-chromosome inactivation. CONCLUSIONS: These findings suggest that melanocytic nevi are clonal/neoplastic lesions. As such, they cannot be discriminated from melanoma on the basis of clonality.

Clone Cells↗
PubMed2000

An essential role in liver development for transcription factor XBP-1.

XBP-1 is a CREB/ATF family transcription factor highly expressed in hepatocellular carcinomas. Here we report that XBP-1 is essential for liver growth. Mice lacking XBP-1 displayed hypoplastic fetal livers, whose reduced hematopoiesis resulted in death from anemia. Nevertheless, XBP-1-deficient hematopoietic progenitors had no cell-autonomous defect in differentiation. Rather, hepatocyte development itself was severely impaired by two measures: diminished growth rate and prominent apoptosis. Specific target genes of XBP-1 in the liver were identified as alphaFP, which may be a regulator of hepatocyte growth, and three acute phase protein family members. Therefore, XBP-1 is a transcription factor essential for hepatocyte growth.

Animals↗
PubMed2000

Prevalence of malnutrition on admission to four hospitals in England. The Malnutrition Prevalence Group.

AIMS: The primary objective was to estimate prevalence of malnutrition on admission to four hospitals. Secondary objectives included assessing the relationship between nutritional status and length of hospital stay, numbers of new prescriptions, new infections and disease severity. METHODS: We entered eligible patients according to predefined quotas for elective and emergency admissions to 23 specialties. We measured height, weight, Body Mass Index and anthropometrics, and recorded history of unintentional weight loss. Patients who had lost > or = 10% of their body weight, had a Body Mass Index <20, or had a Body Mass Index <20 with one anthropometric measurement <15th centile were considered malnourished. RESULTS: Of 1611 eligible patients, 761 did not participate; 269 were too ill; 256 could not be weighed; and 236 refused consent. Eight hundred and fifty were subsequently evaluated. Prevalence of malnutrition on admission was 20%. Length of stay, new prescriptions and infections and disease severity were significantly higher in the malnourished. CONCLUSIONS: One patient in every five admitted to hospital is malnourished. Although this figure is unacceptably high, it may underestimate true prevalence. Malnutrition was associated with increased length of stay, new prescriptions and infections. Malnutrition may also have contributed to disease severity.

Adolescent↗
PubMed2000

Radiation doses to patients undergoing scoliosis radiography.

In this study we computed the radiation doses associated with scoliosis radiography and investigated how these radiation doses are influenced by the weight of the patient. We recorded the radiographic technique factors of 61 consecutive patients (46 females and 15 males) undergoing scoliosis radiography. A wedge-shaped aluminium filter attenuated the X-ray beam in the "chest region" relative to the "abdomen region". X-ray tube air kerma output factors (microGy mAs-1) and half value layers (HVLs) were determined experimentally for the "chest region" and "abdomen region". The energy imparted to each patient was computed from the air kerma area product, X-ray beam HVL and measured patient thickness. Values of patient effective dose were obtained using effective dose-to-energy conversion factors for specified radiographic projections, taking into account each patient's weight. The median patient age was 17 years, and the median patient weight was 53 kg. Entrance skin air kerma values in the "chest region" were approximately a factor of four lower than those in the "abdomen region". The air kerma values increased by a factor of two when the patient weight increased from 30 kg to 70 kg. Approximately 80% of the total energy imparted to a patient undergoing a scoliosis examination was in the "abdomen region", with the remaining 20% imparted to the "chest region". Energy imparted increased with patient weight, and was approximately 3 mJ for a 30 kg patient and approximately 8 mJ for a 70 kg adult patient. Effective doses showed little correlation with patient weight, with an average-sized patient (50 kg) receiving an effective dose of approximately 140 microSv. Patients undergoing scoliosis radiography receive effective doses that are low in comparison with other types of radiographic examination.

Adolescent↗
PubMed2000

Intravenous cereport (RMP-7) modifies topographic uptake profile of carboplatin within rat glioma and brain surrounding tumor, elevates platinum levels, and enhances survival.

Several experiments studied the effects of i.v. infusions of the bradykinin agonist, Cereport (RMP-7), on permeability of the blood-brain tumor barrier in rat gliomas. First, the ability of Cereport to increase uptake of two poorly blood-brain barrier-penetrating drugs (lypophilic paclitaxel and hydrophilic carboplatin) was directly compared to provide new information regarding the scope of delivery effects achieved with Cereport. Next, the increased uptake of platinum into tumor and brain surrounding tumor was shown to closely parallel that of radiolabeled carboplatin, confirming that delivery of a biologically active moiety is increased with Cereport. This study also demonstrated that the elevated tumor levels of platinum persisted for at least 2 h. The enhanced carboplatin uptake was then examined using a novel, high spatial resolution analysis of autoradiography. This revealed that the effects of Cereport were not uniform throughout the tumor, because it especially modified those areas normally impermeable to carboplatin. Finally, a range of i.v. Cereport doses (3.0 and 9.0 microg/kg) was tested in combination with carboplatin to determine whether increased survival might be achieved and to define the relationship between Cereport dose, plasma levels, uptake of carboplatin, and enhanced survival. Survival was enhanced only by the high dose of Cereport; the high dose also produced robust increases in carboplatin uptake and plasma concentrations of Cereport estimated to achieve the K(i), whereas the low dose did not. These data offer fundamental information regarding the effects of Cereport on delivery of chemotherapeutic agents to brain tumors and provide new insight into receptor-mediated permeability of the blood-brain tumor barrier.

Animals↗
PubMed1999

Erythroid Kruppel like factor: from fishing expedition to gourmet meal.

Erythroid Kruppel like factor (EKLF) is the founding member of a family of transcription factors which are defined by the presence of three C-terminal C2H2-type zinc fingers. Since its discovery 6 years ago, the study of EKLF has been intense. In this review I will revisit the discovery of EKLF, and highlight recent advances in our understanding of how it interacts with other proteins to regulate erythroid gene transcription. The current knowledge of the biological role/s of EKLF in erythroid cell differentiation and globin gene switching are summarized.

Amino Acid Sequence↗
PubMed1999

Sexual behaviour of rams: male orientation and its endocrine correlates.

The components of heterosexual behaviour in rams are reviewed as a basis for understanding partner preference behaviour. A small percentage of rams will not mate with oestrous females and if given a choice will display courtship behaviour towards another ram in preference to a female. Some of the endocrine profiles of these male-oriented rams differ from those of heterosexual controls. These differences include reduced serum concentrations of testosterone, oestradiol and oestrone, reduced capacity to produce testosterone in vitro, and reduced capacity to aromatize androgens in the preoptic-anterior hypothalamus of the brain. Our observation that aromatase activity is significantly lower in the preoptic-anterior hypothalamic area of male-oriented rams than in female-oriented rams may indicate an important neurochemical link to sexual behaviour that should be investigated. The defect in steroid hormone production by the adult testes of the male-oriented ram may represent a defect that can be traced to the fetal testes. If this contention is correct, partner preference behaviour of rams may also be traceable to fetal development and represent a phenomenon of sexual differentiation.

Animals↗
PubMed1998

AP-2-null cells disrupt morphogenesis of the eye, face, and limbs in chimeric mice.

The homozygous disruption of the mouse AP-2 gene yields a complex and lethal phenotype that results from defective development of the neural tube, head, and body wall. The severe and pleiotropic developmental abnormalities observed in the knockout mouse suggested that AP-2 may regulate several morphogenic pathways. To uncouple the individual developmental mechanisms that are dependent on AP-2, we have now analyzed chimeric mice composed of both wild-type and AP-2-null cells. The phenotypes obtained from these chimeras indicate that there is an independent requirement for AP-2 in the formation of the neural tube, body wall, and craniofacial skeleton. In addition, these studies reveal that AP-2 exerts a major influence on eye formation, which is a critical new role for AP-2 that was masked previously in the knockout mice. Furthermore, we also have uncovered an unexpected influence of AP-2 on limb pattern formation; this influence is typified by major limb duplications. The range of phenotypes observed in the chimeras displays a significant overlap with those caused by teratogenic levels of retinoic acid, strongly suggesting that AP-2 is an important component of the mechanism of action of this morphogen.

Animals↗
PubMed1998

SEK1 deficiency reveals mitogen-activated protein kinase cascade crossregulation and leads to abnormal hepatogenesis.

SEK1 (MKK4/JNKK) is a mitogen-activated protein kinase activator that has been shown to participate in vitro in two stress-activated cascades terminating with the SAPK and p38 kinases. To define the role of SEK1 in vivo, we studied stress-induced signaling in SEK1(-/-) embryonic stem and fibroblast cells and evaluated the phenotype of SEK1(-/-) mouse embryos during development. Studies of SEK1(-/-) embryonic stem cells demonstrated defects in stimulated SAPK phosphorylation but not in the phosphorylation of p38 kinase. In contrast, SEK1(-/-) fibroblasts exhibited defects in both SAPK and p38 phosphorylation, demonstrating that crosstalk exists between the stress-activated cascades. Tumor necrosis factor alpha and interleukin 1 stimulation of both stress-activated cascades are severely affected in the SEK1(-/-) fibroblast cells. SEK1 deficiency leads to embryonic lethality after embryonic day 12.5 and is associated with abnormal liver development. This phenotype is similar to c-jun null mouse embryos and suggests that SEK1 is required for phosphorylation and activation of c-jun during the organo-genesis of the liver.

Animals↗
PubMed1998

The benefit of second eye cataract surgery.

PURPOSE/METHOD: We prospectively assessed the binocular functions of 50 patients before and after second eye cataract surgery to determine whether limiting cataract surgery to the first eye was justified or not. RESULTS: After the first cataract operation 88% of operated eyes had a visual acuity of 6/12 or better but only 52% met the UK Driver and Vehicle Licensing Agency (DVLA) driving standard for visual acuity and field. Following second eye cataract surgery, visual acuity of the second eye was better than the first in 42% of patients. Moreover, 60% of patients had an improved binocular visual acuity after their second eye operation. Ocular dominance changed in 44% of cases. Stereo acuity improved from 32% after first eye surgery to 90% after second eye surgery. Binocular horizontal field of vision improved by 20 degrees or more in 54% of patients and binocular vertical field of vision improved in 36% after second eye surgery. The proportion of patients meeting the DVLA driving standard improved from 52% after first eye surgery to 86% after second eye surgery. CONCLUSIONS: Surgery on the second eye for cataract improves binocular function and enables a greater proportion of patients to meet the DVLA driving standard by expanding their horizontal field.

Aged↗