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Biomedical subjects

L Clark

Publications and source records attributed to L Clark.

At least 19 recordsLinked to original sources

Sequence and analysis of chromosome 4 of the plant Arabidopsis thaliana.

The higher plant Arabidopsis thaliana (Arabidopsis) is an important model for identifying plant genes and determining their function. To assist biological investigations and to define chromosome structure, a coordinated effort to sequence the Arabidopsis genome was initiated in late 1996. Here we report one of the first milestones of this project, the sequence of chromosome 4. Analysis of 17.38 megabases of unique sequence, representing about 17% of the genome, reveals 3,744 protein coding genes, 81 transfer RNAs and numerous repeat elements. Heterochromatic regions surrounding the putative centromere, which has not yet been completely sequenced, are characterized by an increased frequency of a variety of repeats, new repeats, reduced recombination, lowered gene density and lowered gene expression. Roughly 60% of the predicted protein-coding genes have been functionally characterized on the basis of their homology to known genes. Many genes encode predicted proteins that are homologous to human and Caenorhabditis elegans proteins.

Animals

Golli-induced paralysis: a study in anergy and disease.

The Golli-MBP transcription unit contains three Golli-specific exons as well as the seven exons of the classical myelin basic protein (MBP) gene and encodes alternatively spliced proteins that share amino acid sequence with MBP. Unlike MBP, which is a late Ag expressed only in the nervous system, Golli exon-containing gene products are expressed both pre- and postnatally at many sites, including lymphoid tissue, as well as in the central nervous system. To investigate whether Golli-MBP peptides unique to Golli would result in neurological disease, we immunized rats and observed a novel neurological disease characterized by mild paralysis and the presence of groups of lymphocytes in the subarachnoid space but not in the parenchyma of the brain. Disease was induced by Th1-type T cells that displayed an unusual activation phenotype. Primary stimulation in vitro induced T cell proliferation with increased surface CD45RC that did not become down-regulated as it did in other Ag-stimulated cultures. Secondary stimulation of this CD45RChigh population with Ag, however, did not induce proliferation or IL-2 production, although an IFN-gamma-producing population resulted. Proliferation could be induced by secondary stimulation with IL-2 or PMA-ionomycin, suggesting an anergic T cell population. Cells could adoptively transfer disease after secondary stimulation with IL-2, but not with Ag alone. These responses are suggestive of a chronically stimulated, anergic population that can be transiently activated to cause disease, fall back into an anergic state, and reactivated to cause disease again. Such a scenario may be important in chronic human disease.

Adoptive Transfer

Recurrent ductal carcinoma in situ after total mastectomy.

A case report is presented of a woman with recurrent DCIS occurring several years following a total mastectomy, the diagnosis of which was aided by a subpectoral saline implant. A discussion of factors associated with recurrence and a review of the literature is provided. A role for selective use of mammography in screening postmastectomy reconstructed breasts in patients at high risk for recurrence is suggested.

Adult

Laparoscopic biliary and enteric bypass.

Very few patients with a periampullary neoplasm present with resectable disease. Consequently, various operative and non-operative techniques have been developed to palliate patients with unresectable periampullary disease. Laparoscopic biliary (cholecystojejunostomy) and enteric bypass (gastrojejunostomy) are reasonable options as compared to their open counterparts for operative palliation. However, only a limited number of carefully selected patients meet selection criteria for laparoscopic palliation.

Bile Duct Neoplasms

Determinants of depression and HIV-related worry among HIV-positive women who have recently given birth, Bangkok, Thailand.

HIV-infected pregnant women have been the focus of considerable research related to biomedical issues of mother-to-child transmission worldwide. However, there have been few reports on the psychological well-being of new mothers with HIV, either in developed or developing countries. As part of a perinatal HIV transmission and family impact study in Bangkok, predictors of psychological scales were evaluated from interview data (N = 129) collected 18-24 months postpartum. Standardised questionnaires were used to assess depressive symptoms and HIV-related worry. Depressive symptomatology and HIV-related worry were common amongst these women. Multivariate logistic regression analysis identified several factors that predicted these psychological outcomes. High depression scores were associated with women who were no longer in a relationship with their partner (odds ratio (OR) 5.72, confidence interval (CI) 2.18-14.97) and who used venting coping strategies (OR 2.15, CI 1.44-3.21). Higher levels of HIV-related worry were associated with women whose babies were HIV-infected (OR 3.51, CI 1.28-10.69), who had not disclosed their HIV status to others (OR 3.05, CI 1.29-7.24) and who reported that their HIV-infection was something about which their family would be ashamed (OR 3.44, CI 1.34-9.77). Based on the current findings, intervention strategies we propose are psychological interventions which address disclosure issues, feelings of shame and coping strategies as well as financial assistance for single mothers. Interventions that require few resources such as group counselling or support merit special consideration.

Adaptation, Psychological

Coping strategies and behavior problems of urban African-American children: concurrent and longitudinal relationships.

The development and correlates of 82 inner-city African-American children's coping strategies were examined across three years. Results indicated no change in the mean frequency of self-reported coping strategies over the three years, and a significant correlation of emotion-focused strategies with increased self- and mother-reported behavior problems. Child-reported externalizing problems (and, to a lesser degree, internalizing problems) predicted changes in coping strategies across assessments.

Adaptation, Psychological

Traumatic stress in HIV-infected women.

This study assesses the prevalence of specific traumatic stressors that meet criterion A for the Diagnostic and Statistical Manual of Mental Disorders' (DSM-IV) diagnosis of posttraumatic stress disorder (PTSD) and symptoms of PTSD in a representative sample of HIV-infected women. The study also assesses the impact of these stressors and symptoms on the clinical progression of HIV infection. The Life Stressor Checklist and the Impact of Events Scale-Revised were administered via interview to 67 Africa-American women beyond the initial stages of HIV infection. The ratio of CD4 t-cells to CD8 t-cells were abstracted from medical records at dates that approximated psychological interviews and were examined at two points in time 12 to 14 months apart. The prevalence of traumatic stressors and PTSD symptoms were high among HIV-infected women. Traumatic stressors were significantly associated with a lower CD4 to CD8 ratio at the 1-year follow-up. Among women who reported a traumatic event, those who also met criteria for PTSD evidenced a lower CD4 to CD8 ratio at the follow-up assessment. The study concludes that prevention and treatment efforts targeted at HIV-infected women must take into account traumatic stressors and PTSD symptoms and their potential impact on the course of the disease.

Adolescent

Animal model of vascular inflammation.

Inflammatory mechanisms play a central role in the pathology of a variety of conditions ranging from atherosclerosis, arthritis, cancer and Alzheimer's disease. Under normal conditions the inflammatory response initiates protective actions, but triggers tissue damage under pathological conditions. Acute or chronic inflammation is mediated by nascent expression of a host of proteins such as the cytokines interleukins (IL), tumor necrosis factor (TNF), and interferons. Currently available in vitro or in vivo methods do not offer the specificity to probe the complex inflammatory cascade. We developed an animal model in which a single injection of the proinflammatory cytokines TNF-alpha and IL-1 beta in live rodents initiates a rapid inflammatory reaction which can be monitored by video microscopy and electron microscopy. This model exhibits the characteristic feature of inflammatory reaction such as adhesion and transmigration of leukocytes, and activation and degranulation of platelets and mast cells. This model is applicable to inflammatory processes in the peripheral and cerebral vasculature including the blood-brain barrier disruption in Alzheimer's disease. The animal model of inflammation reported here may prove to be a valuable tool in investigating the pathophysiology of a number of inflammatory diseases and identifying potential targets as well as agents for therapy.

Animals

Impact of HIV on families of HIV-infected women who have recently given birth, Bangkok, Thailand.

The objective of this study was to assess changes in the family situation of HIV-infected women who have recently given birth. As part of a prospective perinatal HIV transmission study, interviews were conducted with a subset of HIV-infected women at 18 to 24 months postpartum, and answers were compared with baseline information obtained during pregnancy. Standardized scales were used to assess levels of psychosocial functioning. A convenience sample of 129 HIV-infected women enrolled during pregnancy was interviewed at 18 to 24 months postpartum. At delivery, the women were young (median age, 22 years), primiparous (57%), and asymptomatic (93%). When baseline and follow-up data were compared, more women were living alone (1% versus 6%; p = 0.03), fewer women were living with their partners (98% versus 73%; p < 0.001), and 30% of families had reduced incomes. At follow-up, 10% of partners had died, and more partners than wives had become ill or died (21% versus 4%; p = 0.02). Most children (78%) were living with their mothers, but only 57% of the HIV-infected women were the primary caretakers. Fewer women had disclosed their HIV status to others (e.g., family, friends) than to their partners (34% versus 84%; p < 0.001), largely because of fear of disclosure. The women appeared to have high levels of depression and worry. The women's greatest worries were about their children's health and the family's future. Within 2 years after childbirth, substantial change within the families of HIV-infected women was evident. These were manifest by partner illness or death, family separation, reduced family income, shifting responsibilities for child care, and signs of depression and isolation. Providing family support is a major challenge in Thailand as the perinatal HIV epidemic progresses.

Adult

Bird repellents: interaction of chemical agents in mixtures.

Numerous studies characterize the concentration-behavioral response for odorants, tastants, and irritants. However, to achieve ecological validity, interaction of agents in mixtures must be considered. Equiresponse and equimolar molar models of interactions have been proposed, and methods for testing whether agents in mixture interact independently have been evaluated. Yet these averaging models cannot a priori predict whether agents will interact antagonistically, independently, or synergistically. I studied the bird repellent properties of several structurally similar and well-described trigeminally mediated avian irritants, singly and in mixture. Compounds within a chemical class, in which the electron withdrawing groups were similar, interacted independently to produce their repellent effects, e.g., 2-amino methyl benzoate v methyl-2-methoxy benzoate, and o-aminoacetophenone v 2-methoxy acetophenone. The response to mixtures drawn from compounds of dissimilar chemical class, e.g., 2-amino methyl benzoate v o-aminoacetophenone, interacted antagonistically at concentrations below 10 mM, suggesting meditation by a different mechanism within the trigeminally mediated sensory modality. At 10 mM and near saturation of the solutions, there was no evidence of interaction between agents, suggesting responses became saturated. These observations underscore our previous findings for the importance of the molecular properties of the carbonyl group for aromatic bird repellents and suggests the possible existence of multiple receptor mechanisms for avian trigeminal repellents. These data also underscore the importance of attending to interactions of agents in mixtures when designing repellents as tools for the management of wildlife and resolution of conflicts between humans and wildlife.

Algorithms

The Family Health Project: psychosocial adjustment of children whose mothers are HIV infected.

The psychosocial adjustment of 87 inner-city African American children 6-11 years old whose mothers were HIV infected was compared with that of 149 children from a similar sociodemographic background whose mothers did not report being HIV infected. Children were not identified as being HIV infected. Mother reports, child reports, and standardized reading achievement scores were used to assess 4 domains of adjustment: externalizing problems, internalizing problems, cognitive competence, and prosocial competence. The results indicated that, on average, children from both groups had elevated levels of behavior problem scores and low reading achievement scores when compared with national averages. Relative to children whose mothers were not infected, those whose mothers were HIV infected were reported to have more difficulties in all domains of psychosocial adjustment. Potential family processes that may explain the findings are discussed.

Achievement

Failure to collect oocytes in assisted reproductive technology: a retrospective.

While there is much information and discussion on pregnancy failure after assisted reproductive technologies, less emphasis is placed on the failure to collect oocytes after apparently successful ovarian stimulation. This retrospective survey reviewed 4973 treatment cycles in order to obtain information about the likelihood of this event. Overall 42 women (43 treatment cycles) failed to have oocytes collected [0.86% of treatments started and 0.92% of women given human chorionic gonadotrophin (HCG)]. However, in only six cases was this failure unexpected (0.1%) with no obvious potential clinical reason (i.e. all six cases had: HCG administered; more than two follicles >15 mm in diameter; oestradiol values >2000 pmol/l; <38 years old; normal body mass index). Indifference concerning uncommon events is fraught with peril, as although rare, the particular outcome may be devastating to the individual, both economically and psychologically. Eighteen of the 42 women did not return for on-going treatment suggesting increased contact by clinic staff may be required when oocyte retrieval is not achieved. These data suggest that the failure to collect oocytes after apparently successful ovarian stimulation is rare and random. The information has proved useful in allaying the fears of couples contemplating assisted reproductive technologies.

Adult

Increasing breastfeeding rates to reduce infant illness at the community level.

OBJECTIVE: Although breastfeeding is associated with lower rates of a variety of infant illnesses, skeptics have suggested that much of the association is attributable to confounding, even after appropriate statistical adjustment. This article utilizes a novel design to investigate changes in infant illness at the community level after a successful breastfeeding promotion program. METHODS: In this population-based cohort study, the medical records of all infants born in one Navajo community the year before a breastfeeding promotion program (n = 977) and the year during the intervention (n = 858) were reviewed. Outcomes assessed include changes after the intervention in: proportion breastfeeding and/or breastfeeding exclusively; incidence of common infant illnesses in the first year of life; and feeding-group specific incidence of illness. RESULTS: The proportion of women breastfeeding exclusively for any period of time increased from 16.4% to 54.6% after the intervention. The percent of children having pneumonia and gastroenteritis declined 32. 2% and 14.6%, respectively, after the intervention. Feeding-group specific rates of these illnesses were unchanged, indicating that the decline observed was attributable to the increased proportion of infants breastfeeding. In contrast, rates of croup and bronchiolitis increased after the intervention among those fed formula from birth, suggesting a viral epidemic which was limited to those never exclusively breastfed. Finally, sepsis declined in both formula-fed and breastfed infants after the intervention, suggesting that other factors affected this illness outcome after the intervention. CONCLUSIONS: Increasing the proportion of exclusively breastfed infants seems to be an effective means of reducing infant illness at the community level. The experimental design suggests that the increased incidence of illness among minimally breastfed infants is causally related to lack of breast milk, rather than being attributable to confounding.

Breast Feeding

Diagnosis of pancreatic carcinoma: role of FDG PET.

OBJECTIVE: The purpose of this study was to investigate the role of positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) in differentiating benign from malignant disease in patients with possible pancreatic malignancy. SUBJECTS AND METHODS: All patients with a possible diagnosis of pancreatic carcinoma based on CT or ERCP findings were eligible for inclusion in this prospective study. PET imaging of the abdomen was performed in 37 patients and was interpreted as positive if FDG activity in the pancreas exceeded background activity and as negative if activity was less than or equal to background activity. Semiquantitative analysis was performed by calculating a standardized uptake ratio. Studies were reviewed independently by two radiologists, and results were correlated with biopsy results and with CT and ERCP findings. Sensitivity and specificity of FDG PET for revealing pancreatic malignancy was determined. RESULTS: FDG activity in the pancreas was increased in 24 patients, and adenocarcinoma was diagnosed in 22 of these patients (92%). Two patients (8%) with increased activity had benign disease, including one patient with chronic pancreatitis who showed no evidence of tumor at laparotomy and one patient with a mucinous cystic tumor who showed no malignant features at laparotomy. FDG uptake was low or normal in 13 patients, 10 of whom (77%) had benign disease. FDG uptake was also low in three patients with adenocarcinoma, whose tumor size ranged from 2 to 4 cm in diameter. The mean standardized uptake ratio value for malignant disease was 5.1 (range, 1.0-10.1) and for benign disease was 1.9 (range, 0.0-5.8) (p < .001). The sensitivity of FDG PET for revealing malignant disease in the pancreas was 88% and the specificity was 83%. CONCLUSION: FDG PET is a sensitive and specific noninvasive technique for the diagnosis of pancreatic malignancy.

Adenocarcinoma

Quality care for cardiology patients.

To evaluate outcome measures in a cardiology unit, patient satisfaction was measured. Patients consistently related problems in two areas: pain management and the waiting period before their procedure. After a major system change, patient satisfaction increased 16% and 29% respectively.

Heart Diseases

Noninvasive detection of allograft rejection in heart transplant recipients by use of Doppler tissue imaging.

BACKGROUND: Allograft rejection in heart transplant recipients is associated with lymphocytic extracellular infiltration and edema resulting in increased myocardial stiffness and abnormal relaxation. We hypothesize that these abnormalities will result in reduced myocardial relaxation velocities. Doppler tissue imaging is a novel noninvasive imaging modality that is capable of quantifying myocardial tissue velocities and may therefore be useful to identify allograft rejection. METHODS: In this observational study, 121 heart transplant recipients underwent pulsed-wave Doppler tissue imaging at the time of their surveillance endomyocardial biopsies. Peak relaxation and systolic velocities were measured from the inferior wall blinded to clinical biopsy. Biopsy results were classified as rejecting (3a, 3b, 4) or nonrejecting (0, 1a, 1b). RESULTS: The peak relaxation velocity in nonrejecting allograft recipients (n = 98) was 0.21 m/sec +/- 0.01. During moderate allograft rejection (n = 16), peak relaxation velocities decreased to 0.14 m/sec +/- 0.01 (p < 0.0001), and subsequently increased to 0.23 m/sec +/- 0.0 after successful treatment (p = 0.0001). Peak systolic velocities did not change during rejection, 0.08 m/sec +/- 0.02 when compared with nonrejecting recipients 0.09 +/- 0.02 (p = NS). With a cutoff value of less than 0.16 m/sec, the sensitivity of peak myocardial relaxation velocities for detection of rejection was 76%. The specificity and negative predictive values were 88% and 92%, respectively. CONCLUSION: Moderate allograft rejection results in reduced myocardial relaxation velocities, which can be detected noninvasively with pulsed-wave Doppler tissue imaging. Hence, Doppler tissue imaging is a useful noninvasive tool to exclude allograft rejection.

Adult