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Biomedical subjects

Richard Thompson

Publications and source records attributed to Richard Thompson.

At least 19 recordsLinked to original sources

A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth.

The unique metabolic profile of cancer (aerobic glycolysis) might confer apoptosis resistance and be therapeutically targeted. Compared to normal cells, several human cancers have high mitochondrial membrane potential (DeltaPsim) and low expression of the K+ channel Kv1.5, both contributing to apoptosis resistance. Dichloroacetate (DCA) inhibits mitochondrial pyruvate dehydrogenase kinase (PDK), shifts metabolism from glycolysis to glucose oxidation, decreases DeltaPsim, increases mitochondrial H2O2, and activates Kv channels in all cancer, but not normal, cells; DCA upregulates Kv1.5 by an NFAT1-dependent mechanism. DCA induces apoptosis, decreases proliferation, and inhibits tumor growth, without apparent toxicity. Molecular inhibition of PDK2 by siRNA mimics DCA. The mitochondria-NFAT-Kv axis and PDK are important therapeutic targets in cancer; the orally available DCA is a promising selective anticancer agent.

Animals↗

Multicomponent semiconducting polymer systems with low crystallization-induced percolation threshold.

Blends and other multicomponent systems are used in various polymer applications to meet multiple requirements that cannot be fulfilled by a single material. In polymer optoelectronic devices it is often desirable to combine the semiconducting properties of the conjugated species with the excellent mechanical properties of certain commodity polymers. Here we investigate bicomponent blends comprising semicrystalline regioregular poly(3-hexylthiophene) and selected semicrystalline commodity polymers, and show that, owing to a highly favourable, crystallization-induced phase segregation of the two components, during which the semiconductor is predominantly expelled to the surfaces of cast films, we can obtain vertically stratified structures in a one-step process. Incorporating these as active layers in polymer field-effect transistors, we find that the concentration of the semiconductor can be reduced to values as low as 3 wt% without any degradation in device performance. This is in stark contrast to blends containing an amorphous insulating polymer, for which significant reduction in electrical performance was reported. Crystalline-crystalline/semiconducting-insulating multicomponent systems offer expanded flexibility for realizing high-performance semiconducting architectures at drastically reduced materials cost with improved mechanical properties and environmental stability, without the need to design all performance requirements into the active semiconducting polymer itself.

Journal Article↗

Posttraumatic stress syndromes: Useful or negative heuristics?

The articles in this special issue provide a wide range of challenges to current conceptions, nosology, and assessment procedures for posttraumatic stress disorders. At best, they overcome the negative heuristic posed by these disorders, reopening issues that have preemptively been closed about dissociation, the presumed causal connection between a life threatening event and the symptoms of posttraumatic stress disorders, and the adequacy of checklist assessments of symptoms. They note discontinuities between current thinking about these disorders and the dominant thinking of the past. We make recommendations for more studies that similarly challenge the validity of current conceptions of posttraumatic disorders and dissociation, and the adequacy of checklist assessments of symptoms. With this goal, we note the value of studying ersatz posttraumatic stress response. Finally, we call for greater transparency in this literature with author disclosure of activity as expert witnesses.

Diagnosis, Differential↗

Genetic and genomic analysis of legume flowers and seeds.

New tools, such as ordered mutant libraries, microarrays and sequence based comparative maps, are available for genetic and genomic studies of legumes that are being used to shed light on seed production, the objective of most arable farming. The new information and understanding brought by these tools are revealing the biological processes that underpin and impact on seed production.

Computational Biology↗

Effect of early childhood adversity on child health.

OBJECTIVE: To examine the effect of child abuse and other household dysfunction on child health outcomes. DESIGN: Data from the Longitudinal Studies of Child Abuse and Neglect collected through interviews and questionnaires administered when target children were 4 years old and 6 years old. SETTING: Children in the South, East, Midwest, Northwest, and Southwest United States. PARTICIPANTS: One thousand forty-one children at high risk for child abuse and neglect (3 cohorts derived primarily from among children recruited through social service mechanisms, 1 cohort recruited at birth from among high-risk infants, and 1 cohort recruited from a medical setting). MAIN OUTCOME MEASURES: (1) Association of 7 adverse exposures (3 categories of child abuse [physical abuse, sexual abuse, and psychological maltreatment] and 4 categories of household dysfunction [caregiver problem drinking, caregiver depression, caregiver treated violently, and criminal behavior in the household]) derived from data collected when the child was 4 years old. (2) Indexes of child physical health at age 6 years (caregiver overall assessment of child health and reports of illness requiring medical attention). RESULTS: Two thirds of the sample had experienced at least 1 adverse exposure. One adverse exposure almost doubled the risk of overall poor health (odds ratio, 1.89; 95% confidence interval, 1.02-3.48), and 4 adverse exposures or more almost tripled the risk of illness requiring medical attention (odds ratio, 2.83; 95% confidence interval, 1.10-7.31). CONCLUSION: Adverse environmental exposures, including child abuse and other household dysfunction, are associated with poor child health even at an early age, although our data do not support a dose-response relationship.

Alcoholism↗

Verbal and physical aggression in World War II former prisoners of war: role of posttraumatic stress disorder and depression.

This study examined the relationship among posttraumatic stress disorder (PTSD), depression, and intimate partner relationship aggression in a community sample of World War II (WWII) male military former prisoners of war (POWs). Sixty percent of these POWs reported verbal aggression in their marriages, and 12% endorsed physical aggression. Both verbal and physical aggression were significantly correlated to the severity of captivity trauma and to PTSD symptoms. Posttraumatic stress disorder symptoms significantly mediated the relationship between severity of trauma and both verbal and physical aggression. Depression was a significant moderator of the relationship between PTSD and both physical and verbal aggression. Theoretical and clinical implications are suggested.

Aggression↗

Caregivers' perceptions of child mental health needs and service utilization: an urban 8-year old sample.

This study extended previous research on mental health utilization to a sample of 214 preadolescent children and their caregivers. Predictors of two distinct phases of service utilization were tentatively examined in multivariate analyses: caregivers' perceptions that children needed services and receipt of those services by children. Of these children, 24.8% were perceived by their caregivers as needing mental health services; 11.7% received mental health services and 13.1% did not. Internalizing behavioral problems increased children's likelihood of being seen as needing services, but failed to increase likelihood of receiving services. Four factors predicted receipt of mental health services: relative lack of poverty, non-African American ethnicity, externalizing behavior problems, and child history of maltreatment. Implications for services targeted at preadolescent children are discussed.

Caregivers↗

Suicidal ideation in veterans receiving treatment for opiate dependence.

Persons with opiate use disorders, especially veterans, have a number of both chronic and acute indicators of risk for suicide, but are not typically screened for suicidal ideation on a routine basis, beyond initial evaluations. One hundred one veterans receiving treatment for opiate dependence at an urban VA medical center were screened for suicidal ideation. Over 24% reported some suicidal ideation. Current ideation was associated with severe chronic pain, ongoing problems with street drugs, firearm ownership, and with having recently enrolled in treatment. It was also associated with a variety of recent negative life events and mental health issues, especially depression, recurring troubling thoughts, hallucinations, loss of jobs, and conflicts with family members. Two veterans endorsing suicidal ideation required immediate hospitalization. The implications of these findings are discussed, and frequent screening for suicidal ideation among patients receiving treatment for opiate dependence is recommended.

Employment↗

Indeterminate colitis: a significant subgroup of pediatric IBD.

BACKGROUND: Indeterminate colitis (IC) is a subgroup of inflammatory bowel disease (IBD) that cannot be characterized as either ulcerative colitis (UC) or Crohn's disease (CD). Our aims are to determine the prevalence of IC in our pediatric patient population and to describe its clinical presentation, natural history,and disease distribution. METHODS: We performed a retrospective database analysis of all children diagnosed with IBD at the Johns Hopkins Children's IBD Center between 1996 and 2001. Patient demographics, including age, sex, and age at disease onset, were tallied. Disease distribution was identified on the basis of a review of all endoscopic, colonoscopic, histopathological, and radiological records. All of the patients were followed up clinically to determine the extent of disease progression on the basis of the initial diagnosis of IC. RESULTS: Among 250 children registered in the database, 127 (50.8%) had a diagnosis of CD, 49 (19.6%) had UC, and 74(29.6%) had IC. Patients with IC had a significantly younger mean +/- SEM age (9.53 +/- 4.8 years) at diagnosis compared with patients with CD (12.4 +/- 3.8 years; P < 0.001) but not compared with patients with UC (7.41 +/- 3.5 years). Among the patients with IC, 59 (79.7%) had a pancolitis at diagnosis, and the remaining 15 had left-sided disease that progressed to a pancolitis within a mean of 6 years. Twenty-five patients (33.7%) with an initial diagnosis of IC were reclassified to either CD or UC after a median follow-up of 1.9 years (range 0.6-4.5 years). Forty-nine patients (66.2%) maintained their diagnosis of IC after a mean follow-up of 7 years (SEM 2.5 years). CONCLUSIONS: IC is a distinct pediatric subgroup of IBD with a prevalence that is higher than that observed in adults. Children with IC have an early age of disease onset and a disease that rapidly progresses to pancolitis. Longitudinal studies are needed to determine the clinical implications of this pediatric IBD subgroup.

Adolescent↗

Exocrine pancreatic function in children with progressive familial intrahepatic cholestasis type 2.

In progressive familial intrahepatic cholestasis type 2 (PFIC-2), severe steatorrhea is often documented. However, pancreatic exocrine secretion has not yet been studied. In 14 children with PFIC-2, pancreatic function was assessed using standard fecal tests. Normal fecal lipase concentrations excluded isolated lipase deficiency. No differences in fecal elastase-1 concentrations and chymotrypsin activities were detected between PFIC-2 patients with or without steatorrhea, nor between these patients and healthy subjects. In conclusion, pancreatic exocrine function in patients with PFIC-2 is normal. Steatorrhea observed in those patients is not related to pancreatic insufficiency.

Adolescent↗

Older adult report of change in depressive symptoms as a treatment decision tool.

OBJECTIVES: To evaluate patient reports of changes in depressive symptoms as information that can be used in treatment decision-making. DESIGN: Longitudinal cohort study. SETTING: The Prevention of Suicide in Primary Care Elderly: Collaborative Trial and the Primary Care Research in Substance Abuse and Mental Health for the Elderly trial, multisite studies investigating the effect of depression interventions on outcomes in primary care. PARTICIPANTS: Fifty-six patients aged 60 and older. MEASUREMENTS: Patient demographics were collected from patient reports. Symptoms of depression were measured using the Centers for Epidemiologic Studies Depression Scale (CES-D) and Hamilton Depression Scale (HAM-D). Changes in depressive symptoms were also measured using the Clinical Global Impressions of Change (CGI-C) as rated by patients in ongoing treatment. RESULTS: Patient ratings of CGI-C were significantly correlated with percentage improvement on the HAM-D as rated by the depression care manager (correlation coefficient (r)=0.44, P<.001) and percentage improvement on the CES-D (r=0.38, P=.005). The patient report of at least "much improved" predicted at least 50% treatment response based on HAM-D scale scores, with a sensitivity of 87.5% and a specificity of 74.2%. CONCLUSION: These findings suggest that patients are able to accurately report their degree of improvement in depressive symptoms. Patient report of at least "much improved" can be used as an estimate of at least 50% depression treatment response. In an era of increasingly fragmented clinical care, these findings demonstrate that older adult primary care patients can accurately self-report overall change in depressive symptoms. When results of repeated depression instruments are not available, patient report of depression treatment response can be used to inform depression treatment decision-making.

Aged↗

Parents' and teachers' concordance with children's self-ratings of suicidality: findings from a high-risk sample.

This study examined concordance between adult and child reports of child suicidality using a sample of 1,046 8-year-old children at risk for, or having experienced, maltreatment. Concordance was low with both caregivers and teachers. For children reporting no suicidality, caregiver-child agreement was associated with few transitions in caregiver and low social withdrawal and aggression, and teacher-child agreement was associated with non-White ethnicity, good academic performance, and low thought problems. For children reporting suicidality, care-giver-child agreement was associated with perceptions of child mental health needs, aggression, and somatic complaints, and teacher-child agreement was associated with thought problems.

Achievement↗

Changes in gene expression in maize kernel in response to water and salt stress.

Increasing pressure on limited water resources for agriculture, together with the global temperature increase, highlight the importance of breeding for drought-tolerant cultivars. A better understanding of the molecular nature of drought stress can be expected through the use of genomics approaches. Here, a macroarray of approximately 2500 maize cDNAs was used for determining transcript changes during water- and salt-stress treatments of developing kernels at 15 days after pollination. Normalization of relative transcript abundances was carried out using a human nebulin control sequence. The proportions of transcripts that changed significantly in abundance upon treatment (>2-fold compared to the control) were determined; 1.5% of the sequences examined were up-regulated by high salinity and 1% by water stress. Both stresses induced 0.8% of the sequences. These include genes involved in various stress responses: abiotic, wounding and pathogen attack (abscisic acid response binding factor, glycine and proline-rich proteins, pathogenesis-related proteins, etc.). The proportion of down-regulated genes was higher than that for up-regulated genes for water stress (3.2%) and lower for salt stress (0.7%), although only eight genes, predominantly involved in energy generation, were down-regulated in both stress conditions. Co-expression of genes of unknown function under defined conditions may help in elucidating their roles in coordinating stress responses.

Down-Regulation↗

Heterogeneity of the epsilon gamma delta beta-thalassaemias: characterization of three novel English deletions.

We have characterized three novel epsilon gamma delta beta-thalassaemia deletions in three English families. Two of the deletions, 114 and 439 kb, removed the entire beta-globin gene complex, including a variable number of flanking olfactory receptor (HOR) genes. The 98-kb deletion extended 90-kb upstream of the epsilon gene to 8 kb upstream of the G gamma-gene, leaving the gamma,delta and beta-genes intact. The 439 kb deletion is the largest deletion reported so far to cause epsilon gamma delta beta-thalassaemia; heterozygotes for this deletion were variably affected by neonatal haemolytic anaemia. Two of the deletions were de novo. Breakpoints of all three deletions occurred within regions of L1 or Alu repeats and contained short regions of direct homology between the flanking sequences, a feature that is likely to have contributed to the illegitimate recombinations.

Anemia, Hemolytic, Congenital↗

Suicidal ideation among 8-year-olds who are maltreated and at risk: findings from the LONGSCAN studies.

Suicidal ideation was examined among 1,051 8-year-old children identified as maltreated or at risk for maltreatment. Of these children, 9.9% reported suicidal ideation. Many variables, including maltreatment, had bivariate associations with suicidal ideation. Severity of physical abuse, chronicity of maltreatment, and the presence of multiple types of maltreatment strongly predicted suicidal ideation. In multivariate analyses of the domains of proximity, only ethnic background remained significant among demographic variables, only witnessed violence and maltreatment remained significant among family or contextual variables, and only child psychological distress, substance use, and poor social problem solving remained significant among child variables. The effects of ethnicity, maltreatment, and witnessed violence on suicidal ideation were mediated by child functioning. There were few interactions between maltreatment and other factors to predict suicidal ideation. Children who are maltreated and those exposed to community and domestic violence are at increased risk of suicidal ideation, even by age 8.

Child↗

Examination of a conceptual model of child neglect.

This study attempted to provide empirical support for conceptual definitions of child neglect. We identified 12 types of needs, conceptualizing neglect as occurring when children's basic needs are not adequately met. We examined measures administered to 377 children and caregivers at ages 4 and 6 years participating in longitudinal studies on child mal-treatment to identify potential indicators of these needs. Indicators were found for latent constructs, operationalizing three of the basic needs (emotional support and/or affection, protection from family conflict and/or violence, and from community violence). These latent constructs were used in a measurement model; this supported the conceptual definitions of neglect. A structural equation model then assessed whether the latent constructs were associated with child adjustment at age 8 years. Low level of perceived support from mother was associated with internalizing and externalizing behavior problems. Exposure to family conflict was also linked to these problems, and to social difficulties. Finally, children's sense of experiencing little early affection was associated with subsequent externalizing behavior and social problems. The approach of conceptualizing neglect in terms of unmet child needs, developing a measurement model to define latent neglect constructs, and relating these constructs to subsequent adjustment can build our understanding of neglect.

Affect↗