Biomedical subjects

John Peterson

Publications and source records attributed to John Peterson.

6 recordsLinked to original sources

PubMed2006

Mitochondrial dysfunction as a cause of axonal degeneration in multiple sclerosis patients.

OBJECTIVE: Degeneration of chronically demyelinated axons is a major cause of irreversible neurological disability in multiple sclerosis (MS) patients. Development of neuroprotective therapies will require elucidation of the molecular mechanisms by which neurons and axons degenerate. METHODS: We report ultrastructural changes that support Ca2+-mediated destruction of chronically demyelinated axons in MS patients. We compared expression levels of 33,000 characterized genes in postmortem motor cortex from six control and six MS brains matched for age, sex, and postmortem interval. As reduced energy production is a major contributor to Ca2+-mediated axonal degeneration, we focused on changes in oxidative phosphorylation and inhibitory neurotransmission. RESULTS: Compared with controls, 488 transcripts were decreased and 67 were increased (p < 0.05, 1.5-fold) in the MS cortex. Twenty-six nuclear-encoded mitochondrial genes and the functional activities of mitochondrial respiratory chain complexes I and III were decreased in the MS motor cortex. Reduced mitochondrial gene expression was specific for neurons. In addition, pre-synaptic and postsynaptic components of GABAergic neurotransmission and the density of inhibitory interneuron processes also were decreased in the MS cortex. INTERPRETATION: Our data supports a mechanism whereby reduced ATP production in demyelinated segments of upper motor neuron axons impacts ion homeostasis, induces Ca2+-mediated axonal degeneration, and contributes to progressive neurological disability in MS patients.

Aged↗

PubMed2006

Treating persistent adolescent aggression.

Adolescent aggressive behavior is a frequently encountered problem for clinicians and society as a whole. Better understanding of biological, social, and familial risk factors for maladaptive aggressive behavior may lead to more effective interventions. The social information processing problems characteristic of this group interfere with treatment and outcome. Although further studies are needed, evidence for the effectiveness of psychopharmacologic treatments is increasing. There is also evidence for several effective psychotherapeutic interventions, especially for those with affective/impulsive aggression. Knowledge of risk factors, psychosocial strategies, and psychopharmacologic treatments can enhance the clinician's ability to intervene with this difficult group.

Journal Article↗

PubMed2004

Psychosocial issues among gay- and non-gay-identifying HIV-seropositive African American and Latino MSM.

This qualitative study examined sociocultural and behavioral factors including sexual health, sexual identity, and sexual risk among HIV-seropositive African American and Latino men who have sex with men (MSM) who also have a history of sexual abuse. Twenty-three men participated in 4 focus groups, responding to conceptually organized questions regarding the relationship between histories of violence and sexual and drug-related HIV risk behaviors for reinfection and transmission. Consensual qualitative research methods were used to analyze audiotaped transcriptions. Seven domains focusing on consensual and nonconsensual sexual practices, cultural and gender-bound beliefs, and social expectations were identified. Implications of these psychosocial issues for HIV-seropositive gay- and non-gay-identifying African American and Latino MSM with histories of sexual abuse in future interventions are discussed.

Adult↗

PubMed2003

Reduced cholesterol levels in African-American adults with sickle cell disease.

In a recent study of boys and girls with sickle cell disease (SCD) in Nigeria, a common finding with this genetic hematologic disorder was a marked reduction in total cholesterol. Epidemiologic studies have identified a relation between low serum levels of total cholesterol (< 130 mg/dL) and increased mortality from all causes. We were interested in knowing if hypocholesterolemia was present in African-American adults with SCD. We therefore compared the plasma lipid profiles of the 16 men and 20 women with SCD who received care at the University of Texas Medical Branch at Galveston between 1996 and 2001 with those of 2,415 gender-matched African Americans who were seen at the same hospital but who did not have SCD. The age-adjusted mean total cholesterol concentrations of the SCD males and females were 147 +/- 42 mg/dL and 179 +/- 36 mg/dL, compared to male and female control values of 200 +/- 75 mg/dL and 216 +/- 61 mg/dL, respectively. These differences between SCD subjects and controls were statistically significant (p < 0.001). The LDL-cholesterol levels of the men and women with SCD (68 +/- 28 mg/dl and 95 +/- 33 mg/dl, respectively) were also significantly reduced relative to the controls (121 +/- 58 mg/dl and 128 +/- 54 mg/dl, respectively, p = 0.001). The triglyceride levels of the men with SCD were much reduced relative to the male controls (102 +/- 34 mg/dL versus 194 +/- 215 mg/dL, p = 0.02), but were not different between the SCD females and their control group. The HDL-cholesterol levels of the SCD subjects and the controls were not different. These results indicate that total cholesterol and LDL-cholesterol concentrations are significantly reduced in adult men and women with SCD in the United States, and should heighten interest in the implication that low levels of cholesterol might exacerbate the medical problems inherent in this genetic disease.

Adolescent↗

PubMed2002

Indoline and piperazine containing derivatives as a novel class of mixed D(2)/D(4) receptor antagonists. Part 1: identification and structure-activity relationships.

Optimization of the lead compound 2-[-4-(4-chloro-benzyl)-piperazin-1-yl]-1-(2,3-dihydro-indol-1-yl)-ethanone 1 by systematic structure-activity relation (SAR) studies lead to two potent compounds 2-[-4-(4-chloro-benzyl)-piperazin-1-yl]-1-(2-methy-2,3-dihydro-indol-1-yl)-ethanone 2n and 2-[-4-(4-chloro-benzyl)-piperazin-1-yl]-1-(2-methy-2,3-dihydro-indol-1-yl)-ethanone 7b. Their related synthesis was also reported.

Animals↗

PubMed2002

Inhibition of pro-inflammatory cytokine generation by CTLA4-Ig in the skin and colon of mice adoptively transplanted with CD45RBhi CD4+ T cells correlates with suppression of psoriasis and colitis.

Transfer of CD45RBhi CD4 + naïve T cells into severe combined immunodeficient (SCID) mice induces colitis and skin lesions. Recipients treated with cyclosporin A (CsA), CTLA4-Ig, or vehicle were evaluated for weight loss, skin lesions, and cutaneous blood flow. Necropsy, histological, hematological and cytokine analyses were performed at the conclusion of the experiment to confirm the clinical findings. Vehicle-treated mice lost weight and had 100% incidence of skin lesions by 46-days. CsA-treated mice also lost weight, but only 3/8 mice developed mild, clinically evident skin lesions. In contrast, all CTLA4-Ig-treated mice gained weight and did not develop skin lesions. Increase in cutaneous blood flow correlated with the development of skin lesions. Granulocyte numbers, which were high or moderately high in the vehicle- or CsA-treated mice, respectively, remained as low in the CTLA4-Ig-treated group as in untreated mice. IFN-gamma, IL-1beta, and TNF-alpha levels in the gut and skin correlated with the extent of inflammation in both organs. Histology revealed that CTLA4-Ig but not CsA effectively prevented both autoimmune disorders. The ability of CTLA4-Ig to prevent both colitis and skin lesions suggests that CD28-dependent co-stimulation of T cells is critical for generation of pro-inflammatory cytokines and induction of clinical disease in such autoimmune disorders.

Abatacept↗