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G A Carlson

Publications and source records attributed to G A Carlson.

At least 37 records · Page 2Linked to original sources
PubMed1999

The mahogany protein is a receptor involved in suppression of obesity.

Genetic studies have shown that mutations within the mahogany locus suppress the pleiotropic phenotypes, including obesity, of the agouti-lethal-yellow mutant. Here we identify the mahogany gene and its product; this study, to our knowledge, represents the first positional cloning of a suppressor gene in the mouse. Expression of the mahogany gene is broad; however, in situ hybridization analysis emphasizes the importance of its expression in the ventromedial hypothalamic nucleus, a region that is intimately involved in the regulation of body weight and feeding. We present new genetic studies that indicate that the mahogany locus does not suppress the obese phenotype of the melanocortin-4-receptor null allele or those of the monogenic obese models (Lep(db), tub and Cpe(fat)). However, mahogany can suppress diet-induced obesity, the mechanism of which is likely to have implications for therapeutic intervention in common human obesity. The amino-acid sequence of the mahogany protein suggests that it is a large, single-transmembrane-domain receptor-like molecule, with a short cytoplasmic tail containing a site that is conserved between Caenorhabditis elegans and mammals. We propose two potential, alternative modes of action for mahogany: one draws parallels with the mechanism of action of low-affinity proteoglycan receptors such as fibroblast growth factor and transforming growth factor-beta, and the other suggests that mahogany itself is a signalling receptor.

Amino Acid Sequence↗
PubMed1999

SOD1 rescues cerebral endothelial dysfunction in mice overexpressing amyloid precursor protein.

Peptides derived from proteolytic processing of the beta-amyloid precursor protein (APP), including the amyloid-beta peptide, are important for the pathogenesis of Alzheimer's dementia. We found that transgenic mice overexpressing APP have a profound and selective impairment in endothelium-dependent regulation of the neocortical microcirculation. Such endothelial dysfunction was not found in transgenic mice expressing both APP and superoxide dismutase-1 (SOD1) or in APP transgenics in which SOD was topically applied to the cerebral cortex. These cerebrovascular effects of peptides derived from APP processing may contribute to the alterations in cerebral blood flow and to neuronal dysfunction in Alzheimer's dementia.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1999

Medication treatment in adolescents vs. adults with psychotic mania.

An epidemiologic sample of first admission psychotic patients is used to examine naturalistic treatment of psychotic mania. Specifically, we examined if 15-20 year olds receive different medications, or respond differently from patients over age 30 who are also early in their course of illness. The major difference in the two groups, besides their age, is the presence of comorbid externalizing disorder and substance abuse in the younger group. This report further examines the impact of this comorbidity on the presence of further episodes and overall outcome. The findings indicate that acute treatment is very similar in the two groups, and that over a 4 year follow-up, about 40% of patients discontinue medication. In spite of that, 32% of the YOUTH subjects and 48% of the ADULT group did not have a second episode. Of those externalizing YOUTH with a single episode, 64% took no medication during follow-up. However, the major difference between admission, 24 month follow-up and 48 month follow-up was the discontinuation of substance/alcohol use and the improvement in functioning. Medication did not invariably make that difference. This community sample reveals that at 48 months, a significant minority of young and adult subjects hospitalized with psychotic mania will have a single episode, and that short term course in younger patients is considerably worse than longer term course.

Adolescent↗
PubMed1998

Conduct disorder and mania: what does it mean in adults.

OBJECTIVE: Because of the relationship between childhood behavior disorders and adult substance abuse, we hypothesized that substance abusing adult bipolars were more likely to have had behavior disorders as children than nonabusing bipolar adults. METHODS: Conduct disorder (CD) symptoms in 132 bipolar adults were compared by age and presence of comorbid substance use problems using data from the Epidemiologic Catchment Area study. RESULTS: Rates of CD were higher in bipolar subjects under age 30 (32.6%) versus those over (16.3% P<0.05). Young BPs with substance use problems (SUBST) had CD rates three times those without SUBST (52% vs. 14.8%) (P < 0.01). Young subjects without mania or SUBST had CD rates of 7.75%. CONCLUSION: Substance abuse in bipolar adults may be more related to childhood conduct disorder than uncomplicated bipolar disorder.

Adolescent↗
PubMed1998

Mania and ADHD: comorbidity or confusion.

The frequency of occurrence of prepubertal mania is contingent on how much adherence to episodic disorder with separate periods of mania and depression is required. While manic symptoms superimposed on other psychiatric disorders is not uncommon, non-comorbid bipolar disorder is rare. A number of developmental, phenomenological and assessment considerations may complicate simple extrapolation of adult criteria onto young children. Nevertheless, it is clear that a significant number of preadolescents found in outpatient and inpatient samples meet at least symptom criteria for bipolar disorder. Such children have significant comorbidity and impairment. It is likely that some may develop classical bipolar disorder, some will continue to have substantial affective and behavioral comorbidity as do some complicated bipolar adults, and some will continue to have affective lability superimposed on their other, primary psychiatric disorders. Further research and follow-up will be necessary to determine who develops which outcome.

Adolescent↗
PubMed1998

"George".

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Attention Deficit Disorder with Hyperactivity↗
PubMed1998

Young referred boys with DICA-P manic symptoms vs. two comparison groups.

A total of 23 boys met DICA-P manic symptom and clustering criteria in a diagnostic investigation of 233 outpatient boys between ages 6 and 10. In this manic-symptom group, the most frequently endorsed of an average of five manic symptoms were extreme mood changes, difficulty concentrating, feeling too 'up' to sit still, and racing thoughts. Comparison groups were 23 non-manic boys seen next in the investigation and 23 non-manic boys matched to the manic-symptom boys on symptoms of three comorbid disruptive disorders (ADHD, ODD and CD). Manic-symptom boys differed significantly from next-seen boys, but not from matched comorbid boys, in number of oppositional symptoms and pervasiveness of problems. Manic-symptom boys differed significantly from next-seen boys on six of eight mother-rated RCBCL factors. In contrast, manic-symptom and matched comorbid boys did not differ on any of eight RCBCL factors, which suggests that the RCBCL differences can be attributed to shared ADHD, ODD and/or CD. However, manic-symptom and matched comorbid boys tended to differ on RCBCL Anxiety/Depression. On the teacher-rated TRF, manic-symptom boys were rated higher than next-seen boys on four internalizing factors, and higher than matched comorbid boys on two of those factors, including Anxiety/Depression. Thus, manic symptomatology also predicted substantial emotionality, which was not a controlled comorbidity. The findings of this and other studies suggest that there is a mania dimension or syndrome, which may be an indicator of true bipolar disorder--or simply a marker for disruptive comorbidity, behavioral and emotional multimorbidity, or general severity of psychopathology.

Attention Deficit Disorder with Hyperactivity↗
PubMed1998

Manic symptoms in psychiatrically hospitalized children--what do they mean?

OBJECTIVE: To examine the clinical implications of manic symptoms in psychiatrically hospitalized children aged 5-12. METHODS: DSMIIIR manic symptoms, along with symptoms of other psychiatric disorders, were rated by parents and teachers on the Child Symptom Inventory IIIR prior to hospitalization. The Child Behavior Checklist (CBCL; was also completed. During hospitalization children were evaluated by structured interview (K-SADS-E), and numerous rating scales weekly. Children with symptoms of mania (mania criteria with/without episodes) were compared to those without mania. Severity of attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), depression, CBCL factors, and comparable factors from teacher and parent inpatient rating scales were examined. Finally, a subgroup of both groups of children treated with stimulants were compared at baseline and at least two weeks of treatment. RESULTS: Children with manic symptoms had more severe ADHD, ODD and depression symptoms. CBCL scores on aggression, social and thought problems were higher. Teachers and nursing staff made similar observations. Time in hospital was greater for children with manic symptoms. Both groups improved significantly on stimulant medication though reduction in overall psychopathology was often modest. CONCLUSIONS: Manic symptoms, regardless of whether or not they represent bipolar disorder, are a marker of serious psychopathology and treatment resistance.

Attention Deficit Disorder with Hyperactivity↗
PubMed1997

Syrian hamster prion protein (PrP(C)) is expressed in photoreceptor cells of the adult retina.

PrP(C), the cellular isoform of the prion protein (PrP) serves as a precursor to abnormal PrP isoforms which accumulate in diseases such as scrapie in sheep, and Creutzfeldt-Jakob disease in humans. Since prions can replicate in photoreceptors we surmised that PrP(C) must be expressed in these cells. Accordingly, monoclonal antisera directed against two epitopes of hamster PrP(C) produced retinal immunostaining in hamsters, and in mice bearing a hamster PrP transgene. Immunostaining was most prominent in the inner and outer segments of rod photoreceptors, coinciding with the earliest site of pathologic changes in scrapie-infected hamsters. These data define PrP(C) expression in an experimentally-accessible population of neurons and suggest that the retina may comprise a useful system for studying the biology of wild-type and mutant prion proteins.

Animals↗
PubMed1997

The physical and genetic map surrounding the Lyst gene on mouse chromosome 13.

During the recent cloning of the mouse Lyst gene we developed both a high-resolution genetic map and a complete YAC and BAC contig of the Lyst critical region on mouse Chromosome 13. We also report the mapping of the human homologue of the mouse Lyst gene (LYST) to 1q43. These data are consistent with LYST being the gene for the human Chediak-Higashi Syndrome and strengthen the synteny relationship between MMU13 and human 1q43.

Animals↗
PubMed1997

Identification of candidate proteins binding to prion protein.

Prion diseases are disorders of protein conformation that produce neurodegeneration in humans and animals. Studies of transgenic (Tg) mice indicate that a factor designated protein X is involved in the conversion of the normal cellular prion protein (PrPC) into the scrapie isoform (PrPSc); protein X appears to interact with PrPC but not with PrPSc. To search for PrPC binding proteins, we fused PrP with alkaline phosphatase (AP) to produce a soluble, secreted probe. PrP-AP was used to screen a lambdagt11 mouse brain cDNA library, and six clones were isolated. Four cDNAs are novel while two clones are fragments of Nrf2 (NF-E2 related factor 2) transcription factor and Aplp1 (amyloid precursor-like protein 1). The observation that PrP binds to a member of the APP (amyloid precursor protein) gene family is intriguing, in light of possible relevance to Alzheimer's disease. Four of the isolated clones are expressed preferentially in the mouse brain and encode a similar motif.

Amino Acid Sequence↗
PubMed1997

Theoretical and empirical issues for marker-assisted breeding of congenic mouse strains.

Congenic breeding strategies are becoming increasingly important as a greater number of complex trait linkages are identified. Traditionally, the development of a congenic strain has been a time-consuming endeavour, requiring ten generations of backcrosses. The recent advent of a dense molecular genetic map of the mouse permits methods that can reduce the time needed for congenic-strain production by 18-24 months. We present a theoretical evaluation of marker-assisted congenic production and provide the empirical data that support it. We present this 'speed congenic' method in a user-friendly manner to encourage other investigators to pursue this or similar methods of congenic production.

Animals↗
PubMed1997

Genetic modification of the phenotypes produced by amyloid precursor protein overexpression in transgenic mice.

Overexpression of Alzheimer amyloid precursor protein (APP) produces dramatically different phenotypes in transgenic mice depending on the genetic background. For example, concentrations of APP that produce amyloid plaques in outbred transgenic lines are lethal for inbred FVB/N or C57BL/6J mice. Expression of SOD1 transgenes is protective, suggesting involvement of oxidative damage in premature death, but ablation of Apoe had no significant effect. In contrast, FGF2 transgene overexpression enhances the lethal effects of APP. Differential survival does not appear to reflect genetic differences in APP processing, but rather host responses to APP or its derivatives.

Alleles↗