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G A Carlson

Publications and source records attributed to G A Carlson.

At least 55 records · Page 3Linked to original sources
PubMed1997

Failure to transmit disease from gray tremor mutant mice.

Mice homozygous for mutant alleles at the gray tremor (gt) locus develop a marked non-intention tremor beginning at 8 days of age. Most homozygous mice die by 3 months. Homozygotes exhibit intense vacuolation of the central nervous system gray matter and vacuolation and hypomyelination of some white matter tracts. Based on neuropathological similarities with scrapie, other investigators inoculated wild-type mice with gray tremor brain homogenates to test the hypothesis of transmissibility. Published reports indicated that spongiform encephalopathy (R. L. Sidman, H. C. Kinney, and H. O. Sweet, Proc. Natl. Acad. Sci. USA 82:253-257, 1985) and disease, including hind limb paralysis in NFS mice (P. M. Hoffman, R. G. Rohwer, C. MacAuley, J. A. Bilello, J. W. Hartley, and H. C. Morse III, Proc. Natl. Acad. Sci. USA 84:3866-3870, 1987), were transmitted by inoculation of gt/gt brain homogenates. In our hands, however, no NFS/NCr animals inoculated intracerebrally with gt/gt or +/+ brain preparations showed any signs of disease or pathological changes in the brain. Positive transmission by other investigators may reflect the microbiological status of their donor or recipient mice.

Animals↗
PubMed1996

Identification and characterization of the mouse obesity gene tubby: a member of a novel gene family.

The mutated gene responsible for the tubby obesity phenotype has been identified by positional cloning. A single base change within a splice donor site results in the incorrect retention of a single intron in the mature tub mRNA transcript. The consequence of this mutation is the substitution of the carboxy-terminal 44 amino acids with 24 intron-encoded amino acids. The normal transcript appears to be abundantly expressed in the hypothalamus, a region of the brain involved in body weight regulation. Variation in the relative abundance of alternative splice products is observed between inbred mouse strains and appears to correlate with an intron length polymorphism. This allele of tub is a candidate for a previously reported diet-induced obesity quantitative trait locus on mouse chromosome 7.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Prion strains.

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Animals↗
PubMed1995

On safari with PrP: prion diseases of animals.

Prions are infectious pathogens that cause fatal neurodegeneration in humans and animals and are composed largely, or entirely, of an aberrant isoform of the host-encoded prion protein (PrP). A post-translational process involving a conformational change in PrP is a significant feature of their replication. Differences in PrP sequences modify the incubation times, neuropathology and properties of prion 'strains'.

Animals↗
PubMed1995

Advances in the study of mood disorders in childhood and adolescence.

Studies summarized in this review explore the nosology, course, and treatment of depression. The observation that depressive disorders in children often occur in conjunction with other psychiatric symptoms seems to affect outcome--in terms of suicidal behavior and possibly recurrence. Family factors seem to contribute to the severity of depressive symptoms, and it is possible that the level of criticism, as operationalized by "expressed emotion," is one of the mediating factors. Unfortunately, although several studies addressed treatment, both psychopharmacologically and psychotherapeutically, it is clear that considerably more research is needed before effective interventions are found for serious and disabling mood disorders in youth.

Adolescent↗
PubMed1995

Impulse control disorders and attention deficit disorder in pathological gamblers.

Little systematic research has been done on psychiatric comorbidity of pathological gambling, an impulse control disorder. This report describes the occurrence of attention deficit disorder and impulse control disorders in 40 pathological gamblers in treatment for gambling problems and 64 controls. Diagnoses were made by structured interviews which utilized operationalized diagnostic criteria. An impulse control disorder other than pathological gambling was noted in 35% of the pathological gamblers, compared to 3% of the controls (p < .001). Compulsive buying (p < .001) and compulsive sexual behavior (p < .05) were significantly higher in pathological gamblers than controls. A strong association was seen among pathological gambling, attention deficit, and other impulse control disorders. Attention deficit disorder was seen in 20% of the pathological gamblers. Rates of impulse control disorders did not differ by gender. Implications of these high rates of comorbidity are discussed.

Adult↗
PubMed1994

Structure and polymorphism of the mouse prion protein gene.

Missense mutations in the prion protein (PrP) gene, overexpression of the cellular isoform of PrP (PrPC), and infection with prions containing the scrapie isoform of PrP (PrPSc) all cause neurodegenerative disease. To understand better the physiology and expression of PrPC, we retrieved mouse PrP gene (Prn-p) yeast artificial chromosome (YAC), cosmid, phage, and cDNA clones. Physical mapping positions Prn-p approximately 300 kb from ecotropic virus integration site number 4 (Evi-4), compatible with failure to detect recombination between Prn-p and Evi-4 in genetic crosses. The Prn-pa allele encompasses three exons, with exons 1 and 2 encoding the mRNA 5' untranslated region. Exon 2 has no equivalent in the Syrian hamster and human PrP genes. The Prn-pb gene shares this intron/exon structure but harbors an approximately 6-kb deletion within intron 2. While the Prn-pb open reading frame encodes two amino acid substitutions linked to prolonged scrapie incubation periods, a deletion of intron 2 sequences also characterizes inbred strains such as RIII/S and MOLF/Ei with shorter incubation periods, making a relationship between intron 2 size and scrapie pathogenesis unlikely. The promoter regions of a and b Prn-p alleles include consensus Sp1 and AP-1 sites, as well as other conserved motifs which may represent binding sites for as yet unidentified transcription factors.

Animals↗
PubMed1994

Prion isolate specified allotypic interactions between the cellular and scrapie prion proteins in congenic and transgenic mice.

Different prion isolates, often referred to as "strains," present an enigma because considerable evidence argues that prions are devoid of nucleic acid. To investigate prion diversity, we inoculated three "strains" of prions into congenic and transgenic mice harboring variable numbers of two different alleles, designated a and b, of the prion protein (PrP) structural gene, Prn-p. The length of the incubation time was inversely related to the number of Prn-p(a) genes in mice inoculated with the Rocky Mountain Laboratory (RML) prion strain. Results with mice lacking this locus (Prn-p0/0) and transgenic mice argue that long incubation times are not a dominant trait as thought for many years, but rather they are due to reduced levels of the substrate PrPC-A (cellular isoform of PrP, allotype A) in (Prn-p(a) x Prn-pb)F1 mice. In contrast, the Prn-p(a) gene extended incubation times in mice inoculated with the 87V and 22A prion strains, whereas the Prn-pb gene was permissive. Experiments with the 87V isolate suggest that a genetic locus distinct from Prn-p controls deposition of the scrapie isoform of PrP (PrPSc) and attendant neuropathology. Each prion isolate produced distinguishable patterns of PrPSc accumulation in brain; of note, the patterns in Prn-p(a) and Prn-pb congenic mice inoculated with RML prions were more different than those in congenic Prn-pb mice with RML or 22A prions. Our results suggest that scrapie "strain-specific" incubation times can be explained by differences in the relative efficiency of allotypic interactions that lead to conversion of PrPC into PrPSc.

Alleles↗
PubMed1994

Genetics of prion diseases and prion diversity in mice.

Linkage of the prion protein (PrP) and scrapie incubation time genes in mice provided strong evidence for the central role of PrP in determining susceptibility to prion disorders. Considerable evidence now argues that the prion protein and incubation time genes are identical. The mouse prion protein gene (Prn-p) may act both quantitatively and qualitatively in modulating prion incubation time. Differences at positions 108 and 189 between PrP-A and PrP-B allotypes can place constraints on interaction between the normal cellular and the scrapie-specific isoforms of PrP (PrPC and PrPSc), although the supply of PrPC available for post-translational conversion to PrPSc can also influence incubation time. Results using transgenic (Tg) mice in studies on scrapie 'strains' or isolates suggest that incubation time characteristics of scrapie isolates can be explained by these two properties of PrP. The final section of this report discusses the novel finding that uninoculated Tg mice overexpressing wild-type (wt) PrP transgenes spontaneously develop a late-onset degenerative neuromyopathy, broadening the spectrum of prion diseases and providing new information on PrP function in both normal and pathological states.

Animals↗
PubMed1994

Degeneration of skeletal muscle, peripheral nerves, and the central nervous system in transgenic mice overexpressing wild-type prion proteins.

Prion diseases of humans and animals are known to be caused by infection with prions containing PrPSc or mutation of the prion protein (PrP) gene. During transgenetic studies, we discovered that uninoculated older mice harboring high copy numbers of wild-type (wt) PrP transgenes derived from Syrian hamsters (SHa), sheep (She), and PrP-B mice developed truncal ataxia, hindlimb paralysis, and tremors. These transgenic (Tg) mice exhibited a profound necrotizing myopathy involving skeletal muscle, a demyelinating polyneuropathy, and focal vacuolation of the central nervous system. Development of disease was dependent on transgene dosage. For example, half of all Tg(SHaPrP+/+)7 mice homozygous for the SHaPrP transgene array developed disease by approximately 460 days of age, while no hemizygous Tg(SHaPrP+/o)7 mice became ill before 650 days. The novel neurologic syndrome found in older Tg(wtPrP) mice implies that overexpression of wtPrPC is pathogenic and widens the spectrum of prion diseases.

Animals↗
PubMed1994

The confusion between bipolar disorder and schizophrenia in youth: where does it stand in the 1990s?

OBJECTIVE: To determine whether the bias against diagnosing bipolar disorder in youth continues, and if so, why. METHOD: Subjects are bipolar and schizophrenic patients taken from a county-wide sample of first admissions for psychosis. Patients are given structured interviews and consensus diagnoses at intake and 6 months. Age of onset of psychosis, gender, and 6-month consensus diagnosis between both groups are compared. To assess diagnostic bias, diagnostic stability and facility discharge diagnoses are examined in young (aged 15 through 20 years) versus adult (aged 30 through 40 years) patients. RESULTS: Bipolar disorder and schizophrenia are diagnosed at similar rates in younger age groups by 6-month consensus. However, bipolar disorder was underdiagnosed by Suffolk County's psychiatric hospitals in the youth. The stability of both disorders in both age groups was similar and excellent. Schizophrenia had a slightly older age at first psychosis than bipolar disorder and an equal gender representation. Bipolar disorder in males was rare after age 30. CONCLUSION: Community psychiatrists no longer call young bipolar patients schizophrenic, but they underdiagnose bipolar disorder. The more complicated nature of early-onset bipolar disorder may be a contributing factor.

Adolescent↗