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G A Carlson

Publications and source records attributed to G A Carlson.

At least 91 records · Page 5Linked to original sources
PubMed1991

Transgenic mice for the amyloid precursor protein 695 isoform have impaired spatial memory.

Transgenic mice for the human amyloid precursor protein 695 (APP695) isoform may provide an animal model of Alzheimer's disease (AD). To evaluate this, the spatial learning abilities of transgenic and wild strain mice were compared in the Morris water maze task. The transgenic mice were significantly retarded in initial learning and in learning a new escape location, although in each case they eventually reached control levels. The transgenic mice also showed slower swimming speed and reduced nocturnal activity, which may contribute to their deficit in spatial learning. Preliminary neuropathological investigations failed to reveal amyloid depositions. Thus, a gene dosage effect of APP695 may account for the memory impairment but not the plaque formation associated with AD.

Amyloid beta-Peptides↗
PubMed1991

The role of somatic complaints in the diagnosis of depression in children and adolescents.

The question of whether somatic complaints are a significant feature of depression independent of anxiety was explored. Structured interview (Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children) and Child Behavior Checklist data from depressed and nondepressed psychiatric controls were analyzed to explore the interaction of somatic complaints, anxiety, and depression. Seventy percent of the children who met criteria for depression also had significant somatic complaints in contrast to 34% of the controls. Findings revealed that frequency of somatic complaints increased with severity of depression regardless of coexisting anxiety.

Adolescent↗
PubMed1991

Child psychiatrists' views of DSM-III-R: a survey of usage and opinions.

The DSM-IV Child Psychiatry Work Group surveyed 460 child psychiatrists about their use of DSM-III-R and their reactions to specific proposed nosological revisions for DSM-IV. This paper presents the responses of the sample as a whole and of respondent subgroups with different theoretical, practice, and training characteristics. The survey indicates that DSM-III and DSM-III-R are widely used and generally accepted by child psychiatrists. Ninety-eight percent of respondents believe a criterion-based diagnostic system is useful, and 65% consider DSM-III-R to be an improvement over DSM-III. Depending on the diagnosis 47% to 66% of the respondents reported that they generally assess all applicable criteria and 28% to 49% often refer to the manual before assigning a diagnosis. A majority of respondents supported proposals for several new diagnostic subtypes. Ninety-three percent of respondents indicated that "adequacy of family support" was very valuable for treatment planning or estimating prognosis. Fifty-five percent of respondents admitted to diagnosing adjustment disorders in order to avoid the stigma associated with other disorders. Child psychiatrists who are psychodynamically oriented or practicing in an office-based setting or out of training for more than 10 years tend to use the DSM-III-R less rigorously.

Adolescent↗
PubMed1991

The utility of a DSM-III-R-based checklist in screening child psychiatric patients.

The Stony Brook Child Psychiatric Checklist, a parent completed rating instrument based on DSM-III-R, was used as part of a psychiatric inpatient admission evaluation. Data were collected on 63 5- to 13-year-old children. Checklist endorsements were compared with the same parent's responses to the Kiddie-Schedule for Affective Disorders and Schizophrenia for School-aged Children-Epidemiologic Version structured interview for the most frequently occurring disorders. Sensitivity scores ranged from 0.69 to 0.93. Results suggest the checklist can be useful in alerting the clinician to diagnostic areas warranting further pursuit.

Adolescent↗
PubMed1991

Serum cholesterol and aggressive behavior in psychiatrically hospitalized children.

The relationship between serum cholesterol and a number of measures of impulsiveness and aggression was examined in 38 prepubertal, psychiatrically hospitalized children. Although care was taken to use reports and direct observations of both variables within 2 weeks of admission and 8 weeks later, no consistent relationship was found. The reasons for these findings are discussed.

Adolescent↗
PubMed1991

Erythema and skin temperature following continuous sitting in spinal cord injured individuals.

Pressure sores are a severe and costly problem for many disabled individuals. There is a need for quantitative tools to assess damage produced by external loads on human skin and underlying tissues. Clinically, intensity and size of skin erythema have been used as indicators of tissue damage. Temperature is a quantifiable measure, and various studies have investigated the thermal response to localized pressure. The purpose of this study was to measure the effect of "long-term sitting" on skin temperature and erythema, in a situation that closely approximated what a spinal cord injured individual encounters on a regular basis. The resulting data indicated that: 1) a consistent skin temperature pattern occurred after pressure relief from the seated position; 2) skin temperature of experimentally-induced erythematous areas often remained elevated, even after one hour of pressure relief; and, 3) a qualitative, but not quantitative, correlation exists between erythema size and intensity and skin temperature. Implications of this research include the potential use of temperature to: 1) monitor the effectiveness of various strategies being used to prevent the development of pressure sores; and, 2) predict incipient tissue damage.

Adult↗
PubMed1991

Daily monitored cardiovascular effects of carbamazepine in chronic crack cocaine users.

During a 20-day, double-blind, placebo-controlled, fixed-dose outpatient trial of carbamazepine (either 200 mg or 400 mg) for potential anticocaine treatment effects in volunteers who were unmotivated for treatment and who lacked any external coercion for cocaine abstinence, we monitored cardiovascular effects in 30 subjects on a daily basis. All individual cardiovascular measures obtained were within clinically normal limits. Corrected QT interval under carbamazepine was shorter than under placebo condition, although both were in the normal range. Systolic pressure was elevated by 2.1 mm Hg. No differences in pulse rate were found. With carbamazepine and concurrent ad lib cocaine use, heart rate was significantly, although not clinically, elevated (mean increase = 2.3 beats/minute). The analysis of these approximately 600 observations indicates that carbamazepine in cocaine users, alone and in combination with ad lib street crack use, causes no clinically significant cardiovascular effects.

Carbamazepine↗
PubMed1990

Transgenetic studies implicate interactions between homologous PrP isoforms in scrapie prion replication.

Transgenic (Tg) mice expressing both Syrian hamster (Ha) and mouse (Mo) prion protein (PrP) genes were used to probe the mechanism of scrapie prion replication. Four Tg lines expressing HaPrP exhibited distinct incubation times ranging from 48 to 277 days, which correlated inversely with HaPrP mRNA and HaPrPC. Bioassays of Tg brain extracts showed that the prion inoculum dictates which prions are synthesized de novo. Tg mice inoculated with Ha prions had approximately 10(9) ID50 units of Ha prions per gram of brain and less than 10 units of Mo prions. Conversely, Tg mice inoculated with Mo prions synthesized Mo prions but not Ha prions. Similarly, Tg mice inoculated with Ha prions exhibited neuropathologic changes characteristic of hamsters with scrapie, while Mo prions produced changes similar to those in non-Tg mice. Our results argue that species specificity of scrapie prions resides in the PrP sequence and prion synthesis is initiated by a species-specific interaction between PrPSc in the inoculum and homologous PrPC.

Animals↗
PubMed1990

Spontaneous Pneumocystis carinii pneumonia in immunodeficient mutant scid mice. Natural history and pathobiology.

The opportunistic pathogen Pneumocystis carinii (Pc) poses a major clinical health problem in individuals with immune deficiency, including those patients with human immunodeficiency (HIV)-associated acquired immune deficiency disease (AIDS). Heretofore, in vivo investigations of the biology of Pc and pathogenesis of pneumocystosis have generally employed steroid-induced immune suppression with antibiotic prophylaxis and protein deprivation. This approach has many drawbacks, chief among them being the widespread, multiple interacting effects caused by the inducing agents. Athymic (nude) mice and rats have been used, but are less than ideal, as the immune defect primarily affects T lymphocytes. This article describes the natural history, pathobiology, and environmental effects on Pc pneumonitis in nonaxenically housed mice homozygous for the autosomal recessive mutation 'severe combined immunodeficiency' (scid), which almost totally lack both cell-mediated and antibody-mediated immune functions. The predictability, unequivocal expression, high morbidity, and well-defined genetic basis make scid/scid mutant mice the model of choice for in vivo studies of spontaneous pneumocystosis.

Animals↗
PubMed1989

Unraveling prion diseases through molecular genetics.

Prions are transmissible pathogens that cause degenerative diseases in humans and animals. Unique attributes of prion diseases include infectious, sporadic and genetic manifestations, as well as progression to death, all in the absence of a detectable immune response. Prions are resistant to chemical procedures that modify or destroy nucleic acids and are composed largely of a protein, designated PrPSc. Molecular cloning of a cognate cDNA established a cellular host origin for PrPSc protein and a convergence with the genetics of host susceptibility. The murine PrP gene is linked to the Prn-i gene which determines incubation times in experimental scrapie. Mice with long incubation times have unusual PrP alleles encoding phenylalanine and valine at codons 108 and 189. Moreover, the ataxic form of Gerstmann-Sträussler syndrome (a rare human neurodegenerative disorder) has been defined as an autosomal dominant disorder with a PrP mis-sense mutation at codon 102 linked to the predisposition locus. These studies argue that amino acid substitutions in 'PrP' genes may modulate initiation and development of prion diseases.

Animals↗
PubMed1989

Psychoneuroendocrine effects of methadone maintenance.

A variety of neuroendocrine and psychiatric dysfunctions have been demonstrated in humans maintained on opiates, but both have not previously been examined in the same population. We performed a series of neuroendocrine challenge tests in men participating in a methadone maintenance clinic and in normal controls. Psychiatric diagnoses were made with DSM-III Criteria, using the Diagnostic Interview Schedule, and subjects also completed the Symptom Checklist. Our results in the methadone group suggest (a) near-maximal stimulation of prolactin secretion, with a blunted prolactin response to insulin hypoglycemia, (b) mild suppression of cortisol levels, but an exaggerated cortisol response to stimulation, (c) a delayed and inhibited insulin response to food ingestion with resulting mild hyperglycemia, (d) low body weight, but elevated calorie ingestion, and (e) inability to concentrate urine when dehydrated, which was partially corrected by administration of arginine vasopressin. Phobic disorder was associated with a lower prolactin response to both inhibitory and stimulatory challenges. Depression did not appear to be related to the increased cortisol response to stimulation. These results suggest several potentially fruitful areas for future investigation, including the prolactin system and anxiety disorders, nutrient ingestion and metabolism, and posterior pituitary function.

Adrenocorticotropic Hormone↗
PubMed1989

Primary structure of prion protein may modify scrapie isolate properties.

Scrapie is an infectious neurodegenerative disease caused by unusual pathogens called prions, in which no scrapie-specific nucleic acid has been detected to date. The only known component of the prion is the scrapie isoform of prion protein (PrPSc), which is encoded by a host gene (Prn-p). Isolates of scrapie agent were prepared by passage of infectivity through inbred strains of mice that differ in scrapie incubation time and produce PrPSc molecules differing by two amino acids. Both the length and variability of the incubation period were increased by inocula containing allogeneic PrPSc. For example, Prn-pb I/Ln mice inoculated with scrapie isolate passaged through Prn-pa NZW mice had incubation times of 283 +/- 21 days compared with a 193 +/- 6 day incubation time seen with isolate passaged once through isologous I/Ln mice. No further shortening of incubation time was observed following further isologous passage. NZW incubation times were prolonged by inoculation with prions from I/Ln mice. Results from (NZW x I/Ln)F2 mice and from using inocula from donors isologous for Prn-p but otherwise allogeneic with respect to the recipient suggest that the primary structure of PrPSc is responsible for these incubation time results. Incubation times in (NZW x I/Ln)F1 mice were constant regardless of the passage histories of the scrapie isolates and were equivalent to those of I/Ln mice inoculated with I/Ln prions, contending that prolongation of scrapie incubation time by the prion incubation time gene Prn-i is fully dominant. I/Ln incubation times longer than those in F1 hybrids may reflect a reduced efficiency of allogeneic PrPSc in initiating disease. Although some investigators propose that differences in behavior among scrapie isolates reflect host selection and argue for a nucleic acid genome, we suggest that the variation observed among our scrapie isolates is epigenetic, reflecting host-directed differences in the amino acid sequence of PrPSc.

Animals↗
PubMed1989

Management of HIV-positive psychiatric patients who fail to reduce high-risk behaviors.

The authors describe clinical and legal dilemmas faced by staff involved in providing inpatient psychiatric treatment to two HIV carriers who continued to practice high-risk behaviors after learning of their HIV infection. Staff were unsure of their obligation to report the patients under a state law giving the commissioner of health broad discretion to limit the freedoms of HIV-infected individuals who continue to practice high-risk behaviors. Treatment of the patients also raised concerns about the appropriateness of treating noncompliant HIV-infected patients in traditional psychiatric settings and the lack of suitable aftercare facilities. The authors advocate developing a specialized treatment approach for noncompliant HIV-infected patients and provide a series of recommendations that might serve as the foundation for such an effort.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Immunoaffinity purification and neutralization of scrapie prions.

The scrapie agent causes a degenerative neurologic disease and can be transmitted to laboratory rodents. The unusual properties of the scrapie agent prompted introduction of the term prion in order to distinguish this class of novel pathogens from viruses and viroids. The scrapie prion protein (PrPSc) is the only component of the infectious scrapie prion identified, to date. Although many biochemical and genetic lines of evidence argue that PrPSc is a major component of the infectious particle, the most convincing data is derived from immunoaffinity purification studies. Limited proteinase K digestion of hamster brain PrPSc produced PrP 27-30. After dispersion of brain microsomes isolated from scrapie-infected hamsters into detergent-lipid-protein complexes (DLPC), copurification of PrPSc and scrapie infectivity was obtained with PrP 27-30 monoclonal antibody affinity columns. PrPSc was enriched approximately 5700-fold with respect to total brain protein while scrapie prion infectivity was enriched approximately -4000-fold. The ratio of prion titer to PrPSc remained constant throughout purification. Heterologous monoclonal antibody columns failed to bind either PrpSc or scrapie infectivity. Polyclonal rabbit PrP antiserum raised against sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)-purified PrP 27-30 reduced scrapie infectivity dispersed into DLPC by a factor of 100. Our findings represent the first direct immunologic and chromatographic demonstrations of a relationship between PrPSc and prion infectivity as well as providing additional support for the contention that PrPSc is a major component of the infectious scrapie particle. While these results and those of other studies establish that PrPSc is a component of the infectious prion, the possibility of a second component such as a small nucleic acid which might be required for infection must still be considered. PrPSc is encoded by a single copy cellular gene and not by a hypothetical-nucleic acid within purified prion preparations. Normal, uninfected cells express the cellular prion protein (PrPC). Both PrPSc and PrPC appear to be translated from the same 2.1-kb mRNA. The N-terminal amino acid sequences of hamster PrPC and PrPSc are identical; both correspond to that predicted by the translated prion protein (PrP) gene sequence. While the chemical difference between PrPC and PrPSc remains unknown, the organization of the PrP gene argues that it results from a posttranslational event. The mouse PrP gene is on chromosome 2 and is linked to a gene controlling the scrapie incubation time (Prn-i).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Genetic control of prion incubation period in mice.

The prion gene complex (Prn) is located on mouse chromosome 2 between the beta-2-microglobulin (B2m) and agouti (A) genes. Within this complex are the prion protein gene (Prn-p), which encodes the only identified macromolecule (PrP) that purifies with infectious scrapie agent, and a scrapie incubation time gene (Prn-i). Using a variety of restriction endonucleases, six allelic forms of the Prn-p gene have been distinguished by their patterns of restriction fragment length polymorphisms. We had previously shown that the exceptionally long scrapie incubation period of I/LnJ mice inoculated with the Chandler isolate (over 200 days) was due to the effects of a scrapie incubation time gene tightly linked to Prn-p. So far, this long scrapie incubation time allele has been found only in those inbred mouse strains (I/LnJ, P/J and IM) that have the b allele of Prn-p. It is not known whether the incubation time gene and prion protein gene are two distinct loci or are one and the same. Putative recombinants between the incubation time phenotype and Prn-p genotype have been observed, but this could be due to effects of other genes segregating in the population. Regardless of whether or not the incubation time and PrP genes are identical, if any differences were found in the amino acid sequences of PrP encoded by the different Prn-p alleles there would be important implications for interpretation of results on 'strains' of scrapie agent. It would not be necessary to invoke nucleic acid as the informational macromolecule of the scrapie agent because differences in prion 'strains' recovered from mice with different Prn-p genotypes need not be the result of host selection but could be due to differences in host-encoded PrP.

Alleles↗
PubMed1988

Genetics and polymorphism of the mouse prion gene complex: control of scrapie incubation time.

The mouse prion protein (PrP) gene (Prn-p), which encodes the only macromolecule that has been identified in scrapie prions, is tightly linked or identical to a gene (Prn-i) that controls the duration of the scrapie incubation period in mice. Constellations of restriction fragment length polymorphisms distinguish haplotypes a to f of Prn-p. The Prn-pb allele encodes a PrP that differs in sequence from those encoded by the other haplotypes and, in inbred mouse strains, correlates with long scrapie incubation time (Westaway et al., Cell 51: 651-662, 1987). In segregating crosses of mice, we identified rare individuals with a divergent scrapie incubation time phenotype and Prn-p genotype, but progeny testing to demonstrate meiotic recombination was not possible because scrapie is a lethal disease. Crosses involving the a, d, and e haplotypes demonstrated that genes unlinked to Prn-p could modulate scrapie incubation time and that there were only two alleles of Prn-i among the mouse strains tested. All inbred strains of mice that had the Prnb haplotype were probably direct descendants of the I/LnJ progenitors. We established the linkage relationship between the prion gene complex (Prn) and other chromosome 2 genes; the gene order, proximal to distal, is B2m-II-1a-Prn-Itp-A. Recombination suppression in the B2m-Prn-p interval occurred during the crosses involved in transferring the I/LnJ Prnb complex into a C57BL/6J background. Transmission ratio distortion by Prna/Prnb heterozygous males was also observed in the same crosses. These phenomena, together with the founder effect, would favor apparent linkage disequilibrium between Prn-p and Prn-i. Therefore, transmission genetics may underestimate the number of genes in Prn.

Animals↗