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Biomedical subjects

C Carlson

Publications and source records attributed to C Carlson.

At least 19 recordsLinked to original sources
PubMed2001

Increased transcription levels induce higher mutation rates in a hypermutating cell line.

Somatic hypermutation, in addition to V(D)J recombination, is the other major mechanism that generates the vast diversity of the Ab repertoire. Point mutations are introduced in the variable region of the Ig genes at a million-fold higher rate than in the rest of the genome. We have used a green fluorescent protein (GFP)-based reversion assay to determine the role of transcription in the mutation mechanism of the hypermutating cell line 18-81. A GFP transgene containing a premature stop codon is transcribed from the inducible tet-on operon. Using the inducible promoter enables us to study the mutability of the GFP transgene at different transcription levels. By analyzing stable transfectants of a hypermutating cell line with flow cytometry, the mutation rate at the premature stop codon can be measured by the appearance of GFP-positive revertant cells. Here we show that the mutation rate of the GFP transgene correlates with its transcription level. Increased transcription levels of the GFP transgene caused an increased point mutation rate at the premature stop codon. Treating a hypermutating transfection clone with trichostatin A, a specific inhibitor of histone deacetylase, caused an additional 2-fold increase in the mutation rate. Finally, using Northern blot analysis we show that the activation-induced cytidine deaminase, an essential trans-factor for the in vivo hypermutation mechanism, is transcribed in the hypermutating cell line 18-81.

Animals↗
PubMed2001

Acute cytomegalovirus infection complicated by vascular thrombosis: a case report.

We present a case report of a previously healthy adult with cytomegalovirus infection that was complicated by extensive mesenteric arterial and venous thrombosis. To our knowledge, this is the first reported case of this syndrome in an immunocompetent individual who had no predisposing risk factors for thrombosis, and it demonstrates the propensity for cytomegalovirus to be involved in vascular disease.

Acute Disease↗
PubMed2001

Clinical effectiveness and cost analysis of patient referral by videoconferencing in orthopaedics.

The clinical effectiveness and costs of videoconferencing in orthopaedics between primary and secondary care were examined in an eight-month prospective, comparative study. The general surgery outpatient clinics of two Finnish district hospitals were compared: Peijas Hospital, with telemedicine, and Hyvinkää Hospital, without it. The three study primary-care centres referred a total of 419 adult patients to the outpatient clinics. The population-based number of referrals to Peijas Hospital was similar to that to Hyvinkää Hospital after adjusting for the proportion of older people living in the Hyvinkää Hospital municipalities. Of the 225 patients referred to Peijas Hospital, 168 (75%) were given appointments at the outpatient clinic of surgery and the rest of the referred patients received a teleconsultation. All patients referred to Hyvinkää Hospital were given appointments at the outpatient clinic. The direct costs of an outpatient visit were 45% greater per patient than for a teleconsultation, with a marginal cost decrease of EU48 for every new teleconsultation. A cost-minimization analysis of the alternative interventions showed a net benefit of EU2500 in favour of teleconsultations. The use of videoconferencing between primary and secondary care was modest in orthopaedics, although the use of this telemedicine method was shown to reduce direct costs and be cost-effective.

Adult↗
PubMed2000

Attention deficit/hyperactivity disorder children with a 7-repeat allele of the dopamine receptor D4 gene have extreme behavior but normal performance on critical neuropsychological tests of attention.

An association of the dopamine receptor D4 (DRD4) gene located on chromosome 11p15.5 and attention deficit/hyperactivity disorder (ADHD) has been demonstrated and replicated by multiple investigators. A specific allele [the 7-repeat of a 48-bp variable number of tandem repeats (VNTR) in exon 3] has been proposed as an etiological factor in attentional deficits manifested in some children diagnosed with this disorder. In the current study, we evaluated ADHD subgroups defined by the presence or absence of the 7-repeat allele of the DRD4 gene, using neuropsychological tests with reaction time measures designed to probe attentional networks with neuroanatomical foci in D4-rich brain regions. Despite the same severity of symptoms on parent and teacher ratings for the ADHD subgroups, the average reaction times of the 7-present subgroup showed normal speed and variability of response whereas the average reaction times of the 7-absent subgroup showed the expected abnormalities (slow and variable responses). This was opposite the primary prediction of the study. The 7-present subgroup seemed to be free of some of the neuropsychological abnormalities thought to characterize ADHD.

Alleles↗
PubMed2000

A physical, chemical, and mechanical study of lumbar vertebrae from normal, ovariectomized, and nandrolone decanoate-treated cynomolgus monkeys (Macaca fascicularis).

Ovariectomized cynomolgus monkeys have previously been investigated as a nonhuman primate model of postmenopausal osteoporosis (Jerome et al., Bone Miner 9:527-540; 1994). In the present study, Fourier transform infrared microspectroscopy (FTIRM) was used to verify that differences in bone mineral quality and quantity in the vertebrae of mature intact (INT) and ovariectomized (ovx) monkeys were analogous to those seen in osteoporotic and nondiseased human bones. FTIRM spectra were acquired from 15 trabeculae per vertebra from three ovx and three INT adult monkeys (mean age 8 years). These spectra were compared with those of both trabecular and previously reported osteonal bone obtained from 3 "normal" and 11 postmenopausal osteoporotic human subjects. While variations in the mineral:matrix ratio (mineral content), carbonate:phosphate ratio, and crystallinity are typical for trabecular bone from iliac crests of normal human subjects, the values of these parameters were relatively static for trabecular bone from postmenopausal osteoporotic human subjects. In general, trabecular bone from postmenopausal osteoporotic human subjects exhibited decreased mineral content (1.0 +/- 0.5 vs. 2.9 +/- 0.6), increased crystallinity, and increased carbonate:phosphate relative to controls. Similarly, trabecular bone from ovariectomized monkeys exhibited lower mineral content (5.8 +/- 0.2) compared with the INT group (6.2 +/- 0.2; p </= 0.05) and contained larger/more perfect apatite crystals (increased crystallinity) with increased carbonate:phosphate ratios. Variations in absolute values were attributable to site differences (ilium vs. vertebrae). To appreciate the importance of mineral properties on mechanical properties, compression testing was performed using cores of monkey L-3 and L-4 vertebral bodies from a separate group of monkeys. Treating monkeys with the anabolic steroid nandrolone decanoate (ND) immediately after ovariectomy and for the next 24 months (ND group), or beginning 12 months after ovariectomy (dND group), increased the ultimate stress compared with an ovx treatment group, despite large interanimal variations in bone architecture and mechanical properties. These data support the hypothesis that ovariectomized adult monkeys are an excellent model for postmenopausal osteoporosis, and can be used for the evaluation of therapeutic modalities.

Animals↗
PubMed2000

Alterations in bilateral force judgment following strenuous eccentric exercise.

This study investigated the effects of strenuous eccentric exercise on bilateral force-matching ability. After unilaterally performing 50 maximal eccentric elbow actions, participants were evaluated for bilateral force-matching ability. Participants were asked to match a reference force held by the control (CNT) arm with their exercised (EXD) arm. The experimental condition was then reversed. Constant error (bias) of the EXD arm was increased through 5 days postexercise, when it underestimated the CNT force in all trials. In contrast, an overestimation of the EXD force by the CNT arm resulted in an increased constant and variable error (variability around the bias) through 5 days postexercise, when the EXD arm served as the force reference. Strenuous eccentric exercise severely compromises bilateral force-matching ability, regardless of whether the EXD attempted to match the reference force or served as the force reference, indicating central or peripheral alterations to force judgment.

Adult↗
PubMed2000

Effects of attentional focus, self-control, and dyad training on motor learning: implications for physical rehabilitation.

In this article, the authors review recent studies on 3 factors that have been shown to affect the learning of motor skills-the performer's attentional focus, self-control, and practice in dyads-and discuss their implications for rehabilitation. Research has shown that directing learners' attention to the effects of their movements can be more beneficial for learning than directing their attention to the details of their own actions. Furthermore, giving learners some control over the training regimen has been found to enhance learning, unlike prescriptive training protocols that dictate when feedback will be delivered, how often, and the order that tasks will be practiced. Finally, not only can practice in dyads (or larger groups) reduce the costs of training, but it can also result in more effective learning than individual practice sessions. The incorporation of these factors into rehabilitation practice can potentially enhance the effectiveness and efficiency of rehabilitation.

Attention↗
PubMed2000

The Texas Children's Medication Algorithm Project: Report of the Texas Consensus Conference Panel on Medication Treatment of Childhood Attention-Deficit/Hyperactivity Disorder. Part I. Attention-Deficit/Hyperactivity Disorder.

OBJECTIVES: Expert consensus methodology was used to develop evidence-based, consensually agreed-upon medication treatment algorithms for attention-deficit/hyperactivity disorder (ADHD) in the public mental health sector. Although treatment algorithms for adult mental disorders have been developed, this represents one of the first attempts to develop similar algorithms for childhood mental disorders. Although these algorithms were developed initially for the public sector, the goals of this approach are to increase the uniformity of treatment and improve the clinical outcomes of children and adolescents with ADHD in a variety of treatment settings. METHOD: A consensus conference of academic clinicians and researchers, practicing clinicians, administrators, consumers, and families was convened to develop evidence-based consensus algorithms for the pharmacotherapy of childhood ADHD. After a series of presentations of current research evidence and panel discussion, the consensus panel met and drafted the algorithms along with guidelines for implementation. RESULTS: The panel developed consensually agreed-upon algorithms for ADHD with and without specific comorbid disorders. The algorithms consist of systematic strategies for psychopharmacological interventions and tactics to ensure successful implementation of the strategies. While the algorithms focused on the medication management of ADHD, the conference emphasized that psychosocial treatments are often a critical component of the overall management of ADHD. CONCLUSIONS: Medication algorithms for ADHD can be developed with consensus. A companion article will discuss the implementation of these algorithms.

Adrenergic alpha-Agonists↗
PubMed2000

The Texas Children's Medication Algorithm Project: Report of the Texas Consensus Conference Panel on Medication Treatment of Childhood Attention-Deficit/Hyperactivity Disorder. Part II: Tactics. Attention-Deficit/Hyperactivity Disorder.

OBJECTIVES: Expert consensus methodology was used to develop a medication treatment algorithm for attention-deficit/hyperactivity disorder (ADHD). The algorithm broadly outlined the choice of medication for ADHD and some of its most common comorbid conditions. Specific tactical recommendations were developed with regard to medication dosage, assessment of drug response, management of side effects, and long-term medication management. METHOD: The consensus conference of academic clinicians and researchers, practicing clinicians, administrators, consumers, and families developed evidence-based tactics for the pharmacotherapy of childhood ADHD and its common comorbid disorders. The panel discussed specifics of treatment of ADHD and its comorbid conditions with stimulants, antidepressants, mood stabilizers, alpha-agonists, and (when appropriate) antipsychotics. RESULTS: Specific tactics for the use of each of the above agents are outlined. The tactics are designed to be practical for implementation in the public mental health sector, but they may have utility in many practice settings, including the private practice environment. CONCLUSIONS: Tactics for psychopharmacological management of ADHD can be developed with consensus.

Adrenergic alpha-Agonists↗
PubMed2000

Patient referral by telemedicine: effectiveness and cost analysis of an Intranet system.

The clinical effectiveness and costs of telemedicine in improving the referral process from primary to secondary care were examined in an eight-month prospective, comparative study with one-year follow-up. The internal-medicine outpatient clinics of two Finnish district hospitals were compared--Peijas Hospital (PH) with telemedicine and Hyvinkää Hospital (HH) without it. The three primary-care centres studied referred a total of 292 adult patients to the outpatient clinics. The population-based number of referrals to PH (7.5/1000) from primary-care centres was twice that to HH (3.8/1000). Thirty-seven per cent of referrals to PH included requests from general practitioners for on-line medical advice (teleconsultation). Forty-three per cent of the total number of intranet referrals resulted in outpatient visits at PH, compared with 79% in the outpatient clinic at HH. Only 18% of the patients receiving a teleconsultation ended up in the outpatient department of PH within one year. These visits were mainly due to progression of chronic disease. No deaths or missed diagnoses could be attributed to telemedicine, but one diagnosis was delayed. The direct costs of an outpatient clinic visit in internal medicine (EU211) were seven times greater per patient than for an e-mail consultation (EU32), with a marginal cost decrease of EU179 for every new intranet consultation. A cost-minimization analysis of the alternative interventions showed a net benefit of EU7876 in favour of the teleconsultation process. General practitioners sought an outpatient visit for 130 of their patients, and advice only for another 77. On-line advice was nonetheless given in 108 cases, and only 88 patient visits were arranged. Eleven referrals were declined. The cost difference between giving on-line medical advice for the 108 cases and a visit to the outpatient clinic for the other 88 was less costly (by EU4140) than investigating the 124 patients whose original clinic referrals to the PH were not declined. Productivity in the hospital increased over threefold by using e-mail consultations instead of traditional outpatient visits. The wide interactive use of the intranet referral system between secondary and primary care improved clinical effectiveness, lowered direct costs, increased productivity and was cost-effective.

Adult↗
PubMed2000

Type 2 diabetes mellitus, hyperlipidemia, and extremity lesions in California mice (Peromyscus californicus) fed commercial mouse diets.

BACKGROUND AND PURPOSE: We characterized abnormalities of carbohydrate and lipid metabolism and determined whether those metabolic abnormalities are associated with extremity lesions in California mice (Peromyscus californicus). METHODS: Blood samples were evaluated for glucose, cholesterol, triglyceride, and insulin concentrations. Necropsy and histologic evaluation were done on selected mice, including staining pancreatic sections for insulin. Physical examinations also were performed. RESULTS: California mice were found to have Type 2 diabetes mellitus (T2DM). Sections of pancreas from diabetic and prediabetic mice had pathologic changes consistent with T2DM. After six months of feeding a low-fat diet, mice were normoglycemic, normotriglyceridemic, and normocholesterolemic. Some mice remained hyperinsulinemic. Traumatic lesions were not associated with T2DM. CONCLUSIONS: California mice develop diet-related T2DM when fed a diet containing 25.8% kcal from fat. California mice may be a useful animal model of human T2DM, and traumatic lesions result from housing California mice in multiple male groups.

Animal Feed↗
PubMed1998

Technetium-99m DTPA aerosol contamination in lung ventilation studies.

UNLABELLED: Contamination of working areas by 99mTc DTPA aerosol is of concern to nuclear medicine technologists. This study sought to determine the extent of 99mTc DTPA contamination to technologists, and to localize sources of aerosol leakage so that methods could be identified that would minimize contamination. METHODS: Fifty to eighty millicuries 99mTc DTPA, diluted to a volume of 4-5 ml with normal saline, were injected into the nebulizing chamber of two commercially available inhalation aerosol systems. The patient's nostrils were clamped and a damp washcloth was wrapped around the patient's mouth. An alcohol swab was placed in the exit port of the exhaust filter in each delivery system, and the technologist involved wore a face mask during the inhalation phase. The patient breathed DTPA-labeled aerosol by mouth until the counting rate in the lungs was four times greater than the counting rate from the pulmonary perfusion phase. Connecting joints of the delivery system were then wipe tested. Last, a Geiger-Mueller detector (pancake probe) was used to survey all device components. Readings above 0.05 mR/hr were considered contaminated. RESULTS: The patient was the greatest source of leakage as determined by the damp washcloth, followed by the joints of the tubes of the delivery system and, finally, the system's exhaust filter. Contamination readings from face masks worn by technical personnel during the lung ventilation studies were slightly greater than 0.05 mR/hr. CONCLUSION: The findings support trace levels of contamination to both the technologist and room while performing 99mTc DTPA aerosol ventilation studies. Comparative data using the two delivery systems revealed little difference in sources of leakage and little variation in contamination measurements.

Aerosols↗
PubMed1997

Characterization and mutation analysis of goosecoid-like (GSCL), a homeodomain-containing gene that maps to the critical region for VCFS/DGS on 22q11.

Velocardiofacial syndrome (VCFS) is a developmental disorder characterized by conotruncal heart defects, craniofacial anomalies, and learning disabilities. VCFS is phenotypically related to DiGeorge syndrome (DGS) and both syndromes are associated with hemizygous 22q11 deletions. Because many of the tissues and structures affected in VCFS/DGS derive from the pharyngeal arches of the developing embryo, it is believed that haploinsufficiency of a gene(s) involved in embryonic development may be responsible for its etiology. A homeodomain-containing gene, Goosecoidlike (GSCL), has been recently described, and it resides in the critical region for VCFS/DGS on 22q11. GSCL is related to the Goosecoid gene (GSC) in both sequence of the homeodomain and genomic organization. Gsc in the mouse is expressed during early and midembryogenesis and is required for craniofacial rib, and limb development. The chick homolog of GSCL, termed GSX, is expressed during early chick embryogenesis. We detected GSCL expression in human embryos and biphasic expression in mouse embryos. It is possible that the vertebrate GSCL gene is also required for embryonic development. Due to its location in the critical region on 22q11, GSCL is an excellent candidate gene for VCFS/DGS. The vertebrate GSC protein has the same DNA binding specificity as the Drosophila morphogen, bicoid. Upon examination of the putative GSCL promoter, we found three sequence elements with an exact match to the reverse complement of the bicoid DNA recognition motif, suggesting that GSC, or possibly GSCL itself, regulates the transcription of GSCL. Sequence analysis of the putative promoter and the coding region of GSCL was performed on the DNA template from 17 VCFS patients who did not have a detectable 22q11 deletion to identify mutations. We did not detect a mutation in this set of VCFS patients. A polymorphism was detected in codon 47 of exon 1.

Abnormalities, Multiple↗
PubMed1997

Expression, purification, and characterization of a soluble form of human cytomegalovirus glycoprotein B.

The human cytomegalovirus glycoprotein B gene (gB; gpUL55) was truncated at amino acid 692 and recombined into Autographa californica nuclear polyhedrosis virus (baculovirus). Infection of insect cells with the recombinant baculovirus resulted in high-level expression and secretion of the truncated gB protein (gB-S) into the culture medium. Purification of gB-S by monoclonal antibody affinity chromatography yielded a protein of ca. 200 kDa. Characterization of the 200-kDa purification product indicated that the recombinant gB protein retained many structural and functional features of the viral gB. Comparison of electrophoretic migration patterns in reduced versus nonreduced protein samples and immune blotting analysis with antibodies specific for the amino or carboxy-terminus of gB demonstrated that the recombinant protein was composed of disulfide linked 69 kDa amino terminal and 35-kDa carboxy-terminal fragments. In addition, recognition of the 200-kDa gB-S by a conformational-dependent, oligomer-specific monoclonal antibody suggested that gB-S was properly folded and dimeric. Like the viral gB, gB-S had heparin binding ability. One heparin binding site was found to reside within the 35-kDa carboxy-terminal fragment (aa 492-692). Heparin binding was abolished when gB-S was denatured. These data suggest that gB contains a novel heparin binding motif that is at least partially conformational dependent.

Cytomegalovirus↗
PubMed1997

Molecular definition of 22q11 deletions in 151 velo-cardio-facial syndrome patients.

Velo-cardio-facial syndrome (VCFS) is a relatively common developmental disorder characterized by craniofacial anomalies and conotruncal heart defects. Many VCFS patients have hemizygous deletions for a part of 22q11, suggesting that haploinsufficiency in this region is responsible for its etiology. Because most cases of VCFS are sporadic, portions of 22q11 may be prone to rearrangement. To understand the molecular basis for chromosomal deletions, we defined the extent of the deletion, by genotyping 151 VCFS patients and performing haplotype analysis on 105, using 15 consecutive polymorphic markers in 22q11. We found that 83% had a deletion and >90% of these had a similar approximately 3 Mb deletion, suggesting that sequences flanking the common breakpoints are susceptible to rearrangement. We found no correlation between the presence or size of the deletion and the phenotype. To further define the chromosomal breakpoints among the VCFS patients, we developed somatic hybrid cell lines from a set of VCFS patients. An 11-kb resolution physical map of a 1,080-kb region that includes deletion breakpoints was constructed, incorporating genes and expressed sequence tags (ESTs) isolated by the hybridization selection method. The ordered markers were used to examine the two separated copies of chromosome 22 in the somatic hybrid cell lines. In some cases, we were able to map the chromosome breakpoints within a single cosmid. A 480-kb critical region for VCFS has been delineated, including the genes for GSCL, CTP, CLTD, HIRA, and TMVCF, as well as a number of novel ordered ESTs.

Abnormalities, Multiple↗
PubMed1997

Molecular analysis of velo-cardio-facial syndrome patients with psychiatric disorders.

Velo-cardio-facial syndrome (VCFS) is characterized by conotruncal cardiac defects, cleft palate, learning disabilities, and characteristic facial appearance and is associated with hemizygous deletions within 22q11. A newly recognized clinical feature is the presence of psychiatric illness in children and adults with VCFS. To ascertain the relationship between psychiatric illness, VCFS, and chromosome 22 deletions, we evaluated 26 VCFS patients by clinical and molecular biological methods. The VCFS children and adolescents were found to share a set of psychiatric disorders, including bipolar spectrum disorders and attention-deficit disorder with hyperactivity. The adult patients, >18 years of age, were affected with bipolar spectrum disorders. Four of six adult patients had psychotic symptoms manifested as paranoid and grandiose delusions. Loss-of-heterozygosity analysis of all 26 patients revealed that all but 3 had a large 3-Mb common deletion. One patient had a nested distal deletion and two did not have a detectable deletion. Somatic cell hybrids were developed from the two patients who did not have a detectable deletion within 22q11 and were analyzed with a large number of sequence tagged sites. A deletion was not detected among the two patients at a resolution of 21 kb. There was no correlation between the phenotype and the presence of the deletion within 22q11. The remarkably high prevalence of bipolar spectrum disorders, in association with the congenital anomalies of VCFS and its occurrence among nondeleted VCFS patients, suggest a common genetic etiology.

Abnormalities, Multiple↗