Search PubMed⌕ Search

Biomedical subjects

M Carlson

Publications and source records attributed to M Carlson.

At least 109 records · Page 6Linked to original sources
PubMed1994

Analysis of the SIP3 protein identified in a two-hybrid screen for interaction with the SNF1 protein kinase.

The Saccharomyces cerevisiae SIP3 gene was identified in a two-hybrid screen for proteins that interact in vivo with the SNF1 protein kinase, which is necessary for release of glucose repression. We showed that the C-terminal part of SIP3, recovered through its ability to interact with SNF1, strongly activates transcription when tethered to DNA. We have cloned and sequenced the entire SIP3 gene. The predicted 142-kD SIP3 protein contains a putative leucine zipper motif located in its C terminus. The native SIP3 protein also interacts with DNA-bound SNF1 and activates transcription of a target gene. A complete deletion of the SIP3 gene did not confer phenotypes characteristic of snf1 mutants. However, in a mutant deficient for the SNF1 kinase activity due to loss of the SNF4 stimulatory function, increased dosage of SIP3 partially restored expression of the glucose-repressible SUC2 gene. Overexpression of the C terminus of SIP3 caused defects in growth and SUC2 expression which were remedied by overexpressing SNF1. Taken together, these genetic data suggest that SIP3 is functionally related to the SNF1 protein kinase pathway.

Amino Acid Sequence↗
PubMed1994

The SNF/SWI family of global transcriptional activators.

The yeast SNF/SWI proteins have a global role in transcriptional activation. This set of five proteins assists many gene-specific activators, most likely by altering chromatin structure to relieve repression. Recent work shows that the SNF/SWI proteins function together in a multiprotein complex and that SNF2 has DNA-dependent ATPase activity. SNF/SWI homologs have now been identified in Drosophila, mice and humans, suggesting a conserved role in transcriptional activation.

Animals↗
PubMed1994

A physical map and candidate genes in the BRCA1 region on chromosome 17q12-21.

We have constructed a physical map of a 4 cM region on chromosome 17q12-21 that contains the hereditary breast and ovarian cancer gene BRCA1. The map comprises a contig of 137 overlapping yeast artificial chromosomes and P1 clones, onto which we have placed 112 PCR markers. We have localized more than 20 genes on this map, ten of which had not been mapped to the region previously, and have isolated 30 cDNA clones representing partial sequences of as yet unidentified genes. Two genes that lie within a narrow region defined by meiotic breakpoints in BRCA1 patients have been sequenced in breast cancer patients without revealing any deleterious mutations. These new reagents should facilitate the identification of BRCA1.

Autoantigens↗
PubMed1994

Altered regulatory responses to glucose are associated with a glucose transport defect in grr1 mutants of Saccharomyces cerevisiae.

The GRR1 gene of Saccharomyces cerevisiae affects glucose repression, cell morphology, divalent cation transport and other processes. We present a kinetic analysis showing that the grr1 mutant is also defective in high affinity glucose transport. In combination with a mutation in SNF3, a member of the glucose transporter gene family, grr1 strikingly impairs growth on glucose. These findings suggest that GRR1 and SNF3 affect glucose transport by distinct pathways. The mutation rgt1-1, a suppressor of snf3, restores both glucose transport and glucose repression to a grr1 mutant, but does not remedy the morphological defect. We suggest that GRR1 affects the glucose sensing process and that the association between transport and regulation may reflect the involvement of a transporter in glucose sensing.

Biological Transport↗
PubMed1994

Synergistic release from glucose repression by mig1 and ssn mutations in Saccharomyces cerevisiae.

In the yeast Saccharomyces cerevisiae, glucose repression of SUC2 transcription requires the SSN6-TUP1 repressor complex. It has been proposed that the DNA-binding protein MIG1 secures SSN6-TUP1 to the SUC2 promoter. Here we show that a mig1 deletion does not cause nearly as dramatic a loss of repression as ssn6: glucose-grown mig1 mutants display 20-fold lower SUC2 expression than ssn6 mutants. Thus, repression by SSN6-TUP1 is not mediated solely by MIG1, but also involves MIG1-independent mechanisms. We report that mig1 partially restores SUC2 expression in mutants lacking the SNF1 protein kinase and show that mig1 is allelic to ssn1, a mutation selected as a suppressor of snf1. Other SSN genes identified in this selection were therefore candidates for a role in repression of SUC2. We show that mig1 acts synergistically with ssn2 through ssn5, ssn7, and ssn8 to relieve glucose repression of SUC2 and to suppress the requirement for SNF1. These findings indicate that the SSN proteins contribute to repression of SUC2, and the pleiotropic phenotypes of the ssn mutants suggest global roles in repression. Finally, the regulated SUC2 expression observed in snf1 mig1 mutants indicates that signals regarding glucose availability can be transmitted independently of the SNF1 protein kinase.

DNA-Binding Proteins↗
PubMed1994

Releasability of human hypereosinophilic eosinophils is related to the density of the cells.

The activity of eosinophils and neutrophils with respect to the release of granule proteins was studied in 11 patients with the hypereosinophilic syndrome (HES). Granulocytes or purified eosinophils were stimulated with serumopsonized Sephadex particles (C3b-induced release), and the released amounts of eosinophil cationic protein (ECP), eosinophils protein-X (EPX) and myeloperoxidase (MPO) were measured by means of specific radioimmunoassays (RIA). Eosinophils obtained from patients with HES released significantly more ECP (P < 0.002) and EPX (P < 0.01) after 20 min of incubation than cells from the control group. The cellular content of ECP and EPX in eosinophils obtained from the patients with HES was significantly reduced to 50% and 62%, respectively, of the content of these granule proteins of eosinophils from the control group. In separated eosinophils light-density eosinophils released more of both ECP and EPX than normal density eosinophils. There was no difference in MPO release between the patients and the control group. We conclude that the eosinophils from patients with HES have an increased propensity to release their granule proteins and the releasability seems to be related to the density of the cells.

Adolescent↗
PubMed1994

The GLC7 type 1 protein phosphatase is required for glucose repression in Saccharomyces cerevisiae.

We cloned the GLC7/DIS2S1 gene by complementation of the cid1-226 mutation, which relieves glucose repression in Saccharomyces cerevisiae. GLC7 encodes the catalytic subunit of type 1 protein phosphatase (PP1). Genetic analysis and sequencing showed that cid1-226 is an allele of GLC7, now designated glc7-T152K, which alters threonine 152 to lysine. We also show that the glc7-1 and glc7-T152K alleles cause distinct phenotypes: glc7-1 causes a severe defect in glycogen accumulation but does not relieve glucose repression, whereas glc7-T152K does not prevent glycogen accumulation. These findings are discussed in light of evidence that interaction with different regulatory or targeting subunits directs the participation of PP1 in diverse cellular regulatory mechanisms. Finally, genetic studies suggest that PP1 functions antagonistically to the SNF1 protein kinase in the regulatory response to glucose.

Alleles↗
PubMed1994

Dosage-dependent modulation of glucose repression by MSN3 (STD1) in Saccharomyces cerevisiae.

The SNF1 protein kinase of Saccharomyces cerevisiae is required to relieve glucose repression of transcription. To identify components of the SNF1 pathway, we isolated multicopy suppressors of defects caused by loss of SNF4, an activator of the SNF1 kinase. Increased dosage of the MSN3 gene restored invertase expression in snf4 mutants and also relieved glucose repression in the wild type. Deletion of MSN3 caused no substantial phenotype, and we identified a homolog, MTH1, encoding a protein 61% identical to MSN3. Both are also homologous to chicken fimbrin, human plastin, and yeast SAC6 over a 43-residue region. Deletion of MSN3 and MTH1 together impaired derepression of invertase in response to glucose limitation. Finally, MSN3 physically interacts with the SNF1 protein kinase, as assayed by a two-hybrid system and by in vitro binding studies. MSN3 is the same gene as STD1, a multicopy suppressor of defects caused by overexpression of the C terminus of TATA-binding protein (R. W. Ganster, W. Shen, and M. C. Schmidt, Mol. Cell. Biol. 13:3650-3659, 1993). Taken together, these data suggest that MSN3 modulates the regulatory response to glucose and may couple the SNF1 pathway to transcription.

Adaptor Proteins, Signal Transducing↗
PubMed1994

Temperature monitoring during radiofrequency catheter ablation procedures using closed loop control. Atakr Multicenter Investigators Group.

BACKGROUND: The purpose of this study was to evaluate electrode temperatures obtained using a radiofrequency ablation system that incorporates closed loop feedback control to achieve preset target electrode temperatures and to determine if closed loop temperature control results in a lower incidence of developing a coagulum. METHODS AND RESULTS: Two hundred seventy patients underwent catheter ablation of atrioventricular nodal reentrant tachycardia, an accessory pathway, and/or the atrioventricular junction using an ablation system incorporating closed loop feedback control. Forty-five patients underwent catheter ablation in the power control mode in which power output was fixed, and 225 patients underwent catheter ablation in the temperature control mode. A coagulum occurred during 0.8% of radiofrequency applications in the temperature control mode versus 2.2% in the power control mode (P < .01). Electrode temperatures were within 10 degrees C of the targeted temperature during 35% of applications in the temperature control mode. Ability to achieve the targeted electrode temperature was related to the target, with radiofrequency energy applications at the atrioventricular junction resulting in the highest temperatures (70 +/- 12 degrees C) and those for ablation of the atrioventricular node the lowest (59 +/- 11 degrees C, P < .001), using a maximum of 50 W of power for both. Electrode temperatures were higher during ablation of left free wall and posteroseptal pathways than during ablation of right free wall and septal pathways. The mean and minimum temperatures associated with success were 64 +/- 12 degrees C and 44 degrees C, respectively. Overall, the electrode temperatures at successful and unsuccessful ablation sites did not differ (P > .05). CONCLUSIONS: Temperature monitoring with closed loop control of power output facilitates radiofrequency catheter ablation procedures by minimizing the probability of developing a coagulum while ensuring maximum lesion formation.

Adolescent↗
PubMed1994

Respiratory mechanics by the passive relaxation technique in conscious healthy adults and patients with restrictive respiratory disorders.

The passive relaxation single-breath technique has been used primarily in anesthetized human subjects to measure total respiratory system elastance and resistance. This method was used to assess the pressure-flow characteristics in 32 relaxed, conscious patients with restrictive respiratory disorders (20 with neuromuscular disease, 12 with sarcoidosis) and 27 similarly aged control subjects free of cardiothoracic disease. Using Rohrer's pressure-flow relationship during passive expiration, P/V = K1 + K2V, considerable curvilinear pressure-flow characteristics were found in both groups. These can be attributed to a combination of the upper airway and viscoelastic and elastoplastic behavior of the respiratory system. Despite the greater elastic recoil pressure (and respiratory elastance) of the restrictive patients, their pressure-flow characteristics were similar to those of the control subjects. These findings imply structural similarities in at least the lower airways, or in the effects of retractile forces along airways compensating for reduced lung volumes.

Adult↗
PubMed1994

Purification and characterization of a human neutrophil lipocalin (HNL) from the secondary granules of human neutrophils.

A 45 kDa-protein was purified from the granules of human neutrophils. The protein consists of two apparently identical subunits. The isoelectric point was pH 8.40, and the molecular weight 45 kDa (unreduced) or 24 kDa (reduced). Treatment of the protein with Endoglucosidase F resulted in a reduction in the molecular weight to 20 kDa, indicating the presence of N-linked carbohydrate. The extinction coeffient was E1%,1cm = 13.76 at 280 nm. The 60 amino acid sequence revealed up to 65% sequence homology with rat alpha 2-microglobulin-related protein, which belongs to the lipocalin family. The protein co-sedimented with secondary (specific) granule marker proteins and correlated to the neutrophil content of Lactoferrin (r = 0.81, p < 0.001) and was estimated to be 0.59 microgram 10(-6) cells. Release studies showed that the neutrophils released 51.4 +/- 9.0% of the total cellular content of the protein when they were exposed to serum-opsonized particles, which was much higher than the release of Myeloperoxidase (12.7 +/- 3.5%) and Lactoferrin (22.9 +/- 4.7%). The N-terminal and four tryptic fragment amino acid sequence of the protein was identical with an N-formyl peptide binding 24 kDa protein and gelatinase associated protein of human neutrophils. In conclusion, we have purified and characterized a protein, human neutrophil lipocalin (HNL), from the secondary granules of human neutrophils and shown that it is readily mobilized from the neutrophils upon stimulation.

Acute-Phase Proteins↗
PubMed1994

Social issues distract.

Explore the source record for details and available documents.

American Speech-Language-Hearing Association↗
PubMed1994

Tactile discrimination capacity in relation to size and organization of somatic sensory cortex in primates: I. Old-World prosimian, Galago; II. New-World anthropoids, Saimiri and Cebus.

Living primates vary considerably in brain organization, in sensorimotor and cognitive abilities, and in natural behavioral repertoires. Comparative studies of primary (SI) and secondary (SII) somatic sensory cortex of primates reveal major differences in the size and in the complexity of topographic projection patterns. The separate projections of the glabrous hand to SI cytoarchitectonic areas 3b and 1 described in the Old World (OW) anthropoid Macaca and in New World (NW) anthropoids Cebus, Saimiri, and Aotus are lacking in NW Saguinus and in the prosimian Galago. The relationship between the size and complexity of SI organization and tactile abilities is explored in this study of four species of primates--Galago, Macaca, Cebus, and Saimiri. These species were trained to discriminate between pairs of objects differing either in cross-sectional diameter (size) or surface roughness (texture). The course of acquisition of such tactile discrimination in normal Macaca and the nature of deficits following SI or SII removals are known. Selective lesions of either cytoarchitectonic area 1 or 2 in Macaca affect only texture or size discriminations, respectively. Removal of area 3b in SI, or of SII, in Macaca affects both size and texture capacities. The single projection of the glabrous hand to area 3b-1 of Galago led to our expectation that the capacity of Galago to discriminate textures would be more similar to an area 1-lesioned than to a normal Macaca. The substantial and persistent differences between Macaca and Galago on texture, but not size, tasks lend support to the view that the evolution of a second projection of the glabrous hand to area 1 in Macaca contributes to increased texture discrimination capacity. The similarity in multiple projection patterns of the glabrous hand to areas 3b and 1 in Macaca, Saimiri, and Cebus led us to expect greater correspondence in texture discrimination capacity between these three anthropoids than to Galago. Contrary to expectations, Saimiri and Cebus showed a tactile capacity more similar to Galago than to Macaca. Furthermore, the texture discrimination capacity of Cebus actually improved substantially after removal of area 1. This provides further evidence, together with the single SI hand area in NW Saguinus and Galago, that the separate cutaneous projections to area 1 in OW and NW primates are not homologous but evolved independently and possibly serve different tactile functions.

Animals↗
PubMed1994

Linkage disequilibrium predicts physical distance in the adenomatous polyposis coli region.

To test the reliability of linkage-disequilibrium analysis for gene mapping, we compared physical distance and linkage disequilibrium among seven polymorphisms in the adenomatous polyposis coli (APC) region on chromosome 5. Three of them lie within the APC gene, and two lie within the nearby MCC (mutated in colon cancer) gene. One polymorphism lies between the two genes, and one is likely to be 5' of MCC. Five of these polymorphisms are newly reported. All polymorphisms were typed in the CEPH kindreds, yielding 179-205 unrelated two-locus haplotypes. Linkage disequilibrium between each pair of polymorphisms is highly correlated with physical distance in this 550-kb region (correlation coefficient -.80, P < .006). This result is replicated in both the Utah and non-Utah CEPH kindreds. There is a tendency for greater disequilibrium among pairs of polymorphisms located within the same gene than among other pairs of polymorphisms. Trigenic, quadrigenic, three-locus, and four-locus disequilibrium measures were also estimated, but these measures revealed much less disequilibrium than did the two-locus disequilibrium measures. A review of 19 published disequilibrium studies, including this one, shows that linkage disequilibrium nearly always correlates significantly with physical distance in genomic regions > 50-60 kb but that it does not do so in smaller genomic regions. We show that this agrees with theoretical predictions. This finding helps to resolve controversies regarding the use of disequilibrium for inferring gene order. Disequilibrium mapping is unlikely to predict gene order correctly in regions < 50-60 kb in size but can often be applied successfully in regions of 50-500 kb or so in size. It is convenient that this is the range in which other mapping techniques, including chromosome walking and linkage mapping, become difficult.

Adenomatous Polyposis Coli↗
PubMed1993

Alleles of the APC gene: an attenuated form of familial polyposis.

An attenuated form of familial adenomatous polyposis coli, AAPC, causes relatively few colonic polyps, but still carries a significant risk of colon cancer. The mutant alleles responsible for this attenuated phenotype have been mapped in several families to the adenomatous polyposis coli (APC) locus on human chromosome 5q. Four distinct mutations in the APC gene have now been identified in seven AAPC families. These mutations that predict truncation products, either by single base pair changes or frameshifts, are similar to mutations identified in families with classical APC. However, they differ in that the four mutated sites are located very close to one another and nearer the 5' end of the APC gene than any base substitutions or small deletions yet discovered in patients with classical APC.

Adenomatous Polyposis Coli↗
PubMed1993

Nonsurgical removal of urocystoliths in dogs and cats by voiding urohydropropulsion.

A technique called voiding urohydropropulsion has been developed that facilitates nonsurgical removal of urocystoliths. Voiding urohydropropulsion was performed in 11 dogs and 10 cats with urocystoliths. Urocystoliths were completely removed from 15 of 21 animals (5 female dogs, 3 male dogs, 5 female cats, and 1 male cat). The number of uroliths removed from any animal varied between 1 and 983. The mean time required to complete voiding urohydropropulsion in the 15 animals from which all uroliths were completely removed was 22 minutes. In 6 animals (2 female dogs, 3 female cats, and 1 male cat), not all urocystoliths were removed. Visible hematuria was induced in all animals as a consequence of voiding urohydropropulsion. In dogs, visible hematuria resolved within 4 hours. Dysuria was not induced by this technique in dogs. In many cats, visible hematuria and dysuria persisted for 1 to 2 days. One male cat developed urethral obstruction after we failed to remove a urolith from the bladder. The urolith was returned to the urinary bladder, and subsequently removed by cystotomy. Voiding urohydropropulsion is a simple and effective method that should be considered for removal of small urocystoliths from dogs and cats before cystotomy is performed.

Animals↗
PubMed1993

Sprouting of peripheral nerve axons in the spinal cord of monkeys.

It has been previously suggested that two conditions must be met in order for sprouting to occur in the dorsal horn of the spinal cord: afferent fibers must be stimulated to grow and alternate synaptic sites must be made available. We show that reversibly deactivating peripheral nerve axons by nerve crush alone, which produces little or no additional available synaptic sites, results in expansion of the peripheral nerve inputs in the spinal cord in both adult and infant macaque monkeys.

Animals↗