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Biomedical subjects

C Campbell

Publications and source records attributed to C Campbell.

At least 145 records · Page 8Linked to original sources

Bacterial overexpression of putative yeast mitochondrial transport proteins.

Thirty-two genes have been identified within the genome of the yeast Saccharomyces cerevisiae which putatively encode mitochondrial transport proteins. We have attempted to overexpress a subset of these genes, namely those which encode mitochondrial transporters of unknown function, and have succeeded in overexpressing 19 of these genes. The overexpressed proteins were then isolated and tested for five well-characterized reconstituted transport activities (i.e., the transport of citrate, dicarboxylates, pyruvate, camitine, and aspartate). Utilizing this approach, we have clearly identified the yeast mitochondrial dicarboxylate transport protein, as well as two additional lower-magnitude transport functions (i.e., tricarboxylate and dicarboxylate transport activities). The implications of these results and the considerations relevant to this approach are discussed.

Carrier Proteins↗

Fringe boundaries coincide with Notch-dependent patterning centres in mammals and alter Notch-dependent development in Drosophila.

In both vertebrate and invertebrate development, cells are often programmed to adopt fates distinct from their neighbors. Genetic analyses in Drosophila melanogaster have highlighted the importance of cell surface and secreted proteins in these cell fate decisions. Homologues of these proteins have been identified and shown to play similar roles in vertebrate development. Fringe, a novel signalling protein, has been shown to induce wing margin formation in Drosophila. Fringe shares significant sequence homology and predicted secondary structure similarity with bacterial glycosyltransferases. Thus fringe may control wing development by altering glycosylation of cell surface and/or secreted molecules. Recently, two fringe genes were isolated from Xenopus laevis. We report here the cloning and characterization of three murine fringe genes (lunatic fringe, manic fringe and radical fringe). We find in several tissues that fringe expression boundaries coincide with Notch-dependent patterning centres and with Notch-ligand expression boundaries. Ectopic expression of murine manic fringe or radical fringe in Drosophila results in phenotypes that resemble those seen in Notch mutants.

Amino Acid Sequence↗

The refractive group.

Spherocylindrical optical elements can be decomposed into a sphere-equivalent component and two cross-cylinder components, oriented at 45 degrees to one another. These components in turn can be represented with a simple matrix formalism. This matrix formalism allows it to be seen that the components also form members of an eight element group, designated the refractive group. The structure of this group is developed including its algebra and its representation with Cayley diagrams. The group is identified as the eight element dihedral group, D4, and is compared to another well-known eight element group, the quaternion group. An example is given using the group formal algebra to develop the transfer equations for spherocylindrical wavefronts. Certain properties of propagating spherocylindrical wavefronts, such as nonrotation of cylinder axes, are seen to come directly as consequences of the group properties.

Eyeglasses↗

Reconstruction of the corneal shape with the MasterVue Corneal Topography System.

This paper explains how the Humphrey MasterVue Corneal Topography System measures the corneal shape and explains what is meant by the various values presented. Covered are the geometrical concepts underlying the method, the necessary reconstruction steps, a description of the arc step reconstruction method used, a description of the cone of focus concept, and definitions of the presented power values.

Cornea↗

Tumor necrosis factor locus polymorphisms in rheumatoid arthritis.

We examined six polymorphic elements in the tumor necrosis factor (TNF) locus and determined their allelic distribution in 98 Caucasian rheumatoid arthritis patients in comparison with 91 ethnically-matched controls. Polymorphic elements at four biallelic sites were distributed similarly between patients and controls, irrespective of the presence or absence of DR4. Differences were observed between the two groups at the TNFa and TNFe loci, but these were consistent with extended MHC haplotypes known to be present in rheumatoid arthritis patients. Therefore, this study suggests that there is little, if any, independent contribution of the TNF locus to the genetic background for rheumatoid arthritis susceptibility.

Adult↗

Drug use history and criminal behavior among 133 incarcerated men.

The present study investigated the relationship between crime and substance abuse in a sample of 133 consecutively evaluated male prisoners. Using the Structured Clinical Interview for DSM-III-R, we assessed the prevalence of various forms of substance abuse in this population and attempted to judge whether substance abuse played a role in the index crime which has led to the present incarceration. In addition, we assessed whether there was a relationship between the nature of substance dependence and the type of crime committed, whether sexual, violent, or non-violent. Among the 133 prisoners, 95% obtained a diagnosis of dependence on one or more substances. Fifty-eight percent of the inmates reported that they were acutely intoxicated with one or more substances at the time they committed the index crime and an additional 6% were withdrawing from a substance at the time of the crime. There was no significant correlation between the type of substance abuse diagnosis and the type of crime committed. Similarly, there was no significant correlation between the number of individuals who reported they were intoxicated at the time of the offense and the type of crime committed.

Adolescent↗

An empirical comparison of rural and urban safety-net hospitals.

This study compares the characteristics of rural hospitals with urban safety-net hospitals and with "other urban hospitals" (non-teaching, non-safety-net urban hospitals that provide mainstream care in the United States). The objective is to examine if there are similarities between rural and urban safety-net hospitals, both of which serve underserved populations. The authors also wish to study if there are areas in which rural and urban safety-net hospitals are closer together compared to "other" urban hospitals. Based on the results, some potential areas of cooperation between rural and urban safety-net hospitals are discussed.

American Hospital Association↗

Cardiac allograft rejection: do trough cyclosporine levels correlate with the grade of histologic rejection?

BACKGROUND: The introduction of cyclosporine to heart transplantation immunosuppressive protocols has been associated with an improvement in the long- and short-term survival rates. The ideal dose of cyclosporine that maximizes its immunosuppressive properties and minimizes its toxicity has remained an enigma since its introduction. This study was undertaken to evaluate which range of cyclosporine levels provided the most effective protection against graft rejection. METHODS: We studied the correlation between cyclosporine levels and histologic grade of rejection, cardiac function, and renal function by retrospectively analyzing the results of 1407 individual whole blood cyclosporine trough levels. One hundred seven heart transplant recipients were studied within 2 years of undergoing transplantation. As a historical comparison, we also studied 146 individual trough cyclosporine levels from a subgroup of patients (n = 14) who had acute cellular rejection with graft dysfunction or failure. We correlated trough cyclosporine levels with the histologic severity of cellular rejection, cardiac function (right cardiac catheterization), and serum creatinine in both groups. The correlation was performed within patient's own data rather than between patient groups to avoid interpatient variations. RESULTS: The mean cyclosporine level was significantly higher (206 ng/ml) when the patients had grade 0 cellular rejection in comparison to grade 3A, with a mean cyclosporine level of 173 ng/ml (p = 0.005). Patients with graft dysfunction or failure had higher mean cyclosporine level (230 ng/ml) when they had no rejection compared with 3A rejection with a mean cyclosporine level of 153 ng/ml (p = 0.001). Furthermore, lower cyclosporine levels were associated with graft dysfunction. There was no correlation between serum creatinine and cyclosporine levels (r = 0.059, r2 = 0.351%). CONCLUSION: We conclude that cyclosporine trough levels above 200 ng/ml in the first 2 years after heart transplantation are associated with reduced cellular rejection without deleterious effects on renal function.

Adult↗

Spinal osteomyelitis presenting with a life-threatening pleural empyema.

STUDY DESIGN: This case report illustrates a rare presentation of spinal osteomyelitis that initially manifested as a life-threatening pleural empyema leading to misdiagnosis. OBJECTIVES: A high index of suspicion is required to make the correct diagnosis of spinal osteomyelitis, especially with unusual presentations. Appropriate antibiotic management should be commenced immediately the diagnosis is made. SUMMARY OF BACKGROUND DATA: A review of the literature reveals five previous cases of vertebral osteomyelitis associated with pleural effusions. In three of these, the effusions were reactive and sterile. There is only one previous case of a pleural empyema related to primary spinal osteomyelitis. There also is one case report of vertebral osteomyelitis presenting as a mediastinal abscess. METHODS: A case is presented of a man thought to have bronchogenic carcinoma with a destructive vertebral metastasis who was sent for palliative radiation therapy. A life-threatening pleural effusion subsequently developed, and after additional investigation, he was found to have spinal osteomyelitis with a pleural empyema. RESULTS: The empyema was drained through an indwelling chest tube, and the patient was administered appropriate antibiotics. He made a complete and uneventful recovery. CONCLUSIONS: The case illustrates a rare presentation of spinal osteomyelitis. It exemplifies the dictum that if a malignant disease is suspected, every effort has to be made to establish a histologic diagnosis to prevent inappropriate management and the potentially devastating consequences of an incorrect diagnosis. It also high-lights the difficulties in diagnosis of vertebral osteomyelitis with empyema. With correct management, the prognosis is excellent.

Abscess↗

Mammalian mitochondria possess homologous DNA recombination activity.

Mitochondrial protein extracts from normal and immortalized mammalian somatic cells catalyze homologous recombination of plasmid DNA substrates. Mitochondrial homologous recombination activity required exogenous adenosine triphosphate, although substantial activity remained when non-hydrolyzable analogs were used instead. There was no requirement for added nucleoside triphosphates, and the reaction was not inhibited by dideoxyadenosine triphosphate or aphidicolin. The majority of recombinant plasmid molecules result from a conservative process, indicating that nuclease-mediated strand-annealing is not responsible for the mitochondrial homologous recombination activity. Affinity-purified anti-recA antibodies inhibited the reaction, suggesting that activity is dependent on a mammalian mitochondrial homolog of the bacterial strand-transferase protein. The presence of homologous recombination activity within mammalian mitochondrial extracts suggests that this process is involved in mitochondrial DNA repair.

Animals↗

Characterization of homologous DNA recombination activity in normal and immortal mammalian cells.

Homologous DNA recombination levels were measured in normal and spontaneously immortalized murine and human fibroblasts, and in a number of primate and murine established fibroblast cell lines. Immortal cell lines and tumor-derived clones homologously recombined extrachromosomal plasmid substrates at frequencies approximately 100-fold higher than did normal cells. To further explore the mechanism responsible for this phenotype, homologous recombination frequency was measured using nuclear extracts derived from normal and immortalized murine and human fibroblasts. Extracts prepared from immortal cells catalyzed high levels of homologous recombination, whereas very little recombination activity was detected in extracts prepared from normal fibroblasts. Similarly, only extracts derived from immortal cells contained strand-transferase activity as measured by the recently described pairing-on-membrane assay. Mixing experiments indicated that a recombination enhancing factor or factors present in immortal cells, rather than a recombination inhibitor in normal cells, was responsible for the enhanced homologous recombination activity observed using extracts derived from the former.

Animals↗

Elevated levels of recombinational DNA repair in human somatic cells expressing the Saccharomyces cerevisiae RAD52 gene.

The Saccharomyces cerevisiae RAD52 gene was introduced into the human fibrosarcoma-derived cell line HT1080. Transfected cell lines that expressed the yeast transgene catalyzed inter-plasmid homologous DNA recombination at frequencies approx. 12-fold higher than did control cells. Additional experiments revealed that yeast RAD52 gene expression increased the level of resistance to the DNA damaging agents diepoxybutane, and methyl methanesulfonate, but did not alter sensitivity to ultraviolet radiation. These results indicate that the S. cerevisiae Rad52 protein can function in a human somatic cell background and provide support for the idea that a homologous recombination-based DNA repair process functions in mammalian somatic cells.

Anti-Bacterial Agents↗

Cloning and characterization of HuR, a ubiquitously expressed Elav-like protein.

The neuronal-specific Elav-like proteins (HuD, Hel-N, and HuC) contain three RNP-type concensus motifs and bind to AU-rich elements. We have identified and cloned a fourth member of this family (HuR) that is expressed in a wide variety of cell types. The purified recombinant protein binds avidly to the AU-rich element in c-fos and interleukin-3 mRNAs. In the case of the c-fos AU-rich element, HuR binds to a core element of 27 nucleotides that contain AUUUA, AUUUUA, and AUUUUUA motifs. Mutational analysis has shown that all three AU motifs are required for maximal binding.

Amino Acid Sequence↗

Identification of a human RAD52 pseudogene located on chromosome 2.

A human testis cDNA library was screened with a hybridization probe encoding the mouse RAD52 gene. Two classes of clones were identified, one derived from the human RAD52 homolog (hRAD52), the other derived from a pseudogene. In addition to many point mutations, several of which encode stop codons, the pseudogene contains a number of frame shifts and a 103-bp deletion. We further determined that the pseudogene is processed and is located on human chromosome 2, in contrast to hRAD52 which is found on chromosome 12. Reverse transcription-PCR analysis of cultured human diploid fibroblasts, as well as fibrosarcoma cells, revealed that while hRAD52 is expressed at low, but detectable levels in these cells, the pseudogene is not.

Animals↗

Elevated levels of homologous DNA recombination activity in the regenerating rat liver.

We have characterized homologous DNA recombination activity in nuclear protein extracts prepared from quiescent and regenerating rat livers. Activity measured in regenerating liver extracts was elevated approximately 35-fold above control, and its appearance closely mirrored the first wave of DNA synthesis, peaking 24 hours after a regenerative stimulus, and returning fairly rapidly to basal levels. We also identified a strand-transferase protein of approximately 100 kDa whose presence in these extracts correlates with homologous recombination activity. Recent evidence suggests that mammalian somatic cells possess a recombinational DNA repair mechanism analogous to that described in the yeast Saccharomyces cerevisiae. Our results indicate that this recombinational repair process may be regulated in vivo by, or play a role in, progression through the cell division cycle.

Animals↗