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Biomedical subjects

G Carroll

Publications and source records attributed to G Carroll.

At least 19 recordsLinked to original sources
PubMed2000

The CafA protein required for the 5'-maturation of 16 S rRNA is a 5'-end-dependent ribonuclease that has context-dependent broad sequence specificity.

The CafA protein, which was initially described as having a role in either Escherichia coli cell division or chromosomal segregation, has recently been shown to be required for the maturation of the 5'-end of 16 S rRNA. The sequence of CafA is similar to that of the N-terminal ribonucleolytic half of RNase E, an essential E. coli enzyme that has a central role in the processing of rRNA and the decay of mRNA and RNAI, the antisense regulator of ColE1-type plasmids. We show here that a highly purified preparation of CafA is sufficient in vitro for RNA cutting. We detected CafA cleavage of RNAI and a structured region from the 5'-untranslated region of ompA mRNA within segments cleavable by RNaseE, but not CafA cleavage of 9 S RNA at its "a" RNase E site. The latter is consistent with the finding that the generation of 5 S rRNA from its 9 S precursor can be blocked by inactivation of RNase E in cells that are wild type for CafA. Interestingly, however, a decanucleotide corresponding in sequence to the a site of 9 S RNA was cut efficiently indicating that cleavage by CafA is regulated by the context of sites within structured RNAs. Consistent with this notion is our finding that although 23 S rRNA is stable in vivo, a segment from this RNA is cut efficient by CafA at multiple sites in vitro. We also show that, like RNase E cleavage, the efficiency of cleavage by CafA is dependent on the presence of a monophosphate group on the 5'-end of the RNA. This finding raises the possibility that the context dependence of cleavage by CafA may be due at least in part to the separation of a cleavable sequence from the 5'-end of an RNA. Comparison of the sites surrounding points of CafA cleavage suggests that this enzyme has broad sequence specificity. Together with the knowledge that CafA can cut RNAI and ompA mRNA in vitro within segments whose cleavage in vivo initiates the decay of these RNAs, this finding suggests that CafA may contribute at some point during the decay of many RNAs in E. coli.

Bacterial Outer Membrane Proteins↗
PubMed2000

Soluble glycoprotein 130 (gp130) attenuates OSM- and LIF-induced cartilage proteoglycan catabolism.

Oncostatin M (OSM) and leukaemia inhibitory factor (LIF) exhibit pleiotropic biological activities and share many structural and genetic features. The two cytokines bind with high affinity to the same receptor (LIF/OSM receptor), which consists of the LIF receptor alpha chain (LIFRalpha) and the signal transduction unit gp130. A soluble form of the beta chain of the receptor complex called soluble gp130 (sgp130) has been cloned. In this study, we sought to determine whether recombinant sgp130 or anti-gp130 Ab could attenuate the resorption of proteoglycans induced by OSM and LIF in articular cartilage explants. The results show that at high concentrations sgp130 is capable of attenuating both LIF and OSM mediated resorption. In contrast, anti-gp130 Ab selectively inhibited the stimulation of proteoglycan (PG) release by OSM, albeit minimally. The failure of anti-gp130 to attenuate LIF stimulated PG resorption may be due to the normal interaction of LIF with LIFRalpha and unfettered heterodimerization of LIFRalpha with gp130 in the presence of the antibody. The results indicate that sgp130 and anti-gp130 can modulate cartilage PG metabolism in vitro. Whether sgp130 may have therapeutic activity in models of arthritis or indeed in arthritic diseases remains to be determined.

Animals↗
PubMed1999

Chronic survival of calves implanted with the DeBakey ventricular assist device.

The DeBakey ventricular assist device (VAD) is a miniaturized, electromagnetically driven axial flow pump capable of generating in excess of 10 L/min output. The VAD was evaluated in 19 calves during experiments designed to test iterative modifications in the system and to determine the safety of the DeBakey VAD for intermediate to long-term implant. Five of the animals died or were euthanized during the perioperative period (i.e., Days 1-5) due to complications associated with bleeding (n = 3), sudden cardiac arrest (n = 1), or pump occlusion due to a muscle remnant associated with coring (n = 1). The remaining 14 animals survived from 7-145 days. Ten of the 14 animals survived 30 or more days, and 2 animals survived 93 and 145 days before elective euthanasia. Pump function was evaluated in the 14 calves that survived beyond the perioperative period. Pump output at implantation averaged 3 L/min while output at 100 days (n = 2) averaged 4.22 L/min. The electrical current did not change across time during the study, indicating normal operation of the bearings. Pumps consumed less than 10.5 W of power for all support durations. Hemolysis did not occur; the average daily plasma free hemoglobin varied from 2.0 to 8.0 mg/dl. Evaluation of serum biochemical data showed that implantation of the DeBakey VAD in calves with normal hearts did not impair end organ function; BUN, creatinine, and total bilirubin varied minimally within the normal range. The white blood cell count of implanted animals remained within the normal range throughout the study.

Animals↗
PubMed1999

Four weeks of safety.

We hope to involve businesses, and organizations all across America should participate in dedicating the month of June to the practice of safety. The ultimate goal is to bring about a serious reduction of unintentional deaths and injuries the entire year.

Accidents, Home↗
PubMed1998

Antagonism of the IL-6 cytokine subfamily--a potential strategy for more effective therapy in rheumatoid arthritis.

Pro-inflammatory cytokines, some of which have the capacity to modulate cartilage and bone metabolism, are important mediators of the frequently sustained and destructive inflammation that characterises rheumatoid arthritis (RA). Tumour necrosis factor alpha (TNF alpha) and interleukin-1 (IL-1) have been studied extensively in this regard. That these proteins are important is no longer in doubt following the demonstration that the IL-1 receptor antagonist and neutralising antibodies directed against TNF alpha are clinically effective. Recent studies suggest that interleukin-6 (IL-6) and other members of the IL-6 cytokine subfamily are also potentially important cytokines in the pathogenesis of RA. The recognition of shared molecular subunits in the receptors for these cytokines raises the possibility that components of these receptors or their derivatives, either alone or in combination, may be useful for antagonising members of the IL-6 cytokine subfamily. Effective antagonism could be therapeutically beneficial in respect to attenuating inflammation and protecting critically important chondral and skeletal tissue. In this review the rationale and possible strategies for such antagonism are discussed.

Animals↗
PubMed1997

Detection of oncostatin M in synovial fluid from patients with rheumatoid arthritis.

OBJECTIVE: To measure oncostatin M (OSM) in synovial fluid from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: 20 samples of synovial fluid from patients with RA and 10 samples from patients with OA were examined using an OSM specific sandwich ELISA. RESULTS: OSM was detected at concentrations ranging from 2.36 to 901.82 pg/ml in 18 (90%) of 20 samples of synovial fluid from RA patients. There was no detectable OSM in synovial fluid from OA patients. In the RA patients, the OSM concentration in synovial fluid correlated significantly with the synovial fluid white blood cell count (r = 0.67, p < 0.01), but not with other laboratory parameters of disease activity. CONCLUSION: These findings suggest that OSM may contribute to joint inflammation in RA.

Adult↗
PubMed1997

Interstitial lung disease in recent onset rheumatoid arthritis.

Interstitial lung disease (ILD) is associated with rheumatoid arthritis (RA); however, the prevalence and natural history are undefined. Our aim was to determine the prevalence of ILD associated with RA using a number of sensitive techniques in patients with joint disease of less than 2-yr duration. Patients who met ARA criteria for RA were recruited from community-based and hospital rheumatologists and assessed using the following measures: clinical, lung physiology, radiology (chest X-ray, high resolution CT [HRCT]), bronchoalveolar lavage (BAL) and 99mTc-DTPA nuclear scan. Thirty-six patients (25 female and 11 male) of joint disease duration of (mean +/- SD) 13.2 +/- 8.6 mo were studied. Abnormalities consistent with ILD were found in one or more investigations in 21 of 36 (58%), which were in lung physiology in 22%, CXR in 6%, HRCT in 33%, BAL in 52%, and 99mTc-DTPA nuclear scan in 15%. Based on the results, they were categorized as having clinically significant ILD (Group 1), abnormalities compatible with ILD, but no clinically significant ILD (Group 2) and no abnormalities compatible with ILD (Group 3). Five of 36 (14%) were in Group 1, 16 of 36 (44%) in Group 2, and 15 of 36 (42%) in Group 3. The only risk factor for the presence of abnormalities compatible with ILD was male gender (p < 0.04, Student's t test). In conclusion, changes consistent with ILD in early RA are frequent. The significance of these changes is being determined in a longitudinal study.

Adult↗
PubMed1996

Oncostatin M (OSM) stimulates resorption and inhibits synthesis of proteoglycan in porcine articular cartilage explants.

Oncostatin M (OSM) is structurally and functionally similar to leukaemia inhibitory factor (LIF), interleukin 6 (IL-6), interleukin 11 (IL-11) and ciliary neurotrophic factor (CNTF). We have previously shown that LIF stimulates proteoglycan release and suppresses proteoglycan synthesis in pig and goat cartilage explants. The aim of this study was to determine whether OSM and related cytokines influence proteoglycan metabolism in pig cartilage explants. Slices of pig articular cartilage were incubated for 6 days in serum free DMEM with or without cytokines. The total proteoglycan content in papain digested cartilage explants and medium was determined by the 1,9 dimethylmethylene blue method. Cytokine activity was assessed by determining the percentage release of total proteoglycan. To evaluate proteoglycan synthesis, cartilage was cultured for 48 h under the same conditions and in the final 6 h the tissue was cultured in sulphate free DMEM containing 35SO4. The radioactivity in the medium and tissue was determined in cetylpyridinium chloride precipitates. Biosynthetic activity was expressed as DPM per mg wet weight of cartilage. Dose dependent stimulation of proteoglycan release and suppression of proteoglycan synthesis were observed with rhOSM. IL-6, IL-11 and CNTF also inhibited proteoglycan synthesis in a dose dependent manner but the degree of inhibition was less than that for OSM and these cytokines had no significant effect on proteoglycan release. New biological effects have been identified for OSM and the related cytokines CNTF and IL-11. All three of these cytokines, like LIF and IL-6, suppress proteoglycan synthesis in pig cartilage explants. This common effect suggests that the gp130 subunit of the receptors for these cytokines may represent a common signalling pathway whereby proteoglycan synthesis is regulated. Whilst OSM and LIF stimulate proteoglycan catabolism; IL-6 IL-11 and OSM do not. Thus these effects are not always coupled and activation of gp130 alone may not be a sufficient signal for proteoglycan catabolism.

Animals↗
PubMed1992

Accuracy of a portable interpretive ECG machine in diagnosis of acute evolving myocardial infarction.

From a study of 526 patients having automatic ECG analysis, criteria were established which diagnosed acute evolving Q wave myocardial infarction with 71% sensitivity and 98% specificity. Specificity was 100% when patients with known previous Q wave infarction were excluded. In pre-hospital practice the high sensitivity and specificity were maintained. This method appears appropriate, when other criteria are met, for paramedic-initiated pre-hospital thrombolysis with remote supervision of a cardiologist by telephone.

Adult↗
PubMed1991

Analysis of the genes involved in the insulin transmembrane mitogenic signal in Chinese hamster ovary cells, CHO-K1, utilizing insulin-independent mutants.

CHO-K1 cells, wild type (WT), grow in a defined medium with insulin as the only essential hormone. When starved for insulin, these cells accumulate in G0/G1 stage. Insulin binding to its receptor stimulates DNA synthesis and cell division and induces an increase in abundance of mRNA for c-fos, c-jun, Krox-20, Krox-24 (zif/268), fra-1, jun-B, c-myc, and JE. The kinetics of induction of these genes are similar to that shown with serum induction of 3T3. These genes show maximum stimulation at insulin concentrations of 20, 160, or 320 ng/ml and their expression is inhibited at higher concentrations. The addition of cycloheximide results in superinduction. The WT and insulin-independent mutants show no detectable signal for KC, fos-b, or nur77 and no increase over the basal level of pI-15, probably eliminating these genes as participants in the insulin mitogenic signal. These mutants synthesize DNA in the absence of insulin at rates that vary from 4 to 12 times that of the quiescent (insulin unstimulated) WT and are further inducible by insulin. The mutants have "constitutive" levels of Krox-24 (zif/268), fra-1, jun-B, c-myc, and JE (INS-type 2 genes) mRNAs that vary from mutant to mutant, reaching a maximum of an 8-fold increase for fra-1 and JE over the quiescent WT levels. There were no detectable levels of mRNA for genes c-fos and Krox-20 and no increase in level of mRNA for c-jun (INS-type 1 genes) as compared to the quiescent WT. Thus, although these INS-type 1 and type 2 genes may be involved in the full insulin mitogenic signal, the constitutive up-regulation of only genes in INS-type 2 is sufficient for insulin-independent DNA synthesis and cell division. Analysis of hybrids constructed between WT and mutant 27 indicate that the mutant phenotype is recessive, pointing to the existence of a regulatory gene producing a negative regulator.

Animals↗