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Biomedical subjects

C Meredith

Publications and source records attributed to C Meredith.

At least 37 records · Page 2Linked to original sources
PubMed1998

Role of interleukin-10 in the lung response to silica in mice.

There is evidence that, following exposure to crystalline silica, the release of several proinflammatory cytokines contributes to the induction of unbalanced inflammatory reaction leading to lung fibrosis. We have examined the potential contribution of interleukin-10 (IL-10), an anti-inflammatory cytokine, in the development of silicosis. In a mouse model of inflammatory lung reaction induced by intratracheal instillation of silica (0.5 mg and 5 mg DQ12/mouse), the levels of IL-10 protein (determined by ELISA) both in cells obtained after bronchoalveolar lavage (BAL) and in lung tissue homogenates were significantly increased when compared with controls. After in vitro lipopolysaccharide (LPS) stimulation (1 microg/ml), BAL cells obtained from silica-treated animals produced significantly more IL-10 protein and mRNA than cells obtained from control animals. To examine the role of IL-10 in the lung reaction induced by silica, IL-10-deficient animals were instilled with 5 mg of silica. Twenty-four hours after treatment, the amplitude of the inflammatory response (lactate dehydrogenase [LDH], protein and number of inflammatory cells in BAL) was significantly greater in IL-10-deficient animals than in the wild type. In contrast, the fibrotic response, evaluated by measuring lung hydroxyproline content and by histopathologic analysis 30 days after silica, was significantly less important in IL-10-deficient than in wild-type mice. Together, these data suggest that increased IL-10 synthesis induced by silica can limit the amplitude of the inflammatory reaction, but also contributes to amplify the lung fibrotic response.

Animals↗
PubMed1997

Association of c-fos mRNA expression and excitotoxicity in primary cultures of mouse neocortical and cerebellar neurons.

The effect of excitatory amino acids (EAAs) on c-fos mRNA expression was studied in primary cultures of mouse cerebellar granule cells and in neocortical neurons after 2 and 7 days in vitro (div). In cultured granule cells at 2 and 7 div, and in cortical neurons at 2 div, exposure to low levels (< or = 10 microM) of a variety of EAAs (viz. glutamate [Glu], S-sulpho-L-cysteine [SC], N-methyl-D-aspartate [NMDA], alpha-amino-3-hydroxy-5-methyl-4-isoxazole [AMPA], and kainate [KA]) resulted in a transient increase in the level of c-fos mRNA which peaked at 30 min but returned to a basal level by 120 min. However, exposure of granule cells (7 div) to high levels (250 microM) of Glu, NMDA, KA, SC and of cortical neurons (7 div) to high levels (250 microM) of Glu, NMDA, KA, SC, or AMPA and to low levels (< or = 10 microM) of Glu and AMPA resulted in a delay in c-fos mRNA induction but a subsequent, progressive increase that was sustained for at least 240 min. Furthermore, this effect was accompanied by a dose-related increase in the release of the cytosolic enzyme, lactate dehydrogenase, used as an indicator of excitotoxicity. A ratio (Q240/30) for the steady-state levels of c-fos mRNA after 30 min and 240 min of exposure to EAAs was determined which showed that Q240/30 >2 correlated reproducibly with excitotoxic cell death, whereas a ratio of < or = 1 correlated with a nonexcitotoxic event. In both cell types at 7 div, coadministration of the selective NMDA receptor antagonist, DL(+/-)-2-amino-5-phosphonopentanoic acid (APV) with cytotoxic levels of Glu 1) protected against EAA-induced neurotoxicity and 2) exhibited a transient c-fos mRNA expression (Q240/30 values approximately 1). In contrast, the AMPA/KA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), provided no protection against excitotoxicity and had no significant effect on the Glu-induced delay in c-fos mRNA expression. These results suggest that the Q240/30 c-fos mRNA ratio may 1) be used as a predictive index for excitotoxic neuronal death, 2) provide information on the identity of the receptor subtype mediating excitotoxicity in different brain cell types, and 3) aid in establishing the role of excitotoxicity during the development of neurons in vitro.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1997

Dynorphin and the kappa 1 ligand [3H]U69,593 binding in the human epileptogenic hippocampus.

The distribution of dynorphin (DYN), one of its binding sites (kappa 1 receptor) and their relationship to neuronal loss and granule cell hyperexcitability was examined in hippocampi from patients with temporal lobe epilepsy (TLE). In hippocampi that were not the seizure focus (mass associated temporal lobe epilepsy, MaTLE; and paradoxical temporal lobe epilepsy, PTLE) DYN-like immunoreactivity was localized in the dentate granule cells and their mossy fiber terminals within the hilus and area CA3. In hippocampi that were the seizure focus (MTLE), 89% showed an additional band of immunoreactivity confined to the inner molecular layer (IML) of the dentate gyrus, representing recurrent mossy fiber collaterals. In 11% of MTLE patients no staining was found in the IML (MTLE/DYN-). The MTLE/DYN- hippocampi were also characterized by a significantly lower degree of cell loss than in MTLE hippocampi in the dentate granule cell layer, the hilus and CA3. Both MTLE and MTLE/DYN- hippocampi showed evoked epileptiform bursting in granule cells while MTLE showed greater polysynaptic EPSPs and spontaneous excitatory activity. Thus granule cell recurrent collateral sprouting may account for only some aspects of hyperexcitability. In 30% of the MTLE group, hilar neurons of a variety of morphological types expressed DYN immunoreactivity in their somata and dendrites. The density of [3H]U69,593 binding sites in MaTLE and PTLE patients was highest in areas CA1 and the subiculum-regions having little or no DYN-staining. In the dentate molecular layer, hilus and CA3--regions with the most DYN immunoreactivity--there was a low density of ligand binding. The significance of this transmitter/receptor mismatch is yet unknown.

Adolescent↗
PubMed1997

Natural spillover of a distinctly Canidae-associated biotype of rabies virus into an expanded wildlife host range in southern Africa.

Rabies enzootics in southern Africa are associated with two genetically distinct groups of viruses, thought to be adapted to two different sets of host species. The virus groups are referred to as the canid biotype (infecting carnivores of the family Canidae) and the viverrid biotype (infecting carnivores of the subfamily Viverrinae). Cross- or spillover infections of one biotype into the host range of the other are thought to occur from time to time. However, very little is known about this phenomenon and its role in the epidemiology of rabies in southern Africa. We have investigated spillover by monoclonal antibody and nucleic acid sequence analysis of a wide range of virus isolates. Although the inverse had been documented, this report constitutes the first evidence of spillover of canid biotype viruses into viverrid hosts. Our genetic analysis was focused specifically on the G-L intergenic region of the virus genome, thought to be a remnant or pseudogene and it was indicated that, with respect to this region of the genome, spillover does not influence the phylogeny of virus isolates.

Animals↗
PubMed1996

Information needs of cancer patients in west Scotland: cross sectional survey of patients' views.

OBJECTIVE: To assess the needs of patients with cancer for information about their condition. DESIGN: Cross sectional survey of patients' views by means of semistructured interview with questionnaire. SETTING: A regional cancer centre and two university hospitals in west Scotland. SUBJECTS: 250 (93%) of 269 cancer patients invited to participate in study who were selected by age, sex, socioeconomic status, and tumour site to be representative of cancer patients in west Scotland. MAIN OUTCOME MEASURES: Patients' need to know whether they had cancer, the medical name of their illness, progress through treatment, how treatment works, side effects, chances of cure, and treatment options. RESULTS: 79% (95% confidence interval 73% to 84%) of patients wanted as much information as possible, and 96% (93% to 98%) had a need or an absolute need to know if they had cancer. Most patients also wanted to know the chance of cure (91% (87% to 94%)) and about side effects of treatment (94% (90% to 97%)). When the replies were cross tabulated with patients' age, sex, deprivation score, and type of treatment there was a linear trend for patients from more affluent areas to want more information and those from deprived areas to want less. There was a strong preference for diagnosis of cancer to be given by a hospital doctor (60% (53% to 66%). CONCLUSION: Almost all patients wanted to know their diagnosis, and most wanted to know about prognosis, treatment options, and side effects.

Adolescent↗
PubMed1995

Excitatory amino acid-induced cytotoxicity in primary cultures of mouse cerebellar granule cells correlates with elevated, sustained c-fos proto-oncogene expression.

An elevated, sustained expression of c-fos mRNA was found in primary cultures of mouse cerebellar granule cells following exposure to toxic concentrations of the excitatory amino acids, L-glutamate, L-homocysteate, S-sulpho-L-cysteine and N-methyl-D-aspartate (NMDA), using leakage of lactate dehydrogenase (LDH) as an indicator of cytotoxicity. In contrast, when used at non-toxic concentrations these compounds induced a rapid and transient increase in c-fos mRNA levels. Both LDH release and elevated, sustained c-fos mRNA induction were blocked (in the case of L-homocysteate) or reduced (in the case of L-glutamate and S-sulpho-L-cysteine) by the selective NMDA receptor antagonist (DL(+/-)-2-amino- 5-phosphonopentanoic acid) whereas 6-cyano-7-nitroquinoxaline-2,3-dione (a selective antagonist at non-NMDA ionotropic receptors) had no effect. These data suggest a role for altered c-fos mRNA expression in excitotoxic mechanisms.

Animals↗
PubMed1995

Are there too many alarms in the intensive care unit? An overview of the problems.

There are many reported problems with auditory warnings in critical care areas of hospitals such as the intensive care unit (ICU) and operating room. There are too many alarms; many of them are unnecessarily loud and continuous, which can be irritating and annoying for staff. The problem of excessive alarms is further complicated by the fact that there are no standards agreed between manufacturers on the auditory warnings used for medical equipment. Therefore, the same piece of equipment manufactured by different companies will have different alarms that could result in confusion. Another possibility as to why confusion could occur is because alarms are often inappropriate in terms of their 'urgency mapping'. This means there is generally no relationship between the urgency of a medical situation and the perceived urgency of the alarm that signals that condition. A further problem involves the number of false alarms that occur; that is, alarms that are not signalling a medical emergency. The following paper discusses these problems and suggests attempts to remedy some of them. There is also a brief discussion of the amount of monitoring that occurs on the ICU as the more monitors there are the greater the number of alarms there will be

Confusion↗
PubMed1995

Autosomal dominant distal myopathy: linkage to chromosome 14.

We have studied a family segregating a form of autosomal dominant distal myopathy (MIM 160500) and containing nine living affected individuals. The myopathy in this family is closest in clinical phenotype to that first described by Gowers in 1902. A search for linkage was conducted using microsatellite, VNTR, and RFLP markers. In total, 92 markers on all 22 autosomes were run. Positive linkage was obtained with 14 of 15 markers tested on chromosome 14, with little indication of linkage elsewhere in the genome. Maximum two-point LOD scores of 2.60 at recombination fraction .00 were obtained for the markers MYH7 and D14S64--the family structure precludes a two-point LOD score > or = 3. Recombinations with D14S72 and D14S49 indicate that this distal myopathy locus, MPD1, should lie between these markers. A multipoint analysis assuming 100% penetrance and using the markers D14S72, D14S50, MYH7, D14S64, D14S54, and D14S49 gave a LOD score of exactly 3 at MYH7. Analysis at a penetrance of 80% gave a LOD score of 2.8 at this marker. This probable localization of a gene for distal myopathy, MPD1, on chromosome 14 should allow other investigators studying distal myopathy families to test this region for linkage in other types of the disease, to confirm linkage or to demonstrate the likely genetic heterogeneity.

Adolescent↗
PubMed1994

A study of acute side-effects related to palliative radiotherapy treatment of lung cancer.

Two recent studies carried out by the Medical Research Council Lung Cancer Working Party have suggested that large fraction radiotherapy to the chest in either 10-Gy single fraction or 17-Gy two-fraction doses, 1 week apart, is safe and effective for patients who require palliation for bronchogenic cancer. The Beatson Oncology Centre, Glasgow, participated in the original MRC trial and anecdotal reports of acute chest pains, fevers, sweats and rigors in some patients during the first 24-hour period after radiotherapy treatment were noted. These acute side-effects were not monitored during the Medical Research Council trials. It was felt that this area warranted further evaluation in order to identify the incidence of such acute side-effects and to what extent they caused a reduction in the patients' remaining quality of life. A pilot study of 10 patients confirmed the manifestation of the side-effects reported anecdotally in the MRC trial. It was on this basis that the study was extended, with a further 51 patients being invited to participate over a 4-month period. The findings indicate a significant incidence of adverse side-effects in patients receiving large fraction radiotherapy to the chest in either 10-Gy single fraction or 17-Gy two-fraction doses, but that these are transient and do not cause unacceptable disruption to the patients over an extended period.

Adult↗
PubMed1992

Secretory and accessory cell functions of the alveolar macrophage.

We have attempted to address the requirements necessary for alveolar macrophage accessory cell function. We have also examined the in vitro and in vivo factors that must be taken into account when interpreting results from experimental studies. Differences in phenotypic expression by rat alveolar pleural and peritoneal macrophages are noted, as well as the differing expression of major histocompatibility complex (MHC) class II molecules. Furthermore, alveolar macrophages, harvested from rat lung, do not express the interleukin (IL)-1 cytokines, and lipopolysaccharide (LPS) treatment of quiescent cells (after 24-hr in vitro culture) induces low levels of expression of IL-1 alpha and IL-1 beta. Short-term inhalation of refractory ceramic fibers, however, results in markedly increased IL-1 beta expression after stimulation with LPS. We suggest that, in vivo, IL-1 beta may be involved in the initial recruitment and activation of inflammatory cells rather than in induction of immune responses. We also postulate, based on recent published evidence, that alveolar macrophages activate the dendritic cells within the respiratory epithelium. Thus alveolar macrophages would release cytokines critical for the activation of dendritic cells during the afferent limb of the immune response, and they would respond to products of sensitized T-cells such as interferon-gamma and IL-4 to interact with T-helper cells in an antigen-specific MHC-restricted manner during the efferent limb of the response.

Animals↗
PubMed1992

The effect of the Valsalva maneuver on the diameter of the common hepatic duct in extrahepatic biliary obstruction.

The internal diameter of the common hepatic duct as measured by ultrasonography is an imperfect predictor of extrahepatic biliary obstruction. This study examined the effect of the Valsalva maneuver on the diameter of the duct in 25 consecutive patients (12 with obstruction; 13 without obstruction) who underwent endoscopic retrograde cholangiopancreatography (ERCP). A normal response was defined as a decrease in the diameter of greater than 1 mm at the level of the portal vein. The response to the Valsalva maneuver improved the predictive outcome (sensitivity, 100%; specificity, 92.3%) suggesting that this maneuver should be part of the routine assessment of the common hepatic duct.

Cholestasis, Extrahepatic↗
PubMed1991

Leucine metabolism during fasting and exercise.

Whole body leucine kinetics were examined in seven healthy young men while in a 14-h postabsorptive state (PAS) and after a 3.5-day fast (FS). Subjects received a primed constant intravenous infusion of L-[1-13C]leucine while resting for 3 h and then while exercising on a cycle ergometer at 45% maximal O2 uptake to exhaustion. Blood samples drawn during isotopic steady state were analyzed for 13C enrichment of leucine and alpha-ketoisocaproic acid, and expired gas samples were analyzed for 13CO2. Resting leucine flux was higher in the FS, and there was a slight increase in leucine oxidation. During exercise, leucine flux did not differ between PAS and FS but leucine oxidation rose markedly. In the FS, leucine oxidation was 25 +/- 7 (SD) mumol.kg-1.h-1 at rest and rose to 75 +/- 21 mumol.kg-1.h-1 during exercise; in the PAS, oxidation was 20 +/- 5 mumol.kg-1.h-1 at rest and 52 +/- 17 mumol.kg-1.h-1 during exercise. These data indicate that the high rate of leucine oxidation previously found during exercise was increased further by a 3.5-day fast.

Adult↗