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Biomedical subjects

G Walker

Publications and source records attributed to G Walker.

At least 19 recordsLinked to original sources
PubMed1995

Interleukin 1 beta-induced expression of nitric oxide synthase in rat renal mesangial cells is suppressed by cyclosporin A.

The expression of inducible nitric oxide synthase (iNOS) is triggered in rat renal mesangial cells by exposure to the inflammatory cytokine interleukin 1 beta (IL-1 beta). Here we report that cyclosporin A (CsA) a potent immunosuppressive drug, inhibits IL-1 beta dependent iNOS expression in renal mesangial cells. Addition of CsA dose dependently suppresses IL-1 beta-induced nitrite formation (IC50 = 0.9 microM). Western- and Northern blot analyses of mesangial cell extracts reveal that the inhibition of IL-1 beta-induced nitrite formation by CsA is due to decreased iNOS protein and iNOS mRNA steady state levels. Using nuclear run on experiments we show that the transcription rate of the IL-1 beta-induced iNOS gene is reduced. Furthermore, by electrophoretic mobility shift analysis we demonstrate reduced DNA-binding of the nuclear factor NF kappa B, an essential component of the IL-1 beta-dependent upregulation of iNOS gene transcription. The data presented in this report suggest that the cellular machinery involved in the IL-1 beta dependent transcriptional upregulation of the iNOS gene in mesangial cells is a target for the action of CsA.

Animals↗
PubMed1995

Pyrrolidine dithiocarbamate differentially affects cytokine- and cAMP-induced expression of group II phospholipase A2 in rat renal mesangial cells.

Renal mesangial cells express group II phospholipase A2 in response to two principal classes of activating signals that may interact in a synergistic fashion. These two groups of activators comprise inflammatory cytokines such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha) and agents that elevate cellular levels of cAMP such as forskolin, an activator of adenylate cyclase. Using pyrrolidine dithiocarbamate (PDTC), a potent inhibitor of nuclear factor NF kappa B, we determined its role in cytokine--and cAMP--triggered group II PLA2 expression. Micromolar amounts of PDTC suppress the IL-1 beta- and TNF alpha-dependent, but not the forskolin-stimulated group II PLA2 activity in mesangial cells. Furthermore, PDTC inhibited the increase of group II PLA2 mRNA steady state levels in response to IL-1 beta and TNF alpha, while only marginally affecting forskolin-induced PLA2 mRNA levels. Our data suggest that NF kappa B activation is an essential component of the cytokine signalling pathway responsible for group II PLA2 gene regulation and that cAMP triggers a separate signalling cascade not involving NF kappa B. These observations may provide a basis to study the underlying mechanisms involved in the regulation of group II PLA2 gene expression.

Animals↗
PubMed1995

Disaster nursing in the Oklahoma City bombing.

The Oklahoma City Federal Building disaster quickly changed a routine day of eye surgical procedures into a chaotic trauma center for the victims with not only eye injuries, but multiple deep lacerations and other injuries. The devastating and disruptive effect of the bombing was stressful for the nursing staff who became disaster survivors of the emotional trauma involved.

Blast Injuries↗
PubMed1994

Incidence of familial melanoma and MLM2 gene.

The overall incidence of melanoma is increasing world wide. We investigated whether there has been an increase in familial melanoma by studying age at onset among different birth cohorts in 18 melanoma kindreds linked to a predisposition gene (MLM2) on chromosome 9. The cumulative incidence of melanoma was 21-fold higher (95% CI 5.2-84.6) among subjects born after 1959 than in those born before 1900. The expected age of onset of the group born after 1959 was 24 years earlier (21.0 vs 45.0 years). These data support the notion that phenotypic penetrance of the MLM2 gene is increasing, presumably as a result of the interaction of sunlight exposure and mutation at this locus.

Adolescent↗
PubMed1994

Dexamethasone differentially affects interleukin 1 beta- and cyclic AMP-induced nitric oxide synthase mRNA expression in renal mesangial cells.

Inducible nitric oxide synthase (iNOS) is expressed in renal mesangial cells in response to two principal classes of activating signals that interact in a synergistic fashion. These two groups of activators comprise inflammatory cytokines such as interleukin (IL)-1 beta or tumour necrosis factor alpha and agents that elevate cellular levels of cyclic AMP (cAMP). We examined whether dexamethasone differentially affects iNOS induction in response to IL-1 beta and a membrane-permeable cAMP analogue, N6,O-2'-dibutyryladenosine 3',5'-phosphate (Bt2cAMP). Nanomolar concentrations of dexamethasone suppress IL-1 beta- as well as Bt2cAMP-induced iNOS protein expression and production of nitrite, the stable end product of nitric oxide (NO) formation. In contrast, dexamethasone prevents induction of iNOS mRNA in response to Bt2cAMP without affecting IL-1 beta-triggered increase in iNOS mRNA levels. These data suggest that dexamethasone acts at different levels, depending on the stimulus used to suppress iNOS induction in mesangial cells.

Amino Acid Oxidoreductases↗
PubMed1994

Two distinct signaling pathways trigger the expression of inducible nitric oxide synthase in rat renal mesangial cells.

The expression of nitric oxide synthase (NOS; EC 1.14.13.39) is induced in rat glomerular mesangial cells by exposure to the inflammatory cytokine interleukin 1 beta (IL-1 beta) or cAMP-elevating agents. Stimulation with IL-1 beta alone leads to an approximately 40-fold increase in NOS activity and nitrite synthesis, whereas the elevation of cAMP with forskolin, cholera toxin, salbutamol, or dibutyryl-cAMP for 24 h resulted in a 2- to 12-fold increase in NOS activity. Moreover, the combinations of IL-1 beta with each of the cAMP-elevating agents greatly enhanced NOS activity in a synergistic fashion. Northern-blot analysis demonstrated a single band of approximately 4.5 kb for the NOS mRNA in rat mesangial cells. IL-1 beta increased NOS mRNA levels in a dose- and time-dependent fashion with a peak of NOS mRNA at 24 h. Dibutyryl-cAMP also increased NOS mRNA levels in mesangial cells in a dose- and time-dependent manner. Furthermore, combination of IL-1 beta and forskolin revealed a strong synergy with maximal mRNA levels 12 h after stimulation. Nuclear run-on transcription experiments suggest that IL-1 beta and cAMP synergistically interact to increase NOS gene expression at the transcriptional level. Furthermore, message stability studies established that NOS mRNA induced by cAMP has a longer half-life than the IL-1 beta-induced message. Moreover, cAMP exposure markedly prolonged the half-life of NOS mRNA from 1 h to 3 h. These data suggest that the level of NOS mRNA is controlled by at least two different signaling pathways, one involving cAMP and the other being triggered by cytokines such as IL-1 beta. The two pathways act synergistically and thus potently up-regulate the expression of inducible NOS in rat mesangial cells.

Amino Acid Oxidoreductases↗
PubMed1994

[Concentration of biocides in indoor rooms using pyrethroids as an example].

Pyrethroids are an analogous substance group to one of the oldest known, naturally occurring insecticides pyrethrum and have replaced a number of pesticides such as Lindane, DDT and PCP on the market. Biocides are more persistent indoors than in nature, which could lead to permanent health hazards for the people concerned. Within a few days after application pyrethroids are rarely detected in room air but can be traced for a long time on textiles, furniture and in dust particles (3, 8). The investigation results of approx. 100 analyses from dust and carpet samples show that approx. 1/3 of these samples are positive for at least one pyrethroid and contain a concentration of > 2 mg substance per kg sample. The evaluation of 35 air samples taken from rooms where substances containing pyrethroids had been used at least a month prior to the investigation (the samples were sampled on active charcoal or Chromosorb) showed that pyrethroids could no longer be traced above the detection limit of 0.05-0.1 micrograms/m3. We therefore think that when investigating a contamination of rooms by biocides it is more advisable to determine pyrethroid and its synergists in the suspended dust portion and corresponding dust sample rather than analysing air by adsorption to active charcoal, Chromosorb or other carrier materials. From the observed concentrations of biocides one could conclude that in an indoor setting secondary contamination by biocides plays a more significant role in the total-body-load than that of air contamination.

Air Pollution, Indoor↗
PubMed1993

'Routine' antenatal care.

The concept of antenatal care is a good model of preventive health targeted towards primary and secondary prevention of diseases and pathological conditions during pregnancy and delivery. A critical evaluation of antenatal care programs demonstrated that these are generally associated with a wide range of positive effects, although the type of care provider is not. However, research methodological limitations such as the selection bias (more care is received by healthier women who will have better outcomes anyway), cannot be ruled out as an explanation for the positive results.

Female↗
PubMed1991

Mapping the binding domain of a myosin II binding protein.

The way in which actin and myosin II become localized to the contractile ring of dividing cells resulting in cleavage furrow formation and cytokinesis is unknown. While much is known about actin binding proteins and actin localization, little is known about myosin localization. A 53-kDa (53K) polypeptide present in the sea urchin egg binds to myosin II in a nucleotide-dependent manner and mediates its solubility in vitro [Yabkowitz, R., & Burgess, D.R. (1987) J. Cell Biol. 105, 927-936]. The binding site of 53K on the myosin molecule was examined in an effort to understand the mechanism of 53K-induced myosin solubility and its potential function in myosin regulation. Blot overlay and chemical cross-linking techniques utilizing myosin proteolytic fragments indicate that 53K binds to fragments proximal to the head-rod junction of myosin. Fragments distal to the head-rod junction do not bind 53K. In addition, the binding of 53K to myosin largely inhibits protease digestion that produces the head and rod fragments. The binding of 53K to the head-rod domain of myosin may be critical in regulation of myosin conformation, localization, assembly, and ATPase activity.

Animals↗
PubMed1991

Africa's health.

Explore the source record for details and available documents.

Africa↗
PubMed1991

Localization of type X collagen in canine growth plate and adult canine articular cartilage.

Type X collagen was extracted from ends of canine growth plates by pepsin digestion after 4 M guanidine hydrochloride extraction, purified by stepwise salt precipitation (2.0 M NaCl in 0.5 M acetic acid), and chromatographed on a Bio-Gel A1.5 M column in 1.0 M CaCl2. Without reduction on sodium dodecyl sulfate (SDS) polyacrylamide gels, the preparation yielded a single, high-molecular-weight (mol wt) band; after reduction, a single band of relative mol wt 5.0 x 10(4) was found. Polyclonal sera were raised against the purified collagen and used in the immunolocalization of canine type X collagen. As expected, indirect immunoperoxidase (IP) or indirect immunofluorescent staining with the polyclonal sera demonstrated that most of the immunoreactivity was localized in the zone of provisional calcification of the growth plate and in cartilage remnants in the metaphyseal region of the physis. A progressive decrease in staining toward the diaphysis of the fetal canine long bone was apparent as the trabecular structures were remodeled to bone. Unexpectedly, type X collagen was also detected in the zone of calcified, mature articular cartilage. It was concentrated in the pericellular matrix of the chondrocytes, appeared at or just above the tidemark, and was expressed immediately before mineralization. Identification of type X collagen in both the canine growth plate and the zone of calcified articular cartilage suggests that cells in the deep layer of cartilage and in the zone of calcified cartilage in the adult animal retain some characteristics of a growth plate and may be involved in regulation of mineralization at this critical interface. The expression of growth plate-like properties would allow the deep chondrocytes of mature articular cartilage to play a role in remodeling of the joint with age and in the pathogenesis of osteoarthritis.

Animals↗
PubMed1991

Safe, stable, whole blood samples for quality assessment of glucose measurement by non-laboratory staff.

A whole blood control material has been used to assess the analytical performance of non-laboratory staff who use glucose meters in clinical areas. It is prepared from sterile horse blood which is readily available from a commercial source. There are no known infection or disease transmission risks to users. When the material is stabilized by the addition of sodium fluoride less than 3% loss of glucose over 48 h is observed from an initial value of 10 mmol/L. However, we prefer to stipulate that the glucose is measured on the day of receipt. The material has been used successfully with Reflolux IIM meters and B-M sticks (Boehringer Mannheim, UK) for over a year in our hospital.

Animals↗
PubMed1991

The morbidity of long-term seizure monitoring using subdural strip electrodes.

The authors report a prospective study of morbidity associated with long-term seizure monitoring using subdural strip electrodes. Three hundred fifty patients were divided into two groups: 175 patients received antibiotics intravenously during the entire period that the electrodes were implanted, and 175 patients received one dose of antibiotics on the morning of surgery. In the group given continuous antibiotic coverage there were two cases of meningitis, both treated without sequelae. In the group receiving one dose of antibiotics, one patient had a brain abscess and three had superficial wound infections. There were no other instances of major morbidity or mortality in either group of patients. The total morbidity rate for both serious and minor complications was 0.85%.

Adult↗
PubMed1991

Transcutaneous magnetic and electrical stimulation over the cervical spine: excitation of plexus roots-rather than spinal roots.

Percutaneous magnetic stimulation (MagStim) and electrical stimulation (ElStim) over the cervical spine were performed in 65 subjects. Compound muscle action potentials (CMAPs) from the abductor digiti minimi (ADM) and the biceps muscles (BICEPS) could be recorded in all subjects tested with both, ElStim and MagStim. Maximal stimulation as determined from the amplitudes of CMAPs was possible in most cases with ElStim but not with MagStim. Latencies after MagStim (centered over C7) and ElStim (cathode over C7/T1, anode positioned 6 cm cephalad in the midline) were not statistically significantly different (P = 0.3). However, in the individual case, it was difficult to predict the precise site at which the motor roots would be activated, since latencies of CMAPs to ElStim and MagStim could differ by up to 1.2 msec. In addition, the excitation site migrated distally when the stimulation intensity was increased with the aim to obtain CMAPs of nearly maximal amplitudes. The results of studying brachial plexus stimulation as well in 22 of the subjects led us to the conclusion that excitation of the motor roots occurs on the average 7 cm (range: 1.4-8.2 cm) proximally to Erb's point. This was confirmed by the finding that when the C7 motor root was stimulated directly intraoperatively within the intervertebral foramen, the excitation site was calculated to be 7.7 cm distal to the foramen and 8.4 cm proximal to Erb's point.

Action Potentials↗
PubMed1991

Performance of techniques used to detect drugs of abuse in urine: study based on external quality assessment.

Twenty-five samples of lyophilized urine from the U.K. External Quality Assessment Scheme for Drugs of Abuse were analyzed by an average of 95 laboratories between April 1987 and December 1989. Samples contained mixtures of analytes and included replicated concentrations of morphine, methadone, amphetamine, and cocaine at 0, 1, 2, and 5 mg/L and of benzoylecgonine at 0, 0.4, 1, 2, and 4 mg/L. Some chromatographic techniques were inadequate for detecting morphine, amphetamine, cocaine, and benzoylecgonine at the lower concentrations of analytes studied: gas-liquid chromatography was least sensitive for morphine; in-house thin-layer chromatography (TLC) was least sensitive for the other analytes. Few significant differences in specificity were detected between techniques, although significant interference from structurally related compounds was demonstrated in assays of morphine, methadone, and amphetamine. Exceptions were the Boehringer (BCL) test for opiates and TLC applied to amphetamine and benzoylecgonine, which demonstrated considerable lack of specificity.

Amphetamine↗