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Biomedical subjects

S Colley

Publications and source records attributed to S Colley.

11 recordsLinked to original sources

Peripheral nerve injury induces cannabinoid receptor 2 protein expression in rat sensory neurons.

We have localized cannabinoid receptor 2 protein in rat and mouse somatic sensory nervous system, using an antibody that recognizes mouse cannabinoid receptor 2. Little or no cannabinoid receptor 2 immunoreactivity was found in sections of naive rat or mouse dorsal root ganglia or spinal cord. This was in accord with the lack of detectable cannabinoid receptor 2 mRNA in (dorsal root ganglion) neurons by in situ hybridization experiments described in the literature. However, we could detect cannabinoid receptor 2 immunoreactivity following unilateral nerve damage-either by sciatic nerve section, or by spinal nerve ligation. It was localized to the superficial laminae of the dorsal horn of the spinal cord, ipsilateral to the nerve damage, coincident with the area of termination of damaged afferents which was marked by loss of isolectin B4 binding. This upregulation was not seen in cannabinoid receptor 2 null mice. The cannabinoid receptor 2 protein in spinal cord appeared to be expressed on sensory neuron afferent terminals as it colocalized with two markers of damaged afferents, namely growth associated protein-43 and the neuropeptide galanin. Moreover, it did not colocalize with markers of activated microglial cells (OX-42) or astroglial cells (glial fibrillary acidic protein) in rat spinal cord. In the peripheral nerve, accumulation of cannabinoid receptor 2 immunoreactivity was seen in nerve sections proximal, but not distal, to the ligation site, suggesting transport down the nerve from the cell bodies. Although convincing cannabinoid receptor 2 immunoreactivity was seen in neither uninjured nor injured dorsal root ganglion neuron cell bodies in tissue sections, expression was detectable in isolated, cultured neurons that had received a prior axotomy in vivo. This clear demonstration of CB(2) receptors on sensory neurons suggests an additional cellular target for CB(2) agonist induced analgesia, at least in neuropathic models.

Animals↗

Role of endothelial nitric oxide synthase in estrogen-induced osteogenesis.

It is well recognized that high-dose estrogen induces a marked osteogenic response in long bones of female mice. In light of evidence which suggests that nitric oxide synthase (NOS) plays a role in regulation of osteoblast activity, we analyzed whether NOS is involved in mediating this response. Intact female mice were administered 17beta-estradiol (E(2)) either alone or in combination with N(G)-nitro-L-arginine methylester (L-NAME) or aminoguanidine (AG), over 24 days. The former inhibits both constitutive and inducible isoforms of NOS, whereas the latter is a selective inhibitor of inducible NOS. Bone mineral density (BMD) of the femur was subsequently measured by dual-energy X-ray absorptiometry (DXA), and histomorphometry performed at the proximal metaphysis on longitudinal tibial sections. As expected, E(2) given alone led to a marked accumulation of cancellous bone at the proximal tibial metaphysis, associated with a significant gain in femoral BMD, and an increase in cancellous mineralizing surfaces as assessed by histomorphometry. Neither L-NAME nor AG affected cancellous histomorphometric indices when given alone. However, when administered in combination with L-NAME, the magnitude of the skeletal response to E(2) was significantly reduced. The tendency for L-NAME to reduce estrogen-induced bone formation within the proximal tibial metaphysis was more marked distally compared with proximally. In contrast, AG showed no tendency to suppress the osteogenic response to E(2). Subsequently, we examined the effect of E(2) administration on expression within mouse femoral bone marrow of endothelial NOS (eNOS), which is the predominant constitutive isoform of NOS within bone. No change in eNOS mRNA levels was observed following E(2) administration, as assessed by reverse transcription-polymerase chain reaction (RT-PCR). Taken together, our results suggest that eNOS plays a role in mediating estrogen-induced bone formation in intact female mice, possibly as a consequence of posttranscriptional regulation of eNOS activity by estrogen.

Animals↗

A novel ADP-ribosylation like factor (ARL-6), interacts with the protein-conducting channel SEC61beta subunit.

We report here the isolation of a new member of the ADP-ribosylation factor (ARF)-like family (ARL-6) present in the J2E erythroleukemic cell line, but not its myeloid variants. Consistent with this lineage-restricted expression, ARL-6 mRNA increased with erythropoietin-induced maturation of J2E cells, and decreased with interleukin 6-induced differentiation of M1 monoblastoid cells. In tissues, ARL-6 mRNA was most abundant in brain and kidney. While ARL-6 protein was predominantly cytosolic, its membrane association increased following exposure to GTP-gammaS, like many members of the ARF/ARL family. Using the yeast two-hybrid system, six molecules which interact with ARL-6 were identified including SEC61beta, a subunit of the heterotrimeric protein conducting channel SEC61p. Co-immunoprecipitation of ARL-6 confirmed a stable association between ARL-6 and SEC61beta in COS cells. These results demonstrate that ARL-6, a novel member of the ADP-ribosylation factor-like family, interacts with the SEC61beta subunit.

ADP-Ribosylation Factors↗

Four outbreaks of Salmonella enteritidis phage type 4 food poisoning linked to a single baker.

An outbreak of gastrointestinal illness occurred among a party of diners at a hotel in South Yorkshire. A case control study identified a gateau, from an outside supplier, as the likeliest vehicle of infection. Further gateaux from the same baker's premises and other outlets were examined microbiologically. Three other outbreaks of food poisoning in neighbouring districts were recognised and found to be associated with gateaux supplied by the same baker. A total of 32 cases were identified. Stool specimens from 24 cases grew Salmonella enteritidis phage type (PT) 4. The same organism was also grown from gateau in the domestic refrigerator of the chef of one hotel, cheesecake made by the same baker, and a gateau and ingredients from the baker's premises. The isolates of S. enteritidis PT4 were all fully sensitive to antibiotics, and had the same plasmid and pulsed field gel electrophoresis profiles. It is most likely that cross contamination occurred from infected raw eggs on the baker's premises. The control measures instituted probably prevented two further outbreaks, and the baker now uses only pasteurised eggs. The benefits of close cooperation between different local and health authority districts in the investigation of the outbreaks are discussed.

Disease Outbreaks↗

Comparison of ranitidine and cimetidine maintenance treatment of duodenal ulcer.

Sixty-one patients with healed duodenal ulcer were studied during a 12-month maintenance trial with either 150 mg ranitidine at night or 400 mg cimetidine at night. Recurrences were determined at endoscopy after 6 and 12 months of treatment or because of symptomatic relapse. Ulcers recurred in 7 of 28 patients receiving ranitidine and in 8 of 33 patients receiving cimetidine. No serious side effects were encountered.

Adolescent↗