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Biomedical subjects

S Bingham

Publications and source records attributed to S Bingham.

At least 55 records · Page 3Linked to original sources
PubMed2001

Inhibition of inflammation-induced thermal hypersensitivity by sumatriptan through activation of 5-HT(1B/1D) receptors.

Migraine is effectively treated by drugs acting via 5-HT(1B/1D) receptors; however, the antinociceptive effects of such agents have not been fully investigated, particularly in models in which sensitization may be present. The aim of these studies was to evaluate the effects of the 5-HT(1B/1D) receptor agonist sumatriptan in specific models of pain states: a mouse model of inflammation-induced thermal hyperalgesia and a rat model of nerve injury-induced thermal hyperalgesia. In female mice, following intraplantar injection of carrageenan 225 min earlier, sumatriptan (300 microg/kg intraperitoneally; i.p.) increased paw withdrawal latency (PWL) from 3.1 +/- 0.4 s in the saline group to 5.6 +/- 0.9 s, measured 240 min postcarrageenan (P < 0.05 ANOVA followed by post hoc Dunnett's test). A similar effect was seen in male mice. Sumatriptan was also effective in male mice when given i.p. and subcutaneously 15 min precarrageenan, with a maximum effect at 30 microg/kg (i.p. latency 7.4 +/- 1.3 s compared to saline group, 2.6 +/- 0.7 s; i.v. latency 5.9 +/- 0.8 s compared to saline group, 2.9 +/- 0.3 s; P < 0.05 ANOVA followed by post hoc Dunnett's test). The number of mice required to give a response that could be reliably attributed to sumatriptan (number needed to treat) was calculated using discriminant analysis and found to be 2.6. The ability of sumatriptan to attenuate the carrageenan-induced reduction in PWL was blocked by the mixed 5-HT(1B/1D) receptor antagonist GR-127935 (3 mg/kg i.p.) but not by the 5-HT(1B) receptor antagonist SB-224289 (10 mg/kg i.p.). Sumatriptan had no effect on thermal hyperalgesia induced by sciatic nerve ligation in the rat at any time point. These data demonstrate that sumatriptan attenuates the hypersensitivity to noxious thermal stimuli induced by intraplantar carrageenan.

Analysis of Variance↗
PubMed2001

Orexin-A, an hypothalamic peptide with analgesic properties.

The hypothalamic peptide orexin-A and the orexin-1 receptor are localized in areas of the brain and spinal cord associated with nociceptive processing. In the present study, localization was confirmed in the spinal cord and demonstrated in the dorsal root ganglion for both orexin-A and the orexin-1 receptor. The link with nociception was extended when orexin-A was shown to be analgesic when given i.v. but not s.c. in mouse and rat models of nociception and hyperalgesia. The efficacy of orexin-A was similar to that of morphine in the 50 degrees C hotplate test and the carrageenan-induced thermal hyperalgesia test. However, involvement of the opiate system in these effects was ruled out as they were blocked by the orexin-1 receptor antagonist SB-334867 but not naloxone. Orexin-1 receptor antagonists had no effect in acute nociceptive tests but under particular inflammatory conditions were pro-hyperalgesic, suggesting a tonic inhibitory orexin drive in these circumstances. These data demonstrate that the orexinergic system has a potential role in the modulation of nociceptive transmission.

Abdomen↗
PubMed2001

Tonabersat (SB-220453) a novel benzopyran with anticonvulsant properties attenuates trigeminal nerve-induced neurovascular reflexes.

1. The effects of tonabersat (SB-220453) were evaluated on trigeminal nerve ganglion stimulation-induced sensory-autonomic neurovascular reflexes in the anaesthetized cat. Comparisons were made to intravenous administration of carabersat (SB-204269), and to valproate, gabapentin and lamotrigine following intraduodenal administration. 2. There were no effects on resting blood pressure, heart rate, carotid blood flow or carotid vascular resistance for any compound evaluated. 3. Trigeminal nerve ganglion stimulation increased carotid blood flow by 65% and reduced vascular resistance by 41% with minimal effect on blood pressure (< 10%) and no effect on heart rate. Intravenous infusion of tonabersat or carabersat (both 3.4 micromol h(-1)) produced time related reductions in stimulation-induced responses with a maximal inhibition (relative to control) of 30 +/- 7% (n=4), at 240 min for tonabersat and 33+/-4% (n=3) at 180 min for carabersat. Tonabersat (11.5 micromol h(-1)) produced a similar inhibitory effect (32 +/- 9%, n=4) after 120 min of infusion. 4. Following intraduodenal administration of tonabersat, the maximal inhibition of nerve stimulation-induced responses was 55 +/- 4% at 120 min (n=4) for tonabersat 10 mg kg(-1), and 24+/-2% after 180 min for 1 mg kg(-1) (n=4). 5. Intraduodenal administration of sodium valproate (10 or 100 mg kg(-1) n=4/group) had no effect on neurovascular reflexes. Maximal inhibition of nerve ganglion-stimulated reductions in carotid vascular resistance were observed at 150 min for lamotrigine (50 mg kg(-1), 52+/-12%, n=4) and gabapentin (100 mg kg(-1), 17+/-13%, n=3). Lamotrigine 10 mg kg(-1) produced 22+/-11% (n=3) inhibition after 180 min. 6. These data demonstrate blockade of trigeminal parasympathetic reflexes with tonabersat, carabersat and other anticonvulsants. These agents may therefore have therapeutic benefit in conditions where this type of reflex is evident.

Anesthesia↗
PubMed2001

Collection of hematopoietic stem cells from patients with autoimmune diseases.

We reviewed data from 24 transplant centers in Asia, Australia, Europe, and North America to determine the outcomes of stem cell collection including methods used, cell yields, effects on disease activity, and complications in patients with autoimmune diseases. Twenty-one unprimed bone marrow harvests and 174 peripheral blood stem cell mobilizations were performed on 187 patients. Disease indications were multiple sclerosis (76 patients), rheumatoid arthritis (37 patients), scleroderma (26 patients), systemic lupus erythematosus (19 patients), juvenile chronic arthritis (13 patients), idiopathic autoimmune thrombocytopenia (8 patients), Behcet's disease (3 patients), undifferentiated vasculitis (3 patients), polychondritis (1 patient) and polymyositis (1 patient). Bone marrow harvests were used in the Peoples Republic of China and preferred worldwide for children. PBSC mobilization was the preferred technique for adult stem cell collection in America, Australia, and Europe. Methods of PBSC mobilization included G-CSF (5, 10, or 16 microg/kg/day) or cyclophosphamide (2 or 4 g/m2) with either G-CSF (5 or 10 microg/kg/day) or GM-CSF (5 microg/kg/day). Bone marrow harvests were without complications and did not affect disease activity. A combination of cyclophosphamide and G-CSF was more likely to ameliorate disease activity than G-CSF alone (P < 0.001). g-csf alone was more likely to cause disease exacerbation than the combination of cyclophosphamide and g-csf (P = 0.003). Three patients died as a result of cyclophosphamide-based stem cell collection (2.6% of patients mobilized with cyclophosphamide). When corrected for patient weight and apheresis volume, progenitor cell yields tended to vary by underlying disease, prior medication history and mobilization regimen. Trends in the approaches to, and results of, progenitor cell mobilization are suggested by this survey. While cytokine-based mobilization appears less toxic, it is more likely to result in disease reactivation. Optimization with regard to cell yields and safety are likely to be disease-specific and prospective disease-specific studies of mobilization procedures appear warranted.

Adolescent↗
PubMed2001

Fruit and vegetable intake and population glycosylated haemoglobin levels: the EPIC-Norfolk Study.

OBJECTIVE: To investigate whether self-reported frequency of fruit and vegetable consumption was associated with HbA(1C) levels in individuals not known to have diabetes, and what dietary and lifestyle factors might explain this association. DESIGN: Cross-sectional study. SETTING: The EPIC-Norfolk Study, a population-based cohort study of diet and chronic disease. SUBJECTS AND METHODS: A total of 2678 men and 3318 women (45-74 y) not known to have diabetes reported weekly consumption of fruit, green leafy vegetables and other vegetables. RESULTS: Among men, 274 (10.2%) reported seldom or never eating fruit and 127 (4.7%) seldom or never eating green leafy vegetables. Corresponding numbers in women were 157 (4.7%) and 92 (2.8%), respectively. Participants who reported never or seldom having both fruit and green leafy vegetables had higher mean (s.d.) HbA(1C) measurements (5.43% (0.71)) than those who reported more frequent consumption (5.34% (0.67); P=0.046). Differences by category of fruit or green leafy vegetable consumption were not substantially changed after adjustment for saturated fat, dietary fibre and plasma vitamin C. CONCLUSION: These findings support the hypothesis that high intake of fruit and green leafy vegetables may influence glucose metabolism independent of dietary fibre or vitamin C alone and that increased consumption may contribute to the prevention of diabetes.

Aged↗
PubMed2001

Nitric oxide potentiates response of trigeminal neurones to dural or facial stimulation in the rat.

Infusing glyceryl trinitrate as a donor molecule, we have used electrophysiological and c-fos immunostaining techniques to study the effects of nitric oxide on neurones in the nucleus trigeminalis caudalis. Following infusion of glyceryl trinitrate, responses of neurones to electrical stimulation of periorbital cutaneous afferents were potentiated and threshold for activation of neurones by stimulation of dural afferents was reduced. Expression of c-fos was unchanged by glyceryl trinitrate compared to saline controls. Intradermal injection of capsaicin in the periorbital area increased c-fos expression in nucleus trigeminalis caudalis; this was significantly potentiated by glyceryl trinitrate. These results suggest that, in the anaesthetized rat, glyceryl trinitrate alone may not acutely activate the trigeminovascular system to a significant degree at doses that cause headache and later trigger migraine headache in migraineurs. Nevertheless, it is susceptible to exogenous nitric oxide in that activation of trigeminal neurones through cutaneous or dural pathways is potentiated. This may in some measure underlie the pathogenesis of migraine headache.

Afferent Pathways↗
PubMed2001

Dietary assessment in Whitehall II: comparison of 7 d diet diary and food-frequency questionnaire and validity against biomarkers.

The aim of the present cross-sectional study was to examine the agreement and disagreement between a 7 d diet diary (7DD) and a self-administered machine-readable food-frequency questionnaire (FFQ) asking about diet in the previous year, and to validate both methods with biomarkers of nutrient intake. The subjects were an age- and employment-grade-stratified random subsample of London-based civil servants (457 men and 403 women), aged 39-61 years, who completed both a 7DD and a FFQ at phase 3 follow-up (1991-1993) of the Whitehall II study. Mean daily intakes of dietary energy, total fat, saturated, monounsaturated and polyunsaturated fatty acids, linoleic acid, total carbohydrate excluding fibre, sugars, starch, dietary fibre, protein, vitamin C, vitamin E (as alpha-tocopherol equivalents), folate, carotenes (as total beta-carotene activity), Fe, Ca, Mg, K and alcohol were measured. Serum cholesteryl ester fatty acids (CEFA), plasma alpha-tocopherol and beta-carotene were also measured as biomarkers. Estimates of mean energy intake from the two methods were similar in men, and some 10 % higher according to the FFQ in women. Compared with the 7DD, the FFQ tended to overestimate plant-derived micronutrient intakes (carotenes from FFQ v. 7DD men 2713 (SD 1455) v. 2180 (SD 1188) microg/d, women 3100 (SD 1656) v. 2221 (SD 1180) microg/d, both differences P<0.0001) and to underestimate fat intake. Against plasma beta-carotene/cholesterol, carotene intake was as well estimated by the FFQ as the 7DD (Spearman rank correlations, men 0.32 v. 0.30, women 0.27 v. 0.22, all P< or =0.0001, energy-adjusted data). Ranking of participants by other nutrient intakes tended to be of the same order according to the two dietary methods, e.g. rank correlations for CEFA linoleic acid against FFQ and 7DD estimates respectively, men 0.38 v. 0.41, women 0.53 v. 0.62, all P< or =0.0001, energy-adjusted % fat). For alpha-tocopherol there were no correlations between plasma level and estimated intakes by either dietary method. Quartile agreement for energy-adjusted nutrient intakes between the two self-report methods was in the range 37-50 % for men and 32-44 % for women, and for alcohol, 57 % in both sexes. Disagreement (misclassification into extreme quartiles of intake) was in the range 0-6 % for both sexes. The dietary methods yielded similar prevalences (about 34 %) of low energy reporters. The two methods show satisfactory agreement, together with an expected level of systematic differences, in their estimates of nutrient intake. Against the available biomarkers, the machine-readable FFQ performed well in comparison with the manually coded 7DD in this study population. For both methods, regression-based adjustment of nutrient intake to mean dietary energy intake by gender appears on balance to be the optimal approach to data presentation and analysis, in view of the complex problem of low energy reporting.

Adult↗
PubMed2001

Dose-dependent effect of dietary meat on endogenous colonic N-nitrosation.

Human male volunteers were studied in a metabolic facility whilst they were fed randomized controlled diets. In eight volunteers there was a significant increase in faecal apparent total N:-nitroso compounds (ATNC) and nitrite excretion (P < 0.0001 and P = 0.046, respectively) when randomized doses of meat were increased from 0 to 60, 240 and 420 g/day over 10 day periods. Mean (+/- SE) faecal ATNC levels were 54 +/- 7 microg/day when the diets contained no meat, 52 +/- 11 microg/day when the diets contained 60 g meat/day, 159 +/- 33 microg/day with 240 g meat and 199 +/- 36 microg/day with 420 g meat. Higher concentrations of NOC were associated with longer times of transit in the gut (r = 0.55, P = 0.001) and low faecal weight (r = -0.51, P = 0.004). There was no significant decline in levels in individuals fed 420 g meat for 40 days. The exposures found on the higher meat diets were comparable with other sources of N:-nitroso compounds (NOC), such as tobacco smoke. Many NOC are known large bowel initiators and promotors in colon cancer, inducing G-->A transitions in codons 12 and 13 of K-ras. Endogenous NOC formation, combined with prolonged transit times in the gut, may explain the epidemiological associations between high meat/low fibre diets and colorectal cancer risk.

Adult↗
PubMed2001

Epidemiological assessment of diet: a comparison of a 7-day diary with a food frequency questionnaire using urinary markers of nitrogen, potassium and sodium.

BACKGROUND: Validation studies of dietary instruments developed for epidemiological studies have typically used some form of diet record as the standard for comparison. Recent work suggests that comparison with diet record may overestimate the ability of the epidemiological instrument to measure habitual dietary intake, due to lack of independence of the measurement errors. The degree of regression dilution in estimating diet-disease association may therefore have been correspondingly underestimated. Use of biochemical measures of intake may mitigate the problem. In this paper, we report on the use of urinary measures of intakes of nitrogen, potassium and sodium to compare the performance of a semi-quantitative food frequency questionnaire (FFQ) and a 7-day diet diary (7DD) to estimate average intake of these nutrients over one year. METHODS: In all, 179 individuals were asked to complete an FFQ and a 7DD on two occasions separated by approximately 12 months. The individuals were also asked to provide 24-hour urine samples on six occasions over a 6-9-month period, covering the time at which the record FFQ and 7DD were completed. The urine was assayed for nitrogen, potassium and sodium. The protocol was completed by 123 individuals. The data from these individuals were analysed to estimate the covariance structure of the measurement errors of the FFQ, the 7DD and a single 24-hour urine measurement, and to estimate the degree of regression dilution associated with the FFQ and 7DD. RESULTS: The results demonstrated that: (1) the error variances for each of the three nutrients was more than twice as great with the FFQ than the 7DD; (2) there was substantial correlation (0.46-0.58) between the error of both the FFQ and the 7DD completed on different occasions; (3) there was moderate correlation (0.24- 0.29) between the error in the FFQ and the error in the 7DD for each nutrient; (4) the correlation between errors in different nutrients was higher for the FFQ (0.77-0.80) than for the 7DD (0.52-0.70). CONCLUSIONS: The regression dilution with the FFQ is considerably greater than with the 7DD and also, for the nutrients considered, greater than would be inferred if validation studies were based solely on record or diary type instruments.

Adult↗
PubMed2001

Cigarette smoking and glycaemia: the EPIC-Norfolk Study. European Prospective Investigation into Cancer.

BACKGROUND: Previous prospective studies have suggested that cigarette smoking may be associated with an increased risk of type 2 diabetes, but the possibility of confounding, particularly by dietary factors has not been fully examined. METHODS: Cross-sectional analysis of the association between cigarette smoking and HbA(1C), a marker of long-term glucose homeostasis in 2704 men and 3385 women, aged 45--74 years who were recruited to a population-based study of diet and chronic disease. RESULTS: Twelve per cent of men and 11% of women reported being current smokers. Mean HbA(1C) was lowest in never smokers, intermediate in former smokers and highest in current smokers. There was a dose-response relationship between HbA(1C) levels and number of cigarettes smoked per day and a positive association with total smoking exposure as measured by pack-years. The unadjusted increase in HbA(1C) for 20 pack-years of smoking was 0.12% (95% CI : 0.09--0.16) in men and 0.12% (95% CI : 0.08--0.17) in women. After adjustment for possible confounders including dietary variables, the values were 0.08% (95% CI : 0.04--0.12) and 0.07% (95% CI : 0.02--0.12) for men and women, respectively. Mean HbA(1C) was inversely related to time since quitting smoking in men. CONCLUSIONS: These results add support to the hypothesis that smoking has long-term effects on glucose homeostasis, an association that cannot be explained by confounding by dietary factors as measured in this study.

Aged↗
PubMed2001

Fat consumption and HbA(1c) levels: the EPIC-Norfolk study.

OBJECTIVE: To describe the relationship between total dietary fat and the pattern of fat intake and HbA(1c). RESEARCH DESIGN AND METHODS: In this cross-sectional study, 2,759 men and 3,464 women (40-78 years of age) without a previous diagnosis of type 2 diabetes were recruited from a population-based sampling frame. Diet was assessed using a self-reported semiquantitative food frequency questionnaire. RESULTS: The HbA(1c) level was negatively associated with the polyunsaturated fat-to-saturated fat ratio (P:S ratio) of the diet (beta = -0.0338 HbA(1c)% per SD change in P:S ratio; P < 0.001) and positively associated with the total level of fat intake (beta = 0.0620 HbA(1c)% per SD change in total fat intake; P < 0.001), adjusted for age and total energy intake. The associations remained significant when adjusted for each other and for total energy, protein, age, sex, family history of diabetes, BMI, waist-to-hip ratio, physical activity, and smoking (for P:S ratio, beta = -0.0200 HbA(1c)% per SD change in P:S ratio, P = 0.013; for total fat, beta = 0.420% HbA(1c)% per SD change in total fat intake, P < 0.001). The benefits from a high P:S ratio were attributed to a lower saturated fat intake. CONCLUSIONS: These findings demonstrate independent associations between HbA(1c) concentration across the normal range of HbA(1c) and both total fat intake and the pattern of dietary fat intake. They provide further support to efforts promoting modifications in the intake of dietary fat.

Adult↗
PubMed2000

Carrageenan-induced thermal hyperalgesia in the mouse: role of nerve growth factor and the mitogen-activated protein kinase pathway.

NGF is an important link between inflammation and hyperalgesia and interacts with many different mediators of inflammation, including the MAPK signaling pathway. In these studies, carrageenan-induced thermal hyperalgesia was evaluated in the mouse and the role of NGF and the MAPK pathway investigated. Carrageenan induced a time-dependent inflammation and thermal hyperalgesia, which was maximal 4 h post administration. Both indomethacin (0.3, 1.0 and 10 mg/kg s.c., 30 min pre-carrageenan) and morphine (0.4, 1.2, 4.0 mg/kg; s.c., 30 min pre-hyperalgesia measurement) significantly inhibited carrageenan-induced thermal hyperalgesia and indomethicin inhibited paw inflammation, demonstrating the model as suitable for the assessment of anti-hyperalgesic and anti-inflammatory agents. Anti-NGF (0.67 mg/kg sc, 60 min pre-carrageenan) produced a significant inhibition of thermal hyperalgesia, but not inflammation. NGF itself produced a time-dependent hyperalgesia, but not inflammation, following intraplantar injection. The specific MAPK pathway inhibitor, PD98059 (0.1, 0.3 and 1 mg/kg sc, 30 min pre-carrageenan) significantly inhibited carrageenan-induced hyperalgesia, but not inflammation. These data demonstrate a role for both NGF and the MAPK signaling pathway in the production of thermal hyperalgesia, but not inflammation, in the mouse.

Analgesics, Opioid↗
PubMed2000

Department of Veterans Affairs Cooperative Studies Program genetic linkage study of schizophrenia: ascertainment methods and sample description.

To help clarify the genetics of schizophrenia, the Department of Veterans Affairs Cooperative Studies Program has completed data collection for a genetic linkage study of schizophrenia. This article describes the methodological details of the data collection. Subsequent articles will describe the results of our genome scan, which is now in progress. The data collection protocol included the Diagnostic Interview for Genetic Studies, the Family Interview for Genetic Studies, a review of medical records, and the collection of blood for transformation into lymphoblast cell lines. Among relatives of schizophrenic probands, we assessed auditory attention and verbal memory with neuropsychological tests. Among the 166 families ascertained for the study, 143 had a single affected sib-pair, 17 had three affected siblings, one had five affected siblings and five had two sets of affected siblings. There was a total of 216 affected sib-pairs in these families. Using the n-1 rule, these families contain 188 independent affected sib-pairs.

Adult↗
PubMed2000

Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia.

The vanilloid receptor-1 (VR1) is a ligand-gated, non-selective cation channel expressed predominantly by sensory neurons. VR1 responds to noxious stimuli including capsaicin, the pungent component of chilli peppers, heat and extracellular acidification, and it is able to integrate simultaneous exposure to these stimuli. These findings and research linking capsaicin with nociceptive behaviours (that is, responses to painful stimuli in animals have led to VR1 being considered as important for pain sensation. Here we have disrupted the mouse VR1 gene using standard gene targeting techniques. Small diameter dorsal root ganglion neurons isolated from VR1-null mice lacked many of the capsaicin-, acid- and heat-gated responses that have been previously well characterized in small diameter dorsal root ganglion neurons from various species. Furthermore, although the VR1-null mice appeared normal in a wide range of behavioural tests, including responses to acute noxious thermal stimuli, their ability to develop carrageenan-induced thermal hyperalgesia was completely absent. We conclude that VR1 is required for inflammatory sensitization to noxious thermal stimuli but also that alternative mechanisms are sufficient for normal sensation of noxious heat.

Adenosine Triphosphate↗
PubMed2000

Nerve injury-associated kinase: a sterile 20-like protein kinase up-regulated in dorsal root ganglia in a rat model of neuropathic pain.

Partial injury of the rat sciatic nerve elicits a variety of characteristic chemical, electrophysical and anatomical changes in primary sensory neurons and constitutes a physiologically relevant model of neuropathic pain. To elucidate molecular mechanisms that underlie the physiology of neuropathic pain, we have used messenger RNA differential display to identify genes that exhibit increased ipsilateral expression in L4/5 dorsal root ganglia, following unilateral partial ligation of the rat sciatic nerve. One set of partial complementary DNA clones identified in this screen was found to encode a protein kinase, nerve injury-associated kinase. Cloning of the full-length human nerve injury-associated kinase complementary DNA, together with recombinant expression analysis, reveal nerve injury-associated kinase to be a functional member of a subgroup of sterile 20-like protein kinases characterised by the presence of a putative carboxy terminal autoregulatory domain. Induction of nerve injury-associated kinase expression in dorsal root ganglia in the rat neuropathic pain model was confirmed by quantitative reverse transcription-polymerase chain reaction, and RNA in situ hybridization analysis revealed enhanced levels of nerve injury-associated kinase within neurons.Together, our data implicate nerve injury-associated kinase as a novel upstream component of an intracellular signalling cascade that is up-regulated in dorsal root ganglia neurons in response to sciatic nerve injury.

Amino Acid Sequence↗
PubMed2000

Identification of differentially expressed genes in dorsal root ganglia following partial sciatic nerve injury.

Partial sciatic nerve injury, a model of neuropathic pain, elicits a variety of neurochemical, electrophysiological and neuroanatomical changes in primary sensory neurons. We have used the technique of messenger RNA differential display to identify genes with altered expression in these neurons which may contribute to the development of aberrant sensation following such peripheral nerve damage. This approach identified 14 distinct complementary DNA clones, representing transcripts with increased ipsilateral expression in L4/5 dorsal root ganglia, two weeks after unilateral partial ligation of the rat sciatic nerve. Both Zucker diabetic fatty rats and their lean counterparts were used in this study but none of the transcripts identified showed an induction that was confined to one of the two groups. The majority of the clones did not show significant sequence similarity to previously reported genes and therefore may represent novel messenger RNA sequences or, alternatively, unknown regions of partially characterised messenger RNAs. Two of the clones represented transcripts for the known proteins muscle LIM protein and acidic epididymal glycoprotein, neither of which had previously been associated with expression in the nervous system. Reverse transcriptase-polymerase chain reaction analysis and in situ hybridization confirmed that the messenger RNA expression of both muscle LIM protein and acidic epididymal glycoprotein was induced in an ipsilateral-specific manner. Their localisations, examined with in situ hybridization in L5 dorsal root ganglia, were limited in each case to a sub-population of neuronal profiles. Those neuronal profiles that demonstrated muscle LIM protein hybridization were distributed across the profile size range, whereas the distribution of acidic epididymal glycoprotein-positive profiles appeared to be skewed towards smaller profiles. The induction of muscle LIM protein and acidic epididymal glycoprotein in dorsal root ganglia may play an important functional role in the adaptive response of primary sensory neurons following partial sciatic nerve injury.

Animals↗