Search PubMed⌕ Search

Biomedical subjects

J E Simpson

Publications and source records attributed to J E Simpson.

At least 19 recordsLinked to original sources
PubMed2002

The humoral response in the pathogenesis of gluten ataxia.

OBJECTIVE: To characterize humoral response to cerebellum in patients with gluten ataxia. BACKGROUND: Gluten ataxia is a common neurologic manifestation of gluten sensitivity. METHODS: The authors assessed the reactivity of sera from patients with gluten ataxia (13), newly diagnosed patients with celiac disease without neurologic dysfunction (24), patients with other causes of cerebellar degeneration (11), and healthy control subjects (17) using indirect immunocytochemistry on human cerebellar and rat CNS tissue. Cross-reactivity of a commercial IgG antigliadin antibody with human cerebellar tissue also was studied. RESULTS: Sera from 12 of 13 patients with gluten ataxia stained Purkinje cells strongly. Less intense staining was seen in some but not all sera from patients with newly diagnosed celiac disease without neurologic dysfunction. At high dilutions (1:800) staining was seen only with sera from patients with gluten ataxia but not in control subjects. Sera from patients with gluten ataxia also stained some brainstem and cortical neurons in rat CNS tissue. Commercial anti-gliadin antibody stained human Purkinje cells in a similar manner. Adsorption of the antigliadin antibodies using crude gliadin abolished the staining in patients with celiac disease without neurologic dysfunction, but not in those with gluten ataxia. CONCLUSIONS: Patients with gluten ataxia have antibodies against Purkinje cells. Antigliadin antibodies cross-react with epitopes on Purkinje cells.

Aged↗
PubMed2001

Extracellular nucleotides differentially regulate interleukin-1beta signaling in primary human astrocytes: implications for inflammatory gene expression.

The cytokine interleukin-1beta (IL-1beta) is a potent activator of human astrocytes, inducing or modulating expression of multiple proinflammatory genes via activation of the transcription factors nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). In this study, we examined whether IL-1beta signaling is regulated in these cells by extracellular nucleotides that are released at high concentrations under inflammatory conditions and act as ligands for members of the P2 receptor family. Using reporter constructs and electromobility shift assays, we found that cotreatment of astrocyte cultures with ATP (1-100 microm) significantly potentiated IL-1beta-mediated activation of NF-kappaB and AP-1 and that ATP alone activated AP-1. These effects were blocked by the P2 receptor antagonists XAMR 0721, periodate-oxidized ATP, and suramin. A role for ATP in modulating IL-1beta-mediated inflammatory gene expression was supported further by the observation that ATP potentiated the IL-1beta-induced expression of IL-8 mRNA and protein but strongly downregulated IP-10 expression. Reverse transcription-PCR and cloning demonstrated expression of the ATP-responsive P2 receptor subtypes P2Y(1), P2Y(2), and P2X(7), as well as the ATP-insensitive receptor P2Y(4). ADP, a selective agonist for P2Y(1), produced results similar to or greater than those obtained using ATP, whereas 2'-3'-O-(4-benzoyl-benzoyl)-ATP, a selective agonist for P2X(7), was less effective than ATP. In contrast, UTP, a selective agonist for P2Y(2) and P2Y(4), was ineffective. These studies indicate that different P2 receptor subtypes play distinct roles in the modulation of IL-1beta-mediated signal transduction in human astrocytes, and that signaling via P2 receptors may fine-tune the transcription of genes involved in inflammatory responses in the human CNS.

Adenosine Triphosphate↗
PubMed2000

Expression of the interferon-gamma-inducible chemokines IP-10 and Mig and their receptor, CXCR3, in multiple sclerosis lesions.

The recruitment of leucocytes to sites of inflammation is an important feature of multiple sclerosis (MS) pathology. Chemokines are involved in the activation and specific directional migration of monocytes and T-lymphocytes to sites of inflammation. Using immunocytochemistry, the expression of the alpha-chemokines, interferon (IFN)-gamma-inducible protein-10 (IP-10) and monokine induced by IFN-gamma (Mig), and their receptor CXCR3 have been examined in post-mortem central nervous system (CNS) tissue from MS cases at different stages of lesion development. In actively demyelinating lesions both IP-10 and Mig protein were predominantly expressed by macrophages within the plaque and by reactive astrocytes in the surrounding parenchyma. CXCR3 was expressed by T cells and by astrocytes within the plaque. Interferon-gamma may stimulate glial cells to express IP-10 and Mig, which continue the local inflammatory response by selectively recruiting activated T-lymphocytes into the CNS.

Adult↗
PubMed1998

Expression of monocyte chemoattractant protein-1 and other beta-chemokines by resident glia and inflammatory cells in multiple sclerosis lesions.

Beta-chemokines induce the directional migration of monocytes and T lymphocytes and are thus associated with chronic inflammation. Using immunocytochemistry and in situ hybridisation (ISH) techniques, we have examined the expression of the beta-chemokines monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES (regulated upon activation, normal T cell expressed and secreted) in post-mortem human brain from multiple sclerosis (MS) cases, at different stages of lesion development. In actively demyelinating MS plaques RANTES expression was restricted to the blood vessel endothelium, perivascular cells and surrounding astrocytes, suggesting a role in the recruitment of inflammatory cells from the circulation. MCP-1 was expressed by astrocytes and macrophages within acute MS lesions, but was restricted to reactive astrocytes in the parenchyma surrounding the lesion. MIP-1alpha was expressed by astrocytes and macrophages within the plaque, while MIP-1beta was expressed by macrophages and microglia within the lesion, and by microglia in surrounding white matter. Glial cells may be stimulated to produce chemokines and continue the local inflammatory response by forming chemotactic gradients to attract T cells and mononuclear phagocytes from the circulation and surrounding tissue.

Adult↗
PubMed1997

Structure-activity relationship of a series of C-terminus modified aminoalkyl, diaminoalkyl- and anilino-containing analogues of the benzoic acid mustard distamycin derivative tallimustine: synthesis, DNA binding and cytotoxicity studies.

As part of our investigations into the design of more cytotoxic analogues of the experimental anticancer drug tallimustine, 1, C-terminus modified aminoalkyl-, 2a-c, diaminoalkyl-, 3, and anilino-containing, 4, derivatives have been synthesized. Compounds 2a-c differ by 2, 3, or 4 methylene units in the C-terminus, respectively. Results from an ethidium displacement study on poly(dA-dT), poly(dG-dC), calf thymus DNA and T4 coliphage DNA showed that compounds 2-4 interact in the minor groove of the polynucleotides with a preference for poly(dA-dT) over poly(dG-dC). Compound 4 bound more weakly to the DNAs than 2a-c and 3. Using a CD dilution assay compounds 2a-c and 3 were demonstrated to bind irreversibly to calf thymus DNA. The sequence selectivity by which compounds 2-4 alkylate DNA was demonstrated using a Taq polymerase stop assay. All the compounds alkylated preferentially at the 3'-purine residue in a 5'-TTTTGPu-3' sequence (Pu = A or G). This observed sequence specificity is similar to that of tallimustine and a related compound 5. At an equimolar concentration the aminoalkyl compounds 2a-c (2b > 2a > 2c), and diaminoalkyl compound 3 were more efficient at alkylating these sequences than the anilino compound 4. Following a one hour exposure of human chronic myeloid leukemia K562 cells, compounds 2b and 3 have lower IC50 values (1.64 microM and 3.03 microM, respectively) than tallimustine (5 microM) and similar values to a related compound 5 (2.2 microM). The order of cytotoxicity for all the compounds is 2b > 5 > 3 > 2a > 1 > 2c = 4. These results indicate that the cytotoxicities of these compounds are related to their relative ability to alkylate the consensus DNA binding sequence.

Alkylation↗
PubMed1979

Hypertrophic scarring: Dexon suture in a randomized trial.

In a randomized prospective trial of three methods of skin suture an increased incidence of hypertrophic scarring in paramedian and inguinal wounds has been found to be associated with the use of 2/0 Dexon suture subcuticularly. However, the variance associated with the type of suture was less than that associated with the sex of the patient. The patient's opinion of the appearance of the scar was the same for all three suture methods used in skin closure.

Abdomen↗
PubMed1978

Them and us.

Explore the source record for details and available documents.

Allied Health Personnel↗
PubMed1978

Relative efficacy of two oxytetracycline formulations and doxycycline in the treatment of acute anaplasmosis in splenectomized calves.

The efficacy of 3 antibiotic formulations was measured in the treatment of artificially induced anaplasmosis in the early stages of an ascending parasitemia (1% to 4%) in 23 splenectomized calves. Group 1, consisting of 5 calves, served as nontreated controls. Four calves (group 2) were treated 1 time with 10 mg of oxytetracycline (T-50)/kg of body weight IM; 5 calves (group 3) were treated 3 times with 10 mg of T-50/kg IM; 5 calves (group 4) were treated 1 time with 20 mg of an experimental oxytetracycline (T-200)/kg IM; and 4 calves (group 5) were treated 1 time with 10 mg of a synthetically derived antibacterial agent, doxycycline (D-100)/kg IM. All control calves died and 1 of 4 calves died that was treated 1 time with T-50. Other deaths did not occur. All treatments were effective in moderating the infective process, but T-50 given 3 times and T-200 given 1 time were markedly more effective than T-50 and D-100 given 1 time. There appeared to be little or no difference in therapeutic efficacy between T-50 and D-100 given 1 time and between T-50 given 3 times and T-200 given 1 time.

Acute Disease↗
PubMed1978

Elimination of the carrier state of bovine anaplasmosis with a long-acting oxytetracycline.

A long-acting formulation of oxytetracycline (L-200) was injected at a dose level of 20 mg/kg intramuscularly into 12 yearling cattle that had been experimentally inoculated with Anaplasma marginale 64 days previously. Four cattle were treated twice, 4 were treated 3 times, and 4 were treated 4 times. All injections were given once ever 7 days. Previous work (unpublished) with this formulation has revealed prolonged blood values following a single injection. The blood (80 ml) of each calf was inoculated into a susceptible test calf 83 days after the last treatment dose. Anaplasmosis did not occur in any of the test calves. Two infected cattle were treated with 12 daily injections of oxytetracycline (L-50) at a dose level of 11 mg/kg to establish the sensitivity of the parasite to oxytetracycline. Subsequent calf inoculation tests showed that A marginale was eliminated. Two unmedicated, infected cattle remained infected throughout the study. Complement-fixation tests with A marginale antigen at 6 months after treatment showed average sera titers of less than 5 in the treated cattle and 45 in the unmedicated cattle.

Anaplasmosis↗
PubMed1978

Efficacy of a new oxytetracycline formulation against clinical anaplasmosis.

A study was conducted to determine whether 1 intramuscular injection of an experimental long-acting oxytetracycline formulation was effective in treatment of induced acute anaplasmosis in cattle and to compare this with the drug response resulting from repeated treatments with an existing, approved oxytetracycline product. The new formulation was supplied in solutions of 200 mg of oxytetracycline/ml and was administered 1 time at the rate of 20 mg/kg of body weight. The experimental formulation was compared with a product providing 50 mg of oxytetracycline/ml which was administered on 2 consecutive days at the dose rate of 10 mg/kg for each treatment. The response to treatment observed in the study animals indicates that 1 injection of the experimental formulation was equivalent to 2 daily injections of the 50 mg/ml product in treating animals with acute bovine anaplasmosis compared with infected nonmedicated control animals. The need for new chemotherapeutic compounds such as this formulation for use in the treatment and control of anaplasmosis is discussed.

Anaplasmosis↗
PubMed1977

"Right" stay in hospital after sugery: randomised controlled trial.

A randomised controlled trial was carried out on 100 patients to compare the effects of discharge after certain pre-specified clinical criteria had been fulfilled--"right" stay--with those of discharge at an arbitrary 10 days after surgery--"fixed" stay. The operations concerned (cholecystectomy and vagotomy) were more hazardous than those previously included in studies of early discharge. Patients in the right-stay group were discharged, on average, 7-6 days after operation--that is, two days earlier than those in the fixed-stay group. In terms of clinical progress, social factors such as return to work, and the acceptability to patients and relatives of the implications of right stay, patients in this group fared as well as those in the fixed-stay group, and in some respects slightly better. Right stay entailed the transfer of some work from hospital to community medical and nursing staff, but this also was acceptable. The concept and use of the right-stay principle is of value in planning the postoperative discharge of suitable patients.

Adult↗
PubMed1977

Length of stay.

Explore the source record for details and available documents.

Convalescence↗
PubMed1976

Comparative study of short-term recovery of mental efficiency after anaesthesia.

Two common general anaesthetic techniques were compared to evaluate the time taken for the patient's mental efficiency to recover sufficiently for him to be escorted home after inguinal herniorrhaphy. Recovery in performance efficiency to at least 60% of the patient's own maximum is suggested as a criterion for discharge, and this needs a stay in hospital of seven to nine hours.

Anesthesia, General↗