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Biomedical subjects

D Mitchell

Publications and source records attributed to D Mitchell.

At least 163 records · Page 9Linked to original sources
PubMed1992

Fever response of sheep in the peripartum period to gram-negative and gram-positive pyrogens.

We have measured body temperatures and serum iron concentrations of sheep in the peripartum period following administration of endotoxin and Staphylococcus aureus cell walls. Both the rise in rectal temperature and the fall in serum iron concentration following intravenous injection of S. aureus were the same immediately pre- and postpartum as they were 5 weeks after parturition. The rise in rectal temperature following intravenous endotoxin injection immediately pre- and postpartum was significantly less than that of the same ewes 5 weeks later. However, the fall in serum iron concentration following endotoxin injection was significantly suppressed only prepartum. We conclude that fever is not suppressed in sheep in the peripartum period, but the response to endotoxin is suppressed, through complex processes incidental to the mechanism responsible for the maintenance of gestation and induction of labour.

Animals↗
PubMed1992

Identification and characterization of rat intestinal lamina propria cells: consequences of microbial colonization.

Germ-free (GF) animals exhibit an abnormally diminished, cell-mediated immune response which can be rapidly normalized by bacterial colonization of the intestine. This conventionalization suggests that the development and/or regulation of the immune system is dependent upon intestinal bacteria or their products. Here we consider the ontogeny of gut-associated lymphoid tissue (GALT) immunocytes by isolating and characterizing the intestinal lamina propria cells (LPC) of GF rats responding to bacterial colonization or an irrelevant protein antigen, and compared to LPC of specific pathogen-free (SPF) rats which were conventionalized (CV) from birth. Isolation of cells was accomplished by successive EDTA washings of small intestine to remove the epithelium, and enzymatic digestion of the tissue generating single-cell suspensions. Resulting cell suspensions were characterized by monoclonal antibodies directed against leukocyte epitopes using flow cytometry. Functional characterization was measured by the tritiated thymidine proliferation assay with concanavalin A (Con A) and lipopolysaccharide (LPS) as co-stimulators. Germ-free and SPF rats had fewer total LPC than CV rats. Antibody staining revealed that GF rats had fewer total leukocytes than CV and SPF rats, and that CV rats had a greater percentage of T-cells and cells positive for the C3 receptor than GF rats. Co-stimulation of LPC with mitogens only increased proliferation of cells from CV rats compared to GF and SPF rats. In addition, spleen cells from CV rats demonstrated significantly enhanced proliferative responses compared to spleen cells from GF rat and were more analogous to spleen cells from SPF rats in their ability to proliferate in vitro, with and without mitogens. We conclude that T-cells and CD35-positive (C3BR+) cells are recruited and/or proliferate in response to intestinal bacteria and/or their products, and that this results in the induction of immune competency.

Animals↗
PubMed1992

Isolation of a yeast artificial chromosome clone that spans the (12;16) translocation breakpoint characteristic of myxoid liposarcoma.

Cytogenetic analysis of liposarcomas has demonstrated that translocation (12;16) (q13.3;p11.2) is characteristic of the myxoid subtype of this adipose tissue tumor. Our previous results suggested that the GLI gene is close to the translocation breakpoint on chromosome 12. We now describe a yeast artificial chromosome (YAC) that contains GLI and spans the chromosome 12 region involved in the t(12;16) breakpoint. This clone will permit rapid definition of the genetic region surrounding the breakpoint and allow isolation of the gene presumably affected by the translocation.

Chromosomes, Fungal↗
PubMed1992

Effects of systemic non-steroidal anti-inflammatory drugs on nociception during tail ischaemia and on reperfusion hyperalgesia in rats.

1. We have investigated the effects of five non-steroidal anti-inflammatory drugs (NSAIDs) on nociception during ischaemia and on reperfusion hyperalgesia in rats. 2. We induced tail ischaemia in conscious rats by applying a tourniquet at the base of the tail until the rats exhibited co-ordinated escape behaviour when we released the tourniquet. 3. We assessed hyperalgesia by measuring the tail flick latency following tail immersion in water at 49 degrees C, before applying and immediately after releasing the tourniquet, and then at 30 min intervals for 2 h. 4. Intraperitoneal injection of NSAIDs prior to applying the tourniquet had no effect on the co-ordinated escape behaviour during ischaemia, nor on tail flick latency in the absence of prior ischaemia. However all the drugs attenuated reperfusion hyperalgesia in a log dose-dependent manner. Doses required to abolish hyperalgesia, were indomethacin 5 mg kg-1, diclofenac sodium 42 mg kg-1, ibuprofen 54 mg kg-1, dipyrone 168 mg kg-1 and paracetamol 170 mg kg-1. 5. We conclude that the mechanisms underlying nociception during ischaemia are not the same as those underlying reperfusion hyperalgesia. Moreover our procedure provides a rapid and more humane method for measuring the antinociceptive potency of NSAIDs.

Animals↗
PubMed1992

Fetal and maternal body temperatures measured by radiotelemetry in near-term sheep during thermal stress.

Using implanted radiotelemeters, we have measured amniotic temperature and fetal lamb and pregnant ewe body temperatures continuously over the last 34 days of gestation and during conditions of thermal stress. Body temperature of the fetus was approximately 0.6 degrees C higher than that of the mother, and the fetomaternal temperature difference remained constant over the last 25 days of gestation, until the immediate prepartum period, when it rose. During exposure to mild heat stress (35 degrees C dry-bulb temperature, 24 degrees C wet-bulb temperature), ewe and fetal body temperatures rose, but fetal temperature rose at a slower rate. Thus the fetomaternal temperature gradient fell significantly in the initial exposure period. In an environment of 4 degrees C, body temperature of the pregnant ewes fell, but the fetomaternal gradient did not change significantly. During maternal fever, heat loss from the fetus was compromised; body temperature of the fetus rose more than that of the mother, and the fetomaternal temperature gradient rose significantly. We suggest that mild heat or cold exposure in pregnant animals constitutes little risk of fetal thermal stress. During maternal fever, however, the fetus may be at risk of thermal injury.

Animals↗
PubMed1992

Contrasting properties of bradykinin receptor subtypes mediating contractions of the rabbit and pig isolated iris sphincter pupillae preparation.

Bradykinin contracts both the pig and rabbit iris sphincter preparations. In the pig, the bradykinin antagonists Lys,Lys-[Hyp3, Thi5,8,D-Phe7]-BK and D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]-BK (HOE140) inhibited responses with pKB estimates of 6.0 and 8.4, respectively. These affinities are markedly lower than in the rabbit preparation, suggesting that different receptors are present in each of the two species.

Animals↗
PubMed1992

Impressions for oculofacial prosthetics.

Primary to the development of an acceptable and functional facial prosthesis is the impression procedure. The fabrication of a facial prosthesis combines the art and science of anatomy, cosmesis, and function, to develop a nonliving substitute to replace altered, missing, or defective regions of the head and neck area. Success depends on patient's cooperation, motivation, and commitment to treatment as well as the technical and artistic scope of the facial prosthetic service.

Colloids↗
PubMed1992

Successful therapy with ribavirin of late onset respiratory syncytial virus pneumonitis complicating allogeneic bone transplantation.

A 21-year-old patient developed interstitial pneumonitis nine months post bone marrow transplant for acute myeloblastic leukaemia. Immunofluorescence of broncheoalveolar lavage fluid revealed the presence of respiratory syncytial virus (RSV). Aerosolized ribavarin therapy resulted in rapid resolution of the pneumonitis with full recovery without any side effects. Ribavarin therapy should be considered early in the management of BMT patients who develop RSV pneumonitis.

Adult↗
PubMed1991

Neurokinin receptors in the rabbit iris sphincter characterised by novel agonist ligands.

We have used novel selective agonist ligands to examine neurokinin receptors mediating the contractile response to tachykinins in the rabbit iris sphincter preparation in vitro. The selective NK-1 receptor agonist delta-amino valeryl-[L-Pro9,N-Me Leu10]SP-(7-11) (GR73632) and the NK-3 receptor-selective agonist succ-[Asp6,N-Me-Phe8] SP-(6-11) (senktide) were both very active (concentration range 0.032 pM-10 nM and 0.1 pM-32 nM respectively), and were 933 and 16.6 times more potent than substance P, respectively, in contracting the iris. In contrast, the NK-2 selective agonist [Lys3,Gly8-R-gamma-lactam,Leu9]NKA-(3-10) (GR64349) was active only at the highest concentrations tested (3.2 nM-32 microM), and had 0.054 the activity of substance P. The presence of several peptidase inhibitors was without effect on the concentration-response relationship to substance P, GR73632, GR64349 or senktide. Tachykinins differed in their offset kinetics. Responses to GR73632, GR64349 and senktide were rapid in offset (times to reach half maximal responses were 1.5, 1.1 and 5.1 min, respectively), whereas responses to substance P were very much more prolonged in duration (time to reach half maximal response was 35.3 min). These results suggest the presence of both NK-1 and NK-3 receptors mediating contraction of the rabbit iris sphincter preparation. In addition, differences in response offset kinetics seem not to be due to differences in peptide metabolism, and suggest a property of substance P not shared by the other tachykinins used in this study.

Animals↗
PubMed1991

Lymphoedema/hypercalcaemia syndrome mediated by parathyroid-hormone-related protein.

A 24-year-old woman presented with a cryptogenic, hypercalcaemic syndrome with metastatic pulmonary calcification and leg and massive breast enlargement and bilateral chylous pleural effusions compatible with a generalised lymphatic abnormality. The patient's serum parathyroid hormone-related protein concentration was very high at a time when she was significantly hypercalcaemic, implying that the hypercalcaemia was mediated by this protein.

Adult↗
PubMed1991

Nongenital pelvic leiomyosarcoma metastatic to the heart.

A patient who had a 5-year history of a low-grade nongenital pelvic leiomyosarcoma was evaluated for worsening dyspnea, hypertension, and jugular venous distension. An echocardiogram revealed a large right atrial mass. At surgical exploration, metastatic leiomyosarcoma was found within the inferior vena cava extending from below the renal veins up into the right atrium. Using cardiopulmonary bypass with profound hypothermia and circulatory arrest, the inferior vena cava was opened below the renal veins, and the tumor was transected. That portion of the tumor above this transection was then extracted through a right atriotomy. Resection of the pelvic tumor was not thought to be feasible. The patient remains asymptomatic with stable pelvic tumor 1 year after the procedure.

Female↗
PubMed1991

A revised rotarod procedure for measuring the effect of antinociceptive drugs on motor function in the rat.

Tests of putative antinociceptive agents that rely on a motor response of an experimental animal to a noxious stimulus will give false positive results, and may be unethical, if the agent compromises motor function. We report a procedure for measuring potential effects of antinociceptive agents on motor function in the trained rat, using an 80 mm diameter rotarod. Rats were selected for ability to exercise on the rotarod and trained to increasing speeds. In test trials, we measured the time that trained rats could stay on the rod, rotating at 25 rpm, with a cut off at 60 min. Morphine administration decreased rotarod performance significantly at doses of 5.0 mg/kg (P less than 0.05, n = 10) and 7.5 mg/kg (P less than 0.005, n = 10). We also assessed the response to a noxious thermal stimulus by measuring tail flick latency following tail immersion in water at 49 degrees C. A significant dose-dependent increase in tail flick latency was found for dosages of morphine between 2.5 mg/kg and 7.5 mg/kg (P less than 0.005, n = 10). Our rotarod procedure, which incorporates selection, training, and a 60 min trial, provides a sensitive and consistent means of assessing motor function. Our results, implying that morphine indeed compromises motor function in rats at doses at which it is antinociceptive, confirm the necessity for investigating the motor effects of any putative antinociceptive agent.

Analgesics↗
PubMed1991

Effects of alpha-melanocyte stimulating hormone on fever caused by endotoxin in rabbits.

1. We measured the effect of intravenous and intracerebroventricular injections of alpha-melanocyte stimulating hormone (alpha-MSH) on changes in body temperature and serum iron concentration following i.v. injection of endotoxin in rabbits. 2. Intravenous alpha-MSH (2.5 micrograms) significantly reduced both phases of endotoxin fever and attenuated the fall in serum iron concentration which follows endotoxin injection. 3. Intracerebroventricular alpha-MSH (200 ng) reduced only the second phase of the fever and had no effect on the fall in the serum iron concentrations. 4. We conclude that alpha-MSH, in doses that are known to inhibit endogenous pyrogen fever, inhibits the fever induced by endotoxin in rabbits, probably by blocking the actions of endogenous pyrogens mediating the endotoxin fever.

Animals↗
PubMed1991

Cerebrospinal fluid angiotensin converting enzyme levels in the diagnosis of neurosarcoidosis.

Cerebrospinal fluid angiotensin converting enzyme (CSF-ACE) level was measured in two patients considered to have neurosarcoidosis, three patients with possible neurosarcoidosis and in 38 control patients suffering from prolapsed intervertebral discs. Both neurosarcoidosis patients had elevated levels (1.8 and 5.4 mumol/l/min) while the possible neurosarcoidosis patients had values similar to the control patients (mean 0.59 +/- 0.42 mumol/l/min). We suggest that CSF-ACE values may be of use in some patients as a diagnostic test for neurosarcoidosis and provide a reference range of normal controls.

Adult↗
PubMed1991

Modulation of MHC class II antigen expression in human myoblasts after treatment with IFN-gamma.

Some investigators have proposed myoblast transfer as a potential therapy for the treatment of Duchenne muscular dystrophy. Little is known about the immunobiology of myoblast transplantation. Transplantation rejection is mediated to a large extent by CD8+ T cells, which recognize alloantigens encoded by class I HLA genes, and by CD4+ T cells, which recognize alloantigens encoded by class II HLA genes. Gamma interferon (IFN-gamma) is a potent inducer of HLA class II molecules as well as beta 2-microglobulin, which is co-expressed with HLA class I. IFN-gamma may be a critical cytokine involved in graft rejection. We purified human myoblasts by flow cytometry and incubated them in vitro for varying time periods with recombinant human IFN-gamma. The inducibility of HLA-DR and -DP molecules raises a note of caution concerning possible rejection phenomenon which might occur following myoblast transplantation.

Cells, Cultured↗
PubMed1991

Epstein-Barr viral genome in lymph nodes from patients with Hodgkin's disease may not be specific to Reed-Sternberg cells.

A possible etiologic role for Epstein-Barr virus (EBV) in Hodgkin's disease (HD) was investigated by probing for EBV genome in 52 biopsy specimens involved with HD and 43 hyperplastic lymph node specimens. Using dot-blot hybridization (Bam HIW probe), Southern blot hybridization (Xho I probe), and polymerase chain reaction analyses, 27%, 27%, and 58% of the nodes with HD were positive for EBV genome, respectively, as compared to 16%, 14%, and 43% in the hyperplastic lymph nodes. Clonal and nonclonal episomal EBV and linear replicating EBV genome were present in both conditions. Immunoglobulin heavy chain gene rearrangements were found in two clonal and two nonclonal EBV-positive HD cases, but not in the lymphoid hyperplasia cases. These findings and other recent reports showing EBV genome in benign lymphoid cells by in situ hybridization in Hodgkin's disease suggest that the characteristics of EBV infection in HD could be explained by the reactive cellular milieu, especially in the setting of defective immunity. The identification of EBV genome in Reed-Sternberg cells may, therefore, be a nonspecific phenomenon.

Gene Rearrangement↗