Does substance P release mediate NANC nerve-mediated responses to field stimulation and ligands, in the rabbit isolated sphincter pupillae?
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
D Mitchell
Publications and source records attributed to D Mitchell.
Selective and nonselective stages in homing of T lymphocytes to the central nervous system during experimental allergic encephalomyelitis.
The diversity of Ag-specific receptors on T cells homing to an inflammatory infiltrate in the central nervous system has been analyzed. Experimental autoimmune encephalomyelitis, a T cell-mediated inflammatory disease of the central nervous system, was induced in Lewis rats with a CD4+, CD8- T cell line specific for peptide 68-86 of myelin basic protein. Within the line a wide array of TCR V beta genes was transcribed including the V beta 8, V beta 10, V beta 15, V beta 16, and V beta 19 families. Accumulation of T cells at the site of inflammation was determined by using RNA-polymerase chain reaction amplification of rearranged TCR V beta transcripts derived from brain. By 8 to 10 h after i.p. infusion of the pathogenic T cell line, TCR V beta transcripts, including mainly V beta families that were predominantly rearranged by the line, could be identified in brains. Restricted TCR V gene transcripts with predominance of the V beta 8 family were identified in brain 48 h after injection, before onset of disease. Paralysis was apparent by 4 to 5 days after injection. At this time diverse V beta gene transcripts were detected in brain, reaching a maximum by day 9, when paralyzed rats have recovered. By day 14 a second stage of limited heterogeneity in the T cell infiltrate could be identified with predominant expression of V beta 8, V beta 9, V beta 10, and V beta 19. Interestingly, three out of these four V beta families were predominantly expressed within the encephalitogenic line. Thus, T cell migration to brain in experimental autoimmune encephalomyelitis is characterized by a rapid penetration of T cells followed by a selective trapping of T cells before the clinical manifestations of disease. When clinical disease was present the T cell infiltrate was diverse, whereas in the post-acute phase of disease the T cells in the central nervous system had limited heterogeneity with selective accumulation of T cells transcribing the same V regions that were detected in the line that incited disease.
Animals↗
Selection for T-cell receptor V beta-D beta-J beta gene rearrangements with specificity for a myelin basic protein peptide in brain lesions of multiple sclerosis.
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system in which a restricted cellular immune response has been observed. In order to establish whether such T cell responses are likely to be antigen-specific particularly with regard to myelin basic protein (MBP), we analysed T-cell receptor (TCR) gene rearrangements directly from MS brain plaques, using the polymerase chain reaction on reverse transcribed messenger RNA, and compared these with TCR of previously described MBP-specific T cell clones from MS and the rat model experimental allergic encephalomyelitis. Rearranged V beta 5.2 genes were detected in the brains of all patients who were HLA DRB1*1501, DQA1*0102, DQB1*0602, DPB1*0401. The V beta 5.2-D beta-J beta sequences in these MS brain plaques revealed five motifs. One of the common motifs was identical to that described for the VDJ region of a V beta 5.2 T-cell clone. This clone was from an MS patient who was HLA DRB1*1501, DQB1*0602, DPB1*0401, and it was cytotoxic towards targets containing the MBP peptide 89-106 (ref. 1). The deduced amino-acid sequence of this VDJ rearrangement, Leu-Arg-Gly, has also been described in rat T cells cloned from experimental allergic encephalomyelitis lesions, which are specific for MBP peptide 87-99 (ref. 2). VDJ sequences with specificity for this MBP epitope constitute a large fraction (40%) of the TCR V beta 5.2 N(D)N rearrangements in MS lesions. The capacity of rat T cells with these VDJ sequences to cause experimental allergic encephalomyelitis and the prevalence of such sequences in demyelinated human lesions indicate that T cells with this rearranged TCR may be critical in MS.
Amino Acid Sequence↗
Dye-mediated photolysis is capable of eliminating drug-resistant (MDR+) tumor cells.
We evaluated the potential role of photoradiation therapy with a benzoporphyrin derivative, monoacid ring A (BPD-MA), and dihematoporphyrin ether (DHE), for the ex vivo purging of residual tumor cells from autologous bone marrow (BM) grafts. BPD-MA and DHE photosensitizing activity was tested against two human large-cell lymphoma cell lines and colony-forming unit-leukemia (CFU-L) derived from patients with acute myelogenous leukemia (AML). In mixing experiments, 4-log elimination of tumor cell lines was observed after 1 hour of incubation with 75 ng/mL of BPD-MA or 30 minutes of treatment with 12.5 micrograms/mL of DHE followed by white light exposure. By comparison, using the same concentration of BPD-MA, the mean recovery of normal BM progenitors was 4% +/- 0.8% (mean +/- SD) for granulocyte-macrophage colony-forming unit (CFU-GM) and 5% +/- 0.8% for burst-forming unit-erythroid (BFU-E). Similarly, DHE treatment resulted in the recovery of 5.2% +/- 2% and 9.8% +/- 3% of CFU-GM and BFU-E, respectively. Furthermore, equivalently cytotoxic concentrations of both DHE and BPD-MA and light were found not to kill normal pluripotent stem cells in BM, as demonstrated by their survival in two-step long-term marrow culture at levels equal to untreated controls. The T-lymphoblastic leukemia cell line CEM and its vinblastine (VBL)-resistant subline CEM/VBL, along with the acute promyelocyte leukemia cell line HL-60 and its vincristine (VCR)-resistant subline HL-60/VCR, were also tested. BPD-MA at 75 ng/mL was able to provide a greater than 4-log elimination of the drug-sensitive cell lines, but only a 34% and 55% decrease of the drug-resistant HL-60/VCR and CEM/VBL cell lines, respectively. On the contrary, 12.5 micrograms/mL of DHE reduced the clonogenic growth of all the cell lines by more than 4 logs. Further experiments demonstrated decreased uptake of both BPD-MA and DHE by the resistant cell lines. However, all the cell lines took up more DHE than BPD-MA under similar experimental conditions. Our results demonstrate the preferential cytotoxicity of BPD-MA and DHE toward neoplastic cell lines and CFU-L from AML patients. In addition, DHE was slightly more effective in purging tumor cells expressing the p-170 glycoprotein. These results suggest that photoradiation with DHE would be useful for in vitro purging of residual drug-resistant leukemia and lymphoma cells.
Bone Marrow↗
Final height after treatment for childhood acute lymphoblastic leukemia: comparison of no cranial irradiation with 1800 and 2400 centigrays of cranial irradiation.
We analyzed growth and final heights in 127 patients (68 female patients) treated for childhood acute lymphoblastic leukemia. Central nervous system prophylaxis included either no cranial radiation therapy (CRT) (n = 38), irradiation with 1800 centigrays (cGy) (n = 36), or irradiation with 2400 cGy (n = 53). None of the patients received spinal irradiation. Mean (+/- SEM) age at diagnosis was 6.4 +/- 0.25 years, mean height standard deviation score (SDS) at diagnosis was 0.28 +/- 0.12, and mean age at final height was 18.26 +/- 0.19 years. The change in height SDS between diagnosis and achievement of final height was significant for all treatment groups: -0.49 +/- 0.14, no CRT; -0.65 +/- 0.15, 1800 cGy; and -1.38 +/- 0.16, 2400 cGy. Irradiated patients had a greater loss in height SDS compared with the nonirradiated patients (p < 0.01), and those treated with 2400 cGy CRT had a greater decrease in final height SDS than the patients treated with 1800 cGy (p < 0.01). Both younger age and female sex were significantly associated with a greater decrease in height SDS in the patients treated with CRT; girls < or = 4 years of age at diagnosis had a mean loss in height SDS that was more than twice that observed for others treated with the same dose of CRT. Thus, although modern regimens for acute lymphoblastic leukemia (no CRT or 1800 cGy CRT) appear overall to have only a modest impact on final height, patients, especially girls, treated with 1800 cGy CRT at a young age remain at risk for clinically significant growth failure.
Age Factors↗
Renal capsular hemangioma.
We present a rare example of hemangioma of the renal capsule. This benign mesenchymal tumor can present diagnostic difficulties, since it can radiographically and macroscopically simulate more common tumors of the kidney, including renal cell carcinoma. If the diagnosis is made or suspected preoperatively or during surgery a more conservative surgical approach should be considered.
Adult↗
Pneumothorax in patients with AIDS.
Eighty-seven inpatients were treated for 93 episodes of Pneumocystis carinii at St Mary's Hospital between January 1989 and December 1990. During this period, 298 patients with the acquired immunodeficiency syndrome (AIDS) were treated at this hospital. Sixteen episodes of pneumothorax occurred and 12 of these, occurring in ten patients, were unrelated to procedure. In six of 12 (50%), the pneumothoraces occurred concurrently with Pneumocystis carinii pneumonia (PCP) and in ten (83%) cases there was a past history of PCP. Bilateral pneumothorax occurred in five cases (42%). In seven (58%) of the cases, patients had been using aerosolized pentamidine as prophylaxis for PCP. This retrospective study confirms the association of pneumothorax with current PCP and also shows an association with previous infection. The use of aerosolized pentamidine was not associated with pneumothorax development. It is important to suspect pneumothorax in a patient with PCP who deteriorates acutely. The high incidence of bilateral pneumothorax means that pleurodesis should be considered early.
AIDS-Related Opportunistic Infections↗
Relative sensitivity of leukemic (CML) and normal progenitor cells to treatment with the photosensitizer benzoporphyrin derivative and light.
Normal bone marrow and peripheral blood committed progenitor cells were found to be significantly more resistant to treatment with the photosensitizer benzoporphyrin derivative (BPD) and white fluorescent light (11 J/cm2) than were clonogenic cells from two cell lines (K562 and EM2) derived from nonremission patients with myelogenous leukemias. Bone marrow and peripheral blood committed progenitor cells from normal donors were also found to be more resistant to this treatment than were equivalent cells from patients with chronic myelogenous leukemia (CML). Normal bone marrow mononuclear cells grown in long-term marrow culture (LTMC) following treatment with BPD and light showed that no differences in stem cell productivity existed between control and treated samples. When bone marrow from CML patients was treated in the same manner, the numbers of progenitors detected in the nonadherent population during culture were greatly reduced compared to control material. Two rounds of PCR using nested primers to detect BCR-ABL mRNA showed that while this treatment significantly decreased the numbers of stem cells bearing the Philadelphia chromosome, it did not eliminate them.
Blood Cells↗
Tachykinin receptors mediating responses to sensory nerve stimulation and exogenous tachykinins and analogues in the rabbit isolated iris sphincter.
1. We have used selective tachykinin receptor agonists and antagonists to investigate the nature of the receptors mediating responses to endogenous and exogenous tachykinins in the rabbit iris sphincter preparation in vitro. 2. The NK1-selective agonist, substance P methyl ester, induced contraction with a pD2 of 9.16 indicating the presence of NK1 receptors. In confirmation, the NK1-selective antagonist, GR82334, competitively antagonized responses to substance P methyl ester with high affinity (pKB 7.46). 3. NK3 receptors also mediate contraction since NK3-selective agonists exhibited high potency, e.g. the pD2 of [Me-Phe7]-neurokinin B was 9.67, and their responses were not inhibited by GR82334 (10 microM). 4. NK2 receptor activation does not seem to contribute to contraction since the NK2-selective agonist [beta-Ala8]-neurokinin A(4-10) had relatively low potency (pD2 6.43), and the NK2-selective antagonists MEN10207 (1 microM) and L-659,877 (10 microM) were inactive or had low affinity, respectively. 5. GR82334 (1 microM) significantly inhibited responses to electrical field-stimulation of non-adrenergic non-cholinergic sensory nerves (3, 10 and 30 Hz), and caused a rightward shift of the log concentration-response curve to bradykinin (lateral shift ca. 1000 fold). Higher concentrations of GR82334 (10 microM) significantly attenuated responses to capsaicin (1-60 microM) whilst completely abolishing responses to field-stimulation (3, 10 and 30 Hz) and bradykinin (1 nM- 3 microM). 6. In conclusion, NK1 and NK3 receptor activation results in contraction of the rabbit iris sphincter. The contractile response following sensory nerve stimulation by bradykinin, capsaicin and electrical field stimulation results from NK1 receptor activation.
Animals↗
Attenuation of reperfusion hyperalgesia in the rat by systemic administration of benzodiazepines.
1. An investigation into whether reperfusion hyperalgesia is modulated by prior systemic administration of two benzodiazepine agonists (diazepam and chlordiazepoxide), and an antagonist (flumazenil) was conducted. 2. Transient ischaemia was induced in conscious rats by applying an inflatable tourniquet to the base of the tail; when the rats exhibited a co-ordinated escape response, the tourniquet was deflated and reperfusion of the tail was allowed. Reperfusion hyperalgesia manifested as a decrease in tail flick latency, following tail immersion in 49 degrees C water, after the release of the tourniquet. 3. Intraperitoneal administration of diazepam, chlordiazepoxide and flumazenil had no effect on the co-ordinated escape to the noxious ischaemic stimulus nor on tail flick latency after application of a sham tourniquet. 4. The hyperalgesia evident during reperfusion, was abolished by diazepam (1 and 5 mg kg-1) and chlordiazepoxide (5 and 25 mg kg-1). The antihyperalgesic effects of both diazepam (5 mg kg-1) and chlordiazepoxide (25 mg kg-1) were inhibited by flumazenil (1 mg kg-1). 5. Rotarod performance was impaired in rats given diazepam and chlordiazepoxide at the same doses at which the benzodiazepines were antihyperalgesic. The impairment to motor function did not extend to the motor systems involved in the tail flick response. 6. In conclusion, benzodiazepines have antinociceptive properties during hyperalgesia.
Animals↗
Compensation and turnover of direct-care staff in developmental disabilities residential facilities in the United States. I: Wages and benefits.
This study was based on a representative national sample of more than 1,600 residential facilities serving individuals with developmental disabilities in all 50 states and the District of Columbia. The mean starting wage for direct-care workers in publicly operated institutions in FY 1990 was approximately 31% more than the wage for similar workers in privately operated facilities. The mean starting wage in private facilities was only about 3% above the poverty level for a family of three. Wages, in real economic terms, have declined significantly during the last decade. The wage differential between public and private facilities has doubled during the past 10 years. Implications of these findings for the field and for future research were discussed.
Caregivers↗
Evidence for human immunodeficiency virus infection of the lung.
Pulmonary disease is a frequent manifestation in the terminal stages of acquired immune deficiency syndrome (AIDS), and is caused mainly by a number of opportunistic microorganisms, most commonly Pneumocystis carinii. Despite the extensive involvement of the lung in the pathogenesis of AIDS, until recently little was known about the role of human immunodeficiency (HIV). In this review we will discuss the cellular tropism and phenotypic characterisation of HIV strains isolated from the lung. The available literature on HIV infection of the lung is reviewed, and the mechanisms of HIV-induced pathogenesis in the lung is discussed.
AIDS-Related Opportunistic Infections↗
Lofgren's syndrome.
Lofgren's syndrome consists of a triad of erythema nodosum, bilateral hilar adenopathy, and arthritis and heralds the acute onset of sarcoidosis. A single symptom may be misdiagnosed and mistreated by an unsuspecting physician. We present a case of Lofgren's syndrome that was initially believed to be cellulitis. We briefly review the course and treatment of Lofgren's syndrome.
Adult↗
Rapid development of lymphoma following liver transplantation in a recipient with hepatitis B and primary hemochromatosis.
We report a case of a posttransplant lymphoproliferative disorder (PTLD) which presented in a liver allograft shortly after transplantation. The patient, who had been transplanted because of cirrhosis due to primary hemochromatosis and chronic hepatitis B infection (HBV), developed early recurrent HBV in the graft, and 2 months after transplantation, liver biopsies showed a malignant large-cell lymphoma. The neoplastic cells demonstrated Epstein-Barr virus DNA by in situ hybridization. The patient died 3.5 months posttransplant due to liver failure. At autopsy, the liver showed nodules of malignant lymphoma, massive hepatic necrosis, and iron overload, but no evidence of rejection. This report suggests that the grafted liver can be the site of PTLD in recurrent HBV and hemochromatosis.
Adult↗
A randomized double-blind comparison of epidural fentanyl infusion versus patient-controlled analgesia with morphine for postthoracotomy pain.
The authors conducted a prospective, randomized, double-blind comparison of an epidural fentanyl infusion versus patient-controlled analgesia (PCA) with morphine in the management of postthoracotomy pain. Thirty-six patients were randomized into one of two groups. The epidural group received an epidural fentanyl infusion, 10 micrograms/mL, and saline through their PCA machine. The PCA group received an epidural saline infusion and morphine, 1.0 mg/mL, through their PCA device. The infusions were escalated according to a study protocol when pain relief was deemed inadequate by the patients. Pain relief was evaluated by a visual analog pain scale (VAS), both at rest and during coughing, and by verbal rating scores (VRS) of pain relief. Degree of sedation and the frequency of nausea, vomiting, and pruritus were also noted. The VAS, VRS, degree of sedation, and side effects were evaluated every 2 h from 7 AM to 7 PM, for 72 h after surgery. Forced vital capacities were determined before surgery and at 24, 48, and 72 h after surgery. The VAS were significantly lower (P = 0.001), and the Total Pain Relief scores higher (P < 0.02) in the epidural group, signifying better analgesia. There were no differences in postoperative forced vital capacity between the two groups. More patients in the PCA group had greater degrees of sedation on postoperative day 1 (P = 0.005), whereas pruritus was more frequent (P < 0.02) in the epidural group. We conclude that an epidural fentanyl infusion is superior to that of PCA with morphine in the management of pain after thoracotomy.
Aged↗
pH-adjusted local anaesthetics.
Explore the source record for details and available documents.
Anesthesia, Local↗
Pyrimidine dimer removal enhanced by DNA repair liposomes reduces the incidence of UV skin cancer in mice.
UV exposure has been linked to skin cancer in humans by epidemiology and the rare genetic disease xeroderma pigmentosum. However, UV produces multiple photoproducts in DNA, and their relative contribution is uncertain. An enzyme which specifically repairs cyclobutane pyrimidine dimers in DNA, T4 endonuclease V, was encapsulated in liposomes for topical delivery into mouse and human skin. In both species, liposomes applied after UV exposure localized in the epidermis and stimulated the removal of cyclobutane pyrimidine dimers. UV-irradiated mice treated with these liposomes had a dose-dependent decrease in the incidence of squamous cell carcinoma compared to controls. The results demonstrate that unrepaired cyclobutane pyrimidine dimers in DNA are a direct cause of cancer in mammalian skin.
Animals↗
Fever responses in newborn lambs.
Neonatal lambs failed to respond with an increase in body temperature to i.v. injection of both endotoxin (0.4 microgram/kg), a Gram-negative bacterial pyrogen, and the cell walls of Staphylococcus aureus (1 x 10(9), a Gram-positive bacterial pyrogen. However, the fall in serum iron concentration that normally accompanies injection of both the pyrogens in adults was not attenuated in the neonates. We believe that the central nervous system origin of the fever pathway is suppressed in neonatal lambs.
Animals↗