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Biomedical subjects

J Curtis

Publications and source records attributed to J Curtis.

At least 109 records · Page 6Linked to original sources

Nerve damage induced by mycobacterial granulomas in guinea pig sciatic nerves.

A possible model for nerve damage in leprosy has been developed in the sciatic nerve of the guinea pig. Intraneural injection of 10(7) BCG organisms into an unsensitized animal induces an epithelioid cell granuloma in 2 weeks similar to that found in tuberculoid leprosy patients. In contrast, intraneural injection of 10(9) cobalt-irradiated Mycobacterium leprae organisms induces a macrophage granuloma in 5 weeks, similar to that found in lepromatous leprosy patients. Histological, immunohistochemical, electron microscopical and electrophysiological studies have demonstrated that the lesions induced in the experimental animals show many of the features documented in studies of nerve damage in leprosy patients.

Animals↗

Study of DTH and resistance in Mycobacterium lepraemurium infection using a T-cell line isolated from mice infected with Mycobacterium bovis (BCG).

A T-cell line of mixed phenotype (60% L3T4+, 40% Lyt-2+) was isolated from mice infected with Mycobacterium bovis (BCG). This line responded to M. lepraemurium and BCG but not to M. leprae and produced TCGF spontaneously. It also produced factors which stimulated macrophages to secrete hydrogen peroxide and superoxide anion. In vivo studies showed that only L3T4+ cells were required to transfer DTH responses and that Lyt-2+ cells suppressed this response. Both L3T4+ and Lyt-2+ cells were required to inhibit M. lepraemurium multiplication in vivo.

Animals↗

Interleukin 1 and prostaglandin production by cells of the mononuclear phagocyte system isolated from mycobacterial granulomas.

A study has been made of the activity of interleukin 1 (IL-1) and prostaglandins (PGs) in the culture supernatants from unstimulated and lipopolysaccharide (LPS)-stimulated mycobacteria-induced granuloma cells. Both epithelioid cells from bacillus Calmette-Guerin (BCG)-induced granulomas and macrophages from Mycobacterium leprae-induced granulomas, separated on a fluorescence-activated cell sorter using monoclonal antibody specific to guinea pig macrophages, spontaneously secreted low levels of IL-1 (assayed by thymocyte comitogenic and fibroblast mitogenic activities) into culture supernatants. However, culture supernatants from LPS-stimulated epithelioid cells showed significantly higher IL-1 activity than those from unstimulated cells. In contrast, LPS stimulation of M. leprae granuloma macrophages failed to enhance IL-1 production. Nevertheless, IL-1 activity in the culture supernatants from stimulated mycobacterial granuloma cells of both types was much lower than that from LPS-stimulated peritoneal exudate macrophage culture supernatants. There was no detectable amount of prostaglandin E2 (PGE2) in the culture supernatants from both unstimulated and LPS-stimulated BCG- and M. leprae-induced granuloma cells in comparison to much higher levels of PGE2 produced by unstimulated (0.28-6.2 ng/ml) or LPS-stimulated (greater than 15 ng/ml) peritoneal exudate macrophages. However, BCG granuloma cells either secreted prostaglandin F2 alpha (PGF2 alpha) spontaneously or produced comparable levels of PGF2 alpha to those from peritoneal exudate macrophages on stimulation, while M. leprae granuloma macrophages produced much lower levels of PGF2 alpha.

Animals↗

Epithelioid cell granuloma induction in the guinea pig by haptenated Mycobacterium leprae.

Fluorescein isothiocyanate (FITC)-conjugated Mycobacterium leprae (FITC-M. leprae) was injected intradermally into the ears of guinea pigs and granuloma formation in the draining postauricular lymph nodes was studied. At 2 weeks, there was an increase in weights and infiltration of the draining lymph nodes in half of the animals injected with FITC-M. leprae. At 5 weeks, there was a significant increase in the weights and infiltration of these draining lymph nodes in the guinea pigs injected with haptenated M. leprae compared with those injected with unconjugated M. leprae. At 5 weeks, there was also a significant increase in delayed type hypersensitivity responses to 25 micrograms purified protein derivative. Histologically, epithelioid cell granulomas were seen in these lymph nodes as early as 2 weeks when FITC-M. leprae was used as the source of antigen. Enhancement in the immunogenicity of M. leprae by conjugation with FITC has been postulated.

Animals↗

Atypical and malignant neoplasms showing lipomatous differentiation. A study of 111 cases.

One-hundred-eleven cases of histopathologically atypical or malignant lipomatous lesions in the somatic soft tissue and retroperitoneum were studied. These consisted of 48 differentiated fatty neoplasms of the somatic soft tissues (DFT-S), 21 fatty neoplasms of the retroperitoneum (DFT-R), 33 myxoid liposarcomas from various sites and nine pleomorphic liposarcomas. DFT-S were defined as lipomatous lesions composed of mature fat and containing atypical stromal cells or lipoblasts. In the somatic soft tissues, this group included lesions that would be classified using published criteria as "atypical lipoma", "pleomorphic lipoma", "well-differentiated lipoma-like liposarcoma", and "sclerosing liposarcoma". All of the DFT-R met previously published criteria for "well differentiated liposarcoma" or "sclerosing liposarcoma". We found no consistent histologic differences between the DFT-S and DRT-R. No pure "round cell" liposarcomas were encountered although many myxoid liposarcomas had "round cell" areas. Follow-up data were available in 80 cases (72%) with a mean follow-up period of over 7 years. Among the DFT-S there were no uncontrollable recurrences, distant metastases, or tumor-related deaths. The depth of the neoplasm correlated with the tendency for local recurrence; no neoplasms primary in the subcutis recurred; 29% of the tumors recurred when they originated in the deep soft tissues or within the muscle. None of the recurrent tumors demonstrated "dedifferentiation." DFT-R had a recurrence rate of 67% and, although there were no distant metastases, nine patients (43%) died of tumor. Five retroperitoneal tumors dedifferentiated but did not metastasize. In light of this experience, we believe that the term "atypical lipoma" is warranted for the DFT-S and "well differentiated liposarcoma" is an appropriate label for the DFT-R. The overall mean survival for the 52 cases of liposarcoma (excluding DFT-S) was 13.6 years. The mean survival in "well differentiated liposarcoma" (11.25 years) was between that for myxoid liposarcoma (16.25 years) and that for pleomorphic liposarcoma (7 years). Six patients (29%) with myxoid liposarcoma developed local recurrences and 6 patients (29%) developed distant metastases and died. Metastasis was always associated with a round cell (or pleomorphic) component with increased numbers of mitotic figures in either the primary tumor or a local recurrence.

Adolescent↗

Idiopathic small airways pathology in patients with graft-versus-host disease following allogeneic bone marrow transplantation.

In a retrospective analysis (July 1979 to March 1984) of 120 allogeneic adult bone marrow transplant recipients, we identified seven patients with small-airway disease for whom no microbiologic agent was detected. Six had pulmonary function studies demonstrating air flow obstruction. Five of the seven patients had an open-lung biopsy showing pathologic changes within small airways; these varied from early bronchiolar wall damage to bronchiolitis obliterans. The inflammatory cell infiltrate was peribronchiolar, and consisted of polymorphonuclear leukocytes and lymphocytes in varying proportions. Three of the seven patients recovered following increased immunosuppressive therapy; the other four died. Because all seven patients had acute and chronic graft-versus-host disease, in the absence of any identifiable pathogen, we postulate that small-airway damage represents one of the facets of graft-versus host-disease. An additional analysis of 26 patients with respiratory symptomatology and available histologic material supports the hypothesis that small-airway disease in bone marrow transplant patients represents a risk factor for the subsequent development of respiratory opportunistic infections.

Bone Marrow Transplantation↗

Dissociation between delayed-type hypersensitivity and resistance to pathogenic mycobacteria demonstrated by T-cell clones.

One Lyt-2+ clone and fourteen T-helper clones (Lyt-1+ L3T4+ Lyt-2-) were isolated from Mycobacterium lepraemurium-infected BALB/c and C57BL/6 mice. All the clones were tested for their ability to transfer delayed-type hypersensitivity adoptively, and six clones were tested for their ability to transfer resistance. It was found that four L3T4+ clones that transferred delayed-type hypersensitivity responses locally and one L3T4+ clone that did not had no effect on resistance. The Lyt-2+ clone transferred increased resistance locally (77% reduction in the numbers of organisms recovered from the infection site) but did not transfer delayed footpad responses.

Animals↗

Panic disorder.

We note the recent paradigm shift to sub-divide anxiety into endogenous and exogenous forms, with the former (panic disorder) being viewed as a genetically-determined metabolic disorder. We examine some of the supportive evidence and note the limitations of an exclusive biological model for panic disorder. Drug and other therapies are considered briefly and attention is drawn to the pluralistic approaches used in specialized treatment centres in Australia.

Anxiety Disorders↗

Accessory cell function of cells isolated from Mycobacterium leprae-induced granulomas.

The large cells from Mycobacterium leprae-induced granulomas in guinea pig lymph nodes were separated by Percoll discontinuous density gradient centrifugation and on a fluorescence-activated cell sorter (FACS) using cross-reacting monoclonal antibody to human MHC Class II antigens. Large Percoll-separated cells (83% Class II antigen positive and 52% macrophage-specific antigen positive) and FACS-separated cells are able to act as antigen-presenting cells for T-cell proliferation to PPD. In previous studies, macrophage antigen-positive cells consistently failed to act as accessory cells. This indicates that there is a population of accessory cells which are macrophage antigen negative and MHC Class II antigen positive present in these M. leprae-induced granulomas.

Animals↗

Oxidation of (+)-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene by mouse keratinocytes: evidence for peroxyl radical- and monoxygenase-dependent metabolism.

The role of prostaglandin H (PGH) synthase and peroxyl radicals as well as cytochrome P-450 in the metabolism of 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP-7,8-diol) was examined in fresh skin keratinocytes isolated from hairless mice. Labeled (+)-BP-7,8-diol was oxidized after incubation with the keratinocytes to syn- and anti-diolepoxides in greater than a 4:1 ratio as estimated by h.p.l.c. analysis of the stable hydrolysis products. Formation of diolepoxides was dependent on cell number and the concentration of BP-7,8-diol. Incubation in the presence of the PGH synthase substrate, 20:4 or the inhibitor, indomethacin did not alter the total formation or the ratio of diolepoxides. However, the addition of butylated hydroxyanisole (1 micron) an inhibitor of peroxyl radical dependent-metabolism significantly inhibited diolepoxide formation. The time course for the formation of the anti-diolepoxide and lipid peroxidation, measured as malondialdehyde was determined. The results suggest an excellent correlation between peroxyl radical and diolepoxide formation. Pretreatment of mice with the cytochrome P-450 inducer, beta-naphthoflavone greatly altered the metabolism of (+)-BP-7,8-diol by keratinocytes. The major metabolite was the syn-diolepoxide with significant formation of two unknown metabolites. Pretreatment of mice with BP-7,8-diol did not induce aryl hydrocarbon hydroxylase activity but did increase the yield of syn-diolepoxide formed from labeled (+)-BP-7,8-diol by 1.5-fold. Our results suggest that peroxyl radical-mediated metabolism is primarily responsible for the oxidation of (+)-BP-7,8-diol in control animals while the cytochrome P-450 system is primarily responsible for oxidation in animals pretreated with inducers.

Animals↗

Influence of atrioventricular synchrony on hemodynamics in patients with normal and low ejection fractions following open heart surgery.

The authors wished to test the hypothesis that atrioventricular synchrony has a relatively greater effect on hemodynamic parameters in postoperative patients with low ejection fractions compared to those with normal ejection fractions. Temporary pacing wires were placed on the right atrium and right ventricle of patients undergoing open heart surgery. Duplicate thermodilution cardiac outputs were determined during atrial pacing and ventricular pacing at 100 beats/min. Mean left atrial and systemic blood pressures were monitored. Thirteen patients with ejection fractions of 45 per cent or less (range 24 to 45%, mean 37.3%) were included in the low ejection fraction group, and 27 patients with ejection fractions of 59 per cent or greater (range 59 to 80%, mean 66.8%) were considered in the normal ejection fraction group. All hemodynamic parameters improved significantly when changing from ventricular pacing to atrial pacing in both the normal ejection fraction group and low ejection fraction group (P less than 0.05). The magnitude of change between the groups showed no significant difference for all parameters except left atrial pressure, which decreased by a greater percentage in the low ejection fraction group with atrial pacing (P less than 0.001). The atrial contribution to hemodynamic enhancement is important in patients with normal and low ejection fraction following open heart surgery. Patients with low ejection fractions do not sustain a relatively greater reduction in cardiac output, stroke volume index, or systemic blood pressure with loss of atrioventricular synchrony when compared to patients with normal ejection fractions.

Cardiac Output↗

Accessory cell function of cells of the mononuclear phagocyte system isolated from mycobacterial granulomas.

Epithelioid cells from BCG-induced granulomas and macrophages from Mycobacterium leprae-induced granulomas were examined for their ability to act as accessory cells for T-cell proliferation to mitogen (Con A) and antigen (PPD). The granuloma cells were separated on a FACS using monoclonal antibody specific to guinea pig macrophages. Epithelioid cells (which are Ia negative) were able to support proliferation to Con A but not to antigen. Cultures containing Ia positive granuloma macrophages from M. leprae sensitized animals did not show responsiveness to Con A or to PPD. Oil-induced peritoneal exudate macrophages from BCG or M. leprae immunized animals were able to act as accessory cells for both mitogen and antigen proliferation. The nonresponsiveness of cultures containing epithelioid cells stimulated with PPD or M. leprae granuloma macrophages stimulated with Con A was not due to suboptimal or supraoptimal accessory cell:lymphocyte ratios.

Animals↗

The effect of hydrocortisone and cyclosporin A on bacillus Calmette-Guérin epitheloid cell granulomas.

The injection of bacillus Calmette-Guérin (BCG) intradermally into the ear of guinea pigs leads to the formation in the draining lymph node of granulomas containing epithelioid cells with rough endoplasmic reticulum (RER) and an absence of phagocytosed material. BCG granulomas in hydrocortisone- or cyclosporin A (CsA)-treated animals contain mononuclear phagocytes with no RER. In CsA-treated animals, these cells contain fragments of phagocytosed organisms. CsA was given at two doses, 25 mg/kg orally and 50 mg/kg ip. The higher dose completely suppressed the delayed hypersensitivity (DH) response to purified protein derivative (PPD) but the lower dose did not affect the level of the DH response, but had a profound effect on epithelioid cell formation. The role of lymphokines in the maturation of the monocyte/macrophage to epithelioid cells is discussed.

Animals↗

Isolation and analysis of circulating immune complexes in leprosy.

Circulating immune complexes (CIC) were isolated by two antigen nonspecific methods from 60 leprosy patients belonging to borderline tuberculoid (BT) and lepromatous (LL) types with and without reactions. CIC were elevated in both BT and LL reactions. CIC from BT in reaction (BTR) were found to consist largely of IgG and C3, whereas, C-reactive protein could be found in CIC from LL reactions (LR). In addition, IgM and rheumatoid factor were demonstrated in the complexes of LR patients who had mainly arthritis. Antimycobacterial antibody was seen in the complexes of two-thirds of LR patients who had predominantly skin manifestations as part of their reaction. The relevance of these findings to the clinical manifestations of different types of reactions is discussed.

Animals↗

Efficacy of clear antacid prophylaxis in obstetrics.

We studied 33 women scheduled to undergo general anesthesia for cesarean section. Prior to induction of anesthesia, each patient received in a random fashion one of two prophylactic antacids. Group I (n = 17) received 30 ml Gelusil orally and Group II (n = 16) received 30 ml of 0.3 mol/l sodium citrate. After induction of general anesthesia an oro-gastric tube was passed. The amount and pH of the gastric aspirate were measured at the time of delivery and 45 min after delivery "before extubation." Both antacids elevated gastric pH above 3.5 in all patients but one in the Gelusil group. The pH remained elevated 45 min later. It is concluded that 0.3 mol/l sodium citrate is effective as an antacid when given orally prior to induction of anesthesia.

Adult↗