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Biomedical subjects

J M Thompson

Publications and source records attributed to J M Thompson.

At least 181 records · Page 10Linked to original sources

Detection of circulating immune complexes by Raji cell assay: comparison of flow cytometric and radiometric methods.

Several flow cytometric methods for the measurement of circulating immune complexes (CIC) have recently become available. We report a Raji cell flow cytometric assay (FCMA) that uses aggregated human globulin (AHG) as primary calibrator. Technical advantages of the Raji cell flow cytometric assay are discussed, and its clinical usefulness is evaluated in a method comparison study with the widely used Raji cell immunoradiometric assay. FCMA is more precise and has greater analytic sensitivity for AHG. Diagnostic sensitivity by the flow cytometric method is superior in systemic lupus erythematosus (SLE), rheumatoid arthritis, and vasculitis patients: however, diagnostic specificity is similar for both assays, but the reference interval of FCMA is narrower. Significant correlations were found between CIC levels obtained with both methods in SLE, rheumatoid arthritis, and vasculitis patients and in longitudinal studies of two patients with cerebral SLE. The Raji cell FCMA is recommended for measurement of CIC levels to clinical laboratories with access to a flow cytometer.

Antigen-Antibody Complex↗

Punch biopsy for diagnosis of pigmented skin lesions.

Melanoma is a potentially fatal cancer with a relatively high incidence, but it can be cured if the lesions are removed at an early stage. Punch biopsy is a cosmetically acceptable, rapid method for removing small pigmented lesions to allow definitive pathologic diagnosis. The technique, which usually requires only a small amount of local anesthetic and no sutures, can be performed by a busy physician at the time the suspicious lesion is discovered.

Biopsy↗

Antagonism of the in vivo and in vitro effects of leukotriene D4 by SC-39070 in guinea pigs.

Leukotriene D4 (LTD4) causes contractions of guinea pig isolated ilea, evokes pulmonary bronchoconstriction and induces lesions of the dermal vasculature. In the present study, we assessed the antagonism of these actions by SC-39070 compared to FPL-55712, a known LTD4 receptor antagonist. In guinea pig isolated ileum preparations, SC-39070 displayed selective antagonism of LTD4 with a pA2 = 8.20 +/- 0.06 (S.E.) and a Schild plot slope of -1.20. Administered intravenously to artificially-respired guinea pigs one minute prior to the agonist, SC-39070 antagonized (p less than 0.05) the bronchoconstrictive effect of LTD4 in a dose-dependent manner (0.5-10 mg/kg). At a dose of 2.0 mg/kg, i.v. this activity was retained through a 60 minute pretreatment interval. Similarly, after oral administration of SC-39070, there was a dose-dependent antagonism of the bronchoconstrictive activity of LTD4 (MED50 = 3.8 mg/kg). Antagonism of LTD4-induced bronchoconstriction was evidenced after oral administration of SC-39070 within one hour of treatment and efficacy was retained as long as 20 hours after treatment at a dose of 10 mg/kg. Finally, intravenously administered SC-39070 blocked LTD4-induced dermal permeability in guinea pigs with a minimum effective dose of 1.0 mg/kg. In each assay, the LTD4 antagonism evidenced after treatment with SC-39070 appeared to be equal to or greater than that observed after treatment with FPL-55712.

Animals↗

A laminin substrate promotes myogenesis in rat skeletal muscle cultures: analysis of replication and development using antidesmin and anti-BrdUrd monoclonal antibodies.

Cells from newborn rat hindlimb show greatly enhanced myogenicity when grown on surfaces coated with poly-L-lysine followed by laminin (PLL/Lam) instead of the collagens routinely used. Coating with poly-L-lysine (PLL) alone or with PLL followed by collagen does not enhance myogenicity. Both myogenic and nonmyogenic cells, as distinguished by a monoclonal antibody specific for desmin, attach equally well to collagen- and laminin-coated surfaces, but there is a two- to five-fold increase in the number of myogenic cells on PLL/Lam by 72 hr, followed by increased myotube formation. To determine whether this increase in myogenic cells was a consequence of a selective increase in proliferation on PLL/Lam, incorporation of 5-bromodeoxyuridine into DNA followed by labeling with anti-BrdUrd antibody was used as an index of cell proliferation. The results indicate that desmin is expressed in replicating rat myoblasts, and that replication of myogenic cells is greatly enhanced on laminin compared to collagen. The rate of replication of nonmyogenic cells is the same on both substrates. Addition of 10 micrograms/ml laminin to the medium of cells seeded on PLL or collagen has no effect on myogenicity. We conclude that a laminin substrate enhances skeletal myogenesis in vitro by promoting selectively the replication of myoblasts. Cultures prepared from fetuses at 17 and 19 days gestation also show enhanced myogenicity when grown on PLL/Lam, while those from 15-day fetuses do not. Growth and development of fetal myoblasts on collagen were very poor, whereas myoblasts from the newborn rat do proliferate and differentiate on this substrate. Thus myogenic cells at different stages of fetal and neonatal development may require and respond to different extracellular environments. Myotube formation in the E63 clone of L8 rat myoblasts is inhibited by PLL/Lam.

Animals↗

Developmental regulation of chick embryo retina neurite extension by extrinsic factors.

Developmental changes in the control of neurite extension by extracellular factors can be examined by utilizing cultures of neurons from various aged embryos. Several conditioned media and tissue extracts were added to cultures of chick embryo retinal neurons on collagen substrates for 1, 3 and 5 days in vitro. Neurite outgrowth, measured as the percentage of neurons with neurites and the length of neurites, was promoted by optic tectal extract and cornea conditioned medium in retina neurons from younger ages (6- to 12-day embryos), but not from older ages (14- and 16-day embryos). The promotion of neurite outgrowth by optic tectal extracts may be mediated by a promotion of glial cell growth. The developmental changes in neurite extension may be due to either an altered sensitivity to the neurite promoting factors or by an altered intrinsic ability of retinal neurons to extend processes.

Age Factors↗

Verotoxin production among porcine strains of Escherichia coli and its association with oedema disease.

Strains of Escherichia coli isolated from documented cases of disease in pigs and belonging to a wide range of pathogenic serotypes were tested for their ability to produce a heat labile verotoxin (VT). The strains isolated from oedema disease all produced VT, indicating that the cytotoxin detected by the vero-cell assay was identical to "oedema disease principle". Strains belonging to the serotypes associated with enterotoxic diarrhoea were VT-. Not all the strains belonging to the recognised oedema disease serotypes (O141:K85, O139:K82 and O138:K81) produced VT, but the VT- strains were not associated with outbreaks of clinical disease.

Animals↗

Trazodone treatment response in obsessive-compulsive disorder--correlated with shifts in glucose metabolism in the caudate nuclei.

Obsessive-compulsive disorder (OCD) is a severe psychiatric illness that is difficult to treat. The effects of trazodone hydrochloride treatment were studied, both with and without the addition of a monoamine oxidase inhibitor, in OCD patients. Changes in symptoms correlated with changes in local cerebral metabolic rates for glucose (LCMRGlc), as measured by positron emission tomography and the 18F-fluorodeoxyglucose method. All patients whose OCD responded favorably to drug treatment showed a relative increase in glucose metabolism in the heads of the caudate nuclei compared with the metabolic rate in the ipsilateral hemisphere as a whole (ratio LCMRGlc caudate/LCMRGlc hemisphere). Patients who did not respond to treatment did not show an increase in this ratio, and the difference between responders and nonresponders was significant (p less than 0.03). Changes in the ratio LCMRGlc caudate/LCMRGlc hemisphere correlated with changes on OCD and depression rating scales.

Adult↗

Prolongation of survival for high-grade malignant gliomas with adjuvant high-dose BCNU and autologous bone marrow transplantation.

Employment of postoperative brain irradiation in the initial management of high-grade malignant glial tumors has now become standard. The addition of conventional chemotherapy to irradiation has not significantly improved median survival beyond 1 year. We treated 25 consecutive patients (13 pilot patients and 12 protocol patients) with histologically confirmed unresectable grade 3 or 4 malignant gliomas with high-dose BCNU (carmustine) followed by autologous bone marrow transplantation and whole brain irradiation. Within 3 weeks of initial surgery, each patient had autologous bone marrow stored (median 2 X 10(8) nucleated cells/kg), and then received BCNU 1,050 mg/m2 intravenously (IV). Peripheral granulocytes recovered (greater than 500/microL) at a median of 19 days (range, 10 to 37 days), and platelets recovered (greater than 20,000/microL) at a median of 18 days (range, 13 to 40 days), following bone marrow infusion. Patients received 60 Gy whole brain irradiation when granulocytes were greater than 1,500/microL. Toxicity was well tolerated. Nausea occurred in 19 patients (76%); however, only eight patients (32%) experienced vomiting (mild in three, moderate in five). Eleven patients (44%) did not require empiric antibiotics, six of whom never developed an absolute granulocyte count less than 500/microL. Three patients with a poor performance status died early (one seizure with vomiting and asphyxiation; one, klebsiella urinary tract infection (UTI) with bacteremia; one, candidal pneumonia), and one additional patient who was performing well died of pulmonary hemorrhage. The 13 pilot patients have now been followed for a median of 23 months, with a significant survival advantage compared with the 52 consecutive historical control patients who received similar surgery and radiotherapy without high-dose BCNU (P = .037). The overall study group of 25 patients also has a significant survival advantage when compared with the same historical control group, with a projected median survival of 26 months (P = .007). This new approach using early postoperative intensive therapy consisting of high-dose BCNU, autologous bone marrow transplantation, and whole brain irradiation appears to significantly improve survival.

Adult↗

Comparison between sodium aurothiomalate and auranofin in rheumatoid arthritis. Results of a two-year open randomized study.

We compared the effectiveness of Auranofin, and sodium aurothiomalate (SATM) given for 2 years to patients with rheumatoid arthritis. This was an open trial with randomized entry to 2 treatment groups of 60 patients each. Only 40% of patients completed 2 years of treatment but these showed significant improvement in their indices of disease activity. Adverse reactions were a more common reason for withdrawal from SATM than from Auranofin, while insufficient therapeutic response was more common with Auranofin. This study also shows that inefficacy, toxicity, complicating illnesses, and lack of compliance limit the beneficial outcome of long-term chrysotherapy.

Adult↗

In vitro production of anti-influenza virus antibody after simultaneous administration of H3N2 and H1N1 cold-adapted vaccines in seronegative children.

Sixteen doubly seronegative (H3N2 and H1N1) young children were recently enrolled in a study of live, attenuated cold-adapted influenza A vaccines. Twelve children received simultaneously H3N2 and H1N1 live, attenuated influenza vaccine intranasally and four received saline as placebo controls. Peripheral blood lymphocytes (PBL) were obtained sequentially from all children and the in vitro production of anti-influenza H3N2 and H1N1 antibody from unstimulated and influenza stimulated cells was measured by ELISA. In vitro antibody studies were performed at 0, 2, 4, and 12 weeks after immunization. PBL from six of 12 children spontaneously produced H3N2 antibody and eleven of 12 produced H1N1 antibody. Influenza stimulation of PBL induced antibody production in 8/12 for H3N2 and 12/12 for H1N1. PBL from all four placebo immunized children failed to produce specific influenza antibody in vitro at any time studied. In vitro antibody produced after immunization was primarily of the IgG isotype with peak production occurring at 4-12 weeks, supporting the primary nature of the response. The correlation between the presence of positive serum HAI and ELISA titres, and the production of in vitro antibody was good for both H3N2 and H1N1 vaccines. In summary, the simultaneous administration of two attenuated influenza A vaccines into the upper respiratory tract of seronegative children resulted in the stimulation of PBL capable of secreting both H3N2 and H1N1 influenza specific antibody in vitro.

Antibodies, Viral↗

A soluble factor (less than 4000 Da) from chick spinal cord blocks slow hyperpolarizing afterpotentials in cultured rat muscle cells.

The slow hyperpolarizing afterpotential (slow HAP) following an evoked action potential in cultured rat muscle cells is inhibited by coculture with spinal cord neurons, spinal cord-conditioned medium (CM) and by a low-molecular-weight fraction (less than 4000 Da) prepared from this CM. The incidence, amplitude and duration of the slow HAPs decreased significantly after 24 h of incubation. In contrast, chick retinal neuron cocultures or CM did not alter the slow HAP.

Action Potentials↗

Immunity to influenza A virus infection in young children: a comparison of natural infection, live cold-adapted vaccine, and inactivated vaccine.

Live attenuated, cold-adapted (ca) influenza A vaccines administered intranasally have been well characterized as safe and immunogenic, but comparative data on protective efficacy are required for further development. In this study, 59 young children were divided into the following four groups based on prior exposure to influenza A (H3N2) virus: natural infection, live ca vaccine given intranasally, inactivated vaccine given im, and no previous exposure. Virus challenge with homologous live ca vaccine occurred 12 months after vaccination or natural infection. Prior natural infection and live ca vaccine significantly reduced ca virus shedding after challenge compared with inactivated vaccine or no prior exposure to influenza A virus. Prechallenge nasal IgA, detected almost exclusively in subjects naturally infected or vaccinated with live ca virus, was associated with protection. Although inactivated vaccine failed to produce significant local IgA during the primary response, it seemed to prime for secondary local antibody responses after challenge with live ca virus.

Administration, Intranasal↗

Phase II trial of high-dose melphalan and autologous bone marrow transplantation for metastatic colon carcinoma.

Colon carcinoma, the second leading cause of cancer-related deaths in the United States, is resistant to chemotherapy in a large majority of cases. Single-agent and combination chemotherapy have failed to prolong survival. New approaches are clearly needed. In experimental models, a steep dose-response curve for colorectal cancer has been demonstrated using various agents. The hematopoietic toxicity of high-dose therapy with these drugs can be circumvented by autologous bone marrow transplantation. We investigated the use of high-dose melphalan with autologous bone marrow rescue in 20 patients with metastatic colon carcinoma. Each patient received melphalan, 180 mg/m2 intravenously (IV), followed eight hours later by bone marrow infusion. Median duration of granulocytopenia (less than 500 neutrophils/microL) was twelve days (range, 5 to 35 days), while transfusion-dependent thrombocytopenia (less than 20,000 platelets/microL) had a median duration of eight days (range, 3 to 23 days). Time to bone marrow engraftment was not affected by prior 5-fluorouracil therapy. Nausea and vomiting occurred in 14 patients but was generally short lived. Mild stomatitis, esophagitis, and diarrhea were common. Severe gastrointestinal (GI) side effects did not occur. One treatment-related death occurred secondary to intramural tumor necrosis, which resulted in massive lower GI bleeding. Complete responses were observed in three patients (15%) and partial responses in six patients (30%), for an overall response rate of 45%. Median survival was 198 days in this group of patients with extensive disease. High-dose melphalan therapy for metastatic colon carcinoma, when used with autologous bone marrow transplantation, appears to achieve a high response rate with tolerable toxicity. Further investigation is needed to define the role of this therapy in the care of advanced colon carcinoma.

Adult↗

Dietary management of intestinal lymphangiectasia complicated by short gut syndrome.

The dietary management of a child with intestinal lymphangiectasia complicated by short gut syndrome following surgery at the age of 3 weeks is described. Diets containing amino acids and peptides were not tolerated due to high osmolality. Satisfactory nutrition was achieved by using a feed with low osmolality and containing whole whey protein, maltodextrin, medium-chain triglycerides (MCT) and a small amount of long-chain triglycerides (LCT) to supply essential fatty acids (RD231).

Female↗

The optimal application of forward and ninety-degree light scatter in flow cytometry for the gating of mononuclear cells.

Peripheral blood mononuclear cells from ten normal donors were labeled with a monoclonal antibody specific for monocytes and analyzed using a fluorescence activated cell sorter (FACS). Forward and 90 degrees light scatter parameters were studied in order to apply optimal computerized gating to identify and exclude monocytes from lymphocyte populations. An average of 9.45% versus 1.22% of cells, within chosen lymphocyte gates established by forward angle and 90 degrees scatter, respectively, were identified as monocytes. In samples from ten donors, the exclusion of monocytes from the lymphocyte population was more efficient using 90 degrees scatter than forward scatter. Simultaneous use of forward and 90 degrees scatter did not significantly improve the ability to accurately exclude monocytes, but did result in a significant increase in the improper exclusion of lymphocytes. Use of 90 degrees scatter alone, forward scatter alone, and forward and 90 degrees scatter simultaneously to identify lymphoid cells resulted in the exclusion of 12, 17, and 23% of lymphocytes from further analysis. The 90 degrees scatter alone appears to be the optimal method to eliminate monocytes electronically from mononuclear cell populations in which lymphocytes are being studied.

Adult↗

Comparison of long-term systemic and secretory antibody responses in children given live, attenuated, or inactivated influenza A vaccine.

A comparison of inactivated intramuscular and live intranasal influenza A vaccines in young children undergoing primary immunization might be expected to show differences in serum and local mucosal antibody responses. To demonstrate such differences, serum and local respiratory tract antibody responses of young children vaccinated with intranasal live, attenuated, cold-adapted (H3N2 or H1N1), or intramuscular inactivated (H3N2) influenza A vaccines were examined for one year after vaccination. Antibody responses were measured by hemagglutination-inhibition (HAI) and class-specific enzyme-linked immunosorbent assay (ELISA). One year after vaccination, live intranasal vaccinees had significantly less decay of serum HAI (p = 0.025) and IgG antibody (p = 0.01) directed against the influenza hemagglutinin and neuraminidase than did intramuscular inactivated vaccinees. Nasal secretory IgA developed almost exclusively in live vaccinees and persisted for up to one year. Persistent nasal secretory IgG was detected in both live and inactivated vaccinees. Live vaccination not only stimulates a more durable serum antibody response, but also induces long-lasting local respiratory tract IgA antibody that may play an important role in host protection.

Antibodies, Viral↗