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S M Koethe

Publications and source records attributed to S M Koethe.

17 recordsLinked to original sources
PubMed1990

Image analysis confirmation of DNA aneuploidy in flow cytometric DNA distributions having a wide coefficient of variation of the G0/G1 peak.

With nuclei extracted from paraffin-embedded tissues, resolution of normal diploid DNA and abnormal near-diploid/aneuploid populations by flow cytometry (FCM) is especially difficult. These samples, compared with fresh tissue, tend to show a broader DNA distribution, appearing as a wide (high) coefficient of variation (CV) of the G0/G1 peak. To address the question of whether there may be aneuploid populations hidden in wide CV diploid G0/G1 peaks, the authors measured DNA content in nuclei extracted from paraffin-embedded tumor tissue by morphometric image analysis (IA) in addition to FCM. Of 29 samples showing little evidence of DNA aneuploidy by FCM, in 20 of 20 with G0/G1 CVs greater than or equal to 5.50% there was an aneuploid population when analysis was performed by IA. Of the remaining nine samples with CVs less than or equal to 4.41%, all were diploid in the G0/G1 region by both FCM and IA. The presence of aneuploid populations in FCM distributions with wide CV G0/G1 peaks can be confirmed by IA.

Aneuploidy↗
PubMed1990

Failure of T cell receptor-anti-CD3 monoclonal antibody interaction in T cells from marrow recipients to induce increases in intracellular ionized calcium.

There are multiple immune defects in T cells from recipients after bone marrow transplantation (BMT). This study examines recipient T cells for increases in intracellular ionized calcium concentration [( Ca2+]i) after binding the T cell receptor-CD3 complex with anti-CD3 MAb. PBL from 10 of 23 short-term recipients (less than 1 yr after BMT) responded poorly (less than 35% of control) to anti-CD3 stimulation and PBL from 9 of 23 had blunted calcium flux responses (35-70% of control). Purified CD2+, CD56- cells from seven additional short-term recipients including three autologous marrow recipients were closely examined, and a sizable proportion of CD3+ cells from six of seven recipients did not increase [Ca2+]i after anti-CD3 stimulation. The decreased magnitude of the responses was due to decreased numbers of responding cells and not to a decrease in mean CD3 fluorescent intensity or in calcium flux responses on a single cell basis. Five of seven long-term recipients (greater than 1 yr after BMT) had PBL that responded normally and two of seven had PBL with blunted calcium flux responses. The data show that the signal transduction response mediated by the CD3-antigen receptor as measured by calcium flux is defective early after autologus or allogeneic BMT.

Adolescent↗
PubMed1989

Increased density of HLA-DR antigen on monocytes of patients infected with the human immunodeficiency virus.

Monocytes and macrophages play an important role in the pathogenesis of the acquired immunodeficiency syndrome (AIDS). Dysfunction of these cells contributes to the immunocompromised state that characterizes AIDS, and they probably serve as a reservoir for the human immunodeficiency virus (HIV). HIV-infected macrophages may also be responsible for the infection of many CD4-positive lymphocytes by means of cell to cell contact during the initiation of immunological responses. The efficiency of this process would be enhanced by activation of the macrophages, since that is accompanied by increased expression of class II major histocompatibility (HLA-DR) antigen. Using a direct blood antibody marking procedure in conjunction with flow cytometry, we have analyzed the expression of HLA-DR antigen on the surfaces of monocytes present in the peripheral blood of HIV-infected patients. In contrast to the results reported by other investigators who purified the monocytes using Ficoll-Hypaque centrifugation prior to antibody marking, we found that the percentage of monocytes expressing HLA-DR antigen was identical in the patients and normal controls. However, a subpopulation of monocytes was detected in the blood of the majority of the patients that was expressing increased levels of HLA-DR antigen. It was also found that the proportion of monocytes with a high density of HLA-DR antigen on their surfaces negatively correlated with the absolute numbers of CD4-positive lymphocytes present in the peripheral blood of the patient. These findings support the postulated role of monocytes and macrophages in the HIV infection and ultimate destruction of CD4-positive lymphocytes.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Relationships between alternative complement pathway activation, C-reactive protein, and pneumococcal infection.

In the absence of specific antibody, opsonization of Streptococcus pneumoniae may be mediated by the alternative complement pathway (AP) or by C-reactive protein (CRP) via C1 binding. To determine the role of these mechanisms in pneumococcal (PNC) disease, we studied 19 patients with differing severities of PNC infection. C4 and CRP levels and zymosan-induced consumption of 50% hemolytic complement (CH50) were measured in specimens obtained acutely and then weekly. In patients with complicated illness, the modified mean CH50 in acute sera was 178 +/- 57 U/ml, significantly lower than the mean CH50 of 331 +/- 80 U/ml in patients with uncomplicated illness (P less than 0.05). The values of the two groups on a given day approximated each other on days 7, 14, and 23. Consumption of complement by zymosan was also lower in acute sera of patients with complicated illness, with a mean value of 19 +/- 18 U/ml compared with 58 +/- 30 U/ml in those with uncomplicated illness (P less than 0.05). This difference was also seen on day 7 (P less than 0.05). Disease involving lower-numbered PNC serotypes (less than 10) correlated with reduced availability of AP factors in acute sera, independent of illness severity. Mean CRP levels were inversely related to zymosan-induced complement activation in patients with complicated illness. These data suggest that in vivo depletion of AP factors is significantly greater in patients with complicated illness and is associated with high CRP levels. CRP may enhance AP activation via C3 convertase generation and function with it as a preantibody host defense mechanism.

Adult↗
PubMed1985

Complement activation in myasthenia gravis plasma by Torpedo acetylcholine receptor liposomes.

The purpose of this study was to determine if antibodies from patients with myasthenia gravis (MG) react in a biologically relevant manner with membrane bound Torpedo californica acetylcholine receptor (AChR). Antibody-mediated complement activation was measured in plasma from 15 patients with MG and 9 controls following incubation with Torpedo AChR-rich membrane vesicles (AChR liposomes). Significantly more (p less than 0.001) complement activation occurred in the patient samples compared with the controls. Torpedo AChR liposomes are well characterized and have been widely used to study the structure and function of AChR. These results suggest that Torpedo AChR liposomes may also be used in immunologic studies with autoantibodies from patients with MG.

Animals↗
PubMed1984

Plasmapheresis with immunosuppressive drug therapy in progressive multiple sclerosis. A pilot study.

In light of encouraging preliminary data, 45 patients with severely progressive multiple sclerosis underwent long-term plasmapheresis in conjunction with low-dose cyclophosphamide and prednisone therapy. The disease progression was monitored by the Kurtzke disability status scale (DSS) and functional systems scale, neuro-ophthalmologic evaluations, evoked potentials, computed tomographic scans, and suppressor cell function assays. The conditions of 28 of the 45 patients improved significantly, the conditions of 14 patients showed limited improvement, and the conditions of three patients neither improved nor worsened. Improvement in other parameters correlated with the clinical results. Significant improvement in suppressor cell function was noted in those patients whose conditions had improved by one or more steps on the DSS.

Adult↗
PubMed1984

Immune reactivity against membranes containing ganglioside GM1 in chronic-progressive multiple sclerosis: observation by spin-membrane immunoassay.

A spin-membrane immunoassay has been employed to examine the immune reactivity of whole serum from patients with chronic-progressive multiple sclerosis (CPMS) against liposomes containing ganglioside GM1. Exposure to serum resulted in complement-mediated lysis of the GM1-liposomes. No lysis occurred with liposomes devoid of ganglioside. The mean (+/- S.E.M.) lysis values were 52.6 (+/- 9.8)% for fifteen CPMS patients and 32.9 (+/- 7.2)% for nine controls. The difference between the means was highly significant (student's t-test, P less than 0.0001), indicating increased anti-ganglioside immunity in patients with CPMS.

Cytotoxicity, Immunologic↗
PubMed1978

The prevalence of HLA-B7 in presumed ocular histoplasmosis in patients with peripheral atrophic scars.

Patients identified in the Walkersville, Maryland, epidemiologic study of presumed ocular histoplasmosis as having only peripheral atrophic scars showed no increase in frequency of HLA-B7 over a control population. Because this antigen is increased in patients with a history of active macular or peripapillary lesions, these findings indicate an inherent predisposition in some patients to develop posterior pole lesions after an ocular infection with Histoplasma capsulatum. The precise mechanisms by which the histocompatibility complex participates in the pathogenesis of these lesions is unknown, but our data are compatible with previous suggestions that alterations in the immune response of these individuals are in some way important in the development of disciform scarring in the posterior pole.

Eye Diseases↗
PubMed1978

Acquired angioedema associated with rectal carcinoma and its response to danazol therapy. Acquired angioedema treated with danazol.

Cases of the acquired form of angioedema have been recognized as a separate entity since 1972. Previously reported cases have been related to various hematologic malignancies. We have recently studied a patient with rectal carcinoma who manifests a complement pattern compatible with the acquired form of angioedema. No previous personal or family history of allergic disease or angioedema was present. Because the episodes of angioedema were laryngeal in location and required emergency intubation to maintain an adequate airway, a trial of danazol prophylaxis, which has been shown to be effective in hereditary angioedema, was undertaken. His beneficial response to this form of therapy is also documented.

Adenocarcinoma↗
PubMed1978

The prevalence of HLA-B7 in presumed ocular histoplasmosis.

Eighteen patients with the presumed ocular histoplasmosis syndrome were typed for HLA histocompatability antigens and 78% were found to have the B7 antigen. This data implies an underlying immunogenic predisposition to the development of the clinical eye findings and active posterior pole lesions in the presumed ocular histoplasmosis syndrome. It is likely that some feature of the immune system of these patients renders them more susceptible either to the initial infection or to a later activation of posterior pole lesions mediated through immunologic mechanisms.

Eye Diseases↗
PubMed1978

Some hemodynamic determinants of immune complex trapping by the kidney.

This study was undertaken to help clarify the relationship between capillary hemodynamic events and the tissue uptake of circulating immune complexes (IC). In each of 23 dogs, bovine serum albumin (BSA) and rabbit antiBSA soluble IC labeled with 125I were given by constant i.v. infusion, and IC uptake by a normally perfused kidney was compared to that of the contralateral kidney in which renal blood flow (RBF) was changed by renal artery constriction or raised ureteral pressure. In these same animals, IC uptake in 15 other major organ systems was also measured simultaneously. During IC infusion microspheres of 85Sr were injected to measure cardiac output and tissue blood flow, and red cells labeled with 51Cr were infused to mark tissue vascular volume. At completion of the IC infusion, tissue samples were taken from the kidneys and the 15 other major organs systems. From the isotope content of each tissue, we determined IC content, blood flow rate, vascular transit time, and fractional uptake of IC (FIC). In addition, glomeruli were isolated from renal cortex to assess IC uptake in glomerular versus renal nonglomerular tissue. We found that 1) for kidney, IC delivery rate, capillary hydrostatic pressure, and capillary ultrafiltration rate are less important than the plasma IC concentration in determining IC uptake; 2) for each organ studied, the principal determinant of IC uptake per gram of tissue, at any given PIC, is vascular volume per gram of tissue; 3) tissue vascular volume per gram of tissue may determine IC uptake per gram of tissue because tissue vascular volume determines the capillary surface area in contact with circulating IC or because tissue vascular volume determines tissue vascular transit time, at any given tissue blood flow rate.

Animals↗
PubMed1978

Relations between surface charge and in vitro lysis of red blood cells in paroxysmal nocturnal haemoglobinuria.

The effects of neuraminadase on the electrophoretic mobility and in vitro lysis of PNH, glutathione treated and normal erythrocytes was determined. Neuraminidase strongly affected the in vitro haemolysis of PNH and glutathione treated erythrocytes by substantially elevating the lysis in the Ham acid test while virtually eliminating lysis in the sucrose test. Findings suggest that membrane bound sialic acid or the level of cell surface charge may have a role in the susceptibility of PNH erythrocytes to complement mediated lysis.

Complement C4↗
PubMed1976

Alternative complement pathway activity in sera from patients with sickle cell disease.

The low molecular weight cobra venom factor (CoVF) was used to activate the terminal sequence of the alternative complement pathway in thirty-one sera from patients with sickle cell disease (SCD). The SCD sera were compared with normal sera as a source of the alternative complement pathway factors C3 proactivator (C3PA) and C3PA convertase. These factors are required for formation of the enzymatically active CoVF-C3PA complex which is capable of cleaving C3 and thus initiating generation of the cytolytic C5b-9 complex. CoVF cofactor activity was significantly less than normal in SCD sera as measured in an indirect lysis assay, indicating reduced C3PA or C3PA convertase activity in these sera. Qualitative (immunoelectrophoresis) and quantitative (radial immunodiffusion) measurement of C3PA showed, however, that this protein is normal or elevated in SCD sera. Taken together, the reduced CoVF cofactor activity and normal or elevated C3PA in SCD sera suggests that sera from patients with sickle cell disease have reduced C3PA convertase activity.

Adolescent↗