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Biomedical subjects

P R Greipp

Publications and source records attributed to P R Greipp.

At least 145 records · Page 8Linked to original sources
PubMed1986

Elevated glucocorticoid receptor binding in cultured human lymphoblasts following hydroxyurea treatment: lack of effect on steroid responsiveness.

While studying the effects of chemotherapy on glucocorticoid receptor (GR) binding levels in hematological malignancies, we observed a sizable increase in nuclear GR binding of [3H]dexamethasone in peripheral leukocytes from a chronic basophilic leukemia patient following treatment with hydroxyurea plus prednisone, but not after prednisone alone. This apparent clinical effect of hydroxyurea led to an examination of hydroxyurea effects on GR binding and sensitivity in the glucocorticoid-sensitive human lymphoblast cell line GM4672A. GR binding levels in GM4672A cells were measured following a 3-day exposure to 50 microM hydroxyurea, a concentration chosen to have a minimal but measurable effect on cellular growth rates with little or no effect on cellular viability. Under these conditions, nuclear [3H]dexamethasone receptor binding measured by Scatchard analysis using a whole-cell assay was elevated 2.4-fold over control values (P less than 0.05), while cytosolic residual receptor binding (measured at 37 degrees C) remained unchanged. Thus, the total cellular content of measurable GR was increased, and this increase was totally accounted for by GR capable of nuclear binding. Hydroxyurea treatment of GM4672A cells had no effect on the affinity of nuclear or cytosolic GR for [3H]dexamethasone. The increase in measurable nuclear-bound receptors occurred in a time-dependent manner over a period of 3 days and was fully reversible within 3 days following removal of hydroxyurea. The increase in receptor binding could not be explained by the slight alterations in cell cycle kinetics which occur at this low level of hydroxyurea. Despite increased receptor binding, cellular glucocorticoid responsiveness was unaltered as assessed by dexamethasone inhibition of cell growth and dexamethasone inhibition of a urokinase-like plasminogen activator. Thus, increased nuclear and total cellular GR binding levels in hydroxyurea-treated GM4672A cells are not associated with increased glucocorticoid responsiveness.

Cell Cycle↗
PubMed1985

Pyostomatitis vegetans. A reactive mucosal marker for inflammatory disease of the gut.

Pyostomatitis vegetans is a rarely occurring disorder of the oral mucosa, which has a dramatic clinical picture and a striking histopathologic pattern. Moreover, the condition is a highly specific oral mucosal marker for inflammatory bowel disease, particularly ulcerative colitis. Our findings in two cases and a review of the literature emphasize the relationship of pyostomatitis vegetans to inflammatory bowel disease and the vegetating dermatoses.

Adult↗
PubMed1985

Immunofluorescent plasma cell labeling indices (LI) using a monoclonal antibody (BU-1).

Tritiated thymidine labeling indices (LI), although useful in diagnosis and prognosis of multiple myeloma, have not found wide-spread application because autoradiographic analysis is difficult and time consuming. Using a monoclonal antibody (BU-1) reactive with 5-bromo-2-deoxyuridine (BrdUrd), we have developed an immunofluorescent procedure that allows DNA S-phase measurements to be determined in 4 hr. Plasma cells are easily identified by reactivity with a fluorescein isothiocyanate-conjugated antihuman immunoglobulin, and cells in DNA S phase are detected via BU-1 and a rhodamine-conjugated antimouse immunoglobulin. Results using this method on 12 patients with multiple myeloma compare favorably (correlation coefficient 0.84), with those obtained by tritiated thymidine. This immunofluorescent slide method will facilitate application of labeling indices as a clinical test to measure disease activity in patients with multiple myeloma and other hematologic neoplasms.

Antibodies, Monoclonal↗
PubMed1985

A monoclonal antibody reactive with 5-bromo-2-deoxyuridine that does not require DNA denaturation.

We describe a mouse monoclonal antibody (BU-1) reactive with 5-bromo-2-deoxyuridine (BrdUrd). The antibody is different from previously described BrdUrd monoclonal antibodies in that BU-1 does not require pretreatment of cells with strong DNA denaturants in order for the antibody to react with BrdUrd incorporated in the DNA. The antibody can be used in immunocytochemical and indirect immunofluorescent assays and can be used to identify cells that have incorporated BrdUrd. Double staining with BU-1 antibody and propidium iodide has been used to confirm S-phase measurements with the BU-1 antibody. Immunocytochemical stains using the BU-1 antibody do not destroy cell morphology and allow cell identification to be performed simultaneously with S-phase measurements. Flow cytometer two-color fluorescence analysis allows the simultaneous identification of cell surface or cytoplasmic markers and S-phase quantitation. The BU-1 antibody should broaden the application of cell kinetic measurements to individual elements of cell populations that are heterogeneous with respect to morphology, surface marker, and other biological features.

Antibodies, Monoclonal↗
PubMed1985

Infectious mononucleosis mimicking a B cell immunoblastic lymphoma associated with an abnormality in regulatory T cells.

An elderly woman is described with infectious mononucleosis in whom cervical node biopsy was interpreted as showing immunoblastic lymphoma. Concomitant reactive lymphocytosis, Epstein-Barr virus serologic results consistent with an acute infection, and demonstration of polyclonal B cell infiltration of other tissues argued against intervention. Defective in vitro T cell responses were demonstrated during the acute phase of Epstein-Barr virus infection. Infectious mononucleosis has rarely been reported as mimicking a non-Hodgkin's lymphoma. At 18 months, our patient's course has been typical for infectious mononucleosis with no evidence of disseminated malignancy.

Aged↗
PubMed1985

Primary systemic amyloidosis. Comparison of melphalan/prednisone versus colchicine.

This is the first prospectively randomized study of the use of melphalan/prednisone and colchicine in the treatment of primary systemic amyloidosis. One hundred one patients were stratified according to their dominant clinical manifestation. Forty-nine patients initially received melphalan/prednisone and eight subsequently had colchicine added to their regimen. Fifty-two patients initially received colchicine and 35 subsequently required melphalan/prednisone because of progressive disease. There was no difference in survival when the two groups were analyzed in aggregate (melphalan/prednisone, 25.2 months versus colchicine, 18 months; p = 0.23). When the survival of patients receiving only one regimen was analyzed or when survival was analyzed from the time of entry into the study to the time of death or progression of disease, significant differences (p less than 0.001 and p less than 0.0001, respectively) were evident, favoring melphalan/prednisone. This study suggests that melphalan/prednisone is superior to colchicine in the treatment of primary amyloidosis, but to confirm this impression, a study without a crossover group is necessary.

Amyloidosis↗
PubMed1985

Echocardiographic findings in systemic amyloidosis: spectrum of cardiac involvement and relation to survival.

One hundred thirty-two patients with biopsy-proven systemic amyloidosis underwent echocardiographic examination to define the spectrum of cardiac involvement. Echocardiographic abnormalities were then correlated with clinical variables and survival at follow-up. Patients were subgrouped by left ventricular wall thickness: Group I, mean wall thickness 12 mm or less; Group II, mean wall thickness greater than 12 mm but less than 15 mm; Group III, mean wall thickness 15 mm or greater; or Group IV, atypical features such as wall motion abnormalities or left ventricular dilation. Patients with greater wall thickness had a higher frequency of associated echocardiographic abnormalities such as left atrial enlargement or granular sparkling appearance on two-dimensional examination and, more commonly, reduced systolic function. The occurrence of clinical congestive heart failure was strongly correlated with greater wall thickness and multiple other echocardiographic abnormalities. Survival was negatively influenced both by greater wall thickness and reduced systolic function. The median survival of the entire group was 1.1 years. Echocardiographic examination is an important tool for establishing the presence of cardiac amyloid involvement and may be useful in estimating prognosis in such patients.

Aged↗
PubMed1985

Splenectomy does not cure the thrombocytopenia of systemic lupus erythematosus.

Fourteen patients with systemic lupus erythematosus had splenectomies done between 1960 and 1982 for treatment of severe thrombocytopenia. Thrombocytopenia persisted or recurred within 1 month postoperatively in five patients and within 6 months in three others. Three patients had late recurrence (18, 30, and 54 months after splenectomy); in two it was probably related to withdrawal of immunosuppressive agents or corticosteroids. Median lowest platelet count before splenectomy and median platelet count at relapse or failure of splenectomy were both 8000/microL. Only two patients maintained normal platelet counts without need for corticosteroids or other treatment. These results differ from those in patients with idiopathic thrombocytopenic purpura. Other treatments should be tried before splenectomy is done for thrombocytopenia in patients with systemic lupus erythematosus.

Adult↗
PubMed1985

The clinical significance of cytogenetic studies in 100 patients with multiple myeloma, plasma cell leukemia, or amyloidosis.

Chromosome studies were done on 82 patients with multiple myeloma, 11 with amyloidosis, 2 with multiple myeloma and amyloidosis, and 5 with plasma cell leukemia to investigate their chromosomal abnormalities and to determine the usefulness of cytogenetic studies. A chromosomally abnormal clone was found in 29 patients but was observed most often in those with active disease: in 18% of patients with newly diagnosed multiple myeloma, in 63% with aggressive disease, and in 40% with plasma cell leukemia. Survival among the newly diagnosed patients was significantly shorter (P = .0089) for those in whom an abnormal clone was identified (median survival, six months) than for those in whom only normal metaphases were observed (median survival, greater than 12 months). Among all of the patients, survival from the time of chromosome analysis was shorter for those in whom a chromosomally abnormal clone was found: the median survival was three months for patients with all abnormal metaphases and eight months for patients with normal and abnormal metaphases and has not yet been reached for patients with only normal metaphases. The most common anomalous chromosomes in patients with a plasma cell proliferative disorder were 1, 11, and 14: 11 patients had an abnormality involving chromosome 14q32 and nine patients had an anomalous chromosome 11. The single most common abnormality, a t(11;14)(q13;q32), occurred in three patients. Among the patients who developed preleukemia or acute nonlymphocytic leukemia, the most common anomaly involved chromosome 7. The results suggest that cytogenetic studies are useful for identifying patients who have a poor prognosis and can help distinguish patients with a cytopenia because of preleukemia from those with an aggressive plasma cell proliferative process.

Amyloidosis↗
PubMed1985

Gamma heavy-chain disease involving upper airway.

Gamma heavy-chain disease is a rare disorder. It is a plasma cell dyscrasia, with the patient's age at onset being 9 to 87 years. Identification of IgG heavy chains in the serum and urine is diagnostic. Histopathologic features are nonspecific. Although the clinical presentation is diverse, many signs and symptoms lead to early otorhinolaryngologic consultation. For this reason gamma-heavy-chain disease should be considered in the differential diagnosis of inflammatory lesions of the upper aerodigestive tract.

Heavy Chain Disease↗
PubMed1985

Multiple myeloma: significance of plasmablastic subtype in morphological classification.

We classified 100 cases of myeloma before chemotherapy as mature (28), intermediate (38), immature (19), or plasmablastic (15). The plasmablastic group had an estimated median survival (Kaplan-Meier method) of ten months, compared to 35 months for the other types (P less than .05). Decreased survival in the plasmablastic group was due to more frequent deaths in the first six months. There were no significant differences in survival among the mature, intermediate, and immature groups or among patients with different morphological grade or asynchrony scores. The plasmablastic myeloma group had more frequent renal insufficiency and higher plasma cell labeling indices, which may have contributed to the shorter survival.

Actuarial Analysis↗
PubMed1984

Lymphocyte subsets in patients with aplastic anemia.

Lymphocyte subsets were enumerated in a group of 31 patients with aplastic anemia. Abnormal numbers of immunoregulatory T-cells were found in some patients: 26% of them showed a reversed helper/suppressor ratio. Seven of 18 patients showed significantly decreased proliferation in response to PWM; this hyporesponsiveness was present in 75% of patients with a reversed helper/suppressor ratio and in 10% of those with a normal helper/suppressor ratio (R = 0.66, P = 0.008). Eight of 18 patients showed suppressor activity over PWM-induced allogeneic cell proliferation. This suppressive activity did not correlate with T-cell phenotype. Of the patients with a low number of T-cells, 73% had responded to treatment, whereas of those patients with a normal number of T-cells, 26% had responded (P = 0.016). The results are consistent with abnormal immune response in selected patients with aplastic anemia, and suggest a possible influence of T-cells on disease process.

Adolescent↗
PubMed1984

Serial echocardiographic observations in patients with primary systemic amyloidosis: an introduction to the concept of early (asymptomatic) amyloid infiltration of the heart.

Echocardiography was used for the serial assessment of 27 patients with primary systemic amyloidosis. Thirteen patients had no clinical cardiac deterioration between the two echocardiographic studies (group 1), whereas in 14 patients (group 2), congestive heart failure or arrhythmias (or both) appeared or worsened during a mean observation period of 19 months. The only echocardiographic changes in group 1 were a mild increase in left ventricular mass and a mild decrease in left ventricular wall systolic thickening. Patients in group 2 had significant changes in left ventricular wall thickness (mean increase, 34%), in left ventricular mass (mean increase, 42%), in right ventricular wall thickness (mean increase, 78%), in left atrial size (mean increase, 19%), in left ventricular mass/voltage ratio (mean increase, 68%), in left ventricular radius/thickness ratio (mean decrease, 29%), and in left ventricular fractional shortening (mean decrease, 13%). Significant correlations were found in group 2 between changes in systolic and diastolic blood pressure and changes in ventricular wall thickness and mass. Changes in left ventricular systolic function did not correlate significantly with changes in other clinical, electrocardiographic, or echocardiographic measurements. In six cases (two in group 1), in which amyloid infiltration of the heart was proved by myocardial biopsy or autopsy, the only echocardiographic abnormality when the patients were asymptomatic was a moderate increase in left or right ventricular wall thickness. We found that M-mode and two-dimensional echocardiographic examinations can substantiate progressive amyloid infiltration of the heart and are useful tools for the noninvasive serial assessment of patients with primary systemic amyloidosis.

Adult↗
PubMed1984

Multiple myeloma: circulating lymphocytes that express plasma cell antigens.

The bone marrow and peripheral blood of 14 patients with multiple myeloma were studied with murine monoclonal antibodies that identify antigens on plasma cells (R1-3 and OKT10). Peripheral blood lymphocytes expressing plasma cell antigens were found in six cases. Five of these cases expressed the same antigens that were present on the plasma cells in the bone marrow. Patients that showed such peripheral blood involvement were found to have a larger tumor burden and higher bone marrow plasma cell proliferative activity. In some patients, antigens normally found at earlier stages of B cell differentiation (B1, B2, and J5) were expressed by peripheral blood lymphocytes and/or bone marrow plasma cells.

Antigens, Surface↗
PubMed1983

Localization of eosinophil granule major basic protein in human basophils.

In experiments using an immunofluorescent method to localize human eosinophil granule major basic protein (MBP) in cells and tissues, a small number of cells stained for MBP that subsequently could not be identified as eosinophils. Because the Charcot-Leyden crystal protein, another eosinophil protein, was recently identified in basophils, we tested whether MBP might also be a constituent of blood basophils. Highly purified, eosinophil-free basophil suspensions were prepared using the fluorescence-activated cell sorter (FACS) to sort basophil-containing mononuclear cell preparations stained with fluorescein-conjugated sheep IgG anti-human IgE antibody. Using these FACS-purified basophils, we found that: (a) enrichment for surface IgE-positive cells (greater than 95% basophils) by FACS also enriched for cells staining for MBP by immunofluorescence; (b) MBP appeared to be localized in the histamine-, heparin-containing granules; (c) significant quantities of MBP were measurable by radioimmunoassay (RIA) in freeze-thaw detergent extracts of purified basophils; and (d) RIA dose-response curves for extracts of purified eosinophils and basophils had identical slopes. The MBP content of basophils from normal individuals averaged 140 ng/10(6) cells, whereas purified eosinophils from normal donors and patients with the hyper-eosinophilic syndrome averaged 4,979 and 824 ng/10(6) cells, respectively. MBP was also detected by immunofluorescence and RIA in cells obtained from a patient with basophil leukemia, although the MBP content for basophil leukemia cells was lower than that for normal basophils. We conclude that basophils contain a protein that is immunochemically indistinguishable from eosinophil granule MBP.

Basophils↗
PubMed1983

Multiple myeloma. Houses and spouses.

Two families in which successive spouses who lived in the same house developed multiple myeloma are reported. In the first instance, a man whose first wife died of multiple myeloma remarried, and his second wife also developed myeloma. In the second family, a woman's first husband died of multiple myeloma and her second husband did too. Radiation studies of the houses and yards showed no increased radioactivity. No evidence was found for excessive exposure to chemicals or other environmental agents, for contact with other patients having similar malignancies, or for exposure to viruses or other transmissible factors. The significance of the occurrence of multiple myeloma in subsequent spouses is unknown. It is hoped that this report will stimulate research for other instances and lead to careful epidemiologic, radiologic, and virologic studies.

Environmental Exposure↗
PubMed1983

Discoid lupus erythematosus and monoclonal gammopathy.

Of twelve patients with discoid lupus erythematosus and dysgammaglobulinaemia, eight had a monoclonal gammopathy with a benign course to date, two had 'smouldering' myeloma, and two developed overt multiple myeloma. Six patients had generalized discoid lupus erythematosus, and six had skin lesions localized to the head and neck. Further screening of patients with discoid lupus erythematosus by serum protein electrophoresis is indicated to determine the significance of these findings.

Adult↗