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Biomedical subjects

D A Bell

Publications and source records attributed to D A Bell.

At least 217 records · Page 12Linked to original sources

A naturally occurring polyclonal B cell activator of normal and autoantibody responses.

Previous studies from this laboratory have demonstrated the presence of a suppressor molecule in B/W spleen cultures. Now we present evidence suggesting the existence of a polyclonal B cell activator (sPBA) spontaneously released by B/W splenocytes. Large sPBA (120,000 to 160,000 daltons) was separable from splenic inhibitory factor(s) (less than 10,000 daltons) by ultrafiltration. Reconstitution experiments demonstrated these two molecules had antagonistic effects on splenocyte mitotic events. sPBA is directly mitogenic for T cell-depleted, B cell-enriched cultures. Furthermore, sPBA augments antibody responses in the presence of antigen, or stimulates antibody responses in the absence of antigen. sPBA appears to stimulate IgG as well as IgM antibody production. sPBA stimulates significant in vivo anti-ssDNA responses in preautoimmune B/W but not DBA mice. Physiochemical studies suggest sPBA is a DNA protein complex. sPBA activity is completely lost by heating to 56 degrees C for 30 min. sPBA activity is precipitated at pH 7.8 to 8.0. Furthermore, sPBA preparations do not display significant endotoxin levels or IL 1 and IL 2 activity.

Adsorption↗

Wilms' tumor of the endocervix.

We report a case of primary Wilms' tumor of the endocervix in a 13-year-old girl. The tumor was polypoid, filled the vagina, and was attached to the endocervix by a stalk. Microscopic examination disclosed blastematous, epithelial, and stromal elements characteristic of Wilms' tumor. The patient's kidneys were normal on intravenous pyelographic examination and on palpation at laparotomy, and she has remained free of disease for 9.6 years after hysterectomy.

Adolescent↗

The in vitro production of anti-DNA antibody by cultured peripheral blood or tonsillar lymphoid cells from normal donors and SLE patients.

Anti-DNA antibody responses by cultured circulating lymphocytes from SLE patients and by the tonsillar lymphoid cells of normal donors were detected and enumerated by a sensitive specific ELISA of culture supernatants, or by a hemolytic anti-DNA PFC assay. Although spontaneous IgM and IgG anti-DNA and anti-ssDNA responses were characteristic of SLE lymphocytes and spontaneous IgM anti-ssDNA responses were characteristic of tonsillar lymphocytes, the circulating lymphocytes of normal controls never produced anti-DNA antibodies spontaneously, and rarely after PWM stimulation. The anti-DNA antibody PFC response of tonsil lymphocytes correlated directly with the total number of immunoglobulin-producing cells measured by a reverse hemolytic PFC assay. Mixing experiments in which we employed cultures of comparable numbers of separately enriched autologous circulating and tonsillar B and T cells revealed that tonsillar tissue contained an enriched population of anti-DNA antibody precursor B cells and/or helper T cells.

Adolescent↗

Correlation of ascitic fluid cytology with histologic findings before and after treatment of ovarian cancer.

One hundred thirteen specimens of ascitic fluid from 97 patients with primary, persistent, or recurrent ovarian cancer were examined cytologically. Advanced stage of disease, involvement of the ovarian surface, a moderate or large volume of fluid, and nonbloody serous ascites were factors that correlated with a high rate of positive findings in ascites in these patients. Other factors influencing the positive rate appeared to be the invasive as opposed to borderline malignant histology of the tumor. Involved external surface and volume of ascites were influencing factors only in advanced cases. Therefore, the most important factor influencing the positive rate of ascites cytology was the proportion of cases in advanced stages to total cases.

Ascitic Fluid↗

Distribution of activated B lymphocytes in the circulation and synovial fluid in rheumatoid arthritis.

The circulating peripheral blood of 13/28 patients with definite or classical rheumatoid arthritis (RA) had increased numbers of spontaneous in vivo active immunoglobulin-producing B lymphocytes detected by a reverse hemolytic PFC assay (mean = 3000 (1310-7920) Ig PFC/10(6) B cells) compared to an age/sex-matched control population (mean = 550 (300-900) Ig PFC/10(6) B cells). Among the remaining 16 RA patients who had normal numbers (less than 900 Ig PFC/10(6)) of such circulating B cells, 5 patients had increased numbers of activated B cells in the synovial fluid and 6 patients had no increase. Extraarticular features (nodules and vasculitis) in 11/13 patients and advanced but relatively inactive synovitis characterized those RA patients with increased numbers of active circulating B cells. In contrast, extraarticular features were seldom observed (1/16) among the remaining patients with normal numbers of active circulating B cells. Among these patients, more active generalized synovitis characterized those patients with increased numbers of active synovial fluid B cells compared to those patients with normal numbers. These studies imply that in RA patients, whose disease is primarily articular, active Ig synthesis is limited to the synovial compartment, while in those with extraarticular features active Ig-producing B cells also appear in the circulation.

Adolescent↗

Sarcomas of the uterine corpus: prognostic factors and treatment.

Twenty-eight patients with sarcomas of the uterine corpus were followed at least 22 months or until death. All underwent laparotomy, eleven had radiation therapy, and six had chemotherapy. Three year actuarial survival was 24%, and three year actuarial local control was 36%. Multivariate analysis demonstrated that, as with sarcomas at other sites, the most important factors influencing survival were grade (P = 0.020) and stage (P = 0.022). For local control, multivariate analysis indicated the most important factors to be stage (P = 0.001) and radiation TDF (P = 0.01). Of 21 failures, 16 involved the pelvis, seven involved the upper abdomen, and 11 involved distant sites. The importance of both local and distant disease control is emphasized.

Adult↗

Ependymoma of the broad ligament. A report of two cases.

The clinical and pathological features of two cases of ependymoma that originated in the broad ligament are reported. Metastases developed in both patients. The tumors had the distinctive features of ependymoma on light-microscopical examination, and the diagnosis was confirmed by ultrastructural study in one case and immunoperoxidase staining for glial fibrillary acidic protein in both cases. The tumors presented diagnostic difficulties because of their close resemblance to serous papillary carcinomas of the ovary and the absence of published reports of ependymoma occurring in the female genital tract.

Adnexa Uteri↗

Hashimoto's thyroiditis and polyarthritis: a possible subset of seronegative polyarthritis.

Fifteen patients presenting with inflammatory polyarthritis who had Hashimoto's thyroiditis were investigated. Only 2/15 had frank myxoedema, 8/15 had incipient hypothyroidism (raised levels of thyrotropin or early symptoms of mild hypothyroidism), and 5/15 were euthyroid (thyrotropin levels normal). The presence or absence of rheumatoid factor (RF) distinguished two subgroups with different severity of synovitis. Nine out of 15 (group A) who remained RF negative throughout their follow-up had mild polyarthritis, lacked nodules or erosions on x-ray, and required, in addition to thyroid replacement, non-steroidal anti-inflammatory drugs for control of synovitis. Six out of 15 who remained RF positive (group B) had more severe synovitis, nodules, and erosive x-ray changes, and some required remittive drug treatment to control their disease. HLA-DR2 was present in 67% of group A and 13% of group B patients, while HLA-DR4 was present in 67% of group B and 33% of group A. Group A patients may represent a subset of patients with Hashimoto's thyroiditis and seronegative inflammatory polyarthritis, while group B patients appear to have features suggesting the coexistence of both rheumatoid arthritis and Hashimoto's thyroiditis.

Adult↗

Anti-DNA autoantibody-producing hybridomas of normal human lymphoid cell origin.

Fusion of human myeloma cell line GM 4672 and tonsillar lymphoid cells from a normal donor resulted in 13 primary hybridomas, which produced IgM anti-single-stranded DNA (ssDNA) antibodies, as determined in enzyme-linked immunosorbent assay. Nine of these primary hybridomas have been cloned and a total of 34 clones were obtained. Supernatants of these cloned hybridomas were tested for binding to ssDNA, native DNA, RNA, low molecular weight supernatant DNA, polydeoxyguanylate-polydeoxycitidylate, polydeoxyadenylate-thymidylate sodium salt, and cardiolipin. Supernatants from all clones but one showed polyspecificity when reacting with the antigens tested. That the clones were true hybridomas rather than transformed lymphoid cells was evidence by IgM anti-DNA antibody secretion, karyotype analysis, and HLA typing. These studies imply that immunoglobulin genes encoding for anti-DNA autoantibodies with a spectrum of nucleic acid specificities similar to systemic lupus erythematosus, exist among normal B lymphocytes.

Antibodies, Monoclonal↗

HLA antigens in systemic lupus erythematosus: relationship to disease severity, age at onset, and sex.

Sixty-two Caucasian patients with systemic lupus erythematosus (SLE) were studied to determine whether any significant clinical correlations existed with various HLA antigens. While HLA-B8 and DR3 were significantly increased among the SLE population in general, these or other HLA antigens did not correlate with the severity of renal disease. HLA-B8 was significantly higher only in SLE males compared to male controls. The age of onset of disease in females was clustered into 2 groups, one with early age of onset (mean = 21.6 years, range 12-32 years) and another with later age of onset (mean = 48 years; range 38-60 years). SLE females with later age of onset showed an increased frequency of HLA-DR3 compared to sex and age matched controls, while those with early onset SLE showed no significant increase in any HLA antigens. Therefore any risk conferred by the presence of genes associated with HLA-B8 or DR3 is significant only in SLE males and SLE females whose disease onset was over the age of 35. Despite the greater frequency of HLA-B8, DR3 in SLE females with later onset of disease, this group did not have a greater frequency of anti-Ro antibodies compared to females with early age onset of SLE.

Adolescent↗

A comparison of serologic reactivity among SLE patients with or without anti-Ro (SS-A) antibodies.

The serum from 112 patients with systemic lupus erythematosus (SLE) was examined to compare serologic reactivity among anti-Ro positive and anti-Ro negative patients. While hypergammaglobulinemia, rheumatoid factor (RF) and elevated Clq binding were significantly more frequent among the anti-Ro positive group there was no increase in the frequency of anti-dsDNA antibody measured by the Farr assay or antibodies to ssDNA, dsDNA, poly dG . poly dC, poly (dA-dT) and cardiolipin measured by ELISA. Patients with the highest levels of anti-DNA antibody by the Farr assay did not have any increased frequency of anti-Ro antibodies. We concluded that anti-Ro and anti-DNA antibodies are independently regulated. The frequent occurrence of RF in anti-Ro positive SLE patients may provide a useful screening assay for this autoantibody among pregnant SLE patients.

Antibodies, Antinuclear↗

Antibody to rheumatoid arthritis associated nuclear antigen (RANA) in familial rheumatoid arthritis.

A search was made for the presence of antibody to the rheumatoid arthritis (RA) associated nuclear antigen (RANA) in the sera of 57 affected and unaffected members of 10 families with multiple members affected with RA. While anti-RANA was frequently observed among the seropositive affected individuals with definite or classical RA (60%), it was less frequently observed among those family members who had incompletely expressed disease, and rarely among normal close family members including those sharing haplotypes with the affected index case. An HLA haplotype containing B8, DR3 was more frequently seen among anti-RANA positive (61%) than anti-RANA negative (44%) RA patients. These data do not support a primary early role for the Epstein-Barr virus related antigen RANA in the etiology of RA. They may indicate a possible influence of the complete haplotype HLA-B8, DR3 on the expression of anti-RANA in established RA.

Adult↗

The fine structure of a virilizing human granulosa-theca cell tumor. Observations on the nature of the hormone producing cell.

The ultrastructure of a virilizing granulosa-theca cell tumor is reported. Although the histologic appearance is characteristic of a granulosa-theca tumor, several tumor cells contain crystalloids of Reinke which have not been associated with sex-cord-stromal tumors, but which are often present in ovarian hilus cells and Leydig cells. The steroidogenic cell in this case displays many fine structural features common to mammalian steroidogenic cells, namely abundant smooth endoplasmic reticulum, a dispersed Golgi, mitochondria with tubular cristae, and lipid droplets. Other features of this cell, which contains crystalloids of Reinke, more closely resemble those of a theca-lutein cell than a granulose-lutein or hilus cell and support a stromal origin. However, this tumor illustrates the striking overlap in morphologic features and function among granulosa, theca, hilus, and Leydig cells.

Adult↗

Role of aspiration cytology in the diagnosis and management of mammary lesions in office practice.

Sixteen hundred and eighty breast aspiration specimens obtained from 1410 patients seen in office practice were reviewed. The cytologic diagnosis was unsatisfactory in 230 cases, benign in 1019 cases, atypical in 198 cases, suspicious for malignancy in 102 cases, and malignant in 131 cases. All cases diagnosed as cytologically malignant had a subsequent tissue diagnosis of malignant neoplasm. Four percent of the cytologically benign cases and 17% of the cytologically atypical cases had malignant neoplasms. Clinical and cytologic examination detected more cancers (87%) than did clinical and mammographic examination (79%). Ninety-three percent of malignant neoplasms were detected by the combination of clinical, cytologic, and mammographic examination. Aspiration cytology significantly contributes to the clinical evaluation of mammary lesions in office practice, but it does not replace tissue biopsy or careful follow-up of mammary lesions of clinical concern. Proof of the presence of breast cancer by aspiration in the office may obviate the need for a two-stage procedure in the surgical management of breast cancer. Aspiration of minimally suspicious lesions often is helpful in initiating excisional biopsy in some occult, clinically unrecognized breast cancers.

Adult↗

Immunoregulation in rheumatoid arthritis: evaluation of T lymphocyte function in the control of polyclonal immunoglobulin synthesis in vitro.

Immunoglobulin production by peripheral blood B lymphocytes in cultures containing various combinations of B and T cells was studied by a reverse hemolytic plaque forming cell assay in 21 patients with definite rheumatoid arthritis (RA) and 26 normal controls. Responses were markedly enhanced in controls when T cells were irradiated at 3200 rads or T cells bearing Fc receptors for IgG were removed by rosetting prior to coculture with B cells, while no such responses were observed in rheumatoids. In allogeneic cultures and T depleted cultures supplemented by normal T replacing factors, RA B lymphocytes functioned normally. These data suggest that there is an abnormality in immunoregulation that exists at the level of the T cell and that the defect involves T helper cells and/or their interaction with B lymphocytes. An increase in the ratio of T helper:suppressor (OKT4:OKT5) cells due to a reduction in suppressor cells among active RA patients was observed but did not correlate with this defect that was independent of disease activity. These data imply that functional alterations exist in vitro in circulating helper T cells from RA peripheral blood.

Arthritis, Rheumatoid↗