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Biomedical subjects

D A Bell

Publications and source records attributed to D A Bell.

At least 253 records · Page 14Linked to original sources
PubMed1978

Loss of self-tolerance to single-stranded deoxyribonucleic acid (sDNA) in vitro.

The spleens of many normal and autoimmune-susceptible strains of mice mount a specific, IgM, anti-sDNA plaque-forming cell (PFC) response in vitro in the absence of an exogenous source of antigen. This response was not related solely to levels of xenotropic or ecotropic virus and was generated from a small number of precursor cells capable of binding sDNA. Small numbers of anti-sDNA PFC were also apparent in serum-free medium and the response of low-responder strains could be augmented with pokeweed mitogen. T cells and macrophages were not essential and cell division was required early in culture to obtain a peak response on day 5. These results suggest that autoantigen-sensitive cells may escape normal regulatory mechanisms in vitro and differentiate into clones of autoantibody secreting cells.

Animals↗
PubMed1978

Regulation of the autoimmune plaque-forming cell response to single-strand DNA (sDNA) in vitro.

We have shown that young autoimmune and normal strain mice possess autoantigen-sensitive cells potentially capable of producing anti-sDNA autoantibody in the absence of normal regulatory mechanisms in vitro. In certain strains such as B/W mice, these regulatory mechanisms presumably break down with increasing age, and autoimmunity develops. These regulatory mechanisms might consist of sDNA, T cells, or some combination of these since both of these agents suppressed the anti-sDNA PFC response in vitro. The sDNA may have inhibited PFC development by a receptor blockade mechanism since i) spleen cells pulsed with sDNA for short periods and then washed were suppressed after 5 days of culture; ii) treatment of these blocked cells with trypsin and DNase I restored the anti-sDNA response; iii) the PFC remaining in partially blocked cultures were of lower avidity than PFC in unblocked cultures; and iv) the target of sDNA may be a B cell. Thymocytes and splenic T cells suppressed the anti-sDNA response but not the anti-SRBC response in vitro in a dose-dependent manner. The suppressive capacity of thymus cells did not decline with age in B/W mice. In addition, thymus cells activated by competing foreign antigens could also suppress the anti-sDNA response. The relationship between these modes of regulating autoreactivity remains to be investigated.

Animals↗
PubMed1978

Regulation of the immune response in autoimmune NZB/NZW F1 mice. II. Age dependent release of suppressive factors from spleen cells.

Supressor cells in the spleens of overtly autoimmune NZB X NZW (B/W) mice, but not age matched normal strain mice, were shown to release a small, less than 20,000 Dalton factor which inhibited early events in the anti-SRBC PFC response and the mitogenic response. This splenic inhibitory factor (SIF) was (i) stable on heating (56 degrees, 30 min) and freezine (-70degrees); (ii) non-specific for antigen; (iii) absorbed and/or inactivated by target cells in young B/W spleen cell cultures and (iv) released gradually into the culture medium by metabolically active cells. SIF also blocked the T-cell replacing effect of allogeneic factor (TRF) in the anti-SRBC response. These observations suggest that SIF may lead to the immunodepressed state in overtly autoimmune B/W mice by preventing the activation or differentiation of lymphocytes responding to exogenous antigen.

Aging↗
PubMed1978

Immunological senescence. I. The role of suppressor cells.

The in vitro anti-SRBC response of several murine strains declined markedly with age in parallel with an increase in the activity of suppressor cells in the spleen and bone marrow which prevented early events during the induction of the immune response. These suppressor cells released soluble mediators and lacked the characteristics of mature T cells or macrophages. In addition the suppressor cell in the bone marrow could be removed on anti-Ig columns and fractions of old splenic suppressor cells sedimenting at 0.32 cm/h were greatly enriched in surface Ig bearing cells. Old immunodepressed mice did not lack potentially immunocompetent cells since the antibody response of old spleen cells could be restored by specifically activated T cells or lipopolysaccharide which act on B cells. These results suggest that a rise in the activity of non-T suppressor cells in the spleen and bone marrow may account, in part, for the depression in humoral immunity observed in aging mice.

Aging↗
PubMed1978

Regional differences in the morphology and motility of mesodermal cells from the early wing-bud of normal and talpid3 mutant chick embryos.

A method of culturing has been employed to compare the properties of cells migrating from small mesodermal explants taken from different regions of normal and mutant limb-buds at different stages of development. An analysis by time-lapse cinematography of the morphology and mobility of cells migrating from explants defines a distal region within the limb-bud where these properties are distinct from those of cells from more proximal regions. In the normal wing-bud distal cells subjacent to the apical ectodermal ridge possess a characteristic multipolar morphology and translocate slowly in vitro. Cells from more proximal regions tend to be bipolar and translocate more rapidly. Distal and proximal cells also probably differ in their adhesive strengths. In the mutant, talpid3, distal and proximal cells do not differ in the above properties and cells from all regions of the limb-bud are multipolar, translocate slowly and are more adhesive than normal cells. A study of light micrographs and scanning electron micrographs suggests that these regional differences are found in the limb-bud in vivo and are not merely an effect produced by the in vitro culturing system.

Animals↗
PubMed1976

Cell interaction in B/W mice: a reversible defect at the T-cell level.

The anti-SRBC PFC response of old B/W mice can be restored by adding specifically activated T cells or primed spleen cells in vitro as well as by injecting LPS and SRBC in vivo. Since nonresponsive old B/W bone marrow and thymocytes cooperated in a normal manner upon adoptive transfer, this suggested that the lack of response to SRBC in the intact animal was due to a block in T cell activation and not due to intrinsic defects in lymphoid cells necessary to initiate a response. The block in T cell activation might be mediated by a suppressor cell found in old B/W spleens and it was hypothesized that this suppressor might also lead to a loss of self-tolerance.

Aging↗
PubMed1975

Studies with human leukocyte lysosomes. Evidence for antilysosome antibodies in lupus erythematosus and for the presence of lysosomal antigen in inflammatory diseases.

Human lysosomes were isolated from normal peripheral blood leukoyctes and characterized by electron microscopy, enzyme analysis, and assays for DNA and RNA. Stored sera from 37 unselected patients with systemic lupus erythematosus (SLE), including active and inactive, treated and untreated cases, were tested in complement fixation (CF) reactions with these lysosome preparations. 23 SLE sera exhibited positive CR reactions, as did sera from two patients with "lupoid" hepatitis. The seven SLE sera with strongest CF reactivity also demonstrated gel precipitin reactions with lysosomes. Neither CF nor precipitin reactions with lysosomes were observed with normal sera or with sera of patients with drug-induced lupus syndrome, rheumatoid arthritis (RA), polymyositis, or autoimmune hemolytic anemia. By several criteria the antilysosome CF and precipitin reactions of SLE sera cound not be attributed to antibody to DNA, RNA, or other intracellular organelles. The lysosomal component reactive with SLE sera in CF assays was sedimentable at high speed and is presumably membrane associated. The CF activity of two representative SLE sera was associated with IgG globulins by Sephadex filtration. A search for lysosomal antigen in SLE and related disorders was also made. By employing rabbit antiserum to human lysosomes in immunodiffusion, a soluble lysosomal component, apparently distinct from the sedimentable (membrane-associated) antigen described above, was identified in serum, synovial fluid, or pleural fluid from patients with SLE, RA, ankylosing spondylitis, and leukemoid reaction. An antigenically identical soluble component reactive with the rabbit antiserum could be released in vitro from intact lysosomes by repeated freeze-thaw cycles..

Anemia, Hemolytic, Autoimmune↗
PubMed1975

T cell activation and cellular cooperation in autoimmune NZB/NZW F hybrid mice.

Old (6 months) overtly autoimmune female NZB X NZW F1 (B/W) mice were markedly hyporesponsive to sheep erythrocytes (SRBC). The response to SRBC was restored by a) simultaneously injecting lipopolysaccharide (LPS) with SRBC or b) transferring bone marrow and thymocytes with SRBC into lethally x-irradiated (100 R) syngeneic old recipients. The in vitro PFC response of old B/W spleen cells to SRBC was restored by adding in culture a) theta-positive and radioresistant spleen cells from old B/W mice primed with homologous antigen or b) activated T cells from the spleens of lethally x-irradiated (1000 R) old B/W mice injected with old syngeneic thymocytes and SRBC but not horse erythrocytes. Various populations of unprimed lymphoid cells from young (4 to 6 weeks) female B/W mice, which respond normally to SRBC, were not capable of restoring the response of old syngeneic mice in vitro or in vivo. These results suggest the existence of a suppressor of T cell activation and/or B and T cell interaction in old autoimmune B/W mice.

Absorption↗
PubMedDate not supplied

Percutaneous nephrostomy for nonoperative management of fungal urinary tract infections.

PURPOSE: Percutaneous nephrostomy has proved to be an important modality in the nonoperative treatment of bacterial pyonephrosis. The role of this technique in the management of fungal pyonephrosis continues to evolve. The authors retrospectively reviewed their experience with percutaneous nephrostomy in the management of fungal pyonephrosis. PATIENTS AND METHODS: Seven patients, two neonates and five adults, were identified with proved fungal infections. Eleven percutaneous nephrostomy tubes were placed, all with use of the Seldinger technique. RESULTS: Percutaneous nephrostomy allowed (a) prompt microbiologic diagnosis of fungal infection (Candida albicans in six patients, Torulopsis glabrata in one); (b) urinary diversion with subsequent improvement in renal function, enabling systemic administration of potentially toxic antifungal drugs 5-fluorocytosine and amphotericin B (four patients); (c) local irrigation with amphotericin B (four patients), (d) guidewire fragmentation of fungus balls (two patients); and (e) introduction of a Simpson atherectomy device to obtain biopsy specimens from an obstructing ureteral polypoid lesion (one patient). The funguria was successfully eradicated in six patients, one of whom died on the 39th hospital day of a pulmonary embolus and another of whom died of extensive small bowel infarction during hospitalization. The one patient whose outcome of antifungal treatment remains unknown died at home with a functioning percutaneous nephrostomy 23 days after the procedure. CONCLUSION: Percutaneous nephrostomy may play a role in the non-operative management of fungal urinary tract infection.

Aged↗
PubMedDate not supplied

Detached ciliary tufts mistaken for peritoneal parasites: a warning.

Detached ciliary tufts of columnar epithelial cells from the female genital tract may be mistakenly identified as protozoa when examined in wet mounts of fluid specimens in the laboratory because of their appearance and motility, although they are generally identified correctly in fixed specimens prepared for cytologic examination. A case of such mistaken identity in specimens from a gynecologic patient was documented, and the literature on ciliary tufts was reviewed. Infectious disease and gynecology consultants should be alert to the potential confusion arising from the presence of ciliary tufts in body fluids.

Adult↗
PubMedDate not supplied

Benign glandular cells in posthysterectomy vaginal smears.

OBJECTIVE: To investigate the occurrence and origin of benign glandular cells in posthysterectomy vaginal smears and to propose a categorization for these cells under the Bethesda system. STUDY DESIGN: Among 4,986 posthysterectomy vaginal smears during a 3.5-year period, 82 patients were identified with smears containing benign glandular cells. The review of the smears, related biopsies and charts form the basis of this report. A control group of 236 posthysterectomy smears without glandular cells from the same period was reviewed. RESULTS: Smears were available for review on 76 of 82 patients. All were within normal limits or showed benign cellular changes. All contained clearly benign glandular cells, most frequently present in groups. In all smears, pale pink-red intracellular mucin was identified either diffusely within the cytoplasm or within vacuoles. The glandular cells appeared as hybrid parabasal-endocervical type, squamous metaplastic or columnar cells. Associated cytologic findings included atrophy, inflammation, blood and repair. Reactive atypia was present in 10 (13%) cases. Biopsies were performed on 40 (48%), all showing benign changes. In four of five cases stained, intracellular mucin was seen within glandular cells. Chart review revealed that the patients' hysterectomies were performed for removal of a malignant tumor in 58 (71%) of the study group and in 100 (42%) in the comparison group and that 48 (58%) of the study group had received radiotherapy and/or chemotherapy, while only 26 (11%) of those in the comparison group had similar therapy. CONCLUSION: The presence of benign glandular cells in posthysterectomy vaginal smears is an infrequent but not rare finding. This study indicated an association with benign processes and showed a frequent association with prior radiation or chemotherapy. A more appropriate designation under the Bethesda System is "benign cellular changes" rather than "glandular cell abnormalities." An aggressive workup does not appear to be warranted in this group of patients. We speculate that this phenomenon represents a metaplastic process, possibly secondary to radiation or chemotherapy.

Adenocarcinoma↗
PubMedDate not supplied

Cytologic features of endometrial papillary serous carcinoma.

Endometrial papillary serous carcinoma (EPSC) is an uncommon variant of endometrial carcinoma that histologically resembles ovarian serous carcinoma and has an aggressive clinical course. The cytomorphologic features of 17 patients with histologically confirmed EPSC of the endometrium were reviewed and compared with those of 20 patients with histologically typical endometrial adenocarcinoma (TEC). Preoperative cervicovaginal Papanicolaou smear results were available from 14 of the 17 patients with EPSC; 10 (71%) were positive, 1 (7%) was suspicious and 3 (21%) were negative for malignancy. Initial cervicovaginal smear results were available from all 20 patients with TEC; 7 (35%) were positive, 4 (20%) were atypical or suspicious and 9 (45%) were negative for malignancy. Twelve patients with EPSC had peritoneal washings or fluids examined; seven were positive and five negative. Twelve patients with TEC had peritoneal washings or fluids examined; two (17%) were positive and ten (83%) were negative. The cervicovaginal smears from patients with EPSC revealed numerous large tumor cells (with prominent nucleoli) frequently arranged in papillary clusters with background necrosis and, in two cases, amorphous material suggestive of psammoma bodies. In contrast, the smears of patients with TEC showed small to medium-sized cells with extensive phagocytosis and many background histiocytes. The diagnosis of EPSC should be considered when the cervicovaginal smear contains numerous papillary groups of large tumor cells with macronucleoli but without prominent phagocytosis, especially when structures suggestive of psammoma bodies are present. The peritoneal fluids in these patients are more often positive than in patients with TEC, a finding consistent with the propensity of EPSC to involve peritoneal surfaces.

Adenocarcinoma↗
PubMedDate not supplied

Fine needle aspiration cytology of focal liver lesions. Results obtained with examination of both cytologic and histologic preparations.

The results of 197 consecutive fine needle aspirations (FNA) of focal liver lesions performed on 176 patients were reviewed, and the 176 single most diagnostic aspirates were analyzed in detail. The majority of specimens were obtained using a 20-gauge or 22-gauge needle with ultrasound guidance. An attempt was made to obtain both a cytologic and a tissue specimen from each aspirate. The overall accuracy of the procedure was 85%; the accuracies of the tissue and cytologic specimens were 67% and 73%, respectively. The combined procedure detected 81% of the documented malignant tumors; the tissue specimen detected 62%. Eleven tumors were identified only in the tissue specimen and 23 were identified only in the cytologic specimen. There were no false-positive diagnoses. Six of nine hepatocellular carcinomas were detected. These results show that FNA cytology is a safe, accurate, relatively noninvasive technique whose diagnostic yield may be improved by examination of both a histologic tissue and a cytologic preparation.

Adult↗