PubMed Health⌕ Search

Biomedical subjects

D B Jones

Publications and source records attributed to D B Jones.

At least 253 records · Page 14Linked to original sources

Alteration of H2 receptor sensitivity in duodenal ulcer patients after maintenance treatment with an H2 receptor antagonist.

The effects of a specific H2 receptor agonist impromidine, on gastric acid secretion were measured in six patients with duodenal ulcer in clinical remission before and after three months treatment with ranitidine 150 mg nocte. After treatment basal acid output increased from 1.2 to 2.8 mmol/h and after maximal impromidine stimulation from 36.9 (4.7) to 44.2 (6.2) mmol/h (p less than 0.02). Intravenous ranitidine 50 mg was given at the end of the impromidine infusion on each study day; the antisecretory effect of intravenous ranitidine was accentuated after the treatment with ranitidine from a trough acid output of 8.5 (1.2) mmol/h before, to 3.8 (1.5) mmol/h (p less than 0.05) after, treatment. The increased response to the H2 agonist impromidine and the H2 antagonist ranitidine after treatment with ranitidine suggests an enhanced sensitivity of the H2 receptor. This might be explained on the basis of an increase in the number of H2 receptors ('up-regulation').

Adult↗

CD3+ CD8+ T cell lymphocytosis masking B cell leukaemia.

A patient with CD3, CD8 positive lymphocytosis presented with features consistent with T cell chronic lymphocytic leukaemia/proliferations of large granular lymphocytes. The marrow and blood lymphoid populations (19.4 x 10(9)/l) contained more than 80% CD3 and CD8 positive cells with no evidence of a monotypic B cell population. A biopsy specimen of a vasculitic rash showed a diffuse infiltrate of CD3, CD8 positive cells into the upper dermis, consistent with T cell lymphocytic disease. After follow up for two years without treatment the blood lymphocyte count was 53 x 10(9)/l and was composed of cytologically small lymphocytes. A monoclonal SIg M D k lymphoid population (more than 90%) was demonstrable in sample blood and marrow aspirate. Gene rearrangement studies carried out on DNA extracted from peripheral blood lymphocytes at presentation and at two year follow up exhibited JH and Ck immunoglobulin gene rearrangement but no rearrangement of T cell receptor TcR gamma and beta genes. It is thought that this is the first well documented case of an aggressive CD8 positive lymphocytosis preceding, or in response to, an underlying B cell neoplasm.

Antigens, Differentiation, T-Lymphocyte↗

Mac 387 antibody and detection of formalin resistant myelomonocytic L1 antigen.

The murine monoclonal antibody Mac 387 was raised against a purified protein fraction obtained from human monocytes. By immunoblotting experiments, Mac 387 was shown to react with a previously defined antigen called L1; this is a multichain myelomoncytic protein of about 36 Kd which shows sequence homology with the cystic fibrosis antigen. The L1 protein is present in the cytoplasm of virtually all resting peripheral neutrophils and monocytes; it is also variably expressed on the plasma membrane of these cells, possibly as a secretory product. Because the L1 antigen is resistant to denaturation by formalin, its tissue distribution can be studied in routinely processed biopsy material. In a wide variety of specimens Mac 387 was shown by immunohistochemical analysis, to produce a cytoplasmic staining pattern concordant with that of a well defined polyclonal antibody to the L1 antigen. Cytoplasmic reactivity was obtained with granulocytes and infiltrating macrophages but generally not with several categories of dendritic cells. In addition, squamous epithelium of mucous membranes was strongly positive, in contrast to normal epidermis.

Antibodies, Monoclonal↗

Comparison of the detection of breast carcinoma metastases by routine histological diagnosis and by immunohistochemical staining.

The detection of metastases in 371 axillary lymph nodes by immunohistochemical staining and by routine histological examination was compared in the surgically removed tissue from 50 consecutive patients with breast carcinoma. The primary tumour and axillary lymph nodes were stained with three monoclonal antibodies directed against epitopes of the human milk fat globule (HMFG1; HMFG2; E29), and an anticytokeratin antibody (CAM 5.2), in a double-bridge immunoalkaline phosphatase staining technique. Metastases revealed by further sectioning through the tissue were identified before the immunohistological comparison. The use of immunohistochemical staining resulted in an increased detection of metastases in both infiltrating ductal carcinoma (13.1%) and infiltrating lobular carcinoma (37.5%), an overall increase of 17.3%. The follow-up data over a minimum period of 2 years is available for these patients.

Adenocarcinoma↗

Rapid development of nephrotic syndrome, hypertension, and hemolytic anemia early in pregnancy in patients with IDDM.

In recent years, the prognosis for a successful pregnancy has greatly improved for women with insulin-dependent diabetes mellitus (IDDM) who are under good glycemic control and free of complications such as vascular disease and nephropathy. We report the rapid development of severe nephrotic syndrome, malignant hypertension, and microangiopathic hemolytic anemia during the first trimester of pregnancy in a 29-yr-old woman with IDDM of 18 yr duration. Our patient had no pregestational history of retinopathy or hypertension and only minimal proteinuria. Significant improvement in blood glucose levels had been achieved over the 6 mo before conception. Kidney biopsy performed before the termination of pregnancy at 10 wk gestation revealed diabetic nephropathy. No other etiology for her renal disease could be found. An arteriole was noted to have entrapped red blood cell fragments and platelet thrombi, revealing the probable source of her hemolytic process. By 8 wk postpartum, her nephrotic syndrome and hemolysis had completely resolved. At 3 mo postgestation, the patient's hypertension was still present but less severe. Her serum creatinine has continued to decrease toward normal. This is the first report of a woman with IDDM in White's classification C who developed a toxemia-like syndrome during the first trimester of pregnancy, attributable to the underlying diabetic state.

Adult↗

Quantitative and qualitative enzyme studies of Hodgkin's disease-derived cell lines.

Any extensive analysis of Hodgkin (H) and Reed-Sternberg (RS) cells is limited by the scarcity of available material and by the common contamination with "by-stander" cells. The establishment of Hodgkin's disease-derived cell lines provides the opportunity to undertake studies in which large numbers of cells are required, as these cell lines are by definition monoclonal populations with unlimited cell growth. In this study, we analyzed the enzyme profiles of eight Hodgkin's disease cell lines (Co, Ho, Fox, HDLM-2, KM-H2, L428, L540, and L591) whereby cellular alpha-naphthyl acetate esterases, acid phosphatases, and dipeptidylpeptidase IV were examined quantitatively or qualitatively by IEF or chromatographic techniques. The results indicate that all of the H-RS cell lines examined had enzymatic features typical for lymphoid cells and, in particular, a monocyte/histiocyte origin of the cell lines could be excluded. Extrapolation of the available immunological, molecular biological, and enzymological evidence gained in vitro on cultured representatives of H-RS cells suggests a lymphoid origin for in vivo H-RS cells.

Acid Phosphatase↗

An immunohistological study of CD4+ lymphocyte subsets within inflammatory lesions with special reference to rheumatoid arthritis and inflammatory bowel disease.

The monoclonal antibodies (mAbs) WR16, UCHL1 and WR19 identify subsets of CD4+ lymphocytes that have been functionally characterized as suppressor inducer cells or helper inducer cells. These were applied as components of a panel of lymphocyte-specific mAbs for the phenotypic analysis of lymphocyte populations within biopsies taken from rheumatoid synovial membrane and normal and inflamed gut. The phenotype of peripheral blood lymphocytes from patients with rheumatoid arthritis were also compared to normal controls. The rheumatoid synovium was characterized immunohistologically by a lymphocytic infiltrate composed predominantly of CD4+ lymphocytes and a CD4:CD8 ratio of 2.4. The CD4+ population was composed of UCHL1+ cells to the exclusion of WR16+ cells. This finding was confirmed by double immunofluorescence staining using directly conjugated Leu-3a and WR16. The UCHL1+/WR16-/CD4+ phenotype was maintained in the synovial biopsies regardless of whether the patient had commenced treatment with disease modifying drugs. The absence of WR16+ cells within the rheumatoid synovium was shown to be a localized phenomenon as there was a slight elevation of circulating WR16+ lymphocytes in the peripheral blood of rheumatoids whilst the levels of UCHL1+ and WR19+ lymphocytes remained unchanged. As no appropriate normal control tissue is available for comparison to the rheumatoid synovium we also examined the lymphocytes present within Crohn's disease-involved bowel biopsies and compared them to normal gut tissue lymphocytes using WR16 and UCHL1 mAbs. The CD3+ lymphocytes present within normal tissue comprised a mixture of WR16+ and UCHL1+ cells. In contrast the CD3+ lymphocytes within Crohn's involved tissue were exclusively UCHL1+ as previously observed in the rheumatoid synovium. These data indicate that the CD4+ lymphocyte infiltrate present within inflammatory lesions of presumed distinct aetiology exhibit a localized selective loss of cells with the CD45R+/CD4+ suppressor inducer phenotype. This may be a consequence of the selective extravasation of CD4+ helper induced cells or more likely, in view of the previously documented loss of the p220 molecule identified by CD45R mAbs upon T-cell activation, the result of CD4+ T-cell activation at sites of inflammation.

Arthritis, Rheumatoid↗

Small bowel and colonic permeability to 51Cr-EDTA in patients with active inflammatory bowel disease.

51Cr-EDTA was administered both orally and per rectum via a catheter to controls and to patients with inflammatory bowel disease. The patients were divided into two groups, either with active inflammation of the small bowel or with active inflammation of the colon. Fifteen patients with Crohn's disease of the small bowel and 19 patients with either Crohn's disease of the colon or ulcerative colitis were investigated. After oral administration of the probe, controls showed a median excretion of 1.17%/24 h of the dose compared to 3.47%/24 h by patients with small bowel disease and 6.07%/24 h by patients with colonic disease. After rectal administration, controls showed a median excretion of 0.74%/24 h of the dose compared to 0.93%/24 h by patients with small bowel disease and 5.73%/24 h by patients with colonic disease. The rectal test differentiated small bowel disease from colonic disease with an accuracy of 85%. The results confirmed the inflamed colon as a site of increased intestinal permeation.

Adult↗

Reye's syndrome-like illness in a patient receiving amiodarone.

A 16-yr-old boy who was receiving amiodarone for ventricular arrhythmias developed a Reye's syndrome-like illness several days after an upper respiratory infection. Liver biopsy revealed microvesicular fat and spotty hepatocellular necrosis, typical of Reye's syndrome. Recovery was complete. This case report suggests that medications other than aspirin may predispose to Reye's syndrome, and that children receiving amiodarone should receive prophylaxis against influenza B and chicken pox.

Adolescent↗

Phenotype versus immunoglobulin and T-cell receptor genotype of Hodgkin-derived cell lines: activation of immature lymphoid cells in Hodgkin's disease.

Three Hodgkin-derived cell lines (L428, L540, and CO) were studied for rearrangements and expression of immunoglobulin and T-cell receptor genes, and their genotype was compared to the phenotype. As far as the genotype is concerned, all 3 cell lines have characteristics of lymphoid cells; L428 of B, and L540 and CO of T-cell origin. L428 cells have one Ig heavy chain allele rearranged to C gamma and transcribed into RNA, while the second is deleted. Furthermore, L428 cells show an unusual immunoglobulin kappa light chain gene rearrangement involving deletion of the kappa constant gene in one allele, while the remaining kappa and lambda loci are in germline configuration. L540 and CO have, in contrast to L428 cells, the immunoglobulin genes in germline and T-cell receptor genes rearranged. The T-cell receptor beta and gamma genes are rearranged in both L540 and CO, whereas a rearrangement in the alpha locus was detected in L540 cells only. RNA of the size of functional beta chain transcripts was found in CO cells and of the size of functional alpha chain transcripts in L540 cells. All 3 cell lines are classified as immature lymphoid cells with respect to the limited expression of B- and T-cell antigens, respectively, and to the incomplete expression of their antigen receptor. The immaturity of lymphoid differentiation contrasts with the expression of activation antigens, i.e. Ki-1, Ki-24, HLA-DR, and IL-2 receptor. The immaturity of the cells excludes the possibility that the cells were activated along the physiological pathway, i.e. by interaction of the cell with antigen. The results obtained on the cell lines are in accordance with in vivo studies and suggest that Hodgkin and Sternberg-Reed cells are immature lymphoid cells which are activated by a still unknown mechanism.

Cell Line↗

Lens capsule abnormalities in Alport's syndrome.

The ultrastructure of the glomerular basement membrane in Alport's syndrome is well known and characteristic of this disease, but the anterior lenticonus that frequently occurs in this syndrome has not been similarly studied. An anterior lens capsule from a 30-year-old patient with lenticonus who had Alport's syndrome was obtained at capsulectomy and found to be one third the normal thickness centrally and to be more fibrillar than usual. There were large numbers of partial capsular dehiscences containing fibrillar material and vacuoles. Cellular debris and more recent ruptures of lens epithelial cell membranes underlaid the breaks. The anterior capsule is clearly fragile in this disease, forming the basis for the progressive lenticonus and anterior polar cataract. These abnormalities correlate well with a defect in the type IV collagen molecule, as has been recently reported in Alport's syndrome.

Adult↗

Use of the monoclonal antibody WR17, identifying the CD37 gp40-45 Kd antigen complex, in the diagnosis of B-lymphoid malignancy.

The distribution of the gp40-45 Kd antigen bound by the WR17 monoclonal antibody of IgG2 subclass in normal lymphoid tissue was characterized by immunohistochemistry and immunofluorescence staining with flow cytometric analysis. The predominant staining pattern observed was characteristic of an anti-pan-B-lymphocyte reagent. Weak reactions were observed by immunofluorescence staining of viable cell suspensions with all neutrophils and T-lymphocytes in some normal donors. In tissue sections, B-lymphocytes were stained and no cross reactions were observed with T-lymphocytes, although macrophages stained in some sections. A range of T- and B-cell malignancies were stained with WR17 and the reactivity compared to that observed with other monoclonal antibodies in the CD19, CD21 and CD22 clusters. All B-non-Hodgkin's lymphomas, B-chronic lymphocytic, prolymphocytic and hairy cell leukaemia cells examined were stained by WR17 in indirect immunofluorescence assays, whilst the T-cell tumours were negative. The same pattern was observed in cryostat sections of malignant tissue and in addition some tissue macrophages expressed the CD37 antigen cytoplasmically. Intra-tumour heterogeneity of staining was observed with all the monoclonal antibodies tested, although overall WR17 consistently stained B-cell tumours even when expression of the CD19 pan-B-lymphocyte antigen could not be detected with some monoclonals. Monoclonal antibodies, such as WR17, within the CD37 cluster and binding to the gp 40-45 Kd molecule, bind to mature B-lymphocytes and identify the majority of B-cell malignancies.

Antibodies, Monoclonal↗

Identification of cells of the human mononuclear phagocyte system with rat monoclonal antibodies.

Five rat monoclonal antibodies (McAbs) to human macrophages are described: YTH 8.18, YTH 25.7, YTH 51.1, YTH 85.12.1, and YHB 65.5. These McAbs are divided into three groups, since YTH 8.18, YTH 51.1, and YHB 65.5 are thought to identify the same antigen. These McAbs react with some bone marrow blast cells, granulocytes, and different percentages of peripheral blood monocytes. When studied on different body tissues, they were found to identify all members of the mononuclear phagocyte system (MPS), except Langerhans cells of skin and epithelium and in the case of one group (YTH 8.18/YTH 51.1/YHB 65.5) osteoclasts. In nine reactive lymph nodes the anti macrophage McAbs identified germinal centre macrophages, sinus macrophages, and interdigitating cells, but not dendritic reticulum cells. They also identified epithelioid macrophages and Langhans-type multi-nucleated giant cells in lymph nodes involved in granulomatous lesions (sarcoidosis and toxoplasmosis). In 24 cases of non-Hodgkin's lymphoma, the antimacrophage McAbs identified reactive macrophages in cases of B- or T-lymphocyte origin, whereas in three selected cases of true histiocytic lymphoma all the McAbs were found to be reactive with the vast majority of neoplastic macrophages as they were with the cells of a neoplastic macrophage line (U937). The possible use of these McAbs in the identification of benign and malignant macrophages in different systems is discussed.

Animals↗