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Biomedical subjects

W F Doe

Publications and source records attributed to W F Doe.

106 records · Page 6Linked to original sources
PubMed1972

Five cases of alpha chain disease.

Five patients suffering from alpha chain disease are described. Clinically the patients presented with clubbing and the symptoms of malabsorption. There was a characteristic, predominantly plasma cell infiltrate of the wall of the small intestine. Spread of the plasmacytosis beyond the small intestine to bone marrow (1), peripheral blood (1), and probably the nasopharyngeal lymphoid tissue (1) is described. Fragments of the heavy chain of IgA (alpha chain) were found in serum (5), urine (3), jejunal fluid (2), and saliva (1). The jejunal biopsy of one patient was shown to synthesize free alpha chain in tissue culture. A new and simple immunoselection technique for the identification of free alpha chain is described. Marked clinical remissions were achieved in two patients treated with intermittent cytotoxic and steroid therapy, and in a third patient who received intermittent cytotoxic therapy and tetracycline.

Abdomen↗
PubMed1972

Intrajejunal volatile fatty acids in the stagnant loop syndrome.

In the stagnant loop syndrome an abnormal anaerobic flora colonizes the small bowel. Anaerobic organisms are characterized by fermentation reactions leading to the production of volatile fatty acids. This paper describes the measurement of intrajejunal volatile fatty acid concentrations in 11 patients with the stagnant loop syndrome. Nine normal persons and 18 patients with gastrointestinal disease without intestinal stasis acted as controls. Acetate and propionate concentrations were greatly increased in the patients with the stagnant loop syndrome and returned to normal in those patients treated with antibiotics. The measurement of intrajejunal volatile fatty acid concentrations as an index of overgrowth of anaerobic organisms is discussed.

Acetates↗
PubMed1972

Coeliac disease, vasculitis, and cryoglobulinaemia.

Four patients are described with the association of adult coeliac disease, vasculitis, and cryoglobulinaemia. In each patient the cryoglobulinaemia was of the mixed type consisting of more than one immunoglobulin class. It is suggested that the mixed cryoglobulins represent circulating immune complexes and that their deposition in small vessels causes the vasculitis. This is supported by immunofluorescent studies of skin biopsies from one of these patients. The significance of these findings in the four adult coeliac patients is discussed.

Adult↗
PubMedDate not supplied

Immunopathology of coeliac disease.

Coeliac disease may be defined as a condition in which there is an abnormal jejunal mucosa with loss of villi, which improves morphologically after treatment with a gluten-free diet. Pathologically, there is damage to the jejunal enterocytes, with hyperplasia of crypt cells so that overall enteropoiesis is increased. On conventional or scanning electron microscopy the enterocytes are markedly abnormal. Histochemically, the normal punctate appearance of the lysosomes is lost and sensitive lysosomal enzyme assays on mucosal biopsy samples using isopycnic centrifugation techniques show that there is an increase in total lysosomal activity with reduction in lysosomal latency. Studies following gluten feeding in patients whose mucosa has returned to normal after treatment with a gluten-free diet show that pathological abnormalities appear within 4--8 hours of gluten challenge. Complement together with extracellular IgM can be demonstrated in the lamina propria, suggesting the formation of immune complexes. In untreated coeliac disease there is a significant reduction in serum levels of C3 and C4. There is also evidence indicating the presence of immune complexes in the serum. Coeliac disease may therefore be an intestinal model of an immune complex disease, in which an antigen derived from gluten reacts with an antibody formed locally in the gut, fixing complement and causing damage to the enterocyte by activation of lysosomes.

Adult↗
PubMedDate not supplied

Intestinal lymphokine-activated killer cells in inflammatory bowel disease.

The role of non-specific cytotoxicity in the pathogenesis of inflammatory bowel disease (IBD) was investigated by assaying the natural killer (NK) and lymphokine-activated killer (LAK) cell activity of lamina propria mononuclear cells (LPMC) from 22 specimens of intestinal mucosa affected by IBD. Only minimal levels of NK activity were detected against K562 cells, as well as colon carcinoma cells, adenoma cells and fibroblasts freshly isolated from the intestinal mucosa. Culture of LPMC from IBD in the presence of interleukin-2 (IL-2) generated LAK cells that mediated high levels of activity against K562 cells and against neoplastic epithelial cells and fibroblasts derived from the intestinal mucosa. A group of 20 histologically normal specimens of intestinal mucosa showed similar levels of LAK activity against the K562 and intestinal cell targets. The minimal mucosal NK activity in IBD suggests that the cytotoxic properties of NK cells are not important in the pathogenesis of IBD. The presence of LAK precursor cells in the inflamed mucosa of IBD and their ability to lyse biologically relevant targets in vitro suggests that LAK cells have the potential to contribute to intestinal mucosal injury in IBD.

Colitis, Ulcerative↗
PubMedDate not supplied

Chromosomal localization of the human urokinase plasminogen activator receptor and plasminogen activator inhibitor type-2 genes: implications in colorectal cancer.

Activation of the proenzyme of urokinase (uPA) on the surface of cancer cells has been implicated in the initiation of focal proteolytic mechanisms that permit invasion and metastasis by colon cancers. The activity of uPA on the cell surface appears to be a function of the number of uPA-specific receptors (uPAR) and the extent of inhibition of uPA by plasminogen activator inhibitors (PAI). The mapping of the genes coding for uPAR, and for PAI-2, was performed to determine whether their chromosomal localization suggested their involvement in the genetic alterations associated with cancer cell DNA. This study confirms the localization of the human urokinase plasminogen activator receptor gene to chromosome 19q and, using in situ hybridization, provides a precise localization to chromosome 19q13.2. In addition, our results confirm the previous allocation of the human plasminogen activator inhibitor-2 gene to a location 18q21.3-->18q22.1, a location that corresponds to the commonest (> 70%) somatic deletions found in colorectal carcinomas. The mapping of the uPAR and PAI-2 genes enables the elucidation of their possible involvement in the genetic alterations that determine the invasive and metastatic phenotypes in colorectal cancer.

Chromosome Mapping↗
PubMedDate not supplied

Chromosome 2p linkage analysis in hereditary non-polyposis colon cancer.

Hereditary non-polyposis colon cancer (HNPCC) comprises 2-6% of the total colorectal cancer burden. Two families are described that show linkage between the HNPCC susceptibility gene and the markers D2S123 and D2S119 on chromosome 2p, producing multipoint lod scores of 3.62 and 3.83, respectively, in the largest pedigree. In our third family the multipoint lod scores for D2S123 and D2S119, -2.97 and -3.12, excluded localization of a susceptibility gene in this region indicating that there is at least one more gene that causes predisposition to HNPCC. The exclusion was based on at least one genotype for an individual who had multiple primary colon and extracolonic tumours and could not be considered to have had common forms of cancer. Our results therefore encourage further gene mapping to pursue the localization of additional HNPCC genes. These findings confirm the presence of the susceptibility gene for HNPCC, COCA1, on chromosome 2p. They allow the immediate identification of a subset of HNPCC families, and provide the means for presymptomatic testing of family members if sufficient number of members are available for study.

Chromosomes, Human, Pair 2↗
PubMedDate not supplied

Direct evidence of monocyte recruitment to inflammatory bowel disease mucosa.

Alterations in phenotype and function of intestinal macrophages occur in inflammatory bowel disease (IBD) but it is unclear whether these changes result from the recruitment of circulating monocytes to the intestine or from proliferation of resident intestinal macrophages. We sought to demonstrate the arrival of blood monocytes, the precursors of macrophages, in IBD mucosa. Peripheral blood mononuclear cells were isolated from 23 patients with clinically active intestinal inflammation (13 Crohn's disease, eight ulcerative colitis, two infective colitis), then radiolabelled with 99mtechnetium (Tc)-stannous colloid (n = 13) or 111indium (In)-oxine (n = 10) before re-injection and abdominal scanning. Four patients had demonstrable intestinal monocyte uptake using [99mTc]-stannous colloid, while six [111In]-oxine-labelled monocyte scans were positive. Uptake sites correlated with actively inflamed regions. Patients demonstrating monocyte uptake had been treated with corticosteroids for a significantly (P < 0.02) shorter duration (median 3 vs 20 days) than those with negative scans. There was no significant difference between positive and negative scans for disease category, clinical or histological disease, activity, or radioisotope used. Biopsies of inflamed mucosa from two patients suffering ulcerative colitis who had positive scans showed a high proportion of CD14-positive macrophages, 4-9% of which contained autoradiographic grains. These results demonstrate that blood monocytes are recruited to the mucosa of actively inflamed bowel, and suggest that this process may be inhibited by corticosteroids. Moreover, the phenotype of the recently-arrived monocytes indicates their susceptibility to stimulation by lipopolysaccharide, and suggests a mechanism for the continuing inflammation in the bacterial product-rich milieu of IBD.

Adolescent↗