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Biomedical subjects

G M Wood

Publications and source records attributed to G M Wood.

At least 19 recordsLinked to original sources
PubMed1992

Studies of bone marrow progenitor cells in lupus-prone mice. I. NZB marrow cells demonstrate increased growth in Whitlock-Witte culture and increased splenic colony-forming unit activity in the Thy-1-, lineage- population.

Previous studies have demonstrated that NZB marrow can transfer features of autoimmunity. Therefore, we undertook a study of NZB marrow to determine whether it demonstrated any phenotypic abnormalities. In Whitlock-Witte cultures, NZB marrow cells generated nonadherent cells at low seeding densities, densities at which marrow from other strains did not generate nonadherent cells. In contrast, NZB marrow grew less well than controls in Dexter cultures. Inasmuch as the latter favor growth of granulocyte-macrophage precursors and the former B cells, these results suggest a possible skewing of NZB marrow cells toward lymphocyte production. Unfractionated marrow cells from NZB mice were found to produce 10-fold more splenic colonies in lethally irradiated recipients than marrow cells from control mice. This result was independent of the genotype of the recipient. When the progenitor Thy-1lo, Lin- marrow subpopulation was studied, NZB mice did not differ substantially from controls regarding splenic CFU. Therefore, Thy-1-, Lin- marrow cells were studied as a possible source of the excess splenic CFU in NZB mice. Indeed, the NZB Thy-1-, Lin- population contained 30-fold more splenic CFU than did the Thy-1-, Lin- population from control mice. These results suggest that NZB mice have unusual marrow progenitor cells; such cells may play a role in their autoimmune disease.

Animals↗
PubMed1992

Clinical features of human infection with Scedosporium inflatum.

We report on 17 Australian cases of human infection or colonization with Scedosporium inflatum. The spectrum of clinical manifestations was similar to that in infection caused by Scedosporium apiospermum. The patients were classified into three groups. Four immunocompetent patients who presented with localized infections of a joint, nail bed, eye, or sphenoidal sinus made up the first group. Our first case, in a boy with posttraumatic septic arthritis, responded to surgical drainage with amphotericin B followed by treatment with itraconazole. The other three cases were cured by surgery alone. The second group consisted of five immunocompromised patients who presented with disseminated infections in a variety of sites. Four of these patients did not respond to antifungal therapy and died. The fifth apparently responded to antifungal drugs after correction of his neutropenia. The third group included eight patients with asymptomatic colonization in the external ear (five cases) or respiratory secretions (three cases). The nine isolates of S. inflatum tested by both disk and agar dilution methods were resistant to antifungal drugs. In our first case, which responded clinically to itraconazole, the MIC of this drug for the fungal isolate was 25 micrograms/mL. Thus S. inflatum can cause a broad spectrum of human infections whose severity and prognosis depend largely on the host's immune status.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Isolated hepatitis B core antibody--can response to hepatitis B vaccine help elucidate the cause?

The finding of a positive hepatitis B core antibody (anti-HBc) in the absence of hepatitis B surface antigen (HBsAg) or hepatitis B surface antibody (anti-HBs) is relatively uncommon. This finding is known to occur during the 'window period' of acute hepatitis B between loss of HBsAg and the appearance of anti-HBs. It may also occur with active infection or following resolution. The aim of this study was to determine if response to hepatitis B vaccination would allow the separation of these subgroups of patients with isolated anti-HBc. Seventeen patients with persistent isolated core antibody were vaccinated and serum obtained at 2, 4 and 8 weeks. Results were compared with a seronegative control group. Six subjects (35%) but no control patients (p = 0.016) responded with a titre of greater than 50mIU/mL at two weeks, suggesting an anamnestic response due to prior infection and immunity. A further seven subjects (41%) finally seroconverted (anti-HBs titre greater than 10mIU/mL) thus excluding chronic infection and suggesting initial false positive results. Only two subjects did not respond to a full course of vaccination, but neither they nor any other subjects were positive for HBV DNA. These results indicate that hepatitis B vaccination and subsequent measurement of anti-HBs will identify evidence of past infection in the form of an anamnestic response in up to one third of the patients and will also exclude chronic infection on the grounds of a normal vaccine response in a majority of the remainder.

Adult↗
PubMed1991

Is persistent adenovirus 12 infection involved in coeliac disease? A search for viral DNA using the polymerase chain reaction.

It has been shown that partial amino acid sequence homology between alpha gliadin and an early region protein (E1B-58 kDa) of adenovirus 12 results in immunological cross reaction. This led to the proposal that prior infection by adenovirus 12 could be associated with the development of coeliac disease. To examine this hypothesis, evidence was sought of persistent adenovirus 12 infection in the small intestinal mucosa of patients with coeliac disease. DNA isolated from biopsy samples from 24 control and 18 coeliac disease patients was analysed by the polymerase chain reaction for adenovirus 12 DNA encoding the E1B-58 kDa protein. Four of 18 coeliac disease and two of 24 control patients were positive. There is thus a low prevalence of this infection on both groups of patients but certainly no significantly increased incidence in coeliac disease. These results suggest that persistent adenovirus 12 infection is not a major element in the pathogenesis of coeliac disease.

Adenoviridae↗
PubMed1991

Small bowel morphology in British Indian and Afro-Caribbean subjects: evidence of tropical enteropathy.

Distal duodenal biopsy specimens taken from 30 white, 35 Indian, and 20 Afro-Caribbean residents of West Birmingham during routine endoscopy for dyspepsia, were assessed by dissecting microscopy and morphometry. Finger-shaped villi were significantly less frequent in the Indian and Afro-Caribbean subjects than in the white subjects when assessed by dissecting microscopy (p less than 0.005), and both immigrant groups had decreased mucosal thickness (p less than 0.01), villous height (p less than 0.001), villous:crypt ratios (p less than 0.01) and enterocyte height (p less than 0.05) compared with the white group. In the Indian subjects, villous height and villous:crypt ratios correlated significantly with the time since the last visit to the Indian subcontinent (p less than 0.005). Serum alkaline phosphatase values were significantly higher in the Indian subjects compared with the whites (p less than 0.02), and serum globulins were increased in both the Afro-Caribbean and Indian subjects (p less than 0.01). There were no correlations between morphometric indices and body habitus or biochemical or haematological indices and the long term effect of the morphological changes is not clear.

Adolescent↗
PubMed1989

Chronic liver disease. A case control study of the effect of previous blood transfusion.

A means of assessing hepatitis NANB virus infection, via blood transfusion, as a cause of chronic liver disease was investigated in a hospital in each of two cities in England. Patients with chronic liver disease were matched for age and sex with other patients in the same hospital and histories taken included details of previous operations and blood transfusions; if these were within ten years of the study enquiries were made of hospital records officers. All positive histories were found correct, but about one third of previous transfusions had been omitted by both case and control patients. Sixty-seven male and 35 female patients with chronic liver disease and their controls were included in analyses. The only clear difference which emerged related to residence for more than a year in the Middle or Far East by male case- (40%) or control- (21%) patients (P less than 0.05). The exclusion of patients with this history left only 34 pairs in which five (15%) of the case patients and one (3%) of the control patients had a transfusion history: this difference was not statistically significant. Although the study results have shown no clear evidence of blood transfusion as a major cause of chronic liver disease in Britain, the study method, with sufficient numbers to allow analyses of newly diagnosed patients with confirmed transfusion histories, could be used to provide an ongoing assessment of the risk.

Adolescent↗
PubMed1988

Vitamin K-dependent carboxylase. Stoichiometry of vitamin K epoxide formation, gamma-carboxyglutamyl formation, and gamma-glutamyl-3H cleavage.

The rat liver microsomal vitamin K-dependent carboxylase catalyzes the carboxylation of peptide-bound glutamyl residues to gamma-carboxyglutamyl (Gla) residues with the concomitant formation of vitamin K 2,3-epoxide (KO). These studies have demonstrated that the half-reaction, formation of KO, occurs in the absence of carboxylation at low glutamyl substrate concentration but that the ratio of KO/Gla approaches unity as the glutamyl substrate concentration is increased. Utilization of the carboxylase substrate Phe-Leu-[gamma-3H] Glu-Glu-Leu has demonstrated that the ratios of KO/gamma-C-H bonds cleaved and Gla/gamma-C-H bonds cleaved are equivalent at high substrate concentrations and that these ratios approach unity. At low substrate concentrations, KO formation occurs at a higher rate than gamma-H bond cleavage. These data are consistent with a mechanism involving the formation of an oxygenated intermediate from vitamin KH2 and O2 that is converted to KO during hydrogen abstraction from the gamma-position of the Glu substrate. In the absence of a Glu substrate, the intermediate is converted to KO by a mechanism not coupled to glutamyl activation.

1-Carboxyglutamic Acid↗
PubMed1987

ELISA for measurement of secretory IgA distinct from monomeric IgA.

A micro enzyme-linked immunoassay (ELISA) is described for the quantitation of secretory IgA as distinct from monomeric IgA. The assay is sensitive (linear down to 30 ng/ml) and reproducible (inter-assay variation: 17.0%; intra-assay variation: 11.5%). The assay has the further advantages of rapidity, the ability to handle large numbers of samples, and uses commercially available reagents throughout. Minimal interference from a large (greater than 25-fold) excess of monomeric IgA was observed. The results obtained for serum secretory IgA concentrations by this method correlated well with those reported by other workers for normal control patients, patients with IgA deficiency and patients with liver disease.

Enzyme-Linked Immunosorbent Assay↗
PubMed1987

Chronic hepatitis B carriers found at blood donation: do they need regular follow-up?

It is recommended by the Department of Health and Social Security that hepatitis B virus (HBV) carriers found at blood donation should be followed up by specialist liver units. We attempted to do this in 74 such patients found by the Yorkshire Regional Blood Transfusion Service during a 4.5-year period. Only 32 of the patients eventually attended for further investigation and follow-up. However, 43 chronic HBV carriers found at blood donation have been followed for varying periods from 2 to 14 years, and the prognosis has been good. Although this raises the question as to whether such carriers need to be seen routinely in a specialist unit, we suggest that there are good reasons to continue to advocate this policy.

Biopsy↗
PubMed1987

Disappearing hypercalcaemia.

Four women presented with symptomatic hypercalcaemia and raised concentrations of serum parathyroid hormone (PTH). In each case, serum calcium returned spontaneously to normal. In two patients serum PTH also fell to the normal range and biochemical relapse has not occurred despite prolonged follow-up. In the others, serum PTH remained elevated and subsequent symptomatic hypercalcaemia necessitated parathyroidectomy. In the first two cases, autoparathyroidectomy is the most likely explanation; the initial fall in serum calcium in the other two patients is unexplained. Large fluctuations in serum calcium may occur in some patients with hyperparathyroidism and prolonged and careful observation is required when this occurs.

Aged↗
PubMed1987

Jejunal plasma cells and in vitro immunoglobulin production in adult coeliac disease.

IgA, IgE, IgG and IgM plasma cells in small bowel mucosal biopsies from 15 controls, 16 untreated and 14 treated coeliac patients and five patients with selective serum IgA deficiency (four of whom also had coeliac disease) were quantified using an indirect immunoperoxidase technique. The IgA, IgG and IgM plasma cell counts were significantly increased in the untreated coeliac patients. The cell counts were intermediate in the treated coeliac group. These changes were in parallel to production in vitro of IgA and sIgA, IgG, and IgM by cultured mucosal biopsies from the same patients. The IgA deficient patients had very few mucosal IgA cells but elevated IgG and IgM plasma cell numbers; again these changes were reflected in the production in vitro of immunoglobulins. IgE plasma cell counts were very low in all patients and there were no differences between patient groups. The changes in cell counts and mucosal immunoglobulin production were not reflected in serum IgA, IgM and IgG concentrations but serum secretory IgA was significantly elevated in the untreated coeliac patients compared with controls, with the treated coeliac patients being intermediate. The raised mucosal plasma cell counts reflect the local mucosal production of immunoglobulin but not the immunoglobulin concentrations of serum, emphasising the importance of studying the immune function of the gut itself in coeliac disease rather than immunological abnormalities in serum.

Adolescent↗
PubMed1987

Organ culture of fetal rat small intestine for testing gluten toxicity: a reappraisal.

Jejunal segments from fetal rats of 18 days gestation were maintained in an organ culture system for up to 72 h. During this period, villi developed within the intestinal lumen and the epithelium changed from stratified to simple columnar. Peristaltic activity was observed during in-vitro culture. Alkaline phosphatase specific activity of the bowel segments fell after 48 hours culture, compared with pre-culture values (P less than 0.05), but that of alpha-glucosidase increased. The addition of Frazer's gluten fraction III to the culture medium caused slowing in the rate of morphological maturation of the jejunal explants, but there was no additional effect on enzyme specific activities compared with segments cultured in gluten-free medium. The place of organ culture of fetal rat intestine as an animal model for testing cereal toxicity in the study of coeliac disease remains unclear.

Animals↗
PubMed1986

Immunoglobulin production by coeliac biopsies in organ culture.

The production of immunoglobulins by jejunal mucosa during organ culture has been studied. In 18 untreated coeliac patients the amounts of IgA, secretory IgA and IgM in the culture medium were higher than in those from 17 normal controls. The results in 15 treated coeliac patients did not differ from the control subjects. Mucosal biopsies from patients with serum IgA deficiency produced very little IgA, but large amounts of IgG and IgM. The addition of neither Frazer's gluten fraction III, nor alpha-gliadin to the culture system stimulated any additional increased secretion of immunoglobulins from the untreated coeliac patients. Production of IgA and IgM by the small bowel mucosa continues during organ culture, but that of IgG appears insignificant.

Adolescent↗
PubMed1986

Secretion of gliadin antibody by coeliac jejunal mucosal biopsies cultured in vitro.

The role of gliadin antibodies in coeliac disease is unknown. We have investigated this by maintaining jejunal biopsies from control subjects, treated and untreated coeliac patients in organ culture for 24 h. The tissue culture supernatants were assayed by enzyme-linked immunosorbent assay (ELISA) for total IgG, IgM and IgA, anti-gliadin and casein antibodies. Jejunal biopsies from untreated coeliac patients secreted more total IgM and IgA but not IgG, than biopsies from control subjects: values for treated coeliac patients were similar to those from control subjects. There was increased secretion of IgG and IgM gliadin antibody, but not casein antibody, by jejunal biopsies from untreated coeliac patients compared with those from control subjects.

Antibody Formation↗
PubMed1985

The microenvironment of coeliac disease: T cell phenotypes and expression of the T2 'T blast' antigen by small bowel lymphocytes.

Peroral jejunal biopsies were studied by double-label immunofluorescence on cryostat tissue sections from control patients of normal histology and patients with coeliac disease. A panel of monoclonal antibodies was used to identify T cells and T cell subsets, together with antibody markers of cell stimulation (the T2 40 kdalton T blast specificity), proliferation (T9 and Ki67) and activation (HLA-DR and Ig receptors). In normal mucosa, expression of T2 was predominantly found in the T8+ intraepithelial cytotoxic/suppressor population. In coeliac disease there was little alteration of T4:T8 ratios per se, but a much higher percentage of T8-T4+ helper/inducer cells expressed the T2 antigen (approx. 30% compared to approx. 10%), manifest as an accretion of T2+T8- cells in the epithelium and subjacent stroma. Additionally, T cell lymphoid aggregates were observed in the lamina propria, consisting of greater than 90% T4+ cells, of which the majority (60-80%) were also T2+. The increase of stimulated helper cells correlated well with the pathology of coeliac disease, being most marked in untreated cases of maximal tissue damage, and least in well treated cases with restoration of normal morphology. By contrast, an increased tendency for the T8+ cells to co-express T1 in untreated coeliac disease was not observed in treated disease, even in cases where failure to adhere to a strict gluten free diet had resulted in little histological improvement. There was little evidence of T cell activation or proliferation. The observation that T helper cells undergo migration and stimulation suggests an imbalance in immunoregulation which causes a breakdown of normal immune tolerance to dietary gluten, and therefore may be a crucial mechanism of tissue damage in coeliac disease.

Adolescent↗
PubMed1979

The relation between skin histamine concentration, histamine sensitivity, and the resistance of cattle to the tick, Boophilus microplus.

Cattle with different degrees of resistance to Boophilus microplus have responses to tick allergen which correlate with their resistance level. The total amount of histamine in the skin also correlates with both resistance and the immediate hypersensitivity reactions, but the sensitivity to injected histamine does not. Treatment with the antihistamine drug mepyramine maleate suppresses the cutaneous hypersensitivity reactions. The results suggest that the main pharmacologically active agent in these reactions is histamine, and that the total amount of it available locally in the skin may have a role in the resistance to this parasite.

Allergens↗