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Biomedical subjects

N Parker

Publications and source records attributed to N Parker.

At least 37 records · Page 2Linked to original sources
PubMed1994

Proliferative responses of HT29 and Caco2 human colorectal cancer cells to a panel of lectins.

BACKGROUND/AIMS: Altered lectin binding is common in malignant and premalignant epithelia, but its functional significance is unclear. This study examined the proliferative effects of four lectins on HT29 and Caco2 colon cancer cells. METHODS: Proliferation was assessed in log growth and confluent culture by thymidine incorporation and cell counts. Peanut agglutinin (PNA) binding was characterized by Scatchard analysis and electrophoresis of lectin affinity-purified cell surface-radiolabeled preparations. RESULTS: PNA, 5 micrograms/mL, increased thymidine incorporation in HT29 but had no effect on Caco2. Wheat germ agglutinin and concanavalin A stimulated proliferation slightly at 0.5-1.0 microgram/mL but were inhibitory at higher concentrations. Ulex europaeus 1 had no significant effect. Similar results were obtained when proliferation was assessed by cell counts and with confluent cell cultures. Scatchard analysis with both cell lines showed multisite best fit models with similar binding affinities. Three PNA-binding glycoproteins were identified in both cell lines, but two were of lower molecular weight in HT29 than in Caco2. Membrane preparations from a resected colorectal cancer contained a 30-kilodalton PNA-binding glycoprotein similar to that in HT29 cells. CONCLUSIONS: Lectins are plentiful in the normal diet and often escape digestion. This study suggests that altered expression of lectin receptors, particularly the upregulation of PNA receptor seen in colonic malignancy and hyperplasia, may have an important role in growth modulation.

Carcinoma↗
PubMed1994

Peanut lectin stimulates proliferation in colonic explants from patients with inflammatory bowel disease and colon polyps.

BACKGROUND/AIMS: The TF antigen (galactose-beta 1,3-N-acetylgalactosamine alpha) is overexpressed in malignant and premalignant colonic epithelium. Previous studies have shown that peanut lectin (PNA), which binds TF, is mitogenic for normal human colonic epithelium. This study aimed to determine its effect on abnormal colonic epithelium. METHODS: Crypt cell proliferation rate (CCPR) was measured using vincristine arrest and mucus synthesis by incorporation of radiolabeled N-acetyl glucosamine in colonoscopic biopsy specimens cultured with and without PNA. RESULTS: Unstimulated CCPR was greater in patients with ulcerative colitis than in patients with histologically normal colon. PNA (25 micrograms/mL) produced a 25% average increase in CCPR in tissues from patients with ulcerative colitis, Crohn's disease, and colonic polyps. In ulcerative colitic biopsy specimens incubated with PNA, CCPR increased to more than double that of unstimulated normal colonic epithelium. In controls, the response to PNA was greater when adjacent specimens were positive for PNA (avidin-biotin) histochemistry than when they were negative. Mucus synthesis was increased by an average 75% over 24 hours by PNA. CONCLUSIONS: Increased TF expression by premalignant epithelia may allow stimulation of proliferation by dietary galactose N-acetylgalactosamine-binding lectins. If the hyperplasia-dysplasia cancer hypothesis is correct, this could explain the increased colon cancer risk in ulcerative colitis.

Acetylglucosamine↗
PubMed1993

Re-entry syndrome.

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Cross-Cultural Comparison↗
PubMed1993

Dose-dependent induction or depression of cysteine conjugate beta-lyase in rat kidney by N-acetyl-S-(1,2,3,4,4-pentachloro-1,3-butadienyl)-L-cysteine.

The influence of N-acetyl-S-(1,2,3,4,4-pentachloro-1,3-butadienyl)-L-cysteine (NAc-PCBD) on cysteine conjugate beta-lyase in female rat kidney has been examined. After a single, non-nephrotoxic dose of NAc-PCBD (3 mg/kg), cytosolic beta-lyase enzyme activity was increased 1.5 to 3-fold commensurate with a corresponding increase in enzyme protein levels as assessed by both Western blot and ELISA analyses. Using a cDNA probe for beta-lyase, this induction was found to be accompanied by an increase in the cognate mRNA. In contrast, a higher, nephrotoxic dose of NAc-PCBD (10 mg/kg) decreased all the above parameters. These effects appeared to be specific to the cytosolic form of the enzyme as no changes in kidney mitochondrial beta-lyase or enzyme protein levels were observed. Repeated dosing with the lower dose level (3 mg/kg) resulted in either no change, or in some instances, a reduction in the above parameters, suggesting an accumulation of the xenobiotic and a masking of the induction phenomenon. The molecular mechanisms underlying these observations are discussed in terms of the nephrotoxicity of halogenated xenobiotics.

Acetylcysteine↗
PubMed1993

Distribution of O-acetylated sialomucin in the normal and diseased gastrointestinal tract shown by a new monoclonal antibody.

AIMS: To produce and characterise a monoclonal antibody specific for O-acetylated sialomucin and to assess its use in immunohistochemistry on a panel of normal and diseased intestinal tissue samples. METHODS: Mouse monoclonal antibodies were developed following immunisation with highly purified human colonic mucin. One of these (MMM-17) showed strong binding to mucin throughout the normal colon with relative lack of binding to colon cancer tissue. The binding epitope of MMM-17 was then characterised by screening for agglutination activity against a panel of human and animal erythrocytes and by assessment of its binding to a range of normal and chemically treated slot blotted mucins. Further immunohistochemical studies were then performed on formalin fixed, normal, and diseased human intestinal samples. RESULTS: Binding of MMM-17 to slot blotted human colonic mucin was reduced by 38 (SD 14%) (n = 4) by alkali treatment of the mucin, sequential alkali and sialidase treatment completely abolished binding. Sialidase treatment alone, however, caused only an 11 (11%) reduction in binding. MMM-17 failed to agglutinate any human, rabbit, rat or mouse erythrocytes. These findings were compatible with specificity of MMM-17 for sialomucins O-acetylated at the C-7 or C-8 positions on the sialic acid. Strong staining by MMM-17 was found in all goblet cells throughout all 40 normal colonic and rectal samples studied, but staining was absent in seven of 13 colorectal carcinomas. Normal duodenum (n = 16) and normal ileum (n = 3) all showed occasional positive goblet cells. The normal gastric antral mucosa was generally negative B MMM-17, but in all of 15 cases of gastritis with intestinal metaplasia the metaplastic glands were strongly positive for MMM-17. CONCLUSION: Monoclonal antibody MMM-17 has specificity for O-acetylated sialomucins and its binding depends both on the position of O-acetylation and on the adjacent oligosaccharide structure. Preliminary studies using the antibody on archival tissue samples support the previous reports of reduced O-acetylation in colon cancer demonstrated by indirect histochemistry and show the neo-formation of O-acetylated sialomucin in intestinal metaplasia in the stomach.

Animals↗
PubMed1992

A new enzyme-linked lectin/mucin antibody sandwich assay (CAM 17.1/WGA) assessed in combination with CA 19-9 and peanut lectin binding assay for the diagnosis of pancreatic cancer.

BACKGROUND: Mucus glycoproteins are often present in the sera of patients with pancreatic cancer, and their detection and quantification can be used in serologic diagnosis. METHODS: A novel enzyme-linked "sandwich" assay (CAM 17.1/WGA) has been developed in which a lectin, wheat germ agglutinin (WGA), is bound to the solid phase to capture serum glycoproteins, and after addition of test sera, a monoclonal antimucin antibody (CAM 17.1) and peroxidase-tagged second antibody are used as a detection system. RESULTS: The test has been applied to sera from 79 patients with pancreatic cancer and 120 controls. The CAM 17.1/WGA assay alone had a sensitivity of 78% and specificity of 76% in the diagnosis of pancreatic cancer. Combination of the CAM 17.1/WGA test with a previously described peanut lectin binding assay (PNA/ELLA) provided a sensitivity of 92% and specificity of 70%, whereas combination of the CAM 17.1/WGA assay with the CA 19-9 radioimmunoassay had a sensitivity of 85% and specificity of 76%. Combination of all three tests had a sensitivity of 94% and specificity of 66%. In nonjaundiced patients, the combination of CAM 17.1/WGA and PNA/ELLA had a sensitivity of 93% and specificity of 79% in the diagnosis of pancreatic cancer. CONCLUSIONS: This new test adds significantly to the armamentarium of serologic tests for pancreatic cancer. These tests are particularly effective when used in combination to detect different mucin-borne carbohydrate antigens. They deserve more widespread use, particularly in examining nonjaundiced patients with unexplained abdominal pain or weight loss.

Adolescent↗
PubMed1992

Sulphation of colonic and rectal mucin in inflammatory bowel disease: reduced sulphation of rectal mucus in ulcerative colitis.

1. Normal colonic mucin is heavily sulphated and this increases its resistance to degradation by bacterial enzymes. Any defect in mucus sulphation could therefore be important in the pathogenesis of ulcerative colitis. 2. Rectal biopsies taken at colonoscopy from patients with ulcerative colitis (n = 9), patients with Crohn's disease (n = 6) and control subjects (n = 16) were cultured for 24 h in the presence of N-[3H]acetylglucosamine and [35S]sulphate. Mucin was then extracted and purified, and the ratio of [35S]sulphate to N-[3H]acetylglucosamine incorporated into pure mucin was assessed. 3. The ratio of [35S]sulphate to N-[3H]acetylglucosamine incorporated into mucin was significantly reduced in rectal biopsies taken from patients with ulcerative colitis (0.463, 0.305-0.703, geometric mean and 95% confidence intervals) compared with control subjects (0.857, 0.959-1.111, P < 0.01). In patients with Crohn's disease the reduction in this ratio (0.559, 0.378-0.829) did not quite reach statistical significance (P = 0.06). There was no difference between the ratio of [35S]sulphate to N-[3H]acetylglucosamine incorporated into mucin in Crohn's disease and that in ulcerative colitis (P = 0.26). 4. In control subjects the ratio of [35S]sulphate to N-[3H]acetylglucosamine incorporated into mucin was higher in the rectal biopsies (0.882, 0.618-1.022) than in their paired proximal colonic biopsies (0.602, 0.421-0.861; P < 0.01), but this regional variation was not observed in either ulcerative colitis (rectum: 0.450, 0.262-0.773; right colon: 0.470, 0.321-0.690, P = 0.3) or Crohn's disease (rectum: 0.459, 0.260-0.815; right colon: 0.492, 0.260-0.929, P = 0.8).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Ion exchange chromatography of purified colonic mucus glycoproteins in inflammatory bowel disease: absence of a selective subclass defect.

Previous reports of a selective mucin subclass defect in ulcerative colitis have been reassessed using high performance chromatography (Superose 6 and Mono Q) for mucin purification and fractionation coupled with analysis of the fractions obtained using a combination of enzyme linked lectin and mucin antibody assays. Mucin samples purified from snap frozen rectal biopsy specimens obtained from patients with ulcerative colitis (n = 12), Crohn's disease (n = 5), and non-inflammatory bowel disease control subjects (n = 9) were subject to ion exchange chromatography using a continuous 0-0.35 mol/l NaCl salt gradient with a final 2.5 mol/l NaCl step. In all samples the major proportion (mean (SD) 86.7 (8.9)%) of the mucin detectable by wheat germ agglutinin binding eluted between 0.15 and 0.35 mol/l NaCl with no significant difference in elution profile between ulcerative colitis and control subjects. Significant elution of glycoprotein at less than 0.15 mol/l NaCl did occur, however, when a lower molecular weight mucin containing fraction which contained concanavalin A positive (glucose or mannose containing) material was analysed similarly. Similar ion exchange profiles were obtained when (3H)N-acetylglucosamine labelled mucins were studied after tissue culture of rectal biopsy specimens. No significant alteration in the ion exchange profile of purified mucins in ulcerative colitis has been shown in these studies. It is possible that the previously reported relative depletion of mucin subclass IV (eluting with 0.20 mol/l NaCl) may simply have reflected mucin depletion.

Chromatography, Ion Exchange↗
PubMed1991

The Garry David case.

A prisoner with an antisocial personality disorder had almost completed his sentence for attempted murder and there was considerable public concern over his imminent release. The article discusses the many attempts made by the Victorian Government during the past six months to detain him. A recommendation was made to change the Mental Health Act 1986 by including personality disorders as a form of "mental illness". The outcome of such advice has enormous implications for the practice of psychiatry in Victoria.

Antisocial Personality Disorder↗
PubMed1989

Ganser syndrome.

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Accidents↗
PubMed1987

Macrocytic anaemia due to copper deficiency in a patient with late onset hypogammaglobulinaemia.

Very few cases of acquired severe copper deficiency have been described. The principal effects are haematological, but the precise abnormalities are uncertain due to the possible association of other deficiencies. A case of isolated severe copper deficiency associated with late onset hypogammaglobulinaemia is reported in which the chief findings were macrocytic anaemia, neutropenia and a decrease in mean platelet volume. All these abnormalities resolved when copper therapy was instituted and recurred when the medication was stopped.

Agammaglobulinemia↗