Immunoglobin synthesis by fresh biopsy cells and established cell lines from Burkitt''s lymphoma

(1) Freshly dispersed cells from four Burkitt's lymphoma biopsies, and three `lymphoblast' cell lines (OB2, OB3 and OB6) derived from the tumour were tested for capacity to synthesize immunoglobulins in vitro.

Using labelled amino acid incorporation, electrophoretic, radio-immunoelectrophoretic and ultracentrifugation techniques, it was possible to demonstrate the release of labelled proteins with antigenic characteristics of immunoglobulins by all four biopsy samples, and the two cell lines tested by these techniques. Newly synthesized labelled proteins were demonstrable in the culture medium within 1 hour of incubation.

In a separate series of experiments, absorption and immunodiffusion techniques were used in the characterization of proteins synthesized by two cell lines (OB2 and OB3) growing as healthy continuous cultures.

(2) Freshly isolated cells from Burkitt's lymphoma are capable of immunoglobulin synthesis in vitro. Cells from all four fresh biopsy materials produced IgG. One cell line (OB2) produced IgG and type-κ light chains, while OB6 cell line produced IgA. Immunoglobulin synthesis was not detected in OB3 cell line by immunodiffusion technique.

(3) Cells from each biopsy specimen or cell line produced not more than one type of immunoglobulin, although there was a wide variation in the sedimentation coefficient of the protein molecules synthesized by one (OB6) and presumably all other cell lines.

     

Value of whole-cell antigen extracts for serologic detection of Helicobacter pylori.

Whole-cell protein extracts of Helicobacter pylori strains were evaluated by enzyme-linked immunosorbent assay to detect immunoglobulin G antibody against H. pylori in 113 patients with upper gastrointestinal complaints. These antigen preparations were of value for detecting infection by H. pylori in patients with high antibody titers (> or = 12,800), whereas for patients with lower titers, the results were inconclusive.     

Use of H2-receptor antagonists in patients with dyspepsia and heartburn: a cost comparison.

OBJECTIVE: Under the Pharmaceutical Benefits Scheme, the use of H2-receptor antagonists (H2A) in the treatment of dyspepsia and heartburn is only subsidised when there is a proven diagnosis of ulcer. This study compared the costs of this Australian practice with a simulation of British practice, which allows unrestricted prescribing of subsidised H2A. DESIGN: Patients with heartburn and/or dyspepsia were prospectively randomised to either a "British" group treated freely at the discretion of their general practitioner without necessarily being investigated or an "Australian" group where use of H2A was allowed only after gastroscopy or a barium meal had demonstrated a peptic ulcer or ulcerative oesophagitis. The patients were followed up for six months and all direct and indirect costs were recorded. SETTING: Forty-nine Sydney general practitioners recruited primary care patients for the study. PATIENTS: Any patient with heartburn or dyspepsia was considered for recruitment; 139 patients entered the study and 137 completed it. MAIN OUTCOME MEASURES: The outcome measures were the costs of general practitioner consultations, specialist consultations, radiology and gastroscopy, other tests, H2A, other medications, personal costs, and total cost per patient. RESULTS: The cumulative total cost per patient at the end of the study was equivalent in the "Australian" ($392) and "British" ($406) groups. A higher initial cost per patient of H2A in the "British" group was offset by a rapid decrease in the proportion that continued to use H2A and by the cost of specialist consultations and investigations in the "Australian" group. CONCLUSION: Over a six-month period the cost of early investigation of heartburn and dyspepsia was equivalent to the cost of a therapeutic trial of H2A.     

Effect of age, Helicobacter pylori infection, and gastritis with atrophy on serum gastrin and gastric acid secretion in healthy men.

Gastric acid secretion has been considered to decline with increasing age but this view is being re-evaluated as the importance of Helicobacter pylori infection emerges. This study aimed to determine the effect of age, H pylori, and gastritis with atrophy on the serum gastrin concentration, gastric secretory volumes, and acid output in healthy, asymptomatic men. Young men (mean (SD) age 22.9 (0.6) years; n = 22) were compared with old men (72.9 (1.2) years; n = 28) in respect of basal serum gastrin and basal, sham fed, pentagastrin stimulated maximal and peak acid secretion. Antral, corpus, and fundal biopsy specimens were taken for histology and H pylori status (histology, culture, and rapid urease test). H pylori associated gastritis was present in three of 22 young (13.6%) and 16 of 28 old (57.1%) men. Gastritis with atrophy was present in 11 old subjects, 10 of whom were H pylori positive. These subjects had higher mean (SD) serum gastrin concentrations than old subjects without atrophy and young subjects (61.8 (9.2); 40.0 (2.9); 36.8 (2.3) pmol/l respectively; p < 0.001). H pylori infected subjects had higher gastrin values than uninfected subjects, overall (55.3 (5.9); 36.0 (1.8) pmol/l; p < 0.001) and in subjects without atrophy (45.3 (4.2); 36.0 (1.8) pmol/l; p < 0.03). In subjects without H pylori infection, gastrin values did not differ with age (old 37.1 (1.7); young 35.4 (2.1) pmol/l). The maximal gastric secretory volume was lower in old subjects with atrophy. Acid output (mmol/h) in subjects with atrophy was lower than in subjects with no atrophy (basal: 3.0(1.1); 5.1(0.7); p=NS; sham led: 5.4 (1.4); 9.3 (0.8); p<0.02; maximal: 18.9 (4.0); 31.4(1.8); p<0.002; peak: 25.1(5.3); 43.4(2.7); p<0.003). However, acid secretion in old subjects without atrophy was not different to that in young subjects, irrespective of H pylori status. These results did not differ when acid output was expressed as mmol/h/kg lean body mass or mmol/h/kg fat free body weight. Using multiple linear regression analysis, gastritis with atrophy was the only factor that had an independent negative effect on acid secretion. In healthy men without atrophy, gastric acid secretion is preserved with ageing and is independent of H pylori status. Atrophy, which is closely related to H pylori infection, is associated with a decline in acid secretion. Increased basal serum gastrin is related to both atrophy and H pylori infection but not to ageing per se.     

Treatment of Lesch–Nyhan disease with S-adenosylmethionine: Experience with five young Malaysians,including a girl

Background: Lesch–Nyhan disease (LND) is a rare X-linked recessive neurogenetic disorder caused by deficiency of the purine salvage enzyme hypoxanthine phosphoribosyltransferase (HPRT, EC 2.4.2.8) which is responsible for recycling purine bases into purine nucleotides. Affected individuals have hyperuricemia leading to gout and urolithiasis, accompanied by a characteristic severe neurobehavioural phenotype with compulsive self-mutilation, extrapyramidal motor disturbances and cognitive impairment. Aim: For its theoretical therapeutic potential to replenish the brain purine nucleotide pool, oral supplementation with S-adenosylmethionine (SAMe) was trialed in 5 Malaysian children with LND, comprising 4 related Malay children from 2 families, including an LND girl, and a Chinese Malaysian boy. Results: Dramatic reductions of self-injury and aggressive behaviour, as well as a milder reduction of dystonia, were observed in all 5 patients. Other LND neurological symptoms did not improve during SAMe therapy. Discussion: Molecular mechanisms proposed for LND neuropathology include GTP depletion in the brain leading to impaired dopamine synthesis, dysfunction of G-protein-mediated signal transduction, and defective developmental programming of dopamine neurons. The improvement of our LND patients on SAMe, particularly the hallmark self-injurious behaviour, echoed clinical progress reported with another purine nucleotide depletion disorder, Arts Syndrome, but contrasted lack of benefit with the purine disorder adenylosuccinate lyase deficiency. This first report of a trial of SAMe therapy in LND children showed remarkably encouraging results that warrant larger studies.     

Bleeding events and associated factors in a cohort of adult patients taking warfarin in Sarawak,Malaysia

Evidence is emerging that rates of adverse events in patients taking warfarin may vary with ethnicity. This study investigated the rates of bleeds and thromboembolic events, the international normalised ratio (INR) status and the relationship between INR and bleeding events in Malaysia. Patients attending INR clinic at the Heart Centre, Sarawak General Hospital were enrolled on an ad hoc basis from May 2010 and followed up for 1 year. At each routine visit, INR was recorded and screening for bleeding or thromboembolism occurred. Variables relating to INR control were used as predictors of bleeds in logistic regression models. 125 patients contributed to 140 person-years of follow-up. The rates of major bleed, thromboembolic event and minor bleed per 100 person-years of follow-up were 1.4, 0.75 and 34.3. The median time at target range calculated using the Rosendaal method was 61.6 % (IQR 44.6–74.1 %). Of the out-of-range readings, 30.0 % were below range and 15.4 % were above. INR variability, (standard deviation of individuals’ mean INR), was the best predictor of bleeding events, with an odds ratio of 3.21 (95 % CI 1.10–9.38). Low rates of both major bleeds and thromboembolic events were recorded, in addition to a substantial number of INR readings under the recommended target range. This may suggest that the recommended INR ranges may not represent the optimal warfarin intensity for this population and that a lower intensity of therapy, as observed in this cohort, could be beneficial in preventing adverse events.