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Biomedical subjects

A G Johnson

Publications and source records attributed to A G Johnson.

At least 163 records · Page 9Linked to original sources
PubMed1990

A study of the cellular and molecular mediators of the adjuvant action of a nontoxic monophosphoryl lipid A.

A detoxified endotoxin, termed monophosphoryl lipid A (MPL, Ribi), has been shown to increase antibody forming cell numbers in aging Balb mice both in vivo and in vitro. Separation of splenocytes from aging mice into purified T, B and adherent cell populations and subsequent incubation of each with MPL and admixture with their cellular counterparts and antigen, revealed only the T cell compartment capable of transferring the adjuvant action. Incubation of purified T cells from aging mice with MPL for 2 hr, followed by washing and culture for 48 hr, resulted in a supernatant fluid which enhanced antibody formation in cultures of aging spleen cells. This enhancing action was eliminated by an antiserum containing anti-alpha/beta/gamma interferon, but not by an anti-alpha/beta interferon antiserum. These data, as well as evidence gained by others as discussed, suggests the hypothesis wherein MPL increases antibody formation in aging mice by inducing the helper T cell population to secrete interferon gamma. The latter activates the macrophage to secrete increased levels of interleukin 1, thereby resulting in increased responsiveness throughout the ensuing sequence of cellular and molecular events leading to antibody synthesis.

Adjuvants, Immunologic↗
PubMed1990

Involvement of gamma interferon in antibody enhancement by adjuvants.

In a previous study the adjuvant action of a monophosphoryl lipid A, a nontoxic derivative of endotoxic lipopolysaccharide (LPS), was found to be negated by a monoclonal anti-gamma interferon (anti-IFN-gamma) antibody. The present investigation centered on three other adjuvants of diverse microbial origins, testing for their capacity to affect the release of IFN-gamma as an explanation for their antibody-enhancing action. The adjuvant action of each of the three, a wild-type LPS, synthetic poly(A)-poly(U) complexes, and a synthetic muramyl dipeptide, n-acetylmuramyl-L-alanyl-D-glutaminyl-n-butyl ester (murabutide), was transferable by adjuvant-stimulated T cells to normal spleen cells on coculture. Supernatant fluids from these T cells contained increased levels of IFN-gamma. Addition of a monoclonal anti-IFN-gamma antibody to adjuvant-stimulated spleen cell cultures reduced the adjuvant action by approximately one-half. Removal of natural killer cells from spleen cell populations prior to culture with antigen had no effect on the enhancement induced by LPS and monophosphoryl lipid A. It was concluded that the enhancement induced by the adjuvants LPS, poly(A)-poly(U), and murabutide is mediated in part by their action on T cells resulting in release of IFN-gamma suggesting activation of a common transmembrane signal.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1989

Duodenal bulb acidity and the natural history of duodenal ulceration.

Fasting and post-prandial duodenal bulb pH was recorded in 10 subjects with untreated duodenal ulcers (DU), 10 subjects with healed DU, and 15 healthy volunteers. During fasting, pH was less than 4 for a greater percentage of time in healed than in active DU. Ingestion of a solid test meal accentuated this difference: subjects with active DU and controls both showed less bulb acidification than subjects with healed ulcers. Bulb pH was similar in patients with active ulceration and controls. The finding of neutral bulb pH with active ulceration and low bulb pH with healing may explain the typical cycle of spontaneous healing and relapse in duodenal ulcer disease.

Adult↗
PubMed1989

Anorectal varices, haemorrhoids, and portal hypertension.

In a prospective study of 100 consecutive patients with cirrhosis, 44% had anorectal varices. The prevalence of anorectal varices rose with progression of portal hypertension; it was 19% in cirrhotic patients without portal hypertension compared with 59% in those who had bled from oesophageal varices. There was no evidence that endoscopic sclerotherapy directly increased the prevalence of anorectal varices. Haemorrhoids occurred independently of anorectal varices and their presence was unrelated to the degree of portal hypertension. These data provide further evidence that haemorrhoids and anorectal varices are separate and distinct entities. However, both can bleed and careful examination is essential to prevent misdiagnosis and inappropriate treatment.

Adult↗
PubMed1989

Management of bleeding varices in the elderly.

In 207 consecutive patients the outcome of bleeding varices was compared in those aged under 65 (n = 146) and those aged over 65 (n = 61). All patients were seen during seven years and were treated by active initial and maintenance sclerotherapy. Alcoholic cirrhosis was commoner in younger patients (68 (47%) v 12 (20%] and cryptogenic cirrhosis commoner in older patients (21 (34%) v 19 (13%]. Mortality due to the first bleed was dependent on the severity of liver disease and was unrelated to age. Survival corrected for age (life table analysis) was 65% at one year and 60% at two years for both groups of patients. It is concluded that patients should not be denied active treatment for bleeding varices on the basis of age alone. In order to obtain optimum results early endoscopy and sclerotherapy is essential.

Aged↗
PubMed1989

Serum phospholipase A2 activity in acute pancreatitis: an early guide to severity.

Daily measurements of serum phospholipase A2 activity were carried out on 73 consecutive patients admitted to hospital with acute pancreatitis. During the first 6 days there were significant differences in activity in those patients predicted as severe by multiple prognostic criteria when compared with those with mild disease. Follow-up studies at 6 weeks showed no difference between those graded as mild and those graded as severe at the time of attack. In the patients with elevated activity, nine had this at the time of admission and all were raised within 24 h. Elevated activity correlated well with the clinical outcome and showed good agreement with the multiple prognostic criteria in the prediction of severe disease. It is suggested that measurement of serum phospholipase A2 activity may provide a simple test for the early identification of most patients with severe acute pancreatitis.

Acute Disease↗
PubMed1989

Short-term effects of extracorporeal shock wave lithotripsy on the human gallbladder.

Extracorporeal shock wave lithotripsy (ESWL), whereby shock wave energy is focused upon gallstones causing their disintegration into fragments sufficiently small to be passed via the biliary system, offers a promising non-invasive alternative to surgery for gallstone disease. The tissue effects in humans of ESWL are poorly characterized and no systematic study of the tissue effects of ESWL by piezoelectrically generated shock waves has been published. Sixteen patients for elective cholecystectomy were therefore subjected to ESWL before surgery and detailed histology of the gall-bladders (including scanning electron microscopy of the mucosa) was compared with that from 20 age/sex-matched control cases. The gall-bladders treated by ESWL, in addition to showing the histological changes associated with chronic cholecystitis, showed serosal vasodilatation, mural oedema, and serosal and mucosal petechial haemorrhages focally over the entire surface. Between 10 and 90 per cent epithelial denudation was observed, but all cases showed surviving columnar epithelial cells in the crypts. No case showed vascular thrombosis, tissue necrosis, or acute inflammation. These tissue effects are likely to be reversible and unlikely to present a risk of perforation, although the long-term clinicopathological effects await investigation.

Adult↗
PubMed1989

Phospholipase A2 activity in taurocholate-induced acute pancreatitis in the rat model.

The activity of phospholipase A2 (PA2) was measured in the plasma of rats after the induction of acute pancreatitis. Buffered sodium taurocholate (3.75% w/v), injected into the pancreatico-biliary duct, was used to induce acute pancreatitis. Blood was taken at 1-h intervals for the measurement of phospholipase A2, glucose, lipase, and arterial gases. Plasma lipase was markedly elevated in the test groups, indicating acute pancreatitis, but no significant difference in PA2 activity was seen between the controls and the test group. However, in four animals the PA2 activity was elevated and in all cases this was accompanied by a low arterial pO2. This supports the theoretical role of PA2 in the pathogenesis of the respiratory complications observed in severe acute pancreatitis.

Acid-Base Equilibrium↗
PubMed1989

The lessons from in vitro lithotripsy for the clinical treatment of gallstones.

Fifty-eight gallbladder stones were treated in vitro, using a Wolf Piezolith 2300 lithotripter, to discover whether complete fragmentation (i.e., no particles greater than 2 mm diameter) could be achieved by lithotripsy alone. In 16 stones this was accomplished with up to 6000 shocks being administered. The degree of fragmentation was judged first by eye during the experiment and then by both microscopy and sieving of the debris. Eye judgement proved to be an unreliable indicator with 23 of the 42 stones in the failed lithotripsy group receiving 6000 shocks or less. Cholesterol analysis and high resolution radiography revealed no significant differences between the successfully and unsuccessfully fragmented stones, but X-ray diffractometry did show a higher incidence of inorganic calcium salts in the latter group. This study shows that lithotripsy can successfully fragment gallbladder stones, but that a minimum of 6000 shocks, using the Piezolith 2300, should be given to ensure adequate treatment. Additionally, the presence of radiopaque stones does not necessarily preclude successful treatment by this method.

Cholecystectomy↗
PubMed1989

The effects of cisapride on antroduodenal co-ordination and gastric emptying.

Five studies have shown that cisapride increased the antral motility index in the interdigestive and digestive states and three of these studies showed a stimulation of duodenal motility index and increased antroduodenal coordination. In normal volunteers and in patients with dyspepsia (223 subjects), both solid and liquid emptying is speeded by cisapride compared with placebo, and cisapride was as good as, or better than, metoclopramide at the same dosage. In studies in 37 diabetics with gastroparesis, both solid and liquid emptying were speeded and returned to normal, and cisapride was superior to metoclopramide. Solid emptying was speeded in patients with anorexia nervosa, chronic pseudo-obstruction and systemic sclerosis and the delay in gastric emptying induced by both morphine and dopamine was reversed. The effect of cisapride on bile reflux is still uncertain. Eight different methods of measuring gastric emptying were employed in these studies and they all gave similar results; the doses ranged from 2.5-10 mg i.v., and up to 20 mg orally.

Cisapride↗
PubMed1989

T cell and interferon-gamma involvement in the adjuvant action of a detoxified endotoxin.

The adjuvant activities of a detoxified derivative of endotoxic lipopolysaccharides, isolated from the outer membrane of gram-negative bacteria, were evaluated in aging mice. This monophosphoryl lipid A (MPL) (Ribi) was capable of enhancing antibody production in vitro in splenic cultures from 2-3-month-old male Balb/c mice as well as cultures from 22-24-month-old Balb/c mice. Separation of spleen cells from MPL and phosphate-buffered saline-injected mice into adherent and nonadherent populations and subsequent mixing of populations and culture with antigen implicated an adherent cell as being involved in the enhancement of antibody formation induced by MPL. However, separation of normal spleen cells into purified populations of adherent cells, T-lymphocytes, and B-lymphocytes, followed by in vitro stimulation of the individual populations with MPL and subsequent transfer into cultures of normal spleen cells, revealed only the T cell as capable of transferring the enhancement of antibody formation. In addition, culture filtrates from MPL-stimulated T cells were able to enhance antibody production by spleen cell cultures from aging mice twofold above that of filtrates from unstimulated T cells. The enhancement of antibody formation induced by such filtrates and also by MPL in spleen cell cultures from young and aging mice was inhibited by a monoclonal antibody (MAb) to recombinant interferon-gamma (rIFN-gamma) as well as antiserum against IFN-alpha, -beta, and -gamma, but not by an antiserum to IFN-alpha/beta. Enhancement of antibody formation correlated well with an increase in interleukin-1 (IL-1) but not with an increase in IL-2 production. Addition of anti-asialo-GM1 MAb plus complement to the effective spleen populations did not diminish the adjuvant action.

Adjuvants, Immunologic↗
PubMed1989

Malignant haemangiopericytoma of the pelvic retroperitoneum.

A case of malignant haemangiopericytoma of the pelvic retroperitoneum is described. The patient finally died of the complications of radiotherapy. In the absence of any reported long term benefits of adjuvant radiotherapy to the lesion, the lower morbidity of chemotherapy may make this form of adjuvant therapy worthy of further evaluation.

Combined Modality Therapy↗