Analysis of the repertoire of human B-lymphocytes specific for type A and type B blood group terminal trisaccharide epitopes

Naturally occurring serum antibodies specific for the A and B blood group isoantigens are of great importance in medicine. By using A-type terminal trisaccharide (ATS) or B-type terminal trisaccharide (BTS) coupled to albumin as coating antigens, an enzyme-linked immunosorbent assay capable of detecting all ATS/BTS-binding antibodies was performed. The combination of this enzyme-linked immunosorbent assay with limiting-dilution methodology, using a polyclonal B-lymphocyte activator, permitted a monoclonal analysis of the human antibody repertoire that is specific for ATS and BTS in persons of different blood types. Most (78%) positive supernatants from type O cultures were monospecific for either ATS or BTS, and these were present at roughly equivalent frequencies. Nine supernatants with reactivity toward both ATS and BTS were tested by red cell adsorption; six had properties expected for true dually reactive monoclonal antibodies: adsorption with either A1 or B red cells eliminated both anti-ATS and anti-BTS activity. This finding accords with a monoclonal origin for anti-A,B. The analysis of cultures of peripheral blood lymphocytes from type A and B donors unexpectedly showed significant numbers of clones with apparent autospecificity. However, none of the anti-ATS-positive supernatants from type A cultures or anti-BTS-positive supernatants from type B cultures were adsorbable with A1 or B red cells, respectively. Consideration of only true (adsorbable) positives indicates that the type A and B anti-trisaccharide repertoires differ significantly from the type O repertoire, probably as a result of the action of normal self-tolerance mechanisms.     

An intracellular study of the contrast-dependence of neuronal activity in cat visual cortex

Extracellular recordings indicate that mechanisms that control contrast gain of neuronal discharge are found in the retina, thalamus and cortex. In addition, the cortex is able to adapt its contrast response function to match the average local contrast. Here we examine the neuronal mechanism of contrast adaptation by direct intracellular recordings in vivo. Both simple (n = 3) and complex cells (n = 4) show contrast adaptation during intracellular recording. For simple cells, that the amplitude of fluctuations in membrane potential induced by a drifting grating stimulus follows a contrast response relation similar to lateral geniculate relay cells, and does not reflect the high gain and adaptive properties seen in the action potential discharge of the neurons. We found no evidence of significant shunting inhibition that could explain these results. In complex cells there was no change in the mean membrane potential for different contrast stimuli or different states of adaptation, despite marked changes in discharge rate. We use a simplified electronic model to discuss the central features of our results and to explain the disparity between the contrast response functions of the membrane potential and action potential discharge in simple cells.      

An acoustic neuroma as an ophthalmic life-threatening emergency

Headache is a common complaint whereas lesions of the cerebello-pontine angle are rare. Ophthalmoscopy is essential whenever headaches occur for the first time, especially when precipitated by exertion or straining and obviously when associated with cranial nerve dysfunction. This case report details the signs and symptoms of a patient with acoustic neuroma. When papilloedema is present, urgent radiological investigation and neurosurgical evaluation are indicated.     

Serum amyloid P inhibits dermal wound healing

The repair of open wounds depends on granulation tissue formation and contraction, which is primarily mediated by myofibroblasts. A subset of myofibroblasts originates from bone‐marrow‐derived monocytes which differentiate into fibroblast‐like cells called fibrocytes. Serum amyloid P (SAP) inhibits differentiation of monocytes into fibrocytes. Thus, we hypothesized that the addition of exogenous SAP would hinder the normal wound healing process. Excisional murine dorsal wounds were either injected with SAP (intradermal group) or the mice were treated with systemic SAP (intraperitoneal group) and compared with animals treated with vehicle. Grossly, SAP‐treated wounds closed slower than respective controls in both groups. Histologically, the contraction rate was slower in SAP‐treated wounds in both groups and the reepithelialization rate was slower in the intraperitoneal group. Furthermore, significantly less myofibroblasts expressing α‐smooth muscle actin were noted in the intraperitoneal group wounds compared with controls. These data suggest that SAP delays normal murine dermal wound healing, probably due to increased inhibition of fibrocyte differentiation, and ultimately a decreased wound myofibroblast population. SAP may provide a potential therapeutic target to prevent or limit excessive fibrosis associated with keloid or hypertrophic scar formation. Furthermore, SAP removal from wound fluid could potentially accelerate the healing of chronic, nonhealing wounds.     

IS CARDIOVASCULAR DISEASE A RISK FACTOR IN THE DEVELOPMENT OF AXONAL POLYNEUROPATHY?

Objectives: To determine if cardiovascular disease may be a risk factor in the development of chronic idiopathic axonal polyneuropathy (CIAP). Methods: In this incidence case-control study, the prevalence of cardiovascular disease and risk factors in 97 patients with CIAP (mean age 67.5 (SD 7.9) years) and the prevalence of neuropathic features in 97 patients with peripheral arterial disease (PAD) (mean age 67.1 (SD 7.3) years) were investigated. The results were compared with those for 96 age and sex matched controls without diagnosed PAD or polyneuropathy (mean age 67.5 (SD 9.1) years). In a randomly chosen subgroup of 23. patients with CIAP, 42 patients with PAD, and 48 controls, an electrodiagnostic investigation was performed. Results: Patients with CIAP more often had manifest cardiovascular disease and cardiovascular risk factors than controls (stroke 18% v 6% of patients, odds ratio (OR) 3.2 (95% confidence interval (0) 1.8 to 5.9); heart disease 29% v 15%, OR 2.4 (95% Cl 1.2 to 4.9); family history of cardiovascular disease 42% v 21%, OR 2.8 (95% Cl (1.5 to 5.2); hypertension 56% v 39%, OR 2.0 (95% Cl 1.1 to I I 3.6); hypercholesterolaemia 46% v 21%, OR 3.3 (95% Cl 1.5 to 7.3); current smoking 38% v 23%, OR 2.1 (95% Cl I. I to 3.9)). The prevalence of cardiovascular disease and cardiovascular risk factors was lower than in patients with PAD. Patients with PAD more often had polyneuropathy than controls (15% v 5%, OR 3.3 (95% Cl 1.1 to 10.0)). There was a trend towards lower nerve conduction velocities and lower amplitudes on electrodiagnostic investigation compared with controls. Conclusion: This study shows that cardiovascular disease and CIAP often coexist, and therefore cardiovascular disease may be a cofactor in the development of CIAP.