The binding and processing of monoclonal human IgG1 by cells of a human macrophage-like cell line (U937)

The goal of these experiments was to assess the relationship between the binding and processing of IgG by Fc-receptor-bearing cells. Cells of the U937 human macrophage-like cell line were incubated with 125I- labeled monomers, dimers, oligomers (composed of 2-4 IgG1 subunits), and HP (heavy polymers composed of 5 or more subunits per polymer) of monoclonal human IgG1 in vitro. Binding was assessed by spinning cells through a layer of phthalate oils. Internalization of IgG1 was assessed by quantitating residual binding to cells after surface-bound IgG was removed by a brief treatment with a solution containing 0.25 M acetic acid and 0.5 M sodium chloride. Catabolism was assessed by measuring the release of radioactive fragments of IgG1, which were not precipitated by 10% trichloroacetic acid. Unstimulated U937 bound about 10,000 molecules per cell of IgG1 monomer, with an equilibrium binding constant (Ka) of 5 X 10(8) M-1. After stimulation with a conditioned medium in vitro, binding per cell was increased 3-7--fold, and the Ka was decreased 2-4--fold. Both unstimulated and stimulated cells internalized and catabolized labeled IgG1 HP, but stimulated cells internalized and digested much more IgG1 HP per cell than unstimulated cells. Both monomers and dimers of IgG1 were internalized and degraded very slowly by stimulated cells, even though both preparations readily bound to cells. In contrast, oligomers and (to an even greater extent) IgG1 HP were internalized and degraded much more rapidly. Internalization of IgG1 HP was markedly inhibited by incubation at 4 degrees C, but not by incubation with a variety of metabolic inhibitors. Catabolism was inhibited by chloroquine and monensin (inhibitors of lysosomal acidification) and by cytochalasin (an inhibitor of microfilament polymerization). Binding to the surface of cells was not markedly inhibited by any agent tested. The capacity of cells to bind labeled IgG1 was markedly reduced by prior incubation in the presence of unlabeled IgG1. This reduction was in part due to the steric blockade of receptors caused by the avid, but reversible, binding of IgG1. In addition, IgG1 oligomers or HP (but not IgG1 monomers or dimers) also caused an irreversible reduction in the number of Fc receptors by a process analogous to receptor down-regulation, as observed in other receptor--ligand systems.     

Possibility of selection against mtDNA mutations in tumors

Several studies of tumors have revealed substantial numbers of clonally expanded somatic mutations in mitochondrial DNA (mtDNA), not observed in adjacent intact tissues. These findings were interpreted as indicating the involvement of mtDNA mutations in tumorigenesis. Such comparisons, however, ignore an important confounding factor: the monoclonal origin of tumors as opposed to the highly polyclonal nature of normal tissues. Analysis of recently published data on the incidence of somatic mutations in nontumor monoclonal cells suggests that, contrary to the prevailing view, the process of tumorigenesis may be accompanied by active selection against detrimental mtDNA mutations.     

Integrating clinical practice guidelines into daily practice: impact of an interactive workshop on drafting of a written action plan for asthma patients

INTRODUCTION: Written action plans (WAPs) are instructions that enable asthmatics to manage their condition appropriately and are recommended by current asthma clinical practice guidelines (CPGs). However, general practitioners (GPs) rarely draft WAPs for their patients. An interactive, case-based workshop for asthma, combined with an objective structured clinical examination (OSCE), was developed to increase GPs' knowledge and use of WAPs in Québec. METHODS: The study compared 24 GPs receiving an OSCE preworkshop and 12 months post-workshop (group 1) with 16 GPs receiving an OSCE preworkshop and at 6 and 12 months post-workshop (group 2). Participants received no feedback on their OSCE performance. During the workshop, which presented a preformatted tool to aid drafting of the WAPs, all 40 GPs worked individually and in small groups to answer questions on a hypothetical clinical case and then discussed the responses with a facilitator and an asthma specialist. RESULTS: Only group 2 GPs showed a significant improvement in knowledge of WAPs 12 months post-workshop (p = .01). The likelihood of prescribing WAPs to patients increased in group 2 to a degree approaching statistical significance (p = .070), and there was a borderline nonsignificant trend for prescribing practice to improve more among group 2 GPs than among group 1 GPs (p = .052). There was also a nonsignificant trend for 6-month OSCE to increase attendance at the 12-month OSCE. DISCUSSION: An interactive workshop employing a preformatted WAP tool and a reinforcing OSCE at 6 months yielded improved knowledge of WAPs at 1 year. Although originally developed as a form of evaluation, the OSCE appears to have formative value even when correction is not provided and may increase the effectiveness of continuing medical education interventions to enhance CPG implementation.     

Long-term clinical and radiologic results after Eden-Hybbinette operation for anterior instability of the shoulder

A retrospective study was done to assess long-term results after surgery with the Eden-Hybbinette technique for unidirectional anterior glenohumeral instability. Between 1962 and 1976, 118 patients (119 shoulders) were treated. Eighty-seven patients answered a questionnaire. Of 119 shoulders, 77 were examined clinically and 74 radiographically a mean of 29 years after surgery. Forty-two were lost to follow-up. For 74% of shoulders, patients were satisfied, and for 26%, patients had some remaining discomfort. The most common reason for discomfort was persistent instability. The recurrence rate was 20%, although only 8 patients required reoperation. The mean time from surgery until redislocation was 15 months (range, 1-60 months). The mean Rowe shoulder score was 84 +/- 15 (range, 45-100), with 48 of 77 shoulders rated as excellent, 16 of 77 as good, 9 of 77 as fair, and 4 of 77 as poor. The Constant-Murley score averaged 85 +/- 14 (range, 20-100). Glenohumeral arthrosis was seen in 35 of 74 shoulders (47%). There was no significant difference between those with arthrosis and those without as far as age at first dislocation, age at surgery, or follow-up. Shoulders with arthrosis had a tendency to have reduced external rotation (P =.056) when compared with shoulders without radiologic changes. This study showed that most patients were satisfied with their shoulders. There was a high rate of radiologic arthrosis, but in most patients it caused limited restriction of movement as the only symptom.     

RENAL FUNCTION IN CHRONICALLY CATHETERIZED CONSCIOUS DIABETIC RATS USING CONSTANT AND SERVO-CONTROLLED INFUSION

1. Infusion experiments were performed on chronically catheterized conscious rats to assess kidney function before and after the induction of diabetes mellitus with streptozotocin. 2. Two infusion regimens were used, a conventional constant-infusion protocol and a novel computer-driven, servo-controlled fluid replacement technique. The latter enables body fluid status to be maintained throughout a study occasion by servo-controlled replacement of spontaneous urinary fluid losses. 3. The chronically catheterized conscious rat infused using a servo-controlled system appears to be the optimum model for a study of diabetic renal function. The conscious preparation circumvents problems associated with anaesthesia and acute surgery. The servo-controlled infusion protocol maintains the altered fluid status of the diabetic condition. Both hyperfiltration and polyuria, characteristics of human diabetes often absent in anaesthetized and/or constantly infused diabetic rats, were seen in all conscious servo-controlled diabetic animals. 4. The new regimen enables a more accurate assessment of renal function in experimental diabetes than with previous protocols. It should prove useful in future studies, particularly those assessing the role of anti-diabetic drugs on the kidney.     

Unexplained diarrhoea and failure to thrive in 2 siblings with unusual facies and abnormal scalp hair shafts: a new syndrome

A family is described in which 2 siblings born to healthy parents presented with abnormal facies, persistent diarrhoea, and early death. Exhaustive pathological and biochemical investigations failed to find a cause. The scalp hair of both babies had an abnormal amino-acid composition, and presented an appearance that was unique on scanning electron microscopical examination; this fact and the clinical picture probably represents a new syndrome.     

Pineal germinoma: MR imaging

Magnetic resonance (MR) imaging characteristics of pineal germinomas are described in seven patients imaged with MR and computed tomography (CT). In patients with symptoms of an enlarging process in the quadrigeminal plate cistern, MR imaging was as sensitive as CT scanning in detecting the mass. MR imaging did not detect a normal-sized, calcified neoplastic gland. Germinoma, germinoma with embryonal cell carcinoma elements, and pineoblastoma demonstrated different MR signal characteristics. Although direct coronal and sagittal MR images were useful in defining the relationship of the tumor to the posterior third ventricle, Sylvian aqueduct, and vein of Galen, the ease, rapidity, and sensitivity of CT scanning suggest that CT should remain the modality of choice for initial evaluation and screening of the pineal region, especially in the younger pediatric population, in whom detection of calcification may provide the only clue of an abnormality.