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.     

Airway intervention in adult supraglottitis

Background The timing of aggressive airway intervention in adult epiglottitis is controversial. Aims To correlate Friedman’s staging of epiglottitis on admission with the airway interventions undertaken. Methods A retrospective study of 23 adult patients, mean age 51 years (range 29–81 years), who had been admitted with acute supraglottitis between March 1988 and December 2000 was undertaken. Results Three patients (13%) had airway interventions; two with tracheostomy and one with tracheal intubation. All were Friedman stage III and had rapid symptom progression during the 24 hours prior to admission. Three other stage III patients with symptom progression longer than 24 hours and all the remaining patients (stage II or less) were managed with observation and intravenous therapy. Conclusions Friedman originally advocated airway intervention in any patient stage II or worse, but this intubation threshold should probably be lowered to those patients with rapid-onset stage III (moderate respiratory distress, stridor, respiratory rate >30 per minute, pCO₂ >45mmHg) disease.     

Simultaneous drinking and gambling: a risk factor for pathological gambling

The aim of the current study was to determine the effect of simultaneous drinking and gambling on negative consequences from gambling. Data was analyzed from a national telephone survey of 2631 US residents aged 18 or older. Males were more likely than females to drink while gambling. Simultaneous drinking and gambling was more closely associated with video keno, pull tabs, dice (not in a casino) and casino gambling than with other types of gambling. Those who drank while gambling were more likely to be problem gamblers, even when holding constant frequency of gambling, size of the average win or loss, and average alcohol consumption. Those gamblers who are drinkers, but did not drink while gambling, had a prevalence of problem gambling of close to zero. They had a lower prevalence of problem gambling than gamblers who didn't drink alcohol at all in the past year, and a much lower prevalence than those who drank while gambling. These results were interpreted to mean that simultaneous drinking and gambling is an indicator of a more reckless gambler. The results did not support the theory that gambling while under the influence of alcohol causes more risky gambling behavior.     

Internet recovery for substance abuse and alcoholism: an exploratory study of service users

The Internet provides accessible, available, and affordable services for a variety of personal health issues. Use of Internet-based support tools for personal recovery from substance abuse, alcoholism, and mental illness is not new; however, several factors appear to have stalled investigation of the use of these tools in the prevention, outreach, support, recovery, and aftercare for those affected by substance abuse and/or alcoholism. This study was undertaken to begin the process of identifying Internet recovery services (IRS) and describing users of these services. Basic demographic and program affiliation data were obtained via an Internet survey utilizing conservative methodology. An obtained sample of more than 1000 surveys yielded a usable data analysis sample of 928, indicating the widespread use of IRS and diversity of service users, which includes all ethnic groups and age levels within the United States, using more than 70 different recovery programs and services. Future research needs are discussed.     

Adverse effects from inappropriate medication administration via a jejunostomy feeding tube.

Numerous complications can arise when administering medications to patients receiving continuous enteral feeding. We report a case of a patient who could not be fed by mouth and was receiving continuous jejunal enteral feeding who had an adverse event associated with inappropriate administration of a medication via his jejunostomy tube. He had taken an extended-release niacin product before hospitalization for type IIb hyperlipidemia. The patient was inappropriately given a single dose of 750 mg of niacin as the short-acting tablets that were crushed and administered via the jejunostomy tube. He experienced severe cutaneous flushing, a feeling of warmth, itching, nausea, and emesis. He was noted to have "prickly heat" to the forehead, according to the nursing notes. A discussion of problems and guidelines for medication administration in adult patients receiving continuous tube feeding is provided.     

1,25-dihydroxycholecalciferol in renal osteodystrophy. Epiphysiolysis--anticonvulsant therapy

Three children with azotaemic renal osteodystrophy were treated with 1,25-dihydroxycholecalciferol (1,25(OH)2D3). All showed clinical, biochemical, and radiological improvement within 6 months of starting treatment. There were no complications. The dose of 1,25(OH)2D3 required was 0-5 microgram per day for 2 children aged 22 and 30 months, and 2 microgram per day for a 15-year-old boy. 2 of the patients were receiving phenobarbitone and phenytoin and in one of them prior treatment with dihydrotachysterol 0-5 mg daily and 6 microgram 1alpha-hydroxycholecalciferol (1alphaOHD3) daily had failed to induce improvement. In one patient, in whom serial iliac bone samples were available, 2 microgram 1,25(OH)2D3 resulted in histological improvement in previously severe osteomalacia. 1,25(OH)2D3 appears to be an effective and safe drug in the treatment of uraemic osteodystrophy.     

新缩瞳剂包公藤甲素人工合成研究

包公藤甲素是从包公藤(Erycibe obtusifolia Benth.)茎中提得的一个新莨菪烷生物碱,具有强烈的缩瞳作用,临床用于治疗青光眼。本文报道用合成的6β-乙酰氧基托品酮为原料,经卤代、水解、还原和N-去甲基化等反应合成包甲素(8)。经光谱测定证实8与天然包甲素的结构完全一致。合成品系外消旋体,其作用机理与天然品相同,而强度则减半。