Triple check for antigen specificity of B cells during germinal centre reactions

Somatic hypermutation of the immunoglobulin variable genes during germinal reactions might permit the expansion of B-cell clones with unwanted (e.g. autoreactive) specificity. Here, Ernst Lindhout and colleagues propose three antigen-specific checkpoints that ensure the appropriate antigen specificity of activated B cells is maintained by regulating the activation, selection and further differentiation of B cells.     

Biological evaluation of two anomeric glucose analogues iodinated in position 6

Two anomeric analogues of glucose labelled with 123 iodine in position 6, proposed as tracers of glucose transport in vivo, have been synthesized: alpha- and beta-methyl-6-deoxy-6-iodo-D-glucopyranoside (alpha MDIG and beta MDIG). The aim of this study was to determine whether these molecules interact with the glucose transporter and whether they could be used as tracers of glucose transport in vivo. The biodistribution of alpha MDIG and beta MDIG was studied in the mouse in vivo. To determine if these two anomers enter the cell via the glucose transporter, their uptake was measured in isolated perfused rat hearts, in human erythrocytes in suspension, and in cardiomyocytes of neonatal rat in culture. Both alpha MDIG and beta MDIG had similar repartitions in the mouse: myocardial uptake averaged 7% of the injected dose/g of organ at 2 min postinjection and alpha MDIG competed with D-glucose to enter the cells. Insulin produced a 123% increase of its uptake in isolated perfused rat hearts and a 100% increase in cardiomyocytes of neonatal rat in culture. alpha MDIG uptake was lowered in the presence of glucose transport inhibitors in each experimental model. An interaction between beta MDIG and glucose transporters was observed only in human erythrocytes in suspension. Only alpha MDIG interacts with the glucose transporter, and thus could be used to estimate glucose transport in vivo.     

Modified hippocampal long-term potentiation in PKC gamma-mutant mice

Calcium-phospholipid-dependent protein kinase (PKC) has long been suggested to play an important role in modulating synaptic efficacy. We have created a strain of mice that lacks the gamma subtype of PKC to evaluate the significance of this brain-specific PKC isozyme in synaptic plasticity. Mutant mice are viable, develop normally, and have synaptic transmission that is indistinguishable from wild-type mice. Long-term potentiation (LTP), however, is greatly diminished in mutant animals, while two other forms of synaptic plasticity, long-term depression and paired-pulse facilitation, are normal. Surprisingly, when tetanus to evoke LTP was preceded by a low frequency stimulation, mutant animals displayed apparently normal LTP. We propose that PKC gamma is not part of the molecular machinery that produces LTP but is a key regulatory component.     

Treatment and prognosis of secondary glaucoma in Fuchs' heterochromic iridocyclitis

After reviewing the records of 111 patients with Fuchs' heterochromic iridocyclitis, we studied the therapy and prognosis of secondary glaucoma in 30 of these 111 patients (27%) who had glaucoma or could be considered glaucoma suspects. Maximal medical therapy was unsuccessful in 22 of the 30 patients (73%). Surgical intervention (mostly trabeculectomies, half with 5-fluorouracil) successfully controlled intraocular pressure (< or = 21 mm Hg with or without medication) in 13 of the 18 operated-on patients (72%) after a mean follow-up of 26 months. All successfully operated-on patients retained a visual acuity of 20/80 or better. We had favorable results, possibly because of modern surgical techniques (use of 5-fluorouracil, sodium hyaluronate) or earlier surgical intervention, or both.     

STRONG METAL-CERAMIC JOINTS

In this paper the technology for joining metals to ceramics is reviewed. The technologies of metal powder sintering, liquid phase joining with activated brazing alloys and with ceramic frit, solid-state joining, friction welding and mechanical fixation are described. In order to put some perspective on the mechanical data given in the literature, some evaluating remarks on mechanical testing are made.     

Intubation conditions: importance of the rate of repetition of the train-of-four

OBJECTIVES: To assess that neuromuscular relaxation onset of the adductor pollicis (AP) is related to neuromuscular stimulation rate. To assess that train-of-four (TOF) at 0.05 Hz is a more accurate indicator of optimal tracheal intubation time and conditions, than TOF at 0.08 Hz. STUDY DESIGN: Prospective, comparative, randomized double-blind study. PATIENTS: Forty adults, physical class ASA 1 or 2, undergoing general anaesthesia with tracheal intubation were allocated to two groups (n = 20) according to the sequence of stimulation of the AP: either TOF at 0.05 Hz (test group) or TOF at 0.08 Hz (control group). METHODS: Induction of anaesthesia was achieved with thiopentone, fentanyl and vecuronium (0.1 mg.kg-1). Neuromuscular monitoring was obtained with force displacement transducers attached to each AP. Tracheal intubation was performed once AP muscular response obtained with TOF at 0.05 Hz for test group and TOF at 0.08 Hz for control group was abolished. Results are expressed as mean +/- SEM. Fisher exact test was used for intubation conditions comparison. Curarization time between groups was compared with unpaired Student's t test (P < 0.05 accepted). RESULTS: TOF with 0.05 Hz stimulation significantly increased curarization time: 217 +/- 7 versus 162 +/- 6 s (P < 0.001). Intubation conditions were excellent in 95% and good in 5% of patients in the study group, compared to 15 and 40% in the control group, respectively (P < 0.01) in 45% of the control group patients coughing at intubation occurred. CONCLUSION: Low stimulation rate (TOF at 0.05 Hz) of AP is a reliable technique to determine the appropriate intubation time for patients paralyzed with vecuronium.     

Diagnosis of systemic causes of uveitis; a matter of ophthalmologist and internist

OBJECTIVE: To assess how often the aetiology is established in patients with uveitis, what systemic disease are found and what is the contribution of the internist to the diagnostic process. DESIGN: Retrospective study. SETTING: University Hospital Leiden, the Netherlands. METHOD: From January 1987 to April 1992, 342 patients presented with uveitis. All patients underwent a standard ophthalmological examination. Referral to an internist and individualised laboratory screening followed in patients with recurrent, chronic, bilateral or panuveitis. Recorded were: ophthalmological data, results of laboratory screening, results of analysis by the internist, final diagnosis and presence of systemic disease. RESULTS: 149 (44%) patients were examined by the internist, 18 (5.2%) were seen by another specialist. In 169 (49%) patients a specific diagnosis was made. 74 (22%) had a systemic disease, 74 a primary ocular disease. In 28 (8%) a systemic disease was presumed (5% were HLA-B27 positive, 3% had abnormal laboratory results); 5 (1%) patients had endophthalmitis as a complication of a septic process. CONCLUSION: In approximately 1/3 of the patients with uveitis a systemic disease was found. Examination by the internist tailored to the individual patient is essential in the evaluation of uveitis patients.