The immune response against anti-idiotope antibodies. I. Induction of idiotope-bearing antibodies and analysis of the idiotope repertoire

In the present analysis we dissect the idiotype repertoire, independently of haptenbinding specificity, by immunizing different strains of mice with cross-linked monoclonal anti-idiotopet antibodies against antibody B1-8. B1-8 is a monoclonal antibody with specificity for the hapten (4-hydroxy-3-nitro-phenyl)acetyl (NP) and carries a germ line gene-encoded variable region. The results demonstrate that the expression of B1-8 idiotopes and their association with eachother and with NP-binding specificity are strain-specific. Certain idiotopes are expressed on antibodies differing in antigen-binding specificity, whereas one of the idiotopes appears strictly associated with NP-binding antibodies. The genetic analysis provides strong evidence that the strain specificity of the idiotope repertoire is a result of V region polymorphism in the mouse.     

The influence of lateral and anterior angulation of the proximal ulna on the treatment of a Monteggia fracture: an anatomical cadaver study

We have investigated the anatomy of the proximal part of the ulna to assess its influence on the use of plates in the management of fractures at this site. We examined 54 specimens from cadavers. The mean varus angulation in the proximal third was 17.5 degrees (11 degrees to 23 degrees ) and the mean anterior deviation 4.5 degrees (1 degrees to 14 degrees ). These variations must be considered when applying plates to the dorsal surface of the ulna for Monteggia-type fractures. A pre-operative radiograph of the contralateral elbow may also be of value.     

龙血竭胶囊治疗软组织挫伤230例

1 临床资料软组织挫伤460(男300,女160)例,年龄5～72(平均38)岁,面部伤86例,躯干伤98例,四肢伤200例,躯干合并四肢伤76例,均为12 h内收治病例. 实验组(n=230)给于龙血竭胶囊(龙血竭胶囊是由植物防卫素和龙血竭皂甙组成)口服,3次/d,每次1.2 g;对照组(n=230)给于跌打丸口服,2次/d,每次1丸,疗程均为6 d. 实验组总有效率为96.5%,对照组为83.5%,两组间有显著差别(P<0.01). 实验组用药后3和6 d血糖值均较对照组有明显下降(P<0.01). 实验组与对照组用药后总抗氧化能力(TAO, kU/L)均升高(12.5±0.08→42.5±0.03, 12.6±0.05→32.9±0.04),但实验组升高明显(P<0.01).     

MKK3 signalling plays an essential role in leukocyte-mediated pancreatic injury in the multiple low-dose streptozotocin model

In vitro studies have implicated activation of the p38 mitogen-activated protein kinase (MAPK) signalling pathway in cytokine-mediated pancreatic beta-cell injury. Activation of the p38 MAPK occurs through two different upstream kinases, mitogen-activated protein kinase kinase 3 (MKK3) and MKK6. This study examined the role of MKK3 signalling in an in vivo model of cytokine-dependent pancreatic injury induced by multiple low doses of streptozotocin (MLD-STZ). Groups of wild-type (WT) or Mkk3-/- C57BL/6J mice received 5 daily injections of STZ (40 mg/kg) and were killed on day 5, week 2 or week 4. MLD-STZ in WT mice exhibited two distinct phases of pancreatic damage: islet cell apoptosis (immunostaining for cleaved caspase-3) on day 5 in the absence of leukocyte infiltration, and this was followed by islet inflammation (leukocyte infiltration and cytokine production) and further islet cell apoptosis on day 14 resulting in a loss of insulin-producing beta-cells and an 80% incidence of hyperglycaemia. Mkk3-/- mice were not protected from the initial phase of STZ-induced islet cell apoptosis day 5. However, Mkk3-/- mice were completely protected from the induction of hyperglycaemia. This was attributed to inhibition of leukocyte infiltration, production of pro-inflammatory cytokines and islet cell apoptosis at day 14 of MLD-STZ. In vitro studies showed that cultured islets from Mkk3-/- and WT mice are equally susceptible to STZ and cytokine-induced apoptosis. In conclusion, MKK3 signalling plays an essential role in the development of islet inflammation leading to destruction of beta-cells and hyperglycaemia in MLD-STZ-induced pancreatic injury.     

Invasion of erythrocytes by Plasmodium falciparum malaria parasites: evidence for receptor heterogeneity and two receptors

Plasmodium falciparum malaria parasites with different capabilities of invading sialic acid-deficient erythrocytes were identified. Thai-2 parasites cultured in Tn erythrocytes invaded neuraminidase-treated and Tn erythrocytes twice as efficiently as Thai-2 parasites cultured in normal erythrocytes and seven to ten times more efficiently than a cloned line of Camp parasites cultured in normal erythrocytes. All three parasite lines required sialic acid for optimal invasion, but Thai-2 parasites cultured in Tn erythrocytes invaded neuraminidase- treated erythrocytes with 45% efficiency whereas Camp parasites invaded neuraminidase-treated erythrocytes with less than 10% efficiency. P falciparum malaria parasites probably possess two receptors: one that binds to a sialic acid-dependent ligand and another that binds to a sialic acid-independent ligand. Parasites may differ in the quantity or affinity of their receptors for the sialic acid-independent ligand.     

Thoracic positron emission tomography using 18F-fluorodeoxyglucose for the evaluation of residual mediastinal Hodgkin disease.

Residual mediastinal masses are frequently observed in patients with Hodgkin disease (HD) after completed therapy, and the discrimination between active tumor tissue and fibrotic residues remains a clinical challenge. We studied the diagnostic value of metabolic imaging by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in detecting active mediastinal disease and predicting relapse. Twenty-eight HD patients with a residual mediastinal mass of at least 2 cm after initial therapy or after salvage chemotherapy were prospectively assigned to 29 examinations with FDG PET and were evaluated as 29 "subjects." Patients were monitored for at least 1 year after examination and observed for signs of relapse. Median follow-up was 28 months (range, 16 to 68 months). A PET-negative mediastinal tumor was observed in 19 subjects, of whom 16 stayed in remission and 3 relapsed. Progression or relapse occurred in 6 of 10 subjects with a positive PET, whereas 4 subjects remained in remission. The negative predictive value (negative PET result and remission) at 1 year was 95%, and the positive predictive value (positive PET result and relapse) was 60%. The disease-free survival for PET-negative and PET-positive patients at 1 year was 95% and 40%, respectively. The difference was statistically significant. A negative FDG PET indicates that an HD patient with a residual mediastinal mass is unlikely to relapse before 1 year, if ever. On the other hand, a positive PET result indicates a significantly higher risk of relapse and demands further diagnostic procedures and a closer follow-up.     

Recovery from short term intense exercise: Its relation to capillary supply and blood lactate concentration

Summary Muscle force recovery from short term intense exercise was examined in 16 physically active men. They performed 50 consecutive maximal voluntary knee extensions. Following a 40-s rest period five additional maximal contractions were executed. The decrease in torque during the 50 contractions and the peak torque during the five contractions relative to initial torque were used as indices for fatigue and recovery, respectively. Venous blood samples were collected repeatedly up to 8 min post exercise for subsequent lactate analyses. Muscle biopsies were obtained from m. vastus lateralis and analysed for fiber type composition, fiber area, and capillary density. Peak torque decreased 67 (range 47–82%) as a result of the repeated contractions. Following recovery, peak torque averaged 70 (47–86%) of the initial value. Lactate concentration after the 50 contractions was 2.9±1.3 mmol·l⁻¹ and the peak post exercise value averaged 8.7±2.1 mmol·l⁻¹. Fatigue and recovery respectively were correlated with capillary density (r=−0.71 and 0.69) but not with fiber type distribution. A relationship was demonstrated between capillary density and post exercise/peak post exercise blood lactate concentration (r=0.64). Based on the present findings it is suggested that lactate elimination from the exercising muscle is partly dependent upon the capillary supply and subsequently influences the rate of muscle force recovery. Dr. Tesch was on leave from Department of Clinical Physiology, Karolinska Hospital, Stockholm, Sweden