Immunoblotting of Creutzfeldt-Jakob disease prion proteins: host species-specific epitopes

Creutzfeldt-Jakob disease (CJD) is a rare dementia that is generally found in older people and is caused by unusual infectious pathogens or prions. Using rabbit antisera raised against hamster scrapie prion proteins (HaPrPSc), we identified by immunoblotting human CJD prion proteins (HuPrPCJD) in the brains of 14 patients dying of CJD. Extracts from 6 of the patients were transmitted to mice after prolonged incubation. The rabbit antisera raised against HaPrPSc also reacted with the mouse CJD prion proteins (MoPrPCJD) found in the brains of these experimentally infected mice. When mice were immunized with HuPrPCJD, they produced antibodies that reacted with HuPrPCJD but not with MoPrPCJD. Mice immunized with MoPrPCJD produced antibodies to neither murine nor human prion proteins. Our results provide evidence for host species-specific epitopes on prion proteins. The existence of such epitopes is consistent with the apparent lack of an immune response during prion infections and the finding that prion protein molecules are encoded by host genes.     

Primary Immunodeficiency Syndrome in Spain: First Report of the National Registry in Children and Adults

The Spanish Registry for Primary Immunodeficiency Diseases (REDIP) was organized in 1993. One thousand sixty-nine cases of primary immunodeficiency diseases (PID) were registered in patients diagnosed between January 1980 and December 1995. PID diagnosis was made according to the World Health Organization criteria. The most frequent disorders were IgA deficiency (n = 394) and common variable immunodeficiency (n = 213), followed by severe combined immunodeficiency (n = 61), C1 inhibitor deficiency (n = 52), X-Iinked agammaglobulinemia (n = 49), IgG subclass deficiency (n = 48), and chronic granulomatous disease (n = 32). A comparative study between REDIP and data recently obtained from the European registry (ESID Report, 1995) revealed important differences between phagocytic disorders and complement deficiencies reported in both registries, 4.9 vs 8.7 and 6.0 vs 3.6, while percentages of predominantly antibody deficiencies and T cell and combined deficiencies concurred with those reported in the European registry, 69.3 vs 64.7 and 14.7 vs 20.2, respectively. The heterogeneous nature of the geographical distribution of cases submitted may indicate underdiagnosis of PID in some country areas; surprisingly, the interval between the onset of clinical symptoms and diagnosis was significant, even in immunodeficiency diseases, such as IgA deficiency, which are easy to diagnose.     

Laboratory toxicology of six forestry insecticides to four species of bee (hymenoptera: Apoidea)

Laboratory dose-response studies were conducted with four species of adult bees, Apis mellifera (workers), Andrena erythronii (females), Megachile rotundata (females), and Bombus terricola (workers), using six insecticides, permethrin, mexacarbate, aminocarb, fenitrothion, carbaryl, and trichlorfon. All insecticides were applied topically to the thorax of the bees as technical grade in an acetone carrier. Mortality was accumulated over 48 h, and probit analyses were conducted separately on data sets expressed in units of gAI (active ingredient)/g body weight and of gAI/bee. LD₅₀ values with 95% confidence limits and slopes with standard errors are provided for each bee/insecticide combination in each data set. Relative toxicities, relative susceptibilities, and fresh body weights are also provided. The analysis in units of gAI/g body weight indicated that the insecticides were typically ranked in order of decreasing toxicity—permethrin, mexacarbate, aminocarb, fenitrothion, carbaryl, and trichlorfon. Likewise, the bees ranked from the most to least susceptible in the order of A. mellifera, A. erythronii, M. rotundata and B. terricola. Trends within the data set for units of gAI/bee were less consistent. These data are discussed and compared with other published data on the toxicology of insecticides to bees and from the perspective of risk assessment.     

Circular DNA resulting from recombination between V-(D)-J joining signals and switch repetitive sequences in mouse thymocytes

During the course of analyzing circular DNA in mouse thymocytes, novel recombinants were identified with immunoglobulin heavy chain joining gene and switch region probes. These circles represent excision products of recombination between the heptamer-nonamer motif for V-(D)-J joining and a repetitive sequence for class switching. The molecular mechanisms that generate "hybrid circles" are discussed.     

Risk factors for foot fracture among individuals aged 45 years and older

A case-control study undertaken among members of five Northern California Kaiser Permanente medical centers sought to identify risk factors for foot fractures among persons aged 45 years and older. Foot fracture cases (n=920) and frequency matched controls (n=2366) were interviewed between October 1996 and May 2001 using a standardized questionnaire. Foot fractures occurred most often while walking or climbing stairs. While 60% of foot fractures resulted from falls, 20% were attributed to other causes, such as hitting the foot or tripping on sidewalks and curbs. Having a self-reported history of physician-diagnosed diabetes [adjusted odds ratio (OR)=1.45, 95% confidence interval (CI)=1.10–1.91] or cataracts (OR=1.40, 95% CI=1.07–1.83), having a self-reported foot problem (OR=1.38, 95% CI=1.06–1.78 for two or more foot problem versus no foot problems), having difficulty walking in minimum light (OR=1.86, 95% CI=1.14–3.05) and having had a prior fracture (OR=1.20, 95% CI=1.05–1.37) were associated with increased risk. Putative protective factors for osteoporotic fractures, such as menopausal hormone therapy use, thiazide or water pill use, high calcium intake, and high body mass index were not associated with foot fracture risk. These findings suggest that risk factors for foot fractures among older people differ in part from risk factors for other fracture sites generally considered to be osteoporotic, such as the hip, vertebrae, and forearm.     

Surgical Treatment of Morbid Obesity in Schizophrenic Patients

Background: Newer antipsychotic medications have greatly improved the treatment of schizophrenia, but they are known to be associated with serious weight gain. Little is known about treatment of morbid obesity in this population. Methods: 5 patients with schizophrenia and morbid obesity were studied.Weight loss was compared with that achieved by 165 non-psychotic patients who also underwent bariatric surgery during a 1-year period. Results: 5 morbidly obese patients with schizophrenia underwent bariatric surgery between February 1999 and April 2003. All patients were well controlled on antipsychotics. The median BMI was 54 (51-70) and all had obesity-related co-morbities. All patients had been previously treated unsuccessfully with conservative methods of weight reduction. 3 patients had a duodenal switch operation, 1 patient had a sleeve gastrectomy, and 1 had conversion of a silastic ring gastroplasty to biliopancreatic diversion. All patients were maintained on their antipsychotic medications until 24 hours before surgery. Median percent excess weight loss at 6 months was comparable to that achieved in the control group. Conclusions: Good control of schizophrenia may be achieved by newer therapies but at the risk of weight gain. The results of bariatric surgery in such patients are comparable to those of non-psychotic morbidly obese patients. Further follow-up is needed, but the results are encouraging.     

Outcome of simultaneous liver-kidney transplantation in highly sensitized,crossmatch-positive patients

BACKGROUND: In simultaneous liver-kidney transplantation (SLKT), the liver has been described to protect the kidney from rejection, and acceptable results are possible despite a pretransplant positive crossmatch. At our center, 21 SLKT have been performed since 1993, 2 of them against a positive crossmatch. OBJECTIVES: In this study we retrospectively analyzed two cases of SLKT after positive pretransplant crossmatch. METHODS: Two highly sensitized women (30 and 52 years) with hepatic cirrhosis VHC on hemodialysis after a first KT failure were assessed. Pretransplant panel reactive antibodies (PRA) by complement dependent cytotoxicity NIH (CDC) were 81% and 99% respectively. Both patients received a SLKT. CM was performed at pretransplant and 24 and 48 hours posttransplant by CDC and by flow cytometry with double labeling with CD3-PE and antihuman IgG-FITC. Patients received ATG, cyclosporine, and prednisone therapy. RESULTS: CM was positive pretransplant by CDC and flow cytometry. At 48 hours, CDC became almost negative (10%-20% mortality) and flow cytometry became negative. One of the patients experienced an episode of acute rejection at 10 days posttransplant that resolved with steroid pulses. Both patients presently have working grafts 26 and 24 months posttransplant (Cr, 1.1 and 1.5 mg/dL; GOT, 34 and 14 IU/L; GTP, 29 and 12 IU/L; GGT, 9 and 66 IU/L). CONCLUSIONS: Our experience suggests that a positive crossmatch is not an absolute contraindication for SLKT. Good graft and patient survival rates are possible even among highly sensitized patients.