Analysis of host genetic control of scrapie-induced obesity

Summary The potential for induction of obesity during the preclinical phase of scrapie disease in mice was previously shown to be a function of both the strain of scrapie and the strain of inbred mouse. In the present study, host control of obesity induction by a scrapie strain was examined to determine if the effect were dependent on a single gene or multiple genes. The approach used was assessment of the pattern of weight induction in F1 and F2 crosses of parental inbred mouse strains that did or did not show a weight increase with a specific scrapie strain. Analyses of these data indicated that the induction of obesity was controlled by multiple host genes. In an unrelated observation, there was a correlation between the incubation period of a strain of scrapie in F2 generation mice and their coat color, i.e., the average incubation period of yellow-brown mice was significantly less than those of either black or white mice.     

Immune reproductive failure: effect of nonspecific immunostimulation in mouse model.

There is much evidence that pregnancy loss may be immunologically mediated. Failure of the maternal immune system to actively support the pregnancy may be responsible for its demise. Potentiation of immune functions has been attempted in humans; however, the success of immunotherapy is still not clear. Thus immunotherapy experiments in mouse models are important. Nonspecific immuno-stimulation with complete Freund adjuvant (CFA) was shown in our laboratory to reverse the tendency to fetal loss in the CBA/J X DBA/2J mouse combination. CFA elevates the non-T lymphocyte population, decreases T-cell secreted lymphokines, and enhances macrophage-secreted monokines. However, a relationship between these changes and a beneficial effect of CFA on reproductive performance has to be proved. Information obtained from nonspecific immunopotentiation in the CBA/J-DBA/2J model may contribute the assessment of nonspecific immunotherapy in humans.     

In situ saphenous vein bypass grafts: angiographic evaluation and interventional repair of complications

In situ saphenous vein grafts are being used with increasing frequency for bypass procedures involving the femoral and popliteal arteries. Complications of these procedures include anastomotic stenoses and persistent arteriovenous fistulae that may result in failure of the graft. Balloon angioplasty and embolotherapy with detachable balloons were employed successfully in three or four recent cases of patients with complications from in situ grafts. Tailored angiography is essential for evaluating in situ grafts, and interventional techniques are extremely useful for managing complications.     

The association between meningitis and dural puncture in bacteremic rats.

Clinicians have long been concerned that performance of spinal anesthesia during a period of bacteremia may result in the subsequent development of meningitis. In order to determine whether such an association exists, percutaneous dural puncture was performed in 40 animals during a period of Escherichia coli bacteremia. Twenty-four hours later, spinal fluid was obtained for final analysis by surgically draining the cisterna magna. Twelve animals had E. coli recovered from the surgically drained spinal fluid. Only animals with a circulating bacterial count of at least 50 CFU/ml developed meningitis. Microscopic examination of the brains and spinal cords of animals with infected cerebrospinal fluid showed evidence of central nervous system infection. Bacteremic animals not undergoing percutaneous dural puncture always had sterile spinal fluid (n = 40). Cisternal puncture in the absence of bacteremia did not result in infection (n = 30). Treatment with a single dose of gentamicin before the dural puncture eliminated the risk of meningitis after dural puncture in 30 bacteremic animals. These results demonstrate that dural puncture is associated with the development of meningitis in rats, provided the animals are bacteremic at the time of the puncture. However, antibiotic treatment before the dural puncture appears to eliminate this risk.     

Detection of scrapie-associated fibrils (SAF) and SAF proteins from scrapie-affected sheep

Scrapie-associated fibrils (SAF) were detected by negative-stain electron microscopy in the brains (by two different isolation procedures) and spleens of sheep naturally and experimentally infected with scrapie. Although the numbers of SAF varied from case to case, the yield of SAF from brains of naturally affected sheep was lower than that from experimentally affected sheep. SAF-specific, protease-resistant proteins (PrPs) were detected by silver staining and western blot analysis in most samples of brain from experimentally affected sheep. PrPs, however, could be detected in only a limited number of natural cases of sheep scrapie because of the lower yields of SAF. PrPs from sheep SAF appear biochemically and antigenically similar to PrPs from other species infected with unconventional agents. This study further establishes the unique association of SAF and PrPs with natural or experimentally induced scrapie in its natural host.     

Shared care: a review of the literature

This review examines broad issues of concern regarding the primary/secondarycare interface. The main purpose was to identify areas of goodpractice which could be adapted for more general use. One ofthe most fundamental aspects identified was communication, whichis discussed in some detail. Also covered are shared prescribingand disease management. The data suggest that the most effectivesystem(s) of shared care has yet to be established. Furtherqualitative and economic evaluations are required, taking intoaccount patient preferences. Although the literature does describecertain practice exemplars, it is clear that inter- and intra-professionalcommunication continues to be a problem. Whilst informationtechnology may provide some of the solutions, it is concludedthat a culture change, which compels health professionals tomake sharing of patient information a much higher priority,is reauired. Keywords. Shared care, seamless care, hospital, general practice, family practice.     

Localization of a gene for otosclerosis to chromosome 15q25-q26

Among white adults otosclerosis is the single most common cause of hearing impairment. Although the genetics of this disease are controversial, the majority of studies indicate autosomal dominant inheritance with reduced penetrance. We studied a large multi- generational family in which otosclerosis has been inherited in an autosomal dominant pattern. Five of16 affected persons have surgically confirmed otosclerosis; the remaining nine have a conductive hearing loss but have not undergone corrective surgery. To locate the disease- causing gene we completed genetic linkage analysis using short tandem repeat polymorphisms (STRPs) distributed over the entire genome. Multipoint linkage analysis showed that only one genomic region, on chromosome 15q, generated a lod score >2.0. Additional STRPs were typed in this area, resulting in a lod score of 3.4. STRPs FES (centromeric) and D15S657 (telomeric) flank the 14. 5 cM region that contains an otosclerosis gene.      

Anti-idiotypic IgM antibodies to anti-HLA class I antibodies in habitual abortion.

In order to investigate the role of the idiotypic network in miscarriages, sera from 28 habitually aborting women undergoing paternal leukocyte immunization were studied for the presence of HLA antibodies and related anti-idiotypes. Sixty-eight percent of sera from preimmunized patients which did not contain anti-lymphocyte antibodies inhibited the activity of antibodies to the HLA class I antigens expressed by the spouse. This inhibitory activity could be assigned to IgM antibodies, which cross-inhibit antibodies of similar specificity. This suggests that they are anti-idiotypes for the binding site of HLA antibodies. Immune sera of successfully treated patients exhibited both cytotoxic IgG anti-HLA antibodies and inhibitory IgM anti-idiotypic antibodies. A possible role for an intact idiotypic network in maintaining pregnancy is suggested.