Usefulness of osteoprotegerin in assessing responses to neridronate treatment in Paget's disease of bone

Osteoprotegerin (OPG) is a protein that inhibits of osteoclastogenesis. The aim this study was to evaluate the response of serum OPG levels to neridronate treatment in patients with Paget's disease of bone resistant to previous therapy. Nine patients (4 men) affected by active Paget’s disease of bone (6 polyostotic, 3 monostotic) not responsive to clodronate were studied. Serum OPG, osteocalcin, total and bone isoenzyme of alkaline phosphatase (AP and BAP, respectively), and urinary deoxypyridinoline (DPD) were measured before and 5 months after neridronate treatment (100 mg/day, i.v. for two days). A scintigraphic activity index (SAI) was also calculated before treatment. Mean baseline OPG levels were within normal values and were not significantly different 5 months after neridronate treatment. In contrast, there were significant reductions in AP (41.9%, p<0.02) and BAP (38.8%, p<0.04). Serum OPG levels correlated with DPD (r=0.925) and SAI (r=0.689). Although OPG is an important regulator of bone metabolism, in our series of already treated patients it was not a sensitive marker for diagnosing Paget's disease and for monitoring the response to pharmacological treatment, whereas AP and BAP confirmed their clinical usefulness. This preliminary study requires confirmation by a study with a larger population.     

Development of a monoclonal antibody specific for beta/A4 amyloid in Alzheimer's disease brain for application to in vivo imaging of amyloid angiopathy.

We evaluated the efficacy of murine monoclonal antibodies (Mabs) targeted to beta/A4 amyloid for development of procedures for the in vivo identification of amyloid angiopathy (AA) in Alzheimer's disease (AD). Mabs to beta/A4 amyloid were prepared and screened for effectiveness in visualizing AA and senile plaques in postmortem AD brain sections. They were assessed again after enzymatic cleavage to produce Fab fragments and after labeling with 99mTc using a diamide dimercaptide ligand system. Modified and radiolabeled Fab fragments retained activity and specificity towards amyloid-laden blood vessels and senile plaques. A highly specific murine Mab, 10H3, was identified and characterized that fulfills criteria necessary for the development of a diagnostic imaging agent. Expansion and adaptation of these strategies may provide the methods and materials for the noninvasive analysis of AA in living patients, and permit assessment of the contribution of AA to the clinical and pathological features of AD.     

急性胰腺炎的模式转变:意大利全国范围多中心研究结果

1996年我们在意大利全国范围内开展了一次关于急性胰腺炎的调查,并对研究结果进行了计算机统计分析.     

Preparation of a recombinant cDNA library from poly(A+) RNA of the Alzheimer brain. Identification and characterization of a cDNA copy encoding a glial-specific protein

Studies were undertaken to assess the extent to which messenger RNA prepared from the postmortem Alzheimer's disease (AD) brain can be used for the successful preparation of a recombinant cDNA library. Initial experiments focused on the glial-specific marker glial fibrillary acidic protein (GFAP) since GFAP expression appeared to be a model for further studies on mRNAs that may continue to be expressed at high levels in the vicinity of lesioned sites in the AD brain. An AD cDNA library, prepared in the lambda gt11 expression vector system contained GFAP-specific recombinants. One of these was sequenced and the insert was shown to exhibit 88% homology with the similar sequence from mouse GFAP. As established by Northern blots, the size of the GFAP mRNA prepared from the routinely acquired postmortem AD cortex, approximately 2.7 kb, was the same as from a neurologically normal control brain. These results agree with earlier studies on GFAP mRNA from fresh mouse brain. The results demonstrate that in the postmortem AD brain, astroglial-specific mRNA remains sufficiently stable for molecular genetic analysis and may serve as a useful model for examining the genetic expression of mRNAs that may be related to the molecular pathogenesis and the etiology of AD.     

Maternally inherited deafness associated with a T1095C mutation in the mDNA

Hearing loss is a relatively frequent defect in children with a genetic or predisposition basis in about 50% of cases. Mitochondrial DNA (mtDNA)-associated disorder often present with sensorineural hearing loss (SNHL) either in isolation or as a part of a multisystem disorder in adults but the frequency in pediatric cases is unknown. We analysed deafness-related mtDNA mutations in 80 deaf children to assess the relative frequency of alterations in childhood-onset SNHL. In 16 patients in whom maternal inheritance was possible, we screened for new mutations likely to affect mitochondrial protein synthesis. In one child we detected a novel mutation (T1095C) in the 12S rRNA gene. This mutation fulfils the suggested criteria for definition of a disease-related nucleotide variant. No mutations were found in other patients. Although we cannot exclude the presence of still undefined new mtDNA mutations, our data suggest that mtDNA defect are not common in childhood-onset SNHL.