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L Boudreau

Publications and source records attributed to L Boudreau.

11 recordsLinked to original sources
PubMed2001

Assembly of Alzheimer's amyloid-beta fibrils and approaches for therapeutic intervention.

Amyloid plaques are the principal features of Alzheimers disease (AD) pathology and are considered to be a major factor in the disease process. These fibrillar deposits are composed primarily of the 40-42 residue amyloid-beta (Abeta) peptide which is a proteolytic product of a larger membrane precursor protein. Electron microscopy and X-ray diffraction have revealed that the mature amyloid fibrils are assembled as a highly beta-sheet polymer that has a well-defined protofilament quaternary structure. This organization is observed for amyloid fibrils from a wide variety of disorders and appears to represent a structural superfamily. Amyloid plaques also contain a number of other components such as proteoglycans that contain highly sulfated glycosaminoglycan (GAG) chains. These amyloid-associated elements may contribute to the aggregation and/or stabilization of Abeta as insoluble fibrils. We have recently developed an aggressive model for Abeta plaque formation in transgenic mice that exhibits an "early-onset" phenotype. Immunocytochemistry has demonstrated that even with this rapid progression, Abeta deposits within the neuropil and cerebrovascular system all co-localize with heparan sulfate proteoglycans (HSPG). These findings indicate a number of structural features that can be targeted as potential sites for the development of amyloid inhibitors. In addition, the use of small compounds that interfere with the proteoglycan-amyloid pathway may be effective therapeutic agents that can be assessed through the use of these transgenic models.

Alzheimer Disease↗
PubMed1999

New clothes for amyloid enhancing factor (AEF): silk as AEF.

Amyloid enhancing factor (AEF) is an activity that appears naturally during the course of persistent inflammation and precedes, by 24-48 h, AA amyloid deposition in appropriate murine models. AEF is defined by its biological properties, namely, when administered intravenously or intraperitoneally to a mouse, it primes the recipient for the rapid induction of AA amyloid when they are given an inflammatory stimulus. Available evidence indicates that AEF is protein in nature, but a specific molecular species (if a singular species exits) has not been identified. Past work (Ganowiak et al., Biochem. Biophys. Res. Commun. 199:306-312, 1994) has shown that AEF activity may be imparted to two different proteins (IAPP and beta-protein) provided each is organized in the form of an amyloid fibril. Since a characteristic property of proteins in amyloid fibrils is their beta-sheet organization, one possibility is that AEF activity, in part, depends on such organization, and other proteins with such properties may also have AEF activity. To investigate this possibility, silk, a protein which contains substantial beta-sheet content, was denatured in LiSCN and allowed to renature slowly under reducing conditions to form a gel. The denatured silk preparation was then sonicated thoroughly to permit intravenous injection and assessed for AEF activity. The modified silk, presented as small fibrils in a beta-sheet conformation as assessed by electron microscopy and circular dichroism, respectively. This silk at 0-50 micrograms/animal was administered intravenously as "AEF" followed immediately by subcutaneous AgNO3 as the inflammatory stimulus. Six days later the spleens were examined for the presence of AA amyloid and following Congo red staining, the amount of amyloid quantified by image analysis. Modified silk without an inflammatory stimulus, and non-sonicated modified silk, failed to induce AA amyloid. Sonicated modified silk followed by AgNO3 induced large quantities of splenic AA amyloid in a dose dependent fashion. Modified silk in quantities as small as 1-5 micrograms/animal can function as AEF. The AEF properties of the modified silk were stable at 4 degrees C for at least 4 weeks (the longest period tested). This procedure may provide a means of standardizing AEF preparations.

Amyloid↗
PubMed1997

Development of an ostomy competency.

Staff educators and staff nurses developed an ostomy competency, with the guidance and expertise of the advanced practitioner and enterostomal nurse at a large teaching hospital. The competency improved the quality of care for surgical ostomy patients. Care was standardized and staff nurses' clinical knowledge was enhanced. Following the sessions, staff nurses verbalized increased confidence in working with patients with ostomies and demonstrated increased autonomy and problem-solving abilities. No variances in educational aspects of care were noted on clinical pathways.

Clinical Competence↗
PubMed1988

A reproducible model for the study of factor X kinetics in AA amyloidosis.

Factor X clearance was examined in a model of rapid AA amyloid deposition. Accelerated equilibration with extravascular compartments and accelerated removal postequilibration mimic features seen in patients with AL amyloidosis. The handling of Factor X was different from that of two other proteins, mouse albumin and IgG. Each protein had its own specific characteristic clearance properties, although in amyloidotic animals all proteins were cleared more rapidly in the postequilibration phase. The liver was by far the major site of Factor X clearance but this was true in all control groups as well. No significant difference was seen in tissue clearance site in any of the treatment groups, perhaps because the amount of AA amyloid in each tissue 3 days into the protocol was not yet large. Nevertheless, a reproducible model that possesses accelerated Factor X clearance is now available to study the mechanism of coagulation factor abnormalities in amyloidosis.

Albumins↗
PubMed1983

Kinetics of amyloid deposition. I. The effects of amyloid-enhancing factor and splenectomy.

It has long been recognized that amyloid AA deposition occurs in two phases, a predeposition and a deposition phase. The deposition phase has two distinct periods, a period of rapid deposition followed by a plateau stage. This kinetic pattern is seen in both liver and spleen and in animals in which the appearance of AA is accelerated by the administration of amyloid-enhancing factor. Amyloid-enhancing factor recipients have a shorter lag period before AA deposition is evident, but the kinetics of deposition and tissue level attained are similar to that seen in nonrecipients. It is also demonstrated that amyloid-enhancing factor activity may be generated in the liver of splenectomized animals.

Amyloid↗
PubMed1983

Kinetics of amyloid deposition. II. The effects of dimethylsulfoxide and colchicine therapy.

Amyloid (AA) protein, when deposition begins, is deposited in two stages--a rapid deposition period of 2 weeks and a plateau stage. The effect of dimethylsulfoxide (DMSO) and colchicine therapy on the kinetics of amyloid deposition was dependent on the stage of the disease at which therapy began. If given during the rapid deposition period, colchicine delayed the increase in amyloid but did not abolish it. Eventually, splenic and liver amyloid reached the level seen in untreated animals. On the other hand, DMSO given during the rapid deposition period led to significant resorption of both splenic and liver amyloid. By contrast, colchicine and DMSO given after the rapid deposition period were essentially without effect in promoting amyloid resorption. These results correlated well with the serum levels of SAA, the putative AA precursor. Colchicine given during the period of rapid AA deposition caused a transient decline in SAA levels, which eventually returned to levels seen in untreated animals. DMSO given during the rapid deposition period rapidly abolished the high SAA levels and maintained it at a level seen in normal animals. Both colchicine and DMSO therapy, if instituted after the rapid amyloid deposition period, failed to reduce SAA levels significantly below that of untreated controls.

Amyloid↗
PubMed1981

Awareness training and regulated-breathing method in modification of stuttering.

Awareness has been shown to be an important variable in various types of learning in humans. Its role in the modification of different clinical disorders is promising. It is hypothesized that systemic awareness training prior to the introduction of regulated-breathing method would significantly improve fluency in stutterers. 16 stutterers (mean age 25.1 yr.) were randomly assigned to one of two groups, awareness training plus regulated-breathing method or regulated-breathing method only. All clients were seen individually during two 90-min. sessions and were informed that their speech was being recorded. The percentage of stuttering and the rate of speech were analyzed. Awareness training significantly reduced stuttering compared to a control procedure. But the most significant improvement appeared after the introduction of the regulated-breathing method. At a 1-mo. follow-up, although the frequency of stuttering was significantly less than during baseline, the level of disfluency was around 5%. From a clinical perspective, such results are far from satisfactory and no further follow-ups were conducted. The theoretical and practical implications of these results are discussed to improve the efficacy of our therapeutic methods used to counteract stuttering.

Adolescent↗
PubMed1979

The effect of a liver protein synthesis inhibitor on plasma SAA levels in a model of accelerated amyloid deposition.

Animals treated with AgNO3 and amyloid-enhancing factor deposit large quantities of splenic amyloid in 48 hours. The kinetics of SAA production was examined in such a model in the presence and absence of an inhibitor of liver protein synthesis (ethionine). Ethionine had little effect on splenic protein synthesis but inhibited both the production of SAA and liver protein synthesis. When experiments were performed with fed mice, ethionine induced an inhibition of liver protein synthesis lasting 16 hours. Thereafter, liver protein synthesis began to recover, accompanied by a rise in plasma SAA levels. These results are consistent with hepatic but not splenic synthesis of SAA.

Amyloid↗