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PubMedDate not supplied

Demineralization around orthodontic brackets bonded with resin-modified glass ionomer cement and fluoride-releasing resin composite.

PURPOSE: Enamel demineralization adjacent to orthodontic brackets is one of the risks associated with orthodontic treatment. Glass ionomer cements have been shown to decrease enamel demineralization adjacent to brackets and bands but do not exhibit bond strengths comparable to resin composites. The purpose of this in vitro study was to compare a fluoride-releasing resin composite versus a resin-modified glass ionomer cement for inhibition of enamel demineralization surrounding orthodontic brackets. METHODS: Forty-five teeth were randomly assigned to 3 groups of 15 teeth. Fifteen were bonded with Concise (3M), a non-fluoride-releasing resin composite (control); 15 teeth were bonded with Light Bond (Reliance), a fluoride-releasing resin composite; and 15 teeth were bonded with Fuji Ortho LC (GC Corporation), a resin-modified glass ionomer cement. The teeth were placed in an artificial caries solution to create lesions. Following sectioning of the teeth in a buccolingual direction, polarized light microscopy was utilized to evaluate enamel demineralization adjacent to the orthodontic bracket. The area of the lesion was measured 100 microns from the orthodontic bracket and bonding agent. RESULTS: MANOVA (P < .0001) and Duncan's test (P < .05) indicated the resin-modified glass ionomer cement (Fuji Ortho LC) and the fluoride-releasing resin composite (Light Bond) had significantly less adjacent enamel demineralization than the non-fluoride-releasing resin composite control. However, there was no significant difference between the resin-modified glass ionomer cement and the fluoride-releasing resin composite. CONCLUSIONS: Based on the results of this in vitro study, it can be concluded that Fuji Ortho LC and Light Bond exhibit significant inhibition of adjacent demineralization compared to the non-fluoride-releasing control.

Acrylic Resins↗

PubMedDate not supplied

Kinetic cavity preparation effects on secondary caries formation around resin restorations: a polarized light microscopic in vitro evaluation.

The purpose of this in vitro study was to compare the effect of conventional handpiece and kinetic cavity preparation (KCP, air abrasion) techniques of cavity preparation on caries-like enamel lesion formation. After a fluoride-free prophylaxis, twelve human molars were examined macroscopically to ensure that buccal and lingual surfaces were caries-free. Unfilled cavities were prepared in mesiobuccal (conventional [CU]) and mesiolingual (air abrasion [AU]) enamel surfaces. Cavities were prepared in distobuccal (conventional [CF]) and distolingual (air abrasion [AF]) enamel surfaces and restored with composite resin following placement of a bonding agent. Acid-etching of cavity walls was performed only with the conventionally prepared cavities restored with resin. Air abrasion (KCP) prepared cavities were restored without acid-etching of the cavity walls. Teeth were thermocycled (500 cycles, 5 degrees to 50 degrees C, 500 cycles) and exposed to an artificial caries medium for caries initiation and progression. After caries formation, two longitudinal sections were taken from unfilled and filled cavity preparations and examined by polarized light microscopy for wall lesion presence and mean surface lesion depth. Surface lesion depths were similar among groups after the caries initiation period (CU = 225 microns; AU = 237 microns; CF = 241 microns; AF = 251 [p > .05, ANOVA, DMR]), and progression (CU = 437 microns; AU = 415 microns; CF = 405 microns; AF = 429 um [p > 0.05, ANOVA, DMR]). Extensive wall lesions were present in all CU and AU; while small wedge-shaped wall lesions were significantly (p < .05, ANOVA, DMR) fewer in CF (19 percent & 21 percent) and AF (17 percent & 21 percent) following caries initiation and progression compared with unfilled controls. Resin restorations placed in cavities prepared by air abrasion (KCP) and conventional handpiece techniques provided similar degrees of protection against a secondary caries-like challenge.

Acid Etching, Dental↗

PubMed2001

[Effects of diuretic therapy on spontaneous expulsion of urinary calculi, urinary pH, and crystalluria in lithiasic patients].

OBJECTIVE: High urine volume is known to be an effective measure for preventing stone recurrence. However, only few studies have investigated its effects on crystalluria and spontaneous passage of calculi. The aim of the study was to assess the effects of high diuresis on stone expulsion and recurrence. PATIENTS AND METHODS: 219 patients were consulting for a first stone episode in Urology units in the Mostaganem area between September 1996 and December 1999. All stones were under 6 mm in size. The patients were divided in two groups: group I included 129 patients (68 males, 61 females) who agreed to be on a high water intake, at least 3 liters per day, over a two months period and to be followed periodically by crystalluria examination in the first morning urine; group II included 90 patients (63 males, 27 females) who declined diuresis advice and urine collection for crystalluria examination. First morning urine collected in patients of group I were examined before (2.95 voidings per subject) and while on diuresis course (2.84 voidings per subject). For each sample, the urine pH was measured and crystals were looked for by polarizing microscopy. Stones spontaneously passed were collected and analyzed by infrared spectroscopy. Group II represented the control group for stone passing and recurrence. RESULTS: Crystalluria was present in 52.4% of urine samples before starting diuresis and decreased at 22.9% of urine samples on high diuresis. Mean pH value increased from 5.73 +/- 0.46 before to 6.09 +/- 0.47 (p < 10-6) while on diuresis course in males and from 5.8 +/- 0.68 to 6.24 +/- 0.66 in females (p < 10-6). The most frequent crystalline species was weddellite. Over the study period, 98 patients (76%) in group I and only 13 patients (14.4%) in group II passed stones spontaneously (p < 10-6 contre group I). No stone recurrence was observed in group I while 37.8% of patients in group II presented at least one stone recurrence (p < 10-7). CONCLUSION: A high diuresis is an effective measure (1) to make easier the passing of stone under 6 mm in size; (2) to reduce the occurrence of crystalluria; (3) to reduce significantly, because of its favourable effect on urine pH, the formation of pH-dependent crystalline phases, thus decreasing heterogeneous nucleation process of calcium oxalate and stone recurrence.

Adolescent↗

PubMedDate not supplied

[Adhesive ileus caused by a peritoneal reaction to starch].

Peritoneal reaction caused by glove powder is not so rare in surgical practice. We have presented a case report of a patient who was operated on due to the adhesive bowel obstruction, two years after the total gastrectomy for gastric cancer. Changes found on the peritoneal surface were similar to carcinomatous dissemination, but intraoperative frozen section analysis showed granulomatous lesions caused by foreign bodies. Nature of these changes was confirmed by PAS smear and polarization microscopy. Clarification of the peritoneal changes during relaparotomy is possible only with careful microscopic analysis of these granulomas.

Gloves, Surgical↗

PubMed2001

Demineralization of enamel in relation to the fluoride release of materials.

PURPOSE: To examine the reduction in enamel demineralization provided by fluoride release from a conventional glass-ionomer, a resin-modified glass-ionomer and an experimental fluoride-releasing resin-based composite compared to a conventional resin-based composite control, and to correlate the level of fluoride release with demineralization. MATERIALS AND METHODS: Enamel surfaces of extracted human incisors had a 0.4 mm thick layer of the specified test material carefully placed in a band across the mid-facial enamel to simulate a cement layer beneath an orthodontic bracket. The top surface of the test material was covered with nail varnish, leaving only the edges of the material exposed to release fluoride. The teeth were additionally covered with nail varnish to within 1 mm of the test material. Each group of teeth was placed into separate volumes of unstirred demineralizing solution at a pH of 4.7 for 4 days. The specimens were sectioned and examined by polarized light microscopy. Lesion areas were measured at distances from 100-800 microm away from the test material. Fluoride release for the test materials was measured for periods up to 5 months. RESULTS: All of the fluoride-releasing materials demonstrated a statistically significant (P< 0.05) degree of protection of enamel from demineralization compared to the non-fluoride control material. The degree of protection was greatest near the material, but lesion areas increased with distance in an inverse relationship to the amount of fluoride release. Lesions were displaced from the region near the materials and the mean displacement was directly related to amount of fluoride release. The mean lesion areas for each distance decreased with the logarithm of the cumulative fluoride release.

Acetates↗

PubMed2002

Association of changes in the pattern of urinary calculi in Taiwanese with diet habit change between 1956 and 1999.

OBJECTIVE: Due to rapid economic development over the past four decades, urinary stone components may have changed in Taiwan. We studied the changes in urinary stone components over time and the possible association with dietary changes during the same period. MATERIALS AND METHODS: From 1956 to 1999, 9,715 urinary calculi were collected at a single institution and analyzed using polarizing microscopy. Dietary information was obtained from an official national report. Linear regression was used to analyze the possible correlation between the change in stone components with daily consumption of animal protein, vegetable protein, and lipid. RESULTS: Eleven distinct components were identified. Calcium oxalate (Jensen type I stone; found in sterile, acidic urine) was found most frequently (87.3%), and its incidence increased gradually with time. However, the incidence of Jensen type III stone (caused by metabolic abnormality) gradually decreased from 1956 to 1999. The male to female ratio among subjects was 2.3:1, and the modal age was in the forties. Female patients were more likely to suffer from type II stones (found in infected, alkaline urine), whereas type I and III stones were more prevalent in males. Among the dietary components, consumption of animal and vegetable proteins and lipid increased significantly during the same period, and appeared to be coincident with the increased incidence of type I stones during the study period. CONCLUSIONS: Patterns of urinary tract stones in Taiwan have progressively changed in the past four decades and are now similar to those in western populations. The incidence of type I stones has increased during the past four decades, which may reflect the Westernization of dietary habits in Taiwanese during the same period.

Adult↗

PubMedDate not supplied

Fluoride varnishes and caries development in primary tooth enamel: an in vitro study.

This in vitro study evaluated the effect of fluoride varnishes on caries development in primary tooth enamel using polarized light microscopic techniques. A total of forty extracted or exfoliated primary teeth with intact, caries-free smooth surfaces underwent a fluoride-free prophylaxis and soft tissue were assigned to one of the following groups: 1) duraphat (5 percent sodium fluoride, vanish, Colgate, n=10); 2) Duraflor (5 percent sodium fluoride, Pharmascience, n = 10); 3 Cavity Shield (5 percent sodium fluoride varnish, Omni, n=10); and 4) Control (n=10). An acid-resistant coating was applied to the specimens leaving an exposed window of sound enamel (5mm x 1mm). The fluoride varnishes were applied to the primary teeth according to the manufacturer's recommendation. Following thermocycling (500 cycles, 5-50 degrees C) of the fluoride varnish-treated and control teeth, a fluoride-free pumice toothbrushing was performed to remove visible and macroscopically (dissecting microscope at 16x) detectable fluoride varnish. An acid resistant coating was reapplied where necessary, leaving the fluoride varnish treated sound enamel window exposed. Following in vitro caries formation (2.2mM Ca, 2.2mM PO4 50mM acetic acid, 0.5ppm fluoride, pH 3.90), longitudinal sections (5 per specimen) were obtained and evaluated by polarized light microscopy for mean lesion depth. Comparisons were made among treatment and control groups.

Analysis of Variance↗

PubMed2002

Artificial formed caries-like lesions around esthetic restorative materials.

Dental restorations fail for a variety of reasons. Secondary caries is one of the primary causes of failure of dental restorations. One method for reducing frequency and severity of this problem is the use of fluoride containing restorative materials. The ability of a material to inhibit secondary caries formation is an important clinical therapeutic property. This investigation assessed the capacity of esthetic restorative materials to resist caries in vitro. Class V cavities were prepared in buccal and lingual surfaces of 50 extracted sound third molars. The occlusal and gingival cavosurface margin of each preparation was on enamel surface. The five materials were used: Conventional glass ionomer cement Ceramfil beta (PSP), two polyacid modified resin composites Compoglass (Vivadent) and Dyract (Dentsply/DeTrey), non fluoride releasing composite resin Valux Plus (3M) and fluoride releasing composite resin Tetric (Vivadent). After 10 weeks in an acid gel for caries-like lesion formation, the teeth were sectioned occluso-gingivally through the middle of the restorations and examined by polarized light microscopy, while immersed in water. The statistical analysis of the results showed that secondary caries initiation and progression might be reduced significantly when fluoride-containing materials were placed. The conventional glass ionomer cement (Ceramfil beta) provided the highest protection against caries attack and the non-fluoride releasing composite resin (Valux Plus) restoration provided the least (p<0.05).

Acids↗

PubMedDate not supplied

In vitro evaluation of fluoride-releasing restorative materials for sealing the root canals of overdenture abutments.

PURPOSE: The purpose of this study was to evaluate the ability of newer fluoride-releasing restorative materials to protect the root surface from acid attack. MATERIALS AND METHODS: The materials used were glass-ionomer cement (GIC), resin-modified glass-ionomer cement (RM-GIC), and a compomer (Comp). A composite resin (CR) was used as the control. The restored teeth were stored in deionized, distilled water for 14 days and subjected to 300 thermocycles (55 degrees C and 5 degrees C). The teeth were cycled in a demineralizing solution (pH 5.0 or 4.0) for 6 hours and in a remineralizing solution (pH 7.0) for 17 hours for 10 days. The depths of lesions created by acid challenge were measured at the interface of the tooth and the restorative material and then at a distance of 50, 100, and 300 microns from the tooth-restoration margin using polarized light microscopy and contact microradiography. RESULTS: At pH 4.0, there was significant difference in the depth at the interface between the tooth and the restorative material (P < .001). The GIC and RM-GIC were protective, and the lesion depths were significantly shallower than for Comp or CR. The protective effect varied depending on the distance from the interface of the tooth and the restorative material. At pH 5.0, the GIC and RM-GIC had no lesions at the interface, while the Comp and the CR had lesions (P < .001). CONCLUSION: Fluoride-releasing glass-ionomer cement seems to be an appropriate material to seal the root canals of overdenture abutments, because it has an inhibiting effect on demineralization at the cavity wall in vitro.

Aged↗

PubMed2002

Cartilage intermediate layer protein expression in calcium pyrophosphate dihydrate crystal deposition disease.

OBJECTIVE: To elucidate the mechanisms of calcium pyrophosphate dihydrate crystal deposition disease (CPPDCD) in the meniscus, synovium, labrum, tendon, ligament, and soft tissue, we studied the expression of cartilage intermediate layer protein (CILP). METHODS: Histological sections and clinical data from 33 patients who fulfilled the criteria of Ryan and McCarty for CPPD were reviewed. Formalin fixed and paraffin embedded tissue sections of 33 patients with CPPDCD were stained with hematoxylin and eosin (H&E) and alizarin red S. Immunostaining was performed using affinity purified polyclonal antibody to synthetic peptide corresponding to the N-terminal sequence of the 61 kDa domain of porcine CILP. RESULTS: The age of patients ranged from 49 to 89 years (median 73). The knee was the commonest site. Radiologically, almost all lesions exhibited fine, radiopaque, linear deposits in the meniscus, articular cartilage, and synovium or joint capsule. Histopathologically, all cases showed deposits of birefringent monoclinic or triclinic crystals, which were visualized by polarized light microscopy with a red analyzer filter. In alizarin red S staining, more numerous crystals were observed than in H&E staining. Crystal deposition was usually associated with adjacent variable amounts of hypertrophic and/or metaplastic chondrocytes in each type of tissue. Variable intensity of CILP immunostaining was found in deposits of each lesion. Hypertrophic/metaplastic chondrocytes in and around CPPD deposits were also positive for CILP. Small cartilaginous islands remote from the CPPD deposits exhibited a weak positivity for CILP. In addition, weakly positive chondrocytes were noted in a transitional zone between cartilaginous islands with and without the deposits. In addition to cytoplasmic immunoreactivity, immunostaining for CILP was observed in the pericellular fibrous matrix. CONCLUSION: Hypertrophic or metaplastic chondrocytes characteristic of CPPDCD may be directly involved in the formation of CPPD crystals. Our study suggests that increased CILP expression was closely associated with CPPDCD, and might play a role in promoting CPPD crystal formation.

Aged↗

PubMed2002

[Pilar dysplasias].

Pilar dysplasias are congenital or acquired disorders, they are characterized by hair abnormalities in color, density, length and structure. Optic microscopy and polarized light microscopy analysis of piliary shafts provides important informations and contribute to the diagnosis of complex syndromes. Many pathological profiles can be visualized, some are specific, other are not. Some authors use a particularly convenient classification including 3 groups: in the first, piliary shaft abnormalities are isolated, in the second the abnormalities correspond to complex syndromes, and in the third they are associated with various malformations. Based on some clinical cases, we will describe various types of pilar dysplasias and we present recent advances, particularly in genetics.

Hair Diseases↗

PubMed1975

Aflatoxin effects with liquid crystalline cholesteryl esters of duckling sera.

An objective of this study was to determine indicator parameters of blood sera that are symptomatic for degenerative hepatic cholesterogenesis and lipid transformations induced with carcinogenic mycotoxins. A technique was developed for electrophoretic separation of liquid crystalline cholesteryl esters within beta lipoprotein fractions of duckling sera. These birefringent moieties decreased to 110 mug/mg low-density lipoprotein during 10-day bioassay periods for normal, nontoxin fed ducklings, but remained unchanged--179-189 mug/mg-for toxin-fed principals ingesting 0.988 mug aflatoxin/g feed throughout the bioassays. Their composition was principally cholesteryl esters with liquid crystalline characteristics determined by the oleate and linoleate content. Increased cholesterol levels--11.4% to 17.1% within sera of the nontoxin group--resulted in more frequent spherulitic mesoforms. The 0.9% to 1.8% taurochenodesoxycholate content within all sera samples induced stable cubic liquid crystalline forms. With polarized microscopy, cholesteric anisotrophs of sera were unique in composition and iridescent visage for each aflatoxin level regime. This specific dicroism was correlated with the corresponding hepatic histology.

Aflatoxins↗

PubMed2002

[Trichothiodystrophy and congenital heart disease in two sisters].

INTRODUCTION: Trichothiodystrophy refers to a heterogeneous group of autosomal recessive genodermatosis of unknown etiology. Patients with trichothiodystrophy have alopecia with typical hair dysplasia ("tiger-tail"), and abnormally low sulfur content. Numerous unrelated neuroectodermal defects have been observed in trichothiodystrophy. We report here trichothiodystrophy and congenital heart disease in two sisters. CASES REPORT: Two sisters were born as collodion babies and presented ichthyosis and alopecia. The diagnosis of trichothiodystrophy was confirmed by polarizing microscopy of hair and low sulfur content. Both had congenital heart disease. DISCUSSION: Cardiovascular defects have rarely been reported in trichothiodystrophy. The association trichothiodystrophy - congenital heart disease has never been described. The low incidence of both conditions suggests that these abnormalities are linked etiologically rather than by chance. Abnormal Notch signaling, or contiguous gene deletion syndrome could lead to combined phenotype as observed in our family.

Alopecia↗

PubMed2003

[A case of corneal lactoferrin amyloidosis secondary to trichiasis].

PURPOSE: A case of corneal lactoferrin amyloidosis secondary to trichiasis is reported. CASE: A 30-year-old male suffered from trichiasis with an elevated gray whitish lesion just under the center of the cornea in his right eye. The lesion had an irregular surface. METHOD: We excised the corneal lesion, and studied the excised corneal lesion morphologically. RESULT: The deposit observed just under the corneal epithelial layer was positive for Congo red staining, and showed dichroism under polarizing microscopy. The deposit also showed a immunoreactivity against anti-human lactoferrin antibody. CONCLUSION: The morphological study proved that the deposits under the corneal lesion were derived from lactoferrin. Long term injury of the corneal surface by trichiasis may lead to the deposition and structural changes of lactoferrin originating from tears.

Adult↗

PubMed2003

Collagen fibers in human prostatic lesions: histochemistry and anisotropies.

The present study focuses on establishing patterns of collagen fibers distribution in prostatic nodular hyperplasia and adenocarcinomas, in comparison with the normal tissue. Sections of prostatic transurethral resection were subjected to Gömöri's method for collagen fibers and reticulin and analyzed under ordinary and polarized light microscopy. Controls and hyperplastic regions present collagen fibers with variable thickness that run in different directions, establishing a tridimensional network. These fibers exhibit birefringence and dichroism thus demonstrating their fibrillar integrity. On the other hand, increased variability in collagen fiber distribution and anisotropical properties occur in adenocarcinomas evaluated in accordance withthe Gleason's score. In some of their areas, a well-defined collagen network delimitates the base of transformed epithelial cells whereas in other areas the collagen fibers are disorganized and do not establish a boundary between the epithelial structures and the stroma. In these areas, collagen is found in the stroma. It was also observed that adenocarcinoma tumor cells rest on a scaffold of thin and dendritic collagen fibers. Collagen fibers of the prostatic stroma of the adenocarcinomas may show a modification in arrangement and fibrillar compactness. In prostatic nodular hyperplasia, there is no change in collagen molecular integrity, since collagen affinity for silver and collagen birefringence are similar to controls. In adenocarcinoma with high dedifferentiation degree, thin and branched strongly argyrophilic and birefringent collagen fibers are detected in regions of cell proliferation. In the adjacent stroma, hyaline plaques are indicative of matrix degradation or remodellation.

Adenocarcinoma↗

PubMed1992

[Serpentine mine "Nasławice" as the source of contamination of soil and agricultural plants with metals and fibrous minerals].

The study was aimed at evaluation of the effect of dust, produced at crushing the serpentine, on the soil and crops in Nasławice. The serpentine dust, apart from asbestos, contains also magnesium, calcium, chromium and nickel. These elements have been determined in the soil and plants by means of the standard methods generally used in agricultural chemistry, whereas asbestos content was determined by means of X-ray diffractometry and polarization microscopy. The dust of the crops harvested contained asbestos fibres and, in the plants, the increased content of nickel an chromium was found. The highest amount of asbestos was found in soil in the area at a distance of up to 50 km from the emission source. The soil contains also the increased amounts of chromium and sporadically cadmium.

Agriculture↗

PubMed2003

Remodeling of the cardiac extracellular matrix differs between volume- and pressure-overloaded ventricles and is specific for each heart valve lesion.

BACKGROUND AND AIM OF THE STUDY: Different patterns of fibroblast-mediated remodeling of the extracellular matrix (ECM) might be expected between patients with pressure- and volume-induced left ventricular hypertrophy. METHODS: Patients with chronic pressure-overload due to aortic stenosis (AS, n = 19) and chronic volume-overload due to either aortic regurgitation (AR, n = 9) or mitral regurgitation (MR, n = 10) were examined. The amount of interstitial collagen was quantified by using circular-polarization-microscopy in picrosirius red-stained biopsies. Biopsies from 10 patients with mild cardiomyopathy served as controls. In a subgroup, collagen type-I (Coll-I) and collagen type-III (Coll-III) gene expression was evaluated by quantitative RT-PCR. After immunohistological staining, procollagen-I/procollagen-III ratio and density of fibroblasts (FB) per vision-field were analyzed. RESULTS: The amount of interstitial cardiac fibrosis (ICF) was significantly higher in AS (5.7 +/- 4.1 g/m2), AR (8.8 +/- 4.9 g/m2) or MR (4.7 +/- 2.8 g/m2) than in controls (2.3 +/- 1.5 g/m2) (p = 0.003). The amount of thick collagen fibers was higher in AR than in AS, where-by density of fibroblasts did not differ. In volume-overloaded ventricles, the Coll-I/Coll-III ratio was shifted towards Coll-I, and in pressure-overloaded ventricles towards Coll-III. The severity of ECM remodeling was positively correlated with wall stress and impaired diastolic function, but not with systolic function or clinical symptoms. CONCLUSION: Remodeling of the ECM is specific for left ventricular volume and pressure overload, and may serve as an early indicator for inadequate adaptation.

Adult↗

PubMed2003

Fibrillogenesis in gelsolin-related familial amyloidosis.

To clarify the mechanisms involved in amyloid formation in Finnish-type familial amyloidosis (FAF), we have tested the in vitro fibrillogenicity of synthetic wild-type and mutated gelsolin peptide analogs and studied the fragmentation patterns of gelsolin in the circulation of FAF patients with the Asn-187 or Tyr-187 gelsolin mutation. Fibril formation of synthetic peptides having sequence homology with wild-type or mutant gelsolins was monitored by Congo-red staining and polarization microscopy, negative staining electron microscopy and quantitative thioflavine-T fluorometry. Immunoblotting with anti-gelsolin and amyloid-specific antibodies and sequence analyses were used to study the fragmentation pattern of gelsolin. Ultrastructurally amyloid-like fibrils were formed from mutant Asn-187 and Tyr-187 gelsolin peptides. Fluorometric analysis revealed highly accelerated fibril formation from the mutant peptides as compared with the corresponding wild-type peptides. Addition of mercaptoethanol alone or in combination with dithiotreitol tended to enhance fibril formation of the 9-mer and 11-mer Asn peptides. Blocking of the C-terminal carboxyl of the mutant Asn-187 gelsolin182-192 peptide by amidation increased amyloidogenicity. The Tyr-187 gelsolin mutation, corresponding to the naturally occurring mutation in the Danish subtype of FAF, required acidic conditions to form fibrils meeting the criteria of amyloid. In FAF patients, in addition to the full-sized gelsolin, a series of lower-molecular mass C-terminal fragments of gelsolin (70,000-45,000 Da) was found in the circulation. In homozygous FAF(Asn-187) the 65-kDa fragment containing the amyloid forming region and the 55-kDa fragment, devoid of that region, was the major gelsolin species in the plasma. The results indicate that the 65-kDa gelsolin fragment derived by alpha-gelsolinase cleavage at the mutation-induced novel proteolysis site Arg172-Ala173 represents the putative circulating precursor protein of tissue amyloid in FAF and that the Asp187Asn/Tyr substitution in gelsolin creates a conformation that is highly fibrillogenic.

Amino Acid Sequence↗