Biomedical subjects

G Gallo

Publications and source records attributed to G Gallo.

At least 19 recordsLinked to original sources

PubMed2007

Molecular and functional characterization of Lactobacillus sanfranciscensis strains isolated from sourdoughs.

Fifty isolates of Lactobacillus sanfranciscensis from Italian sourdoughs were identified and typed by a polyphasic approach which included genotypic and phenotypic criteria. Genotypic diversity was characterized by Ribosomal Intergenic Spacer Analysis (RISA) of PCR amplified 16S-23S rDNA spacer region, denaturing gradient gel electrophoresis (DGGE) of PCR amplified rpoB (beta subunit of RNA polymerase) gene, and rep-PCR (PCR amplification of repetitive bacterial DNA elements) analyses. The RISA analysis produced a unique electrophoretical profile of four bands (ranging from 300 to 600 bp) for all L. sanfranciscensis isolates. The DGGE analysis of rpoB gene allowed the subdivision of isolates in four clusters. The resolution found by using rep-PCR with primers BOXA1R and REP1R-I/REP2-I allowed the widening of the level of isolates heterogeneity. Phenotypic diversity was evaluated by Biolog System and characterization of several technological traits (e.g., acidification kinetics, proteinase and peptidase activities). L. sanfranciscensis isolates used a large varieties of carbon sources such as dextrin, D-fructose, L-fucose, alpha-D-glucose, maltose, palatinose, L-rhanmose, L- and D,L-lactic acids and L-methionine. The acidification activity and related quotient of fermentation, and the peptidase (PepN, PepV, PepT, PepI, PepX, PepQ and PepR) activities markedly varied among strains. The same was found concerning the capacity to liberate amino acids during sourdough fermentation. This study could be considered as an example of a computerized analysis of the genotypic and phenotypic traits to reliably and rapidly differentiate sourdough isolates. Although some L. sanfranciscensis isolates combined several technological traits, the association of more selected strains seemed to be a requisite to get optimal sourdough characteristics.

Bread↗

PubMed2004

In human gestational diabetes mellitus congenital malformations are related to pre-pregnancy body mass index and to severity of diabetes.

AIMS/HYPOTHESIS: This study analysed the relationship between congenital malformations (CM) and severity of gestational diabetes mellitus. METHODS: A cohort of 2060 infants of mothers with gestational diabetes was studied. Universal screening and 3(rd) Workshop-Conference criteria were used to diagnose gestational diabetes. The severity of diabetes was assessed on the basis of previous hyperglycaemia, blood glucose values in diagnostic OGTT, area under the glucose curve, gestational age and HbA(1)c at diagnosis, insulin requirements during pregnancy, and OGTT after delivery. Potentially confounding variables (age, pre-pregnancy BMI, smoking) were considered. The relationship of potential predictors with CM was analysed with several multivariate logistic regression analyses. RESULTS: The rate of CM was 6% for minor and 3.8% for major malformations (1.4% heart, 0.8% renal/urinary, 0.7% skeletal, 0.3% hypospadias, 0.2% central nervous system, 0.2% cleft lip/palate, 0.1% digestive tract, 0.3% other). In the final models, forward logistic regression analysis identified pre-pregnancy BMI as the predictor of CM (area under receiver operating characteristic curve 0.616); in the backward analysis additional predictors were 1-h blood glucose in diagnostic OGTT and gestational age at diagnosis (area under receiver operating characteristic curve 0.646). Both BMI and severity of gestational diabetes were predictors of heart and minor CM, whereas BMI predicted renal/urinary CM and severity of diabetes predicted skeletal CM. CONCLUSIONS/INTERPRETATION: In these infants of mothers with gestational diabetes, severity of diabetes and pre-pregnancy BMI were predictors of CM, in accordance with the well-documented pathogenic role of BMI (in the general population) and hyperglycaemia (in diabetic pregnancy). BMI was the main predictor of more prevalent CM.

Body Mass Index↗

PubMed2003

Prevention and monitoring of adverse events following immunization: the "Green Channel" of the Veneto region in Italy.

Measures to improve vaccine safety are essential for successful immunization programs. Therefore, an activity for vaccine adverse events prevention and surveillance, named the Green Channel, was established in the Veneto ion of Italy in 1992. This report summarizes the results of 10 years activity of a specialized pre-vaccination counseling service, offered to 543 selected at risk individuals referred for prior AEFIs or suspected contraindications (CI) to vaccine administration. Furthermore, data on 1762 AEFIs reported in this region are analyzed and discussed. This joint activity appeared effective and it is proposed as a model.

Adverse Drug Reaction Reporting Systems↗

PubMed2003

The role of vaccine in controlling hepatitis A epidemics.

We report the conduct and results of a review of recent literature to describe various types of epidemics and outbreaks in Italy or countries with similar epidemiological profiles and to assess vaccine use in outbreak situations. We identified three scenarios most likely to occur in Italy: outbreaks occurring in small closed communities (nursery or a primary school), outbreaks in communities of limited dimensions (small towns or villages) and open community settings in which epidemics occur at regular intervals (person-to-person transmission). In closed communities we recommend vaccination of family members and school personnel living or working in close proximity to the index case as well as classmates. We also recommend vaccination when there is a proof of secondary transmission within the community. In small open communities we recommend vaccination of more susceptible age groups such as children and adolescents. For large open communities the only practicable alternative strategy is vaccination of close family contacts of acute cases couple with non-immunity boosting control measures.

Disease Outbreaks↗

PubMed2003

Case fatality rate of acute viral hepatitis in Italy: 1995-2000. An update.

BACKGROUND: Fulminant hepatic failure is the most serious complication of viral hepatitis. Although this event occurs rarely, it may be fatal. AIMS: To evaluate the case fatality rate (several deaths divided by number of cases x 100) for each viral hepatitis type in Italy from 1995 to 2000. PATIENTS: Acute hepatitis cases identified by the surveillance system for acute viral hepatitis, which covers approximately 58% of the Italian population. RESULTS: Twenty-five deaths (0.1%) occurred among the 18 460 acute viral hepatitis cases observed from 1995 to 2000, a rate threefold lower than the 0.3% reported during the period 1985-1994. The highest case fatality rate (0.4%) was seen for acute hepatitis B (18 deaths among 4257 cases). Only one death (0.01%) occurred among the 11 063 acute hepatitis A cases and two deaths (0.1%) among the 1536 acute hepatitis C cases. No deaths were observed among the 309 acute hepatitis A cases superimposed on chronic HBsAg carriers and the 166 superimposed on chronic HCV carriers. Intravenous drug use (22.2% of cases) and other parenteral exposures (22.2% of cases) were the most frequent non-mutually exclusive sources of infection reported by subjects who died of acute hepatitis B. CONCLUSIONS: Analysis of surveillance system data from 1995 to 2000 indicates that, in Italy, deaths due to acute viral hepatitis are rare, but most commonly observed with acute hepatitis B. There is no evidence that acute hepatitis A may be fatal in chronic HBsAg or HCV carriers. The overall better survival rate may probably reflect improvements in the treatment of fulminant hepatitis in the last few years in Italy.

Acute Disease↗

PubMed2003

Study of viral integration of HPV-16 in young patients with LSIL.

AIMS: To investigate the physical status of human papillomavirus 16 (HPV-16) in low grade squamous intraepithelial lesions (LSILs) as a means of determining the percentage of viral integration. METHODS: Ninety two LSIL/HPV positive Thin Prep(TM) samples were initially tested for the E6 gene by the polymerase chain reaction (PCR) to identify the HPV-16 virus. To avoid false positive results, the specificity of the bands obtained from PCR was confirmed by Southern blot hybridisation with internal oligonucleotide probes. Next, a PCR screen for the E2 gene was performed to identify those samples in which the virus was integrated. Viral integration was detected in just over half of them. RESULTS: Twenty of the 92 samples were HPV-16 positive, as shown by PCR for the E6 gene. Southern blot analysis confirmed that 13 of these samples were positive for the viral E6 gene. Thus, viral integration was detected in just over a half of the samples positive for HPV-16. CONCLUSIONS: These data show that HPV-16 integration occurs in a subset of LSILs. The measurement of HPV-16 integration would be a helpful complementary tool for cytological evaluation in primary cervical screening to identify those patients at risk of developing high grade squamous intraepithelial lesions and cervical cancer.

Adult↗

PubMed2002

Cervico-vaginal dysplasia--papillomavirus-induced and HIV-1 infection: role of correlated markers for prognostic evaluation.

Sexually-transmitted diseases (STD) can facilitate the progression of HIV-1 infection. Among them, as we have previously demonstrated, cervico-vaginal dysplasia-papillomavirus (HPV)-induced, together with HSV-2 co-infection, seems to be correlated with a more evident immunodepression in HIV-positive women, compared with other sexually transmitted diseases. Here we have analysed some of the main correlated markers of HIV-1 infection progression: CD4 + T lymphocyte concentration, CD4 +/CD8 + T cells ratio, HIV-1 RNA loads and haemoglobin (Hb) concentration in 30 HIV-1 positive women co-infected with HPV, and suffering from cervico-vaginal dysplasia, in different stages. In particular, we noticed a positive correlation, evaluated by Spearman's test, between the degree of progression of dysplastic stages (CIN1 --> 3) until invasive carcinoma (IC) and HIV-1 RNA loads (C(s) = +0.78; p < 0.001), and in contrast, a negative correlation between the same stages of progression and respectively CD4 + T cell concentration (C(s) = -0.54; p = 0.01), ratio (C(s) = - 0.63; p = 0.002) and Hb concentration (C(s) = -0.85; p < 0.001). In conclusion, it is important to underline that low levels of Hb generally paralleled the degree of immunodepression. In fact CD4 + T cell levels and ratio positively correlated with Hb concentrations respectively, with C(s) = + 0.83; p < 0.001 and C(s) = + 0.90; p < 0.001. Finally, the most efficacious antiretroviral combined therapy (HAART = Highly Active Antiretroviral Therapy) can improve the above described laboratory parameters in HIV-1/HPV co-infected women and seems to prevent the progression of CIN1 to the following stages of the dysplastic disease.

Adult↗

PubMed2002

Risk of hepatitis A infection following travel.

Travel to endemic areas is one of the most frequently reported risk factors for infection with the hepatitis A virus (HAV). We evaluated the association between HAV infection and travel, by area of destination. We conducted a case-control study on all cases of HAV infection reported to the Italian National Surveillance System for Acute Viral Hepatitis in the period 1996-2000. The study population consisted of 9695 persons with HAV infection (cases) and 2590 with HBV infection (controls). The risk of acquiring HAV was highest for travel to Asia, Africa and Latin America [Odds Ratio = 9.30 (95%CI = 6.71-12.9)]; a three-fold statistically significant excess of risk was found for travel to southern Italy (OR = 3.03) and to the Mediterranean Area and Eastern Europe (OR = 3.15). Travel was implicated in 28% of the cases of HAV infection. When stratifying the analysis by area of residence (northern and central Italy vs southern Italy and the Islands), the above-mentioned risks were confirmed only for those residing in northern and central Italy, with no significant risk for those residing in southern Italy and the Islands. Travel to areas endemic for HAV infection constitutes a considerable risk. Our results highlight the importance of developing health policies for improving environmental and hygienic conditions, as well as the prevention of certain eating habits. Vaccination before travelling to a medium or high endemic area could be a safe and effective means of preventing travel-related HAV infection.

Adolescent↗

PubMed2001

Both the environment and somatic mutations govern the aggregation pathway of pathogenic immunoglobulin light chain.

Deposition of monoclonal immunoglobulin light chain (LC) aggregates in tissues is the hallmark of a class of fatal diseases with no effective treatment. In the most prevalent diseases two different types of LC aggregates are observed: fibrillar deposits in LC amyloidosis (AL) and granular aggregates in LC deposition disease (LCDD). The mechanisms by which a given LC forms either type of aggregate are not understood. Although some LCs are more aggregation-prone than others, this does not appear to be due to specific sequence determinants, but more likely from global properties that can be introduced by multiple somatic mutations. Moreover, a single LC isotype can sometimes form both fibrillar and granular aggregates within the same patient. To better understand how the different aggregation pathways arise, we developed a series of in vitro assays to analyze the formation of distinct aggregate types. The recombinant kappa IV LC (SMA) assembles into fibrils when agitated. We now show that SMA can also form granular aggregates upon exposure to copper, and that this aggregation can occur not only in vitro, but also in cells. A constellation of somatic mutations, consisting of His89/His94/Gln96, is sufficient to confer sensitivity to copper on wild-type kappa IV proteins. The formation of both types of aggregates is inhibited by synthetic peptides derived from the LC variable domain. However, the peptide that inhibits fibrillar aggregation is different from the peptide that inhibits copper-induced aggregation. Thus, distinct molecular surfaces of the LC underly each type of aggregate. We conclude that both the intrinsic properties of the sequence and extrinsic conditions govern the aggregation pathway of a LC.

Amino Acid Sequence↗

PubMed2001

Reactogenicity and immunogenicity of adult versus paediatric diphtheria and tetanus booster dose at 6 years of age.

We evaluated the reactogenicity and immunogenicity of a booster dose of diphtheria-tetanus vaccine administered at the age of school-entry, comparing a low-dose vaccine (dT) to the standard paediatric dose (DT). Participants were randomly assigned to receive one of the two vaccines; the study was evaluator-blinded. The frequency of side-reactions was similar when comparing the two groups, except when considering local redness and swelling, which were significantly more frequent among the DT group. The post-booster geometric mean titre of diphtheria antibodies in the DT group was twice as high as that in the dT group (14.1 IU/ml versus 7.7 IU/ml; P<0.001). The higher antibody response and the comparable reactogenicity indicate that DT should be used as booster at school-entry, particularly if additional booster doses during adolescence or adulthood are not administered.

Antibodies, Bacterial↗

PubMed2001

Novel 7-oxyiminomethyl derivatives of camptothecin with potent in vitro and in vivo antitumor activity.

In an attempt to synthesize potential anticancer agents acting by inhibition of topoisomerase I (Topo I) a new series of oxyiminomethyl derivatives in position 7 of camptothecin (CPT) was prepared. The synthesis relied on the condensation of 20S-CPT-7-aldehyde or 20S-CPT-7-ketones with alkyl, aryl, heteroaryl, arylalkyl, and heteroarylalkyl O-substituted hydroxylamines. The compounds were tested for their cytotoxic activity in vitro against H460 non-small lung carcinoma cell line, the activity being for 24 out of 37 compounds in the 0.01-0.3 microM range. A QSAR analysis indicated that lipophilicity is the main parameter correlated with cytotoxicity. Investigation of the DNA-Topo I-drug cleavable complex showed a rough parallelism between cytotoxicity and inhibition of Topo I. Persistence of the DNA cleavage after NaCl-mediated disruption of the ternary complex suggests that for the most potent compounds, e.g., 15, the cytotoxicity was at least in part related to stabilization of the complex, as also supported by the persistence of the DNA-enzyme complex in drug-treated cells. The in vivo antitumor efficacy of the most potent analogue (15) was evaluated in direct comparison with topotecan using human lung tumor xenograft models. In the range of optimal doses (2-3 mg/kg), the improved efficacy of 15 was documented in terms of inhibition of tumor growth and rate of complete response.

Animals↗

PubMed2001

Efficacy of an inactivated respiratory syncytial virus vaccine in calves.

OBJECTIVE: To determine whether an inactivated bovine respiratory syncytial virus (BRSV) vaccine would protect calves from infection with virulent BRSV. DESIGN: Randomized controlled trial. ANIMALS: 27 nine-week-old calves seronegative for BRSV exposure. PROCEDURE: Group-1 calves (n = 9) were not vaccinated. Group-2 calves (n = 9) were vaccinated on days 0 and 21 with an inactivated BRSV vaccine containing a minimum immunizing dose of antigen. Group-3 calves (n = 9) were vaccinated on days 0 and 21 with an inactivated BRSV vaccine containing an amount of antigen similar to that in a commercial vaccine. All calves were challenged with virulent BRSV on day 42. Clinical signs and immune responses were monitored for 8 days after challenge. Calves were euthanatized on day 50, and lungs were examined for lesions. RESULTS: Vaccination elicited increases in BRSV-specific IgG and virus neutralizing antibody titers and in production of interferon-gamma. Virus neutralizing antibody titers were consistently less than IgG titers. Challenge with BRSV resulted in severe respiratory tract disease and extensive pulmonary lesions in control calves, whereas vaccinated calves had less severe signs of clinical disease and less extensive pulmonary lesions. The percentage of vaccinated calves that shed virus in nasal secretions was significantly lower than the percentage of control calves that did, and peak viral titer was lower for vaccinated than for control calves. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that the inactivated BRSV vaccine provided clinical protection from experimental infection with virulent virus and decreased the severity of pulmonary lesions. Efficacy was similar to that reported for modified-live BRSV vaccines.

Animals↗

PubMed2001

Insulin-like effect of zinc in mytilus digestive gland cells: modulation of tyrosine kinase-mediated cell signaling.

The possible effects of zinc in the modulation of the activity of glycolytic enzymes phosphofructokinase and pyruvate kinase through tyrosine kinase-mediated signal transduction in isolated digestive gland cells from mussels (Mytilus galloprovincialis Lam.) were investigated. Addition of micromolar concentrations of zinc resulted in both time- and concentration-dependent stimulation of glycolytic enzyme activities similar to those previously observed with insulin; however, zinc pretreatment prevented the glycolytic effect of insulin in mussel cells. The insulin-like effect of zinc was mediated by increased tyrosine phosphorylation of multiple proteins, as demonstrated by Western blotting with antiphosphotyrosine antibodies. The pattern of zinc-induced phosphorylation resembled that induced by insulin. Moreover, both zinc and insulin induced activation of mitogen activated protein kinases (MAPKs); however, whereas zinc gave a clear effect on the stress-activated p-38 MAPK, insulin activated extracellular-activated MAPK (ERK2) and inhibited p-38. The results demonstrate that zinc can act as a physiological regulator of tyrosine kinase-mediated cell signaling in mussel digestive gland cells, in particular at the level of MAPK activation. Activation of p-38 by zinc may be a key step in prevention of the glycolytic effect of insulin in mussel cells. These data underline the importance of cross talk between different MAPKs in determination of the response to extracellular stimuli in marine invertebrate cells.

Animals↗

PubMed2001

Risk of parenterally transmitted hepatitis following exposure to surgery or other invasive procedures: results from the hepatitis surveillance system in Italy.

BACKGROUND/AIMS: To evaluate the strength of association between parenterally transmitted viral hepatitis and specific types of invasive procedures. METHODS: Data from the surveillance system for type-specific acute viral hepatitis (SEIEVA) during the period 1994-1999 were used. The association of acute hepatitis B virus (HBV) and hepatitis C virus (HCV) infection with the potential risk factors (odds ratios (OR)) was estimated comparing 3120 hepatitis B and 1023 hepatitis C cases with 7158 hepatitis A cases, used as controls, by multiple logistic regression analysis. RESULTS: Most procedures resulted in being associated with the risk of acquiring acute HBV or HCV. The strongest associations were: for HBV infection, abdominal surgery (adjusted OR = 3.9; 95% confidence intervals (CI) = 2.0-7.5), oral surgery (OR = 2.7; 95% CI = 1.6-4.5) and gynaecological surgery (OR = 2.6; 95% CI = 1.2-5.5); for HCV infection, obstetric/gynaecological interventions (OR = 12.1; 95% CI = 5.6-26.3), abdominal surgery (OR = 7.0; 95% CI = 3.2-14.9) and ophthalmological surgery (OR = 5.2; 95% CI = 1.1-23.2). Biopsy and/or endoscopy were associated with HCV, but not with HBV infection. CONCLUSIONS: Invasive procedures represent an important mode of HBV and HCV transmission. Since a large proportion of the adult general population is exposed to these procedures and an effective HCV vaccine is not yet available, non-immunological means of controlling iatrogenic modes of transmission are extremely important.

Adolescent↗

PubMed2001

Biochemical properties of metalloproteinases from the hemolymph of the mussel Mytilus galloprovincialis Lam.

The expression of matrix metalloproteinases (MMP) with gelatinase activity was found in the whole hemolymph of the marine mussel Mytilus galloprovincialis Lam. Cleavage activity was specific for gelatin; very little activity towards human type-IV collagen, and no activity for cold fish gelatin, casein or bovine serum albumin were detected. EDTA and 1,10-phenanthroline were inhibitory, suggesting that mussel MMPs require divalent cations for their proteolytic activity; in fact, the presence of exogenously added divalent ions significantly protected the MMPs from inhibition. No inhibition was detected with serine or cysteine proteinase inhibitors. The specific vertebrate inhibitors as well as the classical vertebrate activator of MMPs were without effect, whereas sulphydryl reducing agents had a strong inhibitory effect. Mussel MMPs showed an exponential curve of thermal-dependent decay that was not protected by the presence of metal ions. Overall the results indicate both similarities and differences between invertebrate and vertebrate gelatinases, providing information for understanding the biological role of these ancient proteinases.

Animals↗

PubMed2001

Changing epidemiology of parenterally transmitted viral hepatitis: results from the hepatitis surveillance system in Italy.

BACKGROUND: In 1991, compulsory hepatitis B virus vaccination and screening for anti-hepatitis C virus of blood banks were introduced in Italy. AIM: To evaluate the impact of preventive measures on the incidence and risk factors for parenterally transmitted viral hepatitis. METHODS: Data from the surveillance system for acute viral hepatitis for the period 1985-99 were used. Temporal trends in distribution of reported risk factors were analysed by comparing three-year periods: 1987-89 and 1997-99. RESULTS: The incidence (no. cases per 100,000 population) of hepatitis B was 12 in 1985 and 3 in 1999; the incidence of hepatitis non-A, non-B decreased from 5 to 1 in the same period. These decreases were more evident among young adults and before rather than after 1991. Multiple sexual partners, other parenteral exposures and dental treatment remain the most common risk factors for parenterally transmitted viral hepatitis. An increase in frequency over time was observed for other parenteral exposures, whereas a marked decrease was evident for blood transfusion and household contact with an HB-sAg carrier. Invasive medical procedures continue to represent an important source of infection. Intravenous drug use was reported particularly by young adults with non-A, non-B hepatitis, with increased frequency over time. CONCLUSIONS: Non-immunologic measures for preventing hepatitis B and non-A, non B due to iatrogenic and other parenteral exposures, combined with hepatitis B virus vaccination, could further reduce parenteral transmission.

Acute Disease↗

PubMed2001

Risk management of HBsAg or anti-HCV positive healthcare workers in hospital.

Recommendations are made for controlling the transmission of the hepatitis B and hepatitis C viruses from healthcare workers to patients. These recommendations were based both on the literature and on experts' opinions, obtained during a Consensus Conference. The quality of the published information and of the experts' opinions was classified into 6 levels, based on the source of the information. The recommendations can be summarised as follows: all healthcare workers must undergo hepatitis B virus vaccination and adopt the standard measures for infection control in hospitals; healthcare workers who directly perform invasive procedures must undergo serological testing and the evaluation of markers of viral infection. Those found to be positive for: 1) HBsAg and HBeAg, 2) HBsAg and hepatitis B virus DNA, or 3) anti-hepatitis C virus and hepatitis C virus RNA must abstain from directly performing invasive procedures; no other limitations in their activities are necessary. Infected healthcare workers are urged to inform their patients of their infectious status, although this is left to the discretion of the healthcare worker; whose privacy is guaranteed by law. If exposure to hepatitis B virus occurs, the healthcare worker must undergo prophylaxis with specific immunoglobulins, in addition to vaccination.

Algorithms↗

PubMed2001

Amyloid and nonfibrillar deposits in mice transgenic for wild-type human transthyretin: a possible model for senile systemic amyloidosis.

The human serum protein transthyretin (TTR) is highly fibrillogenic in vitro and is the fibril precursor in both autosomal dominant (familial amyloidotic polyneuropathy [FAP] and familial amyloidotic cardiomyopathy [FAC]) and sporadic (senile systemic amyloidosis [SSA]) forms of human cardiac amyloidosis. We have produced mouse strains transgenic for either wild-type or mutant (TTRLeu55Pro) human TTR genes. Eighty-four percent of C57BI/6xDBA/2 mice older than 18 months, transgenic for the wild-type human TTR gene, develop TTR deposits that occur primarily in heart and kidney. In most of the animals, the deposits are nonfibrillar and non-Congophilic, but 20% of animals older than 18 months that bear the transgene have human TTR cardiac amyloid deposits identical to the lesions seen in SSA. Amino terminal amino acid sequence analysis and mass spectrometry of the major component extracted from amyloid and nonamyloid deposits revealed that both were intact human TTR monomers with no evidence of proteolysis or codeposition of murine TTR. This is the first instance in which the proteins from amyloid and nonfibrillar deposits in the same or syngeneic animals have been shown to be identical by sequence analysis. It is also the first time in any form of amyloidosis that nonfibrillar deposits have been shown to systematically occur temporally before the appearance of fibrils derived from the same precursor in the same tissues. These findings suggest, but do not prove, that the nonamyloid deposits represent a precursor of the fibril. The differences in the ultrastructure and binding properties of the deposits, despite the identical sizes and amino terminal amino acid sequences of the TTR and the dissociation of deposition and fibril formation, provide evidence that in vivo factors, perhaps associated with aging, impact on both systemic precursor deposition and amyloid fibril formation.

Aging↗