Areas Of Amyloid Deposition Research Articles

The influence of SARS-CoV-2 on the immune system elements and on the placental structure. Clinical, histological and immunohistochemical study.

The effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy remain relatively unknown. We present this original paper where we analyzed 60 parturients, at term, 30 without associated infection (C-) and 30 with associated infection (C+), present at birth. We analyzed the blood count and placental microscopic structure through classical and immunohistochemical staining and observed the placental areas affected by the presence of SARS-CoV-2. SARS-CoV-2 infection was accompanied by a decrease in the number of lymphocytes, the number of platelets and the presence of placental structural changes, identifying extensive areas of amyloid deposits, placental infarcts, vascular thrombosis, syncytial knots, with a decrease in placental vascular density and the presence of infection in the cells located at decidual level, at syncytiotrophoblast level and at the level of the cells of the chorionic plate, still without overcoming this barrier and without causing any fetal infection in the analyzed cases. This study shows that the invasion of SARS-CoV-2 in the placenta can produce significant structural changes, with a decrease in placental vascular density that can have significant implications on proper fetal perfusion. Also, the presence of immunoreactivity at the level of decidua, the placental villi, as well as the chorionic plate proves that the virus can overcome the maternal-fetal barrier. However, in the analyzed cases there were no fetal infections at birth, which may show that local placental factors can be a protective filter for the fetus.

Deep Learning Algorithms for Corneal Amyloid Deposition Quantitation in Familial Amyloidosis

Objectives: The aim of this study was to train and validate deep learning algorithms to quantitate relative amyloid deposition (RAD; mean amyloid deposited area per stromal area) in corneal sections from patients with familial amyloidosis, Finnish (FAF), and assess its relationship with visual acuity. Methods: Corneal specimens were obtained from 42 patients undergoing penetrating keratoplasty, stained with Congo red, and digitally scanned. Areas of amyloid deposits and areas of stromal tissue were labeled on a pixel level for training and validation. The algorithms were used to quantify RAD in each cornea, and the association of RAD with visual acuity was assessed. Results: In the validation of the amyloid area classification, sensitivity was 86%, specificity 92%, and F-score 81. For corneal stromal area classification, sensitivity was 74%, specificity 82%, and F-score 73. There was insufficient evidence to demonstrate correlation (Spearman’s rank correlation, –0.264, p = 0.091) between RAD and visual acuity (logMAR). Conclusions: Deep learning algorithms can achieve a high sensitivity and specificity in pixel-level classification of amyloid and corneal stromal area. Further modeling and development of algorithms to assess earlier stages of deposition from clinical images is necessary to better assess the correlation between amyloid deposition and visual acuity. The method might be applied to corneal dystrophies as well.

Significant association between renal function and area of amyloid deposition in kidney biopsy specimens in both AA amyloidosis associated with rheumatoid arthritis and AL amyloidosis

The kidney is a major target organ for systemic amyloidosis, which results in proteinuria and an elevated serum creatinine level. The clinical manifestations and precursor proteins of amyloid A (AA) and light-chain (AL) amyloidosis are different, and the renal damage due to amyloid deposition also seems to differ. The purpose of this study was to clarify haw the difference in clinical features between AA and AL amyloidosis are explained by the difference in the amount and distribution of amyloid deposition in the renal tissues.A total of 119 patients participated: 58 patients with an established diagnosis of AA amyloidosis (AA group) and 61 with AL amyloidosis (AL group). We retrospectively investigated the correlation between clinical data, pathological manifestations, and the area occupied by amyloid in renal biopsy specimens.In most of the renal specimens the percentage area occupied by amyloid was less than 10%. For statistical analyses, the percentage area of amyloid deposition was transformed to a common logarithmic value (Log10%amyloid). The results of sex-, age-, and Log10%amyloid-adjusted analyses showed that systolic blood pressure (SBP) was higher in the AA group. In terms of renal function parameters, serum creatinine, creatinine clearance (Ccr) and estimated glomerular filtration rate (eGFR) indicated significant renal impairment in the AA group, whereas urinary protein indicated significant renal impairment in the AL group. Pathological examinations revealed amyloid was predominantly deposited at glomerular basement membrane (GBM) and easily transferred to the mesangial area in the AA group, and it was predominantly deposited at in the AL group. The degree of amyloid deposition in the glomerular capillary was significantly more severe in AL group. The frequency of amyloid deposits in extraglomerular mesangium was not significantly different between the two groups, but in AA group, the degree amyloid deposition was significantly more severe, and the deposition pattern in the glomerulus was nodular. Nodular deposition in extraglomerular mesangium leads to renal impairment in AA group.There are significant differences between AA and AL amyloidosis with regard to the renal function, especially in terms of Ccr, eGFR and urinary protein, even after Log10%amyloid was adjusted; showing that these inter-group differences in renal function would not be depend on the amount of renal amyloid deposits. These differences could be explained by the difference in distribution and morphological pattern of amyloid deposition in the renal tissue.

Can autologous bone marrow transplantation improve systolic function in patients with multiple myeloma related cardiac amyloidosis?

Introduction: Cardiac amyloidosis complicates multiple myeloma (MM) and almost all B-cell dyscrasias, and is the cause of death in about half of these patients [1]. The prognosis of patients with MM has improved with aggressive chemotherapy [2]. Autologous bone marrow transplant (BMT) is also being increasingly used in these patients [3]. Marrow stromal cells used in BMT contain multipotent cells, which can differentiate into cells with cardiomyocyte phenotype [4]. We postulated that these cells may home into regions of damaged myocardium and areas of amyloid deposits, and participate in cardiac repair.

Distribution of amyloid deposits in the kidneys of a patient with reactive amyloidosis associated with rheumatoid arthritis

BackgroundWe previously reported that the amount of amyloid A (AA) amyloid deposited in renal biopsy specimens was highly correlated with parameters of renal function. However, the distribution of amyloid deposits throughout the kidneys of these patients, and the degree of renal abnormality, remained unclear. Therefore, we describe the features of reactive amyloidosis associated with rheumatoid arthritis (RA) in an autopsied patient.Case presentationThe present report case is a 50-year-old female with RA and reactive amyloidosis. She was diagnosed as RA in 1978. Diagnosis of AA amylodosis was made by renal biopsy in 1991 for the reason of proteinuria. Because of the pancreatitis, she was died in 2006 and autopsy was performed. Renal tissues from autopsy specimens were evaluated for their proportions of amyloid-positive areas. A total of 6 specimens (three tissue blocks from each kidney obtained at autopsy) were evaluated in this study. The size of each block was approximately 20 mm × 20 mm. One section of whole tissue was photographed in each case. The borders of the amyloid-positive areas in each specimen were traced in each photograph, excluding any tissue-free spaces. The total amyloid-positive area was measured, and the percentage area of amyloid per whole-tissue section (percent (%) area of amyloid deposition) was calculated. The distribution of amyloid deposits in the kidneys was examined. The significance of differences in the mean percent (%) area of amyloid deposition between the right and left sides and among three long-axis levels (upper, middle and lower) were analyzed by two-way analysis of variance (ANOVA) at a significance level of p <0.05.ConclusionThe area of amyloid deposition in these samples was about 7-11%, and the degree of variability among them seemed to be small. It also shows a comparison of amyloid deposition between the right and left sides and between the long axis samples for quadruplicate determinations; no significant differences were evident, and thus the percent (%) area of amyloid deposition throughout the whole kidneys appeared to be uniform in this patient.

Primary amyloidosis with high grade transitional cell carcinoma of bladder: A rare case report

Primary amyloidosis of bladder is a rare disease that closely resembles bladder cancer on clinical presentation with painless gross hematuria. Pathologically this is a totally benign non-neoplastic lesion and its association with urothelial carcinoma of the bladder is rare. We herein report a 64-year-old diabetic male who has been treated for primary amyloidosis of bladder for the last 26 years presented recently with high-grade solid urothelial cancer with osseous metaplasia and sarcomatoid change of bladder with area of amyloid deposition.

Significant association between renal function and area of amyloid deposition in kidney biopsy specimens in reactive amyloidosis associated with rheumatoid arthritis

The kidney is a major target organ for systemic amyloidosis, resulting in proteinuria and an elevated serum creatinine level. In patients with reactive amyloidosis associated with rheumatoid arthritis, a correlation between the amount of amyloid deposits and clinical parameters is not known. The purpose of this study was to clarify the association between various factors including renal function and the area of amyloid deposition in these patients. Fifty-eight patients with an established diagnosis of reactive AA amyloidosis were studied. We retrospectively investigated the correlation between clinical data and the area occupied by amyloid in renal biopsy specimens. All the patients showed amyloid deposits in renal tissues, and the percentage of the area occupied by amyloid was <10% in 54 of them. Mesangial proliferative glomerulonephritis and membranous nephropathy were frequently combined with renal amyloidosis. For statistical analyses, the percentage of the area occupied by amyloid was transformed to a common logarithmic value (Log(10) % amyloid), as the histograms showed a log-normal distribution. Log(10) % amyloid was found to be correlated with age, creatinine (Cr) level, creatinine clearance (Ccr), blood urea nitrogen (BUN) level, and the estimated glomerular filtration rate (eGFR). Multiple linear regression analyses were then performed to examine the sex- and age-adjusted association between Log(10) % amyloid and each of the clinical variables. Cr, Ccr, BUN, UA, CRP, and eGFR were significantly correlated with Log(10) % amyloid, but urinary protein was not. There was a significant correlation between the area of amyloid deposition in renal tissue and parameters of renal function, especially Cr and Ccr. If amyloid deposition in renal tissue can be arrested or prevented, then it may be possible to maintain renal function at an acceptable level.

Generation and Characterization of Anti-AA Amyloid-Specific Monoclonal Antibodies

AA amyloidosis results from the pathologic deposition in the kidneys and other organs of fibrils composed of N-terminal fragments of serum amyloid A protein (SAA). Given that there are only limited means to visualize these deposits, we have developed a series of mAbs, 2A4, 7D8, and 8G9, that bind specifically with nanomolar affinity to a carboxy-terminal epitope generated following proteolysis of SAA that yields the predominant component of AA amyloid deposits. Notably, these antibodies do not recognize native SAA, they retain their immunoreactivity when radiolabeled with I-125 and, after injection into AA amyloidotic mice, localize, as evidenced by autoradiography and micro-single photon emission computed tomography imaging, to histologically confirmed areas of amyloid deposition; namely, spleen, liver, and pancreas. The results of our in vitro and in vivo studies demonstrate the AA fibril-selectivity of mAbs 2A4, 7D8, and 8G9 and warrant further investigation into their role as novel diagnostic agents for patients with AA amyloidosis.

Effective Anti-TNF-α Therapy Can Induce Rapid Resolution and Sustained Decrease of Gastroduodenal Mucosal Amyloid Deposits in Reactive Amyloidosis Associated with Rheumatoid Arthritis

To examine the effect of anti-tumor necrosis factor-alpha (anti-TNF) therapy in patients with reactive AA amyloidosis associated with rheumatoid arthritis (RA). Fourteen patients with reactive AA amyloidosis associated with RA were prospectively evaluated. Four patients were treated with infliximab and 10 with etanercept. The mean period of anti-TNF therapy was 20.1 +/- 13.8 months. Laboratory findings and renal function were examined before and after initiation of anti-TNF therapy. In 9 patients the area of amyloid deposits in serial gastroduodenal mucosal biopsy specimens was examined and image analysis was performed. C-reactive protein and serum amyloid A protein levels were significantly reduced after initiation of anti-TNF therapy. Twenty-four hour creatinine clearance improved in 4 patients, did not change in 5, and deteriorated in 3. Twenty-four hour urinary protein excretion was significantly decreased in 3 patients, not exacerbated in 6, and increased in 3 after initiation of anti-TNF therapy. The biopsy specimens from the 9 patients who underwent serial gastroduodenal biopsies showed significant decreases in the area of amyloid deposits, from 8.8% +/- 6.4% to 1.6% +/- 0.6% (p = 0.003) after initiation of anti-TNF therapy. Four patients showed a sustained decrease in the areas of amyloid deposits in their third biopsy specimens, and amyloid deposits were not detectable in 2. Our results indicate a striking effect of anti-TNF therapy for rapid removal and sustained disappearance of amyloid deposits in gastric mucosal tissue with amelioration of renal functions in patients with reactive amyloidosis due to RA.

Quantitative assessment of myocardial T2 relaxation times in cardiac amyloidosis

To evaluate cardiac MRI (CMR) in the diagnosis of cardiac amyloidosis by comparing the T2 relaxation times of left ventricular myocardium in a pilot patient group to a normal range established in healthy controls. Forty-nine patients with suspected amyloidosis-related cardiomyopathy underwent comprehensive CMR examination, which included assessment of myocardial T2 relaxation times, ventricular function, resting myocardial perfusion, and late gadolinium enhancement (LGE) imaging. T2-weighted basal, mid, and apical left ventricular slices were acquired in each patient using a multislice T2 magnetization preparation spiral sequence. Slice averaged T2 relaxation times were subsequently calculated offline and compared to the previously established normal range. Twelve of the 49 patients were confirmed to have cardiac amyloidosis by biopsy. There was no difference in mean T2 relaxation times between the amyloid cases and normal controls (51.3 +/- 8.1 vs. 52.1 +/- 3.1 msec, P = 0.63). Eleven of the 12 amyloid patients had abnormal findings by CMR, eight having LGE involving either ventricles or atria and four demonstrating resting subendocardial perfusion defects. CMR is a potentially valuable tool in the diagnosis of cardiac amyloidosis. However, calculation of myocardial T2 relaxation times does not appear useful in distinguishing areas of amyloid deposition from normal myocardium.

Thermosensitive lichen amyloidosis

A 26-year-old male presented with a 3-year history of lichen amyloidosis. On examination, there was a pigmented papular eruption with a ripple pattern affecting the limbs and trunk but sparing the axillae, antecubital and popliteal fossae, central chest, neck and face. There was also prominent sparing of the skin overlying the superficial veins of the limbs. The sparing of the superficial veins of the limbs by lichen amyloidosis raised the possible role of cutaneous temperature in governing the distribution of amyloid deposits in our patient. Total body infrared thermography demonstrated consistent sparing of the amyloid deposits in areas with higher cutaneous temperatures such as the neck and axillae as well as the course of the superficial veins. The cooler areas such as the extensor surfaces of the arms and legs corresponded to areas of amyloid deposition. Narrow band ultraviolet B (NBUVB) phototherapy over a 5-month period resulted in a marked improvement of pruritus and clearing of the amyloid deposits. Our patient clearly demonstrated lichen amyloidosis in a thermosensitive distribution. This may be a gross manifestation of previous reports of in vitro thermosensitivity of amyloid fibril formation and may have potential implications in treatment at least in a subset of patients demonstrating this clinical feature.

In vitro degradation of serum amyloid A by cathepsin D and other acid proteases: possible protection against amyloid fibril formation.

The effects of acid proteases on degradation of serum amyloid A protein (SAA) were investigated in vitro. Human recombinant SAA1 (rSAA1), when incubated with human spleen extracts at pH 3.2, was degraded in the amino-terminal portion of the molecule. This reaction was inhibited by an acid protease inhibitor, pepstatin. The degraded SAA molecules lacking nine or more amino-terminal residues, when exposed to in vitro fibril-forming conditions, failed to form Congo red positive precipitates and did not show amyloid fibril-like structure by electron microscopy. This suggests that the amino-terminal portion of SAA is essential for fibril formation. Cathepsin D, one of the lysosomal enzymes, also initiated degradation of rSAA1 at the amino-terminus. Cathepsin D immunoreactivity was detected in marginal areas of amyloid deposits in spleens from patients with reactive amyloidosis. These findings suggest that cathepsin D or similar acid proteases may be involved in SAA catabolism and may protect against amyloid formation.

Cell death in Alzheimer's disease evaluated by DNA fragmentation in situ

Loss of nerve cells is a hallmark of the pathology of Alzheimer's disease (AD), yet the patterns of cell death are unknown. By analyzing DNA fragmentation in situ we found evidence for cell death not only of nerve cells but also of oligodendrocytes and microglia in AD brains. In average, 30 times more brain cells showed DNA fragmentation in AD as compared to age-matched controls. Nuclear alterations suggestive of apoptosis were rare in degenerating cells. Even though the majority of degenerating cells were not located within amyloid deposits and did not contain neurofibrillary tangles, neurons situated within areas of amyloid deposits or affected by neurofibrillary degeneration revealed a higher risk of DNA fragmentation and death than cells not exposed to these AD changes.

Immunohistochemical classification of 140 autopsy cases with systemic amyloidosis.

One hundred and forty autopsy cases of systemic amyloidosis were examined using the potassium permanganate method for distinction of amyloid A protein from other amyloid proteins and an immunohistochemical technique. Of those cases, amyloid proteins were identified in 121 cases. There were 68 cases of amyloid A-related (AA) amyloidosis and these were the most common type among the cases (56.2%). There were 39 cases of immunoglobulin light chain-related (AL) amyloidosis (32.2%), six cases of beta 2-microglobulin-related (A beta 2M) amyloidosis (5%), and five cases of transthyretin-related (ATTR) amyloidosis (4.1%). Minute areas of amyloid deposits in four cases with AA were resistant to potassium permanganate pretreatment. In A beta 2M amyloidosis amyloid deposits were either resistant or sensitive to potassium permanganate pretreatment, from case to case. The coexistence of two different amyloid proteins was seen in three cases: one case had ATTR and A kappa types, and two cases had A beta 2M and AA types. Some discrepancies were seen between the immunohistochemical typing and clinical classification of amyloidosis referred to in the Annual of the Pathological Autopsy Cases in Japan, for example, one case of AA type in myeloma-associated amyloidosis and one case of AL type in secondary amyloidosis. From the present results, the importance of the immunohistochemical method in classifying amyloidosis is stressed.

Plasma cell tumors with calcified amyloid deposition mistaken for chondrosarcoma.

To report cases of plasmacytoma with a radiologic appearance simulating that of chondrosarcoma. The authors describe four cases of plasma cell tumors with scattered foci of calcification within their matrix, causing them to resemble chondrosarcoma radiographically. Histologic examination was performed in three of these cases. Biopsy specimens demonstrated that the calcification in these tumors was contained in areas of amyloid deposition. Although amyloid formation in association with plasma cell dyscrasias is well known, sufficient calcification within the amyloid to become radiographically identifiable has only rarely been reported. Calcification in amyloid produced by plasma cell tumors may at times simulate the appearance of chondrosarcoma.

A method for the detection of amyloid in human tissue embedded in epon using a combination of polarizing light microscopy and electron microscopy.

This paper describes a method for demonstrating amyloid in human tissue embedded in epon using a combination of congo red staining and polarizing microscopy. The method involves the removal of the embedding medium from semi-thin sections prior to staining with congo red and examination in the polarizing microscope. Typical apple green birefringence was detected in areas of amyloid deposition; these areas were mapped for selective trimming and ultra-thin sections taken serially were examined in the electron microscope. The method was found to be reliable, easy to use and particularly of value as a sampling procedure prior to investigation in the electron microscope.