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PubMed1984

Clinical value of immunohistochemistry with AF-antibody in the diagnosis of familial amyloid neuropathy.

Peripheral polyneuropathy associated with recurrent diarrhoea and orthostatic hypotension was observed in two unrelated German kinships and two sporadic cases. Congo red staining and polarization microscopy of biopsy specimens revealed amyloid deposits. Immunohistochemical investigation using the indirect immunoperoxidase staining with antisera to several purified amyloid fibril proteins showed a positive reaction with an antiserum to the prealbumin-related AF-amyloid in the families and one of the sporadic cases and with an antiserum to the immunoglobulin light chain amyloid (A lambda) in the other sporadic case. Therefore, the amyloid of the families and one of the sporadic cases was identified as the prealbumin-related AF amyloid, while the amyloid of the other sporadic case was of immunoglobulin origin. It is concluded that immunohistochemistry with antisera to the different amyloid proteins is useful in the differential diagnosis of amyloid neuropathy.

Adult↗
PubMed1995

Rapid deposition of amyloid in human islets transplanted into nude mice.

Human islets of Langerhans were transplanted to the subcapsular space of the kidneys of nude mice which were either normoglycaemic or made diabetic with alloxan. After 2 weeks, the transplants were processed for light and electron microscopical analyses. In all transplants, islet amyloid polypeptide (IAPP)-positive cells were found with highest frequency in normoglycaemic animals. IAPP-positive amyloid was seen in 16 out of 22 transplants (73%), either by polarisation microscopy after Congo red staining or by immune electron microscopy. At variance with previous findings of amyloid deposits exclusively in the extracellular space of islets of non-insulin-dependent diabetic patients, the grafted islets contained intracellular amyloid deposits as well. There was no clear difference in occurrence of amyloid between diabetic and non-diabetic animals. The present study indicates that human islets transplanted into nude mice very soon present IAPP-positive amyloid deposits. This technique may provide a valuable model for studies of the pathogenesis of islet amyloid and its impact on islet cell function.

Adolescent↗
PubMed1976

Comparative ultrastructure of thyroid, tongue and eyelid lesions in the neuroma phenotype of medullary carcinoma of the thyroid: association of amyloid with fibroblasts in thyroid tumor and in mucosal neuromas.

Electron-microscopic and histochemical studies of thyroid tumor, tongue neuromas and eyelid neuromas from the lesions of a patient with medullary thyroid carcinoma were compared. In the thyroid tumor, a significant number of the C cells showed heterogeneity of granule types; no C cells, however, were identified in the tongue and eyelid neuromas. Amyloid was clearly shown by Congo red staining in the thyroid neoplasm and in the tongue neuromas. In all tissues, amyloid fibrils were found to be ultrastructurally closely associated with fibroblasts. These fingings suggest that the fibroblast rather than the C cell may have played the important role in the deposition of amyloid in this patient's thyroid carcinoma.

Amyloid↗
PubMed1980

Histochemical analysis of senile plaque amyloid and amyloid angiopathy.

Histochemical methods were used to obtain information on the chemical constituents of brain amyloid in senile dementia of the Alzheimer type. The staining properties of brain amyloid (senile plaque and amyloid angiopathy) were compared with those of extraneural amyloidosis and endocrine amyloid. We found no histochemical differences between amyloid in senile plaques and in amyloid angiopathy. The content of aromatic amino acids was higher in amyloid of plaques and in amyloid angiopathy than in endocrine amyloid. Furthermore, we found persistent birefringence and affinity of brain amyloid for Congo red after exposure to potassium permanganate, suggesting that AA amyloid is not a major constituent of cerebral amyloid.

APUD Cells↗
PubMed1983

Application of thiazole dyes to amyloid under conditions of direct cotton dyeing: correlation of histochemical and chemical data.

The fluorescent brightening agent Phorwhite (Blankophor) BBU imparts intense selective fluorescence to amyloid, but this modern reagent is no longer readily available on the biological dye market. Conventional Thioflavine S and T stains require differentiation and are not specific. To improve selectivity, direct and cationic thiazole dyes were substituted in the alkaline Congo Red and the Phorwhite BBU procedure. With the former technic Diphenyl Brilliant Yellow 8G, Clayton Yellow, Thiazol Yellow, Thioflavine T and Seto Flavine T imparted strong to intense selective fluorescence to amyloid. Under the conditions of the Phorwhite BBU reaction these dyes were suitable only for formalin-fixed amyloid. Several thiazole dyes did not fluoresce. Fluorescence is a function of the molecular orbital system, the thiazole rings per se cannot induce fluorescence. Paper chromatograms indicated two or more fractions in the dyes studied. Different samples of the same dye can vary significantly in their staining and fluorescence properties. This heterogeneity is inherent in the mode of synthesis. In some cases the cationic thiazole dyes rendered certain amyloid deposits, e.g. in vessel walls, intensely fluorescent; other amyloid deposits in the same sections showed only weak fluorescence. Further studies are required to correlate these peculiar patterns with immunological data on amyloid types.

Amyloid↗
PubMed1990

The cytoarchitectonic distribution of senile plaques in three aged monkeys.

The density of senile plaques (SP) was determined in 55 cytoarchitectonic areas of the cerebral cortex in three aged (27+ years) macaque monkeys. In silver-stained sections the SP distributions pattern was variable, with a predilection for frontal areas and the primary somatosensory cortex. In one monkey, SP density in motor and premotor areas reached a level comparable to that found in Alzheimer's disease (AD). Lower SP densities were found in the amygdala and insula, and in cingulate, limbic temporal, and temporal, occipital, and parietal association cortices. Then lowest densities were in the hippocampus and in the primary auditory and primary visual cortices. SP stained with Congo red, to identify the older amyloid-containing plaques, showed a similar distribution but were fewer in number. There was at times a marked shift in SP density between adjacent cytoarchitectonic fields, suggesting that cytoarchitectonics or connectivity may play a role in determining SP distribution. The distribution of the SP in the normal aged human brain according to cytoarchitectonic areas is not known. Their pattern of distribution in these three primates appears to differ from that found in AD, which emphasizes the hippocampus, amygdala, entorhinal cortex, and temporal and parietal lobe.

Aging↗
PubMed1988

Solubility of neurofibrillary tangles and ultrastructure of paired helical filaments in sodium dodecylsulphate.

Temporal cortex from 14 cases of Alzheimer-type dementia and 6 cases of Down's syndrome, all selected for severe Alzheimer pathology, was homogenised in distilled water, NaOH, or sodium dodecylsulphate (SDS) containing 0.1% beta-mercaptoethanol. The homogenates were stained with Congo red, and the neurofibrillary tangles and plaque cores were counted under crossed-polarisation microscopy. The number of tangles and plaque cores in the water-treated extracts was not related to age, sex, post-mortem interval or duration of dementia. The number of tangles after extraction in SDS or NaOH, as a percentage of tangles in water-treated extracts, was 57 +/- 25 (mean +/- SD) for 1% SDS, 43 +/- 17 for 5% SDS and 37 +/- 22 for 0.2 M NaOH. Plaque cores were essentially insoluble in all three agents. The percentage of tangles insoluble in 1% SDS did not correlate with age or post-mortem interval but decreased with increasing duration of dementia. Enhanced tangle solubility with increasing duration of dementia suggests that the nature of tangles changes with time; one possibility is that this reflects transformation of intracellular to extracellular tangles. Paired helical filament (PHF) length and the number of repeats per PHF were measured in electron micrographs of PHF prepared with and without treatment by 1% SDS. There was no significant multimodality of PHF length to suggest that PHF broke at regular intervals. The mean repeat length (PHF length/number of repeats) was greater for PHF isolated in the presence of 1% SDS than in its absence, showing that SDS affects ultrastructure by untwisting PHF.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

Diffuse type of senile plaques in the brains of Alzheimer-type dementia.

We studied the nature of diffuse type of senile plaques (SP) in the brains of six autopsied subjects with Alzheimer-type dementia (ATD). The densities of SP in the entorhinal cortex were evaluated using serial sections stained by four different methods. Compared with beta protein immunostaining (100% as a reference), the modified Bielschowsky stain (103%) and the periodic acid-methenamine silver (PAM) stain (109%) labeled similar numbers of SP, whereas the Bodian stain labeled only a minor proportion (42%) of these. The vast majority of Bodian-negative plaques were diffuse plaques, which were seen as ill-defined areas of fine fibrillar material after beta protein immunostain with formic acid pretreatment, modified Bielschowsky stain, and PAM stain. They were not stained by Congo red or periodic acid-Schiff stains. Double staining using Bodian and beta protein methods demonstrated that diffuse plaques were free of swollen neurites. Argyrophilia of the diffuse plaques shown by the modified Bielschowsky and PAM stains, became undetectable when sections were pretreated with formic acid. Such treatment made the diffuse plaques immunoreactive to beta protein antiserum, suggesting that diffuse plaques consisted mainly of amyloid, but not neuritic components. The diffuse plaques were distributed in various cortical areas and in the amygdala, and comprised a considerable population of the SP in the ATD brains.

Aged↗
PubMed1989

Diffuse type of senile plaques in the cerebellum of Alzheimer-type dementia demonstrated by beta protein immunostain.

We studied senile plaques (SP) in the cerebella of six autopsied subjects with Alzheimer-type dementia (ATD) and ten non-ATD autopsied subjects between the ages of 78 and 90. Neither SP nor amyloid angiopathy (AA) was observed in any of the non-ATD subjects. In the four of the six ATD subjects, diffuse plaques in the molecular layer were seen as ill-defined areas of fine fibrillar materials by beta protein immunostaining with formic acid pretreatment, the modified Bielschowsky stain, and periodic acid-methenamine silver (PAM) stain. The plaques were not visible with Bodian, Congo red, or periodic acid-Schiff stains. Compact plaques in the Purkinje cell or in the granular cell layers were found in three of the six subjects. Their amyloid core was often surrounded by areolar amyloid deposits. AA was observed in three of the six subjects. The argyrophilia of the diffuse and compact plaques, demonstrated by the modified Bielschowsky and PAM stains, became undetectable when the sections were first treated with formic acid. Such treatment made the plaques immunoreactive with beta protein antiserum. The findings suggested that cerebellar diffuse plaques and compact plaques consist mainly of an amyloid component, and are characteristic of ATD.

Aged↗
PubMed1989

Cerebral amyloid angiopathy and astrocytic gliosis in Alzheimer's disease.

Astrocytic reaction at amyloid infiltrated cortical vessels was studied using glial fibrillary acidic protein (GFAP) stain in two cases of Alzheimer's disease (AD). Sections from the visual and prefrontal cortex were stained with H&E, Bodian, Congo red, and thioflavin S in addition to GFAP. Senile plaques and neurofibrillary tangles were present in both cases. The density of astrocytes surrounding vessels infiltrated with amyloid was variable. In the same area, there were vessels with minimal perivascular astrocytic reaction as well as vessels displaying more pronounced perivascular gliosis; there was no constant excessive gliosis around vessels with severe amyloid deposits. However, if amyloid infiltrating the vessel wall protruded into the perivascular neuropil of the cortex, then prolific reaction of astroglia, similar to that seen at interstitial senile plaques was apparent, and a neuritic component was distinct. It appears that once amyloid of AD type is deposited in the neuropil, whether in form of interstitial plaque or perivascular plaque, it causes a similar astroglial and neuritic reaction.

Aged↗
PubMed1989

Senile plaque-like structures: observation of a probably unknown type of senile plaque by periodic-acid methenamine silver (PAM) electron microscopy.

Numerous diffuse senile plaque-like structures (SPLSs) were found in the cerebral cortex from cases with dementia of the Alzheimer type by means of the methenamine-Bodian method. SPLSs varied in shape and size. They were never recognized in the original Bodian, PAS and Congo red preparations, but were positive with anti-beta-protein immunostaining and periodic-acid methenamine silver (PAM) methods, which are thought to specifically stain amyloid substance. With PAM electron microscopy, we found sparse aggregations of amorphous, often ramified, structures with fine granular silver deposits in SPLS. Routine electron microscopic examination on the same portion where SPLS were confirmed by PAM electron microscopy revealed amorphous, partially fibrous structures. These structures might be amyloid or amyloid-precursor substance. In SPLSs only a few degenerated neurites and astrocytic processes with glycogen granules were seen. We consider SPLSs to be a kind of senile plaque.

Adult↗
PubMed1988

A variety of cerebral amyloid deposits in the brains of the Alzheimer-type dementia demonstrated by beta protein immunostaining.

We studied cerebral amyloid deposits in the hippocampal area immunohistochemically, using antiserum to synthetic beta peptide (1-28) in 66 patients with or without dementia and aged 17 to 91 years old. Senile plaques (SP) and amyloid angiopathy (AA) were detected in 36 (55%) and 19 (29%) patients, respectively. Also, cerebral amyloid deposits from the brains of seven patients with dementia and five patients without were studied in serial sections stained with Bodian, modified Bielschowsky, Congo red, and beta protein immunostain. In the patients with Alzheimer-type dementia (ATD) diffuse plaques, typical of this group, were stained with beta protein antiserum but not with Bodian stain, because the plaques were devoid of abnormally swollen neuritic processes. The diffuse plaques often contained one or more neuronal cell bodies. As well as primitive and classic plaques and AA, the beta protein immunostain demonstrated small deposits among the SP, small stellate deposits of layer 1, subpial fibrillar deposits, and focal cribriform deposits of parasubiculum, which may be new types of amyloid deposits. Amyloid plaques within the subcortical white matter were only found in ATD brains. In the non-demented patients various kinds of SP, including diffuse and compact ones, were immunostained. They tended to be small and few. beta protein immunostain with formic acid pretreatment is a useful method for the identification of a variety of senile cerebral amyloid deposits.

Adolescent↗
PubMed1976

[Hereditary neuropathic Portuguese type of amyloidosis (author's transl)].

Report of a 35 year old male with hereditary neuropathic amyloidosis of the portuguese type, the second known case in Germany. There are extensive nodular Congo red positive amyloid deposits in the endoneurium of the peripheral nerves which lead to displacement, compression atrophy and interruption of the endoneural fascicles. The amyloid fibril structure is specially noted by interference contrast microscopy. It can also be documented in unstained microscopic sections. Further extensive nodular deposits are present in the mesangium of the glomerula. The remaining organs show preponderantly affected vessel walls and collagen fibres.

Adult↗
PubMed1986

Histotopographic evidence that amyloid deposits in sclerocalcific heart valves and other chronic lesions of the cardiovascular system are related to old thrombotic material.

Deposition of amyloid in human sclero-calcific heart valves has been reported recently as a localized age-independent and dystrophic form of amyloidosis. Histochemical studies have shown that the deposits are permanganate resistant, contain tryptophan and P component and are immunologically unrelated to any known type of amyloid fibril protein. In this study histological observations from a series of four selected sclerotic heart valves show amyloid deposition in old thrombotic material covering fusing commissures or appositional collagen on the body of the leaflets. Similar cases from extravalvular sites have been added to the series: a partly hyalinized thrombus of the left atrium, a thrombotic aneurysm of the left ventricle, 2 thrombotic atherosclerotic aneurysms of the aorta and popliteal artery respectively, and an encapsulated haematoma of the scalp. The deposits are Congo red positive with typical green dichroism in polarized light, permanganate resistant and contain tryptophan. Electron microscopy of 3 cases displays small fibrils which are typical of amyloid. No patient showed evidence of systemic amyloidosis. The natural history of sclero-calcific valvulopathies and present observations favour the following pathogenesis: first, recurrent thrombotic deposition on thickened and fibrotic endocardium; second, degradation of a coagulation-related protein with beta potential during the aging of the clot with transformation into amyloid fibrils; finally, inclusion of the amyloid in sclerotic replacement tissue.

Adult↗
PubMed1994

Experimental study of laparoscopic selective proximal vagotomy using a carbon dioxide laser.

This study investigated the effectiveness of laparoscopic selective proximal vagotomy using a CO2 laser. Irradiation of the stomach was performed from the serosal aspect using a defocused CO2 laser beam. In the first experiment, the inhibitory effect on cysteamine ulcers in rats was compared between surgical vagotomy and CO2 laser vagotomy using three different irradiation fields. The results suggested that irradiation near the lesser curvature provided sufficient denervation. In the second experiment, CO2 laser vagotomy was performed laparoscopically in dogs. The procedure lasted less than 1 h and a postoperative endoscopic Congo red test confirmed its effectiveness. Subserosal tissues including the vagus nerve branches showed degeneration and were replaced by fibrosis 3 months postoperatively, but the deeper tissues were spared. In conclusion, laparoscopic CO2 laser vagotomy may be as effective for reducing acid secretion as standard surgical vagotomy. Its simplicity and safety suggest that a clinical trial in humans may be warranted.

Animals↗
PubMed1989

Nephrotic syndrome and primary tubular amyloidosis in a child: a case report.

Nephrotic syndrome in a 19-month-old child was associated with an unusual form of primary renal amyloidosis. The amyloid deposit was in the tubulo-interstitium and not in the glomeruli. Although the deposit did not stain with Congo red, it had the ultrastructural characteristics of amyloid. The patient had resistant nephrotic syndrome, and he subsequently developed microhaematuria and glucosuria.

Amyloid↗
PubMed1993

Immunotactoid glomerulopathy in a child with Down syndrome.

A 9-year-old girl with Down (21-trisomy) syndrome was found to have proteinuria and microscopic haematuria at age 6 years. Proteinuria gradually increased during the next 3 years, although blood pressure and renal function remained normal. The patient exhibited no underlying systemic diseases, monoclonal gammopathy, cryoglobulinaemia or histological evidence of plasmacytoma. A percutaneous renal biopsy revealed immunotactoid glomerulopathy (fibrillary glomerulonephritis) characterized by thickening of the glomerular basement membrane, diffuse mesangial expansion and various-sized acid-Schiff-positive nodules that were intensely positive for IgG, light chains (kappa and lambda) and complement components (C3, C4, C1q) along the glomerular capillaries in the mesangium. Congo red dye and amyloid thioflavine T staining were negative. Fibrils (15-17 nm in diameter--larger than amyloid fibrils) were present in the mesangial area and within the glomerular basement membrane. We are not aware of a previous report of immunotactoid glomerulopathy and a patient with chromosomal abnormalities.

Child↗
PubMed1994

A cysteine proteinase in the cercariae of Diplostomum pseudospathaceum (Trematoda, Diplostomatidae).

A cysteine proteinase was detected in extracts from cercariae of the trematode Diplostomum pseudospathaceum. The enzyme preferred protein substrates over synthetic, chromogenic peptides. The optimal pH for hydrolysis of substrates was 7.2 for azocoll, 6.4 and 7.6 for azocasein, 7.6 for azoalbumin, and 6.8 for N-benzoyl-L-arginine-4-nitroanilide. Elastin-Congo red and certain N-blocked L-aminoacyl- and L-peptidyl nitroanilides bearing L-phenylalanine, L-alanine, L-tyrosine, and L-leucine at the P1 subsite were not hydrolyzed. Thiol-reducing and divalent cation-complexing agents stimulated the proteinase activity, whereas thiol-blocking agents inhibited it. The relative molecular weight of the enzyme was approximately 40,000 as determined by SDS-PAGE. Detection of an identical proteinase in water after treatment of living cercariae with praziquantel suggests that the enzyme occupied the penetration glands in the larvae. Thus, when secreted by the parasite during invasion of an appropriate host, the enzyme might act as a penetration-promoting factor.

Animals↗