| 1. |
- Anan, Intissar, et al.
(författare)
-
Comparison of amyloid deposits and infiltration of enteric nervous system in the upper with those in the lower gastrointestinal tract in patients with familial amyloidotic polyneuropathy.
- 2001
-
Ingår i: Acta Neuropathologica. - 0001-6322 .- 1432-0533. ; 102:3, s. 227-32
-
Tidskriftsartikel (refereegranskat)abstract
- Gastrointestinal (GI) complications in familial amyloidotic polyneuropathy (FAP) are invariably present during the course of the disease. The aim of this study was to investigate amyloid deposits in the myenteric plexus of the stomach and small intestine in FAP patients and compare the results with those of the colon. Six FAP patients were included in the study. The myenteric plexus and the number of macrophages (CD68) and blood vessels were immunostained and quantified by computerised image analysis. Double staining for amyloid and nerve elements was used to detect amyloid infiltration in the myenteric plexus. Amyloid was found predominantly in the walls of blood vessels, and was detected in the nerves of five FAP patients and in 18% of the examined ganglia of the myenteric plexus of the stomach. In the small intestine, 6% of examined ganglia showed amyloid deposits. In contrast, no deposits were found in the myenteric plexus of the colon. CD68-positive cells showed no difference in three parts of the GI tract. Most amyloid deposits were noted in the stomach, followed by the small intestine. There are significantly more blood vessels in the stomach and small intestine compared with the colon, and the amount of amyloid correlated with the number of blood vessels, and not with the amount of nerves and ganglia. The enteric nerve system is not a targeted organ for amyloid deposition in FAP.
|
|
| 2. |
- Anan, Intissar, et al.
(författare)
-
Liver transplantation restores endocrine cells in patients with familial amyloidotic polyneuropathy.
- 2000
-
Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 70:5, s. 794-9
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of this study was to investigate familial amyloidotic polyneuropathy, Portuguese type patients' endocrine cell content in the stomach and duodenum before and after liver transplantation, and to relate the findings to the patients' gastrointestinal disturbances.METHODS: Ten liver-transplanted familial amyloidotic polyneuropathy, Portuguese type patients and 10 healthy controls were seen. Endocrine cells were identified by immunohistochemistry and quantified with computerized image analysis. The activity of the cells was appraised by measurements of the cell secretory index and nuclear area. Clinical symptoms were obtained from the patients' medical records.RESULTS: After transplantation, a significant increase of several endocrine cell types were noted, and the pretransplant depletion of several types of endocrine cells disappeared. For no type of endocrine cell was any difference compared with controls noted after transplantation. There was no significant decrease of the amount of amyloid in the biopsies after liver transplantation. The patients' symptoms remained generally unchanged after transplantation, although a substantial time lapse between pretransplant evaluation and transplantation was present.CONCLUSIONS: Liver transplantation restores the endocrine cells in the upper part of the gastrointestinal tract. The restoration was not correlated with an improvement of the patients' symptoms. No decrease of the amyloid deposits was noted.
|
|
| 3. |
- Janunger, T, et al.
(författare)
-
Heart failure caused by a novel amyloidogenic mutation of the transthyretin gene : ATTR Ala45Ser.
- 2000
-
Ingår i: Amyloid. - 1350-6129 .- 1744-2818. ; 7:2, s. 137-40
-
Tidskriftsartikel (refereegranskat)abstract
- Cardiac failure in transthyretin (TTR) amyloidosis patients has been shown to be caused by different mutations in the TTR gene. In the present case, a 73-year-old man from Northern Sweden was evaluated for heart failure. Amyloid deposits were found in subcutaneous fat and in intestinal biopsies. The presence of a variant form of TTR was detected in the plasma by electrospray ionisation mass spectrometry (ESI-MS). The mutation was located by single-strand conformation polymorphism (SSCP) analysis of the TTR gene where a band shift was seen in exon 2. Direct sequencing of exon 2 revealed a single base-pair substitution (G1724T). This transversion results in an amino acid substitution at codon 45, alanine to serine (ATTR Ala45Ser). Mass spectrometry analysis excluded that the variant is a polymorphism, since no similar shift in molecular weight has been present in more than 200 control samples. Congo red and immunostaining of duodenum biopsy specimens confirmed the presence of systemic ATTR amyloidosis, and clinical examination, including echocardiography, found evidence of a restrictive cardiomyopathy. He had 10 years previously been operated for a bilateral carpal tunnel syndrome, but otherwise no symptoms were present that could be attributed to his systemic amyloidosis. No axonal polyneuropathy was noted at nerve conduction studies. This novel mutation is the second amyloidogenic TTR mutation found in the Swedish population.
|
|
| 4. |
- Mambule, C, et al.
(författare)
-
Enhancement of AA-amyloid formation in mice by transthyretin amyloid fragments and polyethylene glycol.
- 2000
-
Ingår i: Biochimica et Biophysica Acta. - 0006-3002 .- 1878-2434. ; 1474:3, s. 331-6
-
Tidskriftsartikel (refereegranskat)abstract
- The mechanism behind amyloid formation is unknown in all types of amyloidosis. Several substances can enhance amyloid formation in animal experiments. To induce secondary systemic amyloid (AA-type amyloid) formation, we injected silver nitrate into mice together with either amyloid fibrils obtained from patients with familial polyneuropathy (FAP) type I or polyethylene glycol (PEG). Mice injected with silver nitrate only served as controls. Amyloid deposits were detectable at day 3 in animals injected with amyloid fibrils and in those injected with PEG, whereas in control mice, deposits were not noted before day 12. Our results indicate that amyloid fibrils from FAP patients and even a non-sulfate containing polysaccharide (PEG) have the potential to act as amyloid-enhancing factors.
|
|
| 5. |
- Matsunaga, Noriko, et al.
(författare)
-
Advanced glycation end products (AGE) and the receptor for AGE are present in gastrointestinal tract of familial amyloidotic polyneuropathy patients but do not induce NF-kappaB activation.
- 2002
-
Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 104:5, s. 441-7
-
Tidskriftsartikel (refereegranskat)abstract
- Familial amyloidotic polyneuropathy (FAP), Portuguese type, is a hereditary amyloidosis caused by mutated transthyretin (ATTR) in which an exchange of valine for methionine at position 30 has taken place (ATTR Val30Met). Gastrointestinal complications, such as nausea, diarrhoea and malabsorption, have a significant impact on survival since the cause of death in the majority of cases is a consequence of extreme malnutrition due to dysmotility of the gastrointestinal tract. Recently, a role of the receptor for advanced glycation end products (RAGE) has been implicated in amyloid toxicity. Transthyretin (TTR) amyloid fibrils have been shown to have affinity for RAGE and subsequently induce NF-kappaB activation and apoptosis. Since gastrointestinal dysfunction plays an important role in FAP, we wanted to investigate if amyloid toxicity in the gastrointestinal tract is related to RAGE, NF-kappaB activation and apoptosis. Gastrointestinal tract autopsy samples were studied for the distribution of amyloid, RAGE, advanced glycation end products (AGE) and NF-kappaB. Furthermore, we examined the immunoreactivity of an apoptotic marker to investigate if an apoptotic pathway contributes to amyloid toxicity. The distribution of RAGE and AGE strongly correlated to that of amyloid deposits. Sequential immunofluorescence staining revealed a clear relationship between TTR, AGE and RAGE. No correlation between NF-kappaB, apoptotic marker and amyloid deposits was found. We conclude that RAGE-AGE or RAGE-TTR interaction might play important roles for gastrointestinal dysfunction and amyloid toxicity, although not through NF-kappaB activation and apoptosis.
|
|
| 6. |
- Nyhlin, N, et al.
(författare)
-
Reduction of free radical activity in amyloid deposits following liver transplantation for familial amyloidotic polyneuropathy.
- 2002
-
Ingår i: Journal of Internal Medicine. - 0954-6820 .- 1365-2796. ; 251:2, s. 136-41
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Liver transplantation halt the progress of familial amyloidotic polyneuropathy (FAP). Oxidative stress has been implicated in amyloid toxicity and formation. The objective of this study was to establish whether markers for oxidant stress and antioxidant capacity change following liver transplantation in patients with FAP.DESIGN: Morphometric and biochemical study.SETTING: Tertiary referral centre.SUBJECTS: Duodenal biopsy samples from 16 patients, taken before and after liver transplantation were used for morphometry. Serum samples from 14 patients, seven of whom had received transplants, were analysed regarding antioxidant capacity.INTERVENTION: Liver transplantation.MAIN OUTCOME MEASURES: Immunohistochemistry was used to stain for the lipid peroxidation product 4-hydroxynonenal (HNE), and Congo red staining was used for amyloid detection. Positive areas were quantified by point counting. Total antioxidant capacity (TAC) was measured with a colourimetric assay.RESULTS: In tissue, a decrease of HNE was noted after liver transplantation, whereas no significant changes were detected for amyloid deposits. No difference between transplanted and not transplanted patients was noted for total antioxidant capacity measured in serum.CONCLUSION: To our knowledge, this is the first description of a reduction of markers for free radical activity after cessation of amyloid formation. The findings implicate that amyloid formation in transthyretin (TTR) amyloidosis generates oxidative stress, whereas amyloid deposits as such are less toxic to sourrounding tissues.
|
|
| 7. |
- Suhr, Ole B, et al.
(författare)
-
Gastric emptying before and after liver transplantation for familial amyloidotic polyneuropathy, Portuguese type (Val30Met).
- 2003
-
Ingår i: Amyloid. - 1350-6129 .- 1744-2818. ; 10:2, s. 121-6
-
Tidskriftsartikel (refereegranskat)abstract
- Liver transplantation is an accepted treatment of familial amyloidotic polyneuropathy (FAP), Portuguese type (Val30Met), and the outcome so far seems promising. Gastric retention with nausea and vomiting are common complications of the disease, and may interfere with immuno-suppression therapy and prolong recovery after liver transplantation. The aim of this study was to assess the frequency of gastric retention in FAP patients and to evaluate the impact liver transplantation has on gastric emptying. Twenty-two patients, who had undergone liver transplantation, and had been re-examined for gastric retention after the procedure, were included in the study. Gastric emptying was recorded by scintigraphy after the ingestion of a 99m-technetium (99mTc)-labelled meal (omelette). The half-time (T50) of the emptying phase was calculated. Gastrointestinal symptoms before and after transplantation were recorded, and the majority of patients were also subjected to an upper endoscopic examination, where the presence of solid residual in the stomach was regarded as consistent with gastric retention. A high frequency of gastric retention was noted among the patients both before and after transplantation, and no significant improvement for the group was noted, even though decreased gastric emptying was noted for patients with a duration of the disease for less that 4 years. Patients who improved their nutritional status after transplantation had a faster gastric emptying than those who deteriorated. From our findings it can be concluded that gastric retention is a common complication of FAP and that gastric emptying in patients with longstanding disease (> or = 4 years) is unchanged after liver transplantation.
|
|
| 8. |
- Suhr, Ole B, et al.
(författare)
-
Scavenger treatment of free radical injury in familial amyloidotic polyneuropathy : a study on Swedish transplanted and non-transplanted patients.
- 2001
-
Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - 0036-5513 .- 1502-7686. ; 61:1, s. 11-8
-
Tidskriftsartikel (refereegranskat)abstract
- Since oxidative stress has been implicated in amyloid diseases, a study of scavenger treatment of hereditary transthyretin amyloidosis was undertaken on 23 familial amyloidotic polyneuropathy (FAP) patients. Nine patients had undergone a liver transplantation for the disease. Twenty patients completed the 6-month study period of scavenger treatment (vitamin C, 1 g, three times daily, vitamin E, 0.1 g, three times daily and acetylcysteine, 0.2 g three times daily). They were evaluated clinically and by immunohistochemical measurement of hydroxynonenal (HNE), a product of lipid peroxidation, in biopsy specimens. For non-transplanted patients, no improvement was found for HNE in relation to the amyloid content in biopsy specimens, whereas a tendency to a decreased amount was noted for transplanted patients. Clinically, no differences were found for non-transplanted patients, but an increased nutritional status, measured by a modified body mass index (mBMI) was noted for transplanted patients. In summary, scavenger treatment with the drugs and doses used in the present study appears to be unable to decrease lipid peroxidation in amyloid-rich tissue in non-transplanted FAP patients. For transplanted patients, lipid peroxidation tended to decrease, and the nutritional status measured by mBMI improved, even though the findings may be explained by liver transplantation alone, scavenger treatment may facilitate recovery after transplantation.
|
|
