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Biomedical subjects

M Pras

Publications and source records attributed to M Pras.

At least 127 records · Page 7Linked to original sources
PubMed1987

Degradation and deposition of amyloid AA fibrils are tissue specific.

The complete amino acid sequences of two related AA proteins (Mr 9700 and 5300) derived from thyroid tissue from a patient, NOR, with the autosomal recessive disease familial Mediterranean fever were determined. Heterogeneity found at position 52 indicates these proteins are fragments of two allelic or isotypic SAA precursor molecules similarly degraded at unusual sites and deposited in the thyroid. Degradation appears to be tissue and/or enzyme(s) specific since the carboxy terminus of both fragments is Ala-Ala and is different from other AA amyloid fibrils extracted from various tissues in different patients. Electron micrographic studies reveal these fragments retain the characteristics of native amyloid fibrils under physiological conditions even after exposure to dissociating agents.

Alleles↗
PubMed1987

Preparative fractionation of amyloid proteins on a microgram scale by high-performance liquid chromatography and polyacrylamide gel electrophoresis.

Preparative separation of amyloid proteins on a microgram scale is presented. Amyloid fibrils solubilized in aqueous 50% acetonitrile containing 0.1% trifluoroacetic acid, are fractionated by reverse-phase high-performance liquid chromatography. Fractionation of amyloids obtained from patients with familial Mediterranean fever allowed isolation of a protein identical with a conventionally isolated AA-protein. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis is used for preparative separation of AL-proteins. Two protein extraction procedures from Coomassie Blue stained gels are applied using elution in 0.1% sodium dodecyl sulfate containing buffer and 6 mol/l guanidine-HCl solution. The eluted proteins are concentrated and sodium dodecyl sulfate and dye are removed by acetonitrile precipitation of sample.

Amyloid↗
PubMed1987

Imaging of experimental amyloidosis with 131I-labeled serum amyloid P component.

131I-labeled human serum amyloid P component, which was injected into mice with experimentally induced systemic AA amyloidosis and into controls, became specifically localized and was retained in amyloidotic organs. In comparison, it was rapidly and completely eliminated from unaffected tissues and from control animals. Distinctive images of this amyloid-specific deposition of labeled serum amyloid P component were derived from whole body scanning, in vivo, of amyloidotic mice. These findings suggest that such imaging may have applications for the diagnosis and quantitation of amyloid deposits in humans.

Amyloidosis↗
PubMed1987

Aurothioglucose overdosage in five patients with rheumatoid arthritis.

Five patients with active seronegative, rheumatoid arthritis, HLA-DR3 negative, received inadvertently 250 to 500 mg of aurothioglucose instead of their usual weekly dose, during standard remission-inducing chrysotherapy. Subsequently a rapid and sustained clinical remission appeared in all five patients.

Adult↗
PubMed1987

Polyarteritis nodosa and familial Mediterranean fever.

A 22-year-old familial Mediterranean fever (FMF) patient was hospitalized for continuous fever, myalgia, hypertension, vertigo and a petechial rash. Laboratory findings revealed hyperglobulinaemia, thrombocytosis and a leukaemoid reaction. While on steroid therapy the patient sustained a haemorrhage into a renal aneurysm which responded to gel foam embolization. After 12 months of follow-up his condition remained stable under treatment with cyclophosphamide, prednisone and antihypertensive medications. This case provides the fourth example of polyarteritis nodosa associated with FMF.

Abdomen↗
PubMed1986

Colchicine in the prevention and treatment of the amyloidosis of familial Mediterranean fever.

To determine whether colchicine prevents or ameliorates amyloidosis in patients with familial Mediterranean fever, we followed 1070 patients with the latter disease for 4 to 11 years after they were advised to take colchicine to prevent febrile attacks. Overall, at the end of the study, the prevalence of nephropathy was one third of that in a study conducted before colchicine was used to treat familial Mediterranean fever. Among 960 patients who initially had no evidence of amyloidosis, proteinuria appeared in 4 who adhered to the prophylactic schedule and in 16 of 54 who admitted non-compliance. Life-table analysis showed that the cumulative rate of proteinuria was 1.7 percent (90 percent confidence limits, 0.0 and 11.3 percent) after 11 years in the compliant patients and 48.9 percent (18.8 and 79.0 percent) after 9 years in the noncompliant patients (P less than 0.0001). A total of 110 patients had overt nephropathy when they started to take colchicine. Among 86 patients who had proteinuria but not the nephrotic syndrome, proteinuria resolved in 5 and stabilized in 68 (for more than eight years in 40). Renal function deteriorated in 13 of the patients with proteinuria and in all of the 24 patients with the nephrotic syndrome or uremia. We conclude that colchicine prevented amyloidosis in our high-risk population and that it can prevent additional deterioration of renal function in patients with amyloidosis who have proteinuria but not the nephrotic syndrome.

Actuarial Analysis↗
PubMed1986

Severe aortic regurgitation: a rare presentation of giant cell arteritis.

A 53-year-old patient with no past history of rheumatic fever or lues presented with severe aortic regurgitation, underwent hemodynamic evaluation, and subsequently, an uneventful aortic valve replacement. The initial pathological interpretation was nonspecific aortitis. Six months following surgery arthralgia, muscular pain, difficulty in mastication, and fatigue occurred. There was no fever, however, sedimentation rate was 100/130. Cardiac examination was normal. Review of the pathological specimens revealed granulomatous arteritis with giant cells, typical of giant cell arteritis. Though the association of aortic regurgitation and giant cell arteritis is well recognized, only two such cases of severe aortic regurgitation requiring valve replacements have yet been described, of them, one probably had Takayasu's arteritis. An accurate diagnosis is of importance since steroid treatment is effective, and if introduced early, the inflammatory process may be arrested.

Aorta↗
PubMed1986

Serum amyloid A (SAA) variations in patients with cancer: correlation with disease activity, stage, primary site, and prognosis.

Serum amyloid A (SAA) was determined in 160 patients with cancer. Active disease was associated with high titre compared with the titre in non-active condition (31.8 v 5.8 micrograms/ml, respectively; p = 0.0002). SAA value showed a direct correlation with the stage of the disease: it was lowest at stages 1 and 2 and highest at the metastatic stage 4 (stage 1 v 4, p = 0.001; stage 2 v 3, p = 0.05). Cancers of the lung and unknown primary site were characterised by highly increased SAA concentration. Initial SAA value had prognostic significance: a value below 10 micrograms/ml correlated with survival advantage, whereas a higher initial value indicated a greater likelihood of a poor outcome (actuarial survival analysis p less than 0.001). When stage was accounted for, initial SAA value had significant prognostic bearing on survival of patients with advanced disease (stages 3 and 4) but not on that of patients with limited disease (stages 1 and 2). Serial testing showed good concordance between changes in SAA titre and clinical course.

Amyloid↗
PubMed1986

[Amyloidosis and familial Mediterranean fever].

Familial Mediterranean Fever (F. M. F.) is an autosomal recessive disorder occurring most commonly in Sepharadi Jews and Armenians. Two phenotypic features characterize the disease: brief episodic febrile attacks of peritonitis, pleuritis or synovitis recurring from childhood or adolescence and the development of systemic amyloidosis. Attacks are accompanied by striking elevations of acute phase proteins, including serum amyloid A protein. The amyloidosis of Familial Mediterranean Fever is of the AA type, and manifest clinically as a nephropathy that passes through proteinuria, nephrotic and uremic stages to renal death. Although there is ethnic variation in the incidence of amyloidosis of F. M. F. in our patient population--predominantly Sepharadi Jews of North African extraction--an amyloidotic death at an early age is their genetic destiny. Since the introduction in 1972 of colchicine to prevent the febrile attacks, the drug has been proven and become the main stay of therapy. Today, colchicine has been shown to be effective in preventing amyloidosis as well as the febrile attacks in Familial Mediterranean Fever. End stage renal disease is not the end of the road for patients with F.M.F. because of improving outlook for dialysis and renal transplantation in these patients.

Amyloidosis↗
PubMed1985

The primary structure of human tissue amyloid P component from a patient with primary idiopathic amyloidosis.

The amino acid sequence of human tissue amyloid P component (AP) extracted by a modified method from the spleen of a patient with primary idiopathic amyloidosis was determined. AP is a glycoprotein composed of a pair of noncovalently bound pentameric discs with a subunit size of 23-25 kDa. Each subunit consists of 204 residues, a single disulfide bridge linking Cys 36 to Cys 95, and a carbohydrate moiety attached to Asn 32. The precursor of AP is the serum amyloid protein (SAP). The primary structure of AP presented here differs from the amino acid sequence of SAP previously reported, but is identical to the amino acid sequence of mature SAP deduced from the nucleotide sequence of complementary DNA clones. It shares 52% homology with the amended sequence of human C-reactive protein, an acute phase protein, and 68% homology with the Syrian hamster "female protein," another acute phase protein whose response is modulated by sex steroids. AP/SAP, C-reactive protein, and female protein belong to a family of plasma proteins called pentraxins and their considerable sequence homology is probably the result of gene duplication. Neither the physiological function of AP nor its possible pathological role in amyloidosis are yet known.

Amino Acid Sequence↗
PubMed1985

Circulating hydroxy fatty acids in familial Mediterranean fever.

Episodes of fever, serositis, and arthritis in familial Mediterranean fever (FMF) suggested circulating mediators of acute inflammation (e.g., neutrophil activation). The mean serum neutrophil-aggregating activity of 51 FMF patients was 2.5 +/- 0.2 cm2/min, compared to 1.0 +/- 0.1 cm2/min in 20 normal controls (P less than 0.0002). Lipid extracts of FMF sera retained neutrophil-aggregating activity and had UV absorbance peaks at 269 and 279 nm, indicating the presence of lipids with a conjugated triene structure. Chromatography of extracts yielded peaks that were coeluted with reference dihydroxyicosatetraenoic acids, had UV absorbance peaks at 259, 269, and 279 nm, and possessed neutrophil-aggregating activity. The presence of leukotriene B4 was excluded by chromatography following methyl-esterification. Monohydroxy compounds identified in FMF extracts by gas chromatography/mass spectrometry included 5-hydroxyicosatetraenoic acid, and 9- and 13-hydroxyoctadecadienoic acids. Hydroxy acids were present in 19 of 31 FMF sera and absent in extracts of sera from 8 patients with active systemic lupus erythematosus, 7 with fever from infection, and 12 normal controls. The finding of circulating mono- and dihydroxy fatty acids in FMF suggests that defects in the formation or elimination of these compounds might play a role in the pathogenesis of FMF.

Cell Aggregation↗
PubMed1985

Amyloidotic polyneuropathy in a Jewish family. Evidence for the genetic heterogeneity of the lower limb familial amyloidotic neuropathies.

The first instance of familial amyloidotic polyneuropathy affecting a Jewish family is reported. Vitreous opacities were its presenting feature in the father at age 30 and the son at 25. Severe autonomic dysfunction and progressive peripheral neuropathy affecting initially the lower extremities soon followed. Death, suicidal in the son, occurred after seven and four years of illness. Their amyloid contained three proteins-an entire variant monomer of prealbumin, glycine replacing threonine as residue 49, and both products of its cleavage at the point of substitution. Lower limb familial amyloidotic polyneuropathy has been recorded in many families in Portugal, Sweden and Japan and occasionally in families of various ethnic stocks. This ethnic diversity prompts consideration of genetic heterogeneity. Differentiation on a genetic basis is forestalled since all pedigrees are compatible with autosomal dominant transmission and clinical data are marred by observer variance, even regarding vitreous opacities. Notwithstanding, an isolated British family is unique in the frequent occurrence of intractable peptic ulceration, cataracts, deafness and renal disease not attributable to amyloidosis and a striking predominance of males afflicted. Biochemically, monomeric prealbumin has been demonstrated by electrophoretic and immunologic techniques as the single protein constituent of amyloids isolated from Portuguese, Japanese and Swedish patients. The variant prealbumin of Japanese amyloid is characterised by methionine replacing valine as residue 30 and is identical to that found in plasma (but not as yet in amyloid) of affected Swedes. These limited data suggest that: (a) derivation of their amyloids from prealbumin is the biochemical common denominator of lower limb familial amyloidotic neuropathies regardless of the ethnic derivation of the afflicted; (b) to the extent that ethnic diversity reflects genetic heterogeneity, this will be demonstrable in the amyloid (and hopefully in the plasma) of the afflicted as entity-specific variant prealbumin monomers distinguished by different single amino acid substitutions; (c) on clinical and biochemical grounds, lower limb familial amyloidotic neuropathies include at least three genetic entities. In the upper limb and facial forms of familial amyloidotic polyneuropathy first recorded in Swiss and Finns respectively, the differences in their patterns of neurological disease and ocular lesions could be the result of their amyloids deriving from proteins other than prealbumin.

Adult↗