PubMed Health⌕ Search

Biomedical subjects

H Hintner

Publications and source records attributed to H Hintner.

At least 19 recordsLinked to original sources
PubMed1996

A homozygous deletion mutation in the gene encoding the 180-kDa bullous pemphigoid antigen (BPAG2) in a family with generalized atrophic benign epidermolysis bullosa.

The 180-kDa bullous pemphigoid antigen (BPAG2) is a candidate gene/protein for mutations in some forms of junctional epidermolysis bullosa. In this study, we searched for mutations in BPAG2 in a large Austrian pedigree with generalized atrophic benign epidermolysis bullosa, a distinct nonlethal form of junctional epidermolysis bullosa, using polymerase chain reaction amplification of genomic DNA, heteroduplex analysis of the polymerase chain reaction products, and direct nucleotide sequencing. We identified a homozygous 2-bp deletion within the coding region of BPAG2 in the affected individuals. This mutation results in a frameshift and downstream stop codons on both alleles, predicting an absence of functional protein. These findings illustrate the molecular basis of the skin fragility in this family and attest to the importance of the 180-kDa bullous pemphigoid antigen in the attachment of the epidermis to the underlying dermoepidermal basement membrane.

Autoantigens↗
PubMed1995

Diminished expression of the extracellular domain of bullous pemphigoid antigen 2 (BPAG2) in the epidermal basement membrane of patients with generalized atrophic benign epidermolysis bullosa.

Generalized atrophic benign epidermolysis bullosa (GABEB) is a nonlethal form of junctional epidermolysis bullosa characterized by generalized skin and mucosal blisters that heal with atrophy; other features include alopecia, nail dystrophy, large melanocytic nevi, and autosomal recessive inheritance. The specific aim of this study was to identify an abnormality in epidermal basement membrane adhesion molecules in well characterized GABEB patients that would explain why these subjects' epidermis separates from their epidermal basement membrane. Cryostat sections of nonlesional skin from 8 GABEB patients in 5 different families as well as skin from normal volunteers (controls) were studied by indirect immunofluorescence microscopy using rabbit antiserum directed against a BPAG1 fusion protein or monoclonal antibodies directed against the extracellular domain of BPAG2 (HD18 and 233), epiligrin (P1E1), laminin 5 (GB3), types IV and VII collagen, or integrin subunits alpha 2, alpha 3, beta 1, alpha 6, or beta 4. In these studies, monoclonal antibodies HD18 and 233 showed no reactivity and diminished reactivity, respectively, to the epidermal BM of all GABEB patients. Interestingly, in one patient, the absent or diminished reactivities of monoclonal anti-BPAG2 antibodies were limited to well demarcated portions of an otherwise intact epidermal basement membrane. Moreover, BPAG1, epiligrin, laminin 5, types IV and VII collagen, and all integrin subunits under study were expressed in the same manner in both GABEB and normal human skin. These findings identify an abnormality in the extracellular domain of BPAG2 in the skin of GABEB patients. BPAG2 (type XVII collagen) is a transmembrane, hemidesmosome-associated molecule whose extracellular domain resides at the exact level where blisters develop in the skin of patients with GABEB.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Hereditary complete deficiency of the fourth component of complement: effects on the kidney.

Hereditary complete C4 deficiency has until now been detected in 18 patients. A disturbed clearance of immune complexes probably predisposes these individuals to systemic lupus erythematosus and other immune complex diseases. Renal involvement of hereditary complete C4 deficiency is described in seven patients from three families. Three patients of one family suffered from SLE and a severe mesangial and endocapillary proliferative glomerulonephritis which required immunosuppressive treatment. In two patients from a second family a mild focal and segmental mesangioproliferative glomerulonephritis was present which, except for an episode of acute renal failure in one patient, did not cause serious clinical problems. One additional child died without renal involvement. The patient from a third family developed Henoch-Schoenlein purpura, mesangioproliferative glomerulonephritis with segmental scarring and terminal renal failure. Immunofluorescence studies showed deposition of immunoglobulins and complement C3 in the glomeruli. Severity of renal disease is probably determined by activation of the alternative pathway of complement in the kidney.

Adolescent↗
PubMed1992

Life history of cutaneous vascular lesions in Sneddon's syndrome.

Sneddon's syndrome is a potentially fatal arterio-occlusive disorder characterized by generalized livedo racemosa and cerebrovascular lesions. Skin biopsies often fail to yield diagnostic arterial lesions. In the present series, affected vessels were found in skin biopsies from 12 of 15 patients with Sneddon's syndrome. Selection of the correct biopsy site (seemingly uninvolved skin at the center of a livedo racemosa area), adequate biopsy size (1 to 2 cm), and serial sections are essential for the detection of relevant vascular pathology. Only small to medium-sized arteries of the dermis-subcutis boundary were found to be involved. Lesions follow a distinct course. The initial stage displays partial detachment of endothelial cells, adhesion of mononuclear cells interspersed with fibrin ("endothelitis"), a marked edema of the surrounding connective tissue with numerous dilated capillaries, and a predominantly lymphohistiocytic infiltrate with polymorphonuclear leukocytes. In the early phase a sponge-like plug is formed from mononuclear cells, fibrin, and red blood cells, leading to partial to complete obstruction. A perivascular inflammatory infiltrate, devoid of polymorphonuclear leukocytes, is located around affected arteries; in the adventitia of the occluded vessel, a very regular corona of dilated capillaries appears that is continuous with more peripheral dilated and branching vessels. Organization of the occluding plug ensues in the intermediate stage by "subendothelial cell proliferation," most likely due to immigrating smooth muscle cells. In the final stage, the occluding artery undergoes fibrosis, shrinkage, and atrophy.

Adult↗
PubMed1992

[Typing of infiltration cells in primary, localized, nodular, cutaneous amyloidosis].

Amyloid tumours in two patients with primary localized nodular cutaneous amyloidosis contained very dense infiltrates consisting mainly of plasma cells and lymphocytes. In one case IgM was detected on many cells of the infiltrate, while in the other IgA was found in morphologically apparently normal plasma cells. Immunohistochemical investigations did not reveal any immunoglobulin light chain restriction in either of the tumours. Numerous cells expressed B cell markers, such as CD20 or CD38. Rearrangement studies on material from the amyloid tumour of one of the patients confirmed the monoclonality of plasma cells. This observation indicates that the nodules of primary localized nodular cutaneous amyloidosis indeed represent an extramedullary plasmocytoma, which consists of amyloid-producing plasma cells. Of special interest was the unexpectedly high proportion of cells expressing T cell markers (CD3, CD5, CD4 greater than CD8) in the amyloid nodules of both patients. After excluding co-expression of B and T cell markers on identical cells by immunohistochemical studies on serial sections and also after molecular biological studies, we assume that this is a separate T cell population that may have a regulatory effect on the production of amyloid.

Aged↗
PubMed1991

Acquired perforating dermatosis. Transepidermal elimination of DNA material and possible role of leukocytes in pathogenesis.

A patient had acquired perforating dermatosis and suffered from renal disease, diabetes mellitus, and lupus vulgaris. Histologic and immunohistochemical studies revealed that the bulk of the coarse granular basophilic material being extruded by transepidermal elimination was of nuclear origin obviously derived from polymorphonuclear leukocytes that were particularly abundant in an early, nonperforated lesion. At the lower boundary of the material being eliminated transepidermally, leukocytes were seen to accumulate, to undergo pyknosis and karyorrhexis, and to transform into nuclear debris. As a minor component, the material contained collagen fibers with altered staining qualities and, in an early lesion, elastic fibers. We speculate that accumulation, disintegration, and enzyme release from polymorphonuclear leukocytes may represent an important, hitherto disregarded driving force in transepidermal elimination. Lysosomal enzymes may later be responsible for the alteration of staining properties in collagen fibers, the degradation of elastic fibers, and for opening up the transepidermal route by impairing intercellular keratinocyte cohesion.

Aged↗
PubMed1991

Tissue vitronectin in normal adult human dermis is non-covalently bound to elastic tissue.

Vitronectin is a multifunctional human plasma glycoprotein that is also found in constant association with elastic tissue fibers in normal adults. We have investigated the nature of the association of vitronectin with elastic tissue, and compared it to that of other elastic fiber-associated proteins, namely fibrillin and amyloid P component. Samples of normal human dermis were incubated with a variety of extraction agents, including high molar salt solution, non-ionic detergent (Nonidet P-40), the reducing agents dithiothreitol or 2-mercaptoethanol, and the chaotropic agents sodium dodecyl sulfate or guanidine hydrochloride. Vitronectin purified from serum typically migrates as two bands of 75 and 65 kD. By contrast, immunoblotting studies of residual dermal material after extraction with the various agents revealed only lower molecular weight (58, 50, 42, 35, and 27 kD) anti-vitronectin reactive bands. Although these bands may represent degradation products of vitronectin generated as a result of the extraction procedure, we cannot exclude the possibility that tissue vitronectin is distinct from plasma vitronectin. Anti-vitronectin reactive polypeptides co-migrating with the 58-, 50-, and 42-kD bands were solubilized following extraction with sodium dodecyl sulfate or guanidine hydrochloride, but not with the other extraction agents. Immunofluorescence studies using residual dermal material after extraction with guanidine hydrochloride demonstrated a marked reduction in elastic fiber staining intensity with anti-vitronectin and anti-amyloid P component, but not with anti-fibrillin. Thus the majority, if not all of dermal vitronectin, is, like amyloid P component, non-covalently associated with, and not an integral constituent of, elastic fibers.

Blood Proteins↗
PubMed1991

Gene rearrangement studies in the diagnosis of primary systemic and nodular primary localized cutaneous amyloidosis.

Difficulties may arise in the diagnosis of patients with clinical features suggestive of plasma cell dyscrasia-related amyloidosis (amyloidosis L), but without evidence of a paraprotein. We have employed gene rearrangement methodology to demonstrate the clonality of bone marrow cells not only in a patient with myeloma-associated systemic amyloidosis, but also in a patient with "primary" systemic amyloidosis without overt myeloma or a detectable paraprotein. Furthermore, we have shown the clonality of the amyloid-producing plasma cells within a skin nodule of a patient with primary localized cutaneous amyloidosis; by contrast, clonal rearrangement was not detected in bone marrow cells from this patient. This finding provides definitive proof that organ-limited nodular primary localized cutaneous amyloid deposits arise in relation to cutaneous plasmacytomas. Gene rearrangement studies may enable early diagnosis and initiation of treatment in patients with systemic amyloidosis L, as well as their differentiation from patients with organ-limited nodular cutaneous amyloidosis, who do not require aggressive therapy.

Aged↗
PubMed1991

[Urticarial vasculitis as a symptom of Muckle-Wells syndrome?].

A patient is reported with a history of several years of chronic urticaria, transient fever, arthralgias and secondary systemic amyloidosis. A biopsy of an urticarial lesion showed necrotizing vasculitis and amyloid deposits in the eccrine sweat glands. Amyloid A deposits were also detected in kidney and rectum biopsies. This patient is likely to represent a variant of the Muckle-Wells syndrome (chronic relapsing urticaria, fever, arthralgia, deafness and renal amyloidosis). Hitherto undescribed is the presence of a necrotizing vasculitis as cause of the urticarial rash; further investigation will determine whether or not this finding represents the rule rather than an exception.

Adult↗
PubMed1991

[Vitronectin in normal human skin and in skin lesions].

Vitronectin (S-protein of complement, serum spreading factor) is a multifunctional glycoprotein present in human plasma and in the elastic tissue of various organs. It belongs to the group of adhesion proteins and is of importance in the terminal stages of both the coagulation and complement system and in fibrinolysis. In human skin it is localized on dermal elastic fibers and on pathologically altered elastic material (solar elastosis, pseudoxanthoma elasticum) as well as on keratin filament material such as keratin bodies in lichen planus or amyloid deposits in localized cutaneous amyloid. It is also found in the abnormally thickened cutaneous blood vessels in erythropoietic protoporphyria and porphyria cutanea tarda. Late-stage inhibition of the complement cascade in bullous disorders in which activation of the complement system is of pathogenetic significance may be an additional important function of vitronectin in skin diseases.

Blood Coagulation↗
PubMed1991

[Scurvy in trisomy 21].

We report a case of Down's syndrome in a 22-year-old woman who developed vitamin C deficiency with subsequent appearance of the characteristic joint pains and cutaneous and mucosal lesions of scurvy. A low intake of vitamin C due to peculiar eating habits and reduced absorption due to cardiac insufficiency and treatment with a platelet-aggregation inhibitor were considered to have caused the deficiency. Follicular purpura is a diagnostic skin sign of scurvy.

Adult↗
PubMed1990

[Long-term danazol therapy for hereditary angioedema].

Three patients with hereditary angio-oedema, two men of 19 and 35 years and a woman of 69 years, have been treated for 10 years with danazol, an androgen preparation with diminished androgenic effects. The 19-year-old man started taking it at the age of nine years and continued throughout puberty. Maintenance therapy with 200 mg twice a week, together with occasional booster doses of 200 mg daily, started at the age of 16 years and given when required cut the frequency of attacks from one a week to roughly six a year and greatly reduced their severity. Sexual maturation was entirely normal. The 35-year-old man, who had previously had three severe attacks a week, became symptom-free on a dose of 200 mg four or five times a week. During treatment he fathered a healthy child. The 69-year-old woman had had attacks every four weeks after the menopause, but obtained complete relief from a dose of 200 mg six times weekly. C1-Esterase inhibitor--originally depressed to around 30% of normal in all these patients--rose to about 50% during treatment. Endocrine, metabolic and toxic side-effects were minimal.

Adult↗
PubMed1990

Amyloid elastosis: analysis of the role of amyloid P component.

We report the second case of amyloid elastosis. Our patient had an underlying primary systemic amyloidosis with lambda light chain paraproteinemia. Salient clinical features included a sclerodermatous facial appearance, cordlike thickening of superficial blood vessels, neck skin resembling that in pseudoxanthoma elasticum, livedo reticularis-like changes on the trunk, Raynaud's phenomenon, arterial and venous thromboses, and the nephrotic syndrome. Amyloid deposits were present in the dermis, around appendages, in blood vessel walls, and in a striking distribution surrounding individual elastic fibers, that appeared shortened and fragmented. Immunofluorescence, electron microscopic, and immunoultrastructural studies with antibodies to lambda light chain, localized the amyloid deposits to the region of the elastic fiber microfibrils, with which amyloid P component (AP) is invariably associated in normal tissues. Because AP binds amyloid fibrils, codistribution of amyloid deposits and AP in amyloid elastosis strongly supports the theory that elastic fiber-associated AP may act as a nidus for amyloid deposition.

Amyloidosis↗
PubMed1990

Deposition of C3, C9 neoantigen and vitronectin (S-protein of complement) in lichen planus pemphigoides.

We have compared the distribution of C3, C9 neoantigen (C9n) and vitronectin at the dermoepidermal junction in lichen planus pemphigoides with that in bullous pemphigoid. Eight out of 30 biopsies from patients with lichenoid lesions had linear C3 deposition at the basement membrane zone (BMZ); four of these patients had bullae and fulfilled the criteria for lichen planus pemphigoides. C9n immunoreactivity was detected as a linear or an intermittent linear/granular band at the BMZ only in these four patients, suggesting a role for the membrane attack complex of complement (MAC) in the pathogenesis of blister formation in lichen planus pemphigoides. Faint linear deposition of vitronectin, in addition to C9n, at the BMZ was seen in two of the four cases of lichen planus pemphigoides and three of six cases of bullous pemphigoid. This suggests that vitronectin may be deposited in association with C9n not only as part of the non-lytic SC5b-9 complex, but also as a regulatory step following the lytic action of MAC. A regulatory function for vitronectin in limiting tissue damage following activation of MAC is supported by our finding of a heavy deposition of vitronectin in association with C9n in a lichen planus pemphigoides patient in whom bulla formation had ceased.

Adult↗
PubMed1990

Renal disease in a patient with hereditary complete deficiency of the fourth component of complement.

Hereditary complete deficiency of the fourth component of complement (C4) is an extremely rare disorder with 17 cases reported so far. Twelve of these patients suffered from a systemic-lupus-erythematosus-like illness. The patient we here describe presented with severe Henoch-Schönlein purpura (HSP) at the age of 17. Immunofluorescence of a kidney biopsy showed granular deposits of IgG, IgA, IgM, C3 and fibrinogen in the mesangium and segmentally along the basement membrane. Six years later, the patient developed hypertension and nephrotic syndrome. Renal function deteriorated rapidly. He was on hemodialysis for 12 months and then received a cadaveric kidney graft. After 2 years of uncomplicated course, microhematuria and proteinuria developed. Immunofluorescence of a transplant biopsy was virtually identical to the pattern in the patient's own kidneys. We thus conclude that the patient had recurrence of his primary disease in the graft. Three and a half years after transplantation hemodialysis had to be restarted. This unique case supports the current view that deficiency of classical pathway components predisposes to the development of immune complex diseases and that the complement system is activated via the alternate pathway in HSP. Furthermore, we assume that complete C4 deficiency was the major cause for the recurrence and unfavorable outcome of HSP in the graft.

Adult↗