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Biomedical subjects

M M Frank

Publications and source records attributed to M M Frank.

At least 19 recordsLinked to original sources
PubMed1992

Detection of complement in relation to disease.

If a single component is lowered, it is reasonable to question whether the patient has a genetically-controlled defect. Studies of family members may be required. If split products, complexes, or neoantigens are present, it is likely that there is ongoing complement activation. If most of the components of a pathway are lowered, a reasonable supposition is that complement is being activated. We then turn to a consideration of the factors that may activate complement. When hypocomplementemia is associated with a decrease in titer of several components, it is often possible to determine whether the classic or alternative pathway is the major pathway being activated; this, in turn, may suggest certain diagnoses and rule out other diagnoses. The nature of the circulating complexes or split products may provide the same information. Thus, a consideration of the pathophysiology of the complement system and of the factors that activate complement provides an approach to an understanding of the function of complement and the role of complement causing a damage in a clinical setting.

Complement Pathway, Alternative↗
PubMed1992

The mechanism by which microorganisms avoid complement attack.

The complement system provides a critical level of defense against bacterial invasion. Various microorganisms have evolved a variety of mechanisms to allow them to avoid complement lytic and opsonic activity. These range from the formation of factors that destroy activity of complement proteins to the evolution of surface structures that fail to bind, facilitate degradation of, or shed, complement proteins. The range of factors associated with bacterial complement resistance is reviewed here.

Animals↗
PubMed1992

Regulation of complement activity by vaccinia virus complement-control protein.

A major protein secreted by vaccinia virus-infected cells has structural similarity to the super-family of complement-control proteins. This vaccinia complement-control protein (VCP) was studied to determine how it regulates complement activation. VCP was bound by C4b and C3b and served as a cofactor with factor I in cleaving these two molecules. VCP inhibited the formation and accelerated the decay of the classical C3 convertase. It also accelerated decay of the alternative pathway convertase, although higher concentrations were apparently needed. In vitro, therefore, VCP interfered with the classical and alternative complement pathways at several steps. In vivo, this interference may increase the virulence of vaccinia virus by enabling it to escape attack by the host's complement system.

Complement Activation↗
PubMed1979

Defective reticuloendothelial system Fc-receptor function in systemic lupus erythematosus.

To determine whether reticuloendothelial-system immunospecific Fc-receptor function is abnormal in patients with systemic lupus erythematosus, we studied the clearance of IgG-sensitized 51Cr-labeled erythrocytes by these splenic macrophage membrane receptors in 15 untreated patients. Fc-specific clearance rates were strikingly abnormal in 13 of 15 patients (half-times ranging from 80 to 2256 minutes, P less than 0.001 as compared to controls). Abnormal clearances correlated with immune-complex levels (as measured by the C1q-binding assay) and with disease activity. C1q-binding activity and anti-DNA titers also correlated with disease activity. The correlations of C3, C4, CH50 and factor B with abnormal clearance and disease activity were weaker or nonexistent. The significant correlations among clearance, disease activity and C1q-binding activity suggest that the defect in Fc-receptor function may lead to the prolonged circulation of immune complexes, thereby contributing to tissue deposition and damage.

Adult↗
PubMed1979

Immunologic reactivity in the hypereosinophilic syndrome.

Because previous studies have suggested an important link between eosinophilia and immunologic reactivity, we investigated various components of the immune system in a large number of patients with the idiopathic hypereosinophilic syndrome (HES) to elucidate a possible role for immunologic phenomena in the etiology and pathogenesis of this disease. Immunoglobulin G, A, or M levels were only rarely abnormal. However, in 8 of 21 (38%) patients with HES, IgE levels were markedly elevated suggesting an association of an IgE-mediated mechanism with eosinophilia in this subgroup. Severe dermatographism was present in three fourths of patients, and 2 patients with intermittently elevated histamine levels manifested an unusual form of immediate-pressure urticaria. Serum complement determinations showed elevated C4 and C3 levels in 27% and 77% of patients, respectively. Antigen-antibody complexlike material measured by C1q binding was elevated in the serum of 7 of 22 (32%) patients; this finding may relate to the known ability of eosinophils to avidly phagocytose antigen-antibody complexes. When compared with normals, lymphocytes from patients with HES showed a variety of abnormalities of lymphocyte surface receptors and lymphocyte function. Thus, patients with HES demonstrate a variety of immunologic abnormalities which may be related primarily or secondarily to the pathogenesis of this syndrome.

Antigens, Surface↗
PubMed1979

Acquired C1 esterase inhibitor deficiency and angioedema: a review.

A case of acquired C1INH deficiency with angioedema is described. Fifteen cases are thus far recorded. The clinical syndrome of angioedema in these patients closely resembles hereditary angioedema (HAE). Most cases are associated with a paraprotein, cryoglobulin, or autoantibody, which presumably initiates C1 activation and C1 Inhibitor consumption. C1INH, C4 and C2 levels are low in acquired C1INH deficiency, as in HAE. A distinguishing feature is that C1 titers are very low in the acquired disease and only minimally depressed, if at all, in HAE. Most cases have appeared in patients with an underlying lymphoproliferative or autoimmune disease. Therapy is directed at the underlying disorder, but androgen therapy may be helpful in preventing attacks. Future potential therapeutic approaches are discussed.

Angioedema↗
PubMed1979

Response of variant hereditary angioedema phenotypes to danazol therapy. Genetic implications.

Hereditary angioedema (HAE), an auto-somal dominant disorder characterized by attacks of episodic edema is associated with decreased functional levels of the C1 esterase inhibitor. Approximately 85% of patients have lowered antigen levels of a normal inhibitor protein. 15% of patients have normal or elevated antigenic levels of functionless protein. We have examined the response to danazol therapy of patients with the variant HAE phenotypes possessing the abnormal protein in an effort to determine if these patients possess a normal structural C1 inhibitor allele. Four patients with a variant HAE phenotype were treated successfully with danazol. In two patients, distinguished by the presence of a functionless, albumin-bound, C1 inhibitor (phenotype 2), phenotypic analysis of the danazol response by bidirectional immunoelectrophoresis revealed the appearance of the normal C1 inhibitor gene product during danazol therapy. This relatively cathodal C1 inhibitor peak appears in conjunction with the development of nearly normal functional activity. All of the functional C1 inhibitory activity which appeared in the phenotype 2 treatment serum was associated with the electrophoretically normal inhibitor. This normal protein could be separated from the functionless inhibitor protein by immunoadsorption and molecular sieve chromatography. Danazol therapy of the two patients with an electrophoretically normal, functionless C1 inhibitor (phenotype 3) also resulted in a clinical remission associated with development of a significant increment in functional serum C1 inhibitory activity and C1 inhibitor protein. These findings demonstrate that these two HAE phenotypic variants are heterozygous for the normal serum C1 inhibitor, a finding which was not apparent before phenotypic analysis of this serum during danazol therapy. These data provide strong evidence for a basic similarity between the common form of HAE and its phenotypic variants. They also suggest that a structural gene lesion may result in the abnormalities of serum C1 inhibitor function and disease expression in all three of these HAE phenotypes.

Angioedema↗
PubMed1979

Sjögren's syndrome: a defect in reticuloendothelial system Fc-receptor-specific clearance.

To determine the functional status of reticuloendothelial system Fc receptors in patients with Sjögren's syndrome, we studied the rate of clearance from the circulation of 51Cr-labeled IgG-sensitized autologous erythrocytes in 19 patients. Fc-receptor-mediated clearance was abnormal in 12 of the 19 patients, with half-lives ranging from 80 to 356 min. There was a significant correlation between clearance rates and clinical manifestations of disease. Clearance rates tended to be normal in patients with disease limited to exocrine glands and abnormal in patients with widespread disease. In contrast, there were no correlations between the rate of clearance of IgG-sensitized erythrocytes and serum immune complex levels, serum complement component levels, or rheumatoid factor titers. The striking correlation between clearance rates and disease manifestations suggests that decreased clearance of immune complexes by defective reticuloendothelial system Fc receptors may contribute to disease pathogenesis.

Adult↗