Gunnar Husby

Synovial localization of tumor necrosis factor in patients with rheumatoid arthritis

Tissue localization of tumor necrosis factor (TNF alpha) was examined in synovial tissues from 10 patients with active rheumatoid arthritis (RA) and three osteoarthritis controls using both monoclonal and polyclonal antibodies to TNF alpha and immunoperoxidase technique. No prominent staining for TNF alpha was noted in any of the osteoarthritis non-inflammatory synovial samples; however, six out of 10 RA synovial tissues displayed strongly positive tissue distribution of TNF alpha epitopes particularly within synovial lining cells, and interstitial monocyte/macrophage cells within inflammatory infiltrates. The amounts of TNF alpha visualized within synovial lining cells appeared to parallel the extent of inflammatory cell collections within the rheumatoid synovial tissues examined. Similar studies using renal biopsy tissues from seven patients with Systemic Lupus Erythematosus (SLE) nephritis (including diffuse proliferative nephritis, nephrotic syndrome, focal glomerulonephritis, and membranous nephritis) showed no tissue localization of TNF alpha. These findings emphasize that a potent lymphokine (TNF alpha), which may be important in the underlying inflammatory process, appears to be localized and perhaps produced by synovial lining cells within active RA synovial tissues.

Tissue T and B cell infiltration of primary and metastatic cancer.

Immunofluorescent techniques were utilized to identify the types of infiltrating lymphocytes adjacent to human malignant tumors arising from a wide range of anatomic sites. 24 of 29 primary tumors and 5 of 8 metastatic lesions showed varying degrees of lymphocytic infiltration. T cells predominated in the infiltrates in primary tumors (mean 80%, range 50-100%) and this pattern was evident regardless of anatomic site or the presence or absence of metastatic spread. By contrast, B cells predominated at the margins of three of five tumor metastases. Mononuclear cells bearing the Fc receptor were not a prominent component of the infiltrates associated with either primary tumors or metastases, but tumor cell binding of fluoresceinated IgG aggregates was observed in 12 of 29 primary tumors. A significant reduction in peripheral blood T cell numbers occurred in a third of the patients studied. This decrease was not clearly related either to the extent of local tumor T cell infiltration or to the presence of disseminated disease. These preliminary findings provide a descriptive analysis of the local and systemic distributions of immunocompetent cells in cancer.

Amyloid and amyloidosis 1990

Amyloid and amyloidosis 1990 , Amyloid and amyloidosis 1990 , کتابخانه دیجیتالی دانشگاه علوم پزشکی و خدمات درمانی شهید بهشتی

Characterization of renal tissue lymphocytes in patients with interstitial nephritis

Five patients with interstitial nephritis who presented with a variety of clinical profiles were studied with particular emphasis on documentation of the cellular types of potentially immunocompetent lymphocytes and mononuclear cells present within interstitial renal infiltrates. Immunohistologic studies coupled with conventional light and electron microscopic observations indicated that most mononuclear cells making up renal interstitial infiltrates were T cells. Some chronic inflammatory cell foci within renal interstitium were characterized by clusters of Ia antigen-positive T cells considered to be markers for activated lymphocytes. B cells were present in very small proportions (5 percent or less). The profile of immunocompetent cells present in lesions of interstitial nephritis suggests a major role for cell-mediated immunity in this disorder. Increase in tissue lymphocytes of the T gamma subclass with receptors for the Fc portion of immunoglobulin G (IgG) also suggests local activation of intrinsic suppressor cell mechanisms.

Direct immunochemical detection of prostaglandin-E and cyclic nucleotides in human malignant tumors.

Immunofluorescent localization of prostaglandin‐E (PGE), cyclic AMP (cAMP), and cyclic GMP (cGMP) was studied in tumor tissues from 40 patients with a variety of solid tumors. Representative normal tissues served as controls. Rabbit antisera specific for PGE or the cyclic nucleotides were used, and the reactions observed were correlated with the degree and type of lymphocytic reaction at the tumor margins. Strong PGE immunofluorescence was detected in tumor cells in 27 of 42 malignancies; by contrast nine of 13 normal tissues showed weak PGE reactions, cAMP was detected in 30 of the 42 malignancies; cGMP was noted in only seven of the 42 malignant tissues and in none of the normal tissues studied. The most common malignant tumor profile (17/42) was that of positive PGE and cAMP and negative cGMP staining. Tumors showing strong staining with anti‐PGE or cAMP demonstrated a distinct trend towards heavier lymphocytic infiltration with a predominance of T cells at their margins, although this association did not reach statistical significance in the present material.

Evidence for Fc IgG receptors and complement factor C3b receptors in human choroid plexus

Abstract Human, monkey and rabbit choroid plexus were examined for immune adherence in a closed-chamber technique. IgGEA and IgMEA C3b indicator cells adhered to the tissues. Incubation of tissue sections with aggregated IgG and with aggregated Fc fragments of IgG inhibited the adherence of IgGEA, whereas incubation with unaggregated IgG and F(ab′)2 IgG fragments did not inhibit the IgGEA adherence. These data suggest that human, monkey, and rabbit choroid plexus have receptors for Fc IgG and complement factor C3b.

Smooth Muscle Antibody in Heroin Addicts

The occurrence of autoantibodies and the concentrations of serum immunoglobulins were studied in 102 heroin addicts, 20 former addicts who had abstained from heroin for 1 year or more, and 40 normal control subjects. Antibodies to smooth muscle (46%) and lymphocytotoxic antibodies (30%) were detected in the active heroin users, and there was a significantly positive correlation between these autoantibodies. Absorption experiments strongly suggested antigenic cross-reactivity between smooth muscle and lymphocyte membrane antigens. The presence of smooth muscle antibody in addicts was not clearly correlated with signs of active liver disease. The occurrence of smooth muscle antibody (10%) and lymphocytotoxic antibodies (15%) was significantly lower in the former heroin addicts than among active drug users. A significant elevation of IgM was found in the active heroin addicts. Gamma-M globulin was lower among the former heroin addicts but still elevated when compared with normal controls.

Oncogenes, Viruses, or Rheumogenes?

T he fact that proto-oncogenes are important in cellular events that promote normal or nonmalignant B cell differentiation was first pointed out by Kelly et al [ 11. It was clearly shown that B cell mitogens were capable of activating the c-myconcogene within B cells and that expression of greatly expanded c-myc oncogene products was associated with what appeared to be a normal cell differentiation process. Moreover, concanavalin A, a T cell specific mitogen, also produced transient increases in levels of c-myc RNA in activated T cells. Similar results have also been reported for markedly increased c-myc protein in human peripheral blood mononuclear cells activated with the T cell mitogen phytohemagglutinin [2]. Oncogenes and the oncogene hypothesis evolved from early experiments by Gross, Kaplan, and Huebner [3-51 who showed that infectious leukemia and sarcoma retroviruses appeared in murine tumors produced either by radiation or chemical carcinogens. These observations suggested that latent tumor viruses might exist in normal cells and could be activated in a manner similar to temperate phages. Huebner and Todaro [5] further suggested that unexpressed or what were termed silent oncogenes might be present in all normal cells and that activation of these silent genes by retroviruses or known carcinogens might produce cancer. This, simply stated, became known as the oncogene hypothesis. After the discovery of reverse transcriptase, Temin [6] proposed the protovirus hypothesis, which suggested that normal cells contain potential (proto) oncogenes that might become viral or cellular oncogenes either after somatic mutation or retroviral cellular reverse transcription. The protovirus hypothesis suggested that a qualitative rather than a quantitative alteration was necessary to change normal cellular genes to oncogenes. Between 1970 and 1973, the first viral one gene, src, was definitively characterized using src deletion mutants [7-91. The characteristic features of src and all other retroviral one genes are their specific sequences, which appear to be unrelated to essential viral genes. Thus, not being essential, the oncgene sequences could perhaps be considered as excess baggage. At present, a number of different one genes have been identified. It is thought that viral one genes may have originated from rare transductions of normal cellular sequences by retroviruses without one genes. Cellular genes within normal mammalian cells contain onorelated sequences and are therefore probably compatible with a spectrum of normal functions. An attempt to apply this information to a better understanding of what have been called autoimmune diseases has probably only scratched the surface of an extremely important new concept-namely, that normal events in cellular proliferation and possibly differentiation may actually require or be dependent upon oncogene activation and expression.

Characterization of brain proteins reacting in vitro with anti-neuronal antibodies in patients with Huntington's disease.

Abstract Antibodies to neuronal antigens have been found in serum of approximately half of the patients with Huntingtons disease (HD). Experiments were designed in order to characterize brain antigen(s) reactive with such antibodies. Brain tissue extracts were used to absorb HD sera containing anti-neuronal antibodies. Absorbed and control sera were tested for the presence of anti-neuronal antibodies by indirect immunofluorescence using frozen sections from monkey or human caudate nucleus as tissue substrate. Complete absorption of anti-neuronal activity was achieved with proteins extractable with perchloric acid (PCA). PCA-soluble brain proteins were fractionated using ion-exchange chromatography and gel filtration on Sephadex G-50. A basic/neutral fraction of the PCA-soluble proteins with a molecular weight of approximately 21,000 was capable of complete absorption of the anti-neuronal antibodies. This fraction produced two closely juxtaposed bands on polyacrylamide gel electrophoresis, corresponding to proteins of 11,000 and 13,000 molecular weight.

IgG subclass, variable H-chain subgroup, and light chain-type composition of antineuronal antibody in Huntington's Disease and Sydenham's chorea

Abstract Antineuronal antibodies from patients with Huntingtons Disease and Sydenhams chorea were analyzed for the IgG subclass, light chain type, and V H subgroup composition, using specific antisera against the various antigens in indirect immunofluorescent technique. The antineuronal antibodies were heterogeneous and showed little restriction to the parameters tested for, except for the antineuronal antibodies from patients with Huntingtons Disease which in 8 of 10 cases were restricted to one light chain type. In 6 of these the antibodies belonged exclusively to the λ light chain type. The results indicate that the neuronal antibodies may be directly against different antigenic determinants.