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N R Rose

Publications and source records attributed to N R Rose.

At least 73 records · Page 4Linked to original sources
PubMed1996

Silicone gel and octamethylcyclotetrasiloxane potentiate antibody production to bovine serum albumin in mice.

Earlier studies, in the rat, have shown that silicone gel acts as a potent adjuvant for antibody production against bovine serum albumin (BSA). The purpose of the present study is to determine whether components of the silicone breast implant (silicone oil, silicone gel, and octamethylcyclotetrasiloxane [D4]) potentiate the antibody response to BSA in mice. Groups of ten A/J mice received a single subcutaneous injection of 0.1 ml of BSA emulsified with the following: a) silicone preparations, b) incomplete Freund's adjuvant, or c) saline alone. Antibodies to BSA were measured using an enzyme-linked immunosorbant assay. The results indicate that both D4 and the silicone gel potentiate antibody production to BSA in mice. Known adjuvants have been shown to induce autoimmune syndromes in animal models. Whether silicones can act in a similar mechanism is still unclear.

Adjuvants, Immunologic↗
PubMed1996

Silicone binding immunoglobulins in human sera.

We have evaluated two recently published test procedures for demonstrating antibodies to silicone. Positive control serum samples provided to us by the original authors were positive in our hands, using the methods described. However, serum samples from patients with certain connective tissue diseases but no history of silicone implants were also positive. The question of silicone-specific antibodies remains unresolved.

Connective Tissue Diseases↗
PubMed1996

Development of scleroderma-like syndrome in Tsk/+ mice is not enhanced by silicone administration.

The possible role of silicone in the pathogenesis of a scleroderma-like syndrome is still unresolved. It has been proposed that silicone escaping from breast implants potentiates the progression of the disease. To clarify whether silicone enhances development of fibrotic skin lesions and autoantibodies, we tested its effect on tight skin (TSK/+) mice. TSK/+ mice spontaneously develop skin fibrosis and characteristic autoantibodies which resemble human scleroderma. The results of the present study indicate that silicone administration does not enhance development of skin fibrosis nor synthesis of autoantibodies to RNA polymerase and topoisomerase in TSK/+ mice.

Animals↗
PubMed1996

Autoimmune myocarditis.

We have developed two models of myocarditis in mice. The first is produced by infection with Coxsackievirus B3; the second results from immunization with cardiac myosin. Both forms of myocarditis occur in the same genetically predisposed strains. Genetically resistant mice can be rendered susceptible to myocarditis by co-treatment with cytokines IL-1 or TNF. Moreover, the disease is inhibited by administration of an antagonist of IL-1. These models will be useful for clarifying outstanding issues related to human myocarditis or dilated cardiomyopathy.

Animals↗
PubMed1996

Thyroid peroxidase autoantibody epitopic 'fingerprints' in juvenile Hashimoto's thyroiditis: evidence for conservation over time and in families.

In Hashimoto's thyroiditis, the humoral component is manifest by autoantibodies to thyroid peroxidase (TPO). Epitopic 'fingerprinting' of polyclonal serum TPO autoantibodies has been facilitated by the molecular cloning and expression as Fab of a repertoire of human TPO autoantibody genes. To investigate whether TPO autoantibody fingerprints are (i) stable over long periods of time (approximately 15 years), and (ii) inherited, we studied a cohort of nine patients with juvenile Hashimoto's thyroiditis and 21 first degree relatives of four of these patients. Fingerprints were determined by competition between four selected FAB and serum autoantibodies for binding to 125I-TPO. Regardless of titre, the TPO epitopic profile was stable in 10/12 individuals whose TPO autoantibody levels were sufficient for analysis on two or three occasions over 12-15 years. Although the TPO epitopic fingerprint profiles in two families raised the possibility of inheritance, overall the data from all four families did not reveal an obvious pattern of genetic control. In no family was the TPO epitopic fingerprint associated with HLA A, B or DR. In conclusion, TPO autoantibody epitopic fingerprints are frequently conserved over many years. Studies on additional families are necessary to establish whether or not the epitopic profiles of TPO autoantibodies are inherited.

Adolescent↗
PubMed1996

Mouse thyroglobulin: conservation of sequence homology in C-terminal immunogenic regions of thyroglobulin.

cDNA encoding 287 amino acids of the C-terminus of mouse thyroglobulin was cloned and sequenced. The amino acid homology between mouse and rat thyroglobulin was 96%, and was 78% between mouse and human. It was found that mouse thyroglobulin completely shared homology with two thyroiditogenic peptides described by other investigators. These findings are consistent with our hypothesis that in murine experimental thyroiditis, the primary thyroiditogenic epitopes are encoded by mouse-specific regions of thyroglobulin.

Amino Acid Sequence↗
PubMed1996

Influence of diet on the induction of experimental autoimmune thyroid disease.

Immunization of CBA/J mice with thryoglobulin (Tg) emulsified in complete Freund's adjuvant induces experimental thyroiditis (EAT), a well-characterized model of Hashimoto's disease. Recent studies have suggested that dietary factors play a role in the modulation of the immune response and that diet can have a profound effect on the induction of autoimmune diseases. In this study, we examined the influence of diet on autoimmune thyroiditis in mice. EAT was induced in mice fed ad libitum one of the three diets, a standard maintenance chow (Agway H1000), Purina 5020 Breeding Chow, and Purina 5010 Autoclavable (unautoclaved) Diet. Tg-immunized mice fed the Agway 1000 diet were found to be resistant to the development of autoimmune thyroid disease, with only 4 out of 25 mice developing mild thyroiditis. In contrast, 16 out of 25 mice fed the Purina 5010 diet developed moderate to severe thyroiditis. Mice fed the 5020 diet were partly susceptible: 7 out of 25 developed a mild to moderate thyroiditis. Histologic examination of thyroid glands of diseased mice fed the 5010 and 5020 diets showed marked lymphocytic infiltration with destruction of follicles, compared with mice fed the Agway diet, the latter showing only mild infiltration with preservation of thyroid follicles. Titers of antibody to Tg did not differ among the groups, and there was no significant difference in the IgG isotype subclass usage. The results demonstrate that diet can markedly affect the severity of autoimmune disease in the EAT model. In contrast, diet has little effect on the humoral autoimmune response in this system. These results implicate diet as a factor in the severity of cell-mediated autoimmune destruction and suggest that dietary modification could decrease pathology in some forms of autoimmune disease.

Animal Feed↗
PubMed1995

Association of chronic lymphocytic thyroiditis and thyroid papillary carcinoma. A study of surgical cases among Japanese, and white and African Americans.

BACKGROUND: An association between lymphocytic thyroiditis and thyroid papillary carcinoma is still controversial. To determine a definite statistical relation, a histopathologic study was performed on tissues from in three races, because there is a racial and age-related difference in the susceptibility to thyroiditis. METHODS: The prevalence and severity of thyroiditis combined with adenomatous goiter, follicular adenoma, or papillary carcinoma was defined by examination of surgically resected materials from Japanese (626 patients), and white and African Americans (330 and 90 patients, respectively). RESULTS: The prevalence of lymphocytic infiltrates, which are indicative of autoimmune thyroiditis, was significantly higher in patients with papillary carcinoma than in patients with adenomatous goiter or follicular adenoma among Japanese females (63.0%) and males (50.0%), white females (76.0%), and African American females (46.2%). Lymphocyte infiltration into the follicular adenoma or papillary carcinoma correlated with the severity of combined thyroiditis. CONCLUSION: An association between chronic lymphocytic thyroiditis and papillary carcinoma was confirmed in the Japanese, and white and African American populations. The possibility of autoimmune thyroiditis as a predisposing factor for papillary thyroid carcinoma, is suggested.

Adenoma↗
PubMed1995

A clinical trial of immunosuppressive therapy for myocarditis. The Myocarditis Treatment Trial Investigators.

BACKGROUND: Myocarditis is a serious disorder, and treatment options are limited. This trial was designed to determine whether immunosuppressive therapy improves left ventricular function in patients with myocarditis and to examine measures of the immune response as predictors of the severity and outcome of disease. METHODS: We randomly assigned 111 patients with a histopathological diagnosis of myocarditis and a left ventricular ejection fraction of less than 0.45 to receive conventional therapy alone or combined with a 24-week regimen of immunosuppressive therapy. Immunosuppressive therapy consisted of prednisone with either cyclosporine or azathioprine. The primary outcome measure was a change in the left ventricular ejection fraction at 28 weeks. RESULTS: In the group as a whole, the mean (+/- SE) left ventricular ejection fraction improved from 0.25 +/- 0.01 at base line to 0.34 +/- 0.02 at 28 weeks (P < 0.001). The mean change in the left ventricular ejection fraction at 28 weeks did not differ significantly between the group of patients who received immunosuppressive therapy (a gain of 0.10; 95 percent confidence interval, 0.07 to 0.12) and the control group (a gain of 0.07; 95 percent confidence interval, 0.03 to 0.12). A higher left ventricular ejection fraction at base line, less intensive conventional drug therapy at base line, and a shorter duration of disease, but not the treatment assignment, were positive independent predictors of the left ventricular ejection fraction at week 28. There was no significant difference in survival between the two groups (P = 0.96). The mortality rate for the entire group was 20 percent at 1 year and 56 percent at 4.3 years. Features suggesting an effective inflammatory response were associated with less severe initial disease. CONCLUSIONS: Our results do not support routine treatment of myocarditis with immunosuppressive drugs. Ventricular function improved regardless of whether patients received immunosuppressive therapy, but long-term mortality was high. Patients with a vigorous inflammatory response had less severe disease.

Adult↗
PubMed1995

Enhanced cellular proliferative activity and cell death in chronic thyroiditis and thyroid papillary carcinoma.

For the analysis of cellular proliferative activity and cell death in thyroid diseases, the Ki-67 labeling index, bcl-2 protein expression and cell death of follicular epithelia by immunohistochemistry and in situ DNA nick-end labeling methods were evaluated in normal thyroid tissues as well as in surgical specimens from cases of Hashimoto's disease (16 cases), focal lymphocytic thyroiditis (13 cases), Graves' disease (15 cases), follicular adenoma (20 cases) and papillary carcinoma (43 cases). Cellular proliferative activity and cell death were both enhanced in cases of thyroiditis, including Hashimoto's disease and focal lymphocytic thyroiditis. Thyroids from patients with follicular adenoma and papillary carcinoma also showed increased cellular proliferative activity and cell death. In addition, predominant high cellularity and partial loss of bcl-2 protein expression in papillary carcinoma suggested that the overgrowth and dedifferentiation were associated with malignancy.

Carcinoma, Papillary↗
PubMed1995

Amino acid sequence of a tryptic peptide of human thyroglobulin reactive with sera of patients with thyroid diseases.

Autoantibodies to human thyroglobulin (hTg) are found in the sera of many patients with thyroid diseases. To localize epitopes recognized by these autoantibodies, hTg was incubated with tryspin for 4 hours at 37 degrees C under non-reducing conditions. Releasing peptides from hTg in their natural conformation. These peptides were then analyzed by western immunoblot using either autoantibodies from patients with autoimmune thyroiditis or murine monoclonal antibodies (mAb) produced against hTg. The autoantibodies reacted primarily with two low molecular weight peptides with apparent molecular weights (MWap) of 15 and 20 kDa. The pattern of tryptic peptides recognized by these autoantibodies resembled that of one of the mAbs (137C1), as shown by immunoblots in either one or two dimensional SDS-PAGE. To characterize these peptides further, they were separated by a high performance liquid chromatography (HPLC). The column separated the 4-hour tryptic digest of hTg into multiple peptide peaks. Further analysis by SDS-PAGE showed that one of these peaks contained the 15 kDa peptide. The 15 amino acid sequence at the amino-terminus of this peptide was determined. This amino acid sequence (KVPTFATPWPDFVPR) corresponds to a unique sequence near the carboxyl-terminal end of hTg, starting with amino acid 2657. The size of the peptide indicates that it extends to the carboxyl-terminal end of hTg. This fragment contains one of the antigenic sites of hTg that binds autoantibodies from patients with autoimmune thyroid disease.

Amino Acid Sequence↗
PubMed1994

Induction of multiple heart autoantibodies in mice with coxsackievirus B3- and cardiac myosin-induced autoimmune myocarditis.

When mice of certain strains are infected with the cardiotropic virus coxsackievirus B3 or are immunized with mouse cardiac myosin, myocarditis, accompanied by immune recognition of the myocardium, ensues. That both target organ injury and peripheral immunization lead to similar disease manifestations raise questions about the role of tissue damage in eliciting autoantibodies. A/J mice were infected with coxsackievirus B3 or immunized with mouse cardiac myosin and killed at weekly intervals for 4 wk. A portion of each heart was examined histologically for evidence of myocarditis and antibodies were eluted from the remaining heart tissue. Heart eluates and serum were tested for IgG antibodies to myosin and to adenine nucleotide translocator and branched chain ketoacid dehydrogenase molecules by ELISA. At each sampling time, coxsackievirus B3-infected mice exhibited high titers of circulating antibodies to myosin, adenine nucleotide translocator, and branched chain ketoacid dehydrogenase with successively increasing myocardial deposition of antibodies of each specificity. Among myosin-immunized mice, antibodies of all three specificities were eluted from the myocardium and were found in the serum, but only antibodies to myosin were present in appreciable amounts in the circulation. Antibodies to myosin, adenine nucleotide translocator, and branched chain ketoacid dehydrogenase were rarely observed in serum and heart eluates from control animals. This study indicates that myocardial injury may be a prerequisite for the induction of cardiac autoimmunity and suggests that as tissue damage accrues, recognition of additional cardiac Ag may occur.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1994

Immunoreactivity of multiple molecular forms of human thyroglobulin.

Human thyroglobulin (Tg) was purified from thyroids of normal individuals and of patients with Graves' disease using gel filtration (Sephacryl S-400) and ion-exchange (DEAE) column chromatography. We isolated five protein peaks of Tg from the DEAE column, using a step gradient, characterized them for protein and iodine content, and assessed their immunological properties by reactivity to polyclonal and monoclonal antibodies (mAbs). Normal and Graves' Tgs differed in the relative protein content of these five protein peaks from the DEAE column. In the case of normal Tg, the majority of Tg was eluted in peak 2 but in the Graves' Tg, most of the protein was eluted in peak 1 of this column. The immunoreactivity of these five protein peaks of Tg was studied using 11 mouse mAbs prepared against human Tg, sera from patients with autoimmune thyroiditis and polyclonal antibody from a rabbit immunized with human Tg. All of five protein peaks of Tg reacted equally with rabbit antibody. The sera of five thyroiditis patients showed greater binding to peak 1 of Graves' Tg than peak 1 of normal Tg. Similarly, most mAbs showed greater binding to peak 1 of Graves' Tg than the peak 1 of normal Tg. Of particular interest was one mAb (42C3) which reacted only with Tgs containing iodine. The immunoreactivity of this mAb paralleled the iodine content of Tg. This mAb might be useful for evaluating the role of iodine in the antigenicity of human Tg.

Antibodies, Monoclonal↗
PubMed1994

The IgG2a antibody response to thyroglobulin is linked to the Igh locus in mouse.

The IgG-subclass usage by several strains of mice in the response to immunization with mouse thyroglobulin (mTg) was examined in the experimental autoimmune thyroiditis model. While the subclass usage by most mouse strains was similar, the Ighb allotype-bearing mice consistently produced lower IgG2a levels to mTg. Using CBA-Ighb congenic and recombinant inbred strains of mice, the lower level of IgG2a in the Ighb mouse was mapped to the Igh locus. The regulation of IgG2a appeared to be cis controlled, as the CBA x C57BL/6F1 mouse also produced reduced IgG2a of the Ighb (B6) allotype but not of the Ighj (CBA) allotype.

Animals↗
PubMed1994

Thymus function, ageing and autoimmunity.

We suggest that the thymus is the critical time-keeper in the ageing process with respect to immune responses. Because the thymus involutes asymmetrically, a clonal imbalance occurs with ageing since the proportion of autoantigen-specific helper/inducer T cells increases relative to the number of autoantigen-specific regulatory T cells. As a result, circulating autoantibody levels rise with age. On the other hand, nonspecific immunoregulatory mechanisms increase with age. As the thymic cortex atrophies, the response to foreign antigens declines, whereas the response to self-antigen rises, generating the ageing paradox.

Adult↗
PubMed1994

Racial and age-related differences in incidence and severity of focal autoimmune thyroiditis.

To determine possible racial and age-related differences of focal autoimmune thyroiditis between white and black Americans, autopsy material from American subjects was evaluated for incidence and severity of chronic lymphocytic thyroiditis. The overall incidence of lymphocytic infiltration in thyroid sections from subjects aged more than 20 years was 41.4% in white females, 20% in white males, 17.4% in black females, and 8.5% in black males. An increase to 54.8% in incidence of thyroiditis from the first decade onward was noted in white females older than 80 years of age. Age did not cause a remarkable increase in incidence of thyroiditis in white males, in black females, or black males. The susceptibility to chronic thyroiditis in American white males and females was almost the same as that of British white males and females. The incidence of thyroiditis in black females and males was similar to that in Japanese females and males. These findings showed clear racial differences in susceptibility to chronic thyroiditis.

Adult↗