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S H Roman

Publications and source records attributed to S H Roman.

34 records · Page 2Linked to original sources
PubMed1989

Induction of microsomal antigen and comparison with histologic localization of HLA-DR in Graves' thyroid tissue.

We have characterized thyroid microsomal antigen (M-Ag) prepared from Graves' and normal thyroid tissues using 100,000 x g thyroid membrane fractions in enzyme-linked immunosorbent assays with pooled polyclonal human sera containing high titers of antibody to M-Ag. A ten-fold parallel increase in dose inhibition potencies occurred with M-Ag preparations from Graves' as compared to normal thyroid tissue. The M-Ag preparations were further evaluated by SDS-polyacrylamide gel electrophoresis and proteins visualized by Western blot using high titer microsomal antibody (M-Ab) sera (n = 2) devoid of thyroglobulin antibody activity. We found discrete 100 kD relative molecular mass bands in Graves' M-Ag preparations (n = 3) under nonreducing conditions which were only poorly resolved in normal thyroid M-Ag (n = 3) using up to 100 micrograms of protein per lane. The cellular localization of M-Ag was then investigated using the avidin-biotin-peroxidase technique on frozen sections of Graves' and normal human thyroid tissue with a murine monoclonal antibody reactive with human M-Ag and thyroid peroxidase. M-Ag reactivity was similar in both Graves' and normal thyroid tissues and localized to the entire follicular cell membrane with more intense staining occurring on the inner follicular cell membrane. This was in contrast to follicular cell staining for HLA-DR antigen which was present in 6 of 10 Graves' tissues examined and absent in normal thyroid tissue. Staining for HLA-DR antigen also occurred on the follicular cell surface membrane with occasional enhancement at the thyrocyte apical cell membrane. We conclude: a) M-Ag is induced approximately 10-fold in Graves' thyroid tissue and can be objectively quantified in ELISA systems, 2) There were no detectable qualitative differences between M-Ag from Graves' and normal thyroid tissue, and 3) HLA-DR antigen was detected on 60% Graves' tissues in a cell surface distribution similar to that observed for M-Ag in both Graves' and normal tissues.

Adult↗
PubMed1988

HLA class II antigen expression and the autoimmune thyroid response in patients with benign and malignant thyroid tumors.

To further understand the relationship between the immune system and the neoplastic human thyroid cell we investigated the degree of intrathyroidal lymphocytic infiltration and thyroid HLA class II expression in 17 patients with thyroid tumors. In another 60 thyroid tumor patients the association of thyroidal lymphocytic infiltration with thyroid autoantibody production was analyzed. In total 117 thyroid tissues were examined including tissue obtained at autopsy (n = 28), fetal thyroid tissue (n = 4), thyroid samples obtained from areas distant from benign follicular adenomas (n = 5), and 80 abnormal thyroids including patients with benign (n = 53) or malignant (n = 24) thyroid tumors and Hashimoto's thyroiditis (n = 3). Normal adult and fetal thyroid tissue had no significant lymphocytic infiltration and no detectable HLA-DR, -DP, or -DQ antigens on their thyroid follicular epithelial cells. The degree of lymphocytic infiltration in the nonneoplastic thyroid tissue of thyroid glands with benign and malignant thyroid tumors varied considerably and correlated with the presence and titer of serum thyroid autoantibodies measured by sensitive ELISA techniques. However, all but one of the benign follicular adenomas had thyroid cells negative for HLA class II determinants despite the presence of infiltrating lymphocytes, while 7 of 10 thyroid carcinomas expressed class II antigen (principally HLA-DR) even when only minor degrees of lymphocytic infiltration were present. These data indicate a correlation between lymphocytic infiltrates and serum thyroid autoantibody titers but the relationship with HLA class II expression is more complex. Since we have previously shown that HLA class II antigen expression can be induced by local interferon-gamma secretion, presumably from activated T cells, we conclude that estimates of simple thyroid lymphocytic infiltration and serum autoantibody secretion do not correlate with the degree of intrathyroidal T-cell activation. Furthermore, our observation of increased expression of HLA class II antigens in thyroid cancer suggests considerable cellular heterogeneity in susceptibility to HLA class II antigen induction in human thyroid disease.

Adenoma↗
PubMed1988

Allospecific DR gene expression on the human thyroid cell.

Human thyroid epithelial cells, stimulated with recombinant gamma interferon (IF) (100 U/ml), were HLA-DR typed by means of antibody-dependent, complement-mediated cytotoxicity. The thyroid cell lysis reaction patterns were found to be similar to those obtained with autologous peripheral B cells in four of five separate experiments. Since the cytotoxic reactions with thyroid cells were sometimes incomplete with many antisera, a two-color fluorescence technique was developed to measure the specificity of the antibody-dependent, complement-mediated lysis. Using constitutively HLA-D antigen-positive Raji B lymphoblastoid cells as controls, we showed that non-polymorphic HLA-D and HLA-DR determinants could be detected on the thyroid cell surfaces by this cell lysis approach. In addition, gamma IF stimulated thyroid cells from a DR3 positive individual were lysed to a significantly greater than unstimulated autologous thyroid cells with the use of a specific monoclonal antibody to HLA-DR3, thus confirming the original HLA typing studies. These data demonstrate, for the first time, that the expression of HLA-DR antigen on the surface of human thyroid cells is allospecific and may, therefore, play an important role in the immunopathology of autoimmune thyroid disease.

Cytotoxicity, Immunologic↗
PubMed1987

HLA-DP, DQ and DR gene expression in Graves' disease and normal thyroid epithelium.

HLA class II antigen expression by human thyroid epithelium may influence the pathogenesis of autoimmune thyroid disease. HLA-DP, DQ and DR alpha chain-specific RNA probes and monoclonal antibodies specific for the three HLA-D subregion products were used to analyze class II antigen expression in thyroid epithelial cells from normal thyroid tissue and thyroid tissue obtained from patients with Graves' autoimmune thyroid disease. Class II alpha chain RNA transcripts, as well as immunoreactive protein representing all three HLA class II antigens, were detected in Graves' thyroid tissue, and the levels of class II antigen expression appeared to correlate with the degree of lymphocytic infiltration within the gland. Thyroid epithelial cells from normal thyroid glands contained low or absent levels of HLA class II alpha chain mRNA and contained no detectable immunoreactive HLA class II antigen. Thyroid cell monolayer cultures prepared from both Graves' disease and normal thyroid glands exhibited coordinate induction by lectin or human recombinant gamma interferon of HLA-DP, DQ and DR gene expression. These data demonstrate the potential for HLA-DP, DQ and DR antigen expression in thyroid epithelium, and imply a dose relationship between lymphocytic infiltration and coordinate transcription and translation of HLA class II genes.

Epithelium↗
PubMed1987

Thyroid cell MHC class II antigens: a perspective on the aetiology of autoimmune thyroid disease.

An association exists between certain MHC polymorphisms and autoimmune thyroid disease in animals and humans. The observation of MHC class II antigen expression by the thyroid suggests that such associations may have mechanistic explanations at the level of the thyroid cell. Such class II antigen expression, rather than being a constitutive property of thyroid epithelium, appears to be primarily mediated by lymphokine secretion from intrathyroidal T lymphocytes and a variety of agents, for example TSh and TSH receptor antibodies, may amplify such lymphokine action. Thyroid cell class II antigens participate in activation and amplification of T cells and are involved in presentation of thyroid antigen to the immune system. The relationship between these local immune interactions and the initial events leading to the development of autoimmune thyroid disease requires a more fundamental understanding of the workings of the immune system at the site of antigenic stimulation.

HLA-D Antigens↗
PubMed1986

Thyroid autoantibodies in HLA-genotyped type 1 diabetic families: sex-limited DR5 association with thyroid microsomal antibody.

Thyroid autoantibodies are common in Type 1 diabetics and their first degree relatives and may be part of the autoimmune diathesis present within such families. We have measured the prevalence of microsomal (M-Ab) and thyroglobulin (Tg-Ab) autoantibodies in 84 HLA-typed families having a Type 1 diabetic child, using enzyme-linked immunosorbent assay techniques. Thyroid autoantibodies were detectable in 201/407 (49%) individuals in these families. Both autoantibodies were significantly more frequent in the subsets of parents, diabetic children and their non-diabetic siblings than in groups of control adults and children. The prevalence of these autoantibodies in the diabetic families was increased in both sexes with a female:male ratio of 1.4:1. Antigen DR5 was significantly associated with M-Ab production but only for male subjects (P = 0.005 after correction for the number of DR antigens tested). No significant associations were encountered for Tg-Ab. Within-family analyses indicated that thyroid autoantibodies occurred with increased prevalence in HLA-identical or haplo-identical siblings of autoantibody-positive index cases in comparison to control children. We conclude the DR association with thyroid autoantibody production in this diabetes-selected population was thyroiditis-related and not diabetes-related, and the DR5 association was restricted to males and the production of M-Ab. These data are consistent with the hypothesis that multiple genetic and non-genetic factors played a role in the high prevalence of thyroid autoantibodies in this population.

Adolescent↗
PubMed1985

T-cell sensitization to autologous thyroid cells and normal non-specific suppressor T-cell function in Graves' disease.

We have employed a syngeneic system utilizing thyroid cell monolayers initiated following thyroid surgery co-cultured with autologous T cells to demonstrate T cell autosensitization in patients with Graves' disease. Antigen-induced blastogenesis was monitored using 24 h [3H]thymidine uptake. Control experiments with 5 d cultured normal human thyroid cells from tissue around benign adenomata showed no evidence of syngeneic T cell autosensitization. Human thyroid cells alone were unable to incorporate [3H]thymidine in the presence of bTSH. In three of four experiments with Graves' thyroid cells there was significant induction of autologous T cell blastogenesis with a mean stimulation index of 220%. In parallel experiments we explored the non-specific helper and suppressor T cell function of these and similar patients with Graves' disease. In normal controls (n = 6) increasing numbers of T cells added to a constant number of B cells (consisting of a T cell depleted peripheral mononuclear cell preparation) showed a marked helper effect measured as increasing IgG secretion. As the ratio of T:B cells increased above 4:1 there was a suppression of IgG secretion. One of two hyperthyroid Graves' patients was observed to have deficient T cell function as demonstrated by lack of IgG suppression. The remaining five patients (all but one of whom were euthyroid at the time of testing) had results similar to the controls indicating normal suppressor T cell function in this disease. Such data showed that patients with Graves' disease possessed circulating T cells which exhibited autosensitization to syngeneic thyroid cell surface antigens, a phenomenon not demonstrable in control individuals. Furthermore, this specific T cell autosensitization did not interfere with non-specific T cell function as judged by its influence on IgG secretion.

Adult↗
PubMed1985

Prevalence and clinical associations of intraocular pressure changes in Graves' disease.

We investigated an unselected series of 55 patients with treated or untreated hyperthyroid Graves' disease, assessing their clinical and laboratory status and ophthalmological findings, including the difference in intraocular pressure (dIOP) between upgaze and straight gaze using applanation tonometry. An increased dIOP (greater than 2 mm Hg) was detected in only 22% of Graves' patients [who had a mean dIOP of 3.5 +/- 1.6 (+/- SEM) mm Hg]. dIOP did not correlate with age, sex, age at disease onset, duration of disease, mode of antithyroid treatment, or thyroid function testing at the time of examination. Mean Hertel exophthalmometry measurements in patients with a dIOP greater than 2 mm Hg were 22.0 +/- 2.9 mm compared with 18.4 +/- 3.7 mm in those with a dIOP less than 2 mm Hg (P less than 0.027, by Wilcoxon rank sum test). Only 58% of patients with increased dIOP had clinical exophthalmos, but all had other evidence of Graves' eye disease. Computed tomographic scanning revealed significant proptosis and/or orbital muscle involvement in all of the patients with increased dIOP.

Adult↗
PubMed1984

Congenital rubella syndrome as a model for type 1 (insulin-dependent) diabetes mellitus: increased prevalence of islet cell surface antibodies.

An increased prevalence of Type 1 (insulin-dependent) diabetes has been reported in patients with congenital rubella. Rubella virus multiplies in the pancreas, and we have hypothesized that studies of children with congenital rubella would be of great importance in following the development of Type 1 diabetes in a defined, susceptible population. Two hundred and forty-one children with congenital rubella (mean age 17.4 +/- 0.3 years; 65% black and hispanic) have been evaluated, 30 of whom already have diabetes and 17 of whom have borderline glucose tolerance. In these latter two groups, HLA-DR3 is significantly increased and HLA-DR2 significantly decreased. Pancreatic islet cell cytotoxic surface antibodies are found in 20% of the total congenital rubella population, including in more than 50% in the time period before they develop diabetes and are not related to any specific HLA type. In addition, anti-microsomal and anti-thyroglobulin antibodies are found in 34% of this population. The data demonstrate that Type 1 diabetes developing in congenital rubella patients has the genetic and immunological features of classical Type 1 diabetes, namely the presence of HLA-DR3, the absence of HLA-DR2, islet cell surface antibodies before decompensation and an increased prevalence of anti-thyroid antibodies. Patients with non-diabetic congenital rubella represent an easily identifiable group in whom other immunological factors associated with Type 1 diabetes can be elucidated and possibly modified.

Adolescent↗
PubMed1984

The luteinizing hormone-releasing hormone (LHRH) agonist [D-Trp6-Pro9-NEt]LHRH increased rather than lowered LH and alpha-subunit levels in a patient with an LH-secreting pituitary tumor.

Episodic secretion of LH, and the responses of serum LH, alpha-subunit, and testosterone concentrations to the acute administration of LHRH and the chronic administration of the LHRH agonist analog [D-Trp6-Pro9-NEt]LHRH (D-Trp6-Pro9) were evaluated in a 33-yr-old man previously reported to have an LH-secreting pituitary tumor unaccompanied by FSH hypersecretion. Basal serum LH and alpha-subunit concentrations were elevated [57 +/- 0.7 (SEM) mIU/ml (range, 45-71) and 26 ng/ml, respectively]. Frequent sampling revealed six LH secretory spikes over a 24-h period with increments above basal levels varying from 23-40% and interspike intervals ranging from 1.5-5 h. The concentrations of LH or alpha-subunit after iv administration of 150 micrograms LHRH did not increase above these intrinsic LH secretory increments (delta LH: 23%; delta alpha-subunit: 21%). The low basal serum FSH concentrations (3.5 mIU/ml) and elevated basal serum testosterone levels (1480 ng/dl) were unchanged after LHRH. Administration of clomiphene citrate produced no increase in serum LH, FSH, or testosterone concentrations. An attempt was made to decrease LH secretion in this patient using D-Trp6-Pro9. Administration of 200 micrograms daily sc of this LHRH analog for 21 days was associated with increases in serum LH and alpha-subunit concentrations. Mean serum LH and alpha-subunit levels for the 21 days of analog administration were 110 +/- 5.4 (SEM) mIU/ml (range, 70-170) and 64 +/- 3 (SEM) ng/ml (range, 32-84), respectively. During the 9-day period after discontinuance of the LHRH analog, levels of both serum LH and alpha-subunit declined precipitously and mean serum LH and alpha-subunit levels were 58 +/- 7 (SEM) mIU/ml (range, 18-90) and 22 +/- 3 (SEM) ng/ml (range, 12-44), respectively. We conclude that this patient's pituitary tumor has diminished responsiveness to acute LHRH administration and that the effect of chronic D-Trp6-Pro9 is stimulatory rather than inhibitory, as occurs after chronic administration of this analog to normal subjects. The blunted responsiveness to LHRH administration and the lack of response to clomiphene citrate suggest tumor autonomy. The presence of modest paradoxical responsiveness of serum LH and alpha-subunit concentrations during the course of daily D-Trp6-Pro9 administration suggests that central regulatory mechanisms, if present, are abnormal.

Adenoma↗
PubMed1984

Enzyme-linked immunosorbent microassay and hemagglutination compared for detection of thyroglobulin and thyroid microsomal autoantibodies.

We have evaluated for their potential use in the routine clinical laboratory enzyme-linked immunosorbent assays (ELISA) for human thyroglobulin antibodies (hTg-Ab) and microsomal antibodies (M-Ab). Results are expressed in terms of an "ELISA Index," based on comparison with a laboratory standard. The specificity of both ELISA assays is shown by dose-dependent inhibition of the hTg-Ab and M-Ab activities of the laboratory standards by the appropriate specific antigens. Similar concentrations of ovalbumin had no significant effect on the standard activity in both assays. For consecutive samples evaluated for hTg-Ab (n = 113) and M-Ab (n = 106) by ELISA and hemagglutination, rank order analysis of the results showed a highly significant correlation between the methods (r = 0.81, p = less than 0.001 for hTg-Ab; r = 0.82, p = less than 0.001 for M-Ab). However, 8/47 (17%) of samples positive in the hTg-Ab ELISA were negative by hemagglutination, and 7/69 (12%) of samples positive in the M-Ab ELISA were negative by hemagglutination. We effectively excluded the possibility of false positivity of these specimens by ELISA by blocking specimen positivity with the specific antigens in 12 of 14 specimens investigated. We conclude that ELISA techniques for human thyroid autoantibodies are sensitive and specific, easy to initiate, objective, and capable of use in large-scale screening. They are superior to standard hemagglutination techniques by having an increased detection rate for hTg-Ab and M-Ab.

Autoantibodies↗
PubMedDate not supplied

Influence of an interdisciplinary diabetes specialist team on short-term outcomes of diabetes at a community health center.

OBJECTIVE: To assess the effect on short-term diabetes outcomes of intervention with an interdisciplinary diabetes specialist team at a primary-care community health center in East Harlem, New York City. METHODS: An interdisciplinary diabetes specialist team, consisting of a diabetologist, a bicultural certified diabetes nurse-educator, and a nutritionist, attended weekly clinics at a primary-care community health center in East Harlem. Emphasis was placed on communicating in the patient's primary language and providing nutritional counseling, diabetes education, and diabetes management. After 1 year, a retrospective review of medical records for patients seen by the diabetes team was performed to assess the influence of this intervention on performance of home glucose monitoring (HGM), frequency of hypoglycemia, and changes in diabetes treatment regimens. Of 70 patients referred to the diabetes team by their primary-care providers, 50 underwent follow-up for at least 6 months and were included in the statistical analysis. RESULTS: Of the 50 study patients, 94% had type 2 diabetes, with a mean duration of 11.2 years. Eighty-two percent were Hispanic, and 18% were Afro-American. The mean age was 54.6 years. Microvascular complications were present in 44%, and macrovascular complications were present in 22%. HGM was done by 13 patients (26%) before and 33 patients (66%) after diabetes team intervention (P<0.001). Before intervention by the diabetes team, 14 patients (28%) were having episodes of unrecognized hypoglycemia. Unrecognized hypoglycemia resolved after intervention in all but two patients with type 1 diabetes (P<0.001). Before intervention, diabetes treatment was dietary in 6 patients, a sulfonylurea in 19, and insulin in 25; after intervention, 5 patients had dietary management of their diabetes, 14 were taking a sulfonylurea, and 31 were receiving insulin (P<0.05). CONCLUSION: Providing access to an interdisciplinary diabetes specialist team at the site of primary care had a beneficial effect on short-term diabetes outcomes in inner-city Hispanic and Afro-American patients with diabetes. Providing specialty care in the primary-care setting may be one model for improving the quality and long-term outcomes of diabetes care, particularly in high-risk populations.

Journal Article↗
PubMedDate not supplied

Grading the evidence for diabetes performance measures.

CONTEXT: Grading scientific evidence is a critical step in developing practice guidelines and quality performance measures. GENERAL QUESTION: What is the most useful way to grade evidence? SPECIFIC QUESTION: How should we grade the recommended clinical practices for patients with diabetes? STANDARD APPROACH: Hierarchical grading systems (e.g., grades I, II, and III), such as that used by the U.S. Preventive Services Task Force, have traditionally been used to rank the research designs of studies that support a particular clinical practice. POTENTIAL DIFFICULTIES: Many studies that support the clinical practices of diabetes care do not clearly conform to the categories traditionally used in hierarchical grading systems. As a result, there is a tendency to inaccurately characterize the level of evidence, leading to the phenomenon of evidence inflation or evidence deflation. To avoid exaggerating the evidence, important sources of information may be excluded, resulting in an understatement of the available supporting evidence. ALTERNATE APPROACH: This paper offers a more descriptive typologic system that uses the study design and an explanatory modifier to grade the evidence supporting the clinical practices of diabetes care. The study grades are randomized, controlled trial (RCT); RCT-embedded component; RCT-treatment only; RCT-different population; observational study-risk factor; and expert opinion. Using this grading system, the authors were able to more accurately describe the best available evidence supporting the clinical practices of diabetes care.

Diabetes Mellitus↗