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Biomedical subjects

M Sheinfeld

Publications and source records attributed to M Sheinfeld.

At least 19 recordsLinked to original sources
PubMed1992

Divergent effects of cytokines on human leukocyte antigen-DR antigen expression of neoplastic and non-neoplastic human thyroid cells.

Apparently complex modulatory effects of alpha-interferon (alpha-IFN), tumor necrosis factor (TNF), and epidermal growth factor (EGF) have been found in neoplastic human thyroid cells, which could possibly affect the final outcome in neoplastic disease. This was achieved by examining the influence of alpha-IFN, TNF, and EGF alone and in combination, on human leukocyte antigen-DR (DR) antigen expression and viability of neoplastic and non-neoplastic human thyroid cells in culture. alpha-IFN-induced DR antigen expression on non-neoplastic human thyroid cells, whereas TNF-alpha or EGF alone were ineffective. The addition of the same TNF-alpha concentrations (10 to 100 ng/ml) to alpha-IFN enhanced the expression of DR antigens compared with the effect of alpha-IFN alone. However, EGF inhibited alpha-IFN-induced DR on the same cells and at the same concentrations (10 to 500 ng/ml) at which the growth factor alone was ineffective. In contrast to the common pattern of cytokine effects on DR expression of all nonmalignant thyroid cell lines, neoplastic thyroid cell lines showed divergent responses to alpha-IFN, TNF-alpha, and EGF. In three malignant thyroid cell lines that were DR negative (follicular carcinoma WRO 82-1 and NRO 87-1 cell lines, and anaplastic carcinoma ARO 81-1), DR antigen could be induced by alpha-IFN and enhanced by TNF-alpha, whereas EGF was ineffective. In a fourth cell line (an anaplastic carcinoma SW1736) alpha-IFN, TNF-alpha, and EGF alone were capable of inducing DR, and a combination of either TNF-alpha and EGF with alpha-IFN potentiated DR induction. In a fifth neoplastic cell line (papillary carcinoma, NPA) that constitutively expressed surface DR, its expression was inhibited by both alpha-IFN and TNF-alpha and was not affected by EGF.

Antibodies↗
PubMed1992

Changes in stimulating and blocking TSH receptor antibodies in a patient undergoing three cycles of transition from hypo to hyper-thyroidism and back to hypothyroidism.

We report a patient who underwent, over a mere 3-year period, three successive cycles of oscillation from hypo to hyper-thyroidism and back to hypothyroidism. This unusual sequence of events originated in a rare passage of primary hypothyroidism to hyper-thyroidism. The hyperthyroidism seemed typical of the autoimmune subgroup of toxic multinodular goitre. Stimulating and blocking TSH receptor antibody activities were measured (by cAMP functional bioassays using cultured human thyrocytes) during the course of the fluctuating phases of hypo and hyper-thyroidism. Measurement of such antibody activities revealed the coexistence of both stimulatory and blocking types of antibody in several serum samples from the patient. Throughout the whole course of alterations in thyroid function, thyroid stimulating antibodies were present. This was not the case with thyrotrophin receptor antibodies exhibiting TSH antagonist activity which seemed to appear and disappear. Monitoring such activity indicated that the emergence of blocking antibody seems to herald the onset of hypothyroidism.

Autoantibodies↗
PubMed1992

Divergent effects of thyroid HLA-antigens on T and natural killer (NK) cell cytotoxicity.

We have used non-autoimmune non-neoplastic human thyroid cells to explore the role of surface class I and DR antigens on these cells' sensitivity towards T and Natural Killer (NK) cell cytotoxicity. Non-treated thyrocytes expressed class I but no DR antigens. Following incubation with gamma-interferon (gamma-IFN) class I antigens were markedly elevated and DR expression was induced. Whereas non-treated thyrocytes were minimally lysed by sensitized T cells, they served as appropriate targets for NK cells. Following incubation with gamma-IFN, the thyroid cells became highly sensitive to T cell lysis, with no significant reduction in their vulnerability to NK cell killing. The addition of monoclonal anti class I or DR antigens, or brief acid treatment which specifically eliminates class I molecules, inhibited T cell cytotoxicity but enhanced the sensitivity to lysis by NK cells. Thus, the presence of HLA antigens on the same thyroid cells have an opposite effect on two major cytotoxi mechanisms. Our findings are relevant within the context of recent suggestions of intervening with target HLA antigens for the management of autoimmune and malignant diseases.

Cytotoxicity, Immunologic↗
PubMed1991

Early and late lesion-to-non-lesion ratio of thallium-201-chloride uptake in the evaluation of "cold" thyroid nodules.

Forty-nine consecutive patients with "cold" thyroid nodules were studied using early and late visual and semiquantitative measurements of 201Tl uptake in the nodule to differentiate benign from malignant nodules. The visual method compared 201Tl uptake in the nodule to the normal thyroid tissue. The semiquantitative method used a lesion-to-non-lesion (L/N) ratio of the same areas. Both measurements were carried out early (15 min) and late (3 hr) following 201Tl injection. The reproducibility of the method for the early and late measurements was tested for intraobserver and interobserver variability as well as for repeatability coefficients. The visual method resulted in 43% sensitivity and 79% specificity for the detection of malignant nodules. The L/N method showed that an early threshold of 1.55 chosen by receiver characteristic analysis had a sensitivity of 57% and a specificity of 86%, while the late ratio of 0.99 had a sensitivity of 100% and a specificity of 62%. It is concluded that a L/N 201Tl uptake method performed 3 hr following 201Tl injection is superior to a visual scoring method as well as to the early L/N 201Tl uptake in detecting malignant thyroid nodules.

Adenoma↗
PubMed1990

Class II HLA-DR antigens on non-autoimmune human thyroid cells stimulate autologous T cells with high suppressor activity.

Human autoimmune thyroid cells "spontaneously" express MHC-class II antigens. These antigens have been assumed to trigger thyroid-specific helper T cell clones, leading in turn to the expansion of thyroid autoantibody-secreting B cells. Thyroid cells derived from non-autoimmune subjects do not express MHC-class antigens, but these can be readily induced with gamma-interferon. We have addressed the issue of whether it is sufficient for normal thyroid cells to bear class II antigens in order to trigger autologous T cells. We found that non-autoimmune thyrocytes expressing DR antigens fail to stimulate autologous resting T cells. However, proliferative activity and interleukin-2 secretion were observed when fresh T cells were first triggered by autologous non-T cells and then incubated with thyrocytes. More CD8 than CD4 cells proliferated in the T:thyrocyte cultures, but CD4 cells were necessary for the proliferation and interleukin-2 secretion. Addition of antibodies to thyroglobulin or to DR antigens inhibited T cell proliferation and interleukin-2 secretion, thus pointing to T cell recognition of both thyroid-specific and DR antigens. Evaluation of the function of the thyroid stimulated T cells revealed very potent suppressor but negligible helper and cytotoxic activities. It would seem, therefore, that DR-restricted T cell activation by autologous antigen on non-autoimmune thyroid cells does occur, but since it results in enhanced suppression, its nature seems protective, thus leading to maintenance of immunological self-tolerance.

Antigen-Presenting Cells↗
PubMed1989

The fertilization and cleavage rates of eggs recovered from the cul-de-sac.

Five hundred ninety-one oocytes were laparoscopically recovered in 93 consecutive stimulated cycles. Fifty-three of the 591 oocytes were collected from the cul-de-sac in 39 cycles. The cul-de-sac-originated oocytes had fertilization and cleavage rates of 72 and 79%, respectively; these rates were similar to those achieved in oocytes originating from follicles. A significant decrease in the fertilization rate of cul-de-sac-originated oocytes was noticed in oocytes collected from the cul-de-sac 60 minutes or more after the beginning of the procedure. Oocytes collected from the cul-de-sac yielded 21% of the embryos transferred in cycles where some of the oocytes were recovered from the cul-de-sac. These findings indicate that repeated aspirations of the cul-de-sac may increase the number of embryos transferred.

Body Fluids↗
PubMed1989

Urinary and blood levels of adenosine 3',5'-monophosphate, phosphorus and calcium in infants.

The changes during the first year of life in urinary and nephrogenous cAMP levels were determined in 152 normal, full-term infants using spot urine samples. The use of spot tests simplifies considerably the logistics of the cAMP determination which can be used for the investigation of parathyroid function. Levels of urinary and nephrogenous cAMP (expressed both as a function of creatinine excretion as well as glomerular filtration rate) rose from birth to 1 year of age, whereas plasma cAMP levels did not change significantly. Levels of cAMP (both urinary and nephrogenous) were significantly correlated with age, length, weight, and urinary phosphorus concentrations of the infants. No significant correlation could be observed, however, between serum phosphorus or serum and urinary calcium on the one hand, and urinary or nephrogenous cAMP on the other.

Aging↗
PubMed1988

Pregnancies following the interval double-transfer technique in an in vitro fertilization-embryo transfer program.

In 16 women undergoing IVF-ET, with more than four embryos available, two transfers were performed (24 hr apart), instead of one. The pregnancy rate was 25%, as compared with a pregnancy rate of 6.2% in 16 women having fewer than four embryos available and in whom one conventional transfer was performed. Since in our IVF-ET program, we do not freeze the extra embryos available, the purpose of the double transfer was to use all the embryos available and to improve the chances of finding the "implantation window" open. It is our feeling that multiple transfers may be beneficial to improve the pregnancy rate in an IVF-ET program without freezing facilities. However, a larger controlled clinical trial is necessary, in order to establish the advantages of multiple transfers in terms of pregnancy rate in comparison with the potential disadvantages.

Embryo Transfer↗
PubMed1988

Bioassay of thyroid-stimulating immunoglobulin in cryopreserved human thyroid cells: optimization and clinical evaluation.

We have explored the method of Rapoport et al. (J Clin Endocrinol Metab 1984;58:332-8) for the bioassay of thyroid-stimulating immunoglobulin (TSI) in cultured human thyroid cells, to optimize the assay and to evaluate its utility in clinical diagnosis and management of patients with autoimmune thyroid disease. Here we describe the procedure ultimately adopted, its major properties, and the results it has yielded in various clinical states. Clinical sensitivity of the assay was established by demonstrating TSI activity in all of 60 cases of active Graves' disease. We observed in these patients a nonlinear correlation between concentrations of TSI and of triiodothyronine, as well as between TSI concentration and the clinical severity of the thyrotoxicosis. Specificity of the assay was demonstrated by finding no TSI bioactivity in 13 patients with toxic adenoma, five with cold nodule, and 18 of 19 with nontoxic goiter. Remission of Graves' disease in 25 patients was invariably accompanied by undetectable concentrations of TSI; evidently this assay may be useful in identifying patients who are likely to go into remission. TSI activity was present in eight of 11 patients with euthyroid ophthalmopathy (unilateral and bilateral) associated with a normal response to the thyrotropin-releasing hormone test and absence of increased titers of antithyroid antibodies, suggesting that this assay may provide a powerful tool in the clinical diagnosis of this disorder.

Antibodies↗
PubMed1987

The influence of cryopreservation on the ultrastructural morphology of human thyroid cells.

The purpose of this study was to investigate the effects of the freeze-thaw procedure on the ultrastructural features of human thyroid cells. Four different stages of thyroid cell preparation were compared: (1) fresh surgical tissue, serving as control, (2) cell suspension before freezing, (3) cell suspension after thawing, and (4) monolayer cell culture, obtained from cells after thawing. Electron microscopic examination of cells from each stage showed that the freeze-thaw procedure used caused only minor intracellular alterations restricted to mitochondria. Some of these organelles showed low-amplitude swelling or occasionally appeared condensed. These ultrastructural changes were not paralleled by a decrease in the vitality or sensitivity of the cryopreserved cells to stimulating agents.

Cells, Cultured↗
PubMed1987

Thyrotrophin receptor blocking antibodies: incidence, characterization and in-vitro synthesis.

The prevalence and characteristics of TSH receptor blocking activity were examined in patients with different thyroid disorders. Studies were also performed on the in-vitro synthesis and immunoregulation of the blocking antibody. Blocking activity was tested by measuring the inhibition of TSH-stimulated cAMP production of cultured human thyroid cells by patient immunoglobulin (Ig) preparations. The following patients were investigated (number of cases in parentheses): Hashimoto's thyroiditis (33); primary myxoedema (17); euthyroid ophthalmopathy (8); active Graves' disease (19); cold nodule (5); non-toxic goitre (14); toxic adenoma (8); toxic multinodular goitre (9) and 22 normal controls. TSH receptor blocking activity was only detected in primary hypothyroidism with the following characteristics: (i) Such activity was present in only 16% of the patients (both goitrous, i.e. Hashimoto's thyroiditis, and non-goitrous, i.e. primary myxoedema), and in three patients with previously active Graves' hyperthyroidism who had become hypothyroid. (ii) Blocking activity seems to be associated with the Ig fraction of serum as indicated by protein A adsorption. (iii) The block-positive samples did not bind 125I-TSH, which seems to rule out an antibody directed against TSH. (iv) The specificity of the blocking activity seems to be directed towards the TSH-(thyroid stimulating immunoglobulin, TSI) receptor-mediated cAMP response since no inhibition of prostaglandin E1-stimulated cAMP production was found. Moreover, all cases in which an inhibitory effect was demonstrated towards TSH also exhibited blocking of TSI-stimulated cAMP, with a high correlation between the degree of inhibition of the TSH to that of the TSI response (r = 0.89, P less than 0.001, n = 11). The blocking activity may contribute to the pathogenesis of some cases of primary hypothyroid autoimmune thyroiditis, both goitrous and non-goitrous, as well as in the evolution of hyper- to hypothyroidism. By culturing peripheral blood lymphocytes, as well as B/T lymphocyte co-cultures isolated from three patients with blocking activity present in serum, the in-vitro synthesis of the blocking antibody was demonstrated for the first time. Moreover, in-vitro secretion of the antibody by patients B lymphocytes, as well as T cell regulation of autoantibody production, were also shown.

Adult↗
PubMed1987

Toxic multinodular goiter: a variant of autoimmune hyperthyroidism.

The aim of this study was to examine whether at least a subgroup of patients with toxic multinodular goiter may have autoimmune thyroid disease. Thyroid-stimulating immunoglobulin (TSI) activity, measured by a sensitive bioassay employing cultured human thyroid cells, was determined in patients with toxic multinodular goiter and other thyroid disorders. All patients with active Graves' disease (n = 47) had detectable serum TSI activity, whereas TSI was undetectable in patients with thyroid disease not believed to be of autoimmune origin: toxic adenoma (n = 13), cold nodule (n = 5), and nontoxic goiter (n = 19), with a single exception in the latter group. Toxic multinodular goiter (n = 26) was diagnosed based on clinical and laboratory evidence of hyperthyroidism associated with a multinodular goiter on palpation and scintiscan. The toxic multinodular goiter group was then subclassified according to scintiscan pattern (type A, diffuse but uneven distribution of technetium uptake; type B, multiple discrete nodules of varying size and function). All but 1 of the 11 TSI-positive toxic multinodular goiter patients had a type A scintiscan pattern. The patients with the type A scintiscan pattern were younger and more often had elevated antithyroid antibody titers, ophthalmopathy, and concurrent development of goiter and hyperthyroidism (rather than long-standing goiter preceding hyperthyroidism) compared to the type B patients. Thus, a subgroup of patients with clinically defined toxic multinodular goiter (type A) probably have autoimmune hyperthyroidism (a variant of Graves' disease), while in another subgroup (type B) hyperthyroidism is not related to an autoimmune etiology (a variant of toxic adenoma).

Adenoma↗
PubMed1986

Magnetic resonance imaging of the pituitary gland.

Magnetic resonance imaging (MRI) was performed on 22 patients with a wide spectrum of pituitary disease and on 17 control subjects, in order to determine whether MRI is useful in localising and determining the extent of involvement of large and small pituitary tumours. The results indicate that MRI, with an 0.5 T superconducting magnet (Elscint, Israel), can be used to visualise large pituitary tumours and to determine the extent of parasellar and suprasellar involvement. The 'empty sella' syndrome can also be easily and confidently diagnosed. Some microadenomas can be visualised despite the relatively thick slices (0.7 cm) used in this study. These findings suggest that MRI in its current state of development is very useful in evaluating large pituitary lesions. With further technical refinements, improving the spatial resolution and decreasing slice thickness, this technique may come to be of some importance in the evaluation of pituitary microadenomas.

Acromegaly↗
PubMed1985

Leydig-cell tumor of the ovary: visualization using 131I-19-iodocholesterol scintigraphy.

A Leydig (Hilus)-cell tumor of the ovary was diagnosed in a 54-year-old woman with severe hirsutism and virilization. This case is unique in that it was diagnosed in a postmenopausal female 24 years after ovarian irradiation for sterilization, and the tumor was successfully localized preoperatively using 131I-19-iodocholesterol scintigraphy. This nuclear scanning technique may be of use in documenting the biologic activity of ovarian masses and in localizing functioning ovarian tumors which are too small to palpate or to localize by other means.

19-Iodocholesterol↗
PubMed1985

Do cyclic AMP concentrations in saliva reflect PTH biologic activity?

The aim of this study was to investigate whether the concentration of cAMP in saliva might reflect the biologic activity of parathyroid hormone (PTH), as nephrogenous levels of cAMP reflect parathyroid function. Patients with primary hyperparathyroidism (HPT) with elevated levels of PTH, nephrogenous cAMP, and serum calcium were found to have cAMP levels not significantly different from control subjects. When the levels of these parameters were reduced following parathyroidectomy, salivary cAMP concentrations were not affected. Similarly, an oral calcium loading test (which decreased both PTH and nephrogenous cAMP in normal subjects) failed to influence salivary cAMP levels. Basal salivary cAMP concentrations were low in secondary hyperparathyroid patients due to chronic renal failure and rose almost fivefold following dialysis despite the stable plasma cAMP levels and salivary flow rate. We conclude that salivary cAMP concentrations do not appear to be influenced by changes in circulating biologically active PTH. However, salivary cAMP concentrations do change in response to certain perturbations; this suggests that they are regulated by some other modulator(s).

Adolescent↗