Search PubMed⌕ Search

Biomedical subjects

J M McKenzie

Publications and source records attributed to J M McKenzie.

At least 19 recordsLinked to original sources
PubMed1994

Bulimia comorbidity in the general population and in the clinic.

This study compares rates of comorbidity of lifetime psychiatric disorder in a clinical sample of women with bulimia, with general population base rates, and with rates of comorbidity among bulimic women in the general population. Eighty-four per cent of the clinical sample of bulimic women had a lifetime affective disorder, and 44% a lifetime alcohol or drug disorder. These rates of disorder were significantly higher than the base rates in the general population. Bulimic women in the general population also had more affective and substance-use disorders than the general population base rates, but the rates of these disorders were lower than found in the clinical sample. In the general population, quite similar rates of other disorders including generalized anxiety, panic, phobia and obsessive-compulsive disorder, are found among those with bulimia, substance-use disorder and depression. Furthermore, among those with depression and substance-use disorder in the general population, rates of eating disorder are comparable. Rather than suggesting a specific relationship between bulimia and either depression or substance-use disorder, the data from this study suggest that the presence of any disorder is associated with a non-specific increase in the likelihood of other psychiatric disorder.

Adolescent↗
PubMed1994

Perforin expression by thyroid-infiltrating T cells in autoimmune thyroid disease.

Infiltration of the thyroid gland by lymphocytes is a hall-mark of autoimmune thyroid disease; it is particularly evident in Hashimoto's thyroiditis but is also seen in most patients with Graves' disease. Infiltrating cells are comprised primarily of T lymphocytes, of which only a minority appears to be activated. Their precise pathogenic role is largely unknown. Since perforin has been a marker for functionally activated cytotoxic T cells in situ we elected to assess the presence of perforin-containing cells in thyroid-infiltrating lymphocytes and establish their phenotype. Cells were isolated from seven subtotal thyroidectomy specimens, five from patients with Graves' disease and two with Hashimoto's thyroiditis. The novel findings were as follows: CD4+ perforin-containing T cells occurred only in Hashimoto's glands, suggesting a class II-restricted component of cytotoxicity; in Graves' disease, and to a lesser extent in Hashimoto's, perforin-expressing cells were primarily T cell receptor alpha beta- CD4-CD8- (double negative); double negative perforin-containing cells in peripheral blood of normal individuals were largely gamma delta + T cells. In Hashimoto's samples, the predominant population of T cells expressing perforin was CD8+. By comparison, in studies of the synovial fluid of knee joints from patients with rheumatoid arthritis only a minor population of the perforin-containing cells was double-negative. The data suggest significant differences in cytotoxic autoimmune mechanisms between the two autoimmune thyroid diseases. Functional characterization of double-negative T cells is necessary to define their role in autoimmunity.

Arthritis, Rheumatoid↗
PubMed1994

Visualization of the thyrotropin receptor on the cell surface by potent autoantibodies.

In autoimmune thyroid disease there are various autoantibodies (Ab) to thyroid cell components. Among the best characterized are those to thyroid peroxidase (TPOAb) and to the thyrotropin receptor (TRAb). While TPOAb were successfully used to visualize TPO in human thyroid cells (HTC) and a rat thyroid cell line (FRTL5) by indirect immunofluorescence (IFL), similar attempts with TRAb and thyrotropin receptor (TSHR) failed. This could have been due to either relatively low serum levels of TRAb and/or low number of TSHR on thyroid cells. To test these hypotheses, we estimated the number of TSH binding sites on HTC, FRTL5 and Chinese hamster ovary (CHO) cells, transfected with cloned human TSHR (JP-26 cells), and for IFL staining employed 3 sera with the highest potency TRAb in our possession. A clear granular surface staining was detected on all 3 cell types with two sera; with the third, the least potent, no staining was seen. The density of staining paralleled the estimated number of TSHR per cell, i.e., JP-26 > FRTL5 > HTC. TSHR was also visualized on transiently transfected cells (COS-7-TSHR), facilitating quantitation of transfection. Our results suggest that the limiting factor in direct visualization of the TSHR is the TRAb concentration.

Animals↗
PubMed1994

Characteristics and clinical correlates of a novel thyroid-stimulating autoantibody.

We reported a patient who gave birth to 3 children with transient neonatal hypothyroidism. She had 3 different antibodies (Ab) to the thyrotropin receptor (TSHR) in her serum, viz., TSH binding-inhibiting (TBIAb), thyroid-stimulating (TSAb) and an additional stimulating Ab (SAb). The SAb differed from TSAb in that its in vitro stimulating effect in human thyroid and FRTL5 cells was not inhibited by TBIAb [similar data now obtained with Chinese hamster ovary (CHO) cells transfected with cloned human TSHR]. Because of symptomatic goiter enlargement the patient underwent subtotal thyroidectomy. About 50% of the gland was infiltrated with lymphocytes; thyroid follicles had columnar epithelium, despite suppression of TSH by thyroxine and the presence of the potent TBIAb. Fifteen months later, when all 3 Ab showed a decline of approximately 3 fold, she gave birth to hypothyroid twins. These data support the following conclusions: 1) thyroidectomy and immunosuppression of pregnancy do not prevent neonatal thyroid disease if TSHR Ab (TRAb) are of high titer; 2) the thyroid is not a major site of TRAb production; 3) SAb is a thyroid stimulator, distinct from TSAb in that it does not share binding epitopes on the TSHR with either TSH or TBIAb; 4) SAb was the probable cause of thyroid growth in this patient.

Adult↗
PubMed1993

Complex segregation analysis of antibodies to thyroid peroxidase in Old Order Amish families.

Autoimmune thyroid disease (AITD) may be characterized by the measurement in serum of antibodies to thyroid peroxidase. A population of Old Order Amish individuals and families was investigated to determine the prevalence of these antibodies and to examine hypotheses about the mode of transmission of thyroid antibodies. Complex segregation analyses were performed on 4 large multigenerational Old Order Amish families composed of 26 nuclear families containing 199 first degree relatives. Several alternative hypotheses of genetic transmission were examined. Hypotheses of no transmission, polygenic inheritance, single locus transmission, and mixed inheritance were compared. The analyses incorporated population prevalences obtained from a random sample of individuals. Results suggest that the pattern of transmission of thyroid antibodies in these families is consistent with a mixed model in which the major gene is transmitted in an autosomal dominant pattern. The mixed model postulates that there is a single gene of major effect as well as a polygenic component that can act separately and/or together to confer susceptibility for this phenotype. The parameter estimates for the major locus are: gene frequency (q), 0.16 +/- 0.01; maximum male penetrance, 0.35; and maximum female penetrance, 0.70. The heritability of the polygenic background is estimated at 0.41.

Adolescent↗
PubMed1993

Retention and strength of silicone-rubber catheters. A report of five cases of retention and analysis of catheter strength.

Five patients had a silicone-rubber catheter that broke during attempted removal. Mechanical testing was performed to determine the tensile strength of silicone-rubber as well as of polyvinyl chloride catheters. Silicone-rubber catheters were found to have a low tensile strength. The pull-out force of ten indwelling silicone-rubber catheters was also measured. The pullout force measured from a patient who had a cast was close to 40 per cent of the strength of the silicone-rubber catheters.

Bone Diseases↗
PubMed1992

Fetal and neonatal hyperthyroidism and hypothyroidism due to maternal TSH receptor antibodies.

Autoimmune thyroid disease is a generic term that includes Graves' disease and Hashimoto's thyroiditis. In the former, there is overactivity of the thyroid due to the action of a thyroid-stimulating antibody (TSAb). Pathogenesis of Hashimoto's thyroiditis is largely cell-mediated immune destruction of the thyroid. Nonetheless, there may be either a goiter or an atrophic gland. There is evidence that in some patients the lack of goiter is associated with the presence in the blood of an antibody that inhibits the binding of TSH to its receptor. This TSH-binding inhibiting antibody (TBIAb), therefore, prevents TSH from stimulating the thyroid and constitutes an acceptable explanation for an agoitrous state. Collectively, TSAb and TBIAb, both of which are IgG, are known as TSH receptor antibodies (TRAb).

Autoantibodies↗
PubMed1992

Evaluation of the biological significance of leukocyte infiltration of the thyroid in Graves' disease.

Graves' goiter size and gland function may be affected by interferon-gamma influencing actions of the thyroid-stimulating antibody. Goiter weight (n = 20), lymphocytic infiltration and class II antigen expression were assessed. The largest goiters, strikingly, has least infiltration but, overall, the looked-for negative correlation between goiter size and lymphocyte infiltration did not materialize. This was presumably due, in part, to inhibiting antibodies in many (8/18) patients' sera. In addition, our data do not support a major pathogenetic role for class II antigen in Graves' disease.

Adolescent↗
PubMed1991

The site of the molecular defect in the thyroid gland of the hyt/hyt mouse: abnormalities in the TSH receptor-G protein complex.

The hyt/hyt mouse has a severe and pervasive primary inherited hypothyroidism with significantly depressed serum T4, elevated serum and pituitary TSH, and reduced thyroid gland iodide uptake. Previous ultrastructural and histologic analysis of the hyt/hyt thyroid gland along with these biochemical abnormalities support an inherited defect in TSH responsiveness of the hyt/hyt thyroid gland. In order to evaluate the potential site of the defect in the hyt/hyt mouse, we have studied the hyt/hyt gland and hyt/hyt TSH from a biochemical and molecular standpoint. Based on demonstrated bioactivity of hyt/hyt serum in the McKenzie bioassay, this reduced responsiveness to TSH in the hyt/hyt mouse is not due to reduced bioactivity of hyt/hyt TSH or a major structural abnormality in the hyt/hyt TSH molecule. In comparison to hyt/ + euthyroid littermates and +/+ BALB/cBY progenitor strain mice, the hyt/hyt mouse demonstrates a twofold reduction in thyroid gland basal cAMP and a markedly diminished response of adenylyl cyclase to exogenous TSH. However, hyt/hyt cAMP production is equivalent to the euthyroid mice after stimulation of thyroid glands by forskolin, cholera toxin, PGE1, and isoproterenol. These results support a defect in the TSH-G protein-adenylyl cyclase system in the hyt/hyt thyroid gland. Specifically, these findings suggest that the hyt/hyt mouse has a defect in TSH responsivity due to an inherited defect in the thyroid gland TSH receptor molecule. Since the hyt/hyt gland makes T3 and T4 but at diminished levels, the proposed defect in the TSH receptor would still impart partial function. Both hyt/hyt and euthyroid hyt/ + littermates make TSH receptor mRNAs of 5500 and 2400 base pairs. This suggests that the receptor defect does not represent a major structural abnormality of the gene. The receptor defect could represent a reduction in receptor number, receptor-TSH affinity, or TSH receptor-G protein coupling. The specificity of this effect on adenylyl cyclase-cAMP is shown by the reduction of TSH-cAMP regulated thyroid peroxidase (TPO) and thyroglobulin mRNAs in the hyt/hyt thyroid gland. Given the importance of TPO and thyroglobulin in normal thyroid hormone synthesis, the reductions in TPO and thyroglobulin mRNAs in the hyt/hyt thyroid gland may underlie the significant decrease in thyroid hormone production by the hyt/hyt mouse.

Adenylyl Cyclases↗
PubMed1991

Case report: hypothyroidism due to pneumocystis carinii thyroiditis in a patient with acquired immunodeficiency syndrome.

Pneumocystis carinii is the most common cause of opportunistic pulmonary infection in AIDS patients and disseminated disease is being recognized with increasing frequency. We describe a patient with cavitary pulmonary disease, lymphadenopathy, thyroiditis, and associated hypothyroidism, all a result of P. carinii. The organism was easily demonstrated in a fine-needle aspirate specimen of the thyroid. This is the second reported case of clinically apparent Pneumocystis thyroiditis and the first reported case of hypothyroidism due to an opportunistic infection in a patient with AIDS. Clinicians should be aware of this entity and request a Grocott-Gomori methenamine-silver nitrate stain of appropriate cytology specimens to make the diagnosis.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Infections at the site of a hip implant. Successful and unsuccessful management.

Thirty-four patients developed the complication of deep infection at the site of a hip implant (n = 35). Multiple factors in existence at the time of implant placement and the time of presentation with infection as well as the therapeutic regimen were retrospectively analyzed. Patients with successful outcomes (n = 15) were relatively younger (mean, 52 years) compared to those that had an unsuccessful outcome (n = 19; mean, 65 years; p less than 0.01). No other factors were predictive of the outcome of treatment. Implant extirpation, expedient wound closure, and, when necessary, muscle transposition favored a successful outcome. Implant retention and open wound packing resulted in prolonged wound healing and, sometimes, hip disarticulation or death.

Adult↗
PubMed1990

Transient neonatal hypothyroidism: characterization of maternal antibodies to the thyrotropin receptor.

Transient neonatal thyroid disease is known to occur as a result of transplacental passage of maternal immunoglobulin G (IgG) that contains antibodies to the TSH receptor (TRAb). Thyroid-stimulating antibody (TSAb) produces hyperthyroidism, and antibody that blocks TSH binding (TBIAb) results in hypothyroidism. We have analyzed in detail the IgG from four women who gave birth to children with transient neonatal hypothyroidism and have shown stimulating and inhibiting antibodies to coexist in three. Human and/or rat thyroid (FRTL5) cells were used to show stimulatory effects in vitro. Inhibition was assessed as prevention of stimulation of these cells (by TSH or TSAb) or by the blocking of binding of [125I] TSH to its receptor. The IgG from two mothers was tested to identify whether the inhibitory and stimulating bioactivities resided in molecules characterized by either or both kappa- or lambda-light chains. Evidence for restricted heterogeneity (implying oligoclonality) was obtained, in that with one, purely inhibitory IgG all activity was with IgG kappa. With the other, stimulating and inhibitory activities were predominantly in IgG kappa and IgG lambda, respectively. In addition, the latter IgG contained a second stimulator that was not suppressed by either its own or other inhibitory IgG. Despite the presence of stimulatory antibodies in these IgG, the clinical effect was neonatal hypothyroidism, reflecting the greater potency of the inhibitory IgG in all instances. Based on the histories of these four women and their offspring it is apparent that TRAb, and in particular TBIAb, can develop at any point in the course of autoimmune thyroid disease, i.e. either at the onset or long after the autoimmune process has been established.

Adult↗
PubMed1989

Graves disease presenting as painful thyroiditis.

Hyperthyroidism associated with subacute (painful, viral) thyroiditis is well-recognized as a clinical entity; the thyroid gland in Graves disease is minimally, if ever, tender and painful. We describe a 10-year-old girl with hyperthyroidism whose initial clinical presentation was predominantly a painful, tender goiter. Graves disease was established by high uptake of 131I with a diffuse pattern of distribution of radioactivity on scan and the presence of thyroid-stimulating antibody. Thyrotropin-binding inhibiting IgG and antibody to thyroid microsomal antigen were both positive. She responded well to treatment with propylthiouracil and had spontaneous regression of her thyroid pain. The cause of the severe pain and tenderness remains speculative.

Child↗
PubMed1989

Variations in the culture medium for FRTL5 cells: effects on growth and iodide uptake.

We evaluated the composition of the medium in which FRTL5 cells were incubated for effects on basal and stimulated growth and differentiated function. Variables included the concentration of calf serum (CS) from 0% (0.2% BSA) to 5% and the addition of insulin or insulin-like growth factor-I (IGF-I); stimulation was by TSH, with some experiments using thyroid-stimulating antibody-immunoglobulin G. The basal rate of incorporation of [3H]thymidine and the content of DNA per well were enhanced progressively by the increasing concentration of CS, whether in a pretreatment period of 3 days or over a subsequent 2 days of incubation. Concomitantly, I- uptake was progressively inhibited. Stimulation of growth by TSH required serum and was greatest with 5% CS; TSH effect on I- uptake was progressively decreased by increments of CS. Insulin and IGF-I had effects comparable to each other, but much smaller concentrations of IGF-I were required; they both augmented growth and enhanced growth stimulation by TSH. These actions were progressively annulled by increasing concentrations of CS. I- uptake (basal and stimulated) was inhibited by insulin and IGF-I, but this inhibitory effect was abolished by CS, particularly at 5% concentrations. Overall, the influences of varying the concentrations of CS and the effects of insulin or IGF-I were consistent; if there was enhancement of growth stimulation, there was inhibition of the TSH effect on I- uptake. Underlying mechanisms for these observations have yet to be elucidated.

Animals↗
PubMed1989

Influence of cytokines on growth and differentiated function of FRTL5 cells.

A functioning rat thyroid cell line (FRTL5) was used to study interactions of TSH with interferon-gamma (IFN gamma) and tumor necrosis factor-alpha (TNF alpha). We examined effects on growth and differentiated function. Growth was assessed by DNA, incorporation of [3H]thymidine ([3H]Tdr) into DNA, and cell number; uptake of 125I (I- uptake) and the concentration of cAMP were measured simultaneously with growth assessment. IFN gamma stimulated the 30-min I- uptake and enhanced the effect of TSH. TNF alpha had minimal effects on growth indices (slight increase in [3H]Tdr incorporation) and had no influence on I- uptake; it inhibited TSH stimulation of both growth and I- uptake. When combined, IFN gamma and TNF alpha synergized in inhibiting TSH-stimulated growth. By itself TNF alpha inhibited stimulation of I- uptake by TSH, but augmented the enhancement seen with IFN gamma. The influence of calf serum (CS) was to increase the rate of incorporation of [3H]Tdr, but a similar qualitative pattern for the actions of the cytokines remained. A reverse profile (stimulation by IFN gamma, inhibition by TNF alpha, and stimulation by the combination) was seen for I- uptake, with CS increasingly diminishing all values. TSH stimulation of growth was progressively effective with increments of CS in the medium, but consistently there was inhibition that was greater with IFN gamma than with TNF alpha and was almost total with the combined cytokines. Stimulation of I- uptake by TSH was enhanced by IFN gamma, reduced by TNF alpha, and, when serum was present, increased to a degree that was greater than additive by the combined cytokines. Growth stimulation by insulin or insulin-like growth factor-I was inhibited partially by the individual cytokines and completely by the combination. Both insulin and insulin-like growth factor-I inhibited TSH stimulation of I- uptake, but similar stimulation by the cytokines was not affected. Simultaneous with inhibition of TSH-stimulated growth, both IFN gamma and TNF alpha enhanced cAMP accumulation. The mechanism of these multiple effects of IFN gamma and TNF alpha, especially on the actions of TSH, may not currently be fully explained, but they almost certainly reflect differing modes of action. The relevance to thyroid function in man is conjectural. Especially in Graves' disease, where thyroid infiltration with cells that secrete these cytokines is common, it seems probable that both IFN gamma and TNF alpha will have significant influences on both growth and differentiated cell function.

1-Methyl-3-isobutylxanthine↗