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Biomedical subjects

F Maloof

Publications and source records attributed to F Maloof.

At least 55 records · Page 3Linked to original sources
PubMed1978

Myocardial function in hypothyroidism. Relation to disease severity and response to treatment.

Systolic time intervals (ST) were used to evaluate myocardial function prospectively in 29 hypothyroid patients. The patients were divided into three categories of disease severity: (1) severe hypothyroidism, (2) mild hypothyroidism, and (3) decreased thyroid reserve or "prehypothyroidism." Groups 1 and 2 showed decreased myocardial contractility with a prolonged preejection period (PEP), shortened left ventricular ejection time (LVET), and increase PEP/LVET, compared with normal controls. The STI were more abnormal (P less than .05) in group 1 than in group 2, suggesting that the severity of myocardial dysfunction correlates with the severity of the hypothyroidism. Group 3 had normal STI. Ten patients were restudied when euthyroid and showed complete normalization of their STI, supporting the thesis that hypothyroidism was the sole cause of the initial myocardial dysfunction.

Female↗
PubMed1978

Lower levels of thyrotropin-releasing hormone-degrading activity in human cord and in maternal sera than in the serum of euthyroid, nonpregnant adults.

Thyrotropin-releasing hormone (TRH)-degrading activity was investigated in human cord, maternal, and euthyroid adult sera by measuring (a) the rate of disappearance of TRH and (b) the rate of formation of degradation products. The rate of TRH degradation in cord and maternal sera was 25-33% of that in euthyroid adult serum. Concomitantly, in cord and maternal sera, the rate of formation of proline, a major TRH degradation product in serum, was one-quarter to one-third that in euthyroid adult sera. The differences were highly significant (P less than 0.001). The decreased levels of TRH-degrading activity in cord and maternal sera cannot be explained by (a) the presence of a dialyzable inhibitor, (b) the absence of an activator of TRH degradation, or (c) a reversal of the degradation process. There was no difference in the types of radioactive degradation products formed by cord, maternal, and euthyroid adult sera. The low level of TRH-degrading activity and its possible relationship to high thyrotropin-stimulating hormone levels in cord serum suggest that TRH-degrading activity may be a factor to consider in investigations of the perinatal pituitary-thyroid axis, but further studies are needed to determine the role of serum degradation of TRH in regulating physiological levels of TRH.

Adult↗
PubMed1978

Decreased thyroid function and high plasma prolactin levels in rats of the Buffalo strain.

Rats of the inbred Buffalo strain have previously been reported to be susceptible to thyroiditis, as defined by histology. We have studied the endocrinology of the pituitary-thyroid axis of this strain by making direct measurements of the plasma concentrations of TSH and T4 in untreated, adult Buffalo rats of both sexes. Plasma PRL levels were also measured. All hormone determinations were by RIA. In addition, relative thyroid weights were noted and, in many cases, preliminary assessment of thyroid histology was made. Our principle findings were as follows. 1) Decreased thyroid function, in addition to the previously reported histological abnormalities, was found to occur spontaneously among the rats studied. Indications of decreased function included elevations of plasma TSH and thyroid weight and depressions of plasma T4. We estimated the incidence of unequivocal thyroid disease as approximately 3% in each sex. 2) Basal plasma PRL concentrations of Buffalo rats averaged three to four times higher than those of outbred CD rats. Our findings strongly suggest that rats of the Buffalo strain will provide a good model for the study of thyroid failure of varying degrees and concomitant changes in the circulating levels of pituitary hormones.

Animals↗
PubMed1978

The irreversible inactivation of thyroid peroxidase by methylmercaptoimidazole, thiouracil, and propylthiouracil in vitro and its relationship to in vivo findings.

A reinvestigation of the mechanism of action of methylmercaptoimidazole, propylthiouracil, and thiouracil on thyroid peroxidase (TPO) was undertaken. A preliminary incubation of TPO and H2O2 with methylmercaptoimidazole, propylthiouracil, or thiouracil was carried out in the absence of oxidizable substrates (i.e. I- or guaiacol). This incubation resulted in irreversible inactivation of TPO. The extent of inactivation could be determined after removal of the drug by gel filtration or by dilution into the assay mixture. Preincubation, as above, in the presence of iodide or thiocyanate prevented the irreversible inactivation of TPO. Rats receiving doses of these drugs which completely inhibited protein-bound iodine formation showed normal levels of TPO in their thyroid glands 30 min after drug administration. These findings suggest that the initial in vivo action of these drugs is to block iodination by trapping oxidized iodide, not by acting as "general inhibitors" of the TPO.

Animals↗
PubMed1978

The developmental pattern of thyrotropin-releasing hormone-degrading activity in the plasma of rats.

The developmental pattern of TRH-degrading activity in rat plasma was determined by measuring the ability of plasma from rats of various ages to degrade TRH into degradation products. From a rate of 0.519 pmol TRH degraded/microliter-1.h-1 on day 8, plasma TRH-degrading activity increased to 18.1 pmol TRH by day 90 in female rats. The increase in rate of formation of proline, a major plasma degradation product, was in very good agreement with the increase in rate of TRH degradation. The major increase in TRH-degrading activity occurred between the third and seventh week of life. A similar pattern of development was observed in male rats; the only significant difference was that plasma from day 90 male rats was approximately 30% more active than that from female rats (P less than 0.002). Daily T3 administration to rats from days 8--26 resulted in a 2-fold increase in plasma TRH-degrading activity (P less than 0.05). The contribution of plasma degradation to the physiological control of TRH activity is not clear, but the magnitude of the increase in plasma TRH-degrading activity (approximately 30-fold) during the maturation of the rat is suggestive of a mechanism of biological significance.

Aging↗
PubMed1978

Large molecular weight TSH-beta: the sole immunoactive form of TSH-beta in certain human sera.

The beta subunit of TSH (TSH-beta) usually cannot be detected (less than 0.2 ng/ml) in the serum of normal individuals, whereas patients with primary hypothyroidism exhibit elevated TSH-beta levels (0.2-9.3 ng/ml), which increase further after the administration of TRH. Two patients were found to have large TSH-beta as the only form of serum TSH-beta immunoactivity. Patient A was a euthyroid woman with a goiter; TSH and alpha subunit levels were normal (1 microU/ml and 0.6 ng/ml, respectively); TSH-beta was elevated (8-24 ng/ml). Patient B was a woman with borderline hypothyroidism, an elevated serum TSH level (19 microunits/ml), a normal serum alpha level (2.4 ng/ml), and an elevated serum TSH-beta level (1.8-3.6 ng/ml). Dilutions of both patients' sera demonstrated nonparallelism of their serum TSH-beta to standard TSH-beta. The elevated serum TSH-beta levels did not increase after TRH, although TSH and alpha subunit increased appropriately. After the administration of dexamethasone or T4 to patient B, serum TSH-beta did not decrease, although TSH and alpha decreased. Gel chromatography and rechromatography of the patients' sera on a Sephadex G-100 column showed elution of all TSH-beta immunoactivity in or near the void volume (Vo; greater than 150,000 mol wt), whereas sera of hypothyroid patients demonstrated less than 7% of TSH-beta immunoactivity in the Vo. By chromatography on a Sephadex G-200 column, the TSH-beta immunoactivity had a 160,000 mol wt in patient A and 200,000 mol wt in patient B. Incubation of labeled or unlabeled TSH-beta with serum or gamma-globulin fractions from both patients resulted in no significant increase in the binding of TSH-beta to serum components, as determined by both gel chromatography and precipitation with antihuman gamma-globulin. Large TSH-beta was stable after incubation with 6 M guanidine. Ribonuclease failed to affect the large TSH-beta. Inter-chain disulfide bonding was not demonstrated in large TSH-beta after treatment with three different reducing agents (mercaptoethanol, sodium sulfite, and dithioerythritol). Treatment with trypsin did not convert the large TSH-beta immunoactivity to standard TSH-beta. These experiments demonstrated that the large TSH-beta immunoactivity was not caused by binding of TSH-beta to an immunoglobulin or other serum protein or by aggregation of TSH-beta molecules. The significance of these apparently covalently bonded large forms of TSH-beta immunoactivity is not yet known; the presence of small amounts of a large molecular weight form in the serum of hypothyroid patients and normal pituitary extracts raises the possibility that they may be components of normal TSH biosynthesis or represent posttranslational modifications.

Adult↗
PubMed1977

Interaction of thyroid peroxidase with concanavalin A covalently coupled to agarose.

We have investigated the interaction between concanavalin A-agarose (Con A-agarose) and thyroid peroxidase, an integral membrane protein found in the 105,000 X g, 1-h particulate fraction of thyroid tissue. An intact form of porcine thyroid peroxidase was obtained by solubilization with the nonionic detergent Triton X-100 and two fragmented, hydrophilic forms of the enzyme were prepared by trypsin treatment of the membrane. The three types of thyroid peroxidase bind to Con A-agarose and can be eluted with alpha-methyl-D-mannoside. The alpha-methyl-D-mannoside eluate of the most purified thyroid peroxidase preparation has been analyzed by polyacrylamide gel electrophoresis. Peroxidase activity corresponds with a glycoprotein band. The binding of thyroid peroxidase to Con A-agarose can be inhibited by sugars in the following order: alpha-methyl-D-mannoside greater than D-mannose greater than alpha-methyl-D-glucoside greater than D-glucose greater than D-galactose. This order of specificity is typical of Con A-sugar interactions. Furthermore, inactivation of the carbohydrate binding site of Con A by demetallization greatly reduces the extent of thyroid peroxidase binding. Reactivation of the carbohydrate binding site by the addition of Ca2+ and Mn2+ to demetallized Con A-agarose restores thyroid peroxidase binding. These and other experiments suggest that htyroid peroxidase is, like several other peroxidases, a glycoprotein. In addition, the interaction between thyroid peroxidase and Con A-agarose may provide a new purification tool for thyroid peroxidase.

Animals↗
PubMed1977

Noninvasive evaluation of cardiac function in hypothyroidism. Response to gradual thyroxine replacement.

Left ventricular performance was studied in 15 patients with severe, primary hypothyroidism (mean serum total thyroxine of 0.8 mug per 100 ml and serum thyrotropin of 160 muU per milliliter). Pretreatment systolic-time intervals were characterized by prolongation of the pre-ejection period (delta PEP = +30) and reduction of the left ventricular ejection period (delta LVET = -23) with a resultant increase in the PEP/LVET ratio (0.47). Nine of 14 patients demonstrated pericardial effusions. These abnormalities were reversed with physiologic thyroxine replacement. Further reductions of the delta PEP and PEP/LVET ratio occurred with supraphysiologic doses (200 to 300 mug per day). During therapy, delta PEP was inversely correlated with serum thyroxine (P less than 0.001) and directly correlated with serum thyrotropin (P less than 0.001). Thus physiologic thyroid hormone replacement, appropriately adjusted to need, appears necessary in hypothyroidism for optimal left ventricular function.

Adult↗
PubMed1977

Metabolic clearance and secretion rates of subunits of human thyrotropin.

Metabolic clearance rates (MCR) of the alpha and beta subunits of human thyrotropin (hTSH-alpha and hTSH-beta) were determined by a constant infusion to equilibrium method. In 15 normal individuals (six men, six premenopausal women, and three post-menopausal women), the mean MCR of hTSH-alpha (68 ml/min per m2) was significantly faster than that of hTSH-beta (48 ml/min per m2) was significantly faster than that of hTSH-beta (48 ml/min per m2); both were two to three times more rapid than the previously determined MCR of hTSH. In patients with primary hypothyroidism, MCR were significantly slower with a mean value of 55 ml/min per m2 for hTSH-alpha and 37 ml/min per m2 for hTSH-beta. However, MCR of subunits were not significantly faster than normal in hyperthyroid patients. Serum concentrations of alpha subunits and hTSH-beta were measured by radioimmunoassay, and secretion rates of alpha and hTSH-beta from the pituitary were calculated using hTSH-alpha and hTSH-beta MCR, respectively. In the normal individuals, alpha secretion rates averaged 91 mug/day per m2, greater than those previously determined for hTSH and human follicle-stimulating hormone. Alpha secretion rates were significantly elevated in the normal postmenopausal women (211 mug/day per m2) and in the premenopausal hypothyroid women (202 mug/day per m2); they were also elevated in the postmenopausal hypothyroid women (277 mug/day per m2). Alpha secretion rates were significantly decreased in the premenopausal hyperthyroid women (66 mug/day per m2). Usually, the secretion rates of hTSH-beta could not be calculated in normal individuals, and the rates in hyperthyroid patients could never be calculated because serum hTSH-beta was not detected. Six normals had detectable hTSH-beta secretion rates (17 mug/day per m2); hTSH-beta secretion rates were significantly increased in patients with primary hypothyroidism (28 mug/day per m2). Although we had previously demonstrated a 50-fold increase in hTSH secretion rates in primary hypothyroidism, there was only a 2-fold increase in alpha and hTSH-beta secretion rates. Thus, increased subunit synthesis appears to be utilized predominantly for production of complete hTSH.

Adolescent↗
PubMed1977

Thyroid function tests during the early phase of subacute thyroiditis.

Six patients with subacute thyroditis were followed with serial measurements of T4, FT4, TSH and RAI uptake. Five of the six underwent TRH stimulation early in the course of their illness. All six patients had elevated or high normal values for T4 and FT4 at the time of their clinical presentation (mean = 13.8 microgram per 100 ml and 3.9 ng per 100 ml, respectively). RAI uptakes were 1% or less in all six. TRH testing revealed a suppressed TSH response (mean deltaTSH less than0.1 muU/ml) in all five patients tested, suggesting hyperthyroidism. After initial studies were performed, five patients were treated with L-triiodothyronine (L-T3) and one with aspirin. All patients improved over a two to four week period of time, no relapses being noted.

Adult↗
PubMed1976

Thyrotropin releasing hormone: development of inactivation system during maturation of the rat.

Whereas thyrotropin releasing hormone is rapidly and extensively degraded by plasma of adult rats, no appreciable loss of biological or immunological activity is caused by plasma from rats 4 or 16 days old. The plasma of neonatal rats does not appear to contain an inhibitor of thyrotropin releasing hormone peptidase or a peptidase with altered substrate affinity. The development of an active peptidase in rat plasma suggests a physiological role for inactivation of thyrotropin releasing hormone.

Age Factors↗
PubMed1976

Solubilization of thyroid peroxidase by nonionic detergents.

We have examined the ability of nonionic detergents to solubilize thyroid peroxidase from a porcine thyroid particulate fraction, as measured by the release of peroxidase activity into the supernatant fraction after centrifugation at 105,000 X g for 1 hour and the retardation of the supernatant peroxidase of Sepharose 6B. The parameters of peroxidase solubilization by Triton X-100 have been investigated in detail. Under optimum conditions, 60 to 95% of the thryoid peroxidase and about 50% of the total protein is released into the 105,000 X g, 1-hour supernatant. Under the optimum conditions established with Triton X-100, a series of Brij detergents of different chemical structure were equally effective in releasing peroxidase and protein. The protein patterns of the supernatants obtained with these detergents were similar on sodium dodecyl sulfate-polyacrylamide electrophoresis gels, suggesting that the detergents studied release similar membrane proteins. The Triton X-100 and Brij 58 supernatants were chromatographed separately on Sepharose 6B equilibrated with 0.1% Triton X-100 or Brij 58, respectively. In both cases, 75 to 80% of the peroxidase activity was retarded, thereby indicating that the nonionic detergents effect solubilization of the peroxidase rather than dispersal of nonsedimentable membrane fragments. These studies report the first successful solubilization of thyroid peroxidase by nonionic detergents. Together with previous evidence from our laboratory, these experiments indicate that thyroid peroxidase is an integral membrane protein.

Animals↗
PubMed1976

Pituitary-thyroid axis in neonatal and adult rats: comparison of the sexes.

Systematic comparisons have been made of the development of the pituitary-thyroid axes of male and female rats, by measuring plasma thyrotropin (TSH) and thyroxine (T4) concentrations in neonates and adults. Observations were made in untreated groups as well as in rats treated with various regimens of exogenous T4, thyrotropin-releasing hormone, or TSH. All hormone determinations were by radioimmunoassay (RIA). Salient findings include the following: 1) In early neonatal life, untreated rats showed no significant sex difference in the plasma concentrations of either TSH or T4. 2) In adulthood, the plasma TSH of untreated males attained levels strikingly higher than those of neonates-the differences averaged 5-fold more. For females, the increase in plasma TSH during development was less marked, averaging slightly less than 2-fold more. Thus, untreated adults exhibited a clear sex difference in circulating TSH concentrations; the male TSH levels averaged 2.8-fold higher than those of females. 3) Plasma T4 concentrations also increased markedly during development. For both sexes, adult T4 levels were approximately 3-fold greater than the T4 levels in early neonatal life. Among untreated adults, the female T4 concentrations averaged 28% greater than those of males. 4) Plasma TSH and T4 concentrations exhibited only minor fluctuations, of borderline statistical significance, during the female estrous cycle. 5) A significant reduction in responsiveness to exogenous TRH was observed in adult male rats which had been treated with high doses of T4 in neonatal life, although the effect was not completely consistent. No significant reduction was observed in females which received the same treatment. We have concluded that major changes occur in the circulating hormone levels of the pituitary-thyroid axis of the rat between birth and adulthood, and that such changes are not identical for the two sexes.

Age Factors↗