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Biomedical subjects

K A Woeber

Publications and source records attributed to K A Woeber.

At least 19 recordsLinked to original sources
PubMed1992

Thyrotoxicosis and the heart.

Many patients with thyrotoxicosis have clinical features that reflect the effects of excess thyroid hormone on the cardiovascular system. Thyrotoxicosis can aggravate preexisting cardiac disease and can also lead to atrial fibrillation, congestive heart failure, or worsening of angina pectoris. In elderly patients, these cardiac manifestations may dominate the clinical picture and warrant the measurement of the serum thyrotropin concentration. In the absence of preexisting cardiac disease, treatment of thyrotoxicosis usually results in a return of normal cardiac function.

Heart↗
PubMed1991

Iodine and thyroid disease.

Iodine is a requisite substrate for the synthesis of the thyroid hormones, the minimum daily requirement being about 50 micrograms. An autoregulatory mechanism within the thyroid serves as the first line of defense against fluctuations in the supply of iodine and also permits escape from the inhibition of hormone synthesis that a very large quantity of iodine induces (Wolff-Chaikoff effect and escape therefrom). Environmental iodine deficiency continues to be a significant public health problem worldwide, compounded in some geographic regions by the presence of other goitrogens in some staple foods. The pathologic consequences of severe iodine deficiency include endemic goiter, endemic cretinism, increased fetal and infant mortality, and an increased prevalence in the community of cognitive and neuromotor disabilities. The implementation of an iodization program prevents endemic cretinism and reduces the frequency of the other pathologic consequences of iodine deficiency. Iodine excess results principally from the use of iodine-containing medicinal preparations or radiographic contrast media. The pathologic consequences of iodine excess will ensue only when thyroid autoregulation is defective, in that escape from the Wolff-Chaikoff effect cannot occur, or when autoregulation is absent. Defective autoregulation characterizes the fetal and neonatal thyroid, Hashimoto's thyroiditis, radioiodine or surgically treated Graves' hyperthyroidism, the thyroid of patients with cystic fibrosis, and the thyroid that has been exposed to weak inhibitors of the organic binding of iodine. In these circumstances, the provision of excess iodine may lead to iodide goiter with or without hypothyroidism. Absent autoregulation may be a feature of longstanding multinodular goiter, and the provision of excess iodine in this circumstance may induce thyrotoxicosis (Jod-Basedow disease). The pathologic consequences of iodine excess will resolve when the source of iodine has been dissipated. In addition to its role in reversing iodine deficiency, iodine is used as adjunctive therapy for hyperthyroidism. By inhibiting the proteolytic release of iodothyronines from thyroglobulin, it induces a prompt slowing of thyroid hormone secretion. This effect is exploited in the treatment of thyrotoxic crisis or severe thyrocardiac disease. Iodine also reduces thyroid cellularity and vascularity and therefore is used in the preparation of the patient for thyroidectomy. Finally, by exploiting the failure of escape from the Wolff-Chaikoff effect, iodine may also be used in the early management of radioiodine-treated Graves' hyperthyroidism.

Humans↗
PubMed1980

Sulfhydryl group modulation and triiodothyronine generation in the human polymorphonuclear leukocyte.

The induction of phagocytosis in the human polymorphonuclear leukocyte and the attendant decrease in endogenous sulfhydryl group content were accompanied by a depression of the generation by the 27,000 x g particulate fraction of L-T3 and L-rT3 from substrate L-T4. A direct correlation between endogenous sulfhydryl group content and L-T3-generating activity was found to exist. The inhibitory influence of phagocytosis was prevented when phagocytosis was induced in the presence of a sulfhydryl group protector.

Dithiothreitol↗
PubMed1978

L-triiodothyronine and L-reverse-triiodothyronine generation in the human polymorphonuclear leukocyte.

Extrathyroidal monodeiodination of l-thyroxine (T(4)) is the principal source of l-triiodothyronine (T(3)) and l-reverse-triiodothyronine (rT(3)) production. To define some of the cellular factors involved, we examined T(3) and rT(3) generation from added nonradioactive T(4) in human polymorphonuclear leukocytes, using radioimmunoassays to quantify the T(3) and rT(3) generated. Under optimum incubation conditions which included a pH of 6.5 in sucrose-acetate buffer, the presence of dithiothreitol as a sulfhydryl-group protector, and incubation in an hypoxic atmosphere, significant net generation of T(3) and rT(3) was observed. Of the several subcellular fractions studied, the particulate fraction obtained by centrifugation at 27,000 g was found to possess the highest T(3)- and rT(3)-generating activities per unit quantity of protein. With respect to T(3) generation from substrate T(4), the K(m) was 5 muM and the V(max) was 7.2 pmol/min per mg protein. Propylthiouracil, methimazole, and prior induction of phagocytosis inhibited both T(3) and rT(3) generation, but T(3) generation was inhibited to a greater extent. rT(3), in a concentration equimolar to that of substrate T(4), did not alter T(3) generation, but inhibited T(3) generation when the molar ratio of rT(3) to T(4) approached 10:1. Under the incubation conditions employed, particulate fractions of leukocytes obtained from five cord blood samples displayed an essentially normal relationship between T(3)- and rT(3)-generating activities, despite the distinctly divergent serum T(3) and rT(3) concentrations in these samples. From our findings, we draw the following conclusions: (a) the human polymorphonuclear leukocyte possesses the ability to generate T(3) and rT(3) from substrate T(4); (b) the T(3)- and rT(3)-generating activities are associated principally with the 27,000 g particulate fraction and display enzymic characteristics with a sulfhydryl-group requirement; (c) T(3)-generating activity appears to be more susceptible to inhibitory influences than rT(3)-generating activity; and (d) in cord blood leukocytes, the putative enzymes catalyzing T(3) and rT(3) generation appear to be functionally intact under the experimental conditions employed.

Adult↗
PubMed1977

Observations concerning the binding of L-triiodothyronine in the human polymorphonuclear leukocyte.

To examine the subcellular locus of L-triiodothyronine (T3) binding in the human polymorphonuclear leukocyte, intact leukocytes (greater than 90% polymorphonuclear) were incubated with small tracer concentrations of [125I]T3 with or without an excess of non-radioactive T3. Measurement of the [125I]T3 content of several subcellular fractions revealed that the non-radioactive T3 had led to significant displacement of [125I]T3 from the nuclear fraction alone. After correction for degradation and non-specific binding of the added T3 in intact leukocytes from hypothyroid patients in which the endogenous T3 concentration would be minimal, the T3-nuclear binding interaction was found to have an equilibrium dissociation constant of 1.1 X 10(-10)M and a binding capacity of 4.3 fmol/1 X 10(7) cells. Pre-incubation of intact cells with non-radioactive T3 did not increase the subsequent specific binding of [125I]T3 by the nuclei isolated therefrom. The data indicate that: 1) the human polymorphonuclear leukocyte possesses saturable nuclear binding sites for T3, and 2) the sites appear to bind T3 without the intermediation of a cytosol receptor.

Cell Nucleus↗
PubMed1976

A granule-associated L-thyroxine deiodinating system in the human leukocyte.

Recent work has shown that leukocytes deiodinate L-thyroxine (T4) and that deiodination is enhanced when phagocytosis is induced. To define the subcellular locus and characteristics of this phenomenon, the deiodinative activities of different cell fractions obtained from human leukocytes (greater than 90% polymorphonuclear) were studied. Of the several fractions obtained, the granule fraction was found to possess the bulk of T4-deiodinative activity; as little as 9 mug/ml of granule protein effected significant deiodination of added labeled T4. Prior exposure of intact leukocytes to opsonized zymosan particles to induce phagocytosis resulted in an increase in the T4-deiodinative activity of the subsequently isolated granule fraction alone, strengthening the validity of the finding that T4-deiodinative activity in the human leukocyte resides in the granule fraction. The characteristics of the granule-associated deiodinating system suggest that it is enzymic in nature with a Km of the order of 10(-6)M.

Cytoplasmic Granules↗
PubMed1976

Influence of superoxide dismutase and catalase on the stimulation by phagocytosis of L-thyroxine and L-triiodothyronine deiodination in the human leukocyte.

Neither superoxide dismutase, which destroys the superoxide radical by catalyzing its conversion to hydrogen peroxide, nor catalase prevented the stimulation by phagocytosis of the deiodination of L-thyroxine or L-triiodothyronine in human leukocytes. On the other hand, superoxide dismutase led to an increase in the proportion of iodinated material, which remained at the origin during chromatography in a butanol-acetic acid-water solvent system, whereas catalase had the opposite effect. The data suggest that neither the superoxide radical nor hydrogen peroxide plays a major role in the stimulation of deiodination of hormone, but that once deiodination has occurred, hydrogen peroxide is more important than that superoxide radical in subsequent iodination reactions within the leukocyte.

Catalase↗
PubMed1973

Accelerated cellular uptake and metabolism of L-thyroxine during acute Salmonella typhimurium sepsis.

The effects of acute Salmonella typhimurium sepsis on the kinetics of peripheral L-thyroxine (T(4)) distribution and metabolism and on serum total and free T(4) concentrations were studied in rhesus monkeys inoculated i.v. with either heat-killed or viable organisms. The rate of disappearance of labeled T(4) from serum was increased within 8 h after inoculation of monkeys with either heat-killed or viable Salmonella. The effects of the heat-killed organisms were transient and no longer evident by 16 h postinoculation. The monkeys inoculated with the viable Salmonella experienced a 2-3 day febrile, septic illness that was accompanied by an increase in the absolute rate of T(4) disposal. In the infected monkeys, serum total T(4) and endogenously labeled protein-bound iodine concentrations fell significantly during the period of acute sepsis and then rose during convalescence to values that exceeded the preinoculation values, suggesting that thyroidal secretion of hormone had increased in response to a primary depletion of the peripheral hormonal pool. Total cellular and hepatic uptakes of T(4) were enhanced by 4 h after inoculation of monkeys with either heat-killed or viable Salmonella, but the increase in total cellular uptake persisted for 24 h only in the monkeys inoculated with the viable organisms. These alterations in T(4) kinetics could neither be correlated with changes in the binding of T(4) in plasma nor attributed to an increase in vascular permeability. Moreover, they could not be ascribed to an in vitro product of bacterial growth, suggesting that the presence of the organisms themselves was required. An acceleration of T(4) disappearance was also observed during Escherichia coli and Diplococcus pucumoniae bacteremias. Our findings are consistent with a primary increase in the cellular uptake and metabolism of T(4) during bacterial sepsis, possibly related to phagocytic cell function in the host.

Animals↗
PubMed1973

Metabolism of L-thyroxine by phagocytosing human leukocytes.

Intact normal human leukocytes deiodinated L-thyroxine (T(4)) with the generation of inorganic iodide, chromatographically immobile origin material, and small quantities of L-triiodothyronine (T(3)). When phagocytosis was induced in the leukocytes through the addition of zymosan particles that had been opsonized by coating with plasma, T(4)-deiodination was greatly stimulated. In addition to the stimulation of T(4)-deiodination, the accumulation by the leukocytes of undegraded T(4) was increased. Anoxia, which has previously been shown not to interfere with phagocytosis, did not prevent the increased cellular accumulation of T(4) that phagocytosis induced, but virtually abolished T(4)-deiodination. On the other hand, calcium, which has previously been shown to be required for optimal phagocytosis, was required for the increase in both the cellular accumulation and deiodination of T(4) that phagocytosis induced. Phospholipase-C, which has previously been shown to induce a metabolic burst that mimics that induced by phagocytosis, did not increase the cellular accumulation or deiodination of T(4). On the other hand, colchicine, which has previously been shown to depress the metabolic burst that accompanies phagocytosis, did not prevent the increase in either the cellular accumulation or deiodination of T(4) that phagocytosis induced. Thus, increased accumulation of T(4) by the leukocytes during phagocytosis appears to be the primary factor responsible for the stimulation of deiodination that phagocytosis induces. The increased accumulation of T(4) did not appear to be owing to engulfment of suspending medium surrounding the particles or to binding of T(4) to the particles themselves. In addition to the enhanced cellular accumulation, other factors related to the metabolic burst that accompanies phagocytosis might also be involved in the stimulation of T(4)-deiodination. In leukocytes from two patients with chronic granulomatous disease, a disorder in which phagocytosis appears to occur normally but in which the metabolic burst and attendant increase in hydrogen peroxide generation do not occur, stimulation of T(4)-deiodination was either greatly diminished or totally lacking. In myeloperoxidase-deficient leukocytes, on the other hand, stimulation of T(4)-deiodination was at least as great as that in normal cells. Thus, we conclude that the primary factor responsible for the increased deiodination of T(4) that phagocytosis induces is the enhanced cellular uptake of hormone. The increased generation of hydrogen peroxide that accompanies phagocytosis may be necessary for the enhanced deiodination of the accumulated T(4), but the latter reaction does not require the mediation of myeloperoxidase.

Calcium↗
PubMed1973

Progressive systemic sclerosis. "Something old, something new, something borrowed, something blue".

These discussions are selected from the weekly staff conferences in the Department of Medicine, University of California, San Francisco. Taken from transcriptions, they are prepared by Drs. David W. Martin, Jr., Assistant Professor of Medicine, and Kenneth A. Woeber, Associate Professor of Medicine, under the direction of Dr. Lloyd H. Smith, Jr., Professor of Medicine and Chairman of the Department of Medicine. Requests for reprints should be sent to the Department of Medicine, University of California, San Francisco, CA 94143.

Age Factors↗
PubMed1973

Renal cystic disease.

These discussions are selected from the weekly staff conferences in the Department of Medicine, University of California, San Francisco. Taken from transcriptions, they are prepared by Drs. David W. Martin, Jr., Assistant Professor of Medicine, and Kenneth A. Woeber, Associate Professor of Medicine, under the direction of Dr. Lloyd H. Smith, Jr., Professor of Medicine and Chairman of the Department of Medicine. Requests for reprints should be sent to the Department of Medicine, University of California, San Francisco, CA 94143.

Adult↗
PubMed1972

Stimulation by phagocytosis of the deiodination of L-thyroxine in human leukocytes.

Intact human leukocytes actively deiodinate L-[(131)1] thyroxine, producing mainly inorganic (131)1 and chromatographically immobile (131)1-labeled origin material. When phagocytosis is induced, the deiodination is enhanced, a suggestion that deiodination in mediated by a peroxidase-hydrogen peroxide system. l-Thyroxine can serve as a source of iodine for iodination reactions within the leukocyte.

Autoradiography↗
PubMed1972

Evidence for enhanced cellular uptake and binding of thyroxine in vivo during acute infection with Diplococcus pneumoniae.

Previous work has demonstrated that acute pneumococcal infections in man and in the rhesus monkey are accompanied by accelerated metabolic disposal of L-thyroxine (T(4)). In order to study the influence of acute pneumococcal infection on the kinetics of hormone distribution, the early cellular uptake of T(4) (CT(4)), reflecting the net effect of plasma and cellular binding factors, was assessed in rhesus monkeys from the differences in instantaneous distribution volumes of T(4)-(131)I and albumin-(125)I during the first 60 min after their simultaneous injection. Hepatic and renal uptakes of (131)I were also determined. Plasma binding of T(4) was assessed by measuring the per cent of free T(4) (% FT(4)) in serum. Six monkeys were studied 12 hr (INF-12) and seven 24 hr (INF-24) after intravenous inoculation with Diplococcus pneumoniae; seven controls were inoculated with a heat-killed culture. CT(4) at 60 min as per cent administered dose was 31.5 +/-2.0 (mean +/-SE) in INF-12 and 33.0+/-0.8 in INF-24, values significantly greater than control (22.4+/-1.3). By contrast, mean% FT(4) was identical in control and INF-12 (0.028 +/-0.002 and 0.028 +/-0.001) and variably increased in INF-24 (0.034 +/-0.003). Thus, in the infected monkeys CT(4) and% FT(4) were not significantly correlated. The increased CT(4) in the infected monkeys could not be ascribed to an increase in vascular permeability and did not correlate with the magnitude of fever. Although the increased CT(4) could not be accounted for by increased hepatic or renal uptake of hormone, hepatic and renal T(4) spaces were increased, results consistent with increased binding by these tissues. Our data indicate that the cellular uptake of T(4) is increased early in acute pneumococcal infection and suggest that this results from a primary enhancement of cell-associated binding factors for T(4).

Animals↗