Triiodothyronine generation from thyroxine in human thyroid: enhanced conversion in Graves' thyroid tissue

Conversion of T4 to T3 was studied in normal, Graves', and neoplastic thyroid tissues obtained at surgery. Homogenates of human thyroid follicular adenoma and carcinomas were incubated with [125I]T4 and dithiothreitol (DTT) at 37 C for 60 min under N2 gas. T3 formation was assessed by measuring [125I]T3 formed, using paper chromatography. In the second series of experiments, the suspensions of the 100,000 X g pellet of normal thyroid tissues adjacent to the tumor and Graves' thyroid tissues were incubated with unlabeled T4 and DTT at 37 C for 60 min under N2 gas. T3 generated was measured by RIA. T3 generation in the thyroid tissue was dependent on incubation time, amount of the tissue used, concentration of DTT, temperature, and pH. Propylthioracil inhibited T3 formation, while methimazole had no effect. A kinetic study with the homogenate of a thyroid adenoma and 100,000 X g pellet suspensions of two normal and three Graves' thyroids gave apparent Km values of 2.7, 4.9, and 4.1 microM for T4, respectively, and Vmax values of 0.8, 3.0, and 10.9 pmol T3/mg protein.min, respectively. Conversion of T4 to T3 was observed in two of three tumor tissues studied and was markedly enhanced in Graves' thyroid tissues (mean +/- SE, 11.9 +/- 2.0 pmol/mg protein.min) compared to that of normal thyroid tissues (3.2 +/- 0.6 pmol/mg protein.min; P less than 0.01). It is concluded that T4 is enzymatically converted to T3 in normal and Graves' thyroids and differentiated thyroid neoplasms. Moreover, enhanced conversion of T4 to T3 was found in Graves' thyroid tissue.     

Islet cell-activating protein reverses anti-fucosyl GM1 ganglioside antibody-induced inhibition of adenosine 3',5'-monophosphate production in FRTL-5 rat thyroid cells

Our previous study revealed that a specific antibody against fucosyl GM1 ganglioside (fGM1) inhibits basal and ligand-stimulated cAMP production in FRTL-5 rat thyroid cells. To further elucidate the mechanism of this inhibitory action of the antibody, the involvement of guanine nucleotide-binding proteins was studied using islet cell-activating protein (IAP) and cholera toxin. When FRTL-5 cells were pretreated with IAP and incubated with the antibody, the inhibitory activity of the antibody on cAMP production was completely abolished. Furthermore, the inhibitory activity of the antibody on TSH- or forskolin-stimulated cAMP production was also abolished by IAP preincubation. The inhibitory activity of the antibody by pretreatment of the cells was also reversed by the addition of IAP. Coincubation of FRTL-5 cells with the antibody and cholera toxin reduced the cAMP inhibitory action of the antibody. Similar results were obtained with anti-fGM1 pretreatment before cholera toxin stimulation. These results provide evidence that anti-fGM1 antibody acts via guanine nucleotide-binding proteins in inhibiting cAMP production in FRTL-5 cells.     

Effect of 1,25-dihydroxyvitamin D3 on insulin secretion: direct or mediated?

In order to clarify the role of vitamin D (D) in regulating insulin secretion, we studied the effect of long term (10 days) and short term (3 days) supplementation with D and/or calcium (Ca) on insulin secretion from the isolated, perfused pancreas of D- and Ca-deficient rats. The influence of the nutritional state induced by D deficiency was also evaluated. The long term supplementation of either D, Ca, or both restored the body weight and improved insulin secretion induced by high glucose concentration to the same extent; thus, no significant difference in insulin secretion was found between the D-only-supplemented group and the Ca-only-supplemented group. When the insulin secretion was compared in D-deplete vs. D-replete rats given the same amount of Ca, insulin secretion was significantly higher in D-replete animals, although plasma Ca levels were also higher. In short term experiments, insulin release was significantly augmented to a similar extent in D- or Ca-replete rats as compared with D- and Ca-deficient rats, despite no significant change in body weight. In a separate experiment, the pancreas from D-deficient rats was perfused with or without 1,25-dihydroxyvitamin D3 [1,25-OH)2D3] to observe its acute effect on insulin release. The perfusion with 1,25-(OH)2D3 did not affect insulin release. This result suggests that impaired insulin secretion in D-deficient rats is caused by a decrease in Ca in the body fluid and possibly by the lack of D effect on the pancreas.     

Quantitative evaluation of the diagnostic thinking process in medical students

OBJECTIVE: To explore the diagnostic thinking process of medical students. SUBJECTS AND METHODS: Two hundred twenty-four medical students were presented with 3 clinical scenarios corresponding to high, low, and intermediate pre-test probability of coronary artery disease. Estimates of test characteristics of the exercise stress test, and pre-test and post-test probability for each scenario were elicited from the students (intuitive estimates) and from the literature (reference estimates). Post-test probabilities were calculated using Bayes' theorem based upon the intuitive estimates (Bayesian estimates of post-test probability) and upon the reference estimates (reference estimates of post-test probability). The differences between the reference estimates and the intuitive estimates, and between Bayesian estimates and the intuitive estimates were used for assessing knowledge of test characteristics, and ability of estimating pre-test and post-test probability of disease. RESULTS: Medical students could not rule out disease in low or intermediate pre-test probability settings, mainly because of poor pre-test estimates of disease probability. They were also easily confused by test results that differed from their anticipated results, probably because of their inaptitude in applying Bayes' theorem to real clinical situations. These diagnostic thinking patterns account for medical students or novice physicians repeating unnecessary examinations. CONCLUSIONS: Medical students' diagnostic ability may be enhanced by the following educational strategies: 1) emphasizing the importance of ruling out disease in clinical practice, 2) training in the estimation of pre-test disease probability based upon history and physical examination, and 3) incorporation of the Bayesian probabilistic thinking and its application to real clinical situations.     

Atrial natriuretic polypeptide is removed by the lungs and released into the left atrium as well as the right atrium in humans

To examine the sites of release and removal of plasma atrial natriuretic polypeptide plasma levels in the femoral vein, right atrium, pulmonary artery, pulmonary capillary bed, left atrium and aortic root were measured in 11 control subjects and 22 patients with mitral stenosis. Mean plasma natriuretic polypeptide levels in the femoral vein, right atrium, pulmonary artery, pulmonary capillary bed, left atrium and aortic root were, respectively, 64 +/- 29, 124 +/- 72, 103 +/- 44, 83 +/- 30, 106 +/- 46 and 101 +/- 35 pg/ml in the control subjects and 321 +/- 170, 500 +/- 234, 458 +/- 266, 356 +/- 209, 434 +/- 222 and 432 +/- 217 pg/ml in the patients with mitral stenosis. In both the control subjects and the patients with mitral stenosis, there was a significant increase between the femoral vein and the right atrium and between the pulmonary capillary bed and the left atrium and a significant decrease between the pulmonary artery and the pulmonary capillary bed. Blood samples were also taken simultaneously from the pulmonary vein and the pulmonary capillary bed, as well as from the pulmonary artery and the left atrium, in 25 patients (11 control subjects, 5 patients with mitral stenosis and 9 patients with atrial septal defect). There was no difference in plasma atrial natriuretic polypeptide levels between the pulmonary capillary bed and the pulmonary vein in these 25 patients. It is concluded that atrial natriuretic polypeptide 1) is released into the left as well as the right atrium, and 2) is removed by the lungs.     

Prediction of motor outcomes and activities of daily living function using diffusion tensor tractography in acute hemiparetic stroke patients

[Purpose] The efficacy of diffusion tensor imaging in the prediction of motor outcomes and activities of daily living function remains unclear. We evaluated the most appropriate diffusion tensor parameters and methodology to determine whether the region of interest- or tractography-based method was more useful for predicting motor outcomes and activities of daily living function in stroke patients. [Subjects and Methods] Diffusion tensor imaging data within 10 days after stroke onset were collected and analyzed for 25 patients. The corticospinal tract was analyzed. Fractional anisotropy, number of fibers, and apparent diffusion coefficient were used as diffusion tensor parameters. Motor outcomes and activities of daily living function were evaluated on the same day as diffusion tensor imaging and at 1 month post-onset. [Results] The fractional anisotropy value of the affected corticospinal tract significantly correlated with the motor outcome and activities of daily living function within 10 days post-onset and at 1 month post-onset. Tthere were no significant correlations between other diffusion tensor parameters and motor outcomes or activities of daily living function. [Conclusion] The fractional anisotropy value of the affected corticospinal tract obtained using the tractography-based method was useful for predicting motor outcomes and activities of daily living function in stroke patients.Key words: Stroke, Diffusion tensor tractography, Activities of daily living function     

Thrombocytosis in patients with tumors producing colony-stimulating factor.

We investigated the cause of thrombocytosis in 14 patients with tumors producing colony-stimulating factor (CSF). Of the 14 patients, 10 had tumors producing granulocyte-CSF (G-CSF) and 4 had tumors producing granulocyte-macrophage--CSF (GM-CSF). Thrombocytosis of greater than 400 x 10(9)/L was noted in 8 of 10 patients with G-CSF-producing tumors and all 4 patients with GM-CSF-producing tumors. Median peak platelet counts were, respectively, 511 x 10(9)/L (range, 384 to 694 x 10(9)/L) and 579 x 10(9)/L (range, 526 to 910 x 10(9)/L) in patients with tumors producing G-CSF and GM-CSF. In most patients, thrombocytosis declined towards the terminal stage. High interleukin-1 (IL-1) and IL-6 levels were found in addition to CSFs in the plasma or culture supernatants of tumor cells obtained from most patients. In patients with GM-CSF-producing tumors, these specimens had megakaryocyte-CSF (Meg-CSF) activity, which was abolished by anti-GM-CSF antibody. These specimens also had megakaryocyte potentiating (Meg-Pot) activity attributable to both GM-CSF and IL-6. In patients with G-CSF-producing tumors, only Meg-Pot activity due to IL-6 was detected. These results indicate that the thrombocytosis in GM-CSF-producing tumors was caused by both the Meg-CSF activity of GM-CSF and the Meg-Pot activity of IL-6 plus GM-CSF, while that in G-CSF-producing tumors was due to the Meg-Pot activity of IL-6.     

Distributions of calcitonin gene-related peptide and substance P in the human maxillary sinus of Japanese cadavers

BackgroundSubstance P (SP) and calcitonin gene-related peptide (CGRP) are released by the nociceptive sensory nerve and are involved in blood flow, pain and inflammation in the nasal mucosa. The purpose of this study was to assess the distribution of the SP and CGRP nerve fibres related to blood supply within human Schneiderian membrane of the maxillary sinus (MS).Material and methodsIn this study, the MS from Japanese cadavers was examined by whole-mount immunohistochemistry. Human male cadavers (ranging in age from 80 to 90 years) were used in this study.ResultsSP- and CGRP-positive fibres were found around large vessels of the medialis superior alveolar branches and also within the floor region of the MS. The floor region of the MS was composed of complex branches of these fibres.ConclusionOur results give useful information for surgical sinus floor elevation in this region of the MS. These anatomical features may assist in the execution of a successful surgical procedure.