Search PubMed⌕ Search

Biomedical subjects

J Unger

Publications and source records attributed to J Unger.

At least 91 records · Page 5Linked to original sources

Modulation of thyroglobulin release by dog thyroid slices.

Nonbutanol-extractable 131I (NBE131I) release by dog thyroid slices in vitro has been shown previously to be primarily thyroglobulin (Tg); it is stimulated by TSH. NBE131I (Tg) release has therefore been considered as an in vitro model of thyroglobulin secretion and was further characterized in this work. TSH-stimulated NBE131I (Tg) release, like TSH-stimulated BE131I (T4, T3 and iodide) release was reproduced by forskolin, an activator of adenylate cyclase. TSH-, (Bu)2cAMP- and forskolin-stimulated NBE131I (Tg) release was inhibited by 10(-5) M carbamylcholine, an effect relieved by 10(-5) M atropine, but not by 10(-4) M 1-methyl-3-isobutylxanthine. NBE131I (Tg) release was observed in the presence of 2 mM methimazole and 2 mM perchlorate. Cooling the slices to 20 degrees C or addition of 10(-5) M monensin completely blocked the formation of apical pseudopods and BE131I release but not NBE131I (Tg) release. Inhibition by 500 microM chloroquine of intralysosomal Tg hydrolysis and BE131I release did not enhance NBE131I (Tg) release. Cytochalasin B induced a concentration-dependent increase in basal and TSH-stimulated NBE131I (Tg) release at concentrations which depressed TSH-stimulated BE131I release. Removal of Ca2+ from the medium and slices by 10(-3) M or 10(-4) M EGTA increased NBE131I (Tg) release. In conclusion, in dog thyroid slices, TSH-stimulated NBE131I (Tg) release was mediated by cAMP and inhibited by 10(-5) M carbamylcholine at a step beyond cAMP. It was not neosynthesized Tg. It did not seem to require the formation of apical pseudopods or to result from the escape from lysosomes of undegraded thyroglobulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Morphometrical studies of erythrophagocytosis in the spleen.

The elimination of altered RBC was investigated morphometrically in the rat spleen by determination of the percentage of erythrophagosomes in macrophages. PHZ and diamide treated RBC led to a time dependent increase of the percentage of erythrophagosomes in comparison to normal spleens. The deformability of the target RBC was lowered as revealed by measurements with glass micropipettes. RBC-microvesicles and diamide treated RBC are primarily loaded with IgG and undergo a rapid elimination. PHZ-RBC and cells with a prolonged stay in the spleen are sequestrated by secondary mechanisms. Details of primary and secondary elimination are discussed.

Animals↗

Is motilin a cerebellar peptide in the rat? A radioimmunological, chromatographic and immunohistochemical study.

Motilin was demonstrated by the immunoperoxidase technique in endocrine cells of the gastrointestinal tract using several specific antisera. Motilin-like immunoreactivity could only be demonstrated with one of these antisera and was observed in Purkinje cells and dendrites of the cerebellum, in pyramidal cells and dendrites of the cerebral cortex and in dendrites of the CA 3 field of the hippocampus of the rat. Very low motilin-like immunoreactivity was found in cerebellum as well as in cerebral cortex using radioimmunoassay. However, using reverse phase liquid chromatography combined with UV-detection and radioimmunoassay, no peak of a peptide corresponding to synthetic motilin was detectable in rat cerebellar extracts, in contrast to findings in rat duodenum. The results do not suggest that motilin is an intrinsic neuroactive substance of the cerebellum.

Animals↗

Relationship between aldosterone and sodium, potassium, and uric acid clearance in cirrhosis with and without ascites.

We have suggested that cirrhotic patients with high uric acid clearances had an increased effective vascular volume. This hypothesis was tested by studying the relationship between the excretion of uric acid, sodium, potassium, and aldosterone in cirrhosis. In 29 consecutive cirrhotic patients, of whom 17 had ascites, and in a control group, the logarithm of urinary sodium and aldosterone excretion highly correlated in control (r = -0.79, p less than 0.001) and cirrhotic patients without (r = -0.72, p less than 0.01) and with (r = -0.80, p less than 0.001) ascites. The regression line significantly shifted to the left in the cirrhotic patients (p less than 0.001). The urinary ratio K/K + Na also correlated with urinary aldosterone in controls (r = +0.66, p less than 0.001) and in cirrhotic patients (r = +0.77, p less than 0.001); this regression line shifted to the right in cirrhosis patients (p less than 0.02). The fractional uric acid excretion significantly correlated with urinary aldosterone only in cirrhotic patients (r = -0.76, p less than 0.001). These data confirmed the existence of hypoaldosteronism in many cirrhotic patients and are consistent with tubular hypersensitivity to aldosterone and emphasize the major role of the effective vascular volume in the control of urid acid clearance in cirrhosis.

Adult↗

Role of exercise thallium 201 imaging in decision making.

This prospective study examined the impact of results of exercise thallium 201 imaging on the estimation of probability of coronary artery disease (CAD) and patient management among cardiologists and internists in our institution. Before exercise testing, the probability of CAD in the 100 patients enrolled in this study was considered low in 31, intermediate in 28, and high in 41 patients. The probability of CAD after exercise thallium imaging was different in four patients (10%) in the high group, 22 patients (79%) in the intermediate group, and three patients (10%) in the low group. Further, the results of exercise testing resulted in changes in patient management in 29 patients (71%) in the high group, 26 patients (93%) in the intermediate group, and 16 patients (52%) in the low group. Overall, the management changed in 71% of the patients. This change included changes in medications, physical activity, frequency of office visits, need for cardiac catheterization, and need for coronary arterial bypass grafting. Thus, exercise thallium imaging is useful in clinical decision making: the diagnostic certainty is improved in patients with intermediate pretest probability of CAD; and some degree of change in patient management is observed, even in patients in whom the probability of CAD is not altered.

Adrenergic beta-Antagonists↗

Relationship between serum thyroglobulin and intrathyroidal stable iodine in human simple goitre.

Serum thyroglobulin levels are increased in many patients with simple goitre. This increase has been attributed to the release of thyroglobulin (Tg) from the colloid of necrosed follicles. To test the hypothesis that increased serum Tg could be related to the low intrathyroidal iodine concentration [I], the main cause of nontoxic goitre, these two variables were measured in 91 euthyroid goitrous patients and compared to serum free T3 and free T4 levels as well as thyroid weight. Thyroid iodine concentration was estimated from the X-ray fluorescence measurement of intrathyroidal iodine stores and from the weight of the gland estimated by planimetry. Serum Tg levels, the free T3/T4 ratio and thyroid weight were negatively correlated to [I] (Spearman's coefficient of correlation = - 0.44 (P = 0.001); -0.30 (P = 0.006); -0.33 (P = 0.001), respectively). Tg levels were also positively correlated to the T3/T4 ratio (R = 0.28, P = 0.008) and to the weight of the gland (R = 0.37; P = 0.001). These data suggest that, in simple goitre, increased serum Tg concentrations are partly related to the reduced concentration of iodine in goitre tissue (as are an increased T3/T4 ratio and the size of the goitre) and is not only the reflection of follicular necrosis.

Goiter↗

Inhibition by lysosomotropic amines of dog thyroid secretion in vitro.

The lysosomotropic amines are well-known inhibitors of lysosomal protein degradation. These drugs were used in dog thyroid slices to ascertain the role of the lysosome in thyroglobulin hydrolysis and in hormone secretion. NH4Cl (1-20 mM) and chloroquine (5-500 microM) inhibited, in a concentration-dependent manner, the TSH-stimulated secretion. The high concentrations of these compounds also inhibited the basal secretion. The inhibition was not toxic since 1) the nonbutanol extractable iodine, an index of follicle disruption, was not increased, except slightly by 20 mM NH4Cl; 2) the compounds did not inhibit the TSH-induced stimulation of protein iodination; 3) the inhibition of secretion caused by these compounds was reversible; 4) the ultrastructural changes induced by NH4Cl were reversed after its withdrawal. The inhibition of secretion was presumably related to the lysosomal trapping of the drugs because: 1) the time lag for the fall in secretion rate after drug addition was shorter than for the inhibition of secretion at the level of pseudopod formation by carbamylcholine and cytochalasin B; 2) for NH4Cl this delay and the degree of inhibition were modulated by the [H+] gradient between the medium and the lysosome; 3) 20 min after NH4Cl addition, 92% of the lysosomes were vacuolated and swollen (median section area, 126 mu2 vs. 50 mu2 for the controls) and 8% of the lysosomes were swollen and still dense (median, 206 mu2); 20 min after chloroquine addition, 90% of the lysosomes remained dense and had a significantly higher section area (median, 79 mu2) than the controls (P less than 0.001), whereas 10% of the lysosomes were vacuolated and large (median area, 438 mu2). The number of pseudopods measured by scanning electron microscopy significantly decreased only after 1 h (P less than 0.001). This late decrease could not account for the early block of secretion and suggested a lack of membrane recycling. In conclusion, lysosomotropic amines interfere with a post phagocytotic, presumably lysosomal, step in secretion by dog thyroid. These data constitute the first biochemical evidence in the intact cell of the role of lysosomes in TSH-induced thyroglobulin hydrolysis and thyroid hormone secretion.

Ammonium Chloride↗

Mechanism of cholinergic inhibition of dog thyroid secretion in vitro.

It has been previously shown that carbamylcholine (10(-5) M) decreases TSH-induced cAMP accumulation and hormone secretion in dog thyroid slices. The mechanism of the latter effect has been investigated in this work. The role of a decrease of cAMP level as the sole mediator of the inhibition of secretion was excluded: the inhibition persisted in the presence of 1-methyl-3-isobutylxanthine at 10(-4) M, which completely abolished the carbamylcholine-induced decrease in cAMP. Moreover, carbamylcholine also inhibited secretion when the slices were incubated with 0.4 mM (Bu)2cAMP. Scanning electron microscopic studies showed that carbamylcholine added at the same time as TSH blocked the formation of pseudopods in response to TSH within 2 min. The kinetic and morphological effects of carbamylcholine added at the same time as, or 90 min after, TSH were similar to those of cytochalasin B (3 micrograms/ml). After carbamylcholine addition at time 90 min, the stimulated secretion rate persisted unchanged for 46 +/- 10 min (mean +/- SD) (n = 6). During this period the colloid droplets disappeared from the cells. Carbamylcholine, like cytochalasin B, did not affect the basal secretion, which is independent of phagocytosis. It is concluded that carbamylcholine (10(-5) M) inhibits stimulated thyroid secretion at a step beyond cAMP accumulation by blocking pseudopod formation and not by inhibiting thyroglobulin hydrolysis or hormone diffusion.

1-Methyl-3-isobutylxanthine↗