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Biomedical subjects

J Unger

Publications and source records attributed to J Unger.

At least 73 records · Page 4Linked to original sources

Novel poly-substituted aryl acridinium esters and their use in immunoassay.

A new series of stable acridinium ester conjugates have been developed for use as non-isotopic labels in immunoassay. They have proved to be a flexible alternative to radioimmunoassay. We present data showing the successful development of immunoassays in sandwich, competitive and receptor formats. In addition, hydrophilic acridinium ester analogues have been synthesized, encapsulated in liposomes, and utilized as labels in immunoassay. The potential of this technology is discussed.

Acridines↗

Future applications of Magic Lite technology.

The features that Magic Lite products offer as an immunoassay delivery system are discussed. The use of paramagnetic particles and acridinium ester labels confers advantages of speed, sensitivity, and stability. The technology has been used to measure analytes of widely varying molecular weights and serum concentrations, indicating its potential to detect the full range of clinically relevant analytes. Initial development efforts have indicated that the advantages of the system can be effectively exploited in an automated instrument.

Autoanalysis↗

Demonstration of atrial natriuretic peptide/cardiodilatin (ANP/CDD)-immunoreactivity in the salt gland of the Pekin duck.

A novel peptide hormone, atrial natriuretic factor/cardiodilatin (ANP/CDD), was recently isolated and characterized from mammalian heart. Its presence has been demonstrated in several organs that contribute to water and sodium homeostasis, such as salivary glands. This study demonstrates the presence of ANP/CDD immunoreactivity in the salt gland of Pekin ducks by high performance liquid chromatography, radioimmunoassay and immunocytochemistry, using a specific antibody against atriopeptide I. A small number of distinct, ovoid or cuboid shaped ANP/CDD-immunoreactive cells were localized in the connective tissue surrounding and separating the central secretory tubules, whereas no immunostaining was observed in the peripheral tubules. Salt glands of ducks that were adapted to salt water revealed a significant hypertrophy of their secretory lobules. However, no differences were found between the number or localization of immunoreactive cells in the salt gland of salt water-acclimatized ducks and nonstimulated glands of ducks that were housed with ad libitum access to fresh water. Our results indicate that ANP/CDD may play a role in the regulation of sodium secretion in the salt gland of aquatic birds.

Animals↗

Distribution of insulin receptor-like immunoreactivity in the rat forebrain.

Previous studies have suggested that insulin may play a role in the hormonal regulation of neurotransmitter metabolisms within the central nervous system. In order to provide additional information to support this hypothesis, we examined the distribution of insulin receptors within the forebrain of adult male rats. Insulin receptors were localized by immunocytochemistry, using an antibody directed against the carboxy-terminus of the beta-subunit of the insulin receptor. The antibody specificity was tested by immunoprecipitation of brain insulin receptors with antiserum and the purity of the receptor-antibody preparation was determined using hormone binding-assays with radiolabeled insulin and insulin-like growth factor-l. Insulin receptor-like immunoreactivity was found in a widespread, but selective, distribution on neurons throughout the rat forebrain. Double-labeling with glial fibrillary acidic protein did not demonstrate any detectable insulin receptor-like immunoreactivity on glial cells. Areas with the highest density of insulin receptor-like immunoreactivity were found in the olfactory bulbs, hypothalamus and median eminence, medial habenula, subthalamic nucleus, subfornical organ, CA 1/2 pyramidal cell layer of the hippocampus and piriform cortex. Double-staining of hypothalamic sections with somatostatin and vasopressin antisera revealed insulin receptor-like immunoreactivity on a subpopulation of somatostatin neurons in the periventricular region and on vasopressin neurons in the supraoptic nucleus. A moderately dense insulin receptor-like immunoreactivity was observed in layers II-IV of cerebral cortex, medial amygdala, reticular thalamic nucleus, zona incerta, and preoptic and septal regions, whereas a low density of insulin receptor-like immunoreactive neurons was found in basolateral amygdala and most thalamic regions. The basal ganglia and most parts of the thalamus were almost devoid of insulin receptor-like immunoreactivity. Our findings provide morphological support for a direct action of insulin on selected regions of the rat forebrain and suggest that the insulin receptor may modulate synaptic transmission or the release of neurotransmitters and peptide hormones in the CNS.

Animals↗

24 h-kinetics of iodide uptake in amiodarone induced hypothyroidism.

Amiodarone induced hypothyroidism (AIH) is assumed to result from a failure of the thyroid to escape from the inhibitory effect of inorganic iodine on its organification as a consequence of uninhibited iodide trapping. This hypothesis was supported by the 24h kinetics of radioiodine uptake in a patient with AIH. 131I uptake reached a maximum after 2h and remained unchanged from 2h to 24h. 131I uptake was in the normal range from 1 1/2h to 7h and clearly subnormal after 9h. The normal early 131I uptake was due to the non inhibition of the iodide-concentrating mechanism and the low 24h radioactivity to the decreased iodide organification. These findings presumably explain the mechanism of AIH.

Aged↗

Treatment of atrial fibrillation associated with hyperthyroidism by amiodarone and methimazole.

We treated a 78-year-old patient with hyperthyroidism and atrial fibrillation with amiodarone 1200 mg/day for 3 days and methimazole 60 mg/day. Sinus rhythm was restored within 3 days and serum levels of triiodothyroxine returned to normal within 4 days. A transient increase in serum rT3 concentrations was observed. Amiodarone associated with methimazole was useful in the management of atrial fibrillation and hyperthyroidism in our patient.

Aged↗

Gallium-67 renal uptake in Sjogren's syndrome.

This case report describes a 61-year-old male with Sjogren's syndrome. Diffuse Ga-67 uptake in the kidneys was seen due to renal involvement with this disorder. Sjogren's syndrome should be considered in the differential diagnosis of diffuse bilateral Ga-67 accumulation in the kidneys.

Gallium Radioisotopes↗

Bartter's syndrome with a salt reabsorption defect in the cortical part of Henle's loop.

The pathogenesis of Bartter's syndrome remains uncertain. The prevailing theory postulates a defect in salt reabsorption, more frequently described in the thick ascending limb of Henle's loop. The patient we studied presents a normal urinary concentration capacity associated with impaired dilution, a free water clearance at the lower end of normal (5.4 ml/min/100 ml glomerular filtrate), a decreased distal fractional chloride reabsorption (54%) when studied during hypotonic saline diuresis, and a normal decrease in free water clearance after furosemide (2.1 ml/min/100 ml glomerular filtrate), suggesting a defect in the cortical part of Henle's loop. When studied during oral water diuresis, the fractional chloride reabsorption was normal (82%). This could be explained by a relative inability of the cortical diluting segment to reach maximal absorptive rates for NaCl. An inappropriate kaliuria related to an excessive delivery of salt load to the distal tubule is suggested by the correlation between urinary potassium and chloride excretion (r = 0.84; p less than 0.001). Aldosterone secretion participates also partially in the urinary potassium loss.

Absorption↗

Inhibition by monensin of dog thyroid secretion in vitro.

Monensin, a carboxylic ionophore, raises the pH of prelysosomal and lysosomal compartments and inhibits lysosomal protein degradation. We tested this drug in dog thyroid slices to ascertain the role of lysosomal pH in thyroglobulin hydrolysis and hormone secretion. Monensin (10(-7)-10(-5) M) and another carboxylic ionophore, nigericin (10(-7)-10(-5) M), inhibited in a concentration-dependent manner TSH-stimulated secretion of T4, T3, and iodide. This inhibition was not toxic since: 1) 10(-5) M monensin did not affect TSH stimulation of protein iodination and cAMP accumulation; and 2) the inhibition was reversible. Secretion was blocked at a postphagocytotic, presumably lysosomal step because the time lag for the fall in secretion rate after 10(-5) M monensin addition was 19 min +/- (SD) 3 min (six experiments), i.e. the same as after lysosomotropic amine addition and significantly shorter than after addition of cytochalasin B (time lag, 43 min +/- 7 min, nine experiments), an inhibitor of phagocytosis. In addition, 10(-5) M monensin blocked the TSH-induced formation of apical pseudopods and colloid droplets and induced a swelling of the Golgi structures. In conclusion, monensin interfered with phagocytosis and with a postphagocytotic, presumably lysosomal, step in secretion by dog thyroid in vitro. Our data provide the first biochemical evidence, in the intact cell, that an acidic pH in the prelysosomal and/or lysosomal compartment is necessary for thyroid hormone secretion.

Ammonium Chloride↗

Fasting induces a decrease in serum thyroglobulin in normal subjects.

Fasting decreases serum T3 concentrations by reducing peripheral conversion of T4 to T3. Whether it affects TSH and thyroid secretion is controversial. Thyroglobulin (Tg) is a secretory product of the thyroid gland. To determine if fasting might alter thyroid secretion, we measured serum Tg concentrations during and after a 4-day fast in seven normal subjects and examined its correlation with serum TSH, T4, and T3 concentrations. Serum TSH concentrations significantly decreased from a mean prefasting value of 1.55 +/- 0.19 (+/- SE) mU/L to a nadir of 0.82 +/- 0.09 mU/L (P = 0.01) after 3 days of fasting. The mean serum Tg level decreased from 30 +/- 5 to 12 +/- 3 micrograms/L (P = 0.005) and serum T3 from 160 +/- 8 (2.46 +/- 0.12) to 69 +/- 7 ng/dL (1.06 +/- 0.11 nmol/L) (P less than 0.0001) after 4 days of fasting. Serum T4 did not change significantly. Serum TSH, T3, and Tg concentrations returned to prefasting values within 3 days after initiation of refeeding. A significant correlation was found between the mean serum TSH and Tg concentrations (r = 0.77; P less than 0.05) and between the mean serum Tg and T3 concentrations (r = 0.78; P less than 0.05). The individual Pearson's correlation coefficients between serum Tg and serum T3 ranged from 0.67-0.93 and were significant (r greater than 0.70; P less than 0.05) in five of the seven subjects. In conclusion, the parallel changes in serum TSH, Tg, and T3 concentrations during fasting suggest that in addition to the well known decrease in serum T3 concentrations, decreased TSH and thyroid secretion (reflected by serum Tg) may be an adaptive response to fasting.

Adult↗

CSF somatostatin is elevated in patients with postzoster neuralgia.

We evaluated the concentration of the neuropeptide somatostatin (SOM) in the CSF of patients with several neurologic diseases. Since SOM is localized in high concentrations in primary sensory pathways, such as the dorsal root ganglia and dorsal horn of the spinal cord, it might be involved in conditions of chronic pain due to functional alterations of nociceptive neurons, such as postinfectious zoster neuralgia. Our study indicated a marked elevation of SOM in patients suffering from postzoster neuralgia compared with controls. Comparison with other neurologic diseases revealed decreased CSF SOM levels in Parkinson's and Alzheimer's disease, unchanged values in patients with amyotrophic lateral sclerosis, and increased concentrations in patients with brain tumors. In neurodegenerative disorders, SOM levels in CSF seemed to reflect the anatomic distribution as well as a reduction or preservation of the peptide in certain brain areas affected by the disease process. In postzoster patients, postinfectious degeneration of dorsal root ganglia cells might cause deafferentation of dorsal horn neurons and activation of SOM-containing systems with increased release either locally from neurons in the dorsal horn of the spinal cord or from descending fiber projections. The results suggested that SOM may take part in the modulation of nociceptive responses.

Herpes Zoster↗

Pheochromocytoma.

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Adrenal Gland Neoplasms↗

Effect of amiodarone on serum T4 and T3 levels in hyperthyroid patients treated with methimazole.

We investigated the course of thyroid hormones levels in the serum of hyperthyroid patients acutely treated with amiodarone. Ten patients were treated either with amiodarone, 3 X 400 mg daily for 3 days in addition to methimazole, 3 X 20 mg daily for 10 days (Group I; n = 5) or with a placebo plus methimazole at the same doses (Group II; n = 5). Basal T3, T4 and rT3 serum concentrations were: 297 ng/dl, 16.6 micrograms/dl and 507 pg/dl, respectively in Group I and 377 ng/dl, 17.6 micrograms/dl and 362 pg/dl in Group II (NS). Compared with basal values, the drop in serum T3 concentration became significant on Day 1 in Group I, but not until day 5 in Group II. The decrease in serum T3 concentration was significantly higher in Group I than in Group II from Day 1 to Day 7. In Group I, T4 concentration was significantly lower on Days 2, 4 and 6; the percentage drop in T4 calculated from the areas under the curves was higher and the T3/T4 ratio lower on Days 3-5, 7 and 9; rT3 was higher on Days 4 and 5 and its rise was significant on Days 1, 3 and 4. During the follow-up period a transient rise in T4 and T3 concentrations was observed in two patients in Group I when the methimazole dosage was tapered or stopped because of agranulocytosis. In conclusion, in our hyperthyroid patients, amiodarone in conjunction with methimazole induced a greater fall in T3 and T4 than did methimazole alone.

Adult↗