Biomedical subjects

T J Theodoropoulos

Publications and source records attributed to T J Theodoropoulos.

8 recordsLinked to original sources

PubMed1991

Two distinct types of intraneuronal neurofibrillary tangles highlighted by polarized light after silver impregnation with a modified Bielschowsky method.

Neurofibrillary tangles (NFTs) are one of the morphological hallmarks of Alzheimer's disease. The birefringency and dichroism of NFTs following congo red staining have long been known. Herein, we report the observation that a subset of NFTs show distinct birefringency induced by a modified Bielschowsky silver impregnation method. Birefringency of NFTs could not be elicited after silver impregnation with one other version of the Bielschowsky method or with the Bodian technique. To our knowledge, these properties of NFTs after metal impregnation have not been previously documented.

Alzheimer Disease↗

PubMed1990

Ultrastructural evidence that insoluble microtubules are components of the neurofibrillary tangle.

The ultrastructure of Alzheimer's neurofibrillary tangles is heterogeneous and includes abnormal paired helical filaments (PHF) and various other insoluble structures. Insoluble non-PHF components isolated from neurofibrillary tangles were examined by electron microscopy. Comparison of these fractions with normal assembled neurofilaments and normal brain microtubules revealed scattered profiles which were morphologically (not chemically) identical to structures present in the microtubule, but not in the neurofilament preparations. These results support the notion that insoluble microtubules contribute to the make up of the neurofibrillary tangle. Based on these findings, preliminary experiments were conducted which suggest that non-enzymatic glycosylation may be a pathway leading to insolubility of the microtubules.

Aged↗

PubMed1990

Dilantin and salicylate effects on hepatic thyroxine bio-availability and dialyzable thyroxine.

Earlier studies have shown that drugs such as dilantin inhibit T4 binding by thyroid hormone binding globulin (TBG) and cause a displacement of T4 from TBG to prealbumin with no change in the albumin-bound T4 fraction. Since recent studies have shown albumin-bound T4 is freely transported into liver, the present studies are designed to investigate drug effects on T4 transport in liver. The effect of salicylate and diphenylhydantoin (Dilantin) on T4 in human serum were examined both in vitro by using equilibrium dialysis and in vivo in the rat liver by using a tissue sampling single injection technique. Serum was obtained from 6 healthy normal volunteers and was made either 0 or 0.5 mM Dilantin and either 0 or 10 mM sodium salicylate. The portal vein injection vehicle contained 125I-T4/3H-water (highly diffusible internal reference) mixed with either a) Ringer's (0.1 g/dl albumin), b) 5% T4 antiserum, or c) 80% human serum. The free dialyzable fraction in vitro was raised by 40 and 125% after the addition of Dilantin and salicylate respectively. However, the percent of total T4 that was transported into liver on one pass, 17 +/- 1%, was not different in the control, the salicylate treated, or the Dilantin-treated sera. Therefore, in contrast to the in vitro dialyzable measurement of free T4, which is elevated by toxic concentrations of Dilantin or salicylate, the bio-available fraction of T4 as determined by the single pass perfusion technique, is unchanged in rat liver in vivo. These drug-induced changes in free T4 in vitro and bio-available T4 in vivo are similar to the ones reported previously in non-thyroidal illness.

Adult↗

PubMed1990

Permanent alterations in the hypothalamic-pituitary-thyroid axis in the rat following phenytoin exposure in utero.

Phenytoin exposure in utero results in permanent alterations of the hypothalamic-pituitary-thyroid axis in the rat. The DPH exposed animals have decreased weight gain, thyroxine and triiodothyronine concentrations. In addition, they have blunted thyroid-stimulating hormone responses to thyrotropin-releasing hormone, propylthiouracil challenge or thyroidectomy. The diminished pituitary response in these animals is similar to that reported in neonatal thyrotoxicosis in the rat. This may be due, in part, to structural similarities between phenytoin and the thyroid hormone.

Animals↗

PubMed1989

Effects of phenobarbital on hypothalamic-pituitary-thyroid axis in the rat.

It has been reported that phenobarbital (PB) increases the peripheral clearance of T4 and T3 and decreases serum T4 and T3 concentrations in the rat, but serum TSH remains unchanged. To explore a possible direct effect of PB on TSH secretion at the hypothalamic-pituitary level, adult male rats were given PB 100 mg/kg or vehicle IP for 10 days. No difference in their thyroid weights was observed. In the PB-treated group serum T4 was decreased (PB, 3 +/- 0.2 micrograms/dl vs. control, 3.8 +/- 0.1 micrograms/dl, mean +/- SE, p less than .002), as was serum T3 (PB, 51 +/- 6 ng/dl vs. control, 70 +/- 5 ng/dl, p less than .05), but serum TSH remained unchanged. Pituitary TSH and hypothalamic TRH contents also were unchanged. Further studies were carried out similarly in the thyroidectomized hypothyroid rat to eliminate the effect of PB on serum T4 and T3 levels. PB or vehicle were started two days after thyroidectomy. By postoperative day 12, TSH levels in the PB-treated rats were lower than in the controls (PB, 697 +/- 62 microU/ml vs. control, 891 +/- 53 microU/ml, p less than .05). Pituitary TSH and hypothalamic TRH contents again were similar in both groups. When TRH (500 ng/kg body weight, IV) was given, the increment in serum TSH at 10 minutes was significantly lower in the PB group (PB, 53 +/- 26 microU/ml vs. control, 131 +/- 18 microU/ml, p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Regulation versus modulation in GnRH receptor function.

Serum luteinizing hormone (LH) concentration after exposure to gonadotropin-releasing hormone (GnRH) indicates that an instantaneous increase occurs in the rate of release of LH directly from the anterior pituitary, as measured dynamically during superfusion in vitro. On the other hand, estradiol-17 beta (E2) alone shows no such instantaneous effect on LH release rate (at least for the first four hours), in either physiologic or pharmacologic concentrations. At the same time, brief (ten to 30 minute) exposure of isolated anterior pituitary plasma membranes to physiologic concentrations of E2 significantly alters the binding of a fully biologically active 125I-GnRH to its plasma membrane receptor protein. In order to characterize the effect of E2 on GnRH binding further, we preincubated dispersed bovine anterior pituitary cells for six hours in the presence or absence of physiologic concentrations of E2 (10(-10)M). Following preincubation in the presence of E2, the cell suspension was incubated for 30 minutes with physiologic concentrations (5 X 10(-11) - 5 X 10(-10)M) of a fully biologically active 125I-GnRH. The treatment, at least, doubled the number of biologically important high affinity GnRH binding sites (Kd's = 7.5 X -10(-11) - 4.5 X 10(-10)M), and changed the binding capacity of some of the binding sites up to three fold, which altered the cooperativity of GnRH-receptor interaction. Thus, the interaction of E2 with GnRH at the level of GnRH receptor is mandatory for the short-term pituitary effect of E2 on LH release in vitro and in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Somatostatin is a regulator of thyrotropin secretion in the perinatal rat.

The perinatal rat exhibits low serum TSH levels in the presence of very low concentrations of T3 and T4. We had reported previously that this animal does not require endogenous TRH for TSH release. We investigated here whether the inhibitory hormone somatostatin (SS) has a role in maintaining the low TSH secretory set-point. To study the effect of SS in the immature model, we passively immunized pregnant rats with SS antiserum to neutralize endogenous SS. Acute iv administration of 0.3 ml SS antiserum to pregnant rats (day 20 of pregnancy) resulted in a significant serum TSH elevation in both mother and fetus 60 min after injection compared to the control values [maternal TSH, 62 +/- 6 muU/ml vs. control, 43 +/- 4 (mean +/- SE; P less than 0.05); fetal TSH, 95 +/- 8 vs. control, 66 +/- 6 (P less than 0.02)]. The binding capacity of the AS in the fetal serum far exceeded the circulating SS in the fetus. Similar results were obtained when neonates 5 and 10 days of age were injected with 0.1 ml AS, ip. Further experiments were done with the use of synthetic SS. Acute iv injection of synthetic synthetic SS (1 microgram) to pregnant rats made hypothyroid by feeding of a low iodine-propylthiouracil diet for the last week of gestation suppressed the elevated serum TSH level in both mother and fetus 15 min after the injection [maternal TSH, 102 +/- 11 vs. control, 163 +/- 22 (P less than 0.05); fetal TSH, 99 +/- 9 vs. control, 143 +/- 13 (P less than 0.02)]. Similar results were obtained when hypothyroid neonates 5 and 10 days of age were injected with 1 microgram SS, ip. These findings suggest that there is similarity in the effects of SS on TSH secretion (suppression) in mother, fetus, and neonate and dependence of the perinatal TSH on SS, in contrast to TRH. It is, then, likely that TSH secretion in the perinatal rat is under the inhibitory influence of endogenous SS.

Animals↗

PubMed1985

Thyrotropin releasing hormone biosynthesis in neonatal rat pancreas.

We studied the in vitro synthesis of thyrotropin releasing hormone (TRH) by pancreatic cells, using [14C]histidine incorporation and radioimmunoassay. Neonatal pancreases were incubated in Krebs-Ringer-bicarbonate buffer, pH 7.4, at 37 degrees C, under 95% O2-5% CO2. [14C]histidine was added and its incorporation into the tissue proteins was followed up to 4 hours. The methanolic pancreatic extracts obtained were subjected to Sephadex G-200 chromatography. Two peaks of [14C] radioactivity were eluted, one small (20% of total radioactivity) with the void volume and one large in a position identical to synthetic TRH. Both radioactive peaks corresponded to immunoreactive TRH peaks present in the same samples. In pulse-chase experiments, excess cold histidine was used and samples taken showed again similar radioactive peaks with an initial increase and a later decrease in the size of the small peak. We conclude that the neonatal rat pancreas actively synthesizes TRH and/or a higher molecular weight TRH-like protein, which may represent a TRH precursor.

Animals↗