Biomedical subjects

M Ozata

Publications and source records attributed to M Ozata.

At least 55 records · Page 3Linked to original sources

PubMed1997

Effects of gonadotropin and testosterone treatments on prostate volume and serum prostate specific antigen levels in male hypogonadism.

It is known that prostate specific antigen (PSA) is strongly androgen dependent, but little is known about the effects of gonadotropin and testosterone treatments on the prostate and serum PSA levels in male hypogonadism. We have therefore determined serum PSA levels before and 3 months after treatment in 13 patients with idiopathic hypogonadotropic hypogonadism (IHH) and 14 patients with Klinefelter's syndrome. Plasma FSH, LH, testosterone, PRL, testis and prostate volumes were also determined before and 3 months after treatments. Patients with IHH were treated with hCG/hMG and patients with Klinefelter's syndrome received testosterone treatment. PSA levels were determined by a kinetic enzyme immunoassay method. In patients with Klinefelter's syndrome FSH and LH levels were significantly decreased but total and free testosterone and PSA levels were significantly increased after 3 months of treatment. Right and left testicular volumes were not significantly changed whereas prostate volumes were significantly increased after treatment. In this group PSA levels were significantly and positively correlated with the prostate volume both before (r=0.54, P=0.048) and after treatment (r=0.61, P=0.012). In the IHH group total and free testosterone and PSA levels were significantly increased after gonadotropin treatment but FSH and LH levels did not change significantly. Right and left testicular volumes and the prostate volumes were also significantly increased after 3 months of gonadotropin treatment. In this group PSA levels were correlated with prostate volume before (r=0.74, P=0.004) treatment but not after therapy (r=0.35, P=NS). Our results show that serum PSA levels increase after gonadotropin and testosterone treatment in male hypogonadism, but this could not be used as an index for the evaluation of the androgen action in the treatment of male hypogonadism, since PSA levels following treatments were correlated with the prostate volume or T levels only in patients with Klinefelter's syndrome but not in the IHH group.

Adult↗

PubMed1997

Auditory even-related brain potentials in hyperthyroidism.

Several studies based on psychometric tests have demonstrated an impairment of cognitive functions in hyperthyroid patients. Long-latency auditory event related potentials (ERPs) allow the measurement of a kind of cerebral reaction time that is unavailable to psychometric tests. However, ERPs alterations in hyperthyroidism have been investigated only in experimentally induced hyperthyroidism in healthy subjects, but no study has reported on thyrotoxic patients so far. Therefore, we investigated alterations of P300 wave latency in hyperthyroid patients before and after antithyroid treatment. ERPs were elicited in 20 untreated patients with hyperthyroidism (mean age: 27.40 +/- 2.10 years) and in 30 sex-, age- and education-matched controls. ERPs recordings were repeated 4 months after attainment of euthyroidism. Untreated patients had longer mean P300 latencies when compared to those in controls (338.3 +/- 26.6) vs 320.7 +/- 16.2 msec, P = 0.020). Slowing of P300 latency was marked in 4 of 20 patients and its normalization was observed after treatment. The mean P300 latencies also returned to normal (320.5 +/- 15.5 msec) 4 months after achievement of euthyroidism. Our study shows that P300 is normal in most cases, while we have found in a subgroup of patients a small but statistically significant slowing. However, these alterations are reversed 4 months after attainment of euthyroidism.

Adult↗

PubMed1996

L-carnitine treatment improves brain stem auditory evoked potentials in diabetic rats.

The effect of L-carnitine (LC) on brain stem auditory evoked potentials (BAEP), was examined in alloxan-diabetic rats. LC (200 mg kg-1, i.p., once daily) was given to diabetic rats starting from the third week after the induction of diabetes, lasting for 4 weeks. Age-matched non-diabetic rats served as controls. The latency of wave I and interpeak latency I-IV were measured once weekly. Diabetes-induced deficits in BAEP latencies (p < 0.05, diabetics vs non-diabetic controls) were improved after LC treatment (p < 0.05, LC-treated diabetic rats vs non-diabetic controls). Weight and glucose levels were not influenced by LC treatment. Our results suggest that LC had beneficial effects on diabetic central neuropathy but these effects are not associated with the regulation of glycaemia in alloxan-diabetic rats.

Animals↗

PubMed1996

Effects of dexfenfluramine on glucose drinking and glucose-conditioned flavour preferences in rats: taste versus post-ingestive conditioning.

A comparison was made of the effects of dexfenfluramine (DF, 3-10 mg kg-1) on intake of and conditioning with glucose solutions varying in orostimulant properties (taste) and post-ingestive actions (calories), in rats. First, sham-feeding, using gastric-fistulated rats, was performed to assess the orostimulant properties of the solutions. Then, two experiments were done. In the first experiment, we examined the effects of DF, given at doses of 13 and 10 mg kg-1, on the intake of two glucose solutions having different orostimulant properties and different caloric values. The solutions were a mix of 1% glucose plus 0.125% saccharin (low caloric, more orostimulant), and 4% glucose (high caloric, less orostimulant). At doses of 10 mg kg-1, DF administration markedly reduced intake of both solutions (P < 0.05 vs Control Group, respectively). In second experiment, we examined the effects of DF (10 mg kg-1) on flavour preference conditioning in two parts. In the first part of the experiment, rats consumed two distinctively flavoured solutions having equal orostimulant properties but different caloric value for a conditioning period of 16 days. The solutions were a mix of 1% glucose plus 0.125% saccharin (low caloric), and 6.1% glucose (high caloric). At the end of the conditioning period, the flavour paired with ingestion of more calories was subsequently preferred (P < 0.05 vs low caloric glucose-saccharin mix). DF, when given during and after the conditioning period, attenuated this flavour-calorie conditioning (P < 0.05 vs Control Group). In the second part of the experiment, rats were conditioned with flavours associated with a mix of 20% glucose plus 0.4% citric acid and 20% glucose solutions. These solutions were equally caloric but differed in orostimulant properties. The flavour paired with better orostimulant properties was subsequently preferred (P < 0.05 vs less orostimulant glucose-citric acid mix). DF, when given during and after the conditioning period, also attenuated this flavour-flavour conditioning (P < 0.05 vs Control Group). These results suggest that DF may impair flavour preference learning.

Animals↗

PubMed1996

Comparison of the effects of aminoguanidine and L-carnitine treatments on somatosensorial evoked potentials in alloxan-diabetic rats.

The effects of aminoguanidine (AG) and L-carnitine (LC) on somatosensorial evoked potential (SEP) latency and neural levels of thiobarbituric acid reactive substances (TBARS), products of lipid peroxidation, were compared in alloxan-diabetic rats. AG and LC were given to diabetic rats starting from the 3rd week after the induction of diabetes and lasting for 4 weeks. SEP latency was measured by stimulating via caudal nerve and recording via cortex, once weekly during the treatments. Diabetes caused deficits in SEP (P < 0.05 vs non-diabetic control rats, respectively). AG and LC restored SEP latencies slightly but not significantly, with the exception of the prominent effect of AG at the first week and both treatments at the 4th week of the treatments (P < 0.05 vs untreated diabetic rats, respectively). Diabetes caused elevation in neural TBARS levels (P < 0.05 vs non-diabetic group), which was prevented by both AG and LC (P < 0.05 vs untreated diabetic rats, respectively). Weight and the glucose levels were not influenced by the treatments. Our results suggest that AG improves SEP latencies better than LC. Our results also suggest that the beneficial effects of both AG and LC on diabetic neuropathy are not associated with the regulation of glycemia, but these effects may be related in part with prevention of lipid peroxidation.

Alloxan↗

PubMed1996

Evaluation of central motor conduction in hypothyroid and hyperthyroid patients.

Deficiency or excess of thyroid hormones is associated with central nervous system (CNS) disturbances. Although the CNS involvement either in hypothyroidism or in hyperthyroidism have previously been shown on the basis of visual, auditory and somatosensory evoked potentials studies, less is known about the function of central motor pathways in both disorders. We studied the motor evoked potentials (MEPs) following the magnetic stimulation of the motor cortex and spinal roots in 20 patients with hypothyroidism and in 19 patients with hyperthyroidism both before treatment and after they became euthyroid and compared with findings in 20 age-, sex- and height-matched control subjects. Disease duration (expressed as time from diagnosis of diseases to the time of neurological testing) is less than one month in both disorders. Central motor conduction time (CMCT) was determined as the differences between MEPs latencies after cortical and spinal stimulation. The mean CMCTs before treatment in hypothyroid patients (8.31 +/- 1.52 msec.) and in hyperthyroid patients (7.92 +/- 1.06 msec.) were significantly prolonged as compared to those in normal controls (6.82 +/- 0.83 msec. p = 0.002 and p = 0.004, respectively). Four of the 20 (20.0%) hypothyroid patients and 2 of 19 (10.5%) hyperthyroid patients had abnormal CMCT (values exceeding mean +2.5 SD of normal control). The mean CMCT values in both groups were not significantly decreased after euthyroidism was achieved, although a tendency of the decrease in CMCT was observed. Improvement of CMCT abnormalities was observed in 1 of 4 hypothyroid patients and in one of 2 patients with hyperthyroidism, who had CMCT abnormalities before treatments, after they became euthyroid. No correlation was found between CMCT and free T3, free T4, or TSH levels as well as the onset age, the severity of the diseases or the disease duration in both disorders. We conclude that abnormal CMCT could be documented in few patients in both disorders. However, these alterations could not be improved completely after restoration of euthyrodism. Thus, it remains to be determined if long-term treatment would completely improve CMCT abnormalities in both disorders. Since abnormal CMCT values in both disorders were observed only in few patients, our results also suggest that CMCT measurement does not have, at present time, a clinical usefulness to assess the peripheral action of thyroid hormones. Thus, the data obtained need a more extensive evaluation.

Adult↗

PubMed1996

Acute hypothyroidism leads to reversible alterations in central nervous system as revealed by somatosensory evoked potentials.

Although functional alterations in the central nervous system (CNS) and peripheral nerves are well documented in overt hypothyroidism, little is known about alterations of CNS in acute hypothyroidism. Sixteen patients with differentiated thyroid carcinoma were studied when prepared for radioiodine scanning after stopping levothyroxine (L-T4) therapy for 6 weeks to determine whether acute hypothyroidism leads to alteration in somatosensory evoked potentials (SSEPs). Repeat SSEPs were performed on the same patients at 6 months following L-T4 therapy when patients were euthyroid. Neurophysiological findings were compared with a group of 20 normal controls with no history of thyroid disease. Peripheral and central conduction in the median and tibial nerve stimulated SSEPs studied. A significant prolongation of central conduction time in SSEPs was found in patients with acute hypothyroidism when compared to those in control subjects. Abnormal latencies were not correlated with thyroid hormone levels. These neurophysiologic abnormalities were completely restored to normal at 6 months after L-T4 therapy. We conclude that acute hypothyroidism leads to reversible alterations in CNS as determined by SSEP recordings. Our results also suggest that SSEPs could be useful tests to monitor functional alteration of the CNS in acute hypothyroidism.

Acute Disease↗

PubMed1996

Effects of octreotide treatment on Graves' ophthalmopathy and circulating sICAM-1 levels.

Efficacy of octreotide treatment for Graves' ophthalmopathy (GO) and the effects of this treatment on the serum levels of the circulating intercellular adhesion molecule-1 (sICAM-1) were evaluated. Ten patients with GO were treated with octreotide three daily SC injections of 100 micrograms, for 3 months. Octreotide treatment was initiated after restoration of euthyroidism with antithyroid drugs. All patients were treated with methimazole to maintain euthyroidism during the study. Sera were collected from all patients before and 3 months after initiation of the study, and from 20 age- and sex-matched healthy subjects for sICAM-1 measurement. sICAM-1 was measured by a sandwich ELISA method. Proptosis in all patients was evaluated by orbital CT scan before and 3 months after initiation of the study. Two of 10 patients did not respond to octreotide therapy, while the remaining eight patients showed regression or improvement after therapy. Octreotide therapy was particularly successful in patients with soft tissue involvement of GO (class II or III disease). Mean proptosis and ophthalmopathy index scores were significantly decreased after 3 months of octreotide therapy. Mean sICAM-1 levels were significantly higher in patients before octreotide therapy (470.5 +/- 52.6 ng/mL, p < 0.0001) when compared to normal subjects (186.5 +/- 53.3 ng/mL). Mean sICAM-1 levels were significantly decreased 3 months after octreotide therapy (from 478.7 +/- 52.6 to 415 +/- 42.8 ng/mL, p = 0.012) in the 8 patients who responded to therapy. In contrast, sICAM-1 levels remained unchanged or increased in two patients with poor response to octreotide therapy. Our results suggest that octreotide therapy could be a treatment modality in patients with GO. The mechanism by which octreotide acts on GO is not clear. The observed decrease in sICAM-1 levels during octreotide therapy suggests that octreotide may have immunomodulatory properties. Further investigation is needed to determine the optimal dose and duration of octreotide therapy.

Adult↗

PubMed1996

Daytime plasma melatonin levels in male hypogonadism.

It has previously been shown that increased nocturnal melatonin (MT) secretion exists in male patients with hypogonadotropic hypogonadism. However, little is known about the effects of gonadotropin and testosterone (T) treatment on early morning plasma MT levels in male hypogonadism. Also, the impact of gonadal steroids on plasma MT levels is an open question. We, therefore, determined early morning plasma MT levels at the same hour before and 3 months after treatment in 21 patients with idiopathic hypogonadotropic hypogonadism (IHH), 10 patients with primary hypogonadism, and 11 male controls. Plasma FSH, LH, PRL, T, and estradiol levels were also determined before and 3 months after treatment. Patients with IHH were treated with hCG/human menopausal gonadotropin, whereas patients with primary hypogonadism received T treatment. Short term treatments did not achieve normal T levels, although significant increases in T were observed in both groups. Plasma MT levels were measured by a RIA with a sensitivity of 10.7 pmol/L. Mean plasma MT levels before treatment were significantly higher in IHH (41.8 +/- 24.4 pmol/L) compared with those in the controls (21.7 +/- 10.8 pmol/L; P < 0.05). However, a slight, but not significant, increase in MT (34.2 +/- 21.1 pmol/L) was found in primary hypogonadism. Mean MT levels did not change significantly 3 months after the initiation of gonadotropin (41.7 +/- 22.8 pmol/L) or T (28.4 +/- 12.6 pmol/L) treatment in either IHH or primary hypogonadism, although a tendency for MT to decrease was observed in both groups. No correlation was found between MT and circulating FSH, LH, PRL, and gonadal steroids either before or after therapy. We conclude that male patients with IHH have increased early morning MT levels, although the pathophysiological mechanism is not clear. Furthermore, our study demonstrated that mean plasma MT levels are not influenced by short term gonadotropin or T treatment in male hypogonadism, although a longer time effect of gonadotropins or T treatment may not be excluded. The lack of correlation between plasma MT and circulating gonadal steroids before and after treatment suggests that there is no classic feedback regulation between the pineal gland and the testes.

Adult↗

PubMed1996

Effects of gonadotropin and testosterone treatments on Lipoprotein(a), high density lipoprotein particles, and other lipoprotein levels in male hypogonadism.

It is known that lipoprotein(a) [Lp(a) is an independent risk factor for developing atherosclerosis, whereas the LpA-I particle of high density lipoprotein (HDL) is an antiatherogenic factor. The effects of androgen replacement therapy on lipid and lipoproteins have previously been reported in male hypogonadism. However, no study reported the effect of gonadotropin or testosterone treatment on Lp(a), LpA-I, or LpA-I;A-II levels in make hypogonadism. We, therefore, determined Lp(a), LpA-I, LpA-I:A-II, and other lipoprotein levels before and 3 months after treatment in 22 patients with idiopathic hypogonadotropic hypogonadism (IHH) and in 9 patients with Klinefelter's syndrome. All patients had been previously untreated for androgen deficiency. Plasma FSH, LH, PRL, testosterone (T), estradiol, and dehydroepiandrosterone sulfate levels were also determined before and 3 months after treatment. Patients with IHH were treated with hCG/human menopausal gonadotropin, whereas patients with Klinefelter's syndrome received T treatment. Three months after treatment, mean T levels role to low normal levels in both groups. Triglyceride, LpA-I:A-II, Lp(a), HDL cholesterol, HDL3 cholesterol, and apolipoprotein (apo) A-I concentrations did not change significantly after treatment, whereas total cholesterol, low density lipoprotein cholesterol, LpA-I, and HDL2 concentrations were significantly increased 3 months after treatment in both groups. The apo B concentration significantly increased in patients with klinefelter's syndrome, whereas no change was observed in the IHH group. Lp(a) concentrations were not related to all hormonal and clinical parameters in both groups. LpA-I concentrations were significantly and negatively correlated with free T (r = -0.80; P = 0.010) in patients with Klinefelter's syndrome and were not correlated with all hormonal and clinical parameters in the IHH group. The LpA-I:A-II concentration was only correlated with body mass index (r = -0.83; P = 0.005) in patients with Klinefelter's syndrome, whereas it was correlated negatively with dehydroepiandrosterone sulfate (r = -0.57; P = 0.005) in the IHH group.2 Overall, our study demonstrates that gonadotropin or T treatment has a complex effect on lipids and lipoproteins. This complexity will be resolved when sufficient large scale androgen treatment data are available for assessment of the long term outcome of androgen treatment. The increases in total cholesterol and low density lipoprotein cholesterol concentrations after treatments are the adverse effects of these treatments, whereas the increases in HDL2 and LpA-I concentrations and the lack of changes in Lp(a) are the beneficial effects. Gonadotropin or T treatment did not modify the Lp(a) concentration, indicating that it is not affected by the hormonal milieu in male hypogonadism. Our study also showed that LpA-I, but not LpA-I:A-II, particles could be modified by androgen replacement therapy.

Adult↗

PubMed1996

Biological variation of serum lipids and lipoproteins in patients with clinically well controlled non insulin dependent diabetes mellitus.

To investigate how the visit-to-visit variation in serum lipids measurements affects the decision making concerning treatment according to the National Cholesterol Education Program (NCEP) guidelines in patients with clinically well controlled non-insulin-dependent diabetes mellitus (NIDDM) we have measured the biological variation (CVb) in serum total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) in 26 patients with NIDDM. We found the CVb as follows: TC, 5.1%; TG, 17.0%; HDL-C 4.4% and LDL-C, 8.3%. Confidence intervals (95%) were determined with total intra-individual variance values around the NCEP cut-off points to evaluate how well one, two and three lipid measurements provided reliable risk classification. A single TC measurements < 177 mg/dL or > 263 mg/dL allowed confident classification as "desirable" or "high risk" respectively. For LDL-C, one measurement was accurate only at below 106.3 mg/dL or above 183.7 mg/dL. The average of three measurements contracted these limits to < 186.7 mg/dL and > 253.3 mg/dL for TC, and < 116.3 mg/dL and > 173.7 mg/dL for LDL-C. For HDL-C also, multiple measurements improved risk assignment in a similar fashion. There were no values which allowed assignment to the "borderline high" category with one TC measurement and with one and two LDL-C measurements. The mean of three TC and three LDL-C measurements allowed assignment to the "borderline high" category, if between 213.3 and 226.7 mg/dL for TC, 143.7 and 146.3 mg/dL for LDL-C. Seven patients (26.9%) in this risk group based on the mean of two LDL-C estimates could be placed into a different category when the mean of three estimates was taken, even though the first two LDL-C test results did not differ by more than 30 mg/dL. Our results suggest that repeated lipid measurement is important especially for the "borderline-high" risk group because big variations existed in some patients, and further that TC is the most reliable quantity.

Aged↗

PubMed1996

Soluble intercellular adhesion molecule-1 concentrations in patients with subacute thyroiditis and in patients with Graves' disease with or without ophthalmopathy.

Increased circulating soluble ICAM-1 (sICAM-1) levels has been previously reported in Graves' disease (GD) patients with or without ophthalmopathy (GO) and in patients with toxic nodular goiter but not in patients with subacute thyroiditis. Conflicting results have also been reported about the usefulness of sICAM-1 levels as a marker for the activity of hyperthyroidism. We have therefore determined sICAM-1 levels by a sandwich enzyme linked immunosorbent assay (ELISA) method in 10 patients with subacute thyroiditis (Group 1), who are at the initial or acute phase of thyroiditis, in 10 hypothyroidic patients with Hashimoto's thyroiditis (Group 2), in 10 patients with euthyroid nodular goiter (Group 3), in 10 patients with untreated GD patients with active ophthalmopathy (Group 4), in 10 hyperthyroid GD patients without clinical ophthalmopathy (Group 5), in 10 patients with GO who are euthyroid and treated with glucocorticoids for 3 months (Group 6) and in 20 normal subjects (Control Group). Groups 1,2,4,5 and 6 (P < 0.00001 for Groups 1,4,5,6 and P < 0.05 for Group 2) but not Group 3 showed increased sICAM-1 levels compared with the control group. However Groups 4 and 6 (patient with GO) showed significantly higher sICAM-1 levels (P = 0.0003 for Group 4 and P = 0.00013 for Group 6) than Group 5. Furthermore Group 4 showed slightly but not significantly higher sICAM-1 levels than Group 6. Mean sICAM levels were significantly decreased 3 months after glucocorticoid treatment (Group 6), but had not returned to normal levels. Three patients did not respond to steroid therapy and their sICAM-1 levels were not decreased. We concluded that patients with GO with or without hyperthyroidism and patients with subacute thyroiditis have elevated sICAM-1 levels. Moreover, sICAM-1 levels reflect the degree of inflammatory activity in the thyroid gland or orbital tissue independent of the thyroidal status, since we found elevated levels in both hyperthyroidism and hypothyroidism.

Adult↗

PubMed1996

Acute promyelocytic leukemia in the course of acromegaly: a case report.

Acromegaly is an uncommon disease due to excessive amounts of growth hormone. Benign and malignant tumors have been reported in acromegalic patients. A 41-year-old female patient who had been followed up because of acromegaly by the endocrinology department for two years, was admitted to the hematology department for the evaluation of pancytopenia and the related signs and symptoms. Dopamine agonists were being used till a diagnosis of 'acute promyelocytic leukemia' was made. Occurrence of 'acute promyelocytic leukemia' in the course of acromegaly may have been caused by excessive endogenous GH or may be a coincidental situation.

Acromegaly↗

PubMed1996

Lipoprotein(a) concentration in subclinical hypothyroidism before and after levo-thyroxine therapy.

Subclinical hypothyroidism is a frequent disorder in populations and has been shown to be a risk factor for coronary heart disease (CHD). Less is known about the contribution of lipoprotein (a) [Lp(a)] to the development of CHD in this disorder. Therefore this study was designed to evaluate Lp(a) and other lipoprotein concentrations before and after L-T4 therapy in 20 patients with subclinical hypothyroidism and 20 normal healthy subjects matched for sex, age and BMI. In the basal state of subclinical hypothyroidism, a significant increase in total cholesterol, LDL-cholesterol and apolipoprotein (apo) B concentrations was observed in patients compared with those in the control group. The mean Lp(a) concentration before treatment was 163 +/- 15 mg/L. This is slightly but not significantly higher than those in the control group (131 +/- 15 mg/L). Treatment of subclinical hypothyroidism with a low dose of L-T4 (25 micrograms daily) for 3 months after restoration of euthyroidism led to decreases in levels of Lp(a) from 163 mg/L to 126 mg/L (23% reduction, P < 0.001), total cholesterol from 5.5 mmol/L to 5.1 mmol/L (7% reduction, P < 0.001), LDL-cholesterol from 4.14 mmol/L to 3.63 mmol/L (12%, P < 0.001), and apo B from 98 mg/dL to 86 mg/dL (12% reduction, P < 0.05), but triglyceride, HDL-cholesterol and apo A-I concentrations were unchanged. These data suggest that L-T4 replacement therapy in patients with subclinical hypothyroidism has beneficial effects on the lipid profile since L-T4 replacement therapy lowered the concentrations of Lp(a) and other atherogenic lipid particles.

Adult↗

PubMed1995

Subclinical hypothyroidism does not lead to alterations either in peripheral nerves or in brainstem auditory evoked potentials (BAEPs).

Functional alterations in the central nervous system and peripheral nerves are well documented in overt hypothyroidism, but not in subclinical hypothyroidism. Twenty-seven patients with subclinical hypothyroidism were compared with a control group of 20 age- and sex-matched subjects to determine whether subclinical hypothyroidism can lead to alterations in peripheral nerves or in the brainstem auditory evoked potentials (BAEPs). None of the patients had carpal tunnel syndrome or any other neurological or metabolic disturbances. Disease duration (expressed as the time from diagnosis of subclinical hypothyroidism to the time of neurological testing) ranged from less than 1 month to 6 months (median 2.5 months). We studied the distal motor latency, nerve conduction velocity (NCV), compound muscle action potentials, and F response in the median and peroneal nerves whereas the sensory nerve conduction velocity and sensory potential amplitude were measured in the sural and median nerves. Electrophysiological parameters and interpeak latencies yielded no significant difference between patient and control groups. The present study indicates that subclinical hypothyroidism of short duration does not lead to abnormalities of peripheral nerves or brainstem auditory evoked potentials.

Action Potentials↗

PubMed1995

Functional analysis of a proline to serine mutation in codon 453 of the thyroid hormone receptor beta 1 gene.

Mutations in the gene encoding human thyroid hormone receptor beta (hTR beta) have been associated with generalized resistance to thyroid hormone (GRTH). This disorder is associated with significant behavioral abnormalities. We examined the hTR beta gene in a family with members who manifest inappropriately normal TSH, elevated free T4, and free and total T3. Sequence analysis showed a cytosine to thymine transition at nucleotide 1642 in one allele of the index patient's genomic DNA. This altered proline to serine at codon 453. The resulting mutant receptor when expressed in vitro bound DNA with high affinity, but the T3 affinity of the receptor was impaired. The mutant TR demonstrated a dominant negative effect when cotransfected with two isoforms of wild-type receptor and also in the presence of TR variant alpha 2 in COS-1 cells. Mutations of codon 453 occur more frequently than at other sites, and four different amino acid substitutions have been reported. Significant differences in phenotype occur among affected individuals, varying from normality to moderately severe GRTH. There is no clear correlation between Ka or in vitro function of the mutant receptor, and phenotype. This study extends the association between GRTH and illness, and indicates that early diagnosis and counseling are needed in families with TR beta 1 abnormalities.

Adult↗

PubMed1995

Sequential changes in serum thyroid peroxidase following radioiodine therapy of patients with differentiated thyroid carcinoma.

To determine the detectability and the time course of serum thyroid peroxidase (TPO) levels before and 1, 2, 4, and 6 months after 131I administration, we evaluated TPO in 13 selected patients with differentiated thyroid carcinoma (DTC) whose sera did not contain antimicrosomal or antithyroglobulin (Tg) antibodies. All patients received 131I therapy 6 or 8 weeks after thyroid surgery for ablation of the postsurgical thyroid remnant. Serum samples were also collected from 10 normal subjects. Measurement of TPO was carried out by using a new commercially available immunoluminometric assay with a sensitivity of 30 pg/mL. Serum Tg was measured by RIA with a sensitivity of 2.6 micrograms/L before and 6 months after 131I administration. In all patients, a standard total body scan was obtained before and 6 months after 131I administration. TPO was undetectable in all sera from normal subjects. However, serum TPO became detectable in all patients with DTC during the study, whereas rescans were either negative or positive and appeared not to be related to the radioiodine dose given, histology of the thyroid tumor, residual thyroid volume, TSH levels, or age of patients. However, a significant negative correlation was present between TPO levels before 131I administration and the time from surgery (r = -0.82, P < 0.001). Six of 13 patients had increased TPO levels 1 month after 131I administration. Serum TPO levels tended to decrease during follow-up in most patients (7 of 10) with a negative rescan. In 3 patients with positive rescans, TPO levels tended to increase during follow-up. Patients with negative rescans had values of serum TPO overlapping the range of values seen in patients with positive rescans, thus demonstrating the inability of TPO assay as a useful marker for following patients with DTC. We found no correlation between Tg and TPO levels measured before and 6 months after 131I administration, thereby excluding TPO levels as a marker for thyroid cancer. Our results suggest that TPO, unlike Tg, does not appear to be a useful marker for following patients with DTC.

Adult↗

PubMed1995

The dominant negative effect of thyroid hormone receptor splicing variant alpha 2 does not require binding to a thyroid response element.

The functionally inactive thyroid hormone receptor splicing variant-alpha 2 (TRv alpha 2) can inhibit transcriptional activation by TR alpha 1 or beta 1, demonstrating a dominant negative effect (DNE). We examine here the three commonly proposed mechanisms, namely, competition for binding to thyroid hormone response elements (TREs), formation of inactive heterodimers, and squelching. A mutation introduced into the DNA-binding domain (DBD) of the TRv alpha 2 was designed to prevent its binding to TREs. In transient cotransfection studies, the DBD mutant has nearly the same DNE as does TRv alpha 2 on three different TRE-containing reporter genes. The DNE of TRv alpha 2 is also not reversed by cotransfection with excess retinoid X receptor-alpha. Extracts of COS cells cotransfected with TR alpha 1 and either TRv alpha 2 or DBD mutant at different ratios were analyzed by gel shift assays. Neither TRv alpha 2 or the mutant altered binding of TR alpha 1 to four radiolabeled TREs. TRv alpha 2 itself can inhibit constitutive transactivation by a thymidine kinase promoter-driven reporter construct. Our results suggest that TRv alpha 2 can function in a dominant negative manner without binding to a TRE, at least for certain TREs. It is concluded that the DNE of TRv alpha 2 may occur through another unrecognized mechanism, perhaps by binding to basal transcription factors.

Animals↗