Biomedical subjects

R Rossi

Publications and source records attributed to R Rossi.

At least 217 records · Page 12Linked to original sources

PubMed1997

[Changes in serum levels of N-terminal procollagen type III propeptide as an index of postinfarction ventricular remodeling].

The levels of aminoterminal propeptide of type III procollagen (PIIINP) can be used as an index of collagen breakdown. The aim of our study was to evaluate modifications in serum concentration of PIIINP (PIIINPs) in patients with a first episode of myocardial infarction. We examined 70 patients admitted at our Institution for acute myocardial infarction and 10 normal subjects. PIIINPs dosage was obtained by radioimmunoassay method utilizing a commercial available kit. All patients underwent three PIIINPs dosages: within 24 hours after admission, at 6 and 12 months after myocardial infarction. Control values were 0.4 +/- 0.1 U/ml. In 38 patients (Group I) PIIINPs levels increased at 6 and 12 months after infarction: 0.53 +/- 0.2, 0.75 +/- 0.2 and finally 0.76 +/- 0.1 U/ml. In the remaining 32 patients (Group II) PIIINPs values increased at 6 months and then returned to baseline at 12 months: 0.56 +/- 0.2, 0.75 +/- 0.1 and then 0.46 +/- 0.1 U/ml. The end-diastolic volume index did not change significantly in Group I (from 93.7 +/- 21 to 79.7 +/- 20 ml/m2) while it decreased after 12 months in Group II (from 88.9 +/- 13 to 58.6 +/- 11 ml/m2; confidence interval 95% from 2 to 55 ml/m2; p = 0.03). Similarly, there was no significant variation in end-systolic volume index (ESVI, from 39.7 +/- 11 to 36.9 +/- 11 ml/m2) and ejection fraction (from 60 +/- 10 to 59 +/- 15%) in Group I; while in Group II ESVI decreased significantly (from 33.6 +/- 13 to 20 +/- 5 ml/m2, confidence interval 95% from 3 to 24 ml/m2; p = 0.02) and ejection fraction improved (from 62 +/- 11 to 72 +/- 15%; confidence interval 95% from -20 to -1%; p = 0.04). In conclusion, patients with elevated levels of PIIINPs at 12 months did not improve ventricular function while patients with PIIINPs returning to baseline at 12 months had an improvement. Our results suggest an active participation of newly formed collagen in post-infarct ventricular remodeling. Therefore PIIINPs may be a marker of this process.

Collagen↗

PubMed1997

[Chronic pancreatitis. A recent national experience with its surgical management].

BACKGROUND: The prevalence of chronic pancreatitis in Chile is not known and there is no local information about the surgical treatment of this disease. AIM: To review retrospectively the results of surgical treatment of chronic pancreatitis. MATERIAL AND METHODS: The charts of 17 patients (12 male), aged 7 to 65 years old, with chronic pancreatitis that were operated in three different Chilean regions, were reviewed. RESULTS: Seven patients had previous endoscopic therapeutic procedures (papillotomy in 4 and stent placing in 3). Seven patients had been subjected to previous biliary surgical procedures. Indications for surgery were severe pain in 14 patients, the suspicion of a pancreatic carcinoma in 4 patients, an infected pseudocyst in one and massive bleeding of multiple pseudo-aneurysms in a pseudocyst in one patient. Twelve patients were subjected to decompressions and 5 to pancreatic resections. There was no operative mortality and one transient pancreatic fistula. After an average follow up of 22 months, pain improved in 94% of cases, pancreatic cancer was diagnosed in one patient and 79% of subjects gained weight. One patient became insulin dependent, one increased his insulin requirements and one had transient steatorrhea, since she could not afford pancreatic enzyme replacement therapy. CONCLUSIONS: The multidisciplinary approach of patients with chronic pancreatitis, with selective use of surgery, may greatly improve their quality of life.

Adolescent↗

PubMed1996

Interrelationships between calcitonin gene-related peptide and sympathoadrenomedullary system: effects of administration of epinephrine and norepinephrine in healthy man.

To investigate the influence of the sympathoadrenomedullary system on the modulation of the circulating levels of calcitonin gene-related peptide (CGRP), the effects of epinephrine (E) and norepinephrine (NE) were studied in 8 normal subjects (4 females and 4 males). The mean basal levels of CGRP in normal subjects were 10.2 +/- 1 pmol/l. After the infusion of E (20 ng/kg per min for 30 min), a significant rise (P < 0.005) in plasma CGRP levels was observed with the expected increases in systolic blood pressure (BP), heart rate (HR) and plasma renin activity (PRA), and decrease in diastolic BP, whereas plasma aldosterone (PA) levels did not significantly change. The infusion of NE (40 ng/kg per min for 30 min) induced an increase in systolic and diastolic BPs, whereas it failed to modify CGRP, HR, PA and PRA. Our data demonstrate that the sympathoadrenomedullary system may modulate CGRP release in man perhaps via the beta-adrenergic pathway. It is likely that the modifications of plasma CGRP levels may be part of the acute vasal response to E.

Adrenal Medulla↗

PubMed1996

Different mechanisms of formation of glutathione-protein mixed disulfides of diamide and tert-butyl hydroperoxide in rat blood.

The mechanisms of glutathione-protein mixed disulfide (GSSP) formation caused by diamide and tert-butyl hydroperoxide were studied in rat blood after in vitro treatment in the 0.3-4 mM dose range. tert-Butyl hydroperoxide formed GSSP, via GSSG, according to the reaction, GSSG + PSH --> GSSP + GSH, whereas diamide reacted first with protein SH groups, giving PS-diamide adducts and then, after reaction with GSH, GSSP. Moreover, after diamide treatment, GSSP patterns were characterized by a much slower or irreversible dose-related return to basal levels in comparison with those observed with tert-butyl hydroperoxide, always reversible. Experiments with purified hemoglobin revealed the existence of a large fraction of protein SH groups which formed GSSP and had a higher reactivity than GSH. Experiments on glucose consumption and role of various erythrocyte enzymes, carried out to explain the inertness of GSSP to reduction after treatment of blood with diamide, were substantially negative. Other tests carried out to confirm the efficiency of the enzymatic machinery of blood samples successively treated with diamide and tert-butyl hydroperoxide, indicated that GSSP performed by diamide was difficult to reduce, whereas those generated by tert-butyl hydroperoxide were reversible as normal. Our results suggest that a fraction of GSSP generated by diamide is different and less susceptible to reduction than that obtained with tert-butyl hydroperoxide.

Animals↗

PubMed1996

Double labelling of subcellular structures with organelle-targeted GFP mutants in vivo.

BACKGROUND: The green fluorescent protein (GFP) of Aequorea victoria is emerging as a unique tool for monitoring complex phenomena such as gene expression and organelle structure and dynamics in living cells. The recent description of GFP mutants with modified spectral properties opens numerous new applications in cell biology. However, the expression and the characteristics of these GFP mutants in living eukaryotic cells have not been verified yet. RESULTS: Here, we demonstrate the usefulness of the GFP mutants for cell biology studies in vivo, by the use of wild-type GFP, a 'bright' GFP mutant (S65T) and a mutant with blue-shifted excitation and emission spectra (Y66H/Y145F). We have constructed two GFP chimeras targeted to mitochondria, mtGFP(S65T) and mtGFP(Y66H/Y145F), with the same strategy used previously for mtGFP. In addition, two GFP chimeras targeted to the nucleus, nuGFP and nuGFP(S65T), were constructed by fusing the wild-type GFP or the (S65T) mutant to the rat glucocorticoid receptor. By co-transfecting mtGFP(Y66H/Y145F) and nuGFP, the nucleus and the mitochondria were visualized simultaneously in living cells. Similarly, mtGFP and mtGFP(Y66H/Y145F) were transfected into different populations of cells, and the events of cellular fusion, and mitochondrial intermixing and/or fusion, were directly monitored. CONCLUSIONS: The successful expression of organelle-targeted GFP mutants in live eukaryotes expands the uses of this fluorescent protein in cell biology, allowing direct access to key biological issues, such as the study of the interactions of different organelles in vivo. These results also open the way to other exciting applications, such as the direct study of protein redistribution and protein-protein interactions in living cells.

Base Sequence↗

PubMed1996

Liver transplantation in HBsAg-positive HBV-DNA--negative cirrhotics: immunoprophylaxis and long-term outcome.

The presence of a positive hepatitis B surface antigen (HBsAg) has been considered a highly questionable indication for orthotopic liver transplantation. We report our experience in the treatment of HBsAg-positive HBV-DNA-negative cirrhotics with liver transplantation, whether or not followed by passive prophylaxis with specific immunoglobulins. Of the 123 cirrhotics who received transplants at our institution since May 1986, 39 (31.7%) were HBsAg positive; of these, 1 was HBV-DNA positive, and 4 were hepatitis Be antigen (HBeAg) positive. Since April 1991, 25 HBsAg-positive HBV-DNA-negative cirrhotics have undergone an original protocol with the periodical intramuscular administration of 5,000 IU of specific immunoglobulins starting in the anhepatic phase and lasting for at least 1 year. There were no differences among cirrhotics in terms of operative mortality and long-term survival with respect to the presence of the HBsAg. Of the 35 HBsAg-positive HBV-DNA-negative patients having a follow-up of 1 month or longer, 12 (34.3%) developed HBsAg recurrence; of them, 4 (33.3%) had received a complete prophylaxis, whereas 8 (66.7%) had not. The recurrence rate was 80% (8 out of 10) in the group of patients who had not received the prophylaxis and 16% (4 out of 25) in the group who had received the prophylaxis (P = .0003). The actuarial recurrence rate in the treated patients was 20.2% and 20.2% after 1 and 3 years, respectively, whereas in the untreated group it was 60.0% and 70.0% (P < .01). The hazard of recurrence of treated patients was reduced to 24.9% compared with untreated patients. Liver transplantation can be performed in HBsAg-positive HBV DNA negative patients without an increase in the operative risk or a worsening of long-term results. Immunoglobulin prophylaxis seems to be effective in preventing hepatitis recurrence after transplantation.

Adolescent↗

PubMed1996

Gastric smooth muscle tumors: diagnostic dilemmas and factors affecting outcome.

We reviewed the 46 gastric stromal tumors that were treated at our institution between 1958 and 1992. The most common presenting symptoms were gastrointestinal bleeding, pain, and fatigue or malaise. The tumors ranged from 4 to 150 mm, with surgery most often being a wedge excision or partial gastrectomy. Abdominal computed tomography was the most specific diagnostic test obtained preoperatively. Factors associated with decreased survival included size >/= 8 cm (p = 0.02), more than 0-3 mitoses per 10 HPF (p < 0. 001), positive margins or unresectability (p = 0.008), and tumor pathologic grade II or more (p = 0.004). These tumors have an unpredictable behavior. Surgical resection with negative margins remains the best therapy, but resection for palliation is sometimes indicated as it can be associated with prolonged survival.

Adult↗

PubMed1996

An evaluation of the antioxidant and antiviral action of extracts of rosemary and Provençal herbs.

Extracts of herbs and spices are increasingly of interest in the food industry because they retard oxidative degradation of lipids. There is also increasing interest in the antiviral activity of plant products. A liquid, deodorized rosemary extract and an oily extract of a mixture of Provençal herbs were tested for antioxidant and antiviral action in vitro. The rosemary extract (Herbor 025) and the extract of Provençal herbs (Spice Cocktail) inhibited peroxidation of phospholipid liposomes with 50% inhibition concentration values of 0.0009% (v/v) and 0.0035% (v/v), respectively. Herbor 025 and the spice cocktail (at 0.2%, v/v) reacted with trichloromethylperoxyl radical with calculated rates of 2.7 x 10(4) s-1 and 1.5 x 10(3) s-1, respectively. The main active components in the herbal preparations, carnosol and carnosic acid, at 0.05% (v/v) react with rate constants of (1-3) x 10(6) M-1 sec-1 and 2.7 x 10(7) M-1 sec-1, respectively. Both extracts show good antioxidant activity in the Rancimat test, especially in lard. Herbor 025 and the spice cocktail inhibited human immunodeficiency virus (HIV) infection at very low concentrations which were also cytotoxic. However, purified carnosol exhibited definite anti-HIV activity at a concentration (8 microM) which was not cytotoxic. Both preparations promoted some DNA damage in the copper-phenanthroline and the bleomycin-iron systems. The two herbal preparations possess antioxidant properties that may make them useful in the food matrix.

Abietanes↗

PubMed1996

Targeting aequorin and green fluorescent protein to intracellular organelles.

Two proteins of Aequorea victoria were molecularly engineered and produced in mammalian cells, in order to serve as specific reporters of subcellular microenvironments. Aequorin (AEQ), a Ca(2+)-sensitive photoprotein, was successfully targeted to three intracellular locations: cytosol, nucleus and mitochondria. The recombinant apoprotein, reconstituted into active AEQ by the addition of the prosthetic group to the culture medium, allows the direct measurement of [Ca2+] within those compartments, thus directly addressing questions of large biological interest. The same approach was utilized for the green fluorescent protein (GFP) for specific labelling, in vivo, of the various subcellular structures. GFP was targeted to mitochondria: the recombinant protein, strongly fluorescent in a highly reducing environment, provides a powerful tool for visualizing these organelles in living cells, and may represent the prototype of a new family of intracellularly targeted fluorescent probes.

Aequorin↗

PubMed1996

Activation of cytokine genes during primary and anamnestic immune response to inactivated c. albicans.

Recent evidence suggests that after repeated stimulations with inactivated C. albicans (CA) cells, CD2F1 mice respond with a cytokine pattern typical of T-helper 1 (ThI) subset development. The purpose of this study was to analyse the sequence of immunological events which, soon after priming mice with CA, lead to the development of primary and anamnestic response. A comprehensive kinetics analysis of cytokine mRNA expression was performed by Northern blot assay, in peritoneal exudate cells (PEC), at different phases of immune response to CA: after priming (one i.p. injection of 2 x 10(7) CA cells mouse), during development of the primary immune response (five progressive CA i.p. injections over a 2-week period) and in the anamnestic response (CA booster 30 days after the primary response). In vitro assays were performed 2 and 24 hr after every CA stimulation. The response to CA priming was characterized by an early and high expression of interleukin-2 (IL-2) and IL-1 beta mRNAs At 24hr. IL-2 mRNA was still at a high level, while IL-1 beta had greatly decreased. A weak expression of IL-10 was only induced at 2 hr. whereas IL-12 p40 subunit, interferon-7 (IFN-7) IL-4 and IL-5 mRNAs were undetectable. In this phase no in vitro proliferative response of PEC to CA was observed, whereas a significant natural killer (NK) activity was induced. From the second CA injection, the IFN-7 mRNA was already induced at 2 hr. Its expression level increased progressively with the number of CA injections persisting up to 24 hr after the fifth stimulation. A progressive increase of IL-2 mRNA expression was also induced whereas IL-1 beta and IL-10 mRNAs were always transiently expressed at 2 hr at levels similar to those observed after the priming. IL-12 p40 subunit. IL-4 and IL-5 mRNAs were never detectable. The expression of this selected cytokine pattern typical of Thl response was correlated with the development of CA-specific T lymphocytes as confirmed by the in vitro proliferative response of CA-5d-induced PEC to CA. NK activity also increased progressively with the number of CA injections and after the fifth stimulation lymphokine-activated killer (LAK) activity was also induced. The anamnestic response to CA was characterized by a very quick induction of high levels of IL-2, II N-gamma and IL-1 beta mRNAs. IL-2 and IFN-gamma mRNAs remained high up to 24 hr while IL-1 beta mRNA decreased strongly. A weak, transient expression of IL-10 mRNA was induced at 2 hr whereas the IL-12 p40 subunit, IL-4 and IL-5 mRNAs were not detectable. The presence of CA-specific memory lymphocytes was confirmed by the in vitro specific proliferative response of PEC to CA. CA booster caused also a very rapid and high level of NK/LAK activation. In conclusion, these results indicate that CA is able to progressively trigger differential on of the Th1 subset which develops in the absence of IL-12, and that Th memory cells retain the same selected Th1 cytokine profile developed in the primary immune response.

Animals↗

PubMed1996

Activity inhibition of cytolytic lymphocytes by omeprazole.

This study examined the in vitro effect of omeprazole (OM) on various types of murine cytocidal lymphocytes. The results show that OM caused a strong inhibition of basal natural killer (NK) activity in spleen cells (SC) from untreated CD2F1 mice; in peritoneal exudate cells and SC activated in vivo by injection of maleic anhydride divinyl ether 1,2-copolymer (MVE-2) or inactivated Candida albicans (CA); in lymphokine-activated killer (LAK) activity generated in vitro from splenocytes cultured with rhIL-2 and in allo-specific cytotoxic lymphocyte-mediated lysis generated in vitro. A significant inhibition of cytotoxic activity of all types of effector cells after 30 min incubation was already induced by OM at 1 x 10(-3) M concentration, after 1 h incubation at 5 x 10(-4) M and after 4 h incubation at 1 x 10(-4) M OM. Complete inhibition of lytic activity was obtained after 4 h incubation of effector cells with 1 x 10(-3) M OM. No inhibitory effect was observed at 5 x 10(-5) M OM concentration. Indomethacin did not abrogate the OM inhibitory effect on NK/LAK activity, suggesting that prostaglandins are not involved in the process leading to suppression of cytocidal activity. When effector cells were incubated with OM in presence of rhIL-2 (500 U/ml), the cytokine failed to antagonize the inhibitory effect of the drug. On the contrary, if OM pretreated cells were incubated with rhIL-2 for a further 18 h after drug removal, this cytokine was able to restore NK activity, but only when NK inhibition was incomplete. These results demonstrate for the first time that in vitro OM causes a rapid, strong effect on various types of cytotoxic lymphocytes ranging from cytotoxicity inhibition to irreversible cell damage.

Animals↗

PubMed1996

Motor recovery after stroke. Morphological and functional brain alterations.

The aim of this study was to evaluate the relationships of morphological and CBF patterns with both the severity and the evolution of the motor deficit in the late phase of stroke and, in particular, to identify morphological and/or functional brain alterations associated with a persistent severe motor deficit or a poor, delayed motor recovery. We analysed CT/MRI and single photon emission tomography (SPET) findings from 37 patients studied in the chronic phase of stroke (mean duration +/- SD = 3.6 +/- 1.6 months), whom we were able to follow clinically for a period of 3 months. The eventual degree of motor recovery correlated significantly (negatively) with the time since stroke at entry, but not with the severity of neurological impairment at entry. The volume, side and location (cortical or subcortical) of the infarct did not correlate with either the severity or the evolution of the motor deficit. Patients with a CT/MRI lesion of the parietal lobe (n = 8) showed a more severe motor deficit than those with other cortical locations. The severity of the motor deficit correlated significantly (negatively) with CBF values in the supplementary motor area (SMA) and parietal areas of the damaged hemisphere, and in the contralateral undamaged primary motor cortex. The degree of motor improvement correlated significantly (positively) with CBF values in the contralateral undamaged thalamus, lentiform and caudate nuclei, and premotor cortex. In the late phase of stroke, the severity of the motor deficit may be positively associated with the functional impairment of associative parietal and frontal areas of the damaged hemisphere. The functional impairment of the basal ganglia-frontal network in the undamaged hemisphere seems to be related to a poor, delayed motor recovery.

Aged↗

PubMed1996

The importance of different atrioventricular delay for left ventricular filling in sequential pacing: clinical implications.

We assessed the influence and clinical consequences of different AV delay on ventricular filling in 30 patients (mean age 60 +/- 5 years) who had DDD pacemakers for AV block. All 30 patients presented a normal ejection fraction, but in 18 cases (Group I), an echo-Doppler examination revealed ventricular hypertrophy (mean end-diastolic wall thickness of 1.4 +/- 0.16 cm, LV mass index 155 +/- 17 g/m2), and an abnormal relaxation pattern (isovolumetric relaxation time = 124.72 +/- 11.82; early to late peak velocity = 0.6 +/- 0.03; deceleration time = 296.83 +/- 34.02 ms). Group II included the remaining 12 patients who had a normal filling pattern. In all 30 patients, the pattern was reassessed following modification of the AV delay (200, 150, 100, and 75 ms). Patients at baseline (AV delay of 200 ms) also underwent an exercise test with determination of respiratory gas exchange. In Group I, 13 (72.5%) patients were classified as Weber class B (VO2 Max 16.8 +/- 1.7 mL/min per kg); and 5 (27.5%) were Class A (VO2 Max 22.5 +/- 1.4 mL/min per kg). In Group II, all 12 patients were classified as Weber Class A. In Group II, changes in AV delay caused no consistent variations in filling pattern, and therefore AV delay was not modified. In Group I patients, since reduction to 100 ms resulted in normalization of the filling pattern, the AV delay was programmed to 100 ms. A graded exercise test repeated after 6 months' follow-up showed an improved Weber class in 13 patients (from B to A) and greater VO2 Max in the remaining five already in Class A. We concluded that, in sequential paced patients with normal ejection fraction but abnormal relaxation pattern, modification in AV delay can induce normalization of filling and improvement in cardiac functional capacity.

Aged↗

PubMed1996

Effect of a reduced vitamin K supplementation on prothrombin time in prematures and high-risk neonates.

Recommendations for vitamin K supplementation were recently changed to 3 x 1 mg orally in healthy term neonates and 0.2 mg parenterally in prematures and high-risk neonates. Prothrombin times (PT) at reduced vitamin K doses (120 patients, 170 samples) during the first 6 weeks of life were below 40% in 6 patients only; all low PTs were unrelated to vitamin K. In the remaining patients, median PT was 100%; 79% of patients had values above 70%. PT was related to birthweight, gestational age and age. There was no decrease over the observation period. Following reduced oral and parenteral vitamin K regimens PTs were well within published reference values for neonates given larger amounts of vitamin K.

Administration, Oral↗

PubMed1996

Hepatic branch vagotomy enhances feeding in response to centrally elicited glucose deprivation in rats.

Intracerebroventricular (I.C.V.) administration of 2-deoxy-D-glucose (2-DG) produces glucose deprivation-induced ('glucoprivic') feeding and sympathoadrenal activation. To find out whether peripheral mechanisms modulate centrally elicited glucoprivic feeding the effect of hepatic branch vagotomy (HBV) compared with sham vagotomy (SV) on the feeding response to I.C.V.-injected 2-DG (1.2 or 2.4 mg per rat) was tested in rats fed a fat-enriched diet (18% fat). 2-DG was injected into the lateral ventricle 1 h after after dark onset, at light onset or 6 h after light onset of the 12 h light-12 h dark cycle. Apart from one (1.2 mg 2-DG injected 1 h after dark onset) out of six experiments, HBV enhanced glucoprivic feeding. This finding is consistent with the assumption that centrally elicited glucoprivic feeding is antagonized by peripheral stimuli signalled to the brain through the hepatic vagus branch.

Animals↗

PubMed1996

Usefulness of 123I-metaiodobenzylguanidine (MIBG) scintiscan in the diagnosis of juxta-adrenal schwannoma.

The adrenal scintiscan with 123I-metaiodobenzylguanidine (MIBG), a reliable morphofunctional technique to evaluate catecholamine turnover in adrenal tumors, can be a useful method to investigate adrenal incidentalomas with arterial hypertension. A male patient, 44 yr old with diabetes, unstable arterial hypertension, and sudden paroxysms of tachycardia is described. The presence of a disomogeneous right juxta-adrenal neoplasm with calcifications was evidenced with ultrasound tomography and confirmed by computerized tomography (CT) scan. Adrenal 123I-MIBG scintiscan revealed a unilateral uptake at level of the right juxta-adrenal region, sized similarly to the neoplasm previously evidence by CT scan. Histological findings of the surgically removed neoplasm were consistent with an ancient schwannoma. Apart from pheochromocytomas, the MIBG uptake is commonly reported in neuroblastomas. In neuroblastoma, a bidirectional process of transdifferentiation has been previously reported in vitro between two coexistent cells: cells with specific uptake system for norepinephrine, with 123I-MIBG uptake capability, and cells oriented toward schwann/melanocytic line. The evidence of in vivo MIBG uptake in our schwannoma may be caused by the same possible phenotypic interconversion of above mentioned cell types. In conclusion, the presence of adrenal tumors with MIBG uptake capability, apart from pheochromocytomas, neuroblastomas, ganglioneuroblastomas, and ganglioneuromas, must be considered in the diagnosis of adrenal tumors.

3-Iodobenzylguanidine↗

PubMed1996

Evidence for androgen receptor gene expression in human thyroid cells and tumours.

Androgen-binding activity has been identified in normal and pathological thyroids, but evidence for the expression of the canonic androgen receptor (AR) in the thyroid has not been provided so far. In this study we have used reverse transcription (RT)-PCR to examine RNA expression of the canonic AR gene in human thyroid tissues, in primary cultures of human thyrocytes and in a variety of neoplastic thyroid cell lines (NPA, TPC and WRO). An AR cDNA fragment with the expected size of 262 bp was detected in normal tissues and cultured thyrocytes as well as in neoplastic cell lines, demonstrating that the gene for AR is indeed expressed in thyroid follicular cells. Immunocytochemical analysis revealed the presence of the AR protein in cancer cell lines and androgen treatment increased nuclear positivity to AR. In a survey of 35 thyroid tissues AR cDNA was detected in all the non-neoplastic samples (6 normal and 3 goitrous) and in 19 of 26 neoplastic samples. AR cDNA was not detected in 4 of the 9 follicular adenomas and in 3 of the 12 papillary carcinomas. AR was revealed by immunohistochemistry in 1 of 2 normal thyroids, in 1 goiter and in 1 of 2 neoplastic thyroids. These findings show the presence of the canonic AR in the human thyroid.

Base Sequence↗

PubMed1996

Inhibitory effect of dihydrotestosterone on human thyroid cell growth.

Sex steroid-binding activities have been identified by several authors in normal and pathological thyroids and the expression of the canonic androgen receptor (AR) has recently been demonstrated in human thyroid follicular cells. In order to assess what influence, if any, androgen exposure has on thyroid cell growth, the effect of dihydrotestosterone (DHT) on [3H]thymidine (thy) incorporation and cell proliferation was investigated in thyroid follicular cells in vitro. In a primary culture of goitrous cells, DHT induced a significant reduction of [3H]thy incorporation at concentrations ranging from 10(-12) to 10(-8) M, with a more pronounced effect at 10(-9) M. At this concentration, the inhibitory effect was evident after both 24 and 48 h of treatment and in various types of primary thyroid cell cultures. In goitrous cells, the DHT-induced decrease of [3H]thy was associated with a reduction of expression of the proliferation-associated nuclear Ki-67 antigen, a protein commonly used to assess cell growth fraction. In TPC cells, an AR-positive thyroid papillary carcinoma cell line, DHT at concentrations between 10(-12) and 10(-8) M significantly decreased the growth rate. DHT (10(-9) M) produced an approximately 50-60% inhibition of cell proliferation and the antiandrogen cyproterone acetate was capable of reversing such effects. The DHT-induced reduction of TPC cell proliferation was associated with a significant reduction of c-myc RNA levels. Thyroperoxidase mRNA levels and thyroglobulin production were not reduced by androgen in primary cultures of goitrous cells. In conclusion, our results indicated that androgens may have a role in this gland by reducing the proliferation, but not the function, of follicular cells.

Blotting, Northern↗