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Biomedical subjects

M Fodor

Publications and source records attributed to M Fodor.

At least 19 recordsLinked to original sources
PubMed2006

Pituitary mRNA expression of the growth hormone axis in the 1-year-old intrauterine growth restricted rat.

Intrauterine growth restriction (IUGR) is one of the major causes of short stature in childhood. Abnormalities in the growth hormone (GH) axis have frequently been observed in children who are born intrauterine growth restricted and GH treatment is effective to improve final height. However, the way that the GH axis is involved is not fully understood. Previously, when investigating the effect of IUGR on the central somatotrophic axis, a hypothalamic effect was discovered with elevated somatostatin and decreased neuropeptide Y mRNA expression levels, whereas serum GH and insulin-like growth factor I (IGFI) were unaltered. These findings were thought to indicate a hypothalamic alteration of the GH axis due to IUGR, probably to compensate pituitary output, thereby normalising peripheral values of GH and IGFI. Therefore, the present study aimed to evaluate the effect of IUGR on the pituitary GH axis in this rat model. Pups from rats that underwent bilateral uterine artery ligation at day 17 of pregnancy were studied. Pituitary glands were collected from 1-year-old offspring for quantitative measurements of GH, GH-receptor (GH-R), GH-releasing hormone receptor (GHRH-R), somatostatin receptor subtype 2 and 5, IGFI and IGFI receptor mRNA levels using a real-time reverse transcriptase-polymerase chain reaction. In addition, liver GH-R and IGFI mRNA expression levels were measured and a radioimmunoassay was performed to determine serum IGFI levels. In the IUGR rat, levels of pituitary GH, GH-R and GHRH-R relative gene expression (RGE) were increased. No differences were found in the RGE level of all other pituitary growth factors, liver GH-R and IGFI, and serum IGFI concentration between IUGR and control rats. The present data show that intrauterine growth failure leads to changes in the pituitary that might counterbalance the effects found previously in the hypothalamus.

Adaptation, Physiological↗
PubMed2005

Cardiac dysfunction induced by high-fat diet is associated with altered myocardial insulin signalling in rats.

AIMS/HYPOTHESIS: Diabetic cardiomyopathy (DCM) is common in type 2 diabetes. In DCM, insulin resistance may alter cardiac substrate supply and utilisation leading to changes in myocardial metabolism and cardiac function. In rats, exposure to excessive alimentary fat, inducing a type 2 diabetic phenotype, may result in myocardial insulin resistance and cardiac functional changes resembling DCM. MATERIALS AND METHODS: Rats received high-fat (HFD) or low-fat (LFD) diets for 7 weeks. Prior to killing, insulin or saline was injected i.p. Contractile function and insulin signalling were assessed in papillary muscles and ventricular lysates, respectively. RESULTS: Fasting and post-load blood glucose levels were increased in HFD- vs LFD-rats (all p < 0.02). Mean heart weight, but not body weight, was increased in HFD-rats (p < 0.01). HFD-hearts showed structural changes and triglyceride accumulation. HFD-muscles developed higher baseline and maximum forces, but showed impaired recovery from higher workloads. Insulin-associated modulation of Ca2+-induced force augmentation was abolished in HFD-muscles. HFD reduced insulin-stimulated IRS1-associated phosphatidylinositol 3'-kinase activity and phosphorylation of protein kinase B, glycogen synthase kinase-3beta, endothelial nitric oxide synthase, and forkhead transcription factors by 40-60% (all p < 0.05). Insulin-mediated phosphorylation of phospholamban, a critical regulator of myocardial contractility, was decreased in HFD-hearts (p < 0.05). CONCLUSIONS/INTERPRETATION: HFD induced a hypertrophy-like cardiac phenotype, characterised by a higher basal contractile force, an impaired recovery from increased workloads and decreased insulin-mediated protection against Ca2+ overload. Cardiac dysfunction was associated with myocardial insulin resistance and phospholamban hypophosphorylation. Our data suggest that myocardial insulin resistance, resulting from exposure to excessive alimentary fat, may contribute to the pathogenesis of diabetes-related heart disease.

Animals↗
PubMed2005

Dendritic cell immunizations alone or combined with low doses of interleukin-2 induce specific immune responses in melanoma patients.

Dendritic cell (DC)-based therapy has proved to be effective in patients with a variety of malignancies. However, an optimal immunization protocol using DCs and the best means for delivering antigens has not yet been described. In this study, 20 patients with malignant melanoma in stages III or IV were vaccinated with autologous DCs pulsed with a melanoma cell lysate, alone (n = 13) or in combination with low doses of subcutaneous (s.c.) interleukin (IL)-2 injections (n = 7), to assess toxicity, immunological and clinical responses. Monocyte-derived DCs were morphological, phenotypic and functionally characterized in vitro. Peripheral blood mononuclear cells (PBMC), harvested from patients either prior to and after the treatment, were analysed using enzyme-linked immunosorbent spot (ELISPOT). After vaccination, 50% of the patients tested (seven of 13) from the first group and (three of seven) from the second, showed an increase in interferon (IFN)-gamma production in response to allogeneic melanoma cell lines but not to controls. Four of five tested human leucocyte antigen (HLA)-A2(+) patients with anti-melanoma activity also showed specific T cell responses against peptides derived from melanoma-associated antigens. Delayed type IV hypersensitivity reaction (DTH) against melanoma cell lysate was observed in six of 13 patients from the group treated with DC vaccines only and four of seven from the group treated with the combination of DCs and IL-2. Significant correlations were found between DTH-positive responses against tumour lysate and both disease stability and post-vaccination survival on the stage IV patients. There were no toxicities associated with the vaccines or evidence of autoimmunity including vitiligo. Furthermore, no significant enhancement was observed as a result of combining DC vaccination with IL-2. Our data suggest that autologous DCs pulsed with tumour lysate may provide a standardized and widely applicable source of melanoma specific antigens for clinical use. It is safe and causes no significant side effects and has been demonstrated to be partially efficient at triggering effective anti-melanoma immunity.

Antigen Presentation↗
PubMed2004

Ligation of the uterine artery and early postnatal food restriction - animal models for growth retardation.

Intrauterine growth restriction (IUGR) is one of the major causes of short stature in child- and adulthood. The cause of IUGR is unknown, however, an impaired uteroplacental function during the second half of human pregnancy might be an important factor, by affecting the programming of somatotropic axis and leading to postnatal growth failure into adulthood. Two rat models with perinatally induced growth retardation were used to examine the long-term effects of perinatal insults on growth. IUGR rats were prepared from pregnant dams, with a bilateral uterine artery ligation at day 17 of their pregnancy. Since the rat is relatively immature at birth, an early postnatal food restriction model was included as another model to broaden the time window of sensitive period of organogenesis. An individual growth curve was calculated of each animal (n = 813). From these individual growth curves the predicted growth curve for each experimental group was calculated by multilevel analysis. The proposed mathematical model allows us to estimate the growth potentials of these rat models with precision and could provide basic information to investigate the relationships among a number of other variables in future studies. Furthermore, we concluded that both pre- and early postnatal malnutrition leads to irreversible slowing down of postnatal growth.

Animals↗
PubMed2004

[Refraction and visual acuity after laser coagulation treatment for retinopathy of prematurity in stage 3+].

PURPOSE: Correlations between myopia < or =-4.0 D, birth weight, gestation age at birth, extension of laser photocoagulation and mild posterior pole changes were assessed in eyes of 1-year-old children who underwent laser treatment for stage 3+ retinopathy of prematurity (ROP). In addition the relationship between best-corrected visual acuity (VA) and mild posterior pole alterations was evaluated at 3 years of age. PATIENTS AND METHODS: Patients who underwent argon or diode laser photocoagulation between 1996 and 2000 for ROP 3+ disease were analyzed in this retrospective study. Cycloplegic refraction was determined in 72 eyes of 1-year old patients ( n=39). At 3 years of age cycloplegic refraction was measured in 36 eyes of 19 patients, and visual acuity was determined in 25 eyes of 13 children. RESULTS: Myopia of < or =-4.0 D significantly correlated only with mild posterior pole changes (i.e. clinically significant dragging of the temporal vessels of the retina or macular heterotopia, p=0.001). The correlation was significant between a VA reduction to <0.8 and mild posterior pole alterations ( p=0.014). CONCLUSIONS: The prevalence of myopia < or =-4,0 D and visual acuity <0.8 appears to be increased even with mild posterior pole changes. Birth weight does not seem to be significant factor in the prevalence of myopia < or =-4.0 D following laser coagulation of stage 3 threshold ROP.

Child, Preschool↗
PubMed2001

Are POMC neurons targets for sex steroids in the arcuate nucleus of the rat?

Testosterone alters the expression of proopiomelanocortin (POMC) mRNA in the neurons of the arcuate nucleus. While observations suggest that both estrogen and androgen receptors (AR) can mediate this action, only a negligible number of POMC neurons has previously been shown to contain estrogen receptor (ER)-alpha. To determine whether the putative action of testosterone is mediated via ER-beta or AR we double immuno- labeled hypothalamic sections from colchicine-pretreated male rats. Only few cells were immunostained for ER-beta and they were never found to co-localize POMC. In spite of the overlap in the anatomical distribution, only 3% of POMC cells appeared to contain AR. These results suggest that sex steroids have an indirect effect on most POMC neurons.

Animals↗
PubMed2001

A phase II study of gemcitabine in gallbladder carcinoma.

BACKGROUND: Due to the high mortality rates from gallbladder carcinoma in Chile, we conducted a phase II trial to test the efficacy and safety of gemcitabine in patients with locally advanced or metastatic gallbladder carcinoma. PATIENTS AND METHODS: From January 1998 to February 2000, 26 patients with metastatic or unresectable gallbladder carcinoma and no prior chemotherapy received gemcitabine 1,000 mg/m2 over 30 minutes weekly for three weeks followed by a week of rest. RESULTS: Patients received a median of 4.2 cycles (range 1-10). Out of the 25 patients whose response could be evaluated, 9 went into partial remission, an overall response rate of 36% (95% confidence interval (95% CI): 17.1% to 57.9%). In six (25.0%) patients, the cancer remained stable, and in 10 (40%) it progressed. Median survival time was 30 weeks (range 7-80+. Hematological toxicities were mild, with no cases of febrile neutropenia or hemorrhage. However, four and one patient(s) had grades 1-2 and 3-4 neutropenia, respectively, and two patients had grade 2 thrombocytopenia. Nine patients experienced grade 1-2 nausea/vomiting, but were able to continue treatment. There were no toxic deaths. CONCLUSIONS: In this phase II trial, gemcitabine is an active chemotherapy in metastatic or inoperable gallbladder carcinoma, with a manageable toxicity profile.

Adult↗
PubMed2001

Absence of androgen receptor in the growth hormone releasing hormone-containing neurones in the rat mediobasal hypothalamus.

Growth hormone (GH) secretory patterns are influenced by gonadal steroids, at least in part, through modulation of hypothalamic somatostatin and GH releasing hormone (GHRH) secretion. In the adult male rat, testosterone appears to stimulate somatostatin gene expression by acting directly on androgen receptors in somatostatin neurones. The mechanism by which gonadal status influences hypothalamic GHRH gene expression is less clear. Gonadectomy reduces GHRH mRNA expression in rats, and this reduction can be prevented by the administration of testosterone or partly by a nonaromatizable androgen. While these observations suggest that androgen receptors mediate the actions of gonadal steroids on GHRH gene expression, they do not provide any information about the location of the androgen receptors involved in this process. To determine whether GHRH neurones themselves express androgen receptors, we double immunolabelled hypothalamic sections from colchicine-pretreated male rats. Although there was an overlap in the anatomical distribution of GHRH and androgen receptor-containing cell bodies, none of the nearly 900 GHRH immunolabelled cells we examined in each mediobasal hypothalamus appeared to contain androgen receptors. These results suggest that GHRH-expressing neurones are not direct targets for androgens and therefore the effects of testosterone on GHRH gene expression must be produced indirectly by some other neural or endocrine intermediary process.

Animals↗
PubMed2001

Sex differences in androgen receptors of the human mamillary bodies are related to endocrine status rather than to sexual orientation or transsexuality.

In a previous study we found androgen receptor (AR) sex differences in several regions throughout the human hypothalamus. Generally, men had stronger nuclear AR immunoreactivity (AR-ir) than women. The strongest nuclear labeling was found in the caudal hypothalamus in the mamillary body complex (MBC), which is known to be involved in aspects of cognition and sexual behavior. The present study was carried out to investigate whether the sex difference in AR-ir of the MBC is related to sexual orientation or gender identity (i.e. the feeling of being male or female) or to circulating levels of androgens, as nuclear AR-ir is known to be up-regulated by androgens. Therefore, we studied the MBC in postmortem brain material from the following groups: young heterosexual men, young homosexual men, aged heterosexual castrated and noncastrated men, castrated and noncastrated transsexuals, young heterosexual women, and a young virilized woman. Nuclear AR-ir did not differ significantly between heterosexual and homosexual men, but was significantly stronger than that in women. A female-like pattern of AR-ir (i.e. no to weak nuclear staining) was observed in 26- to 53-yr-old castrated male-to-female transsexuals and in old castrated and noncastrated men, 67--87 yr of age. In analogy with animal studies showing strong activational effects of androgens on nuclear AR-ir, the present data suggest that nuclear AR-ir in the human MBC is dependent on the presence or absence of circulating levels of androgen. The group data were, moreover, supported by the fact that a male-like AR-ir (i.e. intense nuclear AR-ir) was found in a 36-yr-old bisexual noncastrated male-to-female transsexual and in a heterosexual virilized woman, 46 yr of age, with high levels of circulating testosterone. In conclusion, the sexually dimorphic AR-ir in the MBC seemed to be clearly related to circulating levels of androgens and not to sexual orientation or gender identity. The functional implications of these alterations are discussed in relation to reproduction, cognition, and neuroprotection.

Adult↗
PubMed2001

[Deciduosis of the appendix as cause of acute abdomen in pregnancy].

Ectopic decidua reaction or deciduosis is a physiological phenomenon of pregnancy due to a progesterone induced metaplasia of the pluripotential cells of the subcelomic mesenchyma. Usually it is an incidental finding that has not been associated with clinical symptoms. Isolated cases of ectopic decidua have been reported with symptoms simulating appendicitis. We are reporting a case of deciduosis localized in the appendix with abdominal pain during the last period of pregnancy.

Abdominal Pain↗
PubMed2000

Sex differences in the distribution of androgen receptors in the human hypothalamus.

The present study reports for the first time the distribution of androgen receptor immunoreactivity (AR-ir) in the human hypothalamus of ten human subjects (five men and five women) ranging in age between 20 years and 39 years using the antibody PG21. Prolonged postmortem delay (72:00 hours) or fixation time (100 days) did not influence the AR-ir. In men, intense nuclear AR-ir was found in neurons of the horizontal limb of the diagonal band of Broca, in neurons of the lateromamillary nucleus (LMN), and in the medial mamillary nucleus (MMN). An intermediate nuclear staining was found in the diagonal band of Broca, sexually dimorphic nucleus of the preoptic area, paraventricular nucleus, suprachiasmatic nucleus, ventromedial nucleus, and infundibular nucleus, whereas weaker labeling was found in the bed nucleus of the stria terminalis, medial preoptic area, dorsal and ventral zones of the periventricular nucleus, supraoptic nucleus, and nucleus basalis of Meynert. In most brain areas, women revealed less staining than men. In the LMN and the MMN, a strong sex difference was found. Cytoplasmic labeling was observed in neurons of both sexes, although women showed a higher variability in the intensity of such staining. However, no sex differences in AR-ir were observed in the bed nucleus of the stria terminalis, the nucleus basalis of Meynert, or the islands of Calleja. Species differences and similarities of the AR-ir distribution are discussed. The present results suggest the participation of androgens in the regulation of various hypothalamic processes that are sexually dimorphic.

Adult↗
PubMed1999

Decussations of the descending paraventricular pathways to the brainstem and spinal cord autonomic centers.

Decussations of descending fibers of the hypothalamic paraventricular nucleus (PVN) were investigated by using Phaseolus vulgaris-leucoagglutinin (PHA-L) in intact and brainstem-operated rats. Fibers descend ipsilaterally along the brainstem and spinal cord and decussate at four levels: 1) Supramamillary decussations (SM). PVN fibers reach this area through the lateral hypothalamus and along the third ventricle in the dorsal hypothalamus. In the posterior hypothalamus some fibers crossover in the SM and terminate in the supramamillary region bilaterally. 2) Pontine tegmentum. PVN fibers run in the lateral part of the tegmentum arching to the basis of the pons. Some fibers crossover under the fourth ventricle. The locus ceruleus and the Barrington's nucleus receive bilateral innervation with ipsilateral dominance. 3) Commissural part of the nucleus of the solitary tract (NTS). The major crossover of PVN fibers is found here. The decussated fibers form a dense network here, and loop rostralward to innervate the entire NTS. A midsagittal knife-cut through the NTS eliminated paraventricular-fibers on the contralateral side. Synaptic contacts between PHA-L-labeled boutons and tyrozine hydroxilase-positive neurons were verified in the NTS. The caudal ventrolateral medulla also receives bilateral innervation. 4) Lamina X of the thoracic spinal cord. Paraventricular fibers enter the lateral funiculus ipsilaterally and innervate the intermediolateral cell column (IML). Some fibers cross the midline ventral and dorsal to the central canal running to the contralateral IML, at the level of the decussation. Our results demonstrated that paraventricular projections form a continuous descending pathway on their side of origin, and provide crossover fibers which may terminate segmentally without forming long tracts after crossover.

Animals↗
PubMed1998

Interrelations between hypothalamic somatostatin and proopiomelanocortin neurons.

Somatostatin receptors were visualized by [125I]-Tyr0-DTrp8-somatostatin radioautography on 35% of arcuate neurons containing proopiomelanocortin (POMC) mRNA, as identified by in situ hybridization using a [35S] labelled riboprobe on 5 microm-thick consecutive sections. Furthermore, double immunohistochemical staining revealed contacts of beta-endorphin or alpha-MSH containing fibres with a majority of somatostatin perikarya in the anterior hypothalamic periventricular nucleus. Taken together, these data indicate that hypothalamic somatostatin and POMC neurons are interconnected. The results are discussed in term of intrahypothalamic control of GH secretion.

Animals↗
PubMed1998

[MALT lymphoma of the bladder: report of a case].

Primary malignant lymphomas of the bladder are infrequent. We report a 70 year old woman presenting with hematuria, dysuria, malaise and a 5 kg weight loss. Pelvic ultrasound examination showed a 8 x 8 x 8 cm solid and cystic mass adjacent to the bladder and uterus. Cystoscopic biopsy disclosed a low grade B cell non Hodgkin lymphoma. She was treated with 6 cycles of chemotherapy with disappearance of the mass. Two years after admission, the patient is free of disease.

Aged↗
PubMed1998

[Analgesic response and secondary effects in patients with osteoblastic metastasis, treated with Samarium 153 ethylenediaminotetramethylenephosphate].

BACKGROUND: Samarium153 EDTMP, a beta and gamma emitter, is used in the palliative therapy of painful bone metastases. AIM: To evaluate the analgesic effects and myelotoxicity of Samarium153 EDTMP in patients with prostate, breast and renal carcinoma. PATIENTS AND METHODS: Twenty patients with bone metastases (11 males), aged 65 years old as a mean, received a 1 to 2 mCi/kg intravenous dose of Samarium153 EDTMP, produced in Chile. Patients were followed thereafter during 4 to 40 weeks. Pain was assessed using a visual analogue scale. RESULTS: Pain decreased from a score of 6.4 prior to treatment, to 2.7 at the fourth week of therapy and the effect lasted a mean of 12.5 weeks. Myelotoxicity was observed in 68% of cases (WHO stage I in 21%, stage II in 37%, stage III in 11% and no patients in stage IV). Platelets were the most affected series and neutrophils the least affected. Cell counts returned to normal between the sixth and eighth week. Seventy nine percent of patients decreased their basal analgesic therapy at the sixth week and 88% did so at the eighth week. Forty one percent of these patients discontinued all analgesics. CONCLUSIONS: Samarium153 EDTMP is effective in the treatment of pain in patients with bone metastases and its myelotoxicity is low to moderate. It should be considered as a therapy for this type of pain, with the precaution of performing periodical bood counts.

Adult↗