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Biomedical subjects

A Notaro

Publications and source records attributed to A Notaro.

5 recordsLinked to original sources
PubMed2003

Verapamil inhibits interleukin-6 and vascular endothelial growth factor production in primary cultures of keloid fibroblasts.

An increased secretion of cytokines and growth factors has been hypothesised to play a role in the abnormal growth of keloid fibroblasts. The aim of this study was to evaluate the effect of the calcium antagonist verapamil on the interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) secretion, as well as on cellular growth, in primary cultures of fibroblasts derived from the central part of keloid lesions. These cells grew faster than peripheral keloid and nonkeloid fibroblasts, and, in long-term cultures, became stratified assuming a three-dimensional structure. Compared with peripheral and nonkeloid fibroblasts, central keloid fibroblasts presented an increased production of both IL-6 and VEGF (P<0.03 and P<0.005, respectively). Verapamil (100 microM) decreased IL-6 and VEGF production (P<0.03 and P<0.005, respectively) in central keloid fibroblasts cultures at 72 h. Moreover, verapamil decreased cellular proliferation by 29% and increased apoptosis to an absolute value of 8%. The results of this study demonstrate that in primary cultures of central keloid fibroblasts verapamil reduces the sustained basal IL-6 and VEGF production and inhibits cell growth; these data may offer the link with the beneficial effect of calcium antagonists on keloid scars in vivo.

Analysis of Variance↗
PubMed2003

Sexual differentiation.

In humans, like as in other mammals, the gonads, the internal genital ducts, and the external genital structures all develop from bipotential embryologic tissues. Male or female phenotype develops through a cascade of processes which initiate with sex determination and follow with sex differentiation. The karyotype (46, XY or 46, XX) of the embryo (genetic sex) determines whether primordial gonad differentiates into a testis or an ovary, respectively (gonadal differentiation). A Y-related gene, SRY, acts as a switch signal for testis differentiation. Testis development process involves several steps controlled by other non-OY-linked genes, such as Wilms tumor gene 1 (WT1), EMX2, LIM1, steroidogenic factor 1(SF-1), SRY box-related gene 9 (SOX9). Since other genes, such as Wnt-4 and DAX-1, are necessary for the initiation of female pathway in sex determination, female development cannot be considered a default process. Hormonal production of differentiated gonads is relevant for differentiation of the internal and external genitalia during fetal life, and for the development of secondary sex characteristics at puberty. Antimullerian hormone (AMH) secreted by Sertoli cells inhibits the development of female internal genitalia (tube, uterus, upper part of vagina); testosterone secreted by Leydig cells induces stabilization of wolffian ducts and development of internal male genitalia. Differentiation of external male genitalia requires the transformation of testosterone to dihydrotestosterone by 5alpha reductase type 2 expressed in genital skin and urogenital sinus. The effects of androgens occur in presence of functional androgen receptor (AR) protein. Mutations of genes coding for steroidogenic enzymes, AMH, AMH receptor, AR and 5alpha reductase are all associated with impairment of sex differentiation and result in genital ambiguity.

Embryonic and Fetal Development↗
PubMed2001

Estrogen receptor beta expression in human prostate tissue.

Estrogen receptor subtype beta (ERbeta) is highly expressed in rat prostate epithelium, but its presence in human prostate needs to be confirmed. Here we investigated the expression of ERbeta in five benign (normal and/or hyperplastic) and 10 malignant (Gleasons' score 2-7) prostate tissue specimens using immunohistochemistry. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissue sections, using a commercially available ERbeta polyclonal antibody developed against the C-terminal amino acid residue. Nuclear ERbeta expression was found in the nuclei of glandular epithelium of benign prostate tissue specimens; faint nuclear ERbeta positivity was also present in a few stromal cells around normal epithelium. Nuclear ERbeta specific immunostaining was undetectable in all prostate cancer sections.

Animals↗
PubMed2001

[Somatostatin receptor genes expression and effects of octreotide on orbital fibroblasts from Graves' ophthalmopathy].

BACKGROUND: Recent data demonstrated that somatostatin (SRIH) analogues octreotide is effective in Graves' ophthalmopathy (GO), but their mechanism of action in GO is still unclear. In this study we investigated the expression of SRIH receptor (sst1-5) genes and the effect of octreotide treatment on primary cultures of fibroblasts established from retroorbital tissue of GO patients and of control subjects. METHODS: Retro-orbital connective tissue was obtained from 10 patients with GO and from 6 control subjects undergoing eye surgery. Fibroblasts were established in MEM with 5-10% FCS. The expression of sst1-5 genes was studied by RT-PCR using specific primers and GAPDH as internal control. Cells were treated with octreotide (10-8M, 10-9M) for 48-72-96 h to evaluate cell growth by MTT, cAMP accumulation by RIA and apoptosis by TUNEL techniques. RESULTS: All primary cultures expressed one or more ssts genes that have a high affinity for the two analogues (class 1 sst). The sst2 transcript was found in 9, sst3 in 5 and sst5 in 8 out of 10 GO cell cultures. sst2 was detected in all 6, and sst3 in 4 of the 6 control cell cultures. Octreotide (10-6 and 10-7M) significantly inhibited cell growth (p<0,01-0,05), significantly decreased forskolin-induced-cAMP accumulation, and determined apoptosis (10-18%). CONCLUSIONS: Our study demonstrated that sst transcripts are expressed and functional in cultured retroorbital fibroblasts. The presence of class 1 sst in GO tissue and the inhibition exerted by octreotide on retroorbital cell growth and activity in vitro may account for the effects of SRIH analogue administration in vivo in GO.

Apoptosis↗