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Biomedical subjects

F Minuto

Publications and source records attributed to F Minuto.

At least 73 records · Page 4Linked to original sources
PubMed1991

EGF in breast cyst fluid: relationships with intracystic androgens, estradiol and progesterone.

The relationship between intracystic levels of epidermal growth factor (EGF) and those of dehydroepiandrosterone sulphate (DHEA-S), delta-4-androstenedione (delta-4-A), 17-beta-estradiol (17-beta-E) and progesterone (PROG) have been studied in 77 breast cyst fluid (BCF) samples. EGF and all tested hormones appeared to be inversely correlated with the intracystic Na+/K+ ratio (p less than 0.001). Consequently, when the BCFs were subdivided according to the Na+/K+ ratio, significantly higher levels of EGF, DHEA-S, delta-4-A, 17-beta-E and PROG were found in Na+/K+ less than 3 BCFs compared with Na+/K+ greater than 3 BCFs (p less than 0.001 in all cases). Strong direct relationships were found among all steroid hormones when they were correlated to one another (p less than 0.001). Intracystic EGF concentration was directly and significantly correlated with each tested hormone (p less than 0.001). However, the relationship between EGF and steroid hormones appeared to be different in the 2 BCF types (Na+/K+ less than 3 or greater than 3).

Adult↗
PubMed1991

Paracrine actions of IGF binding proteins.

The paracrine mode of action for IGFs has been hypothesized on the basis of the finding that these peptides are synthesized ubiquitously. As IGFs circulate in very high concentrations (nearly 1 mg/l) they should have an endocrine function; moreover since the liver seems to be responsible for most of the circulating IGF-I it should be recognized that the basis of the "hormonal" IGF-I residues in the liver, whereas the extrahepatic synthesis provides support for local paracrine or autocrine actions. According to the endocrine hypothesis, the liver, which lacks IGF-I receptors, produces both IGF-I and IGF binding protein (IGFBP) and, possibly, the acid-labile subunit. All these components combine in the circulation, and only free IGF-I or small molecular weight complexes cross the capillary wall and reach the target cells. The paracrine hypothesis is based on the fact that fibroblasts are able to synthesize both IGF peptides and IGFBP, whereas keratinocytes are not, although they possess IGF receptors and are sensitive to IGF action. Since affinity of BP3 (which seems to be produced by peripheral fibroblasts) for IGF-I is higher than that of fibroblasts and, to a lesser degree, of keratinocytes, it is likely that IGF-I released from fibroblasts preferentially binds to BP3; the BP3-IGF-I complex reduces the autocrine effects on fibroblasts and preferentially directs the peptide binding to keratinocytes. The secretion of both IGFs and of IGF carrier proteins has been reported in several neoplastic epithelial cell lines.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Identification of breast cyst subpopulations: biochemical and morphological features.

The concentration of insulin-like growth factor-I (IGF-I) and its relationship to other biochemical parameters of cyst fluids was investigated in 94 cyst fluids of 86 women with gross cystic breast disease. The relationship between the biochemical parameters and the cytological features of breast fluids (presence or absence of apocrine cells) was also studied. IGF-I was detected in all tested fluids, with a concentration 50 to 100 times lower than that found in plasma. IGF-I concentration was higher in cysts with a Na+/K+ ratio greater than 3 (greater than 3) and was inversely related to both dehydroepiandrosterone sulfate (DHEA-S) and epidermal growth factor (EGF) concentration (p less than 0.001). It is suggested that Na+/K+ greater than 3 cysts have a higher permeability to plasma and extracellular fluids compared to Na+/K+ less than 3 cysts. Apocrine cells were found in 78% of Na+/K+ less than 3 fluids as well as in 53% of Na+/K+ greater than 3 fluids. A well-defined relationship was found between the biochemical parameters of breast fluids, but the presence of either IGF-I or EGF was not related to the morphology of breast cysts as assessed by cytological examination.

Biopsy, Needle↗
PubMed1990

Thyroid hormone stimulates the production of insulin-like growth factor I (IGF-I) by immature rat Sertoli cells.

The effects of thyroid hormone on insulin-like growth factor I (IGF-I) production by Sertoli cells isolated from immature rats have been investigated. In Sertoli cells from hypothyroid rats the production of IGF-I was significantly lower than in controls and was greatly stimulated by the administration of triiodothyronine (T3) in vivo. The in vitro addition of physiological doses of T3 (1 nmol/l) significantly increased the production of IGF-I by cultured Sertoli cells indicating a direct action of the hormone on local IGF-I production. Our results suggest the involvement of IGF-I in the thyroid hormone-dependent maturation of testicular function.

Animals↗
PubMed1990

Insulin-like growth factor-I (IGF-I) and IGF-I binding protein in the follicular fluids of growth hormone treated patients.

The presence of GH, insulin-like growth factor-I (IGF-I), epidermal growth factor (EGF), oestradiol (E2) and progesterone (PG) were investigated in the fluids obtained from various ovarian follicles of seven patients in whom the induction of super-ovulation was achieved only after GH (0.1 U/kg BW/day) was added to the gonadotrophin therapy. The follicular fluids of six patients responsive to treatment with gonadotrophin alone served as a control. In patients treated with combined therapy, the results demonstrated the presence in the follicular fluids of GH (M +/- SEM: 8.5 +/- 0.6 mU/l), E2 (771 +/- 38 nmol/l), and PG (16.4 +/- 0.7 pmol/l) in significantly higher concentrations compared to that in control follicles (6.2 +/- 0.8 mU/l, 681 +/- 30 nmol/l, and 14.4 +/- 0.6 pmol/l; P = 0.002, 0.012, 0.0001 respectively). Acid-extractable IGF-I (143 +/- 9 ng/ml) and EGF (3.9 +/- 0.3 ng/ml) concentrations were similar to those of control fluids (124 +/- 10 ng/ml and 2.9 +/- 0.7 ng/ml respectively) and were highly correlated with each other (P less than 0.001), suggesting a stimulatory effect of EGF on the local IGF-I production. A correlation between GH and IGF-I (n = 51, r = 0.36), as well as between IGF-I and PG (n = 48, r = 0.77) and E2 (n = 48, r = 0.55) was evident only in the follicular fluid of GH-treated subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Immunoreactive insulin-like growth factor I (IGF-I) and IGF-I-binding protein content in human thyroid tissue.

We measured immunoreactive insulin-like growth factor I (IGF-I) in extracts of normal and nodular thyroid tissue obtained at surgery from patients with nontoxic goiter. The nodular tissues contained a higher concentration [mean, 279.0 +/- 69.7 (+/- SE) mU/g] than paired normal tissues (115.5 +/- 17.9 mU/g; P = 0.024; n = 12); a difference was evident in all but one patient. Sephadex G-50 gel filtration of tissue extracts revealed two immunoreactive peaks, the first in the void volume of the column, and the second in the elution volume of authentic IGF-I. The first peak was identified as IGF-I-binding protein by sodium dodecyl sulfate-polyacrylamide gel electrophoresis after cross-linking with iodinated IGF-I. Isolated thyroid cell membranes contained high affinity IGF-I-binding sites of similar affinity and numbers in both normal and nodular thyroid tissue. The IGF-I content of six thyroid cancer extracts was higher than that of normal thyroid tissue, but the IGF-I content of thyroid tissue from six patients with Graves' disease and five patients with Hashimoto's thyroiditis was similar to that in normal thyroid tissue. These data suggest that the stimulatory effect of TSH on thyroid cell proliferation could be mediated through IGF-I action and suggest that an increase in IGF-I production could sustain the goitrogenic process.

Adult↗
PubMed1989

Insulin-like growth factor I and daily growth hormone profile in the assessment of active acromegaly.

A poor correlation exists between growth hormone levels and the severity of disease in patients with acromegaly. It has been suggested that insulin-like growth factor I correlates better with the clinical condition thaN GH itself, but the presence of a correlation between GH and IGF-I is still a matter of debate. We therefore studied the fasting concentration of acid-extracted IGF-I and the daily GH profile (at 08.00, 12.00, 16.00, 20.00 h) in 28 acromegalic patients, both in basal condition and at different times after treatment. All patients studied before treatment exhibited a GH mean daily concentration always above 5 micrograms/l (range 5.15-1.47 micrograms/l), and IGF-I values (1.99-6.85 U/l) always above the normal range (0.38-1.90 U/l). During the follow-up after medical, surgical or radiation therapy we did not observe normalization of the IGF-I concentration for a GH day curve value above 5 micrograms/l. Compared with the GH day curve, a single morning GH value was slightly less sensitive and definitely less specific. The analysis of covariance evidenced a good correlation (P less than 0.001) between the GH day curve and IGF-I concentration during the first 6 months of medical as well as during the first year of radiation therapy, and after surgical treatment. Our data indicate that a single determination of acid-extractable IGF-I is as reliable as GH multiple sampling to assess the acromegalic disease activity.

Acromegaly↗
PubMed1989

Prolonged fasting or clonidine can restore the defective growth hormone secretion in old dogs.

Age-related changes in GH secretion were studied in dog. In preliminary experiments, administration of GH-releasing hormone (GHRH-40, 2 micrograms/kg, iv) or the alpha 2-adrenoceptor agonist clonidine (4 micrograms/kg, iv) elicited significantly higher plasma GH rises in 3 to 4 years old than in 10 to 14 years old beagle dogs. The pulsatile patterns of GH secretion in both young and old dogs under baseline conditions and after prolonged fasting or clonidine administration were studied. Samples were taken every 10 min from 09.00 to 15.00 h from five young and five old dogs of both sexes. Under baseline conditions, GH peak frequency, total peak area, and integrated GH secretion were significantly lower in old than in young dogs. In old dogs, 5-day complete fasting or 14-day clonidine administration (75 micrograms/dog, po, twice daily) increased the frequency and amplitude of spontaneous GH bursts, the total peak area, and the integrated GH secretion. After either stimulus, the GH secretory pattern was quantitatively and qualitatively indistinguishable from that of young dogs under baseline conditions. Similarly, the foregoing indices were significantly increased in young dogs by either stimulus, except for the inability of clonidine to affect peak frequency. These data demonstrate that the defective GH secretion in old dogs is not irreversible, since it is normalized when old dogs are exposed to central nervous system-directed stimuli.

Age Factors↗
PubMed1989

Ovarian response to combined growth hormone-gonadotropin treatment in patients resistant to induction of superovulation.

The efficacy of combined growth hormone (GH)-gonadotropin treatment has been studied in patients previously resistant to sole gonadotropins for induction of superovulation. Eleven patients (aged 26-41) with a mechanical cause of infertility were treated. All were given the same dosage of gonadotropins as in previous cancelled cycles (6-17 ampules/cycle of menofollitropin; 34-80 ampules/cycle of human menopausal gonadotropin) plus a standard dosage of GH (0.1 IU per kg body weight, daily). Younger patients (n = 6, age 26-36) showed a considerable improvement of ovarian response in terms of number of mature follicles aspirated by laparoscopy (performed on day 11-13). Older patients (n = 5, age 39-41) did not show any significant improvement of ovarian response with combined treatment and all had their stimulatory cycle cancelled. Follicular fluid (FF) levels of GH, 17 beta-estradiol (E2) and progesterone (P) were significantly higher in the group of younger GH-treated patients (n = 53 follicles) than in 4 controls treated with gonadotropins only (n = 32 follicles). FF insulin-like growth factor-I (IGF-I) did not significantly differ between the two groups. A significant positive linear correlation has been found between FF GH and IGF-I in the GH-treated group. In conclusion, GH-gonadotropin combined treatment considerably improves ovarian response in protocols for superovulation induction in younger gonadotropin-resistant patients. A local action of GH and IGF-I in the ovaries may be hypothesized.

Adult↗
PubMed1988

Epidermal growth factor in breast cyst fluid: relationship with intracystic cation and androgen conjugate content.

In recent years, several studies focused on the biochemical analysis of breast cyst fluid composition. It has been shown that breast cysts lined by apocrine epithelium contain higher levels of potassium and dehydroepiandrosterone-sulphate as compared to cysts lined by flattened cells, and that women with apocrine cysts are more likely to develop breast cancer. In the present study, we measured the intracystic levels of sodium (Na+), potassium (K+), dehydroepiandrosterone-sulphate (DHEA-S), and epidermal growth factor (EGF), a factor which could play a role in the autocrine or paracrine control of breast cancer cell growth as recently proposed by some investigators. Breast cyst fluids obtained by fine-needle aspiration from 86 women with gross cystic breast disease were assayed. On the basis of the relative intracystic concentrations of Na+ and K+ two main classes of cysts were defined. An arbitrary cut-off value of 3 for the Na+/K+ ratio seemed adequate to separate these two types of cysts. An inverse relationship was found between the Na+/K+ ratio and DHEA-S concentration, median levels of the androgen conjugate being 3615 micrograms/dl in Na+/K+ less than 3 cysts and 480 micrograms/dl in Na+/K+ greater than 3 cysts (P less than 0.001). EGF levels were found to be significantly higher in Na+/K+ less than 3 cysts as compared to Na+/K+ greater than 3 cysts: 103.26 ng/ml versus 57.22 ng/ml, respectively (P less than 0.001). EGF appeared inversely correlated with total protein concentration in the Na+/K+ greater than 3 cysts, while in the Na+/K+ less than 3 cysts high EGF levels were observed independently of total protein content. In addition, a direct correlation was found between EGF and DHEA-S concentrations. On the basis of these results, the hypothesis can be made that EGF, which is measurable in all breast fluids tested and is nearly undetectable in plasma, is actually produced by the epithelium lining the cyst wall, particularly as far as the Na+/K+ less than 3 cysts are concerned. In view of our results this type of cyst, which has been shown to be lined by apocrine epithelium, appears to be characterized by high DHEA-S and EGF levels. It is suggested that the latter finding could provide a clue for understanding the increased risk of subsequent breast cancer in women bearing apocrine cysts.

Adult↗
PubMed1988

Evidence for autocrine mitogenic stimulation by somatomedin-C/insulin-like growth factor I on an established human lung cancer cell line.

The production of immunoreactive somatomedin-C/insulin-like growth factor I (Sm-C/IGF-I) by the established cell line derived from a human lung carcinoma CALU-6 has been evidenced in the serum-free medium in increasing concentrations as a function of the incubation time. Gel filtration in acid conditions of cell-conditioned medium collected after 72 h showed peaks of immunoreactive Sm-C/IGF-I in the elution volume corresponding to the molecular weight of the synthetic Sm-C/IGF-I, and in the high molecular weight region, where specific binding sites for Sm-C/IGF-I could be also demonstrated. These results indicate that this established cell line produces high amounts of immunoreactive Sm-C/IGF-I and of Sm-C/IGF-I carrier protein. The pooled fractions corresponding to the molecular weight of synthetic Sm-C/IGF-I showed a competitive binding curve parallel to the standard in the Sm-C/IGF-I RIA system, and a mitogenic activity on cells from the same line similar to the one observed using two different pure Sm-C/IGF-I preparations, obtained by chemical synthesis or by DNA recombinant technology. When a monoclonal antibody (sm-1.2) raised against Sm-C/IGF-I was added into the medium, the mitogenic effect observed by both synthetic and cell-derived Sm-C/IGF-I peptide was completely abolished; the monoclonal antibody also partially inhibited the effect of 10% fetal calf serum and the thymidine incorporation observed in serum-free medium without growth factors. In serum-free medium the monoclonal antibody produced a 45% reduction of cells in S phase by thymidine labeling index without modification of the growth fraction as determined by primer-dependent alpha-DNA polymerase labeling index. In conclusion it seems that Sm-C/IGF-I has a critical role in the autocrine stimulation of the replication of this cell line.

Antibodies, Monoclonal↗
PubMed1987

Partial characterization of somatomedin C-like immunoreactivity secreted by breast cancer cells in vitro.

The in vitro secretion of immunoreactive somatomedin C/insulin-like growth factor I (IR Sm-C/IGF-I) by two human breast cancer cell lines, MCF-7 and EVSA-T has been studied. IR Sm-C/IGF-I concentration showed a linear increase in serum-free culture media over 72 h of incubation for both cell lines, and a close correlation with cell number (P less than 0.001). To characterize this immunoreactivity, a pool of conditioned media collected after 72 h of incubation was dialyzed overnight against 1 M acetic acid, lyophilized, and gel filtered on a Sephadex G-50 column. Fractions were determined for Sm-C/IGF-I content and for the presence of a specific carrier for Sm-C/IGF-I. Two peaks of Sm-C/IGF-I-like immunoreactivity were evidenced, the first in the high molecular weight region and the second corresponding to the molecular weight of the free peptide. The first peak evidenced also a specific binding ability for radioiodinated Sm-C/IGF-I, suggesting that the activity found in this region could be interpreted as interference of the specific free binding sites in the immunoassay. Analysis of this peak by polyacrylamide gel electrophoresis demonstrated the presence of a specific binding for Sm-C/IGF-I in a molecular weight range between 35,000 and 45,000 Da, which was not modified in reducing conditions. The binding activity was competitively inhibited by addition of cold Sm-C/IGF-I but not by insulin excess.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗
PubMed1986

Insulin-like growth factor I (IGF I) receptor autophosphorylation and kinase activity. Effect of a human polyclonal antibody (pIgG)

IGF I receptor is a tyrosine kinase capable of phosphorylating the receptor itself and other substrates. A high degree of homology does exist in tyrosine kinase domain among receptors for several polypeptide growth factor receptors and this enzymic activity has been indicated as a possible mediator of biological action. Nevertheless growth factor receptors possess peculiar specificities both in their functions and tissue distribution. A human polyclonal IgG (pIgG), previously characterized as anti insulin receptor antibody, able to inhibit insulin receptor kinase activity, was used to further investigate subunit homologies and differences in antigenicity and functional regulation between IGF I and insulin receptors, IGF I receptor tyrosine kinase was stimulated by a IGF I analog (aIGF I), produced by DNA recombinant technology, pIgG was able to inhibit IGF I receptor kinase activity, thus revealing antigenic homologies between the kinase domains of insulin and IGF I receptors. However the more pronounced inhibition of IGF I receptor-compared with insulin receptor kinase activity by pIgG suggests the existence of different regulatory mechanisms.

Antigen-Antibody Reactions↗
PubMed1986

Growth hormone and somatomedin-C response to synthetic human pancreatic tumor GH-releasing factor in hypopituitary and constitutionally short children.

GH and somatomedin-C response to acute hpGRF-44 iv administration (1 microgram/Kg bw) was studied in 16 patients with hypopituitarism (GHD) and in 7 constitutionally short subjects. GH-deficient patients evidenced a significant GH increase peaking between 15 and 60 min. (4.95 +/- 0.88 ng/ml, mean +/- SE) (p less than 0.01 vs placebo). In non GH-deficient subjects GH increase was more pronounced (peak 18.00 +/- 3.01 ng/ml; p less than 0.01 vs both placebo and GHD group). Acid-extractable somatomedin-C was slightly, but significantly higher than baseline at 12th h (p less than 0.01) in both patients with hypopituitarism (basal value: 0.067 +/- 0.021 U/ml; 12 h: 0.096 +/- 0.024 U/ml) and constitutionally short subjects (basal value 0.62 +/- 0.13; 12h 0.72 +/- 0.16 U/ml). In 3 subjects with hypopituitarism multiple iv administrations (1 microgram/kg bw at 09:30 and 21:30 h for 4 days) produced on the average a modest increase of the GH responsiveness, were more effective to enhance somatomedin-C concentration, but not sufficient to reach normal levels. Sc administration of the same dose at 4-h intervals by a programmable portable pump - performed on 6 GHD subjects - produced an increase of GH peak response on the 4th day of treatment (1.38 +/- 0.31 ng/ml) with respect to the one observed on the first day (0.42 +/- 0.09 ng/ml). Somatomedin-C increase was low and inconstant. These data support the use of a 4-5-day pulsatile treatment in the differentiation between hypothalamic and pituitary deficiency, and the possibility of therapeutical use of GRF with the same protocol when a response is evidenced.

Adolescent↗
PubMed1986

Partial purification and characterization of a neutral insulin-like growth factor. Biochemical and biological properties.

A peptide with an isoelectric point of 6.5-7.0 was purified from Cohn fraction IV on the basis of its capacity to cross react with labelled insulin to human placental cell membrane receptors. It possesses insulin-like activity in the adipocyte bioassay (30 mU insulin equivalent/mg of protein) which is in the same order as its activity in the insulin radioreceptorassay (25.5 mU/mg). Somatomedin bioactivity is 40 U/mg in the porcine cartilage assay. In contrast, although in quiescent human fibroblast this peptide preparation has 6% of the mitogenic potency of somatomedin-C/insulin-like growth factor I on a weight basis, cross-reactivity in radioimmunoassay for somatomedin-C/insulin-like growth factor I, insulin-like growth factor II and insulin are very low. It is concluded that this peptide, although exhibiting the major biological characteristics of an insulin-like growth factor is different from the hitherto described somatomedins.

Adipose Tissue↗