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Biomedical subjects

E Graziano

Publications and source records attributed to E Graziano.

At least 19 recordsLinked to original sources

A maize defective-kernel mutant (longcell) characterized by tubular cells, severe morphological alterations and induction of cell death.

Seeds of the longcell mutant in maize (Zea mays L) have a defective-kernel phenotype: the embryo aborts at the early coleoptilar stage and the endosperm is reduced in size. Mutant embryos have severe alterations in morphogenesis. They have a suspensor-, an embryo axis- and a scutellum-like structure, but the shoot apical meristem (SAM) is not formed. Scanning electron microscopy showed that most of the cells in longcell embryos are tubular and abnormally enlarged. The level of expression of several genes involved in basic metabolism is not severely affected during early and mid embryogenesis, but storage molecule accumulation is reduced. Genes which in normal conditions are only expressed after germination, are expressed during kernel development in the longcell seeds. Mutant embryos undergo cell death in late embryogenesis. Nuclei in dying embryos are TUNEL positive, and different genes coding for hydrolytic enzymes are up-regulated. The expression of genes related to oxidative stress is also altered in longcell embryos. These results lead us to suggest that the longcell mutant may be cytokinesis-defective.

Cell Death↗

An early requirement for FGF signalling in the acquisition of neural cell fate in the chick embryo.

BACKGROUND: In Xenopus embryos, fibroblast growth factors (FGFs) and secreted inhibitors of bone morphogenetic protein (BMP)-mediated signalling have been implicated in neural induction. The precise roles, if any, that these factors play in neural induction in amniotes remains to be established. RESULTS: To monitor the initial steps of neural induction in the chick embryo, we developed an in vitro assay of neural differentiation in epiblast cells. Using this assay, we found evidence that neural cell fate is specified in utero, before the generation of the primitive streak or Hensen's node. Early epiblast cells expressed both Bmp4 and Bmp7, but the expression of both genes was downregulated as cells acquired neural fate. During prestreak and gastrula stages, exposure of epiblast cells to BMP4 activity in vitro was sufficient to block the acquisition of neural fate and to promote the generation of epidermal cells. Fgf3 was also found to be expressed in the early epiblast, and ongoing FGF signalling in epiblast cells was required for acquisition of neural fate and for the suppression of Bmp4 and Bmp7 expression. CONCLUSIONS: The onset of neural differentiation in the chick embryo occurs in utero, before the generation of Hensen's node. Fgf3, Bmp4 and Bmp7 are each expressed in prospective neural cells, and FGF signalling appears to be required for the repression of Bmp expression and for the acquisition of neural fate. Subsequent exposure of epiblast cells to BMPs, however, can prevent the generation of neural tissue and induce cells of epidermal character.

Animals↗

TM20, a gene coding for a new class of transmembrane proteins expressed in the meristematic tissues of maize.

In the course of the analysis of lachrima, a recessive, defective kernel, embryo-lethal mutation in Zea mays that alters embryo and endosperm development, a gene coding for a new class of transmembrane proteins was isolated. The mutant was produced by Ac transposon tagging, and a gene located in the insertion region of the transposon was isolated as well as the corresponding cDNA. The predicted protein contains twenty hydrophobic segments that can be grouped in five repeats formed by four segments that fulfill the criteria for membrane spanning domains, and for this reason the gene has been named TM20. The sequences of the domains in each position of each group can be aligned, indicating that TM20 is formed by a four-domain structure duplicated five times. During embryogenesis in wild-type embryos and in the growing plant, TM20 gene expression is associated with meristems.

Amino Acid Sequence↗

Convergent inductive signals specify midbrain, hindbrain, and spinal cord identity in gastrula stage chick embryos.

In the chick embryo, neural cells acquire midbrain, hindbrain, and spinal cord character over a approximately 6 hr period during gastrulation. The convergent actions of four signals appear to specify caudal neural character. Fibroblast growth factors (FGFs) and a paraxial mesoderm-caudalizing (PMC) activity are involved, but neither signal is sufficient to induce any single region. FGFs act indirectly by inducing mesoderm that expresses PMC and retinoid activity and also directly on prospective neural cells, in combination with PMC activity and a rostralizing signal, to induce midbrain character. Hindbrain character emerges from cells that possess the potential to acquire midbrain character upon exposure to higher levels of PMC activity. Induction of spinal cord character appears to involve PMC and retinoid activities.

Animals↗

[Use of arginine in intruterine growth retardation (IUGR). Authors' experience].

BACKGROUND: Asymmetrical intrauterine growth retardation (IUGR) represents a foetal mechanism, consequent to placental insufficiency, due to many factors: genetic, vascular, malformative. At present, no therapy is really efficient. The aim of this study was to evaluate the efficacy, in these pathological conditions, of the use of L-arginine. This amino-acid improves GH-RH incretion, with consequent increase of plasmatic GH influencing somatic growth. L-arginine moreover, is the obligatory precursor for nitric oxide (NO) enzymatic synthesis (Endothelial-derived relaxing factor). NO helps the prolapse of smooth musculature and, consequently, the improvement of placental blood circulation. METHODS: On the basis of the double activity of NO, vasodilatation and GH-RH induction, 43 pregnant women have been treated suffering from IUGR, diagnosed by ultrasonic examination an by evaluation of Doppler velocimetry values, from 30th week of gestation, administering L-arginine (Bioarginina, 6 g per os/day). Periodically, USG and Doppler velocimetry examinations were performed to evalue foetal growth and possible increase of peripheral vessels resistance. RESULTS: 32 patients improved the clinical course of pregnancy: 19 recovered the whole retardation; 9 only one week; 4 had premature delivery after 36 weeks with foetal weight coincident with gestational age. CONCLUSIONS: The positive results suggest the prosecution of clinical studies in order to attempt the achievement of an effective pharmacological treatment of IUGR.

Amino Acids↗

111In-octreotide scintigraphy in endocrine tumors. Preliminary data.

A large number of endocrine tumors express somatostatin receptors, and the use of radiolabeled somatostatin analogs has been recently introduced for their localization. Using in vivo scintigraphy with 111In-pentetreotide, primary tumor localizations were demonstrated in 3/3 carcinoids (2 intestinal carcinoids and 1 lung ACTH-secreting carcinoid; in 2 patients liver metastases larger than 1 cm were visualized), in 1/1 GH-secreting pituitary macroadenoma, and in 1/1 thyroid localization of MTC. Bone and/or lymph node metastases were imaged in 2/4 patients previously treated for MTC, with persistently high CT and CEA levels; in the other 2 patients the other scintigraphic techniques were also negative. Octreotide scintigraphy was negative in 2/2 insulinomas and in 2/2 ACT-producing pituitary adenomas. In 2 patients with carcinoid syndrome and 1 patient with Cushing syndrome due to ectopic ACTH, octreotide therapy induced a significant decrease in tumoral markers. Our preliminary data are in agreement with the results of larger series reported in literature: octreotide scintigraphy is a useful noninvasive tool to detect endocrine tumors expressing somatostatin receptors, particularly for carcinoids. It is of great use in the differential diagnosis of Cushing syndrome due to ectopic ACTH. Moreover, 111In-pentetreotide scintigraphy may be useful in selecting patients who may benefit from octreotide therapy to control hormonal hypersecretion effects.

ACTH Syndrome, Ectopic↗

Atypical McCune-Albright syndrome associated with growth hormone-prolactin pituitary adenoma: natural history, long-term follow-up, and SMS 201-995--bromocriptine combined treatment results.

A 35-yr-old woman is described as having atypical McCune-Albright syndrome, associated with acromegaly and hyperprolactinemia due to pituitary adenoma. The patient did not present sexual precocity, but primary amenorrhea. After transphenoidal adenomectomy, the GH plasma levels returned to normal, whereas the PRL values decreased; bromocriptine therapy normalized PRL levels and induced ovulatory menses. After 4 uneventful yr the patient developed relapse of active acromegaly that did not recover after a second neurosurgical exploration. Bromocriptine treatment maintained normal PRL levels but did not significantly reduce GH ones; the association with long-acting somatostatin analog SMS 201-995 by continuous sc pump infusion induced definitive control of GH and somatomedin-C secretion. These results suggest an additive inhibitory effect on GH secretion exerted by the two drugs.

Acromegaly↗

Biventricular function in Friedreich's ataxia: a radionuclide angiographic study.

The systolic and diastolic function of both ventricles was assessed by radionuclide angiography in 21 patients with Friedreich's ataxia and hypertrophic cardiomyopathy. The indices of systolic function of the two ventricles and those of diastolic function of the right ventricle were generally normal. But in patients with Friedreich's ataxia the time to peak filling rate divided by the diastolic time of the left ventricle was significantly larger than normal. The increase correlated with the heart rate (r = 0.79) and this suggests an alteration in the timing of ventricle filling that is more evident at high heart rates. Movement of the left ventricle was little impaired; however, in 48% of the patients with Friedreich's ataxia the right ventricle showed evidence of hypokinetic segments. Because there is a tendency for congestive heart failure to develop in patients with Friedreich's ataxia, this hypokinesis of the right ventricle should be monitored at follow up.

Adolescent↗

Hyperthyroidism and high serum levels of TSH associated with pituitary tumour.

We report a 28-year-old male with persistent clinical and laboratory findings of hyperthyroidism associated with marked elevated serum levels of TSH and no response to TRH despite hemithyroidectomy and subsequent antithyroid drug therapy two years previous to admission to our hospital. Subsequent skull X-rays, CT scans and angiographic findings demonstrated the presence of a pituitary tumour. After operation and radiation therapy T3, T4 and TSH levels returned to normal values. Seven years later the patient is still euthyroid. We conclude that hyperthyroidism in our patient was due to excessive secretion of TSH by the pituitary tumour.

Adenoma, Chromophobe↗

The use of scintigraphy with Tc 99 pyrophosphate for the evaluation of meniscal lesions.

The preliminary results obtained in a study of the use of scintigraphy with Tc 99 PYP for the evaluation of meniscal lesions of the knee are presented. Three different captation curves are described. Those with an elevated peak and a restricted base are characteristic of meniscal lesions. The use of this method in a series of 50 patients in whom meniscal lesions were suspected demonstrated a high diagnostic sensitivity and specificity with regard to the presence of the lesion, but not to its type.

Adolescent↗

The relationship between chromosomal origins of replication and the nuclear matrix during the cell cycle.

A cytological investigation into the dynamic behaviour of the origins of replication with respect to the nuclear matrix has been carried out on Xenopus laevis cultured cells. In order to preferentially label origins or 'non-origin' regions along DNA fibres, 5-fluoro-2'-deoxyuridine (FUdR)-treated cells were pulsed with [3H]deoxyadenosine in early or late S phase. Samples were then allowed to proceed through the cell cycle for increasing times. The DNA loops were induced in situ to completely uncoil around the nuclear matrix. The autoradiographic analysis shows that, under the experimental conditions used, 'non-origin' regions behave as expected from previous studies, i.e., they associate with the nuclear matrix only when they become part of a replication fork, whereas active origins of replication remain associated with the matrix throughout the cell cycle.

Animals↗

Fetal prolactin levels and respiratory distress syndrome.

Prolactin levels were measured by radioimmunoassay in cord blood of infants between 28 and 40 weeks of gestation. Also infants, whose mothers received betamethasone prior to delivery, were examined. Between 33 and 36 weeks, the mean plasma cord prolactin levels in infants who developed RDS were significantly lower than HPRL levels in those infants who did not develop RDS. These findings suggest that betamethasone did not alter HPRL levels and point out the possibility of a role of prolactin in fetal lung maturation.

Betamethasone↗

Ultrasound placental study and fetal lung maturity.

This study was undertaken to ascertain the usefulness of placental development ultrasound study in prediction of RDS. We examined 96 women near term of pregnancy; the accuracy of placental maturity grades in predicting fetal lung maturity was compared with lecithin/sphingomyelin ratio and with clinical development of RDS in the infants. We observed good correlation among ultrasound placental grades and fetal maturity.

Amniocentesis↗

Preliminary observations on the neuromelanic pigment in the substantia nigra nucleus of the cat.

The AA. study the behaviour of neuromelanic pigment in the substantia nigra of cats' mesencephalon. To this aim they suppress a first group of animals with MgSO4; a second group with a substance whose action is narcotic and curare-like. They carry out the observations on mesencephalon microtomic sections, some stained with hematoxylin, some treated with PAS reaction and some with Sudan Black. The results are: 1)- in the perikaryon of substantia nigra pars compacta neurons of cats suppressed with MgSO4, the pigment, absent in the early age of life, appears in adult age. It is characterized by brownish-yellow granulations, either scattered or clustered together. This finding is substantially similar to that observed in dogs' substantia nigra. 2)- The substantia nigra neurons of the mesencephalon taken from cats suppressed with a curare-like substance, appear instead, almost wholly, without the peculiar neuromelanic granulations. However intracytoplasmic bodies stained with hematoxylin and PAS positive, can be observed. In order to establish the morphological and histochemical events which occur in the substantia nigra neurons in depigmentation induced in this way the AA. consider further investigations absolutely necessary.

Aging↗

[The hypothalamic-hypophyseal-adrenal axis in obesity].

The HHA axis was assessed in 26 women with essential obesity using a CRF test, insulin hypoglycemia and oral glucose load. Basal values of ACTH and cortisol were similar in obese subjects and controls, whereas peak ACTH values following CRF administration were significantly lower in obese subjects. The net integrated areas under ACTH and cortisol curves after CRF injection were lower in obese subjects but not statistically significant. Glucose inhibited cortisol levels in controls but not in obese subjects. Insulin hypoglycemia provoked a ACTH and cortisol response in obese women which was significantly higher than that provoked by CRF. The lesser response of ACTH to CRF in obesity might be the result of an altered hypophyseal response to CRF mediated by other factors; in addition, the increased ACTH and cortisol response to the insulin stimulus compared to CRF observed in obese subjects leads to suppose that the metabolic stimulus involves the release of other factors.

Adolescent↗