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Biomedical subjects

M Gulisano

Publications and source records attributed to M Gulisano.

At least 73 records · Page 4Linked to original sources

Two vertebrate homeobox genes related to the Drosophila empty spiracles gene are expressed in the embryonic cerebral cortex.

We cloned two homeobox genes, Emx1 and Emx2, related to empty spiracles, a gene expressed in very anterior body regions during early Drosophila embryogenesis, and studied their expression in mouse embryos. Emx1 expression is detectable from day 9.5 of gestation whereas Emx2 appears to be already expressed in 8.5 day embryos. Both genes are expressed in the presumptive cerebral cortex and olfactory bulbs. Emx1 is expressed exclusively there, whereas Emx2 is also expressed in some neuroectodermal areas in embryonic head including olfactory placodes in earlier stages and olfactory epithelia later in development.

Amino Acid Sequence↗

Cytoprotective effect of copper(II) complexes against ethanol-induced damage to rat gastric mucosa.

The cytoprotective effect of various copper(II) complexes on the gastric mucosa damage induced by acute intragastric administration of ethanol was investigated. For in vitro experiments, the following copper(II) complexes were tested: Cu(II)(L-Trp)(L-Phe), Cu(II)(L-Leu)Cu(II)(L-Leu-Leu)(L-Leu), Cu(II)(L-Phe-L-Leu), Cu(II)(Gly-His-Lys), and Cu(II)(cyHis)2(ClO4)2. Inorganic copper such as CuSO4 was also tested. The free radical generating system, acting for 2 hr on cardial and fundic mucosa scrapings or mucosal microsomes, was Fe++ (20 microM)/ascorbate (0.25 mM). We found a marked inhibition to 75% of lipid peroxidation in the range 10-100 mM, regardless of whether copper was given in complexed or inorganic form. The results suggest that nontoxic copper(II)-amino acid complexes are able to neutralize oxygen-derived free radicals. In addition, copper(II) complexes suppressed membrane lipid peroxidation when mucosa homogenates were exposed to t-butyl hydroperoxide (1-20 microM) plus Fe++ (50 microM). In vivo experiments on rat stomachs, pretreated p.o. by gavage either with Cu(II)(L-Trp)(L-Phe) as paradigmatic agent or with copper sulphate at equivalent doses in the range 3-30 mg/kg body weight showed a significant decrease (30 min after 95% ethanol administration) in the number and severity of mucosal hemorrhagic lesions. In the gastric mucosa scrapings of copper-treated rats after ethanol exposure, we found that malondialdehyde and conjugated diene levels were unchanged compared to those of untreated controls; five enzyme activities released from lysosomes were near control values. In isolated mucosal cells, whether or not pretreated with 200 microM solution of either Cu(II)(L-Trp)(L-Phe) or CuSO4, the release of cathepsin D activity was also unmodified. The results suggest that the cytoprotective effect of Cu(II) complexes against ethanol-induced mucosal lesions was not associated in vivo to lipid peroxidation.

Amino Acid Sequence↗

Morphological study of fetal nasopharyngeal epithelium in man.

In 30 human fetuses between 8 and 13 weeks of intrauterine life the lateral wall of the nasopharynx was examined by light microscopy and transmission and scanning electron microscopy. In the subjects between 8 and 9 weeks in utero the mucosa displays still an immature appearance, being mono- or bistratified and lacking the characteristic structures of the respiratory epithelium. Nevertheless, signs of differentiation are to be noticed, with the presence of two distinct cellular types that, in the later periods, will give rise to ciliated cells and microvillus-provided cells. An almost complete differentiation will be reached at 12-13 weeks in utero, even if goblet cells are still lacking in the examined zone during the considered period. Nonrespiratory types of epithelium, such as transitional or squamous, were never found in the studied subjects.

Embryonic and Fetal Development↗

[The shape of the nasopharynx in youth: statistical study].

The particular shape of the nasopharynx in the child can influence morphology and physiopathologic behaviour of the mucosa. In such a perspective, it appeared interesting to evaluate the kind and the entity of its variations by means of nuclear magnetic resonance (NMR) in 50 patients (age range: 2 months-16 years). The results show that the nasopharyngeal shape (represented either by bending radius and shape factor) varies in a statistically significant way during the considered age range, while the dimension of the pharyngeal tonsil remains constant in the studied cases. The statistically significant shape variation of the tonsil appears, so, related to its involvement in the shape variation of the whole nasopharynx.

Adolescent↗

[Dimensions of the human aortic arch and thoracic aorta studied by nuclear magnetic resonance].

The size of the aortic arch and thoracic aorta was measured in 50 healthy volunteers studied by NMR. In each case the following parameters were measured and statistically elaborated: diameter (in mm) of ascending aorta (between onset and arch beginning), of aortic arch (intermediate zone), of isthmus, of descending aorta (between isthmus and diaphragm), of diaphragmatic isthmus; a mean diameter was also calculated, and for every diameter mean and standard deviation were obtained. Moreover, the length (in mm) of superior and inferior contours of the aortic arch, as the ratio of these two values were obtained. At last, total length of considered aortic tract, area of visualized surface and theoretic volume were obtained. For each parameter a diagram was then plotted, with age in ordinates and values of above mentioned parameters in abscissae. Statistical evaluation allows to affirm that the size of the aorta grows with ageing. On the contrary, the ratio between superior and inferior contour of the aortic arch tends to remain unvaried; this fact seems to disagree with the current opinion that the superior wall of the arch grows with age more than the inferior one.

Adolescent↗

[Structural organization of the menisci of the human knee: scanning electron microscopy study].

The structure of the meniscus of the knee joint was studied in 10 human subjects after meniscectomy for acute trauma. The specimens were studied by scanning electron microscopy after cryofracture. Collagen fibres are arranged in two layers: a thin superficial zone with radially oriented fibres and a deep zone with circumferentially oriented ones. Deep fibres are surrounded by oblique fascicules. The cells are rare and oval-shaped. The observations enhance the hypothesis that the meniscus of the knee joint is not a real fibrocartilage.

Adult↗

Isolation and mapping of EVX1, a human homeobox gene homologous to even-skipped, localized at the 5' end of HOX1 locus on chromosome 7.

We isolated and mapped the human homeobox gene EVX1. This gene encodes a protein of 407 amino acid residues containing a homeodomain closely related to the Drosophila even-skipped (eve) segmentation gene of the pair-rule class. EVX1 belongs to a small family of vertebrate eve-related homeobox genes including human EVX1 and EVX2 genes, their murine homologs, Evx 1 and Evx 2, and the frog Xhox-3 gene. We previously reported that EVX2 is localized at the 5' end of the HOX4 locus on chromosome 2. We show here that EVX1 is localized at the 5' end of the HOX1 locus on chromosome 7, 48 kb upstream from the most 5' of the eleven HOX1 genes, namely HOX1J. Both EVX genes are transcribed in an opposite orientation as compared to that of adjacent HOX genes. Human HOX1 and HOX4 complex loci appear to be both closely linked to a homeobox gene of the EVX family.

Amino Acid Sequence↗

A distinct Hox code for the branchial region of the vertebrate head.

The branchial region of the vertebrate head forms through complex interactions involving rhombomeric segments, neural crest and branchial arches. It is though that aspects of their patterning mechanisms are linked and involve Hox-2 genes, whose overlapping and spatially restricted expression domains represent a combinatorial code for generating regional diversity. Vertebrates possess four Hox clusters of Antennapedia class homeobox genes, related to each other by duplication and divergence from a common ancestral complex. In consequence, at equivalent positions in different clusters there are highly related genes known as subfamilies or paralogous groups. As Hox-2 genes cannot fully account for patterning individual rhombomeres, we investigated whether offsets in expression limits of paralogous genes could account for the generation of regional diversity. We report here that, with the exception of the labial subfamily, paralogues show identical expression limits in rhombomeres, cranial ganglia and branchial arches, providing a combinatorial Hox code for the branchial region that seems to be different in organization to that of the trunk.

Alleles↗

Scanning electron microscopic study of nasopharyngeal carcinoma.

The study has been carried out on biopsies taken from four patients affected by squamous cell carcinoma and four patients affected by undifferentiated carcinoma of nasopharyngeal type (UCNT). Three healthy volunteers have served as controls. All the specimens have been studied by SEM. The neoplastic conditions cause obvious alterations both in the mucosal surface and in the morphology of the cellular apex.

Aged↗

The branchial Hox code and its implications for gene regulation, patterning of the nervous system and head evolution.

In this study we have examined the expression of murine Hox homeobox containing genes by in situ hybridisation in the branchial region of the head. Genes from the Hox complexes display segmentally restricted domains of expression in the developing hindbrain, which are correlated with similar restricted domains in the neural crest and surface ectoderm of the branchial arches. Comparison of related genes from the different clusters shows that subfamily members are expressed in identical rhombomeres and branchial arches. These patterns suggest a combinatorial system for specifying regional variation in the head, which we refer to as a Hox code. The Hox genes also display dynamic dorso-ventral (D-V) restrictions in the developing neural tube which mirror the timing and spatial distributions of the birth of major classes of neurons in the CNS. Genes in the Hox-2 cluster all have a similar D-V distribution that differs from that of genes from the other Hox clusters, and suggests that members of a subfamily may be used to specify positional values to different subsets of cells at the same axial level. These results are discussed in terms of a system for patterning the branchial regions of the vertebrate head, and evolution of head structures. We have also examined aspects of the transcriptional regulation of Hox-2 genes in transgenic mice using a lacZ reporter gene. We have been able to reconstruct the major pattern of the Hox-2.6 gene on the basis of identical expression of the transgene and the endogenous gene with respect to timing, spatial restrictions and tissue-specific distributions. Deletion analysis has enabled us to identify three regions involved in generating this pattern. Two of these regions have the properties of enhancers which are capable of imposing spatially-restricted domains of expression on heterologous promoters. We have generated similar Hox-lacZ fusions that reconstruct the highly restricted patterns of the Hox-2.1 and Hox-2.8 genes in the developing nervous system, supporting our in situ analysis and the idea of a Hox code. These transgenic experiments are a useful step in examining regulation in the Hox cascade.

Amino Acid Sequence↗

[Scanning electronic microscopy study of nasopharyngeal carcinoma].

The nasopharyngeal carcinoma is a greatly interesting model of study. Its morphology has been studied in 8 patients affected by squamous cells carcinoma (4 cases) and by undifferentiated carcinoma (4 cases). By means of a fibre-optic pharyngoscope equipped with mechanical biopsy forceps, biopsies have been taken and subsequently studied by scanning electron microscopy (SEM). Squamous cells carcinoma is characterized by large, flattened elements, generally equipped with a network of microridges. Irregular microvilli or smooth apices have been observed too. Desquamating elements often accumulated in waves or vortices, as far as little cornified structures have been described. Undifferentiated carcinoma shows a great morpho-structural disorder. In a rugged surface, it is possible to observe element highly varying for size and shape. The apical plasmalemma is characterized by pleomorphic microvilli, while it must be emphasized the presence of little pseudopod-like extrusions of some cellular apices. Ciliated elements have been observed too, whose apical specializations are distorted or irregularly disposed. Necrotic zones are particularly frequent, in which bacteria or mycetes proliferate. The role of SEM in the study of this tumour is emphasized, because of the close relation between epithelial patterns and natural history of nasopharyngeal carcinoma.

Aged↗

Phase II study of lonidamine in metastatic breast cancer.

Thirty patients with previously treated metastatic breast cancer were entered in a phase II study with oral lonidamine. Twenty-eight patients are evaluable for toxicity and 25 for response. A partial remission was obtained in four patients (16%) and disease stability in 11 (44%): 10 patients progressed (40%). Toxicity was acceptable, consisting mainly of myalgias (39% of patients) and asthenia (21.4%). No myelotoxicity was observed. The drug is active in previously treated metastatic breast cancer and, because of its peculiar pattern of action and toxicity, deserves to be evaluated in combination with cytotoxic chemotherapy.

Adult↗

Study of the nasopharynx in man by scanning electron microscopy.

To date only few and often disagreeing studies about human nasopharynx are available. The present research has the purpose to give a contribution to the knowledge of nasopharyngeal epithelium using S.E.M. The study was carried out on biopsies taken from 20 healthy volunteers. The surface of nasopharynx is covered by ciliated cells, microvilli provided cells and goblet cells. Areas covered with squamous epithelium and presumably transitional epithelium were observed. The possibility that ciliated cells become microvilli provided cells is discussed.

Adolescent↗

Phase II trial of oral idarubicin in advanced non-small cell lung cancer (NSCLC).

The antitumoral activity and toxicity of a new daunorubicin analog (4-demethoxydaunorubicin, IMI 30, Idarubicin) was tested in 20 consecutive patients with non-small cell lung cancer mostly pretreated with chemotherapy. The drug was administered orally at a dose of 15 mg/m2 for three days every 3-4 weeks. There were no clinical responses. Hematological and nonhematological toxicities were mild.

Administration, Oral↗

Sequential administration of cyclophosphamide, methotrexate, 5-fluorouracil, and folinic acid as salvage treatment in metastatic breast cancer.

Experimental data show that sequencing methotrexate (MTX) and 5-fluorouracil (5-FU) may result in synergistic antitumor activity. Moreover, the effect of 5-FU is increased by folinic acid (FA), and finally, cyclophosphamide (CPA) produces an expansion of tumor growth fraction, suggesting an increased cytotoxic effect of cycle-specific drugs subsequently administered. Based on these premises, we have performed a Phase II study with CPA (600 mg/m2 i.v., day 1), MTX (200 mg/m2 1-h i.v. infusion, day 7), 5-FU (600 mg/m2 i.v., day 8), and FA (500 mg/m2 2-h i.v. infusion, day 8 plus 15 mg p.o. every 6 h on days 8 and 9) administered every 3 weeks. Thirty-six patients with metastatic breast cancer were admitted into the study. Median age was 52 years, and all but two patients were postmenopausal. Dominant sites of metastases were soft tissues in 10 patients, bones in 7 patients, and viscera in 19 patients. All patients were pretreated with chemo- and/or hormone therapy. Sixteen patients achieved an objective response (44.5%: 1 complete response and 15 partial responses), 8 had stable disease (SD) (22.2%), and 12 progressed (33.3%). Twenty-one patients had previously received conventional CMF in an adjuvant setting (15 patients) or for metastases (6 patients): 1 complete response (CR) and 7 partial responses (PR) were obtained in the first group and 1 in the second. Major toxic effects were hair loss (56.4%), nausea and vomiting (72%), mucositis (52.5%), and leukopenia (61%). A randomized study could be useful to assess the role of sequential CMF versus conventional CMF in metastatic breast cancer patients.

Adult↗