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Biomedical subjects

G Stella

Publications and source records attributed to G Stella.

At least 19 recordsLinked to original sources

Differential roles of PI3-kinase and Kit tyrosine 821 in Kit receptor-mediated proliferation, survival and cell adhesion in mast cells.

The pleiotropic effects of the Kit receptor system are mediated by Kit-Ligand (KL) induced receptor autophosphorylation and its association with and activation of distinct second messengers, including phosphatidylinositol 3'-kinase (PI3-kinase), p21ras and mitogen-activated protein kinase (MAPK). To define the role of PI3-kinase, p21ras and MAPK in Kit-mediated cell proliferation, survival and adhesion in bone marrow-derived mast cells (BMMC), mutant Kit receptors were expressed in Wsh/Wsh BMMC lacking endogenous c-kit expression. The introduction of both murine Kit(S) and KitL (isoform containing a four amino acid insert) into Wsh/Wsh BMMC restored KL-induced proliferation, survival and adhesion to fibronectin, as well as activation of PI3-kinase, p21ras and MAPK, and induced expression of c-fos, junB, c-myc and c-myb mRNA. Substitution of tyrosine 719 in the kinase insert with phenylalanine (Y719F) abolished PI3-kinase activation, diminished c-fos and junB induction, and impaired KL-induced adhesion of BMMC to fibronectin. In addition, the Y719F mutation had partial effects on p21ras activation, cell proliferation and survival, while MAP kinase activation was not affected. On the other hand, Y821F substitution impaired proliferation and survival without affecting PI3-kinase, p21ras and MAPK activation, and induction of c-myc, c-myb, c-fos and c-jun mRNA, while KL-induced cell adhesion to fibronectin remained intact. In agreement with a role for PI3-kinase in Kit-mediated cell adhesion, wortmannin blocked Kit-mediated cell adhesion at concentrations known to specifically inhibit PI3-kinase. We conclude, that association of Kit with p85PI3-K, and thus with PI3-kinase activity, is necessary for a full mitogenic as well as adhesive response in mast cells. In contrast, tyrosine 821 is essential for Kit-mediated mitogenesis and survival, but not cell adhesion.

Animals

Littoral cell angiosarcoma of the spleen. Case report with immunohistochemical and ultrastructural analysis.

This report describes a case of a malignant vascular tumor of the spleen with the morphologic, immunologic, and ultrastructural features observed in splenic sinus-lining cells (littoral cells). Histological examination showed a well-differentiated neoplasm forming ectatic blood channels with intraluminal papillary fronds. Tumor cells displayed malignant nuclear features and hemophagocytosis. Solid neoplastic areas with mitotic figures were present. Ultrastructurally, the tumor cells showed the concomitant presence of lysosomes and Weibel-Palade bodies. Immunohistochemically, the tumor cells were positive for both endothelial (Factor VIII-AG, CD34) and histiocytic markers (cathepsin D, lysozyme, alpha-1-antichimotrypsin). Our results indicate that angiosarcoma may originate from all the vascular compartments of the spleen, including red-pulp sinuses, and may have morphologic and immunophenotypic similarities to littoral cell angioma, a recently described benign vascular tumor of the spleen.

Aged

A positively selecting thymic epithelial cell line lacks costimulatory activity.

The participation of costimulatory molecule interactions in positive selection of T lymphocytes was addressed by assessing the ability of a positively selecting thymic epithelial cell (TEC) line, 427.1, to stimulate allospecific CTL responses. Stimulation of H-2s spleen cells with the H-2b expressing 427.1 line does not result in the generation of cells capable of lysing H-2b target cell lines. The level of expression of MHC class I molecules by 427.1 is lower than that found in other stimulatory TEC lines. However, this finding does not account for the nonstimulatory phenotype. Up-regulation of MHC class I did not result in stimulation, and fusion of 427.1 cells with stimulatory TEC resulted in a line with low MHC class I molecule expression and stimulatory phenotype. The TEC line 427.1 does not express the costimulatory molecule B7/BB1, and transfection of the B7/BB1-encoding DNA results in expression of the molecule and conversion into a stimulatory phenotype, demonstrating directly that the non-stimulatory phenotype is a result of lack of costimulation. However, B7/BB1 expression does not improve the ability of 427.1 TECs to induce positive selection. Intrathymic injection of the B7/BB1 transfected, compared with mock transfected 427.1 cells, rescued fewer CD8+ mature thymocytes in beta 2-microglobulin negative mice. Therefore, unlike the peripheral T cell responses to Ag, positive selection of T cells in the thymus may not depend on the costimulation provided by the presenting cell.

Animals

Cervical adenocarcinomas express markers common to gastric, intestinal, and pancreatobiliary epithelial cells.

Frequency and pattern of expression of eight markers of gastric, intestinal, and pancreatobiliary duct epithelial cells have been investigated by histochemical and immunohistochemical techniques in 85 cases of cervical adenocarcinomas. M1, a mucin antigen, and Cathepsin E (CaE), an aspartic proteinase, markers of normal gastric superficial/foveolar epithelial cells, are expressed in 40 and 55 tumors, respectively. Periodic acid-concanavalin A-reactive mucin or Pepsinogen (PG) II, markers of gastric mucus neck and pyloric gland cells, are found in 24 tumors, 13 of which also express M1 and CaE. CAR-5 and M3SI, markers of intestinal mucin, are expressed in 68 and 12 tumors and DU-PAN-2, marker of normal pancreatobiliary duct cells, is found in 46 tumors. All but two tumors express at least one of the eight markers studied, none express PG I, marker of gastric chief cells. The different histologic subtypes of cervical adenocarcinomas expressed to a variable degree both gastrointestinal and pancreatobiliary markers. Only endocervical type tumors, however, showed the full spectrum of mucosal pyloric type differentiation, including the expression of PGII which is not present in any other histotype. A correlation between expression of gastroenteropancreatic markers and tumor grade is not apparent in our series.

Adenocarcinoma

New X linked spondyloepimetaphyseal dysplasia: report on eight affected males in the same family.

We report on a probably new form of spondyloepimetaphyseal dysplasia (SEMD) with an X linked inheritance pattern. Eight males were affected in the same family. We were able to examine three adult patients and we studied the skeletal radiological aspect of one of these patients at 2 years 6 months and at 9 years of age. The main clinical features are severe short trunked dwarfism, brachydactyly, normal facies, and normal intelligence. Radiologically, the diaphyses of all the long bones are short and broad. The epiphyses of the distal portion of the femora and those of the proximal and distal portions of the tibia are embedded in their metaphyses and there is marked narrowing of the intercondylar groove. There is moderate platyspondyly. Several vertebrae show an anterior tongue in infancy and severe irregularities of the upper and lower surfaces are present in adulthood. The 11th or 12th thoracic vertebra is wedge shaped. The pelvis is narrow. The distal ulnae and fibulae are disproportionately long. The hands show radial deviation and brachydactyly is present in the hands and feet. This X linked SEMD was not detectable at birth.

Child

[Dysplasia epiphysealis hemimelica].

The Authors present 9 patients affected by Dysplasia Epiphysealis Hemimelica with a mean follow-up of 11 years (range 5 years-21 years). The Authors confirm the benignity of the disease and report the variability of the clinical evolution of this rare type of osteochondrodysplasia. Besides cases with spontaneous evolution characterized by no clinical evidence of the disease, there are cases that require surgical removal of the osteochondromas and, sometimes, corrective interventions because of axial deviations and/or limb discrepancy.

Adolescent

Health status of long-term survivors after cancer in childhood. Results of an uniinstitutional study in Italy.

PURPOSE: This study aims at defining the frequency and severity of late effects in a series of 288 long-term survivors of childhood cancer treated from 1962 to 1982 at the Giannina Gaslini Children's Research Hospital of Genoa, Italy. PATIENTS AND METHODS: All cases with a diagnosis of malignancy in childhood and a minimum of 2.5 years from discontinuation of treatment were considered eligible. For all cases the study included physical, endocrinological, and psychological examination. Groups of patients selected according to treatment underwent cardiac, pulmonary, orthopedic, and ophthalmologic evaluation. The sequelae observed were scored according to a grading system in which asymptomatic subclinical defects are distinguished from those that are sufficiently symptomatic to require some type of corrective measure. RESULTS: Overall, 200 of 288 cases (69.4%) presented with some kind of abnormality. Symptomatic changes were present in 92 cases (42%); in these, severe and life-threatening late toxicity was reported in 61 (21.2%) and 12 cases (4.2%), respectively. The major risk factors appeared to be irradiation, type of tumor, and whether the patient had received therapy before 1974. CONCLUSIONS: In our experience, this study demonstrates that there was a true excess of morbidity caused by the disease and its treatment in long-term survivors from almost any kind of childhood cancer. It also sheds light on how to prevent, diagnose, and adequately treat these patients and proposes specific criteria for the evaluation of the severity of delayed toxicity in long-term survivors of cancer in childhood.

Adolescent

Chicken T-cell receptor beta-chain diversity: an evolutionarily conserved D beta-encoded glycine turn within the hypervariable CDR3 domain.

Unlike mammals, chickens generate an immunoglobulin (Ig) repertoire by a developmentally regulated process of intrachromosomal gene conversion, which results in nucleotide substitutions throughout the variable regions of the Ig heavy- and light-chain genes. In contrast to chicken Ig genes, we show in this report that diversity of the rearranged chicken T-cell receptor (TCR) beta-chain gene is generated by junctional heterogeneity, as observed in rearranged mammalian TCR genes. This junctional diversity increases during chicken development as a result of an increasing base-pair addition at the V beta-D beta and D beta-J beta joints (where V, D, and J are the variable, diversity, and joining gene segments). Despite the junctional hypervariability, however, almost all functional V beta-D beta-J beta junctions appear to encode a glycine-containing beta-turn. Such a turn may serve to position the amino acid side chains of a hypervariable TCR beta-chain loop with respect to the antigen-binding groove of the major histocompatibility complex molecule. Consistent with this hypothesis, the germ-line D beta nucleotide sequences of chickens, mice, rabbits, and humans have been highly conserved and encode a glycine in all three reading frames.

Amino Acid Sequence

Neosartorya fischeri var fischeri (Wehmer) Malloch and Cain 1972 (anamorph: Aspergillus fischerianus Samson and Gams 1985) as a cause of mycotic keratitis.

The first case of mycotic keratitis caused by Neosartorya fischeri var. fischeri the teleomorph of Aspergillus fischerianus, is described. The patient, a 62-year-old man, had no history of trauma to his infected left eye. The infection progressed despite treatment with ketoconazole and the eye had to be eviscerated. Histological studies revealed the presence of hyaline, septate mycelium in the eye tissue. Cultures gave rise to a thermotolerant mould that developed both its asexual and sexual forms. The isolate was identified on the basis of the morphologic features of its anamorphic and teleomorphic states. In the literature only seven other species of Aspergillus have been unequivocally reported as causing mycotic keratitis.

Aspergillosis

Regulation of lymphokine messenger RNA stability by a surface-mediated T cell activation pathway.

Quiescent T cells can be induced to express many genes by mitogen or antigen stimulation. The messenger RNAs of some of these genes undergo relatively rapid degradation compared to messenger RNAs from constitutively expressed genes. A T cell activation pathway that specifically regulates the stability of messenger RNAs for the lymphokines interleukin-2, interferon-gamma, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor is induced by stimulation of the CD28 surface molecule. This pathway does not directly affect the steady-state messenger RNA level, transcription, or messenger RNA half-life of other T cell activation genes, including c-myc, c-fos, IL-2 receptor, and the 4F2HC surface antigen. These data show that stimuli received at the cell surface can alter gene expression by inducing specific changes in messenger RNA degradation.

Antigens, Differentiation, T-Lymphocyte

Regulation of interleukin 3 gene induction in normal human T cells.

The regulation of IL-3 gene induction in human peripheral blood T cells was studied. IL-3 gene expression was inducible by crosslinking of the T cell receptor/CD3 complex using anti-CD3 MAb G19-4. Anti-CD3-induced IL-3 gene expression was found to be limited to the CD28+ T cell subset and could be augmented by costimulating T lymphocytes with antibodies directed against CD28. IL-3 expression could also be induced by costimulation of T cells with both phorbol ester and ionomycin, which are thought to mimic the intracellular effects of T cell receptor-antigen interaction. However, unlike other lymphokines such as IL-2 or granulocyte-macrophage colony-stimulating factor, IL-3 gene expression is not induced by stimulation of cells with phorbol myristate acetate and anti-CD28. We conclude that IL-3 gene regulation is under stringent control since IL-3 gene expression occurs only in the CD28+ subset of T cells, and since IL-3 induction obligately requires increased intracellular calcium.

Adult

[Generalized postoperative peritonitis: the meeting of surgery and resuscitation].

Fifteen cases of generalized post-operative peritonitis (GPP) are reported. Twelve patients underwent surgical treatment with mortality rate of 25%; three patients did not undergo surgery with mortality rate of 66,6%. Diagnostic, prognostic and therapeutic aspects of this severe post-operative complication are considered to underline the importance of a precocius diagnosis and a timely reanimatory and surgical treatment for a favourable prognosis.

Adult