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Biomedical subjects

A Franchi

Publications and source records attributed to A Franchi.

At least 109 records · Page 6Linked to original sources
PubMed1995

Distribution of neuronal and non-neuronal NADPH diaphorases and nitric oxide synthases in rat uterine horns under different hormonal conditions.

Since pharmacological evidence indicates that nitric oxide (NO) operates in the control of uterine motility, we have studied the distribution of NADPH diaphorase and NO synthases in the rat uterus using histochemical and immunohistochemical methods. Numerous nerve fibers displayed NADPH diaphorase activity and immunoreactivity to antisera raised against neuronal NO synthase. Nerve fibers appeared in all stages of the estrous cycle and also after ovariectomy. NADPH diaphorase activity was also present in endothelia and cells dispersed in the different uterine layers. Most NADPH diaphorase-positive (ND) cells had eosinophilic granules with occasional cells expressing the ED1 macrophage-monocyte marker. Immunoreactivity for an inducible NO synthase was found in a small number of macrophage-like cells without NADPH diaphorase activity. Thus, ND cells may express another NO synthase isoform not detected by the available antisera. In normal cycling rats, ND cells were most abundant during proestrus, and their number further increased after estrogen treatment. ND cells were not observed after ovariectomy but were present after estrogen replacement therapy. ND cells could be involved in the estrogenic control of in vivo and in vitro uterine.

Amino Acid Oxidoreductases↗
PubMed1995

Immunolocalization of extracellular matrix components in mixed tumors of the skin.

Mixed tumors of the skin are characterized by a proliferation of epithelial cells embedded in a mesenchymal matrix with a wide spectrum of histologic appearances. The characterization of the extracellular matrix components of mixed tumors of the skin has so far received little attention. We performed an immunohistochemical study of type IV collagen, laminin, fibronectin, and tenascin distribution in a series of 10 mixed tumors of the skin. Laminin localized at the basement membrane around solid epithelial nests and tubulo-alveolar structures, whereas type IV collagen, fibronectin, and tenascin were also expressed in the myxoid stroma. Tenascin and fibronectin localized in the chondroid matrix. The extracellular matrix components were prominently expressed in mixed tumors of the skin, suggesting that they could play an important role in the formation and organization of myxoid and chondroid matrices and in the epithelial-mesenchymal interactions of these tumors.

Adenoma, Pleomorphic↗
PubMed1995

Changes in the hypothalamic interaction between norepinephrine and prostaglandin E2 during sexual maturation in female rats.

The present experiments describe the study of the metabolism of 14C-arachidonic acid and the effect of exogenous norepinephrine (NE) on prostanoid production in the anterior preoptic area and medial basal hypothalamus (APOA-MBH) of prepubertal (16 days of age) and peripubertal female rats (30 days old). Four prostanoids were produced from 14C-arachidonic acid (6-keto-prostaglandin(PG)F1 alpha, PGF2 alpha, PGE2 and thromboxane (TX)B2) and were released to the incubating medium. The basal percent of conversion was not significantly different between them. In prepubertal rats the addition of NE (10(-5) M) to the medium did not modify on the synthesis of these eicosanoids. In peripubertal rats there are no significant differences in the basal production of 6-keto-PGF1 alpha, PGF2 alpha, PGE2 and TXB2 as compared to prepubertal rats. Moreover, the percentage of conversion of arachidonic acid into the different prostanoids was similar in prepubertal and peripubertal hypothalamus. Nevertheless, when NE (10(-5) M) was added to the incubation medium of peripubertal hypothalamus. Nevertheless, significant increase in the synthesis of PGE2 was observed (control: 1.75 +/- 0.1; NE 2.90 +/- 0.3; p < 0.01). This increase in the synthesis was not accompanied by changes in the synthesis of any of the other three prostanoids. Prazosin, a well-known alpha 1-receptor adrenoblocker at a dose of 10(-5) M did not modify the production of 6-keto-PGF1 alpha, PGF2 alpha, PGE2 and TXB2 but did induce a complete inhibition of the stimulation by NE of PGE2 synthesis (NE: 2.85 +/- 0.1; prazosin: 1.9 +/- 0.09; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1995

Cisplatin increases sensitivity of human leukemic blasts to triazene compounds.

High levels of O6-alkylguanine-DNA-alkyltransferase (OGAT) can, at least in part, account for tumor cell resistance to O6-alkylguanine alkylating agents, including triazene compounds. A pilot clinical study indicates that dacarbazine can induce a marked decrease of leukemic blasts in patients affected by acute myelogenous leukemia (AML) with low pretreatment levels of OGAT activity. In this study we show a synergistic antitumor effect between cisplatin (CDDP) and temozolomide (an in vitro active analog of dacarbazine), following combined in vitro treatment of leukemic blasts. Synergistic effect appears to be CDDP-dose dependent. In vivo treatment of leukemic patients with CDDP was followed by a reduction of OGAT activity in 2 out 3 cases. These data point out that CDDP could be a good candidate for depleting OGAT protein of leukemic cells, thus reversing tumor cell resistance to dacarbazine.

Adult↗
PubMed1994

Immunolocalization of alpha 2, alpha 5, and alpha 6 integrin subunits in salivary tissue and adenomas of the parotid gland.

The localization of the integrin subunits alpha 2, alpha 5, alpha 6 was studied immunohistochemically in samples of normal salivary gland and in a series of 8 pleomorphic adenomas, 5 Warthin's tumors, and 2 basal cell adenomas. In normal salivary tissue, acinar and ductal cells expressed alpha 2 and alpha 6 chains at the basal cell pole facing the basement membrane. alpha 2 also localized at sites of cell-cell contact. No staining of the epithelial component was seen with alpha 5. The polarized expression of alpha 2 and alpha 6 subunits was retained in salivary adenomas. These subunits were present at the basal cell pole of solid nests, tubules and ducts of pleomorphic adenomas, as well as of the basal layer of the epithelium of Warthin's tumor, and of the trabecular structures of basal cell adenomas. The alpha 5 subunit was consistently expressed only by cells embedded in the myxoid or chondroid matrix of pleomorphic adenomas. We conclude that the pattern of a integrin subunit expression in salivary adenomas may be related to the "epithelial" or "mesenchymal" phenotype of the neoplastic cells.

Adenolymphoma↗
PubMed1993

Intestinal-type adenocarcinoma of the sinonasal tract: a clinicopathologic study of 18 cases.

BACKGROUND: Intestinal-type adenocarcinoma (ITAC) of the nose and paranasal sinuses is a relatively rare tumor. It commonly affects subjects exposed to wood or leather dust. METHODS: The authors present the clinicopathologic findings of 18 cases of sinonasal ITACs and review the proposed histologic classifications. RESULTS: All patients, except one, were males; mean age was 60 years (range, 41-79); in 9 cases an occupational exposure to wood or leather dust was found. Common presenting symptoms were epistaxis, nasal obstruction and rhinorrhea. Histologically, tumors were divided into four groups: well-differentiated (G1) ITACs = 3 cases; moderately differentiated (G2) ITACs = 8 cases; poorly differentiated (G3) ITACs = 2 cases; mucinous (M) ITACs = 5 cases. Immunocytochemically, 16/17 cases were positive for carcinoembryonal antigen, 1/17 for somatostatin, and 0/16 cases for gastrin. CONCLUSIONS: Sinonasal ITACs are aggressive tumors, often diagnosed in a relatively advanced stage. Owing the close similarity of the microscopic aspects, a histologic classification of ITACs analogous to that of colonic adenocarcinomas is proposed.

Adenocarcinoma↗
PubMed1993

A point mutation of the Na+/H+ exchanger gene (NHE1) and amplification of the mutated allele confer amiloride resistance upon chronic acidosis.

The diuretic drug amiloride and its 5-amino substitute N5-methyl-N5-propylamiloride (MPA) are potent inhibitors of the growth factor-activatable Na+/H+ exchanger isoform 1 (NHE1). This inhibitor competes with Na+, presumably by interacting with the ion-transport site of the NHE molecule. As an approach to identify this site, we previously reported the use of a specific H(+)-killing selection technique for isolating amiloride-resistant variants of Chinese hamster lung fibroblasts. After long-term selection, two variants, AR40 and AR300, 100- and 1000-fold, respectively, resistant to MPA, were isolated. By comparing NHE1 cDNA sequences of parental and two variant cell lines, we show that the 1000-fold resistance to MPA results from two sequential genetic events. (i) In one AR40 allele a point mutation, Phe-167--> Leu, occurs in the middle of the fourth putative transmembrane segment of NHE1. Producing this mutant protein from human NHE1 cDNA by site-directed mutagenesis increased the Ki for MPA by 30-fold, as seen in AR300 cells. (ii) An approximately 10-fold amplification of the mutated allele, which contributes to the acquired MPA resistance, accounts for the Vmax increase. Mutating a close residue, Phe-165--> Tyr, increased by 40-fold the Ki for amiloride and reduced Na+ transport rate 3- to 4-fold, indicating that we have identified a critical domain of the NHE molecule that controls amiloride binding and Na+ transport. Interestingly, the epithelial amiloride-resistant NHE isoforms that occurred naturally possess some of the amino acid substitutions described here.

Alleles↗
PubMed1993

Studies with glycolysis-deficient cells suggest that production of lactic acid is not the only cause of tumor acidity.

Solid tumors have been observed to develop an acidic extracellular environment, which is believed to occur as a result of lactic acid accumulation produced during aerobic and anaerobic glycolysis. Experiments using glycolysis-deficient ras-transfected Chinese hamster lung fibroblasts have been performed to test the hypothesis that lactic acid production within solid tumors is responsible for the development of tumor acidity. The variant cells have defects in glucose transport and in the glycolytic enzyme phosphoglucose isomerase with 1% activity compared to parental cells. Consequently, the in vitro rate of lactic acid production by variant cells was < 4% compared to parental cells. An in vitro correlation between lactic acid production and acidification of exposure medium was observed for parental and variant cells. Implantation of both cell lines into nude mice led to tumors with minimal difference in growth rate. As expected, variant cells died when exposed to hypoxic conditions in culture, and parental tumors were observed to have a larger fraction of cells resistant to radiation due to hypoxia (27%) than variant tumors (2%). Using pH microelectrodes, parental (n = 12) and variant (n = 12) tumors were observed to have extracellular pH (pHe) values of 6.65 +/- 0.07 and 6.78 +/- 0.04 (mean +/- SE, P = 0.13), respectively, whereas normal muscle had a pHe of 7.29 +/- 0.06 (P < 0.0001 for both cell lines). The lactic acid content of variant tumors was found to be similar to that in serum, whereas parental tumors had lactic acid content that was higher than in serum (P < 0.0001). We conclude that there was no correlation between lactic acid content and acidosis for these tumors derived from ras-transfected fibroblasts. These results provide evidence that the production of lactic acid via glycolysis is not the only mechanism responsible for the development of an acidic environment within solid tumors.

Aerobiosis↗
PubMed1993

All-trans retinoic acid plus low doses of cytarabine for the treatment of "poor-risk" acute myeloid leukemias.

Thirteen refractory/resistant AML patients no suitable for additional aggressive chemotherapy, were treated with a combination including all-trans retinoic acid (45 mg/m2 sine die) and low doses of Ara-C (20 mg/m2 subcutaneously, twice in a day, days 1-10, every 28 days). Ten patients were evaluable; 8 of them achieved a complete remission, two patients with an important tumor burden, failed to achieve a response. One complete remission patient relapsed after 7 months but is still receiving the same therapy and is now in partial remission. We believe this combination effective as inducer of complete remission in those AML patients which cannot tolerate additional heavy treatments. The role of tumor burden in affecting response to therapy remains to be still evaluated.

Aged↗
PubMed1992

Adhesion, growth, and matrix production by osteoblasts on collagen substrata.

A number of studies have demonstrated the pivotal role of collagen molecules in modulating cell growth and differentiation. In order to analyze the direct effects of collagen type I on the osteoblastic phenotype, we have devised an in vitro culture system for studying the interactions between bovine collagen type I and Saos-2 cells, a human osteoblastic cell line. Saos-2 cells were cultured both on top of collagen-coated culture dishes as well as inside a three-dimensional collagen network. Plating on dishes treated with collagen induced maximal adhesion of Saos-2 cells after 24-hour incubation. Cells cultured on collagen gel matrix expressed about 2.5-fold more alkaline phosphatase when compared with untreated plastic dishes. On collagen-coated dishes the responsiveness of Saos-2 cells to parathyroid hormone was decreased, whereas no modifications were observed in the effect of vasoactive intestinal peptide on these cells. Using a microfluorimetric measurement of DNA, an increase of proliferation was observed in Saos-2 cells cultured on collagen gel. Saos-2 cells were also able to colonize collagen sponges and in this three-dimensional network they were able to synthesize osteocalcin, as assessed both by immunocytochemistry and radioimmunoassay. In this study we have demonstrated that bovine collagen type I exhibits favorable effects on attachment and functional and growth activities of a human osteoblastic cell line, encouraging its use as a bone graft material.

Alkaline Phosphatase↗
PubMed1992

Cytological and ultrastructural investigation on osteoblastic and preosteoclastic cells grown in vitro in the presence of ipriflavone: preliminary results.

The effects of ipriflavone on bone cells were studied in vitro on pre-osteoclastic (FLG 29.1) and osteoblast-like (Saos-2) cells grown for 48 h either separately or in co-cultures, with or without the addition of PTH. Histological, ultrastructural and histochemical (TRAP-activity demonstration) methods were used. The main results show that ipriflavone reduces replication of FLG 29.1 cells and inhibits TRAP production by these cells both in controls and in co-cultures treated with PTH. Moreover, it has a moderate stimulatory effect on proliferation of osteoblast-like cells and reduces the PTH-induced degenerative changes of Saos-2 cells. These results suggest that the inhibitory effect of ipriflavone on FLG 29.1 cells might be indirect and might be mediated by the osteoblast-like cells.

Acid Phosphatase↗
PubMed1992

Secondary avascular necrosis in coxarthrosis: a morphologic study.

Secondary subarticular avascular necrosis was observed grossly in 11.7% of femoral heads removed surgically because of osteoarthritis (OA). In most cases the necrosis was superficial, however in 15% of the 82 cases of secondary necrosis the necrosis was deep and wedge shaped similar in appearance to the lesions seen in primary subarticular avascular necrosis. Most of the lesions were seen in the early stage of OA and it is suggested that the lesion may interfere with the subsequent reparative phenomenon.

Adult↗