Biomedical subjects

A Franchi

Publications and source records attributed to A Franchi.

At least 73 records · Page 4Linked to original sources

PubMed1999

Reduced E-cadherin expression correlates with unfavorable prognosis in adenoid cystic carcinoma of salivary glands of the oral cavity.

Reduced expression of E-cadherin (E-cad), a transmembrane glycoprotein, is associated with loss of differentiation, acquisition of an invasive phenotype, and an unfavorable prognosis in carcinomas from several sites. We used immunohistochemistry to study the expression of E-cad in 50 adenoid cystic carcinomas (ACCs) in salivary glands to evaluate correlations with clinicopathologic parameters and patient survival. Absent or low E-cad expression was observed more frequently in solid than in cribriform or tubular carcinomas. E-cad expression also was significantly correlated with histologic grade and the growth pattern. In addition, ACCs showing low or absent E-cad expression were more frequently larger than 4 cm in diameter, and distant metastases developed more frequently. Reduced expression correlated with shorter disease-free intervals and actuarial survival rates. Univariate and multivariate analysis identified tumor stage and E-cad expression as the only 2 parameters predictive of the disease-free interval. E-cad expression and tumor stage, grade, and type of growth were significant prognostic factors for survival in univariate analysis, while tumor stage, type of growth, and E-cad expression were the only significant covariates in multivariate analysis. These findings indicate that the loss of E-cad has an important role in the natural history of ACC, as it is associated with loss of differentiation and development of metastases. We also provide evidence that E-cad expression is an independent indicator of clinical aggressiveness in patients with ACC, together with clinical stage and type of growth at the periphery of the tumor.

Adult↗

PubMed1999

Naevus-associated melanomas: cause or chance?

Controversies exist regarding the true incidence and significance of the histological association between melanocytic naevi and melanomas. The current study was undertaken to determine the incidence of melanocytic naevi histologically associated with melanomas, to compare the clinicopathological profiles of melanomas associated with a naevus (MN+) and melanomas not associated with a naevus (MN-), and to verify the interobserver reliability of classifying the naevus remnants as congenital or acquired. We evaluated 131 patients with invasive melanoma < or = 4 mm in thickness with a Clark's level < V. Histological evidence of an associated melanocytic naevus was found in 27 out of 131 melanoma cases (20.6%). MN+ were significantly more frequent among males compared with MN-(P = 0.002) and were predominantly located on the trunk (P =0.001). No significant differences between MN+ and MN- were found in the distribution of histotype, Clark's level and thickness. Among MN-, the naevus component showed acquired features in 14 cases (51.8%), whereas 12 cases (44.5%) had features of small superficial congenital naevi; in one case (3.7%) a confident distinction between congenital and acquired naevus could not be made. Overall, there was concordance among the three observers in the diagnosis of the type of naevus remnants in 81.4% of cases (kappa = 0.78; P<0.0001). We conclude that, although the majority of cutaneous melanomas arise de novo, in approximately 20% of cases an associated melanocytic naevus is found. Our observation that MN+ and MN- have different clinicopathological profiles suggests that, at least for some cases, a causal relationship between the two lesions may be present. However, when the naevus is histopathologically adjacent to the melanoma, the possibility of a collision event cannot be ruled out. Finally, we documented a significant concordance among examiners in the diagnosis of the congenital versus acquired nature of the associated naevus. This suggests that the histopathological criteria generally employed to distinguish between congenital and acquired naevi have good reproducibility.

Adult↗

PubMed1999

Low plasma cholesterol: a correlate of nondiagnosed celiac disease in adults with hypochromic anemia.

OBJECTIVE: Hypochromic anemia is at times attributable to nondiagnosed celiac disease. The aim of this study was to define the correlates of celiac disease in anemic adults without overt malabsorption. METHODS: One hundred patients with hypochromic anemia and without diarrhea underwent a complete diagnostic work-up, including screening for celiac disease, i.e., upper endoscopy with duodenal biopsy and search of antiendomysium antibodies. RESULTS: Patients with hypochromic anemia were from two different Divisions and were analyzed as a single group because they were not significantly different for any variable. Hypochromic anemia was attributable to celiac disease in 10 patients. Compared to anemic patients without celiac disease, anemic patients with celiac disease had significant or borderline significant differences for plasma cholesterol (-17.9%), albumin (-9.4%), and body mass index (-11.8%), but not for gender distribution, age, weight, height, blood hemoglobin, mean corpuscolar volume, plasma iron, and ferritin. All anemic patients with celiac disease had plasma cholesterol < 156 mg/100 ml. Within the entire cohort of anemic patients, plasma cholesterol inversely related to prevalence of celiac disease (p < 0.001); also plasma albumin and body mass index inversely related to celiac disease, but coefficients were borderline significant (p = 0.056 and 0.052, respectively). CONCLUSIONS: The data suggest that among patients with hypochromic anemia, plasma cholesterol in the high-to-normal range could be used to exclude the presence of celiac disease. Other nutritional markers are less sensitive as indices of risk of celiac disease. Hematological indices are not of help to define the risk of celiac disease in anemic patients without signs of malabsorption.

Adolescent↗

PubMed1999

Author's reply

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Journal Article↗

PubMed1999

A reappraisal of the histopathologic criteria for the diagnosis of cutaneous allogeneic acute graft-vs-host disease.

To determine the validity of the Lerner grading system and review the histopathologic findings of cutaneous acute graft-vs-host disease (aGVHD), 78 skin biopsy specimens from 49 bone marrow transplant recipients were evaluated. Histopathologic sections were independently reviewed twice by 3 pathologists and classified (Lerner system), without knowledge of the patients' clinical evolution. Intraobserver agreement in grading aGVHD was substantial to almost perfect. Interobserver agreement between pairs of observers was moderate to substantial on first review and substantial on second review. Overall, we found an almost perfect agreement in diagnosing Lerner grade III, whereas areas of disagreement occurred with Lerner grades 0, I, and II. Histopathologically, specimens of patients who developed aGVHD (aGVHD-positive) showed significantly higher frequency of epidermal atrophy, spongiosis, diffuse basal vacuolization, more than 3 single necrotic keratinocytes per high-power field, satellitosis, inflammatory infiltrate, with a predominantly lichenoid pattern, lymphocytic exocytosis, and dermal melanophages. When considering skin samples classified as grade I and II, we found statistically significant differences between aGVHD-positive and aGVHD-negative cases only for the presence of inflammatory infiltrate, lymphocytic exocytosis, and satellitosis. Lerner grading is reproducible, although lesser agreement occurred when evaluating grades I and II, and the Lerner grading system should be revised by including the estimate of the inflammatory infiltrate as an additional criterion for grade II.

Acute Disease↗

PubMed1998

Progesterone enhances prostaglandin E2 production via interaction with nitric oxide in the mouse acrosome reaction.

In the present study we evidenced that progesterone could directly stimulate sperm nitric oxide synthase (NOS) in capacitated mouse spermatozoa. This stimulation led to an increase in sperm prostaglandin E2 (PGE2) production and subsequent acrosomal exocytosis. However, cGMP levels were not modified during the progesterone-induced acrosome reaction under our experimental conditions. These results suggest a functional role for nitric oxide as an intracellular messenger through, at least, stimulation of PGE2 production during the acrosome reaction triggered by progesterone.

Acrosome Reaction↗

PubMed1998

Role of nitric oxide in angiogenesis and tumor progression in head and neck cancer.

BACKGROUND: Angiogenesis (formation of new blood vessels) is associated with tumor growth and metastasis in patients with solid tumors, including those of the head and neck. Nitric oxide (NO) production may contribute to these processes. We assessed the role of the NO pathway in angiogenesis and tumor progression in patients with head and neck cancer. METHODS: Biochemical assays were used to measure NO synthase (NOS) activity and cyclic guanosine monophosphate (cGMP) levels in specimens of tumor and normal mucosa obtained from 27 patients. Microvessels in tumor specimens were identified by CD-31-specific immunohistochemical staining. Associations between microvessel densities, levels of NOS, and cGMP were examined by use of two-sided statistical tests. Tumor specimens and human squamous carcinoma A-431 cells were grown as explants on the corneas of rabbits, and the effect of the NOS inhibitor N(omega)-nitro-L-arginine-methyl ester (L-NAME) was tested. RESULTS: Levels of total NOS, inducible NOS, and cGMP were higher in tumor specimens than in specimens of normal mucosa (all P<.0001). Tumor specimens from patients with lymph node metastases presented a higher total NOS activity (P = .005) and were markedly more vascularized than tumor specimens from patients with no lymph node involvement (P = .0002). Microvessel density at the tumor edge was an independent predictor of metastasis for this series of patients (odds ratio = 1.19; 95% confidence interval = 1.07-2.89; P = .04). A-431 cells and tumor specimens exhibiting high levels of NOS activity induced angiogenesis in the rabbit cornea assay; when NO production was blocked, tumor angiogenesis and growth were repressed. CONCLUSIONS: The NO pathway appears to play a key role in tumor angiogenesis and spread in patients with head and neck cancer.

Adult↗

PubMed1998

Expression of transforming growth factor beta isoforms in osteosarcoma variants: association of TGF beta 1 with high-grade osteosarcomas.

Studies on osteosarcoma cell lines point to the potential importance of transforming growth factor beta (TGF beta) as an autocrine factor which controls the growth of human osteosarcomas. To define further the role of TGF beta isoforms in these neoplasms, a series of 27 osteosarcomas was studied using immunohistochemical, mRNA in situ hybridization, and reverse transcriptase-polymerase chain reaction (RT-PCR) techniques. All 14 central high-grade osteosarcomas, two telangiectatic osteosarcomas, and one high-grade surface osteosarcoma showed cytoplasmic immunoreactivity for TGF beta 1, -2, and -3. The expression of TGF beta 1 was moderate or diffuse in 14 cases (82.3 per cent), while low expression was detected in only three cases (17.7 per cent). For TGF beta 2 and -3, only moderate or diffuse staining was observed. Low-grade parosteal and periosteal osteosarcomas showed low or undetectable levels of TGF beta 1, while TGF beta 2 and -3 were moderately or diffusely expressed. Finally, three dedifferentiated parosteal osteosarcomas were diffusely positive for TGF beta 1, -2, and -3 in the high-grade component, while in the low-grade component, available for analysis in two of these cases, TGF beta 1 was demonstrated in a few neoplastic cells, and TGF beta 2 and -3 maintained a diffuse distribution. Statistical analysis of these data showed that high-grade osteosarcomas had a significantly higher expression of TGF beta 1 than low-grade osteosarcomas, while levels of TGF beta 2 and -3 were comparable in the two groups (p < 0.001; p = 0.3; p = 0.3, respectively; Fisher's exact test). Similarly, mRNA levels of TGF beta 1 detected by in situ hybridization were significantly higher (p = 0.04, Fisher's exact test) in high-grade osteosarcoma variants, while no differences were found for TGF beta 2 and -3 mRNA (p = 1.0; p = 0.2, respectively; Fisher's exact test). In addition, mRNA analysis performed by RT-PCR in seven cases (five high-grade and two low-grade osteosarcomas) confirmed the presence of high levels of TGF beta 1 in high-grade osteosarcomas, while low-grade tumours had low or absent mRNA expression. In conclusion, this positive association suggests that TGF beta 1 may be involved in determining the aggressive clinical behaviour of high-grade osteosarcomas.

Bone Neoplasms↗

PubMed1998

Prognostic significance of c-erbB-2 oncoprotein expression in intestinal-type adenocarcinoma of the sinonasal tract.

BACKGROUND: The c-erbB-2 gene codes for a putative transmembrane protein, similar in structure to the epidermal growth factor receptor. Amplification and/or overexpression of the gene has been recently described with a prognostic significance in a variety of human adenocarcinomas. METHODS: A monoclonal antibody against the c-erbB-2 oncoprotein has been used immunocytochemically in a retrospective study of formalin-fixed, paraffin-embedded samples from 28 consecutive intestinal-type adenocarcinomas (ITACs) of the nose and paranasal sinuses. RESULTS: Nine out of 28 primary adenocarcinomas (32%) showed positive staining. Clinical follow-up data, available for all patients, suggested in a univariate analysis a correlation between c-erbB-2 expression and poor prognosis, as measured by 5-year disease-free (p = .02) and overall survival curves (p = .07) as well as by recurrence of disease and the appearance of regional and distant metastases (p = .08). In multivariate analysis, c-erbB-2 expression was statistically significant in terms of disease-free survival (p = .046) but not of overall survival (p = .091) in our series. CONCLUSIONS: These data indicate that c-erbB-2 oncogene activation could be involved in sinonasal tract oncogenesis, with possible prognostic implications.

Adenocarcinoma↗

PubMed1998

Synovial chondromatosis in a lumbar apophyseal joint.

A 31-year-old woman presented with painful swelling in the right paravertebral region that had been present for 2 years. Radiography and CT revealed an area of increased density due to multiple calcifications localized at the fourth lumbar vertebra. Histological examination revealed that the lesion consisted of nodules of hyaline cartilage, with focal areas of calcification, growing within synovial tissue.

Adult↗

PubMed1998

Immunohistochemical detection of c-fos and c-jun expression in osseous and cartilaginous tumours of the skeleton.

The products of c-fos and c-jun proto-oncogenes form the heterodimeric complex AP-1 (activator protein 1), which play an important part in the control of bone cell proliferation and differentiation and in the development of bone tumours. We examined the expression of c-fos and c-jun in a series of 52 primary skeletal neoplasms, using an immunohistochemical method on formalin-fixed, paraffin-embedded sections. The expression of c-fos and c-jun was restricted to bone-forming lesions, while cartilaginous tumours were devoid of immunoreactivity. In benign osteoblastic lesions moderate c-fos and c-jun expression was found in 2 cases (18.1%). The highest levels of c-fos and c-jun expression were detected in high-grade central osteosarcomas (7 of 15 cases with moderate/diffuse expression) while 1 telangiectatic osteosarcoma, 2 low-grade central osteosarcomas, 1 low-grade periosteal osteosarcoma and 7 low-grade parosteal osteosarcomas were either negative or had low expression. The high-grade component of a dedifferentiated parosteal osteosarcoma showed diffuse immunoreactivity for both oncoproteins. Comparison of c-fos and c-jun expression by histological grade showed that high-grade osteosarcomas had a significantly higher expression of both oncoproteins than did low-grade osteosarcomas (P = 0.01, Fisher's exact test). Thus, c-fos and c-jun overexpression may be implicated in the development of high-grade osteosarcomas, but they appear to have little or no relevance for the development of low-grade osteosarcomas and cartilaginous skeletal neoplasms.

Bone Neoplasms↗

PubMed1998

Effect of IL-1alpha on prostaglandin synthesis of oestrogenized rat uterus is mediated by nitric oxide.

We examined the possible relationship between cytokines, nitric oxide (NO) and prostaglandins in the oestrogenized rat uterus. Results indicate that: IL-1alpha but not IL-2 enhances the synthesis of prostaglandins in oestrogenized rat uteri; IL-1alpha but not IL-2 induced an augmention of NO production in this tissue; the effect of IL-1alpha on prostaglandin synthesis is abolished by NMMA, an NO antagonist; NS-398, a COX-2 inhibitor, prevents the augmention of prostaglandins produced by IL-1alpha. These results suggest that there is an interaction between IL-1alpha, NO and prostaglandins and that this interrelationship involves COX-2. This mechanism might be important during implantation and labor.

Animals↗

PubMed1998

Aromatase expression and activity in the human leukaemic cell line FLG 29.1.

The recent observation that estrogen synthesis occurs in osteoblast-like cells has suggested the aromatase activity as a possible local modulator of bone remodeling in post-menopausal women. To provide further insights into the androstenedione conversion to estrogen in bone-derived cells, we examined the human leukaemic cell line FLG 29.1, which is induced to differentiate toward the osteoclastic phenotype by TPA and TGF-beta1. Southern blot of RT-PCR products with a 32P-labeled cDNA probe for the human aromatase demonstrated that FLG 29.1 cells express aromatase mRNA. The enzyme activity, determined by measuring [3H]H2O release from [3H]androstenedione, obeyed Michaelis-Menten kinetic with apparent Km and Vmax values ranging from 5 to 10 nM and from 200 to 400 fmol/mg protein/6 h. Gene expression, enzyme activity and protein immunoreactivity, evaluated by immunocytochemistry, were stimulated in a time-dependent fashion by 5% charcoal-stripped FCS and by either 1-100 nM TPA or 0.01-0.5 ng/ml TGF-beta1, with maximal responses after 2-3 h exposure. After 24 h incubation of FLG 29.1 cells in the absence of these stimuli the aromatase mRNA and the protein were barely detectable. These findings demonstrate that cells of the osteoclastic lineage synthesize estrogen in vitro and that local cytokines, such as TGF-beta1, are able to induce androstenedione conversion.

Androstenedione↗

PubMed1998

Malignant melanoma associated with human immunodeficiency virus infection: a case report and review of the literature.

A case of malignant melanoma arising in a young patient suffering from human immunodeficiency virus (HIV) infection is reported, along with a review of the literature. The neoplasm was characterized by aggressive clinical behaviour and, histopathologically, by a peculiar retiform pattern of growth with neoplastic cells interspersed among collagen bundles in the dermis without evident fibroplastic stromal reaction. In addition, a complete absence of host inflammatory cell infiltrate was noted. We hypothesize that this unusual histopathological pattern of growth, which has never been reported in this clinical setting, might be associated to HIV disease, immunosuppression and poor clinical outcome.

Adult↗

PubMed1998

Immunogenetic basis of environmental lung disease: lessons from the berylliosis model.

The role of genetic factors has been hypothesized in the pathogenesis of a number of chronic inflammatory lung diseases. The genes of the major histocompatibility complex (MHC) locus on human chromosome 6 have been identified as important determinants in diseases caused both by inorganic and organic compounds such as beryllium, gold, acid anhydrides, isocyanates and grass pollens. Since many environmental factors are the determinants of the immunopathogenesis of asthma, pulmonary granulomatous disorders, hypersensitivity pneumonitis and fibrotic lung disorders, an understanding of the interaction between environmental factors is crucial to epidemiology, prevention and treatment of these disorders. Berylliosis is an environmental chronic inflammatory disorder of the lung caused by inhalation of beryllium dusts. A human leukocyte antigen class II marker (HLA-DP Glu69) has been found to be strongly associated with the disease. In in vitro studies, the gene has been shown to play a direct role in the immunopathogenesis of the disease. In human studies, the gene has been shown to confer increased susceptibility to beryllium in exposed workers, thus suggesting that HLA gene markers may be used as epidemiological probes to identify population groups at higher risk of environmental lung diseases, to identify environmental levels of lung immunotoxicants that would be safe for the entire population and to prevent disease risk associated with occupation, manufactured products and the environment. Studies on the associations between human leukocyte antigens and chronic inflammatory lung disorders are reviewed in the context of the berylliosis model.

Animals↗

PubMed1998

[Effect of lysine clonixinate and indomethacin on lipoxygenase and cyclooxygenase activity in colon isolated from cancer patients].

The non-steroidal anti-inflammatory drugs (NSAIDS) induced ulcerations in the gastrointestinal tract are possibly associated with the reduction in prostaglandin (PGs) synthesis due to the inhibition of cyclooxygenase. On the other hand, it has been shown that 5-lipooxygenase products (5-LO) are ulcerogenic agents. In some cases, the utilization of NSAIDS stimulates 5-LO pathway to an excess of arachidonic acid because of cyclooxygenase inhibition. In these cases, the damage produced by NSAIDS is greater, since not only the cytoprotective PGs decrease but also the products of 5-LO are increased. The object of the present paper was to study the effects of lysine clonixinate (LC) and indomethacin (INDO) on PGs and 5-HETE synthesis. The concentrations used of LC (4 and 6 micrograms/ml) and INDO (0.035 micrograms/ml and 0.35 micrograms/ml) correspond to the plasmatic values reached with oral therapeutic doses for both drugs. The results show that in no case did LC reduce the production of PGE2. On the contrary INDO inhibited significantly the synthesis of PGe2. It is interesting to mention that LC 4 and 6 micrograms/ml inhibited drastically the production of 5-HETE. Only with the higher concentration of INDO did we observe a similar effect. These results may indicate an inhibitory action on 5-LO, the first enzyme in the metabolic pathway of arachidonic acid in the production of HETEs and LTS. We conclude that LC in therapeutic doses has a mechanism of action different from the classical NSAIDS. The data obtained in this study could explain the low incidence in gastrointestinal lesions with LC.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1998

Clear-cell smooth muscle tumor of the skin.

We report a case of a previously undescribed benign neoplasm characterized by a poorly circumscribed proliferation of clear cells, arranged both singly and in elongated fascicles oriented in haphazard fashion within the middle and lower reticular dermis. The fascicles consisted of spindle-shaped cells that were periodic acid-Schiff positive and diastase labile. These cells were characterized by oval, hyperchromatic, cigar-shaped nuclei and clear cytoplasm. Immunohistochemically, neoplastic cells were diffusely positive for smooth muscle actin (1A4), common muscle actin (HHF-35), and vimentin. Immunoreactivity for fibronectin was also focally noted. The neoplasm, which we designated clear-cell smooth muscle tumor of the skin, should be distinguished from smooth muscle hamartoma and other smooth muscle proliferations at cutaneous level. We highlight in this case report the histopathologic differential diagnosis among other tumors with myofibroblastic, melanocytic, and neural differentiation.

Actins↗

PubMed1997

Structure and chromosomal assignment of the mouse fra-1 gene, and its exclusion as a candidate gene for oc (osteosclerosis).

We have determined the genomic structure of the mouse fra-1 gene, which consists of four exons and three introns at positions also found in the other members of the fos gene family. Fra-1 is expressed rather highly in the brain and testes of adult mice, and at low levels in most other tissues. Absence of c-Fos leads to significantly reduced serum stimulation of fra-1 expression in gene targeted mouse fibroblasts, demonstrating that mitogen induction of fra-1 is partially mediated by c-Fos/AP-1. A polymorphic (CA)n microsatellite marker was found in intron 2 of fra-1 and used to map the gene to the centromeric region of mouse chromosome 19. Since fra-1 maps to the same genomic region as oc (osteosclerosis), an autosomal recessive disorder leading to the bone remodelling disease osteopetrosis, we tested it as a candidate gene for oc. The segregation of fra-1 in two different crosses of mice carrying oc and an allelism test between oc and a targeted disruption of fra-1 demonstrate that fra-1 and oc are two distinct genes rather than oc being a mutant allele of fra-1.

Amino Acid Sequence↗