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Biomedical subjects

C Della Rocca

Publications and source records attributed to C Della Rocca.

At least 19 recordsLinked to original sources

Survivin and Cyclooxygenase-2 are co-expressed in human and mouse colon carcinoma and in terminally differentiated colonocytes.

In the evolution of colon rectal cancer (CRC) the imbalance between cell proliferation and apoptosis is considered one of the prominent causes of tumor induction and/or progression. In order to establish the role of anti apoptotic proteins in colon cancer development, we studied with immunohistochemical techniques the expression of Survivin in a mouse model of colon carcinogenesis induced by 1,2-dimethyl-hydrazine treatment. In this mouse model Survivin was over-expressed during tumor development, showing a distribution mimicking that described in the correspondent human malignancies. We also correlated Survivin distribution with COX-2 and beta-Catenin expression patterns. The co-localization of COX-2/beta-Catenin/Survivin in the same epithelial cells in tumor samples lends credence to possible in vivo regulatory effects of COX-2 and beta-Catenin on the intracellular Survivin levels in mouse and human colon cancer.

1,2-Dimethylhydrazine↗

Inflammatory infiltrate of the edges of a torn rotator cuff.

There is still considerable controversy as to whether or not the inflamed margins of a cuff tear should be excised during surgical suture. We have tried to discover whether anti-inflammatory drugs used before surgical treatment could resolve this issue. Thirty-eight patients were randomly either treated with an anti-inflammatory drug for 2 weeks or not. During the subsequent arthroscopic repair, a few fragments of supraspinatus edge were excised and examined microscopically. No significant differences emerged among samples belonging to the two groups. In all cases, we observed inflammatory infiltrate-lined tear edges. Fibrocytes and newly formed vessels were detected near the margin. Dystrophic calcifications were observed in both groups. Away from the edge, the tendon appeared hypocellular; containing areas with myxoid or fatty degeneration. Our study demonstrates that an anti-inflammatory drug is unable to resolve the inflammatory infiltrate. This failure is probably related to the poor blood supply to the cuff, which, in cases of rupture, is deprived of vessels coming from the humeral periosteum. Further studies are needed to understand how to eliminate the inflammatory process and clarify whether it might inhibit cuff healing and give rise to re-tearing of the sutured cuff.

Aged↗

Atypical disseminated leishmaniasis resembling post-kala-azar dermal leishmaniasis in an HIV-infected patient.

Post-kala-azar dermal leishmaniasis (PKDL) is very uncommon among HIV-positive patients, and very few cases have so far been documented. A case of atypical disseminated leishmaniasis resembling PKDL in an HIV-positive patient successfully treated with N-methylglucamine antimoniate is reported. The polymerase chain reaction performed on the skin lesions was positive for Leishmania infantum.

AIDS-Related Opportunistic Infections↗

The mGlu5 metabotropic glutamate receptor is expressed in zones of active neurogenesis of the embryonic and postnatal brain.

Metabotropic glutamate (mGlu) receptors have been implicated in the regulation of developmental plasticity. Here, we examined the expression of mGlu1a-b, -2, -3, -4a-b, and -5a receptor subtypes from embryonic day 12 (E12) to the early and late postnatal life. While all transcripts (with the exception of mGlu4 mRNA) were detected prenatally, only the mGlu5 receptor protein was found in detectable amounts in the embryonic brain. Immunohistochemical analysis showed that the mGlu5 receptor was mainly expressed by cells surrounding the ventricles at E15, whereas it was more diffusely expressed at E18. In the postnatal life, besides its classical expression sites, the mGlu5 receptor was found in zones of active neurogenesis such as the external granular layer (EGL) of the cerebellar cortex and the subventricular zone. In these regions, the presence of actively proliferating progenitor cells was detected by BrdU staining. No other subtype (among those we have examined) was found to be expressed in regions enriched of BrdU(+) cells. These data suggest a role for mGlu5 receptors in the early brain development and in basic cellular processes such as proliferation and/or differentiation.

Animals↗

Experimental posterolateral spinal fusion with porous ceramics and mesenchymal stem cells.

Alternatives to autogenous bone graft for spinal fusion have been investigated for many years. It has been shown that osteoconductive materials alone do not give a rate of fusion which is comparable to that of autogenous bone graft. We analysed the effectiveness of porous ceramic loaded with cultured mesenchymal stem cells as a new graft material for spinal fusion in an animal model. Posterolateral fusion was carried out at the L4/L5 level in 40 White New Zealand rabbits using one of the following graft materials: porous ceramic granules plus cultured mesenchymal stem cells (group I); ceramic granules plus fresh autogenous bone marrow (group II); ceramic granules alone (group II); and autogenous bone graft (group IV). The animals were killed eight weeks after surgery and the spines were evaluated radiographically, by a manual palpation test and by histological analysis. The rate of fusion was significantly higher in group I compared with group III and higher, but not significantly, in group I compared with groups II and IV. In group I histological analysis showed newly formed bone in contact with the implanted granules and highly cellular bone marrow between the newly formed trabecular bone. In group II, thin trabeculae of newly formed bone were present in the peripheral portion of the fusion mass. In group III, there was a reduced amount of newly formed bone and abundant fibrous tissue. In group IV, there were thin trabeculae of newly formed bone close to the decorticated transverse processes and dead trabecular bone in the central portion of the fusion mass. In vitro cultured mesenchymal stem cells may be loaded into porous ceramic to make a graft material for spinal fusion which appears to be more effective than porous ceramic alone. Further studies are needed to investigate the medium- to long-term results of this procedure, its feasibility in the clinical setting and the most appropriate carrier for mesenchymal stem cells.

Animals↗

Periapical cemental (fibrous) dysplasia. Clinical, radiographic and pathologic aspects in 7 reported cases.

AIM: Periapical cemental dysplasia (PCD) is a relatively common, well-defined pathology. Because of the structural similarities existing in the group of the so-called "fibro-(cemento)-osseus lesions" of the jaws, to which PCD belongs, clinical and radiographic findings are probably more diagnostic than histology. The aim of the present paper is to analyse some new cases of PCD and to compare their clinical, radiographic and histologic features to those reported by the international literature. METHODS: Seven new cases of PCD are presented here; they were observed in a 12-year period of time. All the patients are white women and 6 lesions exceeded 1 cm in diameter. Only 2 patients were surgically treated, but all of them are still today clinically and radiographically followed. RESULTS: Clinical, radiographic and histologic data of our cases are generally in agreement with those provided by the international literature. CONCLUSION: Finally, stress is laid on the existing difficulty, at present as well as in the past, of establishing definitive classification criteria for all fibro-cemento-osseous lesions of the jaws.

Adult↗

Energy from gasification of solid wastes.

Gasification technology is by no means new: in the 1850s, most of the city of London was illuminated by "town gas" produced from the gasification of coal. Nowadays, gasification is the main technology for biomass conversion to energy and an attractive alternative for the thermal treatment of solid waste. The number of different uses of gas shows the flexibility of gasification and therefore allows it to be integrated with several industrial processes, as well as power generation systems. The use of a waste-biomass energy production system in a rural community is very interesting too. This paper describes the current state of gasification technology, energy recovery systems, pre-treatments and prospective in syngas use with particular attention to the different process cycles and environmental impacts of solid wastes gasification.

Conservation of Natural Resources↗

Ultrasonography in the study of hepatocellular carcinoma in woodchucks chronically infected with WHV.

The woodchuck hepatitis virus (WHV)/woodchuck system is studied as animal model of human hepatocellular carcinoma (HCC) induced by chronic hepatitis B virus infection. The aim of the present study was the evaluation of ultrasound (US) liver examination in woodchuck as a routine method to detect HCC nodules and to follow their growth. Sixteen woodchucks were included in the study. US liver examination was carried out in all animals using a 5 MHz convex scanner. Macroscopic and microscopic examinations were performed to evaluate the US findings. The lower limit of nodule detection by US examination was a diameter of 5 mm. Macroscopic and microscopic examinations confirmed US findings in 14 of 16 animals (86.6%). No false negative results were obtained. Increase of nodule size was faster in the early phase of tumour growth. Small nodules (16 +/- 5 mm) appeared as hypoechoic lesions with well-defined margins and homogeneous structure. Large nodules (42 +/- 19 mm) appeared as hyperechoic lesions with irregular margins, heterogeneous or of mixed pattern; microscopical examination showed different degrees of necrosis, inflammation and fibrosis inside these latter neoplasms. The hepatitis reaction was conspicuously more severe around HCC nodules. No fibrosis and/or cirrhosis were found in normal liver parenchyma surrounding tumour nodules. On the whole, US appears to be helpful in the diagnosis of woodchuck HCC even at an early stage. Serial US evaluation can be used to study the growth rate of tumour nodules during natural history or experimental HCC treatments in woodchuck.

Animals↗

Unusual vascular hamartoma of the hard palate. A case report.

Hamartomas are tumour-like malformations usually present since birth or which may develop during puberty. Hamartomas are related to anatomical development errors. Hamartomas are rarely found in the head and neck district. The case of an unusual vascular hamartoma localised in the hard palate of a 50-year-old female with no significant medical or family history is reported. Surgical treatment was performed by means of an excisional biopsy.

Female↗

An improved helper-dependent adenoviral vector allows persistent gene expression after intramuscular delivery and overcomes preexisting immunity to adenovirus.

Helper-dependent adenoviral vectors deleted of all viral coding sequences have shown an excellent gene expression profile in a variety of animal models, as well as a reduced toxicity after systemic delivery. What is still unclear is whether long-term expression and therapeutic dosages of these vectors can be obtained also in the presence of a preexisting immunity to adenovirus, a condition found in a high proportion of the adult human population. In this study we performed intramuscular delivery of helper-dependent vectors carrying mouse erythropoietin as a marker transgene. We found that low doses of helper-dependent adenoviral vectors can direct long-lasting gene expression in the muscles of fully immunocompetent mice. The best performance-i.e., 100% of treated animals showing sustained expression after 4 months-was achieved with the latest generation helper-dependent backbones, which replicate and package at high efficiency during vector propagation. Moreover, efficient and prolonged transgene expression after intramuscular injection was observed with limited vector load also in animals previously immunized against the same adenovirus serotype. These data suggest that human gene therapy by intramuscular delivery of helper-dependent adenoviral vectors is feasible.

Adenoviruses, Human↗

Effect of hyaluronic acid on human chondrocyte cell lines from articular cartilage.

The effects of hyaluronic acid (HA) derivative on the proliferation and metabolism of human chondrocytes were examined. Cells were obtained from cartilage from metatarsal phalangeal joints of 20 adult humans (aged 22-63) and from femoral knee condyles of 10 subjects (aged 22-77). Chondrocytes isolated by collagenase/Dnase digestion were cultured with addition of different doses of HA for 4 weeks. Morphological studies demonstrated that HA enhanced the adhesion of cells to substrate; HA-treated chondrocytes proliferated better than chondrocytes cultured in HA-free medium. This study shows that HA improves in vitro substrate adhesion ability and proliferative activity of human cartilage cells and that the response to the treatment varies on an individual basis.

Adjuvants, Immunologic↗

Evolution of precancerous laryngeal lesions: a clinicopathologic study with long-term follow-up on 259 patients.

BACKGROUND: A wide spectrum of lesions ranging from dysplasia to in situ carcinoma have to be considered when dealing with laryngeal precancerous conditions. Recently the concept of laryngeal intraepithelial neoplasia (LIN) was introduced. METHODS: A series of 259 consecutive cases of laryngeal keratosis was studied from 1976 to 1994. All patients entered the study after microlaryngoscopy and biopsy. Histologic diagnoses were subdivided into keratosis without dysplasia (KWD), with mild dysplasia (LIN 1), with moderate dysplasia (LIN 2), and with severe dysplasia or carcinoma in situ (LIN 3). The follow-up period ranged from 15 months to 19 years (mean, 101 months). RESULTS: KWD had the best prognosis with the lowest recurrence rate (12.5%) after stripping of laryngeal mucous membrane. The recurrence rate after stripping was higher for LIN 1 (25%) and LIN 2 cases (68.7%). The recurrence rate after CO2 laser cordectomy was 16.6% for LIN 2 and 18.7% for LIN 3. The incidence of progression to infiltrative carcinoma was 4.19% for KWD, 7.14% for LIN 1, 21.42% for LIN 2, and 9.37% for LIN 3. CONCLUSIONS: KWD and LIN 1 can be successfully treated by stripping the mucous membrane, close follow-up, and a change in smoking habits. On the contrary, LIN 2 and LIN 3 need a more aggressive therapeutical approach.

Female↗

Medullary thyroid carcinomas in transgenic mice expressing a Polyoma carboxyl-terminal truncated middle-T and wild type small-T antigens.

Medullary thyroid carcinoma (MTC) is a rare human tumor affecting the calcitonin-secreting c-cells of the thyroid. Here we report that two independent strains of transgenic mice expressing a Polyomavirus (Py) truncated middle-T antigen (deltaMT), consisting of the amino-terminal 304 amino acids, and the full length Py small-T antigen, developed multifocal bilateral MTCs with 100% penetrance. Occasionally one strain also developed mammary and bone tumors. Furthermore, offspring from both transgenic lines displayed pronounced waviness of the whiskers and fur, previously associated with defective epidermal growth factor receptor signaling. Transgene transcription, driven by the homologous early promoter/enhancer, and the corresponding translation products were detected in tumors and in many other organs which did not develop pathologies. The subcellular distribution of deltaMT and its interactions with the adapter proteins of the SHC family have also been analysed. Our study describes a novel murine model of MTC and provides evidence that the N-terminal 304 amino acid fragment of Py middle-T antigen, possibly in co-operation with small-T antigen, acts as a potent oncogene in c-cells of the thyroid.

Animals↗

Intraductal papillary carcinoma of the parotid gland with low malignancy.

A peculiar case of papillary carcinoma arising in the parotid gland is reported. A 68-year-old woman presented with a right, painless, parotid mass, measuring approximately 3 cm in greatest diameter. A conservative parotidectomy was performed. Histologically, the neoplasm showed exophytic papillary projections into a cavity. The cells were focally suggestive of epidermoidal differentiation, whereas a transitional differentiation was noted in other portions, as in bladder papilloma. Immunohistochemical studies showed strong positivity of the neoplastic cells for cytokeratin and weak positivity for PCNA and Mib-1. We classified this neoplasm among the papillary tumors with a low-grade of malignancy.

Aged↗

Human chondrocyte cell lines from articular cartilage of metatarsal phalangeal joints.

Chondrocytes can be isolated from human adult cartilage from metatarsal phalangeal joints. After enzymatic digestion to isolate viable cells, confluent monolayers were obtained 2-4 weeks after the start of cell division. Chondrocytes cultures, initiated and maintained in HAM's F12 with bovine fetal serum without the addition of other growth factors, produced in vitro a matrix rich in collagen and proteoglycans. Although several studies reported phenotypic instability, our results showed that the cell retain for more than 5 months in culture their differentiated characteristics, including the ability to produce cartilage-specific molecules. Chondrocyte cell lines should be useful in studying the functions of these cells from normal and abnormal tissue and for pharmacological studies in vitro.

Adult↗

[Synovial healing in reconstructed cruciate ligaments. Our personal experience compared in single interventions and combined reconstructions].

INTRODUCTION: The healing process of tendon grafts used in cruciate ligament reconstruction is called ligamentization. The tendon structural architecture changes progressively into the histological appearance of normal ligament. Amiel and Clancy have demonstrated that this process is time-dependent in anterior cruciate ligament (ACL) reconstruction, the tendon graft taking one year to become similar to a normal cruciate ligament. Three different maturation phases of anterior cruciate graft ligamentization can be seen at MRI: periligamentous proliferation, intraligamentous proliferation and definitive healing. We report our MR findings in the reconstruction of single ACL, posterior cruciate ligament (PCL), and of both ACL and PCL. MATERIAL AND METHODS: January 1995 to January 1999 we selected 60 patients submitted to arthroscopic cruciate ligament reconstruction. The ACL was reconstructed with the patellar tendon in 22 cases and the PCL in 23; fifteen patients underwent double reconstruction of ACL, with hamstring tendons, and PCL, with patellar tendons. Fifty-five patients were followed-up with MRI: 45 with a dedicated permanent magnet (Artroscan, Esaote Biomedica, Genoa, Italy) and 10 with a permanent low-field unit (AIRIS, Hitachi, Japan); the same technical parameters were used in all cases. Forty of 55 patients were examined at 1, 3, 6, 9 and 12 postoperative months, while 15 were followed-up longer (12 to 36 months postoperatively). At the first follow-up MR examination, 5 patients (2 ACL and 3 PCL) were excluded for incorrect tunnel position (1 case), hypertrophic scarring (2 cases) and new trauma (2 cases). MR findings were compared with clinical data of joint stability. RESULTS: MRI showed the different stages of the healing process in 20 ACL patients: proliferating soft tissue around the graft with the low signal intensity typical of tendons (stage I, 1-3 months postoperatively), the graft becomes progressively hyperintense (stage II, 3-9 months postoperatively), and finally the low signal intensity indicating completed ligamentization (stage III, 12 months postoperatively). As for PCL reconstructions, MR findings were similar but the process took longer, even 24 months. Finally, in the 15 cases of double reconstruction, both grafts were difficult to distinguish on T1-weighted images for a very long time (24-36 months postoperatively). DISCUSSION AND CONCLUSIONS: Relative to the ACL, ligamentization takes longer for PCL and combined ACL and PCL reconstructions, probably because the morphological changes in PCL and double grafts may be impaired by many factors, such as gravity, long bone tunnels, hemarthrosis, hyperplastic synovial reaction in the intercondylar notch; also, rehabilitation protocols differ in ACL from PCL patients. No signs of instability were found at physical or arthrometric examinations. MRI demonstrates the different stages of ligamentization and thus proves a useful tool for postoperative follow-up in cruciate ligament reconstructions. Contrast-enhanced (Gd) studies are reserved to the cases of graft impingement or if other abnormalities are suspected.

Anterior Cruciate Ligament↗

Coexpression of IL-6 and soluble IL-6R causes nodular regenerative hyperplasia and adenomas of the liver.

Studies with tumor necrosis factor p55 receptor- and interleukin-6 (IL-6)-deficient mice have shown that IL-6 is required for hepatocyte proliferation and reconstitution of the liver mass after partial hepatectomy. The biological activities of IL-6 are potentiated when this cytokine binds soluble forms of its specific receptor subunit (sIL-6R) and the resulting complex interacts with the transmembrane signaling chain gp130. We show here that double transgenic mice expressing high levels of both human IL-6 and sIL-6R under the control of liver-specific promoters spontaneously develop nodules of hepatocellular hyperplasia around periportal spaces and present signs of sustained hepatocyte proliferation. The resulting picture is identical to that of human nodular regenerative hyperplasia, a condition frequently associated with immunological and myeloproliferative disorders. In high expressors, hyperplastic lesions progress with time into discrete liver adenomas. These data strongly suggest that the IL-6/sIL-6R complex is both a primary stimulus to hepatocyte proliferation and a pathogenic factor of hepatocellular transformation.

Adenoma↗

Transgenic expression in the liver of truncated Met blocks apoptosis and permits immortalization of hepatocytes.

Hepatocyte growth factor induces proliferation, motility and differentiation of epithelial cells through the tyrosine kinase receptor encoded by the MET protooncogene. The cytoplasmic portion of Met (referred to as cyto-Met) is activated but only weakly transforming. In order to determine the effect of activated Met on hepatocytes, we have targeted truncated Met expression to the liver by incorporating the cDNA into a vector carrying the entire human alpha-1-antitrypsin transcriptional unit. Transgenic expression in the liver of truncated human Met, containing the regulatory and the catalytic cytoplasmic domains, renders hepatocytes constitutively resistant to apoptosis and reproducibly permits immortalization. The emerging stable cell lines are not transformed and maintain a highly differentiated phenotype judged by the retention of epithelial cell polarity and the expression of hepatocyte-enriched transcription factors as well as hepatic products.

Animals↗