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Biomedical subjects

E Morello

Publications and source records attributed to E Morello.

11 recordsLinked to original sources

Type I autoimmune hepatitis: clinical course and outcome in an Italian multicentre study.

BACKGROUND: Many reports of autoimmune hepatitis (AIH) were written in the 'pre-Hepatitis C era' and data on the natural history are still incomplete. AIM: To evaluate the clinical presentation and the natural history of type I AIH. METHODS: Seventy-three consecutive patients with a regular follow-up of at least 2 years were prospectively included in the study. The mean follow-up was 91 +/- 61 months. RESULTS: Patients with 'acute' onset at presentation were significantly older than patients with 'chronic' onset (P < 0.05) and had significantly higher serum levels of transaminase, gamma-glutamyltransferase and bilirubin; Prothrombin time was significantly lower in the said group compared with AIH patients with 'chronic' onset. In 4 of 63 (6.3%) female patients, AIH had the onset during pregnancy; in all of them the outcome of pregnancy was favourable. The major events during the follow-up included oesophageal varices (n = 9) and ascites (n = 4), and 60 patients remained in remission while receiving immunosuppression. None of the patients died during the follow-up, but seven patients were transplanted. The cumulative transplant-free probability of survival was 73.5% at 280 months. CONCLUSIONS: Elderly patients have more frequently an acute onset at presentation. Survival in AIH is apparently good; with early diagnosis, and improved medical therapy, liver transplantation for AIH will become a rare event in future.

Adult↗

Immunohistochemical study of STAT3 expression in feline injection-site fibrosarcomas.

STAT3 (signal transducer and activator of transcription 3) is a cytoplasmic transcription factor that plays a role in the G1 to S phase cell-cycle transition and is induced by cytokines and growth factors. In the present study, the relation between histological grade and anti-STAT3 immunoreactivity was evaluated in 39 feline injection-site sarcomas treated surgically, 24 of the cats having received preoperative treatment with doxorubicin. Anti-STAT3 immunoreactivity was significantly lower in cases receiving preoperative doxorubicin, specifically with regard to nuclear localization. Moreover, STAT3 expression (intranuclear) was significantly correlated with mitotic activity in the animals that did not receive doxorubicin (P=0.019), and with differentiation score (P=0.009). STAT3 expression was correlated with the histological grade in both doxorubicin-treated and -untreated cats; in the treated cats, however, this correlation applied only to cytoplasmic STAT3 (P=0.018). Doxorubicin treatment induced a significant decrease in STAT3 expression (nuclear, P<0.0001; cytoplasmic, P=0.033) as compared with cases treated by surgery alone. These findings support existing evidence from human and experimental pathology on the potential role of STAT3 in oncogenesis and tumour progression.

Animals↗

Complementation of the Lactococcus lactis secretion machinery with Bacillus subtilis SecDF improves secretion of staphylococcal nuclease.

Unlike Bacillus subtilis and Escherichia coli, the gram-positive lactic acid bacterium Lactococcus lactis does not possess the SecDF protein, a component of the secretion (Sec) machinery involved in late secretion stages and required for the high-capacity protein secretion in B. subtilis. In this study, we complemented the L. lactis Sec machinery with SecDF from B. subtilis and evaluated the effect on the secretion of two forms of staphylococcal nuclease, NucB and NucT, which are efficiently and poorly secreted, respectively. The B. subtilis SecDF-encoding gene was tested in L. lactis at different levels. Increased quantities of the precursor and mature forms were observed only at low levels of SecDF and at high NucT production levels. This SecDF secretion enhancement was observed at the optimal growth temperature (30 degrees C) and was even greater at 15 degrees C. Furthermore, the introduction of B. subtilis SecDF into L. lactis was shown to have a positive effect on a secreted form of Brucella abortus L7/L12 antigen.

Bacillus subtilis↗

Reversal of multidrug-resistance using Valspodar (PSC 833) and doxorubicin in osteosarcoma.

High-grade osteosarcoma is an extremely aggressive neoplasm, where over 80% of patients present with life-threatening micrometastases at diagnosis. Systemic control of the disease is therefore critical for the treatment of these patients and neoadjuvant chemotherapy using various drugs, including doxorubicin (DXR), which has been demonstrated to be the most effective regimen. Multidrug resistance (MDR) to some anticancer agents, including DXR, mediated by the MDR1 gene product P-glycoprotein (Pgp), has been shown to be a major cause of chemotherapy failure in osteosarcoma. We analyzed the effect of a cyclosporine A derivate Valspodar (PSC 833) on MDR human osteosarcoma cells. We also evaluated Pgp expression in sporadic appendicular canine osteosarcoma. Moreover, dogs were treated with combined administration of DXR and PSC 833. Several blood samples were collected for the determination of DXR and PSC 833 levels. PSC 833 induced a complete reversal of the resistant phenotype at concentrations compatible with the clinical use. Pgp was present in 12/18 (66.6%) of the cases. At the time of DXR administration, adequate blood concentrations of PSC 833, to provide a complete MDR reversal, were obtained without clinical or laboratory findings of toxicity. Combination therapy with DXR and PSC 833 allowed a 30% decrease in DXR dose infusion with equivalent therapeutic exposure. The high incidence of Pgp expression in osteosarcoma confers to the study a rationale for an effective regimen based on down-modulation of MDR.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Autoimmune hepatitis: present knowledge].

Autoimmune hepatitis (AIH) is a rare and chronic disease which may lead to liver cirrhosis if not correctly treated. Its etiology is unknown, but some progresses have been obtained in the knowledge of damage pathogenesis, its immune mechanisms and genetic predisposition (female gender, presence of HLA DR3 and HLA DR4). It seems that such predisposition favours some agents (e.g. drugs or viruses) to trigger the pathological process. Patients present with variable, often few and unspecific symptoms. Diagnosis is made on the basis of anamnestic (absence of other causes, such as virus infections or alcohol abuse), serological (autoantibodies, high levels of aminotransferases, hypergammaglobulinemia), and histological data (piecemeal necrosis further to bridging necrosis, panlobular and multilobular necrosis); these data are processed by a scoring system which is helpful for the diagnostic definition. Therapy is founded in immunosuppressor drugs, mainly steroids and azathioprine, but a lot of other drugs have been studies for cases of recurrence and of intolerance to the standard treatment.

Autoantibodies↗

Bone allografts and adjuvant cisplatin for the treatment of canine appendicular osteosarcoma in 18 dogs.

The results achieved in 18 dogs following the use of frozen bone cortical allografts for limb-sparing resection of non-metastatic canine appendicular osteosarcoma are presented. Three to five cisplatin doses (70 mg/m2) were administered, starting the day after surgery. The mean and median survival times were 478 and 266 days (range 80 to 2,611 days), respectively. The survival rate was 94 per cent at three months, 78 per cent at six months, 35 per cent at 12 months, 23 per cent at 18 months and 19 per cent at 24 months; the disease-free interval was 80 to 1,246 days (mean 365 days, median 266 days). Lung metastasis developed in 55 per cent of the dogs within one year. Complications were observed in 14/18 dogs (78 per cent), comprising local recurrence (28 per cent), allograft infection (39 per cent) and implant failure (11 per cent). Despite complications, limb sparing is a useful alternative to amputation in selected cases of appendicular osteosarcoma.

Animals↗

Osteomyelitis and arthrosynovitis associated with Leishmania donovani infection in a dog.

A 10-month-old male maremma shepherd dog was presented with chronic diarrhoea, moderate polyuria/polydipsia, lethargy, dysorexia and stiffness. Pain was elicited in the distal parts of all four limbs. Radiographs of the limbs showed increased endomedullary radiopacity and lysis, with thick periosteal proliferations at the metadiaphyseal areas of each radius-ulna and tibia and of the distal metacarpus on one side. Polyclonal hypergammaglobulinaemia was documented and a similar electrophoretic protein pattern was also found in the synovial fluid. Leishmania amastigotes were found in the macrophages in a bone marrow aspirate performed at the level of a distal radius and in a synovial fluid sample obtained from a carpal joint. An indirect immunofluorescence test confirmed the infection. Treatment with N-methyl-glucamine antimoniate was successful and the osteoarticular changes progressively disappeared.

Animals↗