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Biomedical subjects

G Rossi

Publications and source records attributed to G Rossi.

At least 109 records · Page 6Linked to original sources

Leishmania infantum and Neospora caninum simultaneous skin infection in a young dog in Italy.

Leishmania infantum, the agent of canine leishmaniasis in Mediterranean countries, and Neospora caninum, a recently recognized protozoal pathogen in dogs, were diagnosed in a 9-month-old Argentine Dogo dog. Both skin lesions and neurological signs were present. Histopathology of cutaneous lesions revealed a suppurative, diffuse dermatitis with numerous intracellular protozoa. Serology was positive for both L. infantum (1:640) and N. caninum (1:800). Double-label immunohistochemical staining of skin samples with hyperimmune serum from L. infantum-infected dogs was positive for protozoa within macrophages, while the polyclonal antibody specific for N. caninum showed positive reactions for protozoa in endothelial cells and fibroblasts. Transmission electron microscopy (TEM) confirmed the infection with both protozoa. This is, to the authors' knowledge, the first case of simultaneous infection with L. infantum and N. caninum in a dog. It is possible that the immunosuppressive effects of Leishmania infection or long-term steroid therapy may have been a contributing factor to the development of N. caninum in this dog.

Animals↗

Hodgkin disease developing in patients infected by human immunodeficiency virus results in clinical features and a prognosis similar to those in patients with human immunodeficiency virus-related non-Hodgkin lymphoma.

BACKGROUND: Unlike aggressive non-Hodgkin lymphoma (NHL), Hodgkin disease (HD) develops rarely in patients who are infected by human immunodeficiency virus (HIV), and its characteristics are not well defined. The authors analyzed the clinicopathologic and prognostic features from a consecutive series of patients with HIV-associated HD who were observed at their institution and compared them with the features observed in a concurrent series of patients with systemic HIV-related NHL. METHODS: Eighteen patients with HIV infection who were diagnosed and treated uniformly from 1985 to 1999 at a single primary referral center were analyzed. Their demographic, immunologic, and clinicopathologic features; responses to treatment; and outcomes were compared with those of 98 patients with systemic NHL of aggressive histology who were diagnosed during the same period and with 165 HIV negative patients with HD. RESULTS: HIV-associated HD and NHL occurred in patients with similar age, gender, HIV risk factors, degree of immunodeficiency, and incidence of previous acquired immunodeficiency syndrome. The clinical presentation of HIV-associated HD was atypical and was more aggressive than in HIV negative patients (mediastinal involvement, 11%; Stage III-IV, 84%; B symptoms, 83%). It was similar to HIV-related NHL, except for the frequency of extralymph node disease, which was seen less frequently in patients who had HD (56%) compared with patients who had NHL (82%; P = 0.025), and the frequency of bone marrow involvement, which was unexpectedly higher in patients who had HD (50%) compared with patients who had NHL (20%; P = 0.011). Potentially curative treatment was administered to 77% of patients with HD and 66% of patients with NHL. Complete remission and disease recurrence rates as well as disease free and overall survival rates did not differ significantly, with estimated overall survival at 5 years of 24% in patients with HD and 23% in patients with NHL. CONCLUSIONS: HIV-associated HD is an aggressive disease with demographic, clinical, and prognostic features nearly identical to those of HIV-related NHL.

AIDS-Related Opportunistic Infections↗

Urokinase-type plasminogen activator up-regulates the expression of its cellular receptor through a post-transcriptional mechanism.

We have recently reported that the urokinase-type plasminogen activator (uPA) up-regulates the cell surface expression of its own receptor (uPAR) in several cell types, independently of its enzymatic activity. uPA has no effect on kidney 293 cells which do not express uPAR and then cannot bind uPA. Kidney cells, transfected with the coding region of uPAR cDNA, express very large amounts of uPAR and respond to uPA stimulation by regulating uPAR both at mRNA and protein levels. uPA effect occurs also in the presence of the transcriptional inhibitor dichloro-ribobenzimidazole, whereas it is abolished by the protein synthesis inhibitor cycloheximide. Moreover, uPA-dependent uPAR up-regulation correlates with the increase of a complex between the coding region of uPAR mRNA and an unknown cellular factor. We then propose that uPA regulates uPAR expression at a post-transcriptional level, by promoting the binding of uPAR mRNA to a stabilizing factor.

3' Untranslated Regions↗

Molecular screening for hereditary nonpolyposis colorectal cancer: a prospective, population-based study.

PURPOSE: Germline mutations in mismatch repair genes predispose to hereditary nonpolyposis colorectal cancer (HNPCC). To address effective screening programs, the true incidence of the disease must be known. Previous clinical investigations reported estimates ranging between 0.5% and 13% of all the colorectal cancer (CRC) cases, whereas biomolecular studies in Finland found an incidence of 2% to 2.7% of mutation carriers for the disease. The aim of the present report is to establish the frequency of the disease in a high-incidence area for colon cancer. PATIENTS AND METHODS: Through the data of the local CRC registry, we prospectively collected all cases of CRC from January 1, 1996, through December 31, 1997 (N = 391). Three hundred thirty-six CRC cases (85.9% of the incident cases) were screened for microsatellite instability (MSI) with six to 12 mono- and dinucleotide markers. MSI cases were subjected to MSH2 and MLH1 germline mutation analysis and immunohistochemistry; the methylation of the promoter region was studied for MLH1. RESULTS: Twenty-eight cases (8.3% of the total) showed MSI. MSI cases differed significantly from microsatellite-stable (MSS) cases for their proximal location (P <.01), high mucinous component (P <.01), and poor differentiation (P =.002). Of MSI cases studied (n = 12), only one with a family history compatible with HNPCC had a germline mutation (in MSH2). Five other patients with a family history of HNPCC (two with MSI and three with MSS tumors) did not show germline mutations. CONCLUSION: We conclude that the incidence of molecularly confirmed HNPCC (one [0.3%] of 336) in a high-incidence area for CRC is lower than in previous biomolecular and clinical estimates.

Adaptor Proteins, Signal Transducing↗

Clinical and biologic heterogeneity of hereditary nonpolyposis colorectal cancer.

MMR gene mutations and MSI are not found in all clinically diagnosed HNPCC families. We evaluated whether MMR genotyping and tumor MSI analysis could identify distinct clinical subgroups among HNPCC families. Twenty-nine clinical HNPCC families were divided into 3 groups: A, families with hMLH1 or hMSH2 gene mutations; B, MMR gene mutations not present but MSI present in at least 50% of tumors tested; C, mutational and MSI analyses negative. We evaluated tumor spectrum, age at onset, risk of cancer in the follow-up and survival for CRC in the 3 groups. Tumors of the target organs in HNPCC (colon and rectum, endometrium, ovary, small bowel, stomach, renal pelvis and ureter) were more frequent in the first 2 groups than in the latter. Colon cancer was more frequently located in the proximal colon and showed an earlier age at onset in families with MMR gene mutation or with MSI than in families with stable tumors. Comparing the occurrence of tumors in the follow-up, in the first 2 groups patients younger than 50 years had a higher RR, which was particularly marked for CRC (RR = 18.6 for group A vs. group C, RR = 16.7 for group B vs. group C). CRC patients in the first 2 groups had a better clinical prognosis. The results of molecular analysis could distinguish, within clinically defined HNPCC families, different subgroups to which specific programs of surveillance could be addressed.

Adaptor Proteins, Signal Transducing↗

Mouse antral oocytes regulate preantral granulosa cell ability to stimulate oocyte growth in vitro.

In this study we evaluated whether mouse oocytes derived from early antral or preovulatory follicles could affect the ability of preantral granulosa cells to sustain oocyte growth in vitro. We found that early antral oocytes with a diameter > or =75 microm did not grow any further during 3 days of culture on preantral granulosa cell monolayers in vitro, while most of the oocytes with a smaller diameter increased significantly in size. Similarly, about 65% of growing oocytes isolated from preantral follicles grew when cultured on preantral granulosa cells. By coculturing with growing oocytes fully grown early antral or preovulatory oocytes, a small proportion (about 10%) of growing oocytes increased in diameter, and changes in granulosa cell morphology were observed. Such effects occurred as a function of the fully grown oocyte number seeded and were not associated with a decrease in coupling index values. By avoiding physical contact between antral oocytes and granulosa cells, the proportion of growing oocytes undergoing a significant increase in diameter was about 36%. These results indicate that fully grown mouse oocytes can control preantral granulosa cell growth-promoting activity through the production of a soluble factor(s) and the maintenance of functional communications with surrounding granulosa cells.

Animals↗

Long-term induction of immune tolerance after blockade of CD40-CD40L interaction in a mouse model of hemophilia A.

A factor VIII-deficient knockout mouse was used as a model for severe hemophilia A to characterize the immune response to recombinant human factor VIII (fVIII) and to study new approaches for induction of immune tolerance to fVIII. Mice initially received periodic injections of fVIII in doses similar to those used for the treatment of human hemophilia A. To induce immune tolerance, a hamster monoclonal antibody specific for murine CD40 ligand (CD40L or CD154) was injected with fVIII. Control mice received fVIII alone or fVIII and hamster immunoglobulin G. After treatment, humoral and cellular immune responses were evaluated. Ninety-five percent of anti-CD40L-treated mice had lower titers of anti-fVIII antibody (less than 1 microg/mL) compared with fVIII-injected control mice (mean, 18 microg/mL). To determine whether anti-CD40L treatment induces long-term immune tolerance, mice were rechallenged 3 times with fVIII alone. At 150 days after treatment, 12 of 22 anti-CD40L-treated mice remained tolerant to fVIII (anti-fVIII antibody titers less than 1 microg/mL). However, tolerant mice immunized with tetanus toxoid (TT) developed high anti-TT antibody, demonstrating that tolerance is fVIII specific. T cells from tolerant mice showed impaired proliferative responses after stimulation with fVIII in vitro and lack of production of the cytokines interleukin-2 (IL-2), IL-4, interferon gamma, and IL-10. These results demonstrate that long-term immune tolerance to fVIII was effectively induced after early blockade of CD40-CD40L interaction. In addition, the lack of tolerance in this model was associated with the expression of a Th2 phenotype.

Animals↗

Temperature-dependent fermi gap opening in the c(6x4)-C60/Ag(100) two-dimensional superstructure.

High-resolution angle-integrated photoemission of one monolayer of C (60) chemisorbed on Ag(100) shows the reversible opening of a gap at the Fermi level at temperatures 25< or =T< or =300 K. The gap reaches a maximum value of approximately 10 meV at T< or =70 K. This finding is the first evidence of an electronic phase transition in C60 monolayers and has implications on the ongoing debate about surface superconductivity in C60-based bulk materials.

Journal Article↗

Microsatellite instability and mismatch-repair protein expression in hereditary and sporadic colorectal carcinogenesis.

Aberrant crypt foci (ACF) are microscopic clusters of altered colonic crypts considered premalignant lesions in the large bowel. Genomic instability at short tandem repeats in the DNA, referred to as microsatellite instability (MSI) is the hallmark of hereditary nonpolyposis colorectal carcinoma (HNPCC) caused by mutations in DNA mismatch-repair genes, mostly hMLH1 and hMSH2. In this study, we evaluated for MSI ACF (n = 16), adenomas (n = 18), carcinomas (n =22), and lymph node metastases (n = 3) from 17 patients with colorectal cancer positive for MSI. Ten patients were members of HNPCC families; 7 patients had no family history of cancer. MSI was found in 7 of 7 (100%) ACF and 11 of 12 (91%) adenomas from patients with HNPCC. MSI was not related to histology and size of ACF. A progressive increase in instability as estimated by the number of shifted bands was observed along the ACF-adenoma-carcinoma sequence. In contrast, two of nine (22%) ACF and none of six adenomas from patients with MSI sporadic carcinoma were unstable at microsatellite loci. hMLH1 or hMSH2 protein expression was altered only in MSI-positive premalignant lesions (ACF and/or adenomas), but not in all MSI-positive lesions in patients with HNPCC. These observations provide evidence of the premalignant nature of ACF in HNPCC and suggest that MSI is a very early event both in HNPCC and in sporadic colorectal carcinogenesis, although in the latter it seems infrequent.

Adaptor Proteins, Signal Transducing↗

Heart rate profiles and energy cost of locomotion during cross-country skiing races.

The purpose of this study was to compare heart rate responses and speed in two cross-country skiing races, which were run by seven male and seven female subjects by using classic and free style. Heart rates and skiing velocities were analyzed over flat, uphill and downhill sections, which were run from one to three times. Heart rates were higher in uphill sections than in flat sections; a steady-state heart rate was never reached in the downhill section. When the same uphill section was repeated, the heart rate tended to increase but the speed to decrease. Oxygen uptake (VO2) was calculated from heart rate:VO2 ratio, measured during uphill walking with the aid of poles. The mean (SD) energy cost of locomotion (i.e., the ratio between net VO2 and speed) was 162.1 (9.4) ml.km(-1).kg(-1) and 147.7 (7.1) ml.km(-1).kg(-1) when male subjects ran the flat section after first downhill by using classic and free style, respectively. Females had lower values for VO2 and speed, but similar energy costs. In general, the variability of the energy cost of locomotion in skiers of a similar competitive level is of the same order as that found in uphill walking on a treadmill.

Adult↗

Presence of a 31-kD protein band in human cumulus--corona radiata--conditioned media and pregnancy outcome.

OBJECTIVE: To investigate relationships between cumulus-oocyte complex (COC) morphology, protein patterns of cumulus-corona (CC) cell-conditioned media, and pregnancy outcome in IVF-ET cycles. DESIGN: Retrospective study. SETTING: Private university IVF center. PATIENT(S): One hundred twenty infertile women who underwent IVF-ET procedures. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): COC grading, analysis of CC cell morphology and conditioned media, and pregnancy rate (PR). RESULT(S): After IVF and embryo transfer, cultured CC cells were classified as high (HA) or low (LA) on the basis of their adhesive properties. Neither adhesion activity nor fertilization rates and embryo quality were correlated with COC grading. PR in cycles with HA cells was 38%, but 14% of cycles showing LA activity also had positive outcome. To find more meaningful parameters of CC cells useful to predict fertilization and pregnancy, the electrophoretic protein patterns of media conditioned by HA or LA cells were studied. Retrospective analysis showed that all cycles in which replaced embryos were associated with the presence of a 31-kD band in conditioned media failed implantation, whereas 83% of cycles lacking this band resulted in positive, ongoing pregnancy. CONCLUSION(S): Pregnancy prediction cannot rely simply on CC cell morphological analysis. Screening of conditioned media may provide more reliable parameters.

Adult↗

Attitude towards psychiatric patients: a pilot study in a northern Italian town.

The stigmatisation of the psychiatric patient is still a strong barrier to the integration process of these subjects in our society. Therefore, it is necessary to identify what types of prejudices exist and the types of variables with which they are linked, in order to plan strategies to reduce them. In this exploratory study we administered a semi-structured interview to 303 subjects in order to examine the relationships between social attitudes towards mental disorders and some social demographic variables, the information about mental disorders and the previous 'contacts' with psychiatric patients. The data analysis shows that there is a relationship between knowledge of psychiatric patients and a more positive attitude towards them (i.e., less fear, more integration and work opportunities). This study is to be considered preliminary as far as people's attitudes towards psychiatric patients are concerned. This result encourages the planning and implementation of sensitisation and information programs concerning mental disorders, in the sense that increasing the knowledge of mental disorders could lead to significant achievements in the important fight against the stigma surrounding psychiatric patients.

Adolescent↗

Antibodies to hepatitis A virus in Italian patients with chronic liver disease.

To improve our knowledge for future hepatitis A virus (HAV) vaccination strategies we carried out a multicentre study on naturally acquired immunological protection against HAV in patients with chronic hepatitis in Italy. We enrolled 830 consecutive patients with chronic hepatitis on their first observation at one of the six Italian liver units participating in the study. Six hundred and fifty-eight patients (79.3%) were positive for total anti-HAV and 172 (20.7%) were negative. The anti-HAV negative patients were younger (median age 33, range 11-78) than the anti-HAV positive (median age 56, 18-87). There was a higher prevalence of cases with circulating anti-HAV among the 508 patients residing in southern Italy than in the 322 residing in northern Italy (88.8% vs. 64%, P < 0.001). No significant difference in the anti-HAV prevalence was observed between patients from northern Italy and those from southern Italy aged 0-30 years or in those over 60 years, while in those 31-60 years old there was a higher prevalence of anti-HAV positive patients from southern Italy (90.2% vs. 65.8%, P < 0.0001). Of the patients with liver cirrhosis in this study, only 3 of the 26 (11.5%) from northern Italy and 8 of the 228 (3.5%) from southern Italy had no immunological protection against HAV infection. The data suggest that the number of patients with chronic liver disease without naturally acquired immunity against HAV is substantial in Italy, particularly in the north of the country, and that new vaccination strategies are needed.

Adolescent↗

High-dose mitoxantrone + melphalan (MITO/L-PAM) as conditioning regimen supported by peripheral blood progenitor cell (PBPC) autograft in 113 lymphoma patients: high tolerability with reversible cardiotoxicity.

Hematological and extrahematological toxicity of high-dose (hd) mitoxantrone (MITO) and melphalan (L-PAM) as conditioning regimen prior to peripheral blood progenitor cell (PBPC) autograft was evaluated in 113 lymphoma patients (87 at disease onset). Autograft was the final part of a hd-sequential (HDS) chemotherapy program, including a debulkying phase (1-2 APO +/- 2 DHAP courses) and then sequential administration of hd-cyclophosphamide, methotrexate (or Ara-C) and etoposide, at 10 to 30 day intervals. Autograft phase included: (1) hd-MITO, given at 60 mg/m2 on day -5; (2) hd-L-PAM, given at 180 mg/m2 on day -2; (3) PBPC autograft, with a median of 11 x 10(6) CD34+/kg, or 70 x 10(4) CFU-GM/kg, on day 0. A rapid hematological recovery was observed in most patients, with ANC >500/microL and Plt >20,000/microl values reached at a median of 11 and 10 days since autograft, respectively. The good hemopoietic reconstitution allowed the delivery of consolidation radiotherapy (RT) to bulky sites in 53 out of 57 candidate patients, within 1 to 3 months following autograft; five of these patients required back-up PBPC re-infusion due to severe post-RT pancytopenia. Few severe infectious complications were recorded. There was one single fatal event due to severe pancytopenia following whole abdomen RT. Cardiac toxicity was evaluated as left ventricular ejection fraction (LVEF), monitored by cardiac radionuclide scan. LVEF prior to and after autograft was significantly reduced (median values: 55% vs 46%) in 58 evaluated patients; however, a significant increase to a median value of 50% was observed in 45 patients evaluated at 1 to 3 years since autograft. At a median follow-up of 3.6 years, 92 patients are alive, with a 7-year overall survival projection and 6.7-year failure-free survival projection of 77% and 69%, respectively. We conclude that a conditioning regimen with hd-MITOIL-PAM fits well within the HDS program. It implies good tolerability and reversible cardiotoxicity and it may have contributed to the good long-term outcome observed in this series of patients.

Adolescent↗

Risk-oriented postremission strategies in adult acute lymphoblastic leukemia: prospective confirmation of anthracycline activity in standard-risk class and role of hematopoietic stem cell transplants in high-risk groups.

INTRODUCTION: Although definite risk classes are well known, risk-adapted modulation of first-line therapy is seldom attempted in adult ALL. So, a prospective validation of the therapeutic efficacy of a protocol (or a component thereof) in specific risk groups is uncommon. MATERIALS AND METHODS: From 1996-1999 a risk-oriented program (08/96) was evaluated in 102/121 unselected patients (median age 35 years, blast count 0-450 x 10(9)/l, 100 B(lin) (lineage), 21 T(lin)) responsive to induction therapy. The standard risk (SR) class was B(lin) CD10+ Ph- with blasts < 10 x 10(9)/l (prior studies: disease-free survival (DFS) rate 52% at five years with dose-intensive anthracycline-containing programs). The SR protocol was therefore anthracycline-rich (early consolidation cycles with total idarubicin 96 mg/m2), and comprised long-term maintenance. High-risk (HR) patients were eligible to the following three options: allogeneic hematopoietic stem cell transplantation (HSCT) from related family donor; short sequence with high-dose cyclophosphamide-cytarabine-methotrexate followed by melphalan/total body irradiation with autologous HSCT; or T(lin) ALL chemotherapy regimen inclusive of high-dose cytarabine and methotrexate. RESULTS: Treatment realization and three-year DFS rates according to risk class, HR subset and postremission treatment intensity were the following. SR group (n = 28): realization rate 93%, DFS 68.5%. HR group (n = 74): realization rate 80%, DFS 39% (P = 0.052 vs SR category). In HR group, three-year DFS rates by disease subtype were the following. B(lin) Ph- (n = 35) 43%; Ph+ (n = 19) 13% at 2.7 years (P = 0.006 vs other HR subtypes); T(lin) (n = 18) 59.5%. And DFS rates by treatment intensity were: allograft (n = 21) 40%; autograft (n = 28) 27%; shift to SR protocol (n = 13) 52% (P = ns vs allograft/autograft); T(lin) program (n = 10) 57%. Matched analyses of treatment protocols and disease subtypes suggested a possible therapeutic role of the autograft regimen in B(lin) Ph- ALL with a blast count < 25 x 10(9)/l, and of T(lin) protocol for T(lin) ALL. Comparisons with retrospective control cohorts were confirmatory of anthracycline activity in SR subclass. CONCLUSION: The intended strategy was applicable to the majority of study patients, confirming the value of anthracyclines in SR class and, preliminarily, the usefulness a T(lin)-specific treatment. Apart from the case of Ph+ ALL, the indications for high-dose procedures with HSCT remains largely undetermined in this study.

Adolescent↗

Primary prophylaxis with lamivudine of hepatitis B virus reactivation in chronic HbsAg carriers with lymphoid malignancies treated with chemotherapy.

Hepatitis B virus (HBV) reactivation of various degrees of severity, including fulminant hepatitis, may develop in 20-50% of hepatitis B virus surface antigen (HbsAg)-positive patients undergoing immunosuppressive or cytostatic treatment. Lamivudine is a nucleoside analogue that can directly suppress HBV replication. We have performed a pilot study to test the efficacy and tolerability of lamivudine as a primary prophylaxis of HBV reactivation in 20 consecutive patients treated for haematological malignancies, mainly of lymphoid origin. Lamivudine, 100 mg/d, was given orally from the start until 1 month after the end of chemotherapy, which included corticosteroids and/or purine analogues in 85% of cases. It was well tolerated and did not cause any unexpected reduction of cytostatic drugs dosages. The chemotherapy programme was completed in all patients without modifications. A transient threefold increase in serum amylase was observed in one case. HBV-DNA levels decreased in six out of six patients (P = 0.039) and ALT levels in five out of six patients (P = 0.057) whose serum levels were abnormal at the onset of therapy. Two patients developed transient hepatitis. HBV reactivation was documented in only one of these patients who had stopped lamivudine 1 month before. No signs of HBV reactivation were detected both during and after treatment in 18 patients with a median follow-up of 6 months (range 3-12). Thus, primary prophylaxis with lamivudine may be a well tolerated and effective method to reduce the frequency of chemotherapy-induced HBV reactivation in chronic HBsAg carriers.

Adult↗

Comparison between minimally invasive video-assisted thyroidectomy and conventional thyroidectomy: a prospective randomized study.

BACKGROUND: Endoscopic procedures for thyroid surgery have been introduced since 1998, but their diffusion has remained limited because their advantages were never demonstrated. METHODS: Forty-nine patients undergoing surgery for either a thyroid nodule or a small papillary carcinoma were allotted to 1 of these procedures, minimally invasive video-assisted thyroidectomy (MIVAT) or conventional thyroidectomy (CT). Exclusion criteria were nodules greater than 35 mm, presence of thyroiditis, and thyroid volume greater than 20 mL. Preoperative diagnosis, operative time, postoperative pain, complications, and cosmetic result were evaluated. RESULTS: MIVAT group included 25 patients and the CT group 24 patients. Operative time was 66 +/- 24 minutes for MIVAT and 45 +/- 15 minutes for CT (P = .001). Postoperative course was significantly less painful in the patients who underwent MIVAT (P = .003). Cosmetic result evaluated by verbal response scale and numeric scale was in favor of MIVAT (P = .003 and P = .01, respectively). One recurrent nerve palsy and 1 transient hypoparathyroidism were present in CT patients; MIVAT patients experienced 2 transient palsies. CONCLUSIONS: Despite some MIVAT advantages in terms of postoperative pain and cosmesis, CT still offers an advantage in terms of operative time and its safety should not differ. Larger series of patients are needed before deciding whether endoscopic thyroidectomy can offer important advantages.

Adolescent↗