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Biomedical subjects

A Bianchi

Publications and source records attributed to A Bianchi.

At least 19 recordsLinked to original sources
PubMed2025

Pituitary tumor-transforming gene 1 and endocrine cancers: an up-to-date review through history, current insights and future perspectives.

Pituitary tumor-transforming gene 1 (PTTG1), discovered in 1997 by Pei and Melmed, takes part in cellular replication, cell cycle control, DNA repair mechanisms, organogenesis, metabolism regulation, cellular transformation, and senescence. Its biological actions include protein-protein interactions, modulation of gene transcription, and other than intracellular and autocrine mechanisms, even paracrine activities. For the reasons mentioned above, PTTG1 stands out as a multifaceted regulator of cancer biology; it is involved in genomic and chromosomal instability, local invasiveness, neo-lymphangiogenesis, and metastatic spreading. In solid neoplasms, endocrine neoplasms, although deemed rare, have experienced a significant increase in diagnostic incidence in recent years. Endocrine cancers are still a major challenge in healthcare and research since several questions remain unanswered, even though researchers have made considerable efforts to uncover their causes. Twenty-seven years have passed since PTTG1's discovery, and several works have been published. However, only the tip of the iceberg has been unveiled. Herein, we review current knowledge of PTTG1's action in endocrine cancers, such as pituitary, thyroid, testicular, adrenal, pancreatic, and ovarian.

Humans↗
PubMed1996

Comparison of granisetron, ondansetron, and tropisetron in the prophylaxis of acute nausea and vomiting induced by cisplatin for the treatment of head and neck cancer: a randomized controlled trial.

BACKGROUND: A single-institution, prospective, randomized, open controlled trial was carried out on head and neck cancer patients to compare granisetron (GRA), ondansetron (OND), and tropisetron (TRO) in the prevention of cisplatin-induced acute nausea and vomiting. All patients were chemotherapy-naive and treated with cisplatin on Day 1 (80 to 100 mg/m2). METHODS: One hundred seventeen patients were treated for a total of 463 cycles of cisplatin-based chemotherapy and randomized to receive 24 mg of OND intravenously (i.v.), 3 mg of GRA i.v., or 5 mg of TRO i.v. for the control of acute nausea and emesis. RESULTS: In the GRA group, complete response (CR) was obtained in 119 of 165 cycles (72.1%), major response (MR) in 32 cycles (19.4%), minor response (MiR) in 5 cycles (3%), and a failure (F) in 9 cycles (5.5%). In the OND group, CR was obtained in 110 of 150 cycles (73.3%), MR in 31 cycles (20.7%), MiR in 2 cycles (1.3%), and F in 7 cycles (4.7%). In the TRO group, CR was obtained in 100 of 148 cycles (67.6%), MR in 26 cycles (17.6%), MiR in 15 cycles (10.1%), and F in 7 cycles (4.7%). Major efficacy (CR + MR) was obtained in 151 of 165 cycles (91.5%) for GRA, in 141 of 150 cycles (94.0%) for OND, and in 126 of 148 cycles (85.2%) for TRO. The difference in major efficacy between OND and TRO was statistically significant. When comparing MiR, both GRA and OND were more effective than TRO. No other significant differences were observed among the three antiemetic agents. CONCLUSIONS: Although our results were achieved in an open trial, they show that GRA and OND are equally effective antiemetic agents in the prevention of cisplatin induced acute nausea and vomiting. TRO provides almost the same protection but is not as effective as OND for major efficacy. All three antiemetics can be administered safely to patients undergoing chemotherapy with cisplatin at doses of 80 mg/m2 or more.

Adult↗
PubMed1996

Ultrastructural changes during adhesion and migration of pre-B lymphoid leukaemia cells within bone marrow stroma.

The ultrastructural changes in leukaemic cells on initial contact with, and during migration into, layers of bone marrow stroma in vitro were examined in a variety of types of acute leukaemia and leukaemic cell lines. Bone marrow fibroblasts (BMF) were grown on polycarbonate microporous membranes, and acute leukaemia cells added to cultures and allowed to adhere to BMF for variable periods of time before fixation. Acute lymphoblastic leukaemia (ALL) blasts showed rapid development of surface membrane microvilli on contact with BMF layers. ALL blasts, and the pre-B ALL cell line NALM-6, showed evidence of movement in to the BMF layer within 15-30 min, with intrusion of extended cytoplasic processes into gaps between BMF cytoplasm. ALL cells were frequently seen within the layers of fibroblasts after 30 min incubation, and had pronounced morphological changes, with pseudopodia and attenuated and elongated microvilli interdigitating with the surface of fibroblasts or with strands of extracellular matrix material. Changes were also noted in the surface membrane of BMF adjacent to ALL cells, with invagination of the cytoplasmic membrane and formation of micropits. In contrast to the migratory behaviour of pre-B ALL cells, migration was not observed with acute myeloid leukaemia cells or other leukaemic cell lines. These cells showed membrane activation, with variable degrees of microvillous formation, and in some cases insertion of pseudopodia into BMF layers, but migration was not observed. Ultrastructural immunogold labelling was carried out to determine the localization of leukaemic adhesion molecules and their ligands on BMF. This demonstrated that beta 1 integrins were largely localized to the contact surfaces of both ALL blasts and fibroblasts, with VCAM-1 expressed only on the surface of BMF. These observations confirm the specificity of migratory behaviour for pre-B leukaemic cells, and indicate that a complex pattern of surface and intracellular events mediate this process, including the expression of beta 1 integrins and VCAM-1 at the sites of insertion of leukaemic cells between fibroblast margins.

Acute Disease↗
PubMed1995

Dysregulated Fas and Bcl-2 expression leading to enhanced apoptosis in T cells of multiple myeloma patients.

We have previously reported the presence of activated (HLA-DR+) T cells in multiple myeloma (MM) patients. These cells produce high amounts of interleukin (IL)-2 and interferon (IFN)-gamma and generate a potent antiplasma cell activity after appropriate in vitro stimulation, but they are unable in vivo to hold in check the disease. Activated T cells are highly susceptible to apoptosis, a form of programmed cell death involved in the modulation of immune responses and regulated by molecules such as Fas (CD95) and bcl-2. The aim of this study was to determine the expression of Fas and bcl-2 antigens and the susceptibility to apoptosis in T cells of MM patients. Fas+ cells were significantly higher, whereas bcl-2+ cells were significantly lower in MM patients than in the controls. MM patients with the highest number of HLA-DR+ T cells showed the highest Fas and the lowest bcl-2 expression. Two-color cytofluorometric analysis confirmed in individual cells that HLA-DR+ T cells coexpressed Fas and lacked bcl-2. Susceptibility to apoptosis was then investigated to evaluate the consequence of dysregulated Fas and bcl-2 expression. The percentage of apoptotic cells after incubation in medium alone (spontaneous apoptosis) or in the presence of methylprednisolone (MP) or anti-Fas monoclonal antibody (triggered apoptosis) was significantly higher in MM and mainly restricted to HLA-DR+ T cells. Spontaneous apoptotosis was reverted by exogenous IL-2. In conclusion, MM T cells have a dysregulated expression of Fas and bcl-2 antigens that is associated with an enhanced susceptibility to apoptosis. These data may unravel a novel mechanism by which activated MM T cells are weakened in their ability to exert an effective antitumor activity in vivo.

Antigens, Surface↗
PubMed1995

The phenotypic spectrum related to the human epilepsy susceptibility gene "EJM1".

Linkage studies of families ascertained through patients with juvenile myoclonic epilepsy (JME) suggest that an HLA-linked susceptibility gene on chromosome 6, designated "EJM1," predisposes to a group of idiopathic generalized epilepsies (IGEs) comprising JME, juvenile absence epilepsy (JAE), childhood absence epilepsies (CAE), and epilepsies with generalized tonic-clonic seizures (GTCS). To explore the EJM1-related phenotypic spectrum, we conducted linkage studies with HLA-DQ alpha restriction fragment length polymorphisms in 44 families ascertained through patients with CAE or JAE. Our results for the entire group of families provide evidence against a major susceptibility locus for idiopathic absence epilepsies and broader spectra of IGEs in the HLA region. Lod scores less than -2 were obtained for a region from 10 cM up to 23 cM on either side of the HLA-DQ alpha locus, depending on the assumed trait model. Suggestive evidence for linkage was found only for a subgroup of families with JME patients assuming an autosomal dominant mode of inheritance with 70% penetrance. A maximum lod score was obtained when family members with JME, JAE, CAE, and idiopathic GTCS were included into the affection status. Our results demonstrate that (1) the genetic susceptibility to idiopathic absence epilepsies and broader spectra of IGEs is heterogeneous, (2) the gene effect of EJM1 depends on the familial genetic background, and (3) EJM1 confers genetic susceptibility to idiopathic absence epilepsies and broader spectra of IGEs in the presence of family members with JME.

Disease Susceptibility↗
PubMed1995

Hernia through iliac crest defects. A report of four cases.

Herniation of abdominal contents through the donor site in the ilium occurred in 5% of a series of 59 bone grafts. Four patients had this condition at a 7 year follow up, and 2 were repaired with synthetic mesh. Age, gender, obesity and surgical technique are important causative factors. Preventive measures are proposed which have been successful during the past 3 years.

Aged↗
PubMed1995

Megestrol acetate in neoplastic anorexia/cachexia: clinical evaluation and comparison with cytokine levels in patients with head and neck carcinoma treated with neoadjuvant chemotherapy.

The aim of our study (clinical phase II open pilot study) was to evaluate the toxicity of megestrol acetate and its ability to increase appetite and body weight in patients with advanced-stage (III-IV) primary head and neck squamous cell carcinoma treated with neoadjuvant (primary) chemotherapy. Serum levels of interleukin-1 alpha and beta, interleukin-2 and 6, tumor necrosis factor-alpha, and the soluble receptor for interleukin-2 were evaluated before and after megestrol acetate treatment. The same cytokines and soluble interleukin-2 receptor were also measured in culture medium of peripheral blood lymphocytes from the same patients after stimulation with phytohemagglutinin. From April 1993 to February 1994, 11 male patients were enrolled in our study: their mean age was 57.8 years (range 43-69 years). Megestrol acetate was administered at a dose of 320 mg/day in the interval between chemotherapeutic cycles for a total of three consecutive cycles; 9 of the 11 patients could be evaluated (81.8%). Except for the performance status according to Karnofsky, all parameters were increased after megestrol acetate treatment. The average weight increased by 6.3 kg (13.2%), appetite by a score of 2.4 (38.6%) and the Spitzer's quality of life index by a score of 2.4 (36.2%). The performance status according to Karnofsky decreased in only 1 patient, remained the same in most patients, and in 2 patients was slightly improved. No significant side effects were observed during treatment. Serum levels of interleukin-1 alpha and beta, interleukin-2 and 6, tumor necrosis factor-alpha, and soluble interleukin-2 receptor were significantly higher than in normal subjects, prior to treatment with megestrol acetate. These levels dropped after megestrol acetate treatment with a statistically significant decrease for interleukin-1 alpha and beta and tumor necrosis factor-alpha. There were no significant differences in the production of cytokines by peripheral blood lymphocytes stimulated with phytohemagglutinin from patients before megestrol acetate treatment and normal subjects, with the exception of interleukin-6 (higher in patients) and of soluble interleukin-2 receptor (lower in patients). There was no significant difference in the cytokines and soluble interleukin-2 receptor produced in culture before and after megestrol acetate treatment, except for interleukin-6 which decreased after treatment.

Adult↗
PubMed1995

Mapping of genes predisposing to idiopathic generalized epilepsy.

Idiopathic generalized epilepsy (IGE) is characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Twin and family studies suggest that genetic factors play a key part in IGE. A multilocus model appears to best fit the observed inheritance patterns. Mapping of IGE-related genes has been previously attempted using parametric methods, with conflicting results. In particular, recent evidence argues both for and against a chromosome 6p locus (EJM1) for juvenile myoclonic epilepsy, a subtype of IGE. We have approached the problem of mapping IGE loci using non-parametric methods, which have recently been successful for other complex diseases. No evidence for linkage to chromosome 6p was obtained. However, we obtained evidence for involvement of a locus at chromosome 8q24, close to the marker D8S256. The same 8q24 region was previously implicated in families with benign neonatal familial convulsions (BNFC), a generalized epilepsy syndrome that is inherited as a simple dominant mendelian trait. There is an apparent conserved syntenic group of genes in human 8q24 and a region of mouse chromosome 15, which harbors the stargazer (stg) locus. Homozygous mutant mice at the stg locus show a form of generalized epilepsy that resembles human absence epilepsy. Our findings may have implications for a locus on 8q24 predisposing to IGE.

Chromosome Mapping↗
PubMed1995

CD3-induced T-cell activation in the bone marrow of myeloma patients: major role of CD4+ cells.

A large expansion of activated T cells (CD3+CD25+) with the potential to act as anti-tumour effector cells is inducible in multiple myeloma (MM) patients by culturing bone marrow mononuclear cells (BMMCs) with the anti-CD3 monoclonal antibody (mAb) OKT3. The aim of this study was to provide a greater characterization of CD3-activated T cells. On day 6, most T cells coexpressed the CD11a, CD18, CD54, CD45R0 antigens and consisted of activated (CD25+) CD4+ and CD8+ cells in nearly equal proportions. Kinetics studies showed that CD4+CD25+ cells proliferated more rapidly and peaked earlier than CD8+CD25+ cells. When experiments were performed with purified subpopulations by removing CD4+ cells (resulting in CD8+ BMMCs) or by removing CD8+ cells (resulting in CD4+ BMMCs). T-cell activation and autologous plasma cell decrease were observed in CD4+ BMMCs only. Transwell cultures showed that CD4 help was necessary to make CD8+ BMMCs susceptible to CD3 stimulation. Relevant amounts of IL-2 were found in the supernatants of CD4+ BMMCs cultures, whereas no secretion of IL-4 was detected, indicating a Th1-like profile of CD3-activated CD4+ cells. These data indicate that CD4+ cells proliferate earlier and provide optimal help to induce the subsequent expansion of CD8+ cells after CD3 stimulation of MM BMMCs. Adequate stimulation of CD4+ cells is therefore essential in any strategy aiming to recover T-cell-mediated immunity in MM.

Bone Marrow↗
PubMed1995

Refinement of map position of the human GluR6 kainate receptor gene (GRIK2) and lack of association and linkage with idiopathic generalized epilepsies.

Hereditary factors play a major role in the etiology of idiopathic generalized epilepsies (IGEs). The pivotal function of glutamate receptors (GluRs) in excitatory neurotransmission implicates their involvement in epileptogenesis and genetic susceptibility to IGEs. A trinucleotide repeat polymorphism detected in the 3' untranslated region of the kainate-selective GluR6 receptor gene (GRIK2) on chromosome 6 makes it possible to perform linkage and association studies with this high-ranking candidate gene. The present study tested the hypothesis that allelic variants of GRIK2 contribute to the genetic susceptibility to the common IGEs. Linkage and association analyses were conducted in 63 families ascertained through IGE patients with juvenile myoclonic epilepsy, juvenile absence epilepsy, or childhood absence epilepsy. Our linkage and association results suggest that allelic variants of GRIK2 are not involved in the expression of the common familial IGEs, and radiation hybrid mapping assigns GRIK2 to the chromosomal region 6q16.3-q21. This localization excludes GRIK2 as a candidate for the putative IGE susceptibility locus "EJM1" on the short arm of chromosome 6.

Chromosome Mapping↗
PubMed1995

Functional and phenotypic upregulation of CD13/aminopeptidase-N on precursor-B acute lymphoblastic leukemia after in vitro stimulation.

Acute lymphoblastic leukemia (ALL) cells of precursor-B type were assessed for expression of the cell surface peptidase CD13 (aminopeptidase-N) after 72 hours' culture in 10% B cell growth factor (BCGF), TPA, or medium alone. CD13 was analyzed phenotypically using a specific monoclonal antibody (mAb) by flow cytometry, and also with a spectrophotometric enzyme assay to measure the cleavage of specific peptide substrates. CD13 antigen was induced in all 10 cases of precursor-B ALL after culture with BCGF, with weaker expression seen in cells incubated with TPA or in medium alone. Aminopeptidase-N-like enzymatic activity was also demonstrated in cultured cells, particularly after BCGF exposure. Using the mAb WM-15, which specifically inhibits aminopeptidase-N function, we demonstrated that induction of true aminopeptidase-N activity was largely restricted to BCGF-treated cells, in which approximately 20% of total aminopeptidase activity was due to aminopeptidase-N. Phenotypic expression of the peptidase CD10 (neutral endopeptidase) was not altered on cultured cells. These findings indicate that CD13 expression can be selectively upregulated on ALL cells in response to proliferative stimuli. This peptidase, in cooperation with CD10 and perhaps other surface enzymes, may act to regulate the concentration of molecules at the cell surface which influence the growth of precursor-B ALL cells.

Adolescent↗
PubMed1995

[The immunological assessment of a combined therapeutic approach (chemo- + radiotherapy +/- surgery) including immunotherapy in neoplasms of the head and neck area at an advanced stage].

Fourty-eight patients entered the study, 37 of whom were evaluable, who underwent a nonrandomized combined modality approach plus a randomized immunotherapy treatment assigning the patients to one of the three arms: 1) thymostimulin, 2) beta IFN, 3) thymostimulin + beta IFN. The patients enrollment started in May 1991 and was closed in February 1993: the final evaluation was in February 1994. An immunological evaluation was made for all patients enrolled. The immunological assessment confirms some previous reports, such as the defective proliferative response of PBMC, the high serum level and the low production in culture of soluble IL 2 receptor (s IL 2 R), the low serum level and the low production of IL 2, and moreover shows new data. It is noteworthy that the significant increases--especially for cytokines and s IL 2 R, except for IL 1 alpha which has decreased, both for serum levels and for culture production--are induced by treatment with beta IFN (or with thymostimulin + beta IFN), suggesting that beta IFn is the immunologically effective moiety.

Adult↗
PubMed1995

Autologous gastrointestinal reconstruction.

The patient with short bowel syndrome is essentially unable to absorb sufficient nutrients. This is caused by either short mucosal contact time, insufficient mucosal surface area (enterocyte mass), or a combination of the two. Management consists primarily in sustaining health and growth by intravenous nutrition and in enhancing the natural intestinal adaptation response. Surgery in the form of autologous gastrointestinal reconstruction (AGIR) is designed to redistribute the patient's own residual absorptive bowel to enhance adaptation and, possibly, to increase the absorptive mucosal surface by neomucosal growth. The alternative and ultimate fallback procedure in the management of intestinal failure is bowel transplantation, with its associated serious immunosuppression-related complications. Imaginative AGIR techniques provide new hope for the future.

Humans↗
PubMed1995

[Detection of Chlamydia trachomatis infection by PCR in first voided urines in men].

The goal of this study was to evaluate whether the new commercially available PCR-based assay Amplicor C. trachomatis (Roche Molecular Systems) could improve the diagnosis of chlamydial urogenital infections in men, compared with cell culture of C. trachomatis considered as the reference method. A total of 466 men attending the STD clinic were tested by the Amplicor test in urine and by cell culture in urethra. The prevalence of C. trachomatis was 13.7% (64/466) by cell culture and 14.4% (67/466) by the Amplicor test. After resolution of the discrepant results, the sensitivity of culture was 91.4% in male urethral specimens. The resolved sensitivity of the PCR assay was 92.7% in male urine and the specificity was 99.5%. We concluded that this rapid PCR-based assay showed an improvement in quality for diagnosing C. trachomatis infections in men.

Adolescent↗
PubMed1995

Morphologic and planimetric diagnosis of follicular thyroid lesions on fine needle aspiration cytology.

During 1989-1992, 2,729 fine needle aspiration biopsies were performed; 585 with histologic controls were reviewed. The aim of the study was to demonstrate the incidence of carcinoma in follicular-structured smears without nuclear enlargement, evaluated with planimetric techniques, and to suggest a new cytodiagnostic classification. Of 398 follicular-structured smears, 188 were colloid nodules, 38 were thyreocytic hyperplasias without nuclear atypia, 146 were predominantly follicular lesions (PFL) and 26 were follicular lesions with nuclear pleomorphism. The last showed a high incidence of neoplasia (69.2%) and carcinoma (46.1%) and the largest planimetric values for nuclear area, perimeter and maximum diameter. The second and third categories showed only a difference in the incidence of benign neoplasms (32.9 vs. 15.8%). These results suggest that six months of expectant management might be useful in simple follicular lesions, whereas a follicular pattern with nuclear enlargement requires surgical treatment for the strong possibility of carcinoma.

Adenoma↗
PubMed1995

Open study of topical 0.025% tretinoin in the treatment of vulvar lichen sclerosus. One year of therapy.

OBJECTIVE: To study the use of topical tretinoin for treating vulvar lichen sclerosus. STUDY DESIGN: An open, uncontrolled clinical study on 22 patients affected by histologically confirmed vulvar lichen sclerosus. Topical 0.025% tretinoin was applied once a day, five days a week, for one year. Clinical and histologic parameters were evaluated before and after therapy, and statistical analysis was performed. RESULTS: Symptoms, gross appearance and histopathologic features improved in a highly significant manner (P < .001). Cutaneous side effects were observed but rapidly disappeared, and no patient left the study for this reason. Maintenance of results was observed at the 4-13-month follow-up visits. CONCLUSION: Topical tretinoin seems feasible for use in the topical treatment of vulvar lichen sclerosus.

Administration, Topical↗