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Biomedical subjects

G Palmieri

Publications and source records attributed to G Palmieri.

At least 109 records · Page 6Linked to original sources

Gonadal function after multimodality treatment in men with testicular germ cell cancer.

We evaluated gonadal function in 63 patients with testicular cancer both within 1 month of unilateral orchiectomy before further treatment (pretreatment) and 3 years after treatment discontinuation (post-treatment). Sixteen patients underwent orchiectomy alone (group 1), nine patients underwent infradiaphragmatic radiotherapy (group 2) and 28 patients received four cycles (group 3) and 10 patients received six cycles (group 4) of cisplatin-based chemotherapy (cisplatin, vinblastine and bleomycin-PVB, or cisplatin, etoposide and bleomycin-PEB). Pretreatment semen analyses showed reduced sperm cell density, motility and impaired morphology of spermatozoa in all four groups (p > 0.05). At the same time elevated estradiol and decreased serum follicle-stimulating hormone (FSH) levels in 28.5% of subjects were correlated with high serum beta human chorionic gonadotropin concentrations. Semen analyses revealed the lowest values for all parameters after infradiaphragmatic radiotherapy. Sperm cell count, motility and morphology were significantly better in patients treated with orchiectomy alone or with a conventional dose of chemotherapy than in the groups that received radiotherapy or high doses of chemotherapy (p < 0.05). We also observed a correlation between serum FSH values and sperm cell density for both pretreatment and post-treatment in every group of patients (p < 0.05). Persistent subclinical Leydig cell dysfunction in groups treated with radiotherapy or high doses of chemotherapy was expressed by increased basal luteinizing hormone levels (78% of patients in group 2 vs 60% of patients in group 4) (p < 0.05) and by normal testosterone serum values (89% of patients in group 2 vs 80% of patients in group 4). Spermatogenesis and Leydig cell function are, therefore, persistently impaired in the majority of testicular cancer patients treated with radiotherapy or with more intensive chemotherapy.

Adolescent↗

Rapidly progressive form of Creutzfeldt-Jakob disease without dementia: a case report.

We describe a case of a patient with Creutzfeldt-Jakob disease (CJD) characterized by a rapid clinical course lasting one and a half months, by: presence of focal dystonic movements at onset, absence of mental deterioration in the period preceding the impairment of consciousness, ataxia, myoclonus and periodic EEG abnormalities. The autopsy confirmed subacute spongiform encephalopathy, but no evident neuronal loss was observed. An acute clinical course of CJD may explain this latter histological finding which, in turn, probably provides an explanation for the absence of intellectual impairment.

Aged↗

Modulation of chemosensitivity by alpha interferon in multiple myeloma and non-Hodgkin's lymphoma.

Low-grade non-Hodgkin's lymphoma and multiple myeloma are chemosensitive malignancies, but are rarely curable because of primary or acquired drug resistance. Interferon has been shown to modulate the multidrug resistance phenotype and to reinduce chemosensitivity in patients with chemoresistant tumors. Fifteen patients with multiple myeloma and 64 patients with low/intermediate grade non-Hodgkin's lymphoma unresponsive to initial chemotherapy were treated with alpha 2b interferon for 2 months. In case of an objective response, treatment was continued until disease progression; non-responding patients received the same chemotherapy to which they were resistant, preceded by a 5 day course of interferon. Interferon salvage monotherapy induced an objective response in 1/15 patients with multiple myeloma and in 7/64 patients with non-Hodgkin's lymphoma. An objective response was achieved after retreatment with first-line chemotherapy preceded by interferon in 4/14 patients (28.6%) with multiple myeloma and in 20/56 evaluable patients (35.7%) with non-Hodgkin's lymphoma. Toxicity was moderate, predictable, manageable, and never caused interruption of the treatment. Interferon appears to be able to modulate chemosensitivity of tumors refractory to chemotherapy with several potential mechanisms, including an effect on drug accumulation; its utilization in this setting warrants further evaluation.

Adult↗

Cross-linking of alpha 4 beta 1 and alpha 5 beta 1 fibronectin receptors enhances natural killer cell cytotoxic activity.

Cell/extracellular matrix interactions mediated by integrins regulate differentiation, migration, and effector functions of immune system components. Human NK cells express alpha 4 beta 1 and alpha 5 beta 1 integrins, which mediate their binding to fibronectin (FN). We have investigated the ability of FN and its beta 1 integrin receptors to modulate NK cytotoxicity. Our data show that the presence of immobilized FN significantly augments the spontaneous cytotoxic activity of in vitro cultured human NK cells against several NK-susceptible, but not NK-resistant, target cells; Ab-dependent cytotoxicity against Ab-coated P815 target cells and the redirected lysis of anti-CD16 hybridomas are also enhanced in the presence of FN. Solid-phase-bound anti-human beta 1, or its F(ab')2 fragment, anti-alpha 4 and anti-alpha 5 mAbs, all consistently enhance Ab-dependent cytotoxicity against Ab-coated murine target cells. The 120-kDa (alpha 5 beta 1-binding), but not the 40-kDa (alpha 4 beta 1-binding), FN fragment fully reproduced the enhancing effect observed with the entire molecule. Our data also demonstrate that alpha 4 beta 1 and alpha 5 beta 1 cross-linking on NK cells induces an increase of intracellular Ca2+ concentration that is abrogated by EGTA, thus suggesting that the capacity to mobilize Ca2+ is involved in the coactivating role of alpha 4 beta 1 and alpha 5 beta 1 FN receptors in the cytotoxic functions of NK cells.

Antibodies, Monoclonal↗

Stimulation of protein tyrosine phosphorylation by interaction of NK cells with fibronectin via alpha 4 beta 1 and alpha 5 beta 1.

Recent evidence indicates that integrins do transduce signals that are involved in the regulation of a number of cellular processes. We have shown previously that human NK cells express alpha 4 beta 1 and alpha 5 beta 1 integrins, which mediate their adhesion to fibronectin (FN). Here we investigate whether cross-linking of beta 1 FN receptors on human NK cells stimulates tyrosine kinase activation. Our results indicate that cross-linking of beta 1 integrins on NK cells, either freshly isolated from PBL or generated from 10-day coculture of nonadherent PBMC with an irradiated EVB+ lymphoblastoid B cell line (long-term activated NK cells), altered the tyrosine phosphorylation pattern. In particular, we found stimulation of tyrosine phosphorylation of two proteins migrating with an apparent mass of 105 and 115 kDa, which was not observed after CD16 engagement. Phosphorylation of pp105-115 was already observed at 1 min, raised maximal values at 3 to 5 min, and persisted until 20 min after stimulation. Tyrosine phosphorylation of pp105-115 was also observed upon engagement of alpha 4 beta 1 and alpha 5 beta 1 FN receptors either with mAb directed against the alpha subunits or after NK cell adhesion to FN or its 120- and 40-kDa fragments. Pretreatment of NK cells with the tyrosine kinase inhibitor herbimycin A resulted in marked decrease of phosphorylation stimulated through alpha 4 beta 1 and alpha 5 beta 1 integrins, indicating that ligation of FN receptors on NK cells activates tyrosine kinase(s). Overall our results suggest that beta 1 integrins on NK cells play a major role as signaling molecules in the regulation of NK cell functions.

Animals↗

Peptide immobilization on calcium alginate beads: applications to antibody purification and assay.

Two different procedures were developed for the non-covalent immobilization of peptide antigens on calcium alginate beads. The antigenic peptide is first synthesized in a multimeric form starting from a polydentate lysine core, and then immobilized on alginate beads (average volume 0.05 ml) by entrapment or simply by non-covalent adsorption. Coupling yields, as monitored by RP-HPLC analysis of the immobilization time course and/or by amino acid analysis of derivatized beads, were close to 1-2 mg of peptide per ml of gel. Immobilization yields were not dependent on the peptide net charge, hydrophobicity or length, but mainly on the extent of peptide multimerization. After immobilization on alginate gel, peptide antigenic properties were fully retained, as clearly demonstrated by the batchwise micropreparative purification of anti-peptide antibodies in good yields and with a high degree of purity, directly from crude sera in a single adsorption-elution step. Derivatized beads were sufficiently stable towards repeated washing-equilibration procedures, allowing very limited peptide leakage from the matrix. Peptide beads were also successfully used for the development of solid-phase immunoassays in test-tubes to characterize the corresponding antibodies, with the immobilization yield and signal-to-noise ratio being greatly enhanced in comparison with other types of conventional supports.

Adsorption↗

Interleukin-2-induced renal dysfunction in cancer patients is reversed by low-dose dopamine infusion.

Recombinant interleukin-2 (rIL-2) is widely used in patients with advanced cancer to enhance killer cell functions. However, the main drawback of rIL-2 therapy is the frequent development of oliguric acute renal failure (ARF), presumably due to a vascular leak syndrome. The aim of this study was to evaluate the effect of low-dose dopamine infusion on this form of ARF. Nine patients with metastatic renal cancer and previous unilateral nephrectomy were treated with a continuous intravenous infusion of rIL-2 (3 x 10(6) Cetus units/m2/d) for 5 days (study A). After 1 week, all the patients repeated the same cycle, but with the addition of a continuous intravenous infusion of dopamine (2 micrograms/min/kg body weight) that was started at the third day of treatment (study B). During study A, all patients showed a progressive (up to 34%) decrease of creatinine clearance. After rIL-2 withdrawal, these alterations persisted and were associated with a reduction in urinary output, sodium urinary excretion, and plasma protein. In study B, dopamine administration after renal function impairment (delta glomerular filtration rate = -44%) led to a prompt improvement of creatinine clearance. Creatinine clearance showed a further significant enhancement after the withdrawal of both drugs, reaching a value within the baseline range on the third day of follow-up. Similarly, the decline in urinary output and sodium excretion during rIL-2 was promptly counteracted by dopamine; in addition, after withdrawal of rIL-2 and dopamine, plasma protein levels were normalized. In conclusion, our data suggest that rIL-2-induced ARF in cancer patients is due to renal hypoperfusion mainly caused by a reduction in oncotic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

Vitamin E added silicone gel sheets for treatment of hypertrophic scars and keloids.

BACKGROUND: Trauma of various origins can induce a connective tissue disorder that leads to keloids. This condition has yet not been clearly distinguished from scars and hypertrophic scars. Only electronmicroscopic and biochemical data can help to do this. Among some more or less therapeutic approaches, the use of silicon (polydimethylsiloxane) plates, wrapped on the keloid surface, has been reported effective by some authors. These authors also demonstrated that it is not the mechanical pressure that is the mechanism of action, but a direct action on fibroblasts and a hyperhydration of subcutaneous tissue. The authors of this study conceived that the silicon plate may be able to improve the transdermal penetration of a compound such as vitamin E. This vitamin is capable of preserving some important morphologic and functional features of biological membranes by means of its phytilside chain of the molecule acting as a stabilizer of lysosomal membranes. MATERIALS AND METHODS: Eighty patients of both sexes, aged between 18 and 63 years, who had hypertrophic scars and keloids, were admitted to the trial. The patients were randomized to two groups in a simple-blinded study. Group A: Forty patients whose scars have been covered with silicon plates with added vitamin E. Group B: Forty patients treated with simple silicone gel sheets. No pressure bandages were used, only tape fixing the sheet for 10 hours overnight. The trial lasted for 2 months. The results were recorded at 4 and 8 weeks, evaluating the improvement according to a Scott-Husskinson scale. For objective assessment photos were taken. The results were analyzed by the chi-square test. RESULTS: At the end of the first month, group A had improved by more than 50% in 85% of cases, whereas the improvement in group B was 55% (P < 0.01). At the end of the second month, 95% of patients in group A had improved by 50%, whereas 75% had improved by 50% in group B (P < 0.05). CONCLUSIONS: Vitamin E added to the silicon plate scored better than the simple silicon plate at the end of both periods. We have reported the successful combined action of vitamin E and silicone gel sheets in scar treatment, especially in the short-term prophylaxis of hypertrophic scars or keloids.

Administration, Topical↗

On the vegetative and sensitive innervation of the Retractor clitoridis muscle in some domestic animals.

The retractor clitoridis muscle originates from the coccygeal vertebrae in the cow, ewe, goat and mare, and from the anal musculature in the sow. It terminates at the base of the clitoris. In all the species considered, a vegetative innervation was found. This was represented by isolated or grouped ganglion cells. Nervous sensitive supply was also present. This was represented by Pacinian, Pacinian-like and Golgi-Mazzoni's corpuscles, and by Krauses's end bulbs. A notable difference was found in the amount and type of these receptors. They were numerous in the sow, ewe and goat, and rare in the cow and mare. Additionally, in the sow, ewe and goat, all the above mentioned receptors were found, while, in the cow and mare, only Pacinian and Pacinian-like corpuscles occurred. The morphology of these receptors was described and hypotheses were made concerning their probable functional role.

Anal Canal↗

Cloning and sequencing of a laccase gene from the lignin-degrading basidiomycete Pleurotus ostreatus.

The gene (pox1) encoding a phenol oxidase from Pleurotus ostreatus, a lignin-degrading basidiomycete, was cloned and sequenced, and the corresponding pox1 cDNA was also synthesized and sequenced. The isolated gene consists of 2,592 bp, with the coding sequence being interrupted by 19 introns and flanked by an upstream region in which putative CAAT and TATA consensus sequences could be identified at positions -174 and -84, respectively. The isolation of a second cDNA (pox2 cDNA), showing 84% similarity, and of the corresponding truncated genomic clones demonstrated the existence of a multigene family coding for isoforms of laccase in P. ostreatus. PCR amplifications of specific regions on the DNA of isolated monokaryons proved that the two genes are not allelic forms. The POX1 amino acid sequence deduced was compared with those of other known laccases from different fungi.

Amino Acid Sequence↗

Chlorambucil, vincristine and cytarabine (COA) treatment of low grade lymphomas.

Forty-five patients with stage III-IV low grade non-Hodgkin's lymphoma (NHL) were treated with a non-intensive polychemotherapy regimen including chlorambucil-vincristine and cytarabine (Ara-C), termed COA, for a total of 366 courses, beginning in June 1986. Grade 4 myelotoxicity occurred in only 4/45 patients. No treatment related death was observed. All patients were evaluable for response. Overall, 38 (84%) objective responses, including 31 (69%) complete responses (CR), were observed. At a median follow-up of 57 (21-84+) months, only 8 deaths occurred. Twenty-seven (60%) patients are still disease-free. All disease-free patients were in their first CR. The seven-year estimated survival is 71% and the estimated 7-year progression-free survival (PFS) was 48%. The estimated probability of complete responders to be disease-free at 6 years is 78%. Pretreatment laboratory parameters (serum levels of thymidine kinase, LDH and TNF-alpha showed a good prognostic relevance at using univariate analysis. At multivariate analysis, only the pretreatment serum levels of TNF-alpha were significantly associated with a higher CR achievement probability (p = 0.02) and a longer PFS (p = 0.02). We established a risk model for clinical outcome based on these 3 parameters. Patients having all parameters within the normal range at diagnosis, showed a very good prognosis (100% 7-year PFS and survival), while patients with all parameters increased had a very poor prognosis (0% 7-year PFS and 22% 7-year survival). In conclusion, COA treatment appears to be a non-toxic and very effective treatment for low-grade non-Hodgkin's lymphomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

YAC contig organization and CpG island analysis in Xq28.

One hundred nineteen YACs were assembled into 6 contigs spanning about 7.1 Mb of Xq28. The contigs were formatted with 65 STSs and 136 hybridization probes and were extensive enough to be aligned and oriented by published genetic linkage and somatic cell hybrid panel data. Selected YACs from the entire region were mapped with five rare-cutter restriction enzymes to infer the position of putative CpG islands indicative of gene locations; 48 such sites were identified by the near-coincidence of at least three rare-cutter sites. The analysis defined three subregions of Xq28: 4 Mb of moderate GC and CpG island content from the Xq27 border through the GABRA locus; 1.5 to 2 Mb, extending to the G6PD gene, that is variably and poorly cloned, but contains a high concentration of CpG islands and GC; and about 1.5 Mb between G6PD and the telomere, which is generally low in CpG and GC levels, including a subtelomeric DNA region that shows extensive homology to Yq DNA.

Chromosome Mapping↗

H-2Kb and H-2Db gene transfections in B16 melanoma differently affect non-immunological properties relevant to the metastatic process. Involvement of integrin molecules.

Modification of non-immunological cell adhesion properties plays a major role in the decrease in metastatic ability observed after transfection of the H-2Kb gene in H-2-negative B16-derived melanoma clone cells. To investigate the role played by different class-I major histocompatibility complex (MHC) genes on non-immunological properties relevant for metastasis, transfection with the H-2Db gene alone or in conjunction with the H-2Kb gene was performed. H-2Db gene transfection did not modify either metastatic potential or non-immunological cell adhesion properties. Double KbDb transfectants showed a decreased metastatic ability when compared to control clones and to Db transfectants; a decrease in homotypic adhesive ability was also observed, even though not in all clones studied: therefore expression of the Db gene is also relevant. The mechanisms of homotypic cell adhesion were studied and found to be dependent upon temperature and divalent cations. Adhesion was partially inhibited by an antiserum directed against the beta 1 integrin subunit, whereas anti-alpha IIb beta 3 was ineffective. Cell pre-treatment with anti-beta 1 serum reduced metastatic ability. A decreased expression of alpha 4 and alpha 6 integrin subunits was observed in Kb clones, whereas no difference in the levels of some homophilic cell adhesion molecules, such as N-CAM and alpha IIb beta 3, was found. Adhesion required the activity of tyrosine kinases, as suggested by the decreased adhesive properties and impaired metastatic ability of cells pre-treated with the tyrosine-kinase-inhibitor genistein. These results are compatible with involvement of integrin molecules of the beta 1 family in the adhesive ability of these cells. Our data show that: (a) immunological and non-immunological effects of MHC transfection are correlated and depend on the class-I gene used, suggesting that MHC gene therapy can be highly successful only if appropriate MHC genes are transfected; (b) non-immunological cell-adhesion properties modified after MHC transfection could be related to an impairment of integrin-mediated adhesive interactions.

Animals↗

In vivo phenotypic characteristics of AKR T-cell lymphomas with different leukemic potential: possible role of alpha 4 beta 7 integrin in the progression towards the leukemic phenotype.

The present study was undertaken in order to determine whether the expression of specific surface molecules which mediate immune recognition as well as cell-cell and cell-matrix interactions is associated with the leukemic evolution of T-cell lymphomas. To this end, we have investigated the in vivo phenotypic characteristics and the in vitro natural-killer(NK)-cell susceptibility of a group of MCF-247-induced AKR/J T-cell lymphomas with different leukemic potential. We found that in the AKR/J model, the biological aggressiveness of leukemic cells is not dependent upon an escape from host immune surveillance as a consequence of an in vivo down-regulation of H2-Kk determinants or a resistance to NK lysis. Moreover, NK susceptibility of AKR/J lymphomas does not seem to correlate with the level of H2-antigen expression. No obvious correlation was found between the leukemic phenotype and the amount of MEL-14, LFA-1, ICAM-1, Pgp-1/CD44 and THAM/CD26 antigen expression. An in vivo coordinated up-regulation of alpha 4 and beta 7 integrin chains, with the highest levels of expression detected in secondary sites of leukemic infiltration, was observed in the highly leukemic lymphoma NQ22 and, albeit to a lesser extent, in lymphomas with moderate leukemic potential. Conversely, non-leukemic lymphomas were repeatedly alpha 4- and beta 7-negative. These findings suggest that in the AKR/J system the expression of alpha 4 beta 7 integrin may contribute to leukemic spreading of T-cell lymphomas.

Animals↗

Long term activation of natural killer cells results in modulation of beta 1-integrin expression and function.

Integrin expression and function is largely modulated by cell activation. Here we provide evidence that long term activation of human NK cells results in a marked modulation of beta 1-integrin expression and adhesive functions. By flow cytometry and immunochemical analysis we have detected induction of alpha 1 beta 1 and alpha 2 beta 1, increased expression of alpha 4 beta 1 and alpha 5 beta 1, and decline of alpha 6 beta 1 on CD3-CD56+ NK cells generated from 10-day coculture of nonadherent PBMC with irradiated RPMI 8866 EBV+ lymphoblastoid B cell line. Adhesion assays performed on extracellular matrix-coated plates showed that, unlike fresh NK cells, long term-activated NK cells bind to native collagen I via alpha 2 beta 1 and to heat-denatured collagen I in an RGD-dependent manner, although they lose the ability to bind to laminin. In regard to the adhesion to FN, no major quantitative changes are observed after long term NK cell activation. However, whereas alpha 4 beta 1 and alpha 5 beta 1 completely mediate the adhesion of fresh NK cells to fibronectin, binding of activated NK cells is only partially beta 1-dependent and seems to involve also non-beta 1-integrin(s) recognizing and RGD sequence. The modulation of beta 1-integrin expression and the acquisition of new adhesive properties on long term-activated NK cells may be relevant for their traffic and tissue localization during inflammation and immune response.

Amino Acid Sequence↗

Relationships between risk factors and morphological patterns of human carotid atherosclerotic plaques. A multivariate discriminant analysis.

The histological characterization of the fibroatheromatous plaques and their histogenesis are still to be defined. Factors responsible for the evolution of intimal components and the mechanisms and stages of fibroatheromatous plaque formation are still largely obscure. Focusing on symptomatic plaques, the aim of this study is to determine whether plaque heterogeneity is the result of a haphazard clustering of various components or an organized pattern in response to risk factors. To this end, 180 carotid plaques from patients affected by transient ischemic attacks (TIA) or by stroke, with angiographic stenosis greater than 50%, were studied after endoarterectomy. Clinical and morphological data were collected by means of a pre-defined protocol, quantified and correlated, by using the discriminant analysis, with age, sex, hypertension, diabetes, hypercholesterolemia and smoking habit. Our results show that the relationships between plaque components are non-random and consistent with the knowledge derived from studies on human and experimental plaques. Moreover, some plaque patterns can be significantly correlated with single risk factors. The fibrous plaque was correlated with aging and diabetes; the granulomatous plaque, rich in giant cells, with the female sex and hypertension; the xanthomatous plaque, rich in foam cells and with extensive alcianophilia, with hypercholesterolemia. In the smokers, finally, the plaques were frequently complicated by mural thrombosis.

Adult↗