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Biomedical subjects

G Valente

Publications and source records attributed to G Valente.

At least 73 records · Page 4Linked to original sources

Evidence that a leukocyte type of 12-lipoxygenase is expressed and regulated by angiotensin II in human adrenal glomerulosa cells.

The 12-lipoxygenase (LO) pathway of arachidonic acid plays an important role in angiotensin II (AII)-mediated aldosterone synthesis. Several distinct isoforms of 12-LO have been cloned. However, in humans only the platelet form of 12-LO has been reported to be present. Western immunoblotting analysis in cultured human adrenal glomerulosa cells using polyclonal antibodies to porcine leukocyte 12-LO enzyme or peptide showed a specific 72-kilodalton band, which is identical to the molecular size of the porcine leukocyte form of 12-LO. In addition, AII (10(-7)) increased the intensity of the 72-kilodalton band nearly 2-fold over basal. In situ hybridization analysis indicated a strong positive reaction with the porcine leukocyte type of 12-LO antisense riboprobe in the zona glomerulosa of the adrenal cortex. The 12-LO probe also recognized a near 4-kilobase messenger RNA (mRNA) from human glomerulosa cells in Northern blots. Since the leukocyte type of 12-LO is highly homologous to human 15-LO, a reverse transcriptase and polymerase chain reaction was used to analyze the specific type of 12-LO mRNA in human cells. The mRNA for a porcine leukocyte type of 12-LO was detected in human adrenal glomerulosa cells, and the level of 12-LO transcripts was increased approximately 60-fold by AII (10(-7) M). The leukocyte type of 12-LO also was detected in human monocyte-like U937 cells, but not in IM-9 lymphocytes or human erythroleukemia cells. These results suggest that human adrenal glomerulosa cells and human monocyte-like U937 cells express a 12-LO which has immunological and molecular biological characteristics similar to the porcine leukocyte 12-LO.

Angiotensin II↗

Immunoglobulin light chain restriction and clonal rearrangement in nodular paragranuloma.

B-cell clonality was demonstrated in a typical nodular paragranuloma case (NP) by both immunoglobulin (Ig) surface analysis and Ig genes rearrangement studies. On frozen sections, immunostaining for Ig light chain expression revealed a clear-cut predominance of Ig lambda-expressing cells, recognizable as both small lymphocytes and lympho-histiocytic (L&H) cells. Accordingly, molecular analysis of the Ig genes showed a monoclonal rearrangement of the lambda chain gene, although no specific pattern of heavy chain gene rearrangement could be detected by JH analysis. The C lambda rearranged band was identified with two different restriction enzymes, excluding the hypothesis of a genomic polymorphism. Furthermore, the C kappa gene was almost completely deleted, indicating that the developmental hierarchy of Ig genes rearrangement has been respected. The molecular pattern of the C lambda hybridizing band was consistent with monoallelic rearrangement of almost the entire DNA sample, indicating that clonal proliferation was not limited to L&H cells, but also involved surrounding lymphocytes. This finding is in keeping with the immunohistochemical evidence of a lambda light chain restriction on both L&H cells and small lymphocytes, pointing to a close relationship between these two cell types. Our results as a whole suggest that L&H cells and B lymphocytes share a common origin and may both be involved in clonal proliferation in NP.

Antigens, CD↗

Presence of murine retroviral sequences in human cell line transplanted in immunosuppressed SCID-mice.

The SCID-hu mouse, a severe combined immunodeficient mouse transplanted with human hematopoietic cells, has been proposed as an experimental model for HIV-1 infection. However, like other animal models for infectious diseases, the SCID-hu mouse should provide the replication of the experimental agent without conferring any alteration during growth in the host. In this study using Southern blot hybridization, in situ hybridization and PCR analysis we demonstrate the presence of specific murine retroviral sequences in human cells recovered from the in vivo passages in SCID mice. Since the acquisition of endogenous retrovirus by human cells was demonstrated after their growth in nude mice, the data reported here extend this observation to the SCID model.

Animals↗

[Radiotherapy results in the treatment of malignant tumors of the nasal fossa and vestibule].

The authors report their personal experience in the treatment of malignant tumors of the nasal cavity and vestibule with irradiation alone or combined with surgery. From January 1976 to December 1989 we treated 40 patients with 22 squamous cell carcinomas, 12 adenocarcinomas or other glandular types, and 6 other histologic types of lesions: 23 patients received irradiation alone and 17 patients were treated with surgery and postoperative irradiation. The protocol included surgery as the treatment of choice: irradiation alone was administered to inoperable tumors or to the patients refusing surgery; postoperative irradiation was given when macroscopic or microscopic residual disease was observed after surgery or to particular histologic types. In the whole series of patients, 3- and 5-year local control rates were 70% and 50%, respectively; better results were obtained in the patients receiving the combined treatment (64% at 5 years) than in the patients receiving irradiation alone (43% at 5 years). Disease stages (I and II versus III and IV) were the only statistically significant prognostic factor; worse results in irradiated patients might be due to the higher rate of advanced lesions in this group. Salvage therapy (irradiation in 8 cases, surgery in 2 and chemotherapy in 1) was successfully performed in 5 of 11 treated patients. The 3- and 5-year overall survival rates were 88% and 70%, respectively. Severe complication rate was lower than 10% (3 cases only).

Adenocarcinoma↗

Small bowel metastasis from squamous cell carcinoma of the larynx. A case report.

Small bowel metastases from squamous cell carcinoma of the head and neck are relatively rare and in some cases asymptomatic. In the case herein reported, small bowel metastasis from a laryngeal carcinoma caused a life-threatening complication. The surgical approach was effective in saving the patient's life. Death occurred for neck tumor progression without abdominal signs of secondary lesions. A review of the previously reported cases is provided.

Carcinoma, Squamous Cell↗

Apocrine carcinoma of the skin. A clinicopathologic, immunocytochemical, and ultrastructural study.

BACKGROUND: Apocrine carcinomas of the skin are rare and incompletely studied neoplasms. METHODS: An immunohistochemical and ultrastructural study is reported of specimens from six patients with apocrine skin carcinoma in various body sites. Three tumors were in the axilla; one, the eyelid; one, the ear; and one, the scalp. There were three local recurrences and three regional lymph node metastases, but no patient died of cancer (follow-up, 2-10 years). RESULTS: The most reliable histopathologic criteria for identifying apocrine skin carcinoma appear to be decapitation secretion, periodic acid-Schiff-positive diastase-resistant material in the cells or lumen, and immunoreactivity with gross cystic disease fluid protein 15. All specimens expressed common epithelial antigens (cytokeratins, carcinoembryonic antigen, and epithelial membrane antigen) and histiocytic-secretive antigens (Leu-M1, lysozyme, LN5, alpha-1-antitrypsin, and alpha-1-antichymotrypsin). S-100 protein was found in the three nonaxillary tumors. Ultrastructurally, the primary tumors, and especially the secondary lesions, were dedifferentiated compared with normal apocrine glands. CONCLUSIONS: Apocrine differentiation in skin tumors does not indicate an exclusive origin from the apocrine sweat glands; these neoplasms usually have an indolent clinical course.

Adult↗

Histopathological findings after preoperative chemo-radiotherapy in oral and oropharyngeal carcinoma. A study of 28 resected specimens.

Serial sections of whole surgical specimens from 28 patients with locally advanced oral carcinoma were examined to assess the histopathological effects of a preoperative intravenous (i.v.) chemotherapy and radiotherapy protocol. In 15 cases (54%), no residual neoplastic tissue was found: in 9, the tumour area showed a dense hyalinised connective tissue, whereas in the other 6 cases foci of keratotic material were surrounded by a foreign body-type reaction. In 13 patients (46%), residual neoplastic tissue was observed: small fields of tumour were present in 6 cases, whereas tumour was widely persistent in 7. Lymph node metastases were observed in 9 cases (32%), with extracapsular spreading in 6 (21%). In 93% of cases, pathological staging on the specimen was more favourable than the clinical preoperative staging. 23 patients (82%) are alive without evidence of disease 30-55 months after surgery; 10 (43%) did not show any residual neoplastic tissue in the specimen; 10 patients (43%) showed persistence of tumour, but in 5 (21%) only small fields of tumour were observed. 4 patients (14%) died due to their tumour. The pathological data show that this protocol is successful in the treatment of advanced oral carcinoma; furthermore, they provide reliable information about the response to therapy and the subsequent course of the disease.

Adult↗

Distribution of interferon-gamma receptor in human tissues.

Interferon-gamma (IFN-gamma) is produced by activated T lymphocytes and plays a regulatory role in immune responses. The nature and location of cells that express the IFN-gamma receptor (R) and respond to this lymphokine are not well documented. The distribution of human IFN-gamma-R (HuIFN-gamma-R) was, therefore, investigated in situ by immunohistochemistry, using affinity-purified rabbit polyclonal antibodies directed against the extracellular domain of the receptor. In lymphoid organs, IFN-gamma-R expression is restricted to the B cell areas of lymph nodes, adult and fetal spleen, tonsils, appendix, and mucosa-associated lymphoid tissue of the small bowel. Macrophages and other reticular cells in lymphoid tissues and other organs are strongly positive for IFN-gamma-R, whereas its expression was consistently negative in the cortical and medullary thymocytes. Two-color flow cytofluorometric analysis of blood, lymph node, tonsil, spleen and thymus cells confirms that most B lymphocytes are IFN-gamma-R positive, whereas T lymphocytes are negative. However, after in vitro activation, peripheral blood T cells become IFN-gamma-R+. In non-lymphoid organs, IFN-gamma-R is expressed on endothelial cells of the medium- and small-size vessels. In epithelial tissues, high expression of IFN-gamma-R is detected on trophoblastic epithelium, glandular cells of stomach, ileum and colon, lung alveolar cells, salivary duct cells, renal tubular cells, and endometrial mucosa cells. Hepatocytes are weakly positive, while squamous epithelial cells are negative. The distribution of the HuIFN-gamma-R is discussed in view of the known functions of IFN-gamma.

Animals↗

Results of chemotherapy plus external reirradiation in the treatment of locally advanced recurrences of nasopharyngeal carcinoma.

Between 1982 and 1991, 16 patients with recurrent cancer of the nasopharynx were treated with chemotherapy (CT) and radiotherapy (RT). All patients had received prior RT (45-69, 30 Gy). According to rTNM there were three rT2, one rT3 and 12 rT4. 5 patients were N1. Reirradiation (12-46 Gy, mean: 28) started 3-4 weeks after CT (2-6 cycles of different combinations), but 2 cases involved concomitant therapy. Out of 16 patients 7 had complete response (CR) (43.7%), 7 partial response and 2 no response. Statistically significant prognostic factors for obtaining CR were time of relapse and response to initial CT. Median duration of CR was 22+ months (9-64+). Failures at primary site occurred in 3 patients, 2/2 of those receiving CT without platinum compounds and 1/5 of other ones, with statistically significant difference in local recurrence free-survival between the two groups. Two- and 3-year actuarial overall survival were 28% and 10%. Rates of disease-free survival were 17% and 8%, respectively. The acute toxicity was generally mild. No central nervous system damage or radiation-induced myelitis were observed in survivors.

Adult↗

Histological study of alcoholic, nonalcoholic, and obstructive chronic pancreatitis.

Pancreatic tissue obtained from 26 patients with alcoholic chronic pancreatitis (ACP), nine patients with nonalcoholic idiopathic chronic pancreatitis (NAICP), and seven patients with obstructive chronic pancreatitis (OCP) was studied in an attempt to determine whether clinical or etiologic differences have a morphologic counterpart. Histologically it was easy to distinguish ACP from OCP occurring distal to an obstruction of the pancreatic duct. Nine patients with NAICP showed histological features similar to those found in ACP. Plugs and calcifications were found as frequently in NAICP as in ACP, suggesting that NAICP, whatever the etiology, is truly pancreatolithiasis, which leads to slowly progressive fibrosis and acinar atrophy in the obstructed pancreatic lobule. Nerve fibers were found to be more numerous in all disease categories. Inflammatory foci of lymphocytes associated with nerves were observed in 57 and 35% of cases with OCP and ACP, respectively, but only in one patient with NAICP. These findings may constitute a pathological basis for the existing clinical data showing that NAICP frequently runs a pain-free course.

Adult↗

Argyrophilic nucleolar organizer region counts and Ki-67 scores in human renal cell carcinoma.

The proliferative activity of 21 cases of renal cell carcinoma has been investigated by means of monoclonal antibody Ki-67 and Nucleolar Organizer Regions (AgNORs) analysis. The correlation between AgNOR counts and Ki-67 scores was only slightly significant (r = 0.53, r2 = 0.28) as determined by linear regression. Positive correlation was found between Ki-67 scores and tumour histologic grade. However, no correlation was observed between Ki-67 scores and tumour pathologic stage and between AgNOR counts and tumour histologic grade and/or pathologic stage. The results suggest that AgNOR counts cannot replace Ki-67 scores in evaluating the proliferative activity of renal cell carcinoma and that such activity and both histologic grade and pathologic stage seem to be independent parametres.

Analysis of Variance↗

ATP-dependent control of steady-state cytosolic calcium in cultured gastric smooth muscle.

The regulation of intracellular calcium uptake and release in cultured gastric smooth muscle cells was studied in saponin-permeabilized cells derived from the rabbit antrum. Cells were studied in an ATP-regenerating medium in which the value of the ATP-to-ADP ratio was fixed by variation of the relative concentrations of creatine and creatine phosphate in the presence of a constant concentration of adenine nucleotides and creatine kinase. Free calcium in the medium was measured through the use of the fluorescent probe fura-2. As the ratio of ATP/ADP was increased (8.5, 55.0, and 155.0), the rate of calcium sequestration was increased, resulting in a decrease of steady-state free calcium (275.2, 178.4, and 98.1 nM, respectively). The addition of glucose (5 mM) and hexokinase (15 U/ml), which results in an increase of ADP due to the phosphorylation of glucose in the medium, caused an increase of free calcium concentration to a new set point of approximately 400 nM. Mitochondrial blockade with antimycin A before permeabilization had no effect on calcium sequestration or the resultant free calcium concentration, indicating that under physiological conditions calcium is sequestered predominantly into nonmitochondrial storage sites. Specific variation of ATP/ADP had no effect on the concentration dependence of inositol trisphosphate-induced calcium efflux, suggesting the functional independence of intracellular calcium influx and efflux pathways. These results indicate a significant role for cytoplasmic ATP/ADP in the control of intracellular calcium sequestration and the regulation of steady-state calcium concentration in cultured gastrointestinal smooth muscle cells.

Adenosine Diphosphate↗

The effect of preoperative local interleukin-2 (IL-2) injections in patients with head and neck squamous cell carcinoma. An immunological study.

Clinical, immunological, immunophenotypical, pathological and molecular biological studies were performed on tumor infiltrating lymphocytes (TIL) and lymph node lymphocytes (LN-ly) of 8 patients with squamous cell carcinoma of the oral cavity and oropharynx treated with 10 daily locoregional injections of low doses of IL-2 before surgery. No complications were seen during or after surgery. In 3 cases the LN-ly showed a moderate LAK activity, higher in the LN-ly omolateral to the tumor and near the IL-2 injection site; in 2 of these 3 patients a good LAK activity was induced after 6-day culture with IL-2. The LN-ly derived from nodes next to the tumor showed a decreased NK activity and proliferative ability both in basal conditions and after in vitro lymphokine challenging. LN-ly of 2 IL-2 treated patients showed high levels of mRNA encoding for IL-2-R, while it was absent in 2 untreated cases. Immunophenotypical studies on TIL showed statistically improved levels of CD25+ and LAK1+ cells in treated cases. Clusters of CD11c+ (macrophages) cells were seen close to the neoplastic sheets.

Aged↗

[Recurrences of epithelial tumors of the head and neck: review of the literature and a critical analysis of the problem].

Recurrence is a tumor renewal in a previously treated field or surgical wound after a disease-free period. The present work investigates loco-regional recurrences. In the first part of the work the most frequent recurrence sites, types and their characteristics (i.e. infiltrating, exophytic, ulcerating) are studied along with the problems in clinical and pathological diagnosis, new diagnostic imaging (CT and MR) and the UICC classification system. The second part of the work is dedicated to examining classical treatments (surgery, radiotherapy, chemotherapy and radiochemotherapy associations) as well new therapies (i.e. cryosurgery, hyperthermia, immunotherapy, photodynamic therapy). A review of the literature is made for indications, results and complications. An extensive study of the cases of the Head and Neck Group of the University of Turin during the 1983-1990 period is also reported. This experience is based on 312 cases: 68 (oropharynx and larynx) treated by surgery, 51 (neck nodes and stomal recurrences) treated by radiotherapy and hyperthermia, 35 (neck nodes) by hyperthermia alone, 168 (all sites) by chemotherapy and 20 by immunotherapy. In the third part of this work supportive therapies and practical problems are reported. In conclusion a therapeutic approach is proposed in relation to the site of the recurrence and previous treatments.

Antineoplastic Combined Chemotherapy Protocols↗

CD5-positive B-cells of the fetal and adult spleen lymphoid tissue: an immunophenotypical study.

The lymphoid tissue of the human fetal spleen at various stages of gestation was studied on frozen and paraffin sections and with two-colour flow cytometry. On the sections scattered lymphoid cells and perivascular lymphoid aggregates were found starting from the 15th week of gestation. CD3, CD5, CD19, CD20, CD21, CD22, CD24, CD35, CD38-positive cells were observed. No CD10- and CD23-positive cells were detected. Flow cytometry showed a prevalence of B-lymphocytes. The majority of them expressed CD5 antigen. These cells were also IgM/D, CD19, CD20, CD21, CD22, CD24 and CD35-positive. Only few of them expressed CD10 and CD23. A similar phenotype was found in human cord blood. By contrast, in adult spleens CD5 B-cells never exceeded 8% of the B-cells. The comparison between CD5 B-cells of fetal spleen and CD5 B neoplastic cells of 72 cases of small B-cell lymphomas showed that CD23, which was usually expressed by a high percentage of the neoplastic cells, particularly in B-CLL, was not displayed by the majority of the CD5 non neoplastic cells. The reverse was shown by CD35. These findings suggest that different states of activation distinguish the normal CD5 B-cells from their malignant counterpart.

Adult↗

On a case of early-onset post-traumatic facial hemispasm.

In a 49 year old woman an injury to the right frontotemporal region was quickly followed first by paresis and then by spasm of the right side of the face. The early onset of the spasm prompts a critical review of current views on the pathogenesis of facial spasm.

Brain Concussion↗

Lymphocyte populations of non-scleronodular Hodgkin's disease subtypes in different stages of lymphocyte depletion. An immunophenotypic and quantitative study.

Twenty-one cases of non-scleronodular Hodgkin's disease with variable lymphocyte contents were studied immunophenotypically and quantitatively to analyse the distribution of different lymphocyte populations and to determine whether selective loss of lymphocyte subpopulations accompanies overall lymphocyte depletion. In Hodgkin's tissue B-cells were scanty and unevenly distributed in samples with both many and few lymphocytes. Several large B, LN1-positive (possibly activated) cells were observed in a few cases. CD3-positive T-lymphocytes predominated in all cases; the same cells were also UCHL1-positive, thus expressing characteristics of mature T-memory cells. CD4-positive lymphocytes were usually more numerous than CD8-positive lymphocytes, but quantitative evaluation of the latter showed that they did not decrease in proportion to any diminution of the whole lymphocyte population. This finding suggests that in the process of lymphocyte depletion more CD4-positive lymphocytes than CD8-positive lymphocytes are lost, and this might account for the impairment of cell-mediated immunity in Hodgkin's disease.

Antibodies, Monoclonal↗