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C Pinto

Publications and source records attributed to C Pinto.

At least 73 records · Page 4Linked to original sources

Most human pulmonary infiltrating lymphocytes display the surface immune phenotype and functional responses of sensitized T cells.

Pulmonary infiltrating lymphocytes (PIL) isolated directly from human lung were examined for their surface immune phenotype by monoclonal antibody staining and cytofluorimetry. In order to purify PIL, resected lungs were enzymatically digested with collagenase and DNase and subjected to density centrifugation and nylon-wool column separation. In some cases, CD4+ lymphocytes were further purified with alpha CD8 and complement. The majority of pulmonary lymphocytes were CD2+ (87 +/- 1%) and CD3+ (73 +/- 4%). Virtually all of the CD3+ PIL were Ti alpha beta+. Greater than 90% of both CD4+ or CD8+ PIL were CD45RO+ and CD45RA-, consistent with prior antigen sensitization in vivo. A subset of CD4+ PIL (34 +/- 4%) expressed Leu8, the human congener of the murine MEL-14 lymphocyte homing receptor, whereas most homologous CD4+ peripheral blood lymphocytes were Leu8+ (75 +/- 8; P less than 0.01). HLA-DR surface antigens were expressed by 45 +/- 5% of CD4+ PIL versus 9 +/- 1% of CD4+ peripheral blood lymphocytes (P less than 0.001). There was no significant difference in the percentage of low-affinity interleukin-2 (IL-2) receptor-positive CD4+ lymphocytes in lung and blood (9 +/- 3% versus 13 +/- 2%). Analysis of the DNA synthetic cell cycle showed that approximately 5% of blood CD4+ lymphocytes and approximately 25% of CD4+ PIL were in S/G2/M. Compared to homologous blood T cells, purified PIL displayed enhanced proliferative responses to IL-2 and diminished responses to the lectin phytohemagglutinin. Lectin-stimulated PIL showed greater secretion of interferon-gamma and IL-2 than did blood lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

A preliminary study of reaction time in schizophrenics.

The aim of this study was to make a preliminary study of auditory reaction time (ART) and its significance in cases of schizophrenia. It was found that ART is significantly affected and prolonged in schizophrenia as compared to normal healthy controls (P less than 0.001) when the stimulus is presented to both ears or either car separately. Distractability was higher in schizophrenics as compared to adult controls (P less than 0.001). There was no significant difference in ART within the patient group when the stimulus was presented to the right ear or left ear (P greater than 0.05). There was no significant difference between ART of male and female schizophrenics (P greater than 0.05).

Acoustic Stimulation↗

Nonhuman cells correctly sort and process the human lysosomal enzyme cathepsin D.

Cathepsin D, like most lysosomal enzymes, undergoes multiple proteolytic cleavages during its lifetime. Although the significance of the earliest cleavages of cathepsin D is apparent (loss of the NH2-terminal signal peptide and activation peptide), functions of the two later cleavages are not understood and do not occur in all species. To examine these later events, a cDNA coding for human cathepsin D, which is normally processed to a two-chain form, was isolated and then expressed in mammalian cells from species which do not process the enzyme to the two-chain form. Analysis of the expressed human cathepsin D demonstrated proteolytic processing identical with that seen in normal human fibroblasts. Since processing to the two-chain form of the enzyme occurs in the lysosome, these studies revealed that the human cathepsin D was correctly sorted. The data also indicated that the sorting mechanism was conserved between diverse species and that late proteolytic processing in a variety of species was not determined by the presence or absence of the processing enzymes in the cell.

Amino Acid Sequence↗

Adoptive immunotherapy with interleukin-2 (IL-2) results in diminished IL-2 production by stimulated peripheral blood lymphocytes.

We examined the responses of peripheral blood lymphocytes (PBL) to a panel of T-cell mitogens in patients receiving adoptive transfers of tumor-infiltrating lymphocytes and continuous infusions of interleukin-2 (IL-2) for treatment of advanced cancer. All patients showed diminished proliferative responses to soluble and alloantigens, lectins, anti-CD3, and IL-2 during therapy. The non-major histocompatibility complex (MHC)-restricted cytolytic activities of PBL were increased by treatment and were further augmented by IL-2 in vitro. The expression of approximately 55-kd low-affinity IL-2 receptors (IL-2R) by PBL increased during treatment but functional IL-2R were simultaneously down-regulated. Proliferative responses were partially restored to pretreatment levels when PBL were costimulated with recombinant IL-2 and mitogens. Lectin stimulation of PBL produced little IL-2 secretion during treatment, while IFN-gamma secretion persisted. We conclude that infusions of IL-2 down-regulate the expression of functional IL-2R, decrease the secretion of IL-2, and lead to decreased mitogen responses by PBL.

Antigens, Surface↗

Adoptive immunotherapy with IL-2 results in the loss of delayed-type hypersensitivity responses and the development of immediate hypersensitivity to recall antigens.

Skin testing represents a direct method of assessing immune responses in vivo. Twenty-six patients with metastatic cancer of the lung, kidney, or melanoma were treated with adoptive transfers of autologous tumor-infiltrating or blood lymphocytes and continuous infusions of interleukin-2 (IL-2). Prior to therapy, cutaneous anergy to recall antigens was observed in 19 patients (73%), whereas 6 (27%) displayed normal delayed-type hypersensitivity (DTH) responses. When tested again at the end of therapy, DTH responses could not be elicited in any of the patients. Proliferative responses to skin test antigens, lectins, and IL-2 diminished progressively during therapy but returned to baseline values at 1 month. Unexpectedly, 14 of these patients (53%) developed immediate skin test responses to candida antigens and 5 (19%) to mumps antigens. These immediate responses were characterized by local erythema and induration that developed within minutes of injecting antigen. Biopsies displayed marked dermal edema and infiltration by eosinophils. Although serum IgE levels were not increased, immediate reactivity could be transferred by a heat-sensitive serum factor. The implications of this novel response are uncertain, and its development did not correlate directly with the anti-tumor effects of therapy. We conclude that adoptive immunotherapy with IL-2 produces a reduction in cutaneous DTH and diminished responses to mitogens while simultaneously promoting cutaneous allergy. We hypothesize that this may reflect diminished IL-2 production by antigen-specific helper T cells and that other lymphokines may promote these immediate hypersensitivity responses.

Antigens, Fungal↗

Mesotheliomas following exposure to asbestos used in railroads: the Italian cases.

The available knowledge on the oncogenic risks of asbestos, the data on the uses of asbestos in railroads, with particular regard to the Italian State Railroads (Ferrovie dello Stato = FS), and the groups at risk due to the exposure to asbestos used in railroads were briefly reviewed. The available data on the pathological effects of such exposure, and in particular on the onset of mesotheliomas among machinists and other railroad workers, were also summarized. Eighty-five cases of mesothelioma (80 pleural, 4 peritoneal, and 1 pericardial), related to the exposure to asbestos used in railroads, observed in various Italian regions, were then reported. Twenty-eight of these cases (among which 27 reported in the Emilia-Romagna Region) were submitted to a detailed study at the Bologna Institute of Oncology. Fifty cases of mesothelioma occurred among FS workers, in particular machinists; 30 cases occurred among machinists of rolling-stock workshops not belonging to the FS; 3 cases occurred among travelling workers of rolling-stock not belonging to the FS; and 2 cases were found in family members (a daughter and a wife) of FS workers. This series of cases, together with similar data from the literature, proves the existence of an actually health risk due to asbestos used in railroads, and indicates its gravity. On the basis of the available data, the following steps are considered necessary: the adoption of preventive measures, the performance of medical oncological surveillance, the promotion of systematic epidemiological investigations, and, finally, more emphasis on basic research, aimed at generating information on the biological events taking place during the incubation period of the tumors, to be used for reducing the effect of exposure, and therefore for contrasting the onset of the disease in those who, having been exposed, although healthy, are potentially at high risk.

Adult↗

Oxaliplatin plus raltitrexed in the treatment of patients with advanced colorectal cancer: a phase II study.

UNLABELLED: The combination of Oxaliplatin (OXA) and Raltitrexed (RTX) may represent a more convenient regimen as compared with OXA + 5-FU with Folinic acid (FA) modulation regimens. The present trial has been designed to explore the activity and tolerability of this combination in untreated and pretreated patients with advanced colorectal cancer (ACC). OXA and RTX were administered at the dose of 130 mg/m2 as i.v. 3-hour infusion and 3 mg/m2 over a 15-minute i.v. infusion, respectively, repeated every 21 days. Fifty patients were enrolled between February 1999 and March 2001. A total of 293 cycles were administered, with a median number of 6 cycles (range 1-14) per patient. The median dose intensity for OXA and RTX was 100% (50-100) and 86% (21-100), respectively. Reasons for RTX dose reduction were increases in transaminase serum levels and a reduction in creatinine clearance. Myelotoxicity was limited. A transaminase increase was observed in 74% of patients (14% grade 3 and 10% grade 4). Peripheral sensorial neurotoxicity was the most frequent side-effect (88%), although its intensity was mild in most patients (grade I 48%, grade II 24%, grade III 16%). Of 46 evaluable patients, 3 CR, 5 PR, 22 S and 16 P were observed. The CR + PR remission rate, according to the intention to treat analysis, was 16% with a 95% confidence limit of 7.2%-29.1%; in patients not pretreated for advanced disease the CR + PR rate was 26%, while only 2 out of 27 pretreated patients responded to the treatment (7%). The median time to progression was 5 months (2-11). The median survival was not reached after a median follow-up of 14 months. One-year survival is 60%. CONCLUSION: In this trial the OXA + RTX combination is confirmed to be active in ACC, although the level of activity seems to be lower than that of the other combination including OXA and 5-FU with or without FA modulation. The reasons for the low activity observed could at least in part be related to a reduction in the RTX dose intensity.

Adult↗

Malignant mesothelioma in 2004: How advanced technology and new drugs are changing the perspectives of mesothelioma patients. Highlights from the VIIth Meeting of the International Mesothelioma Interest Group.

Malignant mesothelioma (MMe) is a seemingly uncommon tumour whose incidence has in fact increased steadily and progressively over the last 30 years. Indeed, an actual "epidemic" is expected in the next 20 years, with over 1300 new cases a year till 2020 at least. Despite unquestionable improvement in the diagnostic methods at our disposal and the availability of new treatment strategies, the prognosis of MMe patients remains dramatically poor. For all the above reasons, translational research is the key to success; indeed, ever increasing knowledge of the molecular mechanisms underlying MMe pathogenesis could lead (and is actually leading) to new, hopefully more active, treatment options. To foster discussion among investigators working in this field, and to exchange different viewpoints concerning the newest advances in MMe pathogenesis and treatment, the VII International Mesothelioma Interest Group (IMIG) meeting was held in Brescia (Italy) between 24 and 26 June 2004 in cooperation with the Italian Group for the Study and Therapy of MMe (GIMe). The aim of this report is to summarize the most significant advances in the different disciplines applied to MMe presented and discussed during the IMIG meeting and how these advances will be changing the perspective of patients with MMe.

Angiogenesis Inhibitors↗

[Activity of beta-N-acetylglucosaminidase in chronic alcoholic liver disease].

Serum N-acetyl-B-glucosaminidase (NAG) activity was determined in a control group of 76 normal people and in 23 patients with hepatic cirrhosis: 15 non-compensated patients and 8 with compensated chronic liver fibrosis. NAG is significantly increased in the non-compensated group--mean value of 931.67 units vs 637.71 units for the controls (p less than 0.001). There is no significant elevation regarding the compensated group. No significant correlations were observed between NAG activity and hepatic functional tests. In the follow-up of the non-compensated group, NAG activity returned to normal with the clinical improvement; in 7 cases where this goal was not achieved there was elevation of NAG activity, with higher values in photo-systemic encephalopathy.

Acetylglucosaminidase↗

[Relation of thyroid hormones with the total and specific serum activity of N-acetyl-beta-D-glucosaminidase].

Total serum N-acetyl-beta-D-glucosaminidase (NAG), isoenzyme A (labile) and isoenzyme B (stable) activities were determined in euthyroid controls and in thyroid disease. In twenty hyperthyroid individuals total NAG (856.9 +/- 122,676 nmols/h/ml and isoenzyme A (490.3 +/- 93.592) as well as isoenzyme B (361.6 +/- 66,371), were higher than the levels in nineteen hypothyroid [total NAG = 533.105 +/- 97.927 (p less than 0.001); isoenzyme A = 280.263 +/- 61.463 (p less than 0.001); isoenzyme B = 251,580 +/- 50,530 (p less than 0.001)] or in twenty euthyroid [total NAG = 555.55 +/- 75.59 (p less than 0.001); isoenzyme A = 316.85 +/- 55.0 (p less than 0.001); isoenzyme B = 238.95 +/- 39.60 (p less than 0.001)]. Monthly assays were performed in seven hypothyroid and eleven hyperthyroid over the course of their corrective treatment with L-thyroxine (LT4: 0.1-0.2 mg (day) and propylthiouracil (PTU: 0.3-0.4/day), respectively. Total T4 was taken as the criterion for thyroid status. The reduction of hormone activity in seven hyperthyroid was accompanied by a significant decrease in enzyme activity (NAG = p less than 0.02; isoenzyme A = p less than 0.02). Isoenzyme B displayed no significant variation. In four hyperthyroid submitted to treatment with PTU there was no reduction in NAG activity and although T4 came down to normal levels. These patients still displayed symptoms of hyperthyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗