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Biomedical subjects

S Basso

Publications and source records attributed to S Basso.

At least 19 recordsLinked to original sources

Combined endoscopic and laparoscopic removal of ingested large foreign bodies. Case report and decisional algorithm.

Foreign body ingestion is a rare occurrence, but quite more frequent in children; adults with mental disorders, bulimia, and dentition alterations; and prison inmates. Most foreign bodies pass spontaneously through the first digestive tract and can move along the entire alimentary canal without giving rise to any major damage. On the contrary, when foreign bodies, because of their shape, size or potential for danger, must be removed, endoscopy is the method of choice. In a small percentage of cases, however, it may be necessary to remove the foreign body surgically. In such cases, the laparoscopic technique certainly can prove to be a most valuable tool, and can be recommended as a first approach. We describe a case in which a large foreign body was accidentally ingested. After a brief analysis of the data in the literature, we propose the decision-making algorithm that we follow.

Adult↗

Human alloantigen-specific anergic cells induced by a combination of CTLA4-Ig and CsA maintain anti-leukemia and anti-viral cytotoxic responses.

The success of allogeneic hematopoietic stem cell transplantation from HLA-disparate donors depends on the development of new strategies for graft-versus-host disease prevention able to target specifically donor antihost alloreactivity, while preserving GVL and antiviral immune surveillance. Recent experimental and clinical work has shown the feasibility of an approach based on induction of anergy to host alloantigens through blockade of B7/CD28 costimulatory signal in donor T cells, but data on the impact of this strategy on the recovery of the immune system are still lacking. We devised an ex vivo method for induction of host alloantigen-specific unresponsiveness based on treatment with the B7/CD28 blocking agent CTLA4-Ig associated with CsA. We then proceeded to assess the maintenance of an effective immune response towards viral pathogens and tumor cells after CTLA4-Ig/CsA treatment, by measuring the frequency of CTL precursors directed against CMV- and EBV-infected targets, and against autologous leukemic blasts. We demonstrated that (1) CTLA4-Ig and CsA can act synergistically in inducing a state of unresponsiveness to alloantigens; (2) the number of leukemia-reactive, EBV-specific and CMV-specific CTLp is not impaired by CTLA4-Ig/CsA treatment. Our data provide the first direct in vitro evidence that it is possible to preserve antiviral and antileukemia effector cells after blockade of CD28/B7 interaction during MLR.

Abatacept↗

Localization of parathyroid tumours in the minimally invasive era: which technique should be chosen? Population-based analysis of 253 patients undergoing parathyroidectomy and factors affecting parathyroid gland detection.

A series of 253 consecutive patients with proved primary hyperparathyroidism due to parathyroid tumours was reviewed. There were 68 (26.9%) men and 185 (73.1%) women, with a median age of 57 years (range 13-82 years). All patients, prior to successful parathyroidectomy, underwent one or more preoperative localization procedures such as: neck ultrasonography (US) in 191 (75.5%), (201)Tl/(99m)Tc-pertechnetate subtraction scintigraphy (TPS) in 144 (56.9%), CT scan in 92 (36.4%), (99m)Tc-sestamibi/(99m)Tc-pertechnetate subtraction scintigraphy (MPS) in 90 (35.6%), selective venous sampling (SVS) with parathyroid hormone (PTH) assay in 30 (11.9%), and magnetic resonance imaging (MRI) in 6 (2.4%) patients. The results were compared with operative and histological findings that showed 235 (92.9%) solitary parathyroid adenomas, 13 (5.1%) carcinomas and 5 (2.0%) double adenomas. Sensitivity and positive predictive value were 82.9% and 93.8% for US, 83.6% and 91.8% for TPS, 81.3% and 98.7% for CT scan, 85.1% and 96.1% for MPS, 65.4% and 80.9% for SVS, and 80.0% and 80.0% for MRI respectively. No different results (P=NS) were found using US, TPS, MPS or CT scan, whereas SVS and MRI sensitivity was lower (P<0.05). The combination of MPS and US was 94.0% sensitive (P<0.05) but when TPS, CT scan or MRI were also used overall sensitivity did not improve significantly (P=NS). In conclusion, MPS should be used as the starting preoperative localization procedure, while US and MPS together represent the most reliable noninvasive localization tool. If MPS and US are negative or not in agreement, further studies are not cost-effective and the patient should undergo bilateral neck exploration.

Adolescent↗

A retro-inverso peptide homologous to helix 1 of c-Myc is a potent and specific inhibitor of proliferation in different cellular systems.

In 1998 we reported that an L-peptide derived from H1 of c-Myc (Int-H1-S6A,F8A), linked to an internalization sequence from the third a-helix of Antennapedia, was endowed with an antiproliferative and proapoptotic activity toward a human mammary cancer cell line: The activity apparently depends upon the presence of the Myc motif. In the present work we have added new dimensions to our original findings. It is known that short retro-inverso (RI-) peptides can assume a 3D conformation very close to their corresponding L-forms and can be recognized by the same monoclonal antibody. We synthesized a RI-peptide form of our original L-peptide: It was much more resistant to serum peptidases than the original molecule (a half life of days rather than hours); in addition, the RI-form of the original Antennapedia internalization sequence was perfectly capable of carrying a D-peptide into human cells. We have studied three different potentially active peptides. L-peptides: Int-H1wt, Int-H1-S6A,F8A. D-peptides: RI-Int -H1-S6A,F8A. We have also studied three presumed control peptides: Int and RI-Int (no H1 motif), H1-S6A,F8A (no internalization sequence). Both 'active' and 'control' peptides have essentially confirmed our expectations, however, in cells treated with the higher concentration (10 mM) of the control peptide RI-Int, non-Myc related side effects could be detected. In order to investigate whether the antiproliferative activities displayed by some of our molecules were indeed related to an interference with the role of c-Myc (and molecules of the family), we chose an iso-amphipathic modified peptide of the H1 motif, with a proximity coefficient >50% and where the major change was at position 7 (F-->A). From a family of 73 H1 motifs belonging to (H1-Loop-H2) hu man sequences, the smallest evolutionary distance from our reference peptide was observed for the H1 of N-Myc, L-Myc, c-Myc, H1-S6A,F8A of c-Myc, and Max, in that order. Our reference peptide was therefore appropriate as a check of whether we were indeed observing activities related to Myc functions. Both Int-H1isoamph and the corresponding RI-Int-H1isoamph peptide were synthesized and studied. In terms of biological targets, we added to the human mammary cancer line of our previous work (MCF-7 cells) a colon cancer line (HCT-116 cells) and also a system of normal cells: human peripheral blood lymphocytes (PBLs) stimulated with phytohemoagglutinin (PHA). Peptides carrying an iso-amphipathic-modified H1 sequence were always very clearly (3-10 times) less active than the corresponding peptides carrying a conserved "H1 of Myc" motif. This finding was noted in five independent situations (all the cellular models considered at the present time): MCF-7 cells treated with L-peptides; MCF-7 cells treated with RI-peptides; HCT-116 cells treated with L-peptides; PBLs treated with L-peptides; PBLs treated with RI-peptides. Modulation of transcription levels of ornithine decarboxylase (ODC), p53, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), in PBLs treated with our different molecules, was well compatible with an interference by our active peptides at the level of Myc transcriptional activity. We had already reported a similar observation in MCF-7 cells. On a molar basis, RI-peptides were about 5-10 times more potent and 30-35 times more stable in complete culture medium, than their corresponding L-forms. RI-Int can probably internalize longer peptido-mimetic molecules (for instance molecules mimetic of (H1-Loop-H2), or even more. These possibilities open the way to rodent studies and to more potent/selective Myc inhibitors-two steps closer to a potential drug.

Amino Acid Motifs↗

The combined action of IL-15 and IL-12 gene transfer can induce tumor cell rejection without T and NK cell involvement.

The cooperative antitumor effects of IL-12 and IL-15 gene transfer were studied in the N592 MHC class I-negative small cell lung cancer cell line xenotransplanted in nude mice. N592 cells engineered to secrete IL-15 displayed a significantly reduced tumor growth kinetics, and a slightly reduced tumor take rate, while N592 engineered with IL-12 displayed only minor changes in their growth in nude mice. However, N592 cells producing both cytokines were completely rejected, and produced a potent local bystander effect, inducing rejection of coinjected wild-type tumor cells. N592/IL-12/IL-15 cells were completely and promptly rejected also in NK-depleted nude mice, while in granulocyte-depleted animals a slight delay in the rejection process was observed. Immunohistochemical analyses of the N592/IL-12/IL-15 tumor area in intact nude mice revealed the presence of infiltrating macrophages, granulocytes, and NK cells, and expression of inducible NO synthase and of secondary cytokines such as IL-1beta, TNF-alpha, and IFN-gamma, and at higher levels GM-CSF, macrophage-inflammatory protein-2, and monocyte chemoattractant protein-1. In NK cell-depleted nude mice, numerous macrophages and granulocytes infiltrated the tumor, and a strong expression of macrophage-inflammatory protein-2 and inducible NO synthase was also observed. Finally, macrophages cocultured with N592/IL-12/IL-15 produced NO in vitro, and inhibited tumor cell growth, further suggesting their role as effector cells in this model.

Adjuvants, Immunologic↗

Dissimilar anti-tumour reactions induced by tumour cells engineered with the interleukin-2 or interleukin-15 gene in nude mice.

Interleukin (IL)-15 shares immuno-stimulatory properties with IL-2 and is a potent inducer of natural killer (NK) cell function. The major histocompatibility complex (MHC) class I-negative human small cell lung cancer (SCLC) cell line N592, engineered to express a modified IL-15 cDNA (N592/IL-15), secreted biologically active IL-15 (300-500 pg/ml), capable of boosting T-cell proliferation and NK activity 'in vitro'. The effect of IL-15 gene transfer on natural immunity 'in vivo' was assessed by xenotransplants in nude mice and compared with that of the IL-2 gene. N592 cells engineered with IL-2 (N592/IL-2) were promptly rejected, while N592/IL-15 displayed a significant delay in tumour growth and a slightly reduced take rate. However, in NK-depleted nude mice, N592/IL-15 displayed the same growth kinetics as unmodified N592 cells, and N592/IL-2 grew with slightly reduced kinetics. An impressive reactive cell infiltration, consisting mainly of macrophages and granulocytes, was associated with N592/IL-2 tumour rejection, while a more evident recruitment of NK cells was found in N592/IL-15 tumours. In both N592 transfected tumours, we found expression of chemoattractant molecules, such as granulocyte macrophage-colony stimulating factor (GM-CSF) and monocyte chemoattractant protein (MCP)-1, while macrophage inflammatory protein (MIP)-2 was produced by endothelial cells only in N592/IL-2 tumours. In this tumour, very few and severely damaged microvessels were found, while microvessels were numerous in N592/IL-15 tumours. The potent recruitment of NK cells mediated by IL-15 gene transfer suggests its possible therapeutic use in tumours lacking MHC class I.

Animals↗

Correlates of osteoporosis in chronic obstructive pulmonary disease.

The aim of this study was to analyse the correlates of reduced bone mineral density in patients with chronic obstructive pulmonary disease (COPD), with special regard to a possible protective role of hypercapnia. One hundred and four consecutive COPD inpatients in stabilized respiratory conditions underwent a comprehensive assessment of their health status. Bone mineral density was measured by X-ray absorptiometry at the lumbar site and at the femoral neck site. Differences in health-related variables between patients with (group O, n=62) and without (group N, n=42) lumbar and/or femoral neck osteoporosis were assessed first by univariate analysis and then by logistic regression analysis aimed to identify independent correlates of osteoporosis. Group O was characterized by worse nutritional status, as reflected by indices exploring either lean or fat mass, and by a trend towards lower forced expiratory volume in 1 sec/forced vital capacity ratio. Arterial tension of carbon dioxide lacked any correlation with bone mineral density. According to the logistic regression analysis, body mass index < or = 22 kg m(-2) qualified as the only and positive independent correlate of osteoporosis (odds ratio=4.18; 95% confidence intervals=1.19-14.71). In conclusion, malnutrition characterizes COPD patients with osteoporosis, while mild to moderate hypercapnia lacks either a positive or negative effect on bone mineral density. Longitudinal studies are needed to identify predictors rather than correlates of bone mineral density.

Absorptiometry, Photon↗

Role of spirometric and arterial gas data in predicting pulmonary complications after abdominal surgery.

The aim of this study was to evaluate the predictive value of preoperative spirometric and arterial gas data on severe pulmonary complications (PC) after elective abdominal surgery. We retrospectively studied 480 patients, 254 males and 226 females, mean (SD) age 63 (11) years, at risk for PC according to standardized criteria, who underwent laparotomy for resection of gallbladder for gallstones (44% of patients), resection of colon, rectum or stomach for malignant tumours (37%), and other abdominal surgery (19%). The overall incidence of postoperative PC was 18%. In a logistic regression analysis adjusted for smoking habit and clinical history of chronic bronchitis, FEV1<61% of predicted [odds ratio (OR)=16.86, 95% confidence interval (95%CI)=5.62-50.58] and PaO2<9.33 kPa (OR=6.42, 95%CI=2.48-16.61) were the main determinants of PC. Ischaemic heart disease (OR=3.44, 95%CI=1.08-10.93), operation for malignant tumours (OR=3.24, 95%CI=1.75-6.00) and age (OR=1.04, 95%CI=1.00-1.08) were also independent predictors of PC. Patients with moderate-to-severe airway obstruction combined with hypoxaemia had a significant higher risk of PC in comparison with patients with a normal respiratory pattern. Taking into account age, type of operation, and comorbidity, a preoperative respiratory functional assessment could be useful in identifying an increased risk of major PC in selected patients.

Abdomen↗

Management of incidentally discovered adrenal masses and risk of malignancy.

BACKGROUND: Incidentally discovered adrenal masses of more than 1 cm in size are relatively frequent, but the correct management of such lesions is not well established. METHODS: Between 1980 and 1999, 158 patients (73 men [46.2%] and 85 women [53.8%]; median age, 58 years) with adrenal incidentalomas of more than 2 cm in size were observed. Sixty-eight patients (43.0%) underwent adrenalectomy. The main reasons for surgery were (1) suspicious computed tomography (CT) scan or magnetic resonance imaging (MRI) appearance or no uptake at the 75-Se-norcholesterol scintigraphy (NCS; n = 22 patients), (2) an increase in the size of the mass of more than l cm (n = 15 patients), (3) subclinical endocrine hyperfunction (n = 14 patients), and (4) mass size of more than 5 cm (n = 22 patients), with imaging-guided fine-needle aspiration biopsy with spinal-type narrow-gauge needle (FNAB) that suggested malignancy (n = 5 patients). RESULTS: Pathologic examination showed 39 adrenocortical adenomas (57.4%), 20 adrenal malignancies (29.4%; carcinomas, 15; unsuspected metastases, 3; nonfunctioning malignant pheochromocytomas, 2), and 9 various benign lesions (13.2%). All masses that increased in size were benign. Seven malignant tumors (46.7%) were 3 to 4 cm in size, and 14 benign lesions (29.1%) were 5 to 6 cm in size. Sensitivity and specificity in the detection of malignancy were 100% and 100% for NCS (n = 34 patients) and FNAB (n = 19 patients), 75.0% and 93.7% for CT scan (n = 68 patients), and 87.5% and 100% for MRI (n = 26 patients), respectively. CONCLUSIONS: To differentiate benign and malignant incidentalomas, NCS and FNAB are more sensitive than CT scan and MRI; size criteria are of little value.

Adolescent↗

Characteristics of nonsmoking women exposed to spouses who smoke: epidemiologic study on environment and health in women from four Italian areas.

The aim of this study was to evaluate whether risk factors associated with cardiovascular or respiratory diseases and lung cancer occur differently among nonsmoking women in Italy with and without exposure to environmental tobacco smoke (ETS) from husbands that smoke. We performed a cross-sectional study of 1,938 nonsmoking women in four areas of Italy. Data on respiratory and cardiovascular risk factors and on diet were collected using self-administered questionnaires. Medical examinations and blood tests were administered; urine cotinine levels were measured. Nonsmoking women ever exposed to husbands' smoking were compared with unexposed women for several factors: education, husband's education, household crowding, number of children, current or past occupation, exposure to toxic substances at work, parental diseases, self-perceived health status, physician-diagnosed hypertension, hypercholesterol, diabetes, osteoporosis, chronic respiratory diseases, blood pressure medications, lifestyle and preventive behaviors, dietary variables, systolic and diastolic blood pressure, body mass index, waist-hip ratio, triceps skin folds, plasma antioxidant (pro-) vitamins (- and ss-carotene, retinol, l-ascorbic acid, -tocopherol, lycopene), serum total and HDL cholesterol, and triglycerides. Women married to smokers were more likely to be less educated, to be married to a less educated husband, and to live in more crowded dwellings than women married to nonsmokers. Women married to smokers were significantly less likely to eat cooked [odds ratio (OR) = 0.72; 95% confidence interval (CI), 0.55-0.93] or fresh vegetables (OR = 0.63; CI, 0.49-0.82) more than once a day than women not exposed to ETS. Exposed women had significantly higher urinary cotinine than unexposed subjects (difference: 2.94 ng/mg creatinine). All the other variables were not more prevalent among exposed compared to unexposed subjects. The results regarding demographic factors are easily explained by the social class distribution of smoking in Italy. A lower intake of vegetables among exposed women in our study is consistent with the available literature. Overall, our results do not support previous claims of more frequent risk factors for cardiovascular and pulmonary diseases among ETS-exposed subjects. In Italy, as elsewhere in Europe and North America, women who have never smoked but are married to smokers are likely to be of lower social class than those married to never-smokers. However, once socioeconomic differences are considered, the possibility of confounding in studies on the health effects of ETS is minimal.

Adult↗

Current practice in assessment and treatment of bronchial asthma in young males in Italy.

The aim of the study was to evaluate, in a sample of young asthmatics in Italy, the current practice in assessment and treatment of asthma after the publication of guidelines. Young soldiers who declared bronchial asthma at the beginning of the compulsory military service were evaluated. One-hundred and thirty-eight subjects with confirmed asthma were selected. Sixty-seven subjects (48.5%) had had at last one spirometry, and only one subject had underwent peak flow monitoring at home; most of the subjects (96.8%) had had prick tests. More of the 50% of the subjects with bronchial obstruction or with severe bronchial hyperresponsiveness, with clinical moderate or severe asthma, had used only bronchodilators or no therapy at all in the preceding year. In this sample of young asthmatics, the lung function tests were still underutilized for the diagnosis and follow-up of bronchial asthma; moreover, the inhaled anti-inflammatory drugs were still underutilized.

Adult↗

Electrocardiographic signs of chronic cor pulmonale: A negative prognostic finding in chronic obstructive pulmonary disease.

BACKGROUND: Chronic cor pulmonale (CCP) is a strong predictor of death in chronic obstructive pulmonary disease (COPD). The aims of this study were to assess the prognostic role of individual ECG signs of CCP and of the interaction between these signs and abnormal arterial blood gases. METHODS AND RESULTS: Two hundred sixty-three patients (217 men) with COPD, mean age 67+/-9 years, were grouped according to whether they had no ECG signs (group 1, n=100) or >/=1 ECG signs (group 2, n=163) of CCP and were followed up for 13 years after an exacerbation of respiratory failure. The median survival was significantly shorter in group 2 than in group 1 (2.58 versus 3. 45 years, respectively; Mantel-Cox test, 9.58; P=0.002). The Cox regression analysis identified S1S2S3 pattern, right atrial overload (RAO), and alveolar-arterial oxygen gradient (PAO2-PaO2) >48 mm Hg during oxygen therapy as the strongest predictors of death, with hazard rate (HR)=1.81 (95% CI, 1.22 to 2.69), HR=1.58 (95% CI, 1.15 to 2.18), and HR=1.96 (95% CI, 1.19 to 3.25), respectively. The median survivals of patients having both S1S2S3 pattern and RAO (n=14) and of patients having either S1S2S3 pattern or RAO (n=77) were 1.33 and 2.70 years, respectively (P=0.022). Group 2 patients had a 3-year survival of 18% or 53%, depending on whether their PAO2-PaO2 during oxygen therapy was or was not >48 mm Hg. CONCLUSIONS: Some ECG signs of CCP and PAO2-PaO2 >48 mm Hg during oxygen therapy qualified as a simple and inexpensive tool for targeting subsets of COPD patients with severe or very severe short-term prognosis.

Aged↗

Interleukin (IL)-15 induces survival and proliferation of the growth factor-dependent acute myeloid leukemia M-07e through the IL-2 receptor beta/gamma.

We have analyzed the effects of IL-15, a growth factor with IL-2-like properties produced by dendritic and stromal cells, on 3 GM-CSF/IL-3-dependent AML cell lines: M-07e, UT-7 and TF-1. M-07e cells proliferated in response to IL-15, while UT-7 and TF-1 cells failed to respond. In addition, IL-15 supported long-term proliferation of M-07e cells, thus allowing selection of a subline (M-07SB), which displayed an enhanced sensitivity to IL-15. M-07e and M-07SB cells undergo apoptosis following 48-hr growth factor (GM-CSF or IL-15) starvation, as detected by cytofluorimetric analysis and DNA laddering. IL-15 (20 ng/ml) prevented apoptosis in both cell lines. M-07e and M-07SB expressed IL-2R beta, IL-2R gamma, Jak-1 and Jak-3 mRNA, while IL-15R alpha mRNA was undetectable. In contrast, IL-15R alpha was expressed in UT-7 and TF-1 cells, which lacked expression of IL-2R beta mRNA and, in the case of UT-7, also of Jak-3 mRNA. Accordingly, surface IL-2R beta protein was identified only in M-07e and M-07SB cells, by indirect immunofluorescence, while no expression of IL-2R alpha and IL-15R alpha was detected. Anti-IL-2R beta antibodies (10 microg/ml) efficiently blocked (90% inhibition) the proliferation and the anti-apoptotic effect induced by IL-15, while anti-GM-CSFR alpha antibodies had no effect. Anti-IL-2R gamma antibodies were less efficient at proliferation inhibition but synergized with suboptimal concentrations of anti-IL-2R beta antibodies. Our data suggest a role of IL-15 as an anti-apoptotic and mitogenic growth factor for a subset of myeloid leukemias expressing a functional IL-2R beta/gamma complex.

Acute Disease↗

Expression of two interleukin-15 mRNA isoforms in human tumors does not correlate with secretion: role of different signal peptides.

Interleukin (IL)-15 is a four-helix bundle cytokine sharing several biological properties with IL-2. By reverse transcriptase-polymerase chain reaction analysis, human cancer cell lines of different histotypes are shown to express two IL-15 amplification products: a 524-bp band corresponding to the IL-15 mRNA found in macrophages, and another of 643 bp corresponding to an alternatively spliced mRNA including a 119-bp alternative exon. IL-15 was undetectable in the supernatant of tumor cell lines expressing either one or both of the mRNA isoforms as evaluated by a bioassay or by ELISA, indicating that IL-15 is not secreted. However, IL-15 could be detected intracellularly in some tumor cells by confocal microscopy analysis. Since the pre-proteins encoded by the two mRNA isoforms differ in the signal peptide sequence, we have analyzed the characteristics of these signal peptides and their possible role in controlling secretion. The two IL-15 cDNA isoforms, expressed in COS-7 cells, induced very low levels of IL-15 secretion. However, substitution of the sequence encoding natural signal peptide(s) with the one from IgV kappa chain in the IL-15 cDNA results in a significantly higher secretion of biologically active IL-15 (15-30-fold) upon cDNA transfection. A poor efficiency of natural signal peptides may represent one of the mechanisms involved in the control of IL-15 secretion.

Amino Acid Sequence↗

IFN-gamma gene transfer restores HLA-class I expression and MAGE-3 antigen presentation to CTL in HLA-deficient small cell lung cancer.

In this study, we have analyzed the possibility of inducing T cell responses against small cell lung cancer (SCLC), a still incurable tumor, by cytokine gene transfer approaches. By RT-PCR analysis most SCLC expressed the CTL-defined tumor antigens MAGE-3 (10/11), MAGE-1 (7/11) and less frequently BAGE (4/11) and GAGE1,2 (4/11). Although the surface expression of HLA class I molecules was low on most SCLC, thus preventing CTL recognition, treatment of the cells with IFN-gamma enhanced HLA-class I levels in all cases. Two MAGE3+ SCLC cell lines displaying the A2 HLA-class I allele, involved in MAGE-3 antigen presentation to CTL, were stably transfected with the IFN-gamma gene (alone or co-transfected with IL-2). IFN-gamma-transfected cells displayed a clearcut increase in expression of HLA-class I and beta 2-microglobulin at both protein and mRNA level, and of TAP-1 and TAP-2 mRNA. Perhaps more importantly, IFN-gamma transfected cells were recognized by the MAGE-3-specific A2-restricted antimelanoma CTL clone 297/22, while unmodified cells or cells transfected with the IL-2 gene alone were not. These data indicate that IFN-gamma gene transfection into HLA-deficient SCLC cells is able to restore their ability to present endogenous tumor antigens to CTL and that IFN-gamma gene transfer approaches may be attempted to induce specific CTL responses in SCLC.

Antigen Presentation↗

Postural variations of pulmonary diffusing capacity in insulin-dependent diabetes mellitus.

STUDY OBJECTIVE: To assess whether posture-related changes of diffusing capacity could be considered as an early sensitive marker of pulmonary abnormalities in patients with insulin-dependent diabetes mellitus (IDDM) and whether the postural variations of pulmonary capillary blood volume (Vc) could reflect the lung capillary damage that characterizes the diabetic microangiopathy. DESIGN: Carbon monoxide diffusing capacity (DCO) was measured by the single-breath method. Four DCO measurements, two in sitting and two in supine position, were performed in each subject using gas mixtures containing different oxygen concentrations. Membrane and capillary volume components of the diffusion capacity were calculated and both were expressed as absolute value and corrected by alveolar volume (VA). PATIENTS: Twenty IDDM patients and 20 normal subjects matched for age and sex were studied. MEASUREMENTS AND RESULTS: The IDDM patients showed normal pulmonary volumes and flows. No significant differences between the two groups were found for DCO, coefficient of diffusion, Vc, and pulmonary capillary blood volume corrected by alveolar volume in sitting position. All these indexes significantly increased in normal subjects but not in diabetics, by changing the posture of the subject from sitting to supine position. In a multivariate analysis, the presence of diabetes mellitus and the age of the subjects were the only significant predictors of Vc postural changes. CONCLUSIONS: This postural test, adjusted for age, could be included in a screening diagnostic procedure for an early assessment of pulmonary abnormalities in diabetic patients. The lack of Vc postural increase in diabetics could reflect the presence of a microangiopathy involving the pulmonary small vessels.

Adult↗