PubMed Health⌕ Search

Biomedical subjects

M Caputi

Publications and source records attributed to M Caputi.

At least 37 records · Page 2Linked to original sources
PubMed1997

Prognostic role of the cyclin-dependent kinase inhibitor p27 in non-small cell lung cancer.

Despite its potential role as a tumor suppressor, p27 gene, a member of the Cip/Kip family of cyclin-dependent kinase inhibitor genes, has never been found mutated in human tumors. We investigated p27 protein expression in a series of 108 non-small cell lung cancers (57.4% stage 1, 16.7% stage 2, and 25.9% stage 3) to determine whether the lack or altered expression of this protein correlates with neoplastic transformation and/or progression. We performed immunohistochemistry and Western blot analysis of each specimen. We found that tumors expressing low to undetectable levels of p27 contained high p27 degradation activity. When we evaluated the outcome of the patients in relationship to p27 expression, we found p27 to be a prognostic factor correlating with the overall survival times (P = 0.0012). The possibility of a simple assay, such as the immunohistochemical analysis of p27 expression on routinely formalin-fixed, paraffin-embedded specimens, has considerable value for the prognosis of patients who undergo surgical resection. In addition, confirmation of the involvement of the proteasome-mediated proteolysis in p27 degradation should stimulate new strategies of nonsurgical treatments of non-small cell lung cancer.

Adenocarcinoma↗
PubMed1997

CDC2-related kinase PITALRE phosphorylates pRb exclusively on serine and is widely expressed in human tissues.

Mammalian cell cycle progression is regulated by sequential activation and inactivation of cyclin-dependent kinases (cdks). Recently, several new members of the cdk family were cloned, and some of these were shown to complex with different cyclins and to be active at discrete stages of the cell cycle. PITALRE, a new member of this family, was cloned by our laboratory and was shown to be able to phosphorylate pRb protein in vitro. In the current work, we found that PITALRE kinase activity phosphorylated pRb at sites similar to those phosphorylated by the CDC2 kinase, which itself is known to mimic, in vitro, the in vivo phosphorylation of pRb. Phosphorylation of pRb by the PITALRE-associated kinase activity was on Ser residues exclusively. Moreover, we investigated the expression pattern of PITALRE in normal human tissues, using immunohistochemical techniques so as to gain additional data on the characteristics of this new cdk family member. The protein was widely expressed, although a different tissue distribution and/or level of expression was found in various organs. Some specialized tissues such as blood, lymphoid tissue, ovarian cells, and the endocrine portion of the pancreas showed a high expression level of PITALRE. The specific expression pattern found suggests that PITALRE may be involved in specialized functions in certain cell types.

Antibodies↗
PubMed1997

Prognostic value of p53 in non-small cell lung cancer: relationship with proliferating cell nuclear antigen and cigarette smoking.

p53 mutations are among the most frequent genetic alterations reported in human lung cancer. Although the prognostic value of altered p53 expression is still debated, it is accepted widely that estimation of the proliferation rate has an important prognostic role. Moreover, an association between certain types of human lung cancers and tobacco use is well known. Drawing from this background, we investigated the immunohistochemical expression of mutant oncogenic p53 protein, and related it to the smoking history of 61 patients with non-small cell lung carcinoma (NSCLC) and to the expression pattern of proliferating cell nuclear antigen (PCNA), which is considered to be an important negative prognostic factor in several neoplasms. We found p53 overexpression in 22 (36.1%) specimens, including 16 squamous carcinomas (41%) and six (27.2%) adenocarcinomas. PCNA nuclear staining was detected in 98.4% of the specimens, and a significantly higher PCNA expression score was found in all of the p53-positive samples. When the patient survival time was compared, p53 accumulation had a statistically significant negative prognostic value (P < .001). This was supported by a Kaplan-Meier survival percentage plot of immunohistochemically p53-undetectable specimens and p53-detectable specimens. These latter patients had a greatly reduced survival time. A relationship was established between p53 immunohistochemical detection and the smoking history of the patients. None of the specimens from the nonsmoking patients expressed immunohistochemically detectable p53 protein. Altered p53 expression was detected in 40.7% of smoking patients. Our findings support the hypothesis of involvement of p53 mutations in tobacco-induced carcinogensis and indicate that altered p53 expression plays an important prognostic role in NSCLC in smokers.

Biomarkers, Tumor↗
PubMed1997

Effect of blood gas derangement on QTc dispersion in severe chronic obstructive pulmonary disease: evidence of an electropathy?

Cardiac arrhythmias are common in patients with respiratory failure from chronic obstructive pulmonary disease (COPD). Several factors may be potentially arrhythmogenic in these patients, including hypoxemia and hypercapnia, acid-base disturbances, cor pulmonale and the use of digitalis, methylxanthines, and sympathomimetic drugs. The aim of this study was to examine the effect of hypoxemia and hypercapnia on QTc dispersion (QTcD) in COPD patients, and to evaluate the effect of a partial correction of one of these pro-arrhythmic factors, the hypoxemia, on Qtc dispersion, as QTcD has been proposed as a marker of heterogeneous repolarization and, hence of ventricular electrical instability. We showed that in 15 hypoxemic/hypercapnic COPD patients, compared to 20 controls, the QTcD was significantly higher (49.7 +/- 10.6 vs. 22.9 +/- 9.8 ms; P = 0.0001); furthermore, after only 24 h of oxygen therapy, and hence after a partial correction of hypoxemia, there was a significant reduction in QTcD in COPD patients (49.7 +/- 10.6 vs. 36.3 +/- 10.1 ms; P = 0.018). The data of the present study suggest that the increase in QTcD may be an early marker of a blood gas mediated electropathy in COPD patients.

Adult↗
PubMed1997

The retinoblastoma gene family pRb/p105, p107, pRb2/p130 and simian virus-40 large T-antigen in human mesotheliomas.

The oncoprotein of simian virus-40, SV40 large T-antigen (Tag), is reported to target and to inactivate growth suppressive proteins such as the retinoblastoma family and p53 (ref. 4, 5), leading to transformation of human cell lines in vitro, tumor production in rodents, and detection of Tag in several human cancers including mesotheliomas. The retinoblastoma family contains three members, pRb, p107 and pRb2/p130 (ref. 9), that are phosphorylated in a cell cycle-dependent manner, have cell growth suppressive properties and bind to specific members of the E2F family and various cyclins. Even though mesotheliomas are among the most aggressive human cancers, alterations of important cell-cycle "controllers," such as the Rb family genes, have never been reported in these tumors. We found the presence of SV40-like sequences in 86% of 35 archival specimens of mesothelioma. We also demonstrated that SV40 Tag, isolated from frozen biopsies of human mesothelioma, binds each of the retinoblastoma family proteins, pRb, p107 and pRb2/p130, in four of four specimens. We propose that the tumorigenic potential of SV40 Tag in some human mesotheliomas may arise from its ability to interact with and thereby inactivate several tumor and/or growth suppressive proteins.

Adult↗
PubMed1997

A five-day course of dirithromycin in the treatment of acute exacerbation of severe chronic obstructive pulmonary disease.

Since dirithromycin persists at high concentrations in the lung for at least 3 days following the last dose of a 5-day course, we evaluated the clinical efficacy and tolerance of a 5-day course of dirithromycin in 20 patients with acute exacerbation of severe chronic obstructive pulmonary disease, treated with a total dose of 2.5 g dirithromycin (500 mg once-daily for 5 days) in an open, non-comparative study. Patients were assessed before therapy and after 5 (last administration), 10 (post-therapy) and 20 (late post-therapy) days. Pathogen elimination or presumed elimination was seen in 18/20 patients at the post-therapy visit and at the late post-therapy visit, but two Haemophilus influenzae out 5 were isolated in sputum after 10 days and only one after 20 days (Pseudomonas aeruginosa was the other pathogen). Dirithromycin was well-tolerated and only 2 patients reported mild gastrointestinal pain. This study shows that a 5-day dirithromycin therapy provides a convenient and efficient dosage regimen in acute exacerbation of chronic bronchitis. Notwithstanding its poor in vitro activity against H. influenzae, dirithromycin was fairly active against this microorganism in vivo.

Acute Disease↗
PubMed1997

Prognostic role of cyclin D1 in non small cell lung cancer: an immunohistochemical analysis.

Lung cancer is a worldwide problem and in many countires it is the most lethal malignancy. Because relapse is frequent after resection of non small cell lung cancer, an urgent need exists to define prognostic factors which could help in choosing the best therapeutic approach. We performed immunohistochemistry on 60 formalin-fixed paraffin-embedded non small cell lung cancer specimens in order to evaluate the frequency of cyclin D1 overexpression, and to relate it to the degree of malignancy of these tumors and to the overall survival time of the patients. All specimens were positive for cyclin D1 immunostaining. We found cyclin D1 overexpression in 30 (50%) of our specimens, with no significant difference among the different histological types. Cyclin D1 overexpression correlates in a statistical manner with short-term patient survival. Mantel-Cox analysis of these data generated a significant P value = 0.003. The mean survival time and the five-year survival rate also differed statistically. We did not find any statistically significant correlation between cyclin D1 overexpression and histological grading, tumor stage or TNM status. We concluded that cyclin D1 overexpression in 30 patients is a frequent event in non small cell lung cancer pathogenesis and may have prognostic relevance.

Biomarkers, Tumor↗
PubMed1997

Differential expression of Rb2/p130 and p107 in normal human tissues and in primary lung cancer.

Two proteins, p107 and pRb2/p130, which are structurally and functionally similar to the product of the retinoblastoma gene (pRb), were cloned by taking advantage of their ability to bind transforming proteins of DNA tumor viruses through a particular region called the "pocket domain." Like pRb, both proteins play a fundamental role in growth control. Using immunocytochemical techniques, we examined a variety of normal human tissues for the expression of pRb2/p130 and p107. Both proteins were expressed ubiquitously, although a different tissue distribution and/or level of expression were found in various organs. Terminally differentiated cells, such as neurons and skeletal muscle, showed high expression levels for Rb2/p130, whereas p107 was expressed at higher levels in other cell types such as epithelia of the breast and prostate. We then examined the expression pattern of Rb2/p130 in 158 specimens of human lung cancer and found an inverse correlation between the histological grading of the tumors, the development of metastasis, and the level of expression of Rb2/p130.

Blood Cells↗
PubMed1996

Differential expression of the retinoblastoma gene family members pRb/p105, p107, and pRb2/p130 in lung cancer.

The Rb (retinoblastoma) gene family is composed of three members: the RB gene (one of the best-studied tumor suppressor genes) and two related genes, p107 and pRb2/p130. These three proteins share many structural and functional features and play a fundamental role in growth control. Using immunocytochemical techniques, we evaluated a variety of lung tumor specimens for the expression of this family of proteins and compared protein expression with the histological grading of the tumors and with the expression of the proliferating cell nuclear antigen. These Rb family members displayed distinctive patterns when compared and contrasted using different parameters. The highest percentage of undetectable levels in all of the specimens examined and the tightest inverse correlation (P) with the histological grading and with proliferating cell nuclear antigen expression in the most aggressive tumor types were found for pRb2/p130, which may suggest an important role for this protein in the pathogenesis and progression of lung cancer.

Animals↗
PubMed1995

Analysis of the linkage between fibronectin alternative spliced sites during ageing in rat tissues.

The modulation of fibronectin (FN) functions in cell-cell and cell-substrate interactions in a variety of physiological situations is achieved by the selective expression of different isoforms, which in the rat are generated by alternatively splicing of at least three regions of the molecule: EIIIA, EIIIB and V. Extensive information has been collected on the regulation of the differential processing of the single alternatively spliced regions but up to now there was scant knowledge about a possible coordinated expression of the three regions in the same transcript. Using a long range RT-PCR system we have shown that most of the splicing regulation is autonomous for each individual region but we have also observed a preferential expression of the EIIIA+ form linked to the EIIIB- variant that is age independent. Furthermore the analysis of the single regions showed interesting variations occurring in brain during the ageing. There is a decrease in the V120 form between the 6- and the 24-month-old rat brain (from 57% to 39%), whereas despite a constant prevalence of the EIIIA- form in the young rats (65%) there is a random individual variation of this form in the old animals. Noteworthy no variations have been detected in the EIIIB region (90% EIIIB-). These data suggest a role for the V and EIIIA regions, but not for the EIIIB, during the ageing process at least in brain, since no variations were detected in kidney between the 6- and 24-month-old animals.

Aging↗
PubMed1995

Regulation of fibronectin expression in rat regenerating liver.

Fibronectin (FN) expression displays a complex regulation that results in precisely defined isoform patterns during different developmental stages, ageing and injury. The qualitative and quantitative changes that are observed derive from modulation of the rate of transcription of the single FN pre-mRNA and its specific differential processing in the EIIIA, EIIIB and V regions of rat FN. The liver is the major source of plasma FN which is characterised by the absence of the EIIIA and EIIIB exons. Here we show that in the rat regenerating liver there is a significant reprogramming of the splicing machinery that results in the synthesis by the liver of up to 17% of EIIIA+ FN linked with all the three V forms. On the other hand the EIIIB+ form is totally absent both in normal and regenerating liver. Furthermore there is a variation of the V pattern observed in the regenerating tissue, the V120 form (linked to both EIIIA+ and EIIIA- messengers) increases from 11 to 32%. The quantitative RT-PCR method was used to estimate the FN transcription rate, before and after partial hepatectomy. We have shown a 3-fold increase in FN mRNA in liver that is specifically linked to the regeneration process and not to the surgical stress.

Animals↗
PubMed1995

A comparison of the bronchodilating effects of salmeterol, salbutamol and ipratropium bromide in patients with chronic obstructive pulmonary disease.

Bronchodilator efficacy of salbutamol (200 micrograms), salmeterol (50 micrograms) and ipratropium bromide (40 micrograms) aerosols has been compared in 16 patients with stable chronic obstructive pulmonary disease (COPD) using a double-blind placebo controlled cross-over design. When absolute changes in FEV1 were used as the response criterion, efficacy of the three drugs was significantly better than placebo (P < 0.05). The onset of bronchodilatation after ipratropium bromide was slower than after salbutamol, but ipratropium induced more and longer-lasting bronchodilatation than the adrenergic drug. Salmeterol was slower but its duration was longer than salbutamol. The onset of the effect of salmeterol was slower than ipratropium bromide, but salmeterol showed, on average, superior bronchodilator efficacy compared with the anticholinergic agent, sustaining bronchodilation longer than ipratropium bromide (responses to salmeterol were significantly (P < 0.05) greater than those to ipratropium bromide from 4-12 h time period, but from 15 min to 1 h time periods response to ipratropium bromide exceeded salmeterol). The mean FEV1 area under the curve was significantly (P < 0.05) larger after salmeterol when compared to ipratropium bromide and salbutamol. Moreover, the mean FEV1 area under the curve after ipratropium bromide was significantly (P < 0.05) higher than that after salbutamol. In any case, our data showed individual differences in patient response. We conclude that salmeterol compares favourably with ipratropium bromide in terms of effects on lung function at clinically recommended doses because it has a longer duration of action than ipratropium bromide. The longer dosing intervals, which may enhance compliance, encourage its administration in patients with COPD.

Administration, Inhalation↗
PubMed1995

[Assessment of dispersion++ of ventricular recovery in patients with chronic obstructive pulmonary disease].

Cardiac arrhythmias are common in patients with chronic obstructive pulmonary disease. Several factors may contribute to the development of arrhythmias in these patients including hypoxemia, hypercapnia, acid-base disturbances. The aim of the study was to assess QTc dispersion in patients with chronic obstructive pulmonary disease, who are at high risk of arrhythmias. Interlead QT variability as measured on the 12-lead electrocardiogram is not a technical artifact but probably reflects regional differences in ventricular repolarization. Increased dispersion of ventricular recovery time is believed to provide a substrate which supports serious ventricular arrhythmias. We showed that in patients with chronic obstructive pulmonary disease, free of underlying structural heart disease, the QTc dispersion is significant greater (p = 0.036) than in a control group, despite a similar value in mean QTc value. The data of the present study suggest that the determination of dispersion of repolarization times may be affected by metabolic changes occurring in patients with chronic obstructive pulmonary disease.

Adult↗
PubMed1994

A novel bipartite splicing enhancer modulates the differential processing of the human fibronectin EDA exon.

EDA is a facultative type III homology of human fibronectin encoded by an alternative spliced exon. The EDA+ and EDA- mRNA forms show a cell type specific distribution with their relative proportion varying during development, aging and oncogenic transformation. We have previously demonstrated that an 81 bp nucleotide sequence within the exon itself is essential for differential RNA processing. Fine mapping of cis acting elements within this region has been carried out to identify possible target sites for the modulation of alternative splicing. There are at least two short nucleotide sequences involved. Element A (GAAGAAGA) is a positive modulator for the recognition of the exon, its deletion results in constitutive exclusion of the EDA exon. Element B (CAAGG) is a negative modulator for exon recognition, its deletion results in constitutive inclusion of the EDA exon. This bipartite structure of the splicing enhancer is a novel feature of the mammalian exons.

Alternative Splicing↗
PubMed1991

Influence of sulbactam plus ampicillin on theophylline clearance.

The effect of sulbactam/ampicillin (500 mg/1000 mg) every 12 hours taken for seven days on the steady-state pharmacokinetics of theophylline was studied among 12 patients suffering from chronic obstructive pulmonary disease. Theophylline concentrations were measured serially for 12 h by the method of polarized immunofluorescence (Abbott TDx system). No influence of sulbactam/ampicillin was detectable on the theophylline half-life, clearance or volume of distribution. It was concluded that both drugs could be administered concomitantly without any dosage adjustment of theophylline.

Adult↗
PubMed1991

An in vitro study of the possible interaction between human platelets and cephalosporins.

The effects in vitro of four cephalosporins (ceftazidime, cefuroxime, cefotaxime and ceftriaxone) on adenosine diphosphate-induced human platelet aggregation were investigated. Ceftazidime-induced inhibition of platelet aggregation was significant only at a final concentration of 1 mg/ml, whereas ceftriaxone-induced inhibition of platelet aggregation was also significant at a final concentration of 0.01 mg/ml. Cefotaxime and cefuroxime were less active than ceftriaxone.

Adenosine Diphosphate↗
PubMed1986

Treatment of lower respiratory tract infections with ceftriaxone and cefotaxime. A comparative study.

The microbiological and clinico-therapeutic efficacy and safety of ceftriaxone were compared with those of cefotaxime in an open randomized trial. Fifty-four adult hospitalized patients (37 males and 17 females) suffering from either acute bronchopneumonia (19) or acute exacerbations of chronic bronchopneumonia (35) have been investigated. Four patients were withdrawn from the trial. Underlying diseases were present in 41 patients. Ceftriaxone was administered at a once-a-day dose of either 1 or 2 g (in 13 and 14 patients, respectively) and cefotaxime at a 2 g twice daily dosing regimen (27 patients), both antibiotics being given for 7-12 days. In the ceftriaxone group, 15 out of the 27 patients were cured (55%) and 9 had a favourable clinical response for a total satisfactory response rate of 88%. The causative pathogen was eliminated in 18 (66%) patients. The results obtained in the cefotaxime group did not differ significantly, but 2 patients were excluded from the study because of in vitro resistance of the causative pathogen isolated. Both drugs were well tolerated: no relevant laboratory changes were registered. The results indicate that ceftriaxone at a dosage of 2 or 1 g daily is at least as effective as cefotaxime given daily at a dosage of 4 g in the treatment of severe lower respiratory tract infections.

Adolescent↗