Biomedical subjects
Publications and source records attributed to F Baldi.
We describe a case of relapsing pneumothorax occurring in a male child aged 11 yrs, resulting from the mechanical inflammatory action of Ascaris lumbricoides larvae localized in the pleuropulmonary tissue. Pulmonary ascariasis should still be considered today in the differential diagnosis of spontaneous pneumothorax occurring in children.
The basaloid squamous carcinoma was first described in 1986. It is a rare tumor with particular morphologic and biologic features that separate it from the more common squamous cell carcinoma of the head and neck region. A case with histologic diagnosis of basaloid squamous carcinoma of the tongue treated only with radiotherapy, is reported.
We report a case of congenital malaria in a newborn whose mother is a native of Zaire now living in Italy. The baby developed remittent fever in the 3rd week of life with anaemia and hepatosplenomegaly. Malaria parasites found in blood smears and erroneously diagnosed initially as Plasmodium falciparum were subsequently recognized as Plasmodium vivax. On the basis of the first diagnosis, treatment with quinine chlorhydrate was successfully undertaken without significant side-effects. P. vivax parasites were also recovered a posteriori in blood smears of the mother who was febrile during the week of her delivery. This report suggests that symptomatic congenital malaria may be more common than is generally thought and should be suspected in non-malarious countries in febrile newborns born to mothers who have travelled in or immigrated from malaria-endemic areas.
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In order to clarify critical events during bronchial carcinogenesis, and to evaluate a possible prognostic role for p21 immunohistochemical detection, we assessed the immunohistochemical expression of p21 protein in 60 surgically resected non-small-cell lung cancers (NSCLCs) that had been investigated previously for their p53 protein status. We found that p21 protein was expressed in both normal and neoplastic tissue. In normal tissue, p21 immunoreactivity was detectable in a low percentage of well-differentiated cells. We found immunostaining for p21 in 80% of the investigated neoplasms. In 73.3% of the neoplasms, p21 was considered to be overexpressed. No relationship was found between p21 overexpression and tumor stage or tumor-nodal-metastatic (TNM) status. The histologic grading was slightly correlated with the p21 status (P = -0.51), with no significant differences noted between squamous carcinomas and adenocarcinomas. Survival percentage curves for our lung-cancer patients, based on a comparison of different p21 expression levels and constructed through a Kaplan-Meier analysis, showed significant differences in mean (P < 0.001) and overall (P < 0.001) survival time between patients of different p21 status, suggesting a favorable prognostic value of p21 immunostaining for NSCLC patients.
PURPOSE: The retinoblastoma gene is the prototype of tumor-suppressor genes and has been shown to be involved in the pathogenesis and progression of several human malignancies. In this study, we determined the relation between the expression of a newly discovered retinoblastoma-related gene Rb2/p130 and outcome in patients with endometrial carcinoma. PATIENTS AND METHODS: pRb2/p130 expression was determined immunohistochemically in specimens of endometrial carcinoma (stages I to IV) from 100 patients who underwent surgery as the first treatment. The pRb2/p130 status was analyzed in relation to the length of disease-free survival and disease-specific survival. RESULTS: Decreased levels of pRb2/p130 in endometrial cancer cells was significantly associated with a decreased probability of remaining disease-free after treatment (P = .003) and with decreased probability of survival (P < .0001). In a multivariate analysis, pRb2/p130 status (P = .004), tumor stage (P = .009), and ploidy status (P = .02) were independent predictors of clinical outcome. The risk of dying of disease was increased substantially (risk ratio, 4.91; 95% confidence interval, 1.66 to 14.54) among patients with decreased levels of pRb2/p130 in tumor cells. CONCLUSION: In patients with endometrial carcinoma who did not receive radiotherapy or chemotherapy before surgery, the presence of decreased levels of pRb2/p130 in tumor cells is associated with a significantly increased risk of recurrence and death of disease, independent of tumor stage and ploidy status.
To evaluate the prognostic value of DNA content-ploidy, agoraphilic nucleolar organizing regions (AgNORs) and proliferating cell nuclear antigen (PCNA) for survival among patients with choroidal melanoma choroidal melanomas managed by enucleation in 55 patients with a follow-up of 5 years were studied. AgNor counts were evaluated by two examiners after sections were specifically processed. Immunohistochemistry was performed to evaluate PCNA expression. Kaplan-Meier estimation of survival curves, the log-rank test, and Cox regression analysis were used to compare survival according to the above mentioned factors. Five years after enucleation 62% of patients had died. Patients with spindle cell type melanomas had the best and those with epithelioid cell type had the worst survival (p=0.004). Patients with small tumors had better survival than those with medium or large tumors (p=0.02). Patients having tumors with aneuploid nuclear DNA content had worse survival than those having tumors with diploid DNA content (p=0.004). A high PCNA level correlated with lower survival rates (p=0.02). Patients having a high AgNor count had a worse survival than those with lower counts (p=0.02). DNA content, PCNA level, and AgNOR count each showed a clinically significant influence on patient survival. However, each of these new evaluated prognostic factors was strongly related to one or both of the classic prognostic factors. It is therefore difficult to separate the effects of the two categories of prognostic factors. Results of the Cox regression analysis suggested that these newer evaluated prognostic factors provided little additional information about patient prognosis.
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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.
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.
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.
Three strains of Saccharomyces cerevisiae, SC-1, DBVPG 6173 and DBVPG 6037, were studied for vanadate resistance in complex Sabouraud medium since they did not thrive in different minimal media (yeast nitrogen base with and without amino acids). The strain SC-1 was resistant up to 16 mM of vanadate, whereas the strains DBVPG 6173 and DBVPG 6037 were inhibited by 8 mM and 4 mM vanadate, respectively. The vanadate resistance in strain SC-1 was constitutive and due to the reduction of this oxyanion to vanadyl, which was detected by EPR spectroscopy and visible spectroscopy. The transformation of vanadate to vanadyl took place during the exponential growth phase; 10 mM of vanadate was reduced to vanadyl outside the cells since the oxyanion was not detected in the cell biomass and only a negligible concentration of vanadyl (25 nmoles mg-1 cells dry weight) was found in the biomass. The other two vanadate-sensitive yeast strains only accumulated vanadate and did not reduce the oxyanion to vanadyl.
Mercury chloride toxicity was investigated in two strains of Chlorella and in a strain of Scenedesmus isolated from polluted areas in Tuscany (Italy). No Hg resistance was found in the autotrophic microorganisms isolated, but Scenedesmus sp. strain AR-2489, isolated from the Arno river, was able to grow at concentrations of up to 5 micrograms ml-1 of Hg. This concentration was twice that which inhibited growth of the two Chlorella strains and Scenedesmus acutus 8M, the reference strain from a culture collection. Photosynthesizing cells of Scenedesmus sp. AR-2489 showed reduced Hg uptake, with the highest percentage of Hg removal from the medium. Loss of Hg was not due to Hg(0) volatilization, as shown by a comparison test with the broad-spectrum Hg-resistant Pseudomonas putida FB1. The metabolic differences between Scenedesmus sp. strain AR-2489 and Siacatus strain 8M were: (1) higher growth rate (doubling time of 6.0 h versus 10.6 h); (2) higher O2 production rate (maximum 2 mumol h-1 mg-1 dry weight); and (3) higher intracellular pH during growth. The latter was imaged with a green fluorescence molecular probe (BCEFC-AM) and observed by scanning confocal laser microscopy (SCLM). The distribution of red-autofluorescence chlorophyll-a showed that strain AR-2489 had a rougher and hence more extended specific chloroplast surface than strain 8M. Hg tolerance in strain AR-2489 was related to the rapid increase in dissolved O2 in the medium and in intracellular pH; this caused a loss of soluble mercury transformed to insoluble mercury hydroxide, which is thermodynamically more stable at alkaline pH in highly oxygenated systems.
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.
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Congenital cystic adenomatoid malformation of the lung (CCAM) is characterized by an adenomatoid proliferation of bronchiole-like structures and cysts formation. The condition is most commonly found in newborns and children and it may be associated with other malformations; rarely, the presentation is delayed until adulthood. This paper presents a case of CCAM in a 62-year-old male, who presented with recurrent bacterial pneumonias and breathlessness one exertion. The chest X-rays and CT scan revealed a patchy opacity in the right lower pulmonary zone. Bronchoscopic examination was normal. At surgery, a mass involving the right lower and middle lobes, and enlargement of hilar lymph nodes were found. A bilobectomy was performed without complications. Examination of the gross specimen showed a lesion characterised by multiple small cysts, all less than 1 cm in diameter; they were lined predominately by columnar epithelium, occasionally by ciliated epithelium. Rare cysts were lined by foreign body giant cells. Elastic fibers and smooth muscle were present within the cysts wall. Peripherally, there were normal alveoli and bronchioli mixed with cysts, and plasmalymphocytic infiltrates. The final diagnosis was Stocker's Type II CCAM of the lung. CCAM of the lung is a rare development lesion of the lung and it has no sexual predilection. It is usually unilateral and sublobar or lobar in size, but occasionally it can be multilobar. Typical histologic feature of CCAM are adenomatoid proliferation of bronchiole-like structures and macro- or microcysts lined by columnar or cuboidal epithelium and absence of cartilage and bronchial glands. Inflammatory changes are not found in infants, but may be present in adult patients. Based on the size of the cysts, CCAM may be classified into three different types: type I characterised by multiple cysts, over than 1 cm in diameter; type II with smaller cysts, less than 1 cm in diameter; type III that shows solid lesions composed of bronchiole-like structures. Type II is commonly found in childhood, but is occasionally seen in adult patients, as that one in our report. The insult probably occurs between 4th and 7th week of fetal life. The etiologic agent is unknown. The histologic diagnosis of CCAM is difficult in adult patient, perhaps because of supervening infections that sometimes distort the underlying diagnostic pathologic appearances and make them difficult to recognise, as happened in our case. From the clinical point of view, most of the lesions cause severe respiratory failure; in adult individuals the diagnosis is difficult, since there are very few relevant symptoms and signs. The patients can present with fever, recurrent infections, breathlessness and haemoptysis. The chest X-rays abnormalities are not specific and include homogeneous or multicystic opacities. Similarly, other diagnostic methods add no further useful informations. Surgical treatment is necessary also in adult patients, because of the risk of recurrent pulmonary infections and malignancies associated with CCAM. Lobectomy is the treatment of choice, but sometimes a larger resection is required, when the lesion involves more than one lobe.
Pulmonary blastoma is a rare tumor of the lung consisting of immature mesenchyma and epithelial structures that can mimic the structure of the embryonic lung. In this article, we report a case of pulmonary blastoma occurred in an adult individual. We review the literature concerning this rare neoplasm that includes less than one hundred cases reported. We also describe the pathologic features of this disease which is microscopically divided in two classes: 1) lesions composed solely of malignant gland of embryonic appearance (WDFA: Well-Differentiated Fetal Adenocarcinomas), and 2) lesions with biphasic appearance, containing both neoplastic glands and either adult sarcomatous or embryonic mesenchyme. The adult pulmonary blastomas are considered as an entity distinct from childhood blastomas. This condition may be frequently asymptomatic; if symptomatic, it show the same clinical picture of a mass in the lung impinging on bronchi or pleura; the most usual symptoms include cough, hemoptysis, and chest pain. Chest radiography typically shows a peripheral or central lung opacity without preference for any lobe. The prognosis is poor, due to the high incidence of metastasis. Histologic class and clinical findings can be of prognostic value in pulmonary blastoma. We believe that an early diagnosis is essential: in our case, this allowed a complete resection of the tumor and the patient is still alive without recurrence 3 years after the surgical treatment.