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Biomedical subjects

S Pittaluga

Publications and source records attributed to S Pittaluga.

At least 55 records · Page 3Linked to original sources
PubMed1994

Bone marrow trephines. Findings in patients with hairy cell leukaemia before and after treatment.

Bone marrow trephine biopsies from 20 patients with hairy cell leukaemia were reviewed at diagnosis and during therapy with alpha-interferon (IFN) and with 2-chlorodeoxyadenosine (2-CdA). At time of diagnosis the trephines revealed classical features of hairy cell leukaemia and profound alterations of haematopoiesis. All three lines showed dysplastic features with architectural, qualitative and quantitative changes. Review of consecutive trephine biopsies in patients that received IFN showed that a complete remission with disappearance of the tumour was never achieved and that the dysplastic features persisted. An improvement of haematopoiesis was noted, but recovery, especially of the myelopoiesis, was never completely achieved. By contrast, patients treated with 2-CdA de novo and previously treated with IFN achieved a complete remission in all but three cases. The trephine biopsies showed an improvement of haematopoiesis with progressive disappearance of the dysplastic features and a good recovery of myelopoiesis. A residual lymphocytosis was present, but as it was also present in age-matched control cases it could not be considered as a residual tumour. The disappearance of the leukaemic infiltrate probably constitutes a prerequisite for the recovery and normalization of haematopoiesis, while the dysplastic changes present at diagnosis could be the result of cytokine production by the leukaemic cells.

2-Chloroadenosine↗
PubMed1993

Latent sites of Epstein-Barr virus infection.

Epstein-Barr virus (EBV) has been detected in a wide spectrum of tumors. This study investigates the detection rate of EBV-DNA by Southern blot hybridization analysis (SOBH) and polymerase chain reaction (PCR) in different tissues from persons without apparent EBV-related diseases. Of 20 tonsillectomy specimens studied, SOBH indicated positivity for EBV-DNA in 1 case, and PCR indicated positivity in 10. In autopsies performed on patients with no apparent evidence of EBV-related diseases, the viral DNA was only detected by PCR in the following: parotid gland (7/15), submandibular gland (8/20), nasopharynx (8/10), tonsil (8/10), larynx (5/6), lung (5/9), cervical lymph node (7/10), mediastinal lymph node (7/10), abdominal lymph node (4/10), spleen (6/10), thyroid (5/10), liver (1/10), pancreas (1/4), kidney (4/10), uterine cervix (1/4), ovary (1/5) and testis (1/3). These results provide a baseline for interpreting the role of EBV in carcinogenesis.

Adolescent↗
PubMed1993

Clonal Epstein-Barr virus in lymphoepithelioma-like carcinoma of the lung.

Lymphoepithelioma of the nasopharynx is an undifferentiated carcinoma with a prominent lymphoid infiltrate. A consistent association with Epstein-Barr virus (EBV) has been demonstrated over the years by a variety of methods. More recently, undifferentiated carcinomas with a similar morphology have been described in other anatomical locations, often of foregut origin. However, for lymphoepithelioma-like carcinoma, the association with EBV has been more tenuous, especially in Western countries. Interestingly, these tumors have shown a geographic distribution similar to nasopharyngeal lymphoepithelioma, with relatively high frequency of EBV positive cases in Asian patients. We report five cases of lymphoepithelioma-like carcinoma arising in the lung. In situ hybridization revealed the presence of EBV in all cases with localization to the epithelial cells only. Southern-blot analysis from two cases revealed the presence of clonal episomal EBV in the tumor tissue. These findings further support the hypothesis that EBV is also associated with lymphoepithelioma-like lung carcinomas and suggest that EBV infection has preceded the clonal expansion of the tumor.

Adult↗
PubMed1993

Epstein Barr virus in carcinoma of the cervix.

A group of young patients with invasive carcinoma of the cervix and an age-matched control group were investigated for the presence of Epstein Barr virus (EBV) DNA in cervical biopsies using the polymerase chain reaction. The carcinoma group was further analyzed to evaluate possible associations between the presence of EBV and other prognostic parameters, such as stage, lymph node involvement, and histological tumor type. EBV DNA was found in 20 of 40 (50%) of the carcinoma samples and in 20 of 39 (51%) of the cervical tissues in the control group (p > 0.5). No statistically significant relationship could be noted between the presence or absence of EBV DNA and the effects of other prognostic parameters. In comparison with other studies using similar techniques, this study documented a higher percentage of positive EBV cases in both normal and carcinoma cervical samples. In both groups there was a similar number of positive cases. These results suggest that theories on the possible role played by EBV in the pathogenesis of cervical carcinoma may need to be reconsidered.

Adult↗
PubMed1993

Expression of c-myc and c-fms oncogenes in trophoblastic cells in hydatidiform mole and normal human placenta.

AIMS: To compare the expression of c-myc and c-fms proto-oncogenes in the placenta and hydatidiform mole. METHODS: Twelve hydatidiform moles and six induced abortion cases were collected. c-myc and c-fms proto-oncogene expression was analysed by northern blot hybridisation and immunohistochemical staining. RESULTS: The results of northern blot hybridisation analysis showed that c-fms was expressed more strongly in hydatidiform moles compared with normal placenta of similar gestational age. Moreover, c-fms mRNA concentrations increased with more advanced gestational age in moles but not in normal placentas. c-myc expression was very low in hydatidiform moles and normal placentas. Both oncogenes, however, had no direct correlation with the clinical course of the molar pregnancies. CONCLUSION: The difference in c-fms expression between hydatidiform moles and normal placentas suggests that c-fms may have a role in the development of molar pregnancies.

Antibodies, Monoclonal↗
PubMed1992

Detection of clonal Epstein-Barr virus in malignant proliferation of peripheral blood CD3+ CD8+ T cells.

Epstein Barr virus (EBV) DNA was detected in a monoclonal proliferation of T cells in a three-year-old girl who presented with a history of fever, hepatosplenomegaly, and generalised lymphadenopathy. The disease ran a rapid, fulminant course and the patient died 11 days after presentation. Examination of the blood showed a lymphocytosis of 50 x 10(9)/l with all the cells showing the morphology of large granular lymphocytes. These cells were CD2+3+8+25+. Cytogenetic studies showed the presence of a 6q- clone. Southern blotting and hybridisation with a constant region probe for the T-cell receptor (TCR) beta chain gene showed clonal rearrangement of the TCR beta gene. Hybridisation of the Southern blot to the EBV XhoI probe revealed a clonal pattern of episomal EBV DNA. Our results establish the association between clonal EBV infection to a malignant proliferation of peripheral blood CD8+ T cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1992

Clonal Epstein-Barr virus in lymphoepithelioma-like carcinoma of the stomach: demonstration of viral genome by in situ hybridization and Southern blot analysis.

Lymphoepithelioma (LE), originally described in the nasopharynx, is an undifferentiated carcinoma with heavy lymphocytic infiltrate. The tumor is common in Southeast Asia, particularly in southern China, where the Epstein-Barr virus (EBV) association has been documented more consistently than in Western countries. Tumors histologically similar to LE have been described also in other anatomical sites, mostly of fore-gut origin, such as salivary gland, tonsil, lung, thymus, and more recently stomach. We are reporting a case of poorly differentiated gastric adenocarcinoma with marked lymphocytic infiltrate resembling LE (LE-like carcinoma) in a Chinese without evidence of nasopharyngeal carcinoma. In situ hybridization for EBV revealed that the tumor cells but not the lymphoid cells harbored the virus. Tumor cells both in syncytial and glandular areas were positive for EBV. By Southern blot analysis EBV was demonstrated in the DNA extracted from the tumor, while the adjacent normal gastric tissue was negative. Moreover, analysis of the EBV termini revealed a clonal episomal form of the virus. Our case further supports the hypothesis that EBV is associated with LE-like gastric carcinoma. It also strongly suggests that EBV infection has preceded, and thus most likely contributed to, the clonal expansion in this tumor.

Aged↗
PubMed1991

The causes of death in patients with human immunodeficiency virus infection: a clinical and pathologic study with emphasis on the role of pulmonary diseases.

The clinical records and autopsy data of 75 patients dying with AIDS were reviewed to determine the frequency of individual diseases diagnosed premortem and postmortem, the significance of pulmonary processes found in the lungs at autopsy, and the clinical and pathologic causes of death. Cytomegalovirus (CMV) infection was identified histologically either premortem or postmortem in 81% of patients. The lungs and adrenal glands were infected most commonly. Only one-half of CMV infections were recognized premortem. Pneumocystis pneumonia and Kaposi sarcoma occurred in 68% and 59% of patients, respectively, but were not unsuspected premortem in any patient. Visceral involvement with Kaposi sarcoma, however, was frequently recognized only at autopsy. While disseminated M. avium-intracellulare infection was common (31% of patients), histologically documented pulmonary disease was uncommon (3% of patients). Cryptococcal infection, diagnosed in 10 patients, was confined to the central nervous system in only 1 patient. Toxoplasma, in contrast, infected the brain of only 6 patients. All 75 patients had one or more disease processes identified in their lungs or pleurae at autopsy. These processes included opportunistic infections in 76% of patients, neoplasms in 37% (Kaposi sarcoma in 36% and lymphoma in 3%), and other processes in 60%. The most prevalent pathogen, CMV was found in pulmonary tissue from 44 patients and caused significant disease in 21 patients. Five patients died due to CMV pneumonia. Pneumocystis carinii was found at autopsy in 24 patients. In spite of treatment, pneumocystis pneumonia was fatal in 11 patients. One patient died with concomitant CMV and pneumocystis pneumonia. Kaposi sarcoma, identified in the lungs of 23 patients, led to death in 5 patients via upper airway obstruction, hemorrhage, or parenchymal destruction. Other fatal pulmonary processes included bacterial pneumonia in 9 patients, idiopathic diffuse alveolar damage in 5, cryptococcosis in 2, and pulmonary hemorrhage in 1. Specific clinical criteria were used to determine the cause of death due to organ system failure. Fifty-one percent of patients died due to respiratory failure; 16% from neurologic disease; 17% from hypotension that was not caused by respiratory, neurologic, or cardiac disease; and 3% from cardiac dysfunction. Thirteen percent of deaths did not meet the clinical criteria defining these 4 categories. This clinical assessment was combined with autopsy data to identify specific diseases as causes of death.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1990

Pathologic findings associated with interleukin-2-based immunotherapy for cancer: a postmortem study of 19 patients.

The use of interleukin-2 (IL-2), either alone or in combination with lymphokine-activated killer cells, tumor infiltrating lymphocytes, or other immunotherapeutic agents has added a new list of alternatives to conventional antineoplastic regimens. Little information is available about the pathologic changes occurring in patients treated with these agents. In this study, we reviewed the necropsy materials from 19 patients, 12 men and 7 women, with a variety of malignancies including melanoma, renal cell carcinoma, gastrointestinal and pulmonary adenocarcinoma, and metastatic gastrinoma, who died after receiving IL-2-based immunotherapy. Death occurred at intervals ranging from less than 1 hour to 143 days following the last dose of therapy. All patients dying at or less than 43 days following cessation of therapy had lymphoid infiltrates of varying intensity in residual tumor. At necropsy, the major cause of death unrelated to the presence of metastatic tumor was bacterial sepsis. In addition, we found evidence of significant cardiac and pulmonary toxicity: two patients with acute myocardial infarction, one with and one without significant coronary artery disease, two cases of unexplained lymphocytic myocarditis, and one case of fatal pulmonary capillary plugging following an infusion of lymphokine-activated killer cells. Thus, not unlike other forms of therapy for cancer, IL-2-based immunotherapy does not appear to be without significant toxicity.

Adult↗
PubMed1990

Atypical pathologic manifestations of Pneumocystis carinii pneumonia in the acquired immune deficiency syndrome. Review of 123 lung biopsies from 76 patients with emphasis on cysts, vascular invasion, vasculitis, and granulomas.

The frequency of atypical pathologic manifestations of Pneumocystis carinii pneumonia (PCP) were studied in 123 lung biopsy specimens from 76 National Institutes of Health patients with the acquired immune deficiency syndrome. The following atypical features were observed: interstitial (63%) and intraluminal (36%) fibrosis, absence of alveolar exudate (19%), numerous alveolar macrophages (9%), granulomatous inflammation (5%), hyaline membranes (4%), marked interstitial pneumonitis (3%), parenchymal cavities (2%), interstitial microcalcification (2%), minimal histologic reaction (2%), and vascular invasion with vasculitis (1%). These atypical features are discussed with emphasis on the significance of cavities, vascular invasion, vasculitis, and granulomas. Immunohistochemical staining with monoclonal antibodies to the 2G2 and 6B8 antigens of P carinii in paraffin-embedded lung biopsy specimens did not indicate any diagnostic advantage over routine methenamine silver stains. This study provides an important reminder that a wide variety of pathologic manifestations may occur in PCP in human immunodeficiency virus-infected patients and that atypical features should be sought in lung biopsies from patients at risk for PCP.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Translocation of bcl-2 gene in non-Hodgkin's lymphomas in Hong Kong Chinese.

The close association between translocation of the proto-oncogene bcl-2 and follicular lymphomas has been well established in Caucasian patients and the de-regulation of bcl-2 has been implicated in follicular lymphomagenesis. Similar molecular structural alterations have also been detected in diffuse lymphomas with a previous history of a follicular pattern as well as in a smaller proportion of de novo diffuse lymphomas. There is a lower incidence of follicular lymphomas in Chinese. In order to investigate further this phenomenon, we used bcl-2 translocation as a genetic marker of follicular lymphomas, to study 31 cases of B cell non-Hodgkin's lymphomas in Chinese patients by Southern blot analysis. Eight out of 16 cases of follicular lymphomas showed bcl-2 translocation with involvement of the major breakpoint region (MBR). Six of these cases utilized breakpoints within the 4.3 kb HindIII fragment, while in two cases the breakpoints were more dispersed, but still within the BamHI fragment. An additional case of follicular lymphoma showed translocation of bcl-2 gene with involvement of the minor cluster region (mcr), making a total of nine out of 16. None of the 15 cases of diffuse lymphomas showed similar molecular structural alterations. These data show that bcl-2 translocation is present in 57% of follicular lymphomas in Chinese patients, and support the notion that bcl-2 translocation is a consistent marker for follicular lymphomas irrespective of ethnic differences. As the translocation is not detected in the diffuse lymphomas, there is no evidence to suggest that the low incidence of follicular lymphomas in Chinese patients is due to a greater tendency for follicular tumours to progress rapidly and present as diffuse lymphomas.

Blotting, Southern↗
PubMed1989

Clinically occult Leydig cell tumor presenting with gynecomastia.

An occult Leydig cell tumor is described in a patient who presented with gynecomastia. Diagnosis was established by means of testicular ultrasonography and selective testicular venous sampling. The pathophysiology and management of this rare disease entity are discussed.

Adult↗
PubMed1989

Primary lymphoma of the liver in a patient with acquired immune deficiency syndrome and chronic hepatitis B.

We describe the case of a homosexual man with asymptomatic infection with human immunodeficiency virus and hepatitis B virus who developed primary hepatic lymphoma. The lymphoma presented with rapid enlargement of the liver, and ultrasound examination revealed multiple hypoechoic lesions within the liver. Histological examination of the liver showed massive replacement by lymphomatous tissue, as well as changes of chronic active hepatitis B. Immunohistochemical stains for hepatitis B surface and core antigens were strongly positive in almost all hepatocytes, but not in tumor tissue. Whereas the occurrence of lymphoma probably is related to HIV infection, possible interactions between hepatitis B virus and HIV infection are discussed. Thus, the presence of mass lesions within the liver in a patient with HIV infection should raise the possibility of hepatic lymphoma even if there is no evidence of generalized lymphadenopathy.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Metastasectomy for soft tissue sarcoma. Further evidence for efficacy and prognostic indicators.

Between 1982 and 1987, 74 patients (46 men and 28 women) had exploration for presumed metastases from high-grade soft tissue sarcoma of the head/neck, extremity, or trunk. Ages ranged from 11 to 75 years (median 38 years). Thirty (41%) had multiple procedures for recurrences (range two to six explorations). Median postthoracotomy time for the group of patients with histologically confirmed sarcoma (n = 63) was 20.3 months. Patients rendered free of disease at initial thoracotomy had significantly longer postthoracotomy survival times (26.8 months median) than those with unresectable metastatic disease (9 months median); p2 less than 0.0001). The prognostic significance of age, sex, location of primary tumor, disease-free interval, number of nodules on preoperative computed tomograms or conventional linear tomograms, number of metastases resected, and the use of postoperative chemotherapy were analyzed. In a univariate analysis, sex, age, and location of the primary tumor did not impact significantly on survival, nor did the use of postoperative chemotherapy. Initial disease-free interval of 1 year or less was associated with a significantly shorter survival time, and patients with five nodules or fewer on preoperative computed tomography had significantly longer survival times than patients with six nodules or more. Patients with three nodules or fewer on linear tomography had a longer postthoracotomy survival time than patients with four nodules or more. In patients whose malignant disease could be completely resected, the number of nodules resected at thoracotomy did not impact on long-term survival. According to proportional-hazards modeling, disease-free interval, sex, resectability, and truncal location were found to associate with length of survival after metastasis removal. We conclude that pulmonary metastasis resection in patients with soft tissue sarcoma is associated with long-term survival, and consistent indicators can define which patients may benefit from these interventions.

Adolescent↗
PubMed1988

Stable T3- and T3+ subclones derived from the mosaic human T cell leukemia cell line, CEM.

An unexplained feature of the human T lymphoblastic leukemia cell line, CEM, is a heterogeneous expression of surface membrane T3-TCR complex. CEM cells constitutively maintain two distinct populations whereby a minority of cells (5 to 16%) express T3 but the remainder do not. From the parental cell line, we have derived stable subclones in which all cells express surface T3 and companion subclones that lack surface T3. Inasmuch as surface T3 expression is contingent on assembly and coexpression of the multichain T3 protein complex with the TCR, we compared the surface T3+ and T3- subclones for their rearrangement and expression of genes of the T3-TCR complex. Restricted DNA of both subclone types showed the identical monoclonal pattern of TCR gene rearrangement seen in the mosaic parental CEM line. Northern blot analysis revealed mRNA transcripts of TCR beta subunit and T3 delta in both the surface T3+ and T3- subclones. However, surface T3+ subclones transcribed abundant full length (1.5-kb) TCR alpha mRNA in contrast to the surface T3- subclones in which TCR alpha transcripts were undetectable. Lack of TCR alpha gene transcription was not attributable to either unrearranged or aberrantly rearranged TCR alpha genes because exposure of surface T3- cells to phorbol ester induced a rapid (15-min) and progressive accumulation of full length (1.5-kb) TCR alpha mRNA. This was followed by surface membrane T3 expression in 24 to 72 h. We conclude that the unusual phenotypic mosaicism of CEM cells is attributable to a reversible lack of transcription of the TCR alpha gene.

Antigens, Differentiation, T-Lymphocyte↗