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Biomedical subjects

A Barletta

Publications and source records attributed to A Barletta.

At least 73 records · Page 4Linked to original sources

Thyroid state and mitochondrial population during maturation and ageing.

The authors have determined the serum thyroid hormone levels [total and free triiodothyronine (T3), thyroxine (T4)], the liver T3 content, the mitochondrial alpha-glycerophosphate dehydrogenase activity (alpha-GPDH) and the number of mitochondria per cell in the rat from birth to old age. The serum levels of both thyroid hormones are modified with maturation and ageing in an essentially similar way: they increase from low values at birth to remarkably high values around 12 days, and then remain constant. The T3 liver content firstly increases (from birth to 14 days of life) and then maintains constant values. During the first two postnatal weeks, therefore, free serum T3 and liver T3 display a similar behavior. The alpha-GPDH activity of liver mitochondria was found constant from birth to old age. This might suggest either that the control of the alpha-GPDH activity is, at birth, under complex hormonal control, or that the nuclear receptors associated with the alpha-GPDH genes are precociously synthesized. The number of mitochondria per cell, at birth, is half the adult values, strongly increasing in number at weaning and remaining constant afterwards. The effect of thyroid hormones on the mitochondrial population during maturation, when low levels of serum T3 and T4 occur naturally, appears to be quite different from that induced experimentally by thyroidectomy.

Aging↗

Infectious complications in the renal transplant recipient.

The aim of this study was to estimate the incidence of infectious diseases in a group of patients who underwent kidney transplantation from January 1, 2004 to September 30, 2004, including 121 operations, with 119 from cadaveric and 2 from living donors. The protocol sought herpes viruses (CMV, VZV, and EBV), hepatitis viruses, human immunodeficiency virus, T. gondii, M. tubercolosis, and T. pallidum. Therapy for CMV was used both as prophylaxis in immunoglobulin (Ig)G-negative recipients from IgG-positive donors and preemptive therapy, that is, before the appearance of clinical symptoms, but after viremia reached borderline levels. For VZV infections, the treatment started after the appearance of papulo-vesicular cutaneous eruptions and antibody positivity. The treatment for pneumonia consisted of empirical therapy after radiography; for pyelonephritis, antibiotic therapy was based on the results of kidney echography, blood culture, and urine culture. Infectious complications appeared in 25 patients (20.7%), 3 of the which were polymicrobic: 12 CMV infections, 9 VZV infections, 3 pneumoniae, 4 pyelonephritis, and 1 salmonellosis. The most frequent infection was CMV, which occurred in the first 3 months after transplantation in 9 of 12 cases. This study showed that a knowledge of infection prevalence can help the physician to establish a more specific, efficacious antimicrobial therapy, despite the laboratory response not being available in a short time.

Bacterial Infections↗

Urologic complications in kidney transplantation.

Urologic complications in kidney transplantation have an incidence ranging from 3% to 20%, representing an important cause of organ loss. From January 2001 to September 2004, 123 renal transplantations were performed using an immunosuppressive protocol including basiliximab, mycophenolate mofetil, calcineurin inhibitors, and steroids. The surgical technique was vascular anastomoses to external iliac vessels, and ureteral anastomosis according to Lich Gregoire technique using a JJ ureteral stent. We report 5 renal complications (4.2%) and 4 extrarenal complications (3.5%), the majority of which required corrective surgery. The surgical strategy uses the clinical condition of the donor and the recipient; the anatomic anomalies of the graft, and a reduced cold ischemia time. Moreover, a reduction in acute rejection episodes and immediate renal function has been fundamental to reduce urologic complications. In fact, the main cause of urologic complications is ureteral ischemia, linked both to backtable surgery and to rejection episodes. Another important factor in the reduction of early urologic complications has been the routine use of a JJ stent, which allowed us a conservative approach in this setting.

Graft Rejection↗

Malignancies after kidney transplantation.

The most effective treatment of end-stage renal disease is renal transplantation; its superiority to prolong the longevity of patients is well established. Patient and graft survivals have improved with more potent immunosuppression but this advance has been associated with an increased incidence of cancer. The aim of this study was to assess the prevalence of cancer among 265 kidney transplant recipients engrafted between 1968 and October 2004. The overall prevalence of de novo malignancies was 3%. The mean age at diagnosis was 53.3 years (range, 28-63 years) and the duration of the transplant was 11.6 years (range, 0.3-33 years). One patient among 127 (0.8%) who had a history of less than 3 years under immunosuppression, developed a posttransplantation lymphoproliferative disorder (PTLD). Among the 138 patients who had more than 3 years immunosuppression, 7 (5%) developed neoplasms of vulva, colon, native kidneys, prostatic gland, and ovary. One patient was affected by de novo carcinoma in the transplanted kidney. Compared with other published studies, our early cancer prevalence is low, possibly due to a careful history before grafting, good HLA matching, and abstinence from anti-T-cell therapy for treatment of acute rejection episodes. The low level of immunosuppression may account for the low prevalence of neoplasia. The risk of developing a malignancy increases with long-term immunosuppression, comparable with most reports.

Adult↗

Mammographic aspect, cell kinetics and hormone receptor status of operable breast cancer.

To investigate the relationships between the mammographic aspects (according to Broberg), proliferative activity and hormone receptor status, we studied 165 patients subjected to radical mastectomy for operable breast cancer. The highest percentage of estrogen receptor-positive cases was observed in mammograph class I (p < 0.02) while classes III and V were highest in progesterone receptor-positive cases. Proliferative activity (111 cases) was significantly lower in class I and IV with respect to all other classes (p < 0.03 and p < 0.01, respectively). This study suggests that certain mammographic signs can be related to the biological characteristics of breast cancer.

Breast Neoplasms↗

Nuclear grade and DNA ploidy in stage IV breast cancer with only visceral metastases at initial diagnosis.

AIMS AND BACKGROUND: The presence of early metastases to distant sites in breast cancer patients is an infrequent event whose mechanisms are still not clear. The aim of this study was to evaluate the biologic and clinical role of DNA ploidy and cell nuclear grade of primary tumors in the metastatic process of a series of stage IV previously untreated breast cancer patients with only visceral metastases. METHODS: DNA flow cytometry analysis on paraffin-embedded material and cell nuclear grading of primary tumors was performed on a series of 50 breast cancer patients with only visceral metastases at the time of initial diagnosis. RESULTS: Aneuploidy was found in 28/46 (61%) of evaluable cases and was independent of site of involvement, clinical response, time of progression and overall survival of patients. Of the 46 cases evaluable for nuclear grade, 5 (11%), 16 (35%) and 25 (54%) were classified as G1 (well-differentiated) G2 and G3, respectively. Nuclear grade also was unrelated to response to therapy and overall survival, whereas time to progression was significantly longer in G1-2 than G3 tumors with the logrank test (P < 0.03) and multivariate analysis. CONCLUSIONS: Our results seem to stress the difficulty to individualize different prognostic subsets from a series of breast cancer patients with only visceral metastases at initial diagnosis according to DNA flow cytometry and nuclear grade.

Adult↗

HER-2/neu gene in primary and local metastatic axillary lymph nodes in human breast tumors.

In order to verify whether the HER-2/neu gene is involved in the initial phases of neoplastic disease or in its progression, we evaluated the amplification and overexpression of this gene in the primary tumor and in synchronous metastatic axillary lymph nodes of 26 women with operable breast cancer. HER-2/neu was amplified in 35% and overexpressed in 33% of the primary sites; similar percentages were found in lymph nodes. The clear correlation between the two disease sites regarding gene, mRNA and protein levels, supports the hypothesis that this gene is involved in the initial and invasive phases of neoplasia. Its actual role with respect to other biological tumor characteristics during the metastatic process should be investigated further.

Adult↗

Expression of GST-mu transferase in breast cancer patients and healthy controls.

The expression of glutathione S-transferase mu was measured by a qualitative immunoenzymatic assay in the blood samples of 108 women (63 breast cancer patients and 45 healthy controls) in order to analyze the relationships of GST-mu phenotype and smoking habits with tumor characteristics of breast cancer patients, such as tumor extension, nodal status, hormone receptor status and DNA content by flow cytometry. GST-mu was expressed in 53/108 (49%) of cases without any significant difference between healthy or neoplastic subjects, smokers or non-smokers, pre or post-menopausal, younger or older subjects. Moreover, the percentages of the GST-mu phenotype did not differ significantly in patients with different ER and PgR tumor status, tumor extension or nodal status. By contrast, aneuploid DNA tumor content was shown to be significantly associated with GST-mu expression (24% and 76% GST-mu positive, respectively, in diploid and aneuploid cases; p < 0.003). The biological meaning of this association remains to be interpreted.

Biomarkers, Tumor↗

Metastatic site and p53 primary tumor expression in previously untreated stage IV breast cancer patients.

p53 mutations have been reported to correlate with prognosis and response to therapy in patients with different tumor types. However, although p53 status is related to the primary tumor aggressiveness, an association between its expression and specific metastatic pattern has not yet been investigated. We immunohistochemically analyzed p53 (Pab1801) and ki67 (mib1) primary tumor expression in a series of advanced breast cancer patients presenting a selected pattern of distant metastases at the time of first diagnosis. Forty-eight percent of the overall series was classified as p53 positive while 22% as mib1 positive tumors. The overall agreement between p53 and mib1 expression was statistically significant (p = 0.03). While mib1 primary tumor expression did not show any association with the type of metastasis, p53 positivity was significantly higher in patients with soft tissue metastasis than in patients with bone or viscera metastasis (p = 0.002). No association with the probability of clinical response or different overall survival was found for patients with different p53 or mib1 status either in the overall series of patients or in subgroups of cases with different sites of distant metastasis.

Bone Neoplasms↗

Prognostic relevance of ploidy and proliferative activity evaluation by flow cytometry in poor prognosis non-Hodgkin's lymphomas.

The DNA content and S-phase fraction (SPF) of pathological paraffin-embedded lymph node tissue from 47 patients with poor prognosis non-Hodgkin's lymphoma (NHL) were analyzed by flow cytometry (FCM). Fifteen of 42 evaluable cases proved to be aneuploid. The DNA aneuploidy was not correlated with age, histology, stage, presence of systemic symptoms, clinical response or overall survival (OS) of patients. Mean SPF evaluated in 35 cases was 22.9%. After 78 months of follow-up, nine patients with diploid low SPF tumors had a significantly longer disease-free survival (DSF) with respect to the group of patients (33 cases) with aneuploid or diploid high SPF tumors (100% vs 59%; log rank test, p = 0.04).

Adult↗

Biological correlation between HER-2/neu and proliferative activity in human breast cancer.

HER-2neu alterations (amplification and overexpression), proliferative activity (3H-Thymidine-Labeling Index, 3H-Tdr-LI) and tumor ploidy (flow-cytometry) were analyzed in a human breast cancer series. Overexpressed tumors showed a significantly higher median 3H-Tdr-LI than normally expressed (p = 0.04), as also did amplified/overexpressed with respect to non-amplified/normally expressed (p less than 0.04). These differences were confirmed only in N-primary tumors. In fact, high expressed cases demonstrated a median 3H-Tdr-LI of 5.5% with respect to 1.9% for low expressed cases (p = 0.04) and amplified/overexpressed had a 3H-Tdr-LI of 9% with respect to 2% for non amplified/low expressed (p = 0.009). HER-2/neu alterations were not correlated with tumor DNA content.

Biomarkers, Tumor↗

Effect of thyroidectomy and in vivo administration of triiodothyronine on DNA synthesis in isolated mitochondria.

The experimental conditions were studied which allow hormonal levels to affect the incorporation of labelled deoxyribonucleosides triphosphates (dNTP's) into mitochondrial DNA by isolated liver mitochondria, obtained either from thyroidectomized young male rats (T) or from animals of the same age thyroidectomized and then treated with triiodothyronine (T + T3). It was demonstrated that: (a) extramitochondrial DNA, on which extramitochondrial DNA polymerase may act, was absent; (b) the permeability to dNTP's, the thymidine kinase activity, the energy supply, and the nuclease activities were unaffected by hormonal conditions; (c) the bacterial contaminations contribute for only 1% to incorporation. The characterization of incorporation product showed that: (a) such product was indeed DNA, as it was DNase-degradable for about 90%; (b) the labelled DNA was indeed mitochondrial DNA, as a 10 minutes preincubation with acriflavine or ethydium bromide (Eth. Br.) inhibited the synthesis by 90%.

Animals↗

[Receptor assessment of primary breast carcinoma and synchronous metastatic lymph nodes: histochemical study].

Several AA, utilizing the biochemical method (DCC) showed the presence or absence of hormonal receptor in either synchronous or metachronous metastatic nodes (N) can reproduce the receptor assessment (AR) of the primary breast tumor (T). We evaluated the AR in T and in synchronous N, by using two morphological methods, immunocytochemical and histofluorescent, to detect the nuclear Estrogen Receptor (ER1) and cytoplasmic sites of the II type (ER2 and PgR2). We studied 50 patients who underwent radical mastectomy for breast cancer N+. In this series we founded a high correlation between AR in T and in N: 82% for ER1, 94% for ER2, and 92% for PgR2. Also we observed 4 cases (2 ER1 and 2 PgR2) which presented the receptor in N only. These data are comparable to results obtained with the DCC method and confirm the opportunity to perform also morphological techniques to evaluate AR in breast cancer to take into consideration also cellularity and tumor heterogeneity informations.

Adult↗