Patellofemoral joint: kinematic MR imaging to assess tracking abnormalities

The patellofemoral joint was imaged with magnetic resonance (MR) in the axial plane while the knee was positioned from 0 degrees to 32 degrees of flexion (nine positions). These multiple sequential images obtained within the early phases of flexion of the knee were viewed in a "cine-loop" format, producing a kinematic study that clearly demonstrated the relationship of the patella to the trochlear groove. Four healthy subjects and one patient with known bilateral subluxing patellae were studied. The preliminary results suggest that kinematic MR imaging of the patellofemoral joint is potentially useful for the evaluation of patellar tracking abnormalities.     

FAS and FAS-L expression by tumor cells and lymphocytes in breast carcinomas and their lymph node metastases

FAS receptor (FAS, CD95) and FAS ligand (FAS-L, CD95-L) are complementary members of a particular apoptotic pathway that plays a major role in immune regulation. The activation of FAS-L may trigger cytotoxic mechanisms leading to the death of FAS-expressing cells. Tumor cells and tumor-infiltrating lymphocytes (TIL) may express FAS and FAS-L in various proportions, and their interplay may affect tumor behavior. In the present study, we explored the expression of FAS and FAS-L in 28 mammary carcinomas (19 ductal and 9 lobular) and in their lymph node metastases. The expression of these mediators in immunostained sections was graded and evaluated comparatively between normal and neoplastic mammary epithelium, between tumor cells and TILs, and between mammary carcinoma cells and their lymph node metastases. We demonstrated the coexpression of FAS and FAS-L by breast carcinoma cells and TIL, with FAS expressed more strongly by normal epithelial cells and TIL than tumor cells. FAS-L was better stained on tumor cells than on TIL. There was equal or greater expression of FAS and FAS-L in the primary tumors and their TIL than in the metastatic counterparts. Comparing the expression of FAS with that of FAS-L, we recorded FAS equal or stronger than FAS-L in the primary mammary tumors and the reversal of their expression, FAS-L greater than FAS in the lymph node metastases. These results are consistent with reports of studies with other tumors, suggesting that the upregulated FAS-L indicates an increased ability of tumor cells to induce apoptosis in TIL and in the normal tissues invaded. However, it is understood that the FAS/FAS-L system, although essential for apoptosis, is only a contributing factor to the complex process of tumor invasion and antitumor defense.     

HMGA1 protein overexpression in human breast carcinomas: correlation with ErbB2 expression.

We measured, by immunohistochemistry, HMGA1 protein expression in 212 breast tissue specimens: 6 normal samples, 28 hyperplastic lesions (13 with cellular atypia), 11 fibroadenomas, 10 in situ ductal carcinomas, 144 ductal carcinomas, and 13 lobular carcinomas. HMGA1 was not expressed in normal breast tissue; HMGA1 staining was intense in 40% of hyperplastic lesions with cellular atypia and in 60% of ductal carcinomas and weak in fibroadenomas and in hyperplastic lesions without cellular atypia. Because HMGA1 expression was similar among ductal breast carcinomas with different histologic grading, we evaluated the association between HMGA1 expression and that of other markers of breast carcinoma invasion (estrogen and progesterone receptors, Ki-67 antigen, and ErbB2) in 21 cases of grade 3 breast ductal carcinomas and 7 cases of breast lobular carcinomas. We found that HMGA1 expression tended to be associated only with c-erbB-2 expression (Spearman rho: 0.36; P=0.065). Taken together, these results suggest that HMGA1 expression might be a novel indicator for the diagnosis and prognosis of human breast cancer.     

Reduction of risk factors for cardiovascular diseases in morbid-obese patients following biliary-intestinal bypass: 3 years' follow-up

BACKGROUND: Obese patients are often affected by hypertension, dyslipidaemia, impaired glucose metabolism, and suffer from cardiovascular disease (CVD), related to the characteristic metabolic alterations. AIM OF THE STUDY: To evaluate reduction of risk factors for CVDs in morbid-obese patients (body mass index (BMI)>40 kg/m2) after weight loss upon bariatric surgery intervention of biliary-intestinal bypass. SUBJECTS: 45 (17 men, 28 women) morbid-obese patients (age: 19-49 y, BMI>40 kg/m2). All patients were selected on the basis of medical history, physical and biochemical evaluation and of psychiatric tests, which were performed on all individuals admitted to our Day Hospital to verify the safety of surgical intervention. MEASUREMENTS: Body weight, body composition (by dual X-ray absorptiometry, DXA), blood pressure, lipid profile, fibrinogen and glucose metabolism were monitored at baseline and 1, 3, 6, 9, 12, 24 and 36 months after surgery. RESULTS: A significant and persistent weight loss was present in all patients at the end of the 3 y follow-up period (P<0.001), with a progressive reduction of total and trunk fat mass as evaluated by means of DXA. Additionally, a parallel significant reduction in systolic (P<0.001) and diastolic (P<0.001) blood pressure was observed. Total and LDL cholesterol were significantly reduced (P<0.001), while HDL showed no modifications; triglycerides declined progressively during the 3 y follow-up (P<0.001). Fibrinogen decreased from 364.5+/-82.4 to 266.4+/-45.7 mg/dl at the end of the period (P<0.001). Fasting glucose levels and glucose levels 120 min after an oral glucose tolerance test were reduced from 95.1+/-20.3 to 78.6+/-9.1 mg/dl (P<0.001) and from 116.9+/-34.7 to 77.6+/-15.5 mg/dl (P<0.001), respectively, at baseline and at the end of the study. Moreover, fasting insulin decreased from 30.0+/-20.4 to 8.6+/-2.9 microUI/ml (P<0.001) after 3 y, while insulin levels after (120 min) oral glucose load decreased from 105.5+/-61.5 to 12.0+/-6.0 microUI/ml (P<0.001). CONCLUSION: Our results show that biliary-intestinal bypass may represent a valid and alternative therapeutic approach in patients with morbid obesity since it induces a significant and stable reduction of body weight and obesity-related risk factors for CVD.     

Increased gene transfer into human hematopoietic progenitor cells by extended in vitro exposure to a pseudotyped retroviral vector

Retroviral-mediated gene transfer is the most attractive modality for gene transfer into hematopoietic stem cells. However, transduction efficiency has been low using amphotropic Moloney murine leukemia virus (MoMLV) vectors. In this study, we investigated modifications of gene transfer using amphotropic MoMLV vectors in cell-free supernatant for their ability to increase the currently low transduction of both committed hematopoietic progenitors, granulocyte-macrophage colony- forming units (CFU-GMs), and their precursors, long-term culture- initiating cells (LTC-IC). First, based on the observation that bone marrow cells express more gibbon ape leukemia virus (GALV) receptor (Glvr-1) than amphotropic receptor (Ram-1), PG13/LN, which is a MoMLV vector pseudotyped with the GALV envelope, was compared with the analogous amphotropic envelope vector (PA317/LN). Second, progenitor cell transduction efficiency was compared between CD34 enriched and nonenriched progenitor populations. Third, the duration of transduction in vitro was extended to increase the proportion of progenitor cells that entered cell cycle and could thereby integrate vector cDNA. In 20 experiments, 1 x 10(6) marrow or peripheral blood mononuclear cells (PBMCs)/mL were exposed to identical titers of pseudotyped PG13/LN vector or PA317/LN vector in the presence of recombinant human interleukin-1 (IL-1), IL-3, IL-6, and stem cell factor (SCF; c-kit ligand) for 5 days. 50% of fresh vector supernatant was refed daily. Hematopoietic progenitor cells as measured by G418-resistant granulomonocytic colony (CFU-GM) formation were transduced more effectively with PG13/LN (19.35%) than with PA317/LN (11.5%, P = .012). In 11 further experiments, enrichment of CD34 antigen positive cells significantly improved gene transfer from 13.9% G418-resistant CFU-GM in nonenriched to 24.9% in CD34-enriched progenitor cells (P < .01). To analyze gene transfer after extended growth factor-supported long-term culture, 1 x 10(6) marrow cells/mL were cultured with IL-1, IL-3, IL-6, and SCF (50 ng/mL each) for 1, 2, and 3 weeks. Fifty percent of PG13/LN supernatant with growth factors was refed on 5 days per week. Five percent of marrow CFU-GM and 67% of LTC-IC were G418 resistant at 1 week (n = 4), 60% of CFU-GM and 100% of LTC-IC were resistant at 2 weeks (n = 2) and 74% of CFU-GM (n = 4) and 82% of LTC-IC (n = 2) were resistant at three weeks.(ABSTRACT TRUNCATED AT 400 WORDS)