Integrin LFA-1 interacts with the transcriptional co-activator JAB1 to modulate AP-1 activity.

Integrin adhesion receptors transduce signals that control complex cell functions which require the regulation of gene expression, such as proliferation, differentiation and survival. Their intracellular domain has no catalytic function, indicating that interaction with other transducing molecules is crucial for integrin-mediated signalling. Here we have identified a protein that interacts with the cytoplasmic domain of the beta2 subunit of the alphaL/beta2 integrin LFA-1. This protein is JAB1 (Jun activation domain-binding protein 1), a coactivator of the c-Jun transcription factor. We found that JAB1 is present both in the nucleus and in the cytoplasm of cells and that a fraction of JAB1 colocalizes with LFA-1 at the cell membrane. LFA-1 engagement is followed by an increase of the nuclear pool of JAB1, paralleled by enhanced binding of c-Jun-containing AP-1 complexes to their DNA consensus site and increased transactivation of an AP-1-dependent promoter. We suggest that signalling through the LFA-1 integrin may affect c-Jun-driven transcription by regulating JAB1 nuclear localization. This represents a new pathway for integrin-dependent modulation of gene expression.

Diabetes and complications after cardiac surgery: comparison with a non-diabetic population.

Diabetes is a well-recognized independent risk factor for mortality due to coronary artery disease. When diabetic patients need cardiac surgery, either coronary-aortic by-pass (CABP) or valve operations (VO), the presence of diabetes represents an additional risk factor for these major surgical procedures. Because of controversial data on mortality rates and post-operative complications in diabetic patients, probably due to not exactly comparable groups of patients, this retrospective study aimed to compare two homogeneous populations, which were different only for the presence or absence of diabetes. We studied 700 patients undergoing cardiac surgery: 350 with and 350 without diabetes, mean age 62 +/- 9 years (67% males); 441 underwent CABP and 259 VO. Apart from the diabetes, the two groups were strictly matched for age, body mass index, concomitant pathologies and smoking habits, except for previous neurological injuries (more frequent in diabetic patients), and for a slightly lower ejection fraction in the diabetic group. Intra- and post-operative complications or events were evaluated carefully: death, number staying in post-operative intensive care unit (ICU), renal, hepatic and respiratory complications, necessity for reoperation and hemotransfusions. Anesthesia and surgical procedures (including extra-corporeal circulation techniques) remained substantially unchanged over the period of recruitment of patients (1996-1998) and applied equally to both groups of patients. All diabetic patients were treated with insulin by using standard procedures in order to optimize metabolic control. Diabetic patients in our study, did not show higher rates of mortality in comparison with non-diabetic patients, but had more total neurological complications, more renal complications, a higher re-opening rate, more prolonged ICU stay, and they needed more blood transfusions. Diabetes remains an independent risk factor for these events even in a multivariate logistic regression model analysis. In the subgroup of diabetic patients who underwent CABP a higher rate of renal dysfunction, re-opening, need for hemotransfusions and prolonged ICU stay were confirmed. In the subgroup of diabetic patients undergoing VO we found a higher rate of renal dysfunction, reopening, prolonged ICU stay and major lung complications. In conclusion, diabetes does not seem to increase the mortality rates of cardiac surgery, but diabetic patients undergoing CABP have, on the basis of the relative risk evaluation, a 5-fold risk for renal complications, a 3.5-fold risk for neurological dysfunction, a double risk of being hemotransfused, reoperated or being kept 3 or more days in the ICU in comparison with non-diabetic patients. Moreover, diabetic patients undergoing VO have a 5-fold risk of being affected by major lung complications.

[The energy cost and the use of individual protective devices in firefighters]. / Costo energetico e uso di D.P.I. nei vigili del fuoco.

Firefighters are required to wear fire-protection devices when involved in hazardous work situations. To determine whether fire protective clothing and self-contained breathing apparatus (SCBA) affect maximal physical work performance and to assess their additional energy requirement, we studied a cohort of Italian firemen while performing a rapid air-stair climbing (Mt. 29). Heart rate (HR) and maximal speed (time/distance) were measured in 23 firemen during the exercises, performed either wearing fire protection clothing and SCBA (p2) and service dress (p1). We also measured maximal oxygen consumption (VO2 max, indirect determination), WBGT and the speed/HR ratio (iR) as an arbitrary index of physical work performance. The participant reached the sub-maximal HR in both exercises (p1 87.01%; p2 88.84%). Fire protection devices significantly reduced the exercise maximal speed (p < 0.001) and increased the maximal HR (p < 0.01). IR index was significantly (p < 0.001) lower for p2, indicating a reduction of physical work performance (-26.9%); VO2 max was inversely related with mean and maximal HR (p < 0.001). These results suggest that only well trained firefighters should be employed in emergency actions requiring fire protection devices and SCBA.

[Thyroid metastasis of carcinoma of the breast. Considerations on 2 cases]. / Metastasi tiroidee da carcinoma della mammella. Considerazioni su due casi.

Two cases of thyroid metastasis from breast cancer are reported, both occurring in patients previously given radical mastectomies. It is emphasised that postoperative follow-up should also monitor rarely affected sites of metastasis from breast cancer.

Myofibroblasts in the epithelial-stromal junction of basal cell carcinoma.

The epithelial-stromal junction of basal cell carcinoma (BCC) has been investigated at the electron microscope level. The fibroblast-like cells surrounding the epithelial nests of BCC appear to be myofibroblasts. According to the present view of the function of myofibroblasts, their presence around BCC could be related to the slow invasiveness of this tumour.

IgA pseudo-linear deposits in glomerular basement membranes in dermatitis herpetiformis.

An 18-year-old-woman, with dermatitis herpetiformis, acute glomerulonephritis, malabsorption and villous atrophy due to massive infiltration of IgA producing plasma cells was studied. By light microscopy, her renal biopsy specimen showed heavy immunofluorescence for IgA, a mixed proliferative and membranous lesion with occasional crescents and focal sclerosis. Electron microscopic examination revealed three main lesions: (1) swelling and bleb formation in endothelial cells, (2) extensive fusion of foot processes of podocytes, and (3) a dense quasi-linear, continuous deposition of immune complexes, encompassing several loops; they were characteristically located within the basement membrane at the boundary between the lamina densa and the lamina rara interna. At occasional points where the immune complexes had reached the outer aspects of the basement membrane, there was damage to the podocyte cytoplasm. This electron microscopic aspect supports the interpretation that these immune complexes, although non-complement fixing, exhibit a high damaging potential, leading to relentless disease progression.

Primary Kaposi's sarcoma and Hodgkin's disease in the same lymph node.

The occurrence of primary Kaposi's sarcoma in a lymph node affected by Hodgkin's disease is reported. The case concerns a 43-year-old woman with a recurrence of Hodgkin's disease 13 years after its initial diagnosis. In one of four excised supraclavicular nodes a Kaposi's sarcoma was unexpectedly found. The present observation stresses once more that the two diseases are closely related and possibly share the same pathogenesis.

Evidence for collagen fibrils inside the cells of granular cell myoblastomas.

An electron microscope study was performed on two cases of subcutaneous granular cell myoblastomas. Phosphotungstic acid staining reveals the intracellular formation of collagen fibrils both inside the granules and scattered outside them, but always in relation with ribosomes or ergastoplasmic sacs. Pericellular deposition of basal-membrane-like material is a constant feature; however it appears to be more a precollagen material, extruded by cells, than a true basal membrane. This observation strongly supports the view that granular cells in Abrikossoff tumors are fibroblasts of muscle (and nerve?) sheaths abnormally producing precollagen material.