Outcomes of bilateral mammoplasty for early stage breast cancer.

AIM: Long-term oncological follow-up of oncoplastic breast surgery. METHODS: Sixthy-one (63 cancers) patients affected by breast cancer suitable for breast conservation, were treated with bilateral breast reductions. Tumours located in the inferior pole of the breast were treated by a superior pedicle technique; lesions in the upper pole or in the infero-lateral or infero-medial quadrants of the breast were removed with an inferior pedicle reduction. Small and medium size breast irrespective of tumour location required a periareolar, or comma-shaped approach. RESULTS: Fifty-six patients were alive at a mean follow-up of 68 months. One patient recurred locally and she is currently alive free of disease. CONCLUSION: Results from this study are in accordance with those reported by other similar papers. Oncoplastic breast surgery maximizes cosmetic results and with wider excisions provides effective local control.

Nipple sparing subcutaneous mastectomy: sixty-six months follow-up.

AIM: Validation of oncological and reconstructive efficacy of nipple sparing subcutaneous mastectomy. METHODS: We enrolled 50 patients on behalf of Humanitas Centro Catanese di Oncologia fulfilling appropriate reconstructive and oncological criteria to undergo nipple sparing subcutaneous mastectomy. We preferably selected women with medium size-small breast affected by early stage breast cancer peripherally located with intra-operative negative frozen section of the major ducts. RESULTS: fourty-six patients were alive after a mean follow-up of 5.5 years. We observed a single case of local recurrence in the nipple successfully treated with local excision. Five patients presented metastatic disease. One is currently alive, 4 died because of progressive disease. CONCLUSIONS: Our study supports other findings regarding safety and efficacy of nipple sparing subcutaneous mastectomy for selected patients.

Taurine administration during lactation modifies hippocampal CA1 neurotransmission and behavioural programming in adult male mice.

Taurine plays a role in neuronal development. In this study, we examined whether postnatal taurine administration influences the long-term consequences induced by mild neonatal stressors (10 min maternal deprivation plus sham injection, applied daily to neonatal mice up to 21 days). At 30 days of age stressed mice showed higher pain threshold both in the tail-flick--which measures mostly the spinal mechanisms of pain--and in the hot-plate test--which reflects mainly the supraspinal mechanisms of pain. The latter effect was prevented completely by neonatal taurine administration, while the tail-flick test was not affected, thus suggesting that spinal pain is not sensitive to taurine treatment. At 140 days of age, mice which were stressed during the neonatal period showed consistent decrease in immobility time in forced swimming test, and taurine did not influence this parameter. At the same age, the fear/anxiety axis, measured with elevated plus maze test, did not show any consistent changes. Electrophysiological experiments in brain slices obtained from adult mice showed that input-output curves in hippocampal CA1 were increased by taurine administration in lactation. Hence, neonatal administration of taurine might permanently modify the functioning of hippocampus, a brain area which is known to be crucial for learning and memory.

A possible solvent effect of adenosine diphosphate influences the binding of 1,N6 ethenoadenosine diphosphate to myosin from skeletal muscle.

Skeletal muscle myosin displays two independent and equivalent binding sites for 1,N6 ethenoadenosine diphosphate, with a dissociation constant of 24.7 microM. MgADP, 10 to 40 microM, behaves as a pure competitive type inhibitor (K(SI)=8-9 microM) for the binding of 1,N6 ethenoadenosine diphosphate to skeletal muscle myosin. On the contrary, the inhibition by MgADP, 0.11-1.54 mM, is neither competitive nor non-competitive nor mixed, as is revealed by the analysis with the general kinetic equation (K.J. Laidler, P.S. Bunting, The Chemical Kinetics of Enzyme Action, 2nd ed., Clarendon, Oxford, 1973, p. 94). To explain our finding we propose that MgADP operates a complex type of inhibition, acting both directly as a competitor for myosin active sites, and indirectly by perturbing the regions of the solvent near to the protein.

Cervical dysplasia, ploidy, and human papillomavirus status correlate with loss of Fhit expression.

PURPOSE: The tumor suppressor gene, FHIT, has been cloned and mapped at chromosome region 3p14.2, one of the regions most frequently deleted in cervical carcinoma. In this report, we show that the expression of the Fhit protein in relation to human papillomavirus (HPV) subtype, the type of the intraepithelial lesion, HIV-induced immunodeficiency, and the DNA content (ploidy) correlates with the biological behavior of the lesions. EXPERIMENTAL DESIGN: To investigate involvement of the FHIT gene in squamous intraepithelial lesions of low and high grade (LGSILs and HGSILs, respectively) of the uterine cervix, we examined the Fhit protein expression by immunocytochemistry in 131 cervical smears of 96 HIV-seropositive patients (42 with LGSILs and 10 with HGSILs) and 35 HIV-seronegative (5 with LGSILs) persons. RESULTS: Fhit protein was detected in normal cells, whereas dysplastic cells (independently of HPV infection and HPV subtypes) showed reduced expression of Fhit (P = 0.00001). Lesions from 52 HIV-seropositive patients, 42 LGSILs and 10 HGSILs, showed diploid DNA content in 63.5%, aneuploid in 32.7%, and polyploid in 3.8%, but 90% of the HGSILs showed an aneuploid DNA content, and all were infected by HPV 16/18 subtypes. 23.8% of LGSIL cases were associated with HPV 16. CONCLUSIONS: These data clearly suggest that loss of Fhit expression occurs in the early stages of cervical carcinogenesis. Pap test represents one of the most convenient and rapid procedures available in identification of cellular changes; hence, Fhit staining might be used as an useful tool in larger population screening to detect early alteration in cellular behaviors.

Dissecting the free energy of formation of the 1:1 actomyosin complex.

The behaviour of solutions of pure myosin, of pure F-actin and of the equimolar mixture of myosin and of F-actin is studied. It is found that the chemical potential of the two proteins, in separate solutions, increases monotonically with the increase of protein osmotic pressure. A method is presented to determine the chemical potential of the 1:1 actin-myosin complex formed from equimolar solutions of myosin and of F-actin (as monomer). This is the first evaluation of the chemical potential of actomyosin under conditions similar to those of skeletal muscle. It is found that the filament suspensions of myosin and of the 1:1 actin-myosin complex display a high non-ideal behavior as well as distinctly different energy profiles as a function of protein osmotic pressure. This supports the hypothesis that, in muscle: (a) detached cross-bridge change significantly their free energy when sarcomere is shifting from the relaxed to the active or to the rigor state; and (b) the cross-bridge attachment-detachment process is accompanied by changes of muscle protein osmotic pressure.

Anomalous binding of MgADP to myosin of skeletal muscle.

Binding of adenosine diphosphate to skeletal muscle myosin was studied using a range of concentrations from 0 to 2 mM. Up to 0.2 mM adenosine diphosphate two equivalent and independent nucleotide binding sites were detected, characterized by the single association constant of 5 x 10(4)M(-1). At greater adenosine diphosphate concentrations a decreasing binding capacity was noticed, bound nucleotide being essentially approximately 0.1 mol/mol at a 1-2mM adenosine diphosphate concentration. We tentatively propose that nucleotides act indirectly on myosin by promoting the perturbation of the solvent, which is supported by the fact that polyphosphates are known powerful kosmotropes.

Immunohistochemical study of fatty acid synthase, Ki67, proliferating cell nuclear antigen, and p53 expression in hyperplastic parathyroids.

Patients with secondary hyperparathyroidism following chronic renal disease frequently develop hyperplastic parathyroids. Hyperplastic parathyroids have an increased number of chief cells, a decreased amount of stromal fat, and a nodular or diffuse histologic pattern. Hyperplastic parathyroids may also express higher proliferative activity compared with controls. We evaluated the morphologic features and immunohistochemical expression of fatty acid synthase (FAS), Ki67, proliferating cell nuclear antigen, and p53 protein in 78 hyperplastic parathyroids from 20 patients with secondary hyperparathyroidism. Twenty normal parathyroids incidentally removed during nonneoplastic thyroid surgery were used as controls. Our results showed that hyperplastic glands overexpress FAS (P =.06). Statistical analysis also revealed a significant association between FAS and p53 protein (P =.006) and between FAS and hyperplastic glands with a predominant nodular pattern (P =.02). Hyperplastic parathyroids from patients with chronic renal failure strongly express FAS. Fatty acid synthase may therefore be a potential biological indicator of highly proliferating parathyroid cells.

Fatty acid synthase (FAS) predictive strength in poorly differentiated early breast carcinomas.

AIMS AND BACKGROUND: Many normal and human cancer tissues express fatty acid synthase (FAS), the major enzyme required for endogenous fatty acid biosynthesis. Strong expression of FAS seems to be associated with a poor prognosis. This study examines the strength of FAS and other common markers of relapse in poorly differentiated breast carcinoma. MATERIALS AND METHODS: Fifty-one patients with poorly differentiated ductal infiltrating breast carcinomas were followed up for more than 10 years. Immunohistochemical detection of FAS was associated with morphological features of the tumors, with immunohistochemical expression of c-erbB-2, cathepsin D, estrogen and progesterone receptor status and with DNA ploidy in order to detect a statistical correlation. RESULTS: The chi-square test revealed a correlation between FAS and peritumoral lymphatic vessel invasion (PLVI) (P = 0.001). Univariate analysis showed that FAS was correlated with disease-free survival (DFS) (P = 0.0001). Other prognosticators associated with DFS were PLVI (P = 0.002), estrogen (P = 0.008) and progesterone receptor status (P = 0.007). Bivariate analysis showed that FAS was a further prognostic discriminant of DFS within the ER, PgR and PLVI subsets. DISCUSSION: FAS is a reliable prognosticator of recurrence in poorly differentiated early breast carcinomas. Association of FAS with PLVI may be useful to plan a correct follow-up in patients with breast neoplasms.

Inflammatory pseudotumour of the liver--evidence for malignant transformation.

A case of inflammatory pseudotumour of the liver is reported, and evidence is presented for its subsequent evolution into malignant non-Hodgkin's lymphoma. Such postulated malignant transformation challenges the assumption that hepatic inflammatory tumours are entirely benign lesions.

Immunohistochemical expression of fatty acid synthase, apoptotic-regulating genes, proliferating factors, and ras protein product in colorectal adenomas, carcinomas, and adjacent nonneoplastic mucosa.

The normal mucosa-adenoma-carcinoma sequence in colon pathology provides an attractive model of tumor progression. The role of tumor suppressor genes, oncogenes, and proliferative markers in tumorogenesis has evolved considerably in the last decade. By immunohistochemistry means, we have studied p53, bcl-2, c-myc, p21-ras, ki67, and fatty acid synthase (a fatty-acid-synthesizing enzyme) in normal, dysplastic, and neoplastic mucosa. The results were correlated with clinicopathological features and overall survival (OS). Formalin-fixed, paraffin-embedded archival material from 100 nonconsecutive adenomas and 100 adenocarcinomas (ADCs), including adjacent-to-tumor nonneoplastic mucosa (ANNM), from patients with a 5-year follow-up period were studied. Negative controls were obtained from colon resections for nonneoplastic disease. Fatty acid synthase was associated with ADC (P = 0.0001). p53 protein was associated with high-grade dysplasia adenoma (AHGD), ADC (P = 0.0001), and pT stage (P = 0.003). bcl-2 was associated with adenomas with low-grade dysplasia (P = 0.009); c-myc was associated with ANNM (P = 0.005) and pT stage (P = 0.006). p21-ras was associated with AHGD (P = 0.0001) and ANNM (P = 0.01). Ki67 was associated with AHGD (P = 0.02) and ADC (P = 0.0001). Univariate analysis on neoplastic tissue revealed histological grade, pT stage, pN stage, p21-ras, and p53 to be significant markers of OS; p21-ras, p53, and c-myc were reliable markers when evaluated on ANNM. Multivariate analysis revealed pT stage, pN stage, and p21-ras to be independent prognosticators of OS on ADC; p21-ras and c-myc staining in the ANNM were correlated with worse survival (OS). We suggest that the evaluation in concert of clinicopathological data and immunohistochemical markers on both normal and abnormal colon tissue provides an attractive model of tumor progression; moreover, it may give important messages about the prediction of survival.

Protein cross talking through osmotic work: the free energy of formation of the MgADP-myosin complexes at the muscle protein osmotic pressure.

A method is presented to determine the energy of formation of the myosin-ADP complexes at the muscle protein osmotic pressure. It is found that, at 18 kP, the putative protein osmotic pressure in skeletal muscle, the increase of MgADP from 0.05 to 2 mmolal, increases the free energy of myosin-ADP and of myosin-(ADP)2 by 0. 756 and by 9.85 kJ/mol, respectively, and decreases the free energy of myosin by 8.34 kJ erg/mol. It is pointed out that the local changes of water chemical potential, induced by the binding of MgADP to myosin, can be sensed by other structures of the contractile machinery, which per se may even be insensitive to MgADP. Cross talking between macromolecules can thus be achieved by changes of the water chemical potential.

Intrahippocampal injection of paraquat produces apoptotic cell death which is prevented by the lazaroid U74389G, in rats.

Injection of paraquat, a redox-cycling compound, into the rat hippocampus produces limbic seizures and hippocampal damage. Here we report that a proportion of the neuronal cell death caused by the herbicide occurs via an apoptotic mechanism which appears to be mediated by oxygen free radicals. Adult male Wistar rats (n=12) received a single dose of paraquat (25 nmol/0.5 microl; 0.5 microl/min rate) and were sacrificed 24 h later. Paraquat caused DNA fragmentation, nuclear chromatin marginalization and compaction in all hippocampal subsectors, 24 h after its injection, as revealed by both the TUNEL procedure and hematoxylin eosin staining of coronal brain tissue sections. Pre-treatment with the free radical scavenger lazaroid U74389G (30 mg/kg given i.p. 30 min beforehand) significantly reduced paraquat-induced apoptosis, but did not protect against non apoptotic neuronal cell loss caused by the herbicide.

Myofibrils of skeletal muscle: the activity coefficient of orthophosphate.

In the myofibrils of skeletal muscle, at 22 degrees C, pH 7.1 and at the physiological protein osmotic pressure of 1.8 x 10(5) dynes/cm2, orthophosphate behaves quite ideally, the activity coefficient being 0.85. Under the same conditions and at saturation, 2.67 mumoles of orthophosphate are bound per gram of dry myofibrils, with a dissociation constant of 7 x 10(-5) molal. Work is in progress to determine the activity coefficients of adenine nucleotide analogues. This work is needed to assess the actual value of the free energy of hydrolysis of ATP in muscle.

[A case of multifocal inflammatory pseudotumor of the liver]. / Su un caso di pseudotumore infiammatorio multifocale del fegato.

INTRODUCTION: The inflammatory pseudotumor (IPT) of the liver is a tumor-like lesion of unknown etiology and pathogenesis. Non infectious by definition the lesion is considered to be a long-lasting inflammatory process. CASE: In this report we describe a multifocal liver pseudotumor of a 52 year man who underwent a selective hepatectomy for a clinical and radiological suspicion of a liver cell carcinoma. RESULTS: Grossly the masses consisted of rubbery grey-yellowish nodules well-circumscribed from the liver parenchyma. Histologic examination revealed a double shaped cellular population surrounded by a thin rim of collagen fibres. The main population consisted of fibroblasts and histiocytes with no atypias or mitoses, arranged in a storiform or fascicular pattern; the second population consisted of a mixed population of lymphocytes, plasma cells, neutrophils and monocytes. Fibroblasts and histiocytes revealed diffuse positive immunostaining for vimentin and focal immunostaining for cytokeratin and desmin. The histiocytes were also CD68, CD18, CD14 and CD4 positive. CONCLUSIONS: Our case reveals same histological and immunohistochemical features already reported in literature. Primary and metastatic tumors involving the liver need to enter in the differential diagnosis but IPT lacks features of malignancy and the cell population is mixed. Although there is no specific marker for this lesion in cases featuring malignancy immunohistochemistry may be useful for a differential diagnosis: S-100 in cases of neurofibrosarcomas, actin and myosin for rhabdomyosarcomas, cytokeratin for epithelial tumors.

[Terata catydidymus dicephalus: description of a case]. / Terata catydidymus dicephalus: descrizione di un caso.

Conjoined twinning is the result of an abnormal developmental process of "twinning" in which two similar weighted and sized twins are partially conjoined and show a total symmetry independently from the pattern of conjunction. They are classified in three groups: Terata Catydidymus, Terata Anadidyma and Terata Anacatadidyma. Among Terata Catydidymus the dicephalus subtype is a rare abnormality with a severe prognosis compared to other subtypes as: diprosopus, pyophagus and ischiopagus. We report the case of a fetus at the 15th weeks of pregnancy. The external examination revealed severe diffuse somatic malformations consisting of dicephalia with a double neck in conjunction to a single chest, a single abdomen, a double spine conjoined distally near the sacrum, buds of ribs in between the two spines with mid clavicular and scapular fusion following the major axis of the two bones. Arms and legs revealed no abnormalities. Central nervous system structures were normally developed and the two hemispheres seemed completely separated and independent one to the other. We believe that the case described is interesting being Terata Catydidymus a rare phenomenon, being the dicephalus subtype still lesser frequent and its occurrence in males quite exceptional.

Is nebulin truly a component of the thin filament?

Thin filaments were prepared from rabbit and beef skeletal muscle with three different procedures, both at high and low ionic strength. Nebulin was always found to be associated with the myosin fraction and was always absent from the thin filament fraction.

A model relating protein osmotic pressure to the stiffness of the cross-bridge components and the contractile force of skeletal muscle.

We have modeled the effect of protein osmotic pressure on the orientation of the monomer in F-actin, in tropomyosin-F-actin, in the myosin subfragment-1 decorated F-actin and in the myosin subfragment-1 decorated tropomyosin-F-actin. According to the model, at the physiological protein osmotic pressure (18 kPa), the elastic moduli by bending of the monomer in F-actin and in tropomyosin-F-actin are calculated to be 4.74 MPa and 5.8 MPa, respectively. The elastic moduli by bending of the monomer in the myosin subfragment-1 decorated F-actin and in the myosin subfragment-1 decorated tropomyosin-F-actin are calculated to be 22MPa and 22.3MPa, respectively. These latter values are in excellent agreement with the values of the elastic moduli by stretching found for the fibres of frog and rabbit muscle. We have also calculated that, at the physiological protein osmotic pressure, the myosin subfragment-1 decorated F-actin rigor complex can develop a force of 3.96 pN, a force correctly oriented to promote the sliding of the actin filament toward the center of the sarcomere. The magnitude of this force is comparable to that reported for intact skeletal muscle. In contrast, the myosin subfragment-1 decorated tropomyosin-F-actin rigor complex develops a much smaller driving force, that favours relaxation. Apparently tropomyosin uncouples the osmotic and the mechanical event. It is proposed that the elastic energy for muscle contraction is provided by protein osmotic pressure.