Anatomical variations of the median nerve and of the vascular-nervous structures at the wrist.

Three cases of anatomical variation of the median nerve at the wrist found during our surgical activity led us to take the opportunity to expose anatomical variations by reviewing already published reviews. Consequently, on the basis of anatomical studies, clinical reports and imaging, as a result of careful examination of the published literature, it has been observed that the interventions in such anatomical area must take into account these variations. In particular, the most performed procedure is the lysis of the transverse carpal ligament (TCL), which is not free from complications. In our opinion it is therefore necessary, in order to avoid the complications of the nervous, vascular and tendinous sections, to use some specific technical procedures.

Arthrogenic human synovial cysts: immunohistochemical profile of interleukin-1beta, interleukin-6, tumour necrosis factor-alpha.

BACKGROUND: Synovial cysts are currently classified as degenerative lesions affecting the joint capsule or adjacent structures. MATERIALS AND METHODS: In our study we describe the results obtained in an immunohistochemical study comprising 18 patients with synovial cysts, performed to evaluate the pathophysiological role of some inflammatory cytokines such as: interleukin (IL)-1ß, IL-6 and tumour necrosis factor-alpha (TNF-α). RESULTS: Results showed an over-expression of TNF-α, IL-1ß and IL-6 which appears to be involved in the onset and progression of the disease. At the present time it is not possible to affirm that these molecules play a direct role also due to the absence of further and more specific investigations. The authors therefore hypothesize that inhibition of inflammation may have a significant role in the pathogenesis and regression of synovial cysts. CONCLUSIONS: Hence, these inflammatory cytokines may be considered potential therapeutic targets. The development of synthetic inhibitors of these inflammatory factors could lead to a reduction in the intensity of inflammation, thus inhibiting the onset and development of the disease.

On the coupling of mechanics with bioelectricity and its role in morphogenesis.

The role of endogenous bioelectricity in morphogenesis has recently been explored through the finite volume-based code BioElectric Tissue Simulation Engine. We extend this platform to electrostatic and osmotic forces due to bioelectrical ion fluxes, causing cell cluster deformation. We further account for mechanosensitive ion channels, which, gated by membrane tension, modulate ion fluxes and, ultimately, bioelectrical forces. We illustrate the potentialities of this combined model of actuation and sensing with reference to cancer progression, osmoregulation, symmetry breaking and long-range signalling. This suggests control strategies for the manipulation of cell networks in vivo.

Short-term testicular warming under anesthesia causes similar increases in testicular blood flow in Bos taurus versus Bos indicus bulls, but no apparent hypoxia.

Bull testes must be 4-5 °C below body temperature, with testicular warming more likely to cause poor-quality sperm in Bos taurus (European/British) versus Bos indicus (Indian/zebu) bulls. Despite a long-standing dogma that testicular hyperthermia causes hypoxia, we reported that increasing testicular temperature in bulls and rams enhanced testicular blood flow and O2 delivery/uptake, without hypoxia. Our objective was to determine effects of short-term testicular hyperthermia on testicular blood flow, O2 delivery and uptake and evidence of testicular hypoxia in pubertal Angus (B. taurus) and Nelore (B. indicus) bulls (nine per breed) under isoflurane anesthesia. As testes were warmed from 34 to 40 °C, there were increases (P < 0.0001, but no breed effects) in testicular blood flow (mean ± SEM, 9.59 ± 0.10 vs 17.67 ± 0.29 mL/min/100 g, respectively), O2 delivery (1.79 ± 0.06 vs 3.44 ± 0.11 mL O2/min/100 g) and O2 consumption (0.69 ± 0.07 vs 1.25 ± 0.54 mL O2/min/100 g), but no indications of testicular hypoxia. Hypotheses that: 1) both breeds increase testicular blood flow in response to testicular warming; and 2) neither breed has testicular hypoxia, were supported; however, the hypothesis that the relative increase in blood flow is greater in Angus versus Nelore was not supported. Although these were short-term increases in testicular temperature in anesthetized bulls, results did not support the long-standing dogma that increased testicular temperature does not increase testicular blood flow and an ensuing hypoxia is responsible for decreases in motile, morphologically normal and fertile sperm.

Combination of cetuximab with chemoradiation, trastuzumab or MAPK inhibitors: mechanisms of sensitisation of cervical cancer cells.

BACKGROUND: Cervical cancer (CC) annually kills 288,000 women worldwide. Unfortunately, responses to chemoradiation are partial and are of short duration. As anti-EGFR monoclonal antibodies sensitise tumours, we investigated cetuximab's toxicity plus chemoradiation on CC cells, which express different EGFR levels. METHODS: EGFR, HER2, AKT and MAPK expression and phosphorylation status were determined by western blotting. Cytotoxicity was assessed by MTT or clonogenic assays (CA) in cell lines treated with cetuximab alone or in combinations. RESULTS: Cetuximab with cisplatin and radiation achieved maximum cytotoxic effects for A431, Caski and C33A cells (high, intermediate and low EGFR expression, respectively) in CA. Cetuximab efficiently decreased MAPK and AKT phosphorylation in A431 cells but slightly less in Caski and C33A cells. To check whether further EGFR, HER2 or MAPK inhibition would improve cetuximab's cytotoxicity, we combined it with an EGFR tyrosine kinase inhibitor (TKI), trastuzumab or a MEK1/2 inhibitor (PD98059). In Caski, but not in C33A cells, cetuximab cooperated with the TKI, reducing cell survival and AKT and MAPK phosphorylation. However, cetuximab with trastuzumab or PD98059 reduced survival and MAPK phosphorylation of both cell lines. CONCLUSION: Our data suggest that cetuximab combined with chemoradiation, trastuzumab or MAPK inhibitors has useful applications for CC treatment, independently of EGFR expression.

Functional characterization of a human DNase-like protein encoded by a gene positioned in Xq28.

Xib, a gene recently reported to reside on the q28 region of the human X chromosome [Pergolizzi et al. (1996) Gene 168, 267-270], contains an open reading frame homologous to those of the DNase I family enzymes. The full open reading frame of this gene has been fused to the E. coli gene of the maltose binding protein and expressed in bacteria as a chimeric protein. The partially purified chimeric protein is enzymatically active. It introduces single and double stranded breaks into supercoiled DNA, at 30 degrees C in the absence of divalent cations and at a pH optimum of 5.2. To our knowledge this enzyme represents the first cloned human endonuclease with characteristics similar to those of acidic DNase II.

Expression patterns of ornithine decarboxylase and c-met in growing Yoshida AH-130 hepatoma.

The expression of the two proto-oncogenes ornithine decarboxylase and c-met was examined during various phases of growth of Yoshida AH-130 ascites hepatoma. Ornithine decarboxylase (ODC) and c-met mRNA levels declined progressively from day 5 (exponential growth-phase) until day 14 (quasi-stationary growth-phase). Transcription rate for both the genes remained constant between days 5 and 10, while decreasing at day 14. ODC activity was consistent with ODC mRNA level during hepatoma growth. In host liver, ODC mRNA accumulated 5 and 14 days after tumor transplantation, while c-met mRNA level was elevated until day 10 and diminished at day 14. ODC activity triplicated at day 14 in host liver. The progressive decline in the expression of ODC and c-met observed in hepatoma might be one of the mechanisms important for the control of tumor growth.

Intraneural synovial cyst of the peroneal nerve: report of two cases and review of the literature.

We report two cases of peroneal nerve compression caused by an intraneural synovial cyst and discuss the pathogenesis, clinical and electrophysiological diagnosis, and treatment of these uncommon lesions in the light of the salient published work on the subject.

Lack of TdT and immunoglobulin and T-cell receptor gene rearrangements in Hodgkin's disease.

To study the pathogenesis of Hodgkin's disease (HD), which today remains obscure, we have undertaken a combined experimental approach: determination of TdT and molecular analysis of rearrangements of immunoglobulin heavy chain (IgH), T-cell receptor (TCR) beta chain and the T-cell rearranging gamma (TRG) genes. TdT determination indicate would the presence of immature cells that are not detected in the normal lymphnode; molecular analysis of the rearrangements of these genes would reveal the presence of even a small monoclonal population of both T and B lineages in the lymphnodes. We believe that the combination of these two types of analysis can indicate whether an expanding lymphoid clone is responsible for this disease. TdT determination was negative in all 41 cases tested. Gene rearrangements were studied in 10 cases for IgH and TCR beta genes and in 5 cases for the TRG gene. No abnormal band beside the germ-line ones was detected in any of our cases, ruling out the presence of a minor neoplastic population. We can explain these results in at least three ways: first, the neoplastic population could represent less than 1% of the total, thus escaping detection by current techniques; second, the neoplastic population is not lymphoid in nature or is composed of mature cells that do not rearrange Ig and TCR genes and therefore belongs to a true non-B, non-T lineage; third, the pathogenesis of HD is completely different from that of non-Hodgkin's lymphomas (NHL) and does not involve the clonal expansion of a cell frozen at a particular maturative stage as is thought to happen in most NHL.

Primary intracranial lymphomas.

We present 20 cases of primary intracranial lymphoma and review the most important published series on this subject. The clinical patterns and the differential diagnosis from other intracranial space-occupying lesions on the CT and angiographic evidence are discussed. Surgical treatment was given in 19 of our cases, followed in 17 cases by radiotherapy and in 4 by chemotherapy. One patient was treated by a ventriculo-peritoneal shunt. The effectiveness of the various modalities of treatment is discussed in the light of survival.

Intramedullary subependymoma of the cervical spinal cord.

The authors report a rare case of intramedullary subependymoma of the spinal cord. The case is discussed and a review of the literature is presented.

Prolonged stabilization of multiple and single brain metastases from breast cancer with tamoxifen. Report of three cases.

Cancer frequently metastasizes to the brain, and such lesions, whether multiple or solitary, have a poor prognosis, despite all efforts to treat them. There have been recent sporadic reports of brain metastases from breast cancer responding for some years to antiestrogens (particularly tamoxifen) or bromocriptine. We report three cases of brain metastasis from cancer--two multiple and one a solitary lesion. The long survival of the patients--two for 5 years and one for 6 years, with more than an acceptable quality of life - should prompt therapeutic trials to test tamoxifen and designed to assess its effects on a sizable number of patients.

Interaction of heat with chemotherapy in vitro: effect on cell viability and protein synthesis in human and murine cell lines.

Cell survival in response to doxorubicin (Dx) and cis-diammine-dichloroplatinum (cis-Pt) administration, either alone or combined with hyperthermic treatment, was analyzed in human osteosarcoma (U-2-OS), murine melanoma (B16V) and murine leukemia (P388) cell lines and in Dx-resistant sublines derived from B16V and P388. In all cell lines tested there was an enhancement of drug toxicity by hyperthermia. In U-2-OS, the increase was more pronounced for cis-Pt than for Dx. In B16V and in P388, the increase in Dx toxicity was of the same degree in Dx-sensitive and Dx-resistant sublines, whereas heat-induced sensitization to cis-Pt was higher in Dx-resistant sublines than in their Dx-sensitive counterpart. Analysis of the protein pattern in the various cell lines showed that the synthesis of heat-shock proteins induced by heat was not influenced by the combined use of drugs and heat. Moreover, in spite of some differences in the overall protein pattern, no significant differences in the basal levels of heat-shock protein synthesis or in the extent of its induction after heat shock were observed between murine cell lines relatively sensitive to Dx and their corresponding selected resistant cells.

Constitutive and induced synthesis of heat shock proteins in transplantable hepatomas.

The synthesis of heat shock proteins (HSP) was studied in rat liver and in a series of transplantable Morris hepatomas with different growth rates, subjected to heat shock in vivo and in vitro. Different from the liver, hepatomas synthesized HSP constitutively, i.e., also before exposure to heat. This constitutive synthesis was low and limited to one HSP in the slowest-growing tumor, more marked and involving other HSP in the intermediate- and fast-growing hepatomas. In tumor that synthesized HSP constitutively, the induction of HSP in response to heat was proportionately reduced. These patterns of reaction were essentially similar in vivo ad in vitro. The amount of HSP 68 was well correlated to the levels of its mRNA in liver and in all hepatomas, whereas the increase in HSP 89 was accompanied by a corresponding increase in the related mRNA in liver and in slow-growing hepatoma, not in the other tumors, thus suggesting a different mechanism of control of HSP 89 synthesis in the more malignant hepatomas.

Differential expression of c-jun, c-fos and hsp 70 mRNAs after folic acid and ischemia-reperfusion injury: effect of antioxidant treatment.

The regenerative repair response to folic acid and ischemia-reperfusion injury is characterized by different patterns of renal tubular cell proliferation. The purpose of this study was to examine the time course of the expression of two early growth response genes, c-jun and c-fos, and of the stress response gene hsp70 after such renal injuries and to determine the role played by reactive oxygen species generated during reperfusion, on gene induction. Ischemic injury caused an almost immediate increase of c-jun, c-fos and hsp70 mRNA expression, that reached a maximum at 1 h of reperfusion. Folic acid treatment increased c-fos and hsp70 mRNAs at 2 h, while c-jun accumulated at 1 h, although to a lesser extent. The intravenous administration of two antioxidant drugs, allopurinol or dimethyl sulfoxide (DMSO), 20 min before ischemia, to prevent the generation of oxygen free radicals during reperfusion, did not cause any change in gene expression. In contrast, the combined administration of allopurinol and DMSO reduced c-jun and c-fos mRNA expression as well as tubular cell damage at 1 h of reperfusion, although not at earlier times while hsp70 mRNA expression remained almost unchanged. Taken together, the results suggest that these scavengers, by reducing reactive oxygen species and renal damage during reperfusion, may affect the expression and/or persistence of transcripts involved in the control of epithelial cell proliferation.

eIF-2 initiation factor activity in Yoshida ascites hepatoma AH 130 cells and in 4-dimethylaminoazobenzene-induced liver tumor tissue during growth.

Eukaryotic initiation factor 2 (eIF-2) preparations from mid-log and plateau-phase Yoshida ascites hepatoma AH 130 cells, from the liver of Yoshida ascites tumor-bearing rats and from 4-dimethylaminoazobenzene (DAB)-induced liver tumor tissue were assayed for ternary complex formation with 3H-met-tRNAf and GTP on nitrocellulose filters. The eIF-2 factor was extracted from postnuclear homogenate supernatants by high-salt wash and purified by ion exchange chromatography on DEAE-cellulose and phosphocellulose. The results here reported demonstrate changes of 3H-met-tRNAf X eIF-2 X GTP ternary complex formation under the conditions studied. Higher rates of ternary complex formation are present in control rat liver and in DAB-induced liver tumor tissue. The liver of Yoshida ascites tumor-bearing rats and the Yoshida ascites hepatoma cells show reduced rates of ternary complex formation, that are mostly evident at the plateau-phase of the intraperitoneal ascites cell growth. The present observations may be attributable to changes in the growing conditions of plateau-phase ascites cells, with accumulation in Gl phase, affecting the ability of eIF-2 to enter in the sequential assembly of the eukaryotic protein synthesis initiation complex.

Polyamine acetylations in normal and neoplastic growth processes.

The expression patterns of cytosolic and nuclear polyamine acetyltransferases were studied in normal and neoplastic growth processesin vivo andin vitro to evidentiate the roles played by these enzymes in cell proliferation. In regenerating liver, cytosolic spermidine/spermine N(1)-acetyltransferase showed similar augments of mRNA level and enzymatic activity during the prereplicative period (4-8 h), whereas spermidine N(8)-acetyltransferase activity increased later (24 h) when DNA synthesis was maximally enhanced. In fibroblasts continuously dividing, the messenger for spermidine/spermine N(1)-acetyltransferase rapidly accumulated after serum-stimulation. In cultured Morris hepatoma cells stimulated to logarithmic growth, spermidine N(8)-acetyltransferase activity remained at plateau for 1 day declining thereafter, while spermidine/spermine N(1)-acetyltransferase activity immediately decreased. In Yoshida AH-130 hepatoma cells transplanted in rat peritoneum, spermidine N(8)-acetyltransferase and spermidine/spermine N(1)-acetyltransferase activities rose, respectively, in concomitance with elevated proliferation-rate and quasi-stationary phase of growth. Since the expression of cytosolic and nuclear acetyltransferases underwent different temporal activation, an involvement of these enzymes in separate metabolic processes controlling normal and neoplastic growth may be suggested.

Expression of spermidine/spermine N1-acetyltransferase in growing Yoshida AH-130 hepatoma cells.

Activity and messenger RNA levels of spermidine/spermine N1-acetyltransferase, the rate-limiting enzyme of the polyamine interconversion pathway, were investigated in host liver and in Yoshida AH-130 ascites hepatoma cells as a function of tumor growth phases. Enzyme activity reached maximal values at day 10 in host liver (2.0-fold increase) and at days 10 and 14 in hepatoma cells (4.2- and 5.4-fold increases)--that is, when the cellular growth was nearly arrested. At day 10 the messenger RNA levels of spermidine/spermine N1-acetyltransferase were augmented concomitantly; they were about two and four times higher, respectively, in host liver and tumor cells than in control liver. The in vitro transcription rate seemed to be constant during hepatoma cell growth. Treatment of the animals with N1,N2-bis-(2,3-butadienyl)-1,4-butanediamine (MDL 72527), a specific inhibitor of polyamine oxidase, caused large accumulation of N1-acetylspermidine in hepatoma cells and in the ascitic fluid; the maximal values were reached at day 14. The levels of putrescine in inhibitor-treated rats decreased in hepatoma cells (day 5) and in ascitic fluid (days 5 and 14), whereas values of spermidine and spermine remained unchanged. The proposed role for spermidine/spermine N1-acetyltransferase-enhanced expression is to regulate the cellular polyamine pool by causing their excretion as acetylderivatives from tumor cells into the ascitic fluid, even if putrescine seems also to be excreted. Eventual repeat uptake of putrescine by hepatoma cells could contribute to the control of cellular polyamine levels.

[Acute cerebral multiple sclerosis: importance of a multiple diagnostic approach. Clinical case]. / Sclerosi multipla cerebrale acuta: importanza di un approccio diagnostico multiplo. Caso clinico.

The Authors report a case of acute, apoplectiform, multiple sclerosis, with right hemiparesis and severe motor dysphasia. The way undertaken to arrive to the diagnosis of demyelinating disease is discussed, with special attention to the importance of a multiple diagnostic approach, analysing the sensitivity and the limits of the instrumental methods actually available.