Parietal interhemispheric transfalcine transtentorial approach for posterior incisural space lesions: from the lab to the operative room.

The operative approach to the posterior incisural space is challenging because of its deep location, the surrounding eloquent areas, and the intimate relationship with the deep veins. Several approaches have been proposed to manage the lesions in this region: supratentorial, infratentorial and a combination of them. Brain retraction, injury to the occipital lobe and corpus callosum, and venous bleeding are the principle drawbacks of these routes. We performed anatomical dissection study using 10 embalmed human cadaver specimens injected with colored latex exploring a different route, parietal interhemispheric transfalcine transtentorial (PITT). Then we used a PITT approach on two patients with posterior incisural space (PIS) lesions. The PITT approach led to successful and safe complete removal of PIS lesions in our cases. No complications were reported. The present approach could be a valuable option in case of PIS lesions, especially those associated with downward displacement of the deep venous complex; thanks to the gravity it reduce the complications related to the occipital lobe retraction and manipulation. Moreover, cutting the superior-anterior edge of the tentorium, the sub-tentorial space could be reached.

Spontaneous regression of calcified thoracic herniations: Can Hounsfield-units radiodensity have a predictive value?

INTRODUCTION: Spontaneous regressions of calcified thoracic disc herniations (TDH) have been rarely described. Since now, no previous papers hypothesized that radiological factors could be able to predict the evolution of the herniation. This study shows that the radiodensity of the herniated material in herniations with spontaneous resolution might differ from that of operated herniations. METHODS: This is a retrospective study. A cohort of patients that underwent surgical removal of a calcified thoracic disc herniation has been compared to two cases conservatively treated and a case with spontaneous regression. CT scans were evaluated to compute the average radiodensity [in Hounsfield units (HU)] of the calcified components of the herniations. All the slices of the CT scans involving the calcification were evaluated in their axial images and in their coronal and sagittal reformations. Comparison of the slices radiodensity (spontaneously resolved versus surgically treated) was performed with the unpaired Student's t test. RESULTS: The mean density of calcification in the case with spontaneous regression was found to be 454 HU. In the control group of surgical cases observed, and the conservatively treated cases, the mean HU density showed higher values (respectively, 827 and 853 HU) (p < 0.01). CONCLUSION: Qualitative differences between calcified TDH that resolve spontaneously or need surgical treatment might be shown by differences of radiodensity. This comparative study, in spite of the limitations due to small numbers, provides a new insight in the interpretation of the phenomenon of spontaneous resolution of calcified TDH. These slides can be retrieved under Electronic Supplementary Material.

Neurological outcomes after surgery for spinal metastases in symptomatic patients: Does the type of decompression play a role? A comparison between different strategies in a 10-year experience.

INTRODUCTION: The impact of neurological deficits plays a role of inestimable importance in patients with a neoplastic disease. The role of surgery for the management of symptomatic spinal cord compression (SSCC) cannot be overemphasized, as surgery represents often the first and paramount step in patients presenting with motor deficits. The traditional paradigm of simple bilateral laminectomy for the treatment of spinal cord compression has been reviewed. The need to achieve a proper circumferential decompression of the spinal sac has been progressively highlighted in combination with the development of the more comprehensive and multidisciplinary concept of separation surgery. OBJECTIVE: The aim of this paper is to analyze different strategies of decompression, while evaluating whether circumferential/anterior decompression is able to guarantee a better control and restoration of neurological functions in patients with motor impairment, if compared to traditional posterior decompression. MATERIALS AND METHODS: This is a retrospective observational study investigating symptomatic patients that underwent surgical treatment for spinal metastases at author's Institutions from January 2010 to June 2019. Data recorded concerned patient demographics, tumor histology, peri-operative and follow-up neurological status (ASIA), ambulation ability, stability (SINS), grade (ESCC) and source of epidural compression and type of decompression (anterior/anterior-lateral (AD); posterior/posterior-lateral (PD/PDL); circumferential (CD)). RESULTS: A total number of 84 patients was included. AD/CD patients showed higher chance of neurological improvement and reduced rates of worsening compared to PD/PLD group (94.1%/100% vs 60.4%; 11.8% vs 45.8% respectively). Univariate logistic regression identified immediate post-operative improvement to be a significative protective factor for worsening at last follow-up. Stratifying patients for site of compression and considering anterior and circumferential groups, immediate post-operative neurological improvement, was mostly associated with AD and CD (p 0.011 and 0.025 respectively). Walking at last follow up was influenced by post-operative maintenance of ambulation (p 0.001). CONCLUSION: The necessity to remove the epidural metastatic compression from its source should be considered of paramount importance. Since the majority of spinal cord compression involves firstly the ventral part of the sac, CD/AD are associated with better neurological outcomes and should be achieved in case of circumferential or anterior/anterolateral compression.

Trans-sulcal versus trans-parenchymal approach in supratentorial cavernomas. A multicentric experience.

OBJECTIVES: Cavernous malformations (CM) are low-flow vascular lesions that can cause significant symptoms and neurological deficits. Different intraoperative surgical approaches have been developed. Aim of the present investigation is the comparison between the trans-sulcal approach (TS) and the trans-parenchymal neuronavigation-assisted approach (TPN) in a surgical series from two neurosurgical centers. The technique and clinical outcomes are discussed, with a specific focus on seizure outcome. PATIENTS AND METHODS: Clinical and radiological data from two neurosurgical centers ("A. Gemelli" Hospital in Rome and A.O.U. Città della Salute e della Scienza in Turin) were retrospectively reviewed in order to evaluate the different outcome of TS and TPN approach for cavernous malformation treatment. RESULTS: A total of 177 patients underwent surgical intervention for supratentorial CM, 130 patients with TPN approach and 47 with TS approach. TS approach was associated with higher rate of seizure in early post-operative period both in epileptic patients (p < 0,001) and in patients without history of seizures before surgery (p = 0,002). Moreover, length of incision (p < 0,001), area of craniotomy (p < 0,001) and corticectomy (p < 0,001) were bigger in TS than in TPN approach. Brain contusion (p < 0,001) and fluid collection (p < 0,001) were more likely to be discovered after TS approach. CONCLUSIONS: TPN is a valuable approach for resection of CM. Minor complications are significantly lower in TPN approach when compared with TS approach. In addition, it is associated with lower rate of early post-operative seizure and shorter length of stay.

Inhibition of interferon-gamma may suppress allograft reactivity by T lymphocytes in vitro and in vivo.

The addition to mixed-leukocyte reactions of monoclonal antibodies to interferon-gamma abrogated alloantigen recognition and induction of cytotoxic T lymphocytes by inducing early and highly effective suppressor T lymphocytes. This inhibitory activity was not confined to in vitro models, since daily injection of the antibodies into CBA/J mice blocked the usual rejection of allogenic tumor cells.

Quality of life in renal transplant patients over 60 years of age.

Kidney transplantation not only drastically improves the life-expectancy of hemodialyzed patients, but it also affords psychological and social advantages with improvements in short- and long-term personal and working lives. Quality of life (QoL) is one of the parameters of psychological well-being. There is an improvement of QoL from pre- to posttransplant, but it is not to the level of healthy samples. The aim of this study was to examine QoL in older renal transplant recipients. All recipients older than age 60 were included, with a minimum follow-up of 12 months. To measure QoL, the nationally standardized ShortForm-36 (SF-36) questionnaire was administered. The SF-36 responses by our patients were compared with national age- and gender-appropriate norms, and also between genders. The enrolled population included 19 women (36.5%) and 33 men (63.5%), with a mean age of 66.8 years (range, 60-73 years). Enrolled women reported significant limitations compared to gender- and age-matched norms in social activities (42.11 vs 70.58), perception of pain (22.11 vs 59.17), and general health perception (39.58 vs 48.69). Enrolled men reported significant limitations compared to gender- and age-matched norms in social activities (46.59 vs 78.35), perception of pain (18.18 vs 73.62), psycho-physical energy (50.15 vs 67.88), and general health perception (37.33 vs 61.66). No significant differences were noted between the genders. This study clearly showed how the psychological state was not as good as the clinico-physical recovery following renal transplantation in older recipients.

Analysis of murine interferon-gamma binding to its receptor on intact cells and solubilized membranes. Identification of an 80 kDa receptor.

The receptor for murine-interferon-gamma (Mu-IFN-gamma) has been characterized for its molecular size and equilibrium binding constant on a thymoma cell line, EL-4. Binding of 125I-IFN-gamma to intact cells and their solubilized membranes has shown a single class of receptor with Kd values of 1.9 x 10(-9) M and 1.3 x 10(-8) M, respectively. It was shown that solubilization of the Mu-IFN-gamma receptor with a Zwitterionic detergent (Chaps) preserves its binding activity. A direct comparison of the molecular mass of the Mu-IFN-gamma receptor on intact cells versus detergent-solubilized membranes was performed using a radiolabeled photoactivated crosslinking reagent and direct hybridization with 125I-labeled IFN-gamma on Western blots of solubilized receptor. The results indicate that both types of receptors have an identical molecular mass of approximately 80 kDa.

The murine IFN-gamma receptor does not transduce the activation signal to a murine promoter in human cells.

MuIFN-gamma receptor cDNA has been stably transfected in the human WISH cell line. A stable transfectant, denominated WISH-C2, expressed 46;000 receptors/cell whose affinity was similar to that observed on murine cells (Kd = 2.6 x 10(-9) M). When WISH-C2 cells were treated with Hu- or MuIFN-gamma, antiviral and antiproliferative activities were observed with HuIFN-gamma only. These findings suggest that other species-specific components associated to the binding site are required for the signal transduction. To overcome the complexity of measuring biological functions that very likely involve more than one regulatory and structural gene, we set up for the first time a system where a reporter gene driven by a murine promoter was used to directly evaluate the interaction of MuIFN-gamma receptor with an inducible promoter through the missing transducer factor.

Treatment of proteinuric patients with a vegetarian soy diet and fish oil.

Our aim was to determine whether a longer period of treatment with a vegetarian soy diet with addition of fish oil supplements would accentuate the beneficial effects on hyperlipidemia and proteinuria of nephrotic patients we found in a previous study. After an 8-week baseline period on free diet, patients were randomly allocated either on soy diet alone (SD) or to SD plus 5 g/day of fish oil (SD + FO) orally for two months. Then they crossed over to the other treatment for two additional months. They finally resumed eating the free diet for 3 months. We selected 20 outpatients with chronic glomerulonephritis, proteinuria in the nephrotic range, fasting serum cholesterol > 250 mg/dl, mean serum creatinine concentrations 1.75 +/- 0.23 mg/dl. Serum lipid profile, urinary protein loss and nutritional parameters were monitored. With the soy diet, we obtained a significant decrease both of hyperlipidemia and of proteinuria. The effect of the soy diet on proteinuria increased over the 4 months. The addition of a moderate amount (5 g/day) of fish oil in a randomized cross-over design had no further beneficial effect. Stability of serum albumin, transferrin and the body mass index documented good nutritional status. In conclusion, the dietary manipulation with our vegetarian soy diet confirmed the beneficial effects on hyperlipidemia and proteinuria of nephrotic patients. Such effects persisted and even ameliorated after 4 months of diet. The addition of moderate oral supplements of fish oil did not potentiate the beneficial effect.

A method for the rapid detection of streptococcal group A antigen by specific monoclonal antibody.

In this study we evaluate the efficacy of a method for the rapid detection of group A streptococci employing a hybridoma mouse antibody specific against group A streptococcal carbohydrate. Using coagglutination technique we demonstrated an absolute specificity. The sensitivity was absolute if the preparation contained greater than or equal to 5 X 10(4) cocci. This test seems therefore a valid criterion for symptomatic patients with a larger number of group A streptococci in throat specimens, more sensitive than other methods, but not sensitive enough for carriers of few bacteria.

Binding of murine 125I-labelled natural interferon-gamma to murine cell receptors.

Natural murine interferon-gamma (naMuIFN-gamma) produced by T-lymphoma cells (L12-R4) stimulated with phorbol myristic acetate was purified by use of an anti-MuIFN-gamma immunoadsorbent and was labelled with 125I to study its binding to murine cell receptors. All the cell lines examined bound naMuIFN-gamma, although the binding affinity varied considerably. By adding increasing concentrations of unlabelled naMuIFN-gamma in competition binding assays we determined dissociation constants (KD) of 8.2 X 10(-10) and 7.4 X 10(-10) M for L1210 and TS/A cells, respectively, and of 6.5 X 10(-9)M for L-929 cells. The numbers of receptors present per cell of these lines were 3000, 1000 2000 respectively. Highly purified naMuIFN-gamma as well as recombinant MuIFN-gamma competed for binding sites with 125I-labelled IFN-gamma on L1210 cells, although the latter displayed a KD greater than the former (5.8 X 10(-9) M compared to 8.2 X 10(-10) M). Moreover, protease, but not endoglycosidase, treatment of target cells prevented the subsequent binding of 125I-labelled IFN-gamma, suggesting that a protein moiety is involved in the binding of the ligand. These studies demonstrate that naMuIFN-gamma binds in a specific manner and with high affinity to murine cell receptors.

Production of polyclonal antibodies against the cellular IFN-gamma receptor.

In this work we consider the possibility to produce a polyclonal antibody against murine interferon gamma receptors by immunizing rabbits with the complex receptor-IFN-gamma immunoprecipitated by a monoclonal antibody (AN-18) recognising the ligand bound to the receptor. Using the Western Blotting technique it has been found a polyclonal serum directed against a protein (90 kDa) that could represent the murine IFN-gamma membrane receptor.

Activation of protein kinase C down-regulates IFN-gamma receptors.

Treatment of mouse EL-4 cells with intracellular activators of protein kinase C, namely 4-phorbol 12-myristate 13-acetate (PMA) and diacylglycerol, resulted in 90% reduction in cell surface interferon-gamma (IFN-gamma) receptors as judged by iodinated-IFN-gamma binding. This did not seem to be due to a decreased in the receptor affinity, since that of the remaining surface receptors appeared to be significantly increased as shown in Scatchard plot analysis. Kinetics experiments revealed that a PMA treatment as short as 15 min was sufficient to induce a decrease of 30% of IFN-gamma receptors, whereas the highest levels of down-regulation were observed after 60-90 min. Treatment of EL-4 cells with calcium ionophore, A23187, although ineffective by itself, dramatically increased the ability of suboptimal PMA concentrations to mediate IFN-gamma receptor down-regulation. Finally, specificity studies revealed that PMA is particularly effective in decreasing the binding of IFN-gamma to T-lymphocytes. Altogether these results suggest a possible involvement of protein kinase C in the regulation of IFN-gamma receptor expression.

[Increase of fibronectin-dependent phagocytosis by immune interferon of the mouse]. / Aumento della fagocitosi fibronectina-dipendente da parte dell'interferon immune di topo.

In the present study we have investigated the capability of IFN-gamma to increase the Mac fibronectin-dependent phagocytosis. We demonstrate that IFN-gamma (50 U/ml) induces an increase of phagocytosis by elicited (PP-Mac), but not by normal Mac (R-Mac) when latex-beads particles are coated with gelatin.

Natural macrophage cytotoxicity against Trichomonas vaginalis is mediated by soluble lytic factors.

Mechanisms of lysis of the extracellular protozoan Trichomonas vaginalis by uninduced resident macrophages were analyzed. Supernatants obtained by culturing such macrophages with T. vaginalis were cytotoxic for the protozoa in a dose-dependent manner. Supernatants from macrophages cultured alone were cytotoxic at lower levels, whereas those obtained from T. vaginalis alone and from macrophages cultured with unrelated cells (B77) were not cytotoxic. Cytotoxic activity appeared after 4 h of contact between effectors and target cells and reached a plateau at 18 to 24 h. Microtubule disrupting agents (colchicine and vinblastine) enhanced protozoan lysis, whereas cytochalasin B, an inhibitor of microfilaments, completely blocked T. vaginalis lysis. Treatment of macrophages with protein synthesis inhibitors (cycloheximide and puromycin) impaired effector cytotoxicity. Lytic activity remained after dialysis of supernatants, treatment with 10% bovine fetal serum, and treatment at 56 degrees C for 1 h, but it was completely prevented by treatment at 90 degrees C for 10 min. In conclusion, our data show that natural cytotoxicity against T. vaginalis is performed by normal resident macrophages through the release of at least two heterogeneous soluble factors.

[Analysis of the gamma interferon receptor in mice]. / Analisi del recettore per l'interferon gamma murino.

Natural murine interferon-gamma (IFN-gamma) produced by the T lymphoma, L12R4, stimulated with phorbol myristic acetate was purified by anti-murine IFN-gamma immunoadsorbent and labeled with 125I to study its binding to receptors of mouse cells. By adding increasing concentrations of unlabeled natural murine IFN-gamma in competition binding assays we determined a KD of 8.2 X 10(-10) M for L1210 cells and a number of receptors of about 3000. Moreover protease, but not endoglycosidase treatment of target cells prevented the subsequent binding of the ligand. These studies demonstrate that natural murine IFN-gamma binds in a specific manner and with high affinity to receptors on murine cell lines.

Mouse gamma interferon produced by a cloned T-cell lymphoma. I. Purification and physicochemical characterization.

Mouse gamma interferon (IFN-gamma) was produced from a cloned T-cell lymphoma, L12-R4, stimulated with phorbol myristic acetate (PMA) at a concentration of 2 X 10(-7) M/ml. Absorption of crude IFN-gamma on silicic acid resulted in a 100-fold concentration and 10-fold purification. After application of this IFN-gamma to a Sephacryl S-200 column, 100% of the IFN activity was recovered in fractions containing molecular weights of 40 kD. When this material was applied to a Con A-Sepharose column, IFN activity was completely eluted with a linear gradient of alpha-methyl-mannoside. The specific activity of the recovered IFN-gamma was about 3.6 X 10(6) mg/ml of protein with 11,390-fold purification. Further investigations with Phenyl-Sepharose CL-4B and Chromatofocusing revealed that L12-R4 IFN-gamma is highly hydrophobic and has a pI around 5.4. Thus, by different types of chromatography procedures, L12-R4 IFN-gamma was found to be highly homogeneous with physicochemical properties similar to those produced by normal T-lymphocytes.

[Production of anti-idiotypic monoclonal antibodies that recognize the receptor for murine gamma interferon]. / Produzione di anticorpi monoclonali anti idiotipo che riconoscono il recettore per l'interferon gamma murino.

In this work we consider the possibility to produce a monoclonal antibody against murine interferon gamma receptor using an approach based on the anti-idiotypic network theory of Jerne. We have found a rat monoclonal antibody (C-28) directed against the combining site of AN-18, a rat monoclonal antibody neutralizing murine interferon gamma activity, that is able to bind interferon receptor.

[Effect of gamma-interferon on the adherence of streptococci to different murine cell lines]. / Effetto dell'interferon-gamma sull'aderenza degli streptococchi a differenti linee cellulari murine.

In the present study we analyze IFN-gamma capability to modulate bacterial adherence of group A Streptococci to murine cells such as fibroblast (L-929) or phagocytic cells (P 388 and PP-induced macrophages). IFN-gamma increases adherence of Streptococci to macrophages but not to L-929 cells. This finding could have important implication for the "in vivo" adhesion of bacteria to phagocytic cells.