Plasma levels and vascular effects of vasopressin in patients undergoing coronary artery bypass grafting.

OBJECTIVE: Recent studies have suggested that endogenous vasopressin (AVP) acts as a spasmogen during coronary artery bypass grafting (CABG). Given that AVP could induce vasospasm in the grafted vessel, we assessed the release of this peptide during and after CABG, and explored ways of counteracting its contractile effect on the internal mammary artery (IMA). METHODS: Plasma levels of AVP were determined by radioimmunoassay in 16 patients before, during and after CABG. Using isometric force recording techniques, we also investigated the mechanisms involved in the contractile effect of AVP in ring preparations of IMA specimens taken from 95 patients. RESULTS: Plasma AVP levels peaked after the start of cardiopulmonary bypass (CPB) and correlated well with serum osmolality (Pearson's r=0.9490; P<0.0001; n=16). An inverse correlation was observed between plasma AVP levels recorded at this stage and the maximal contraction induced in vitro by AVP in vascular rings from the same patients (Pearson's r=-0.6968; P<0.01; n=16). No change in the AVP response was produced by endothelium removal, exposure to the NO precursor (3 x 10(-4)M L-arginine), inhibition of nitric oxide (NO) synthase (3 x 10(-5) M L-NAME) or soluble guanylate cyclase (3 x 10(-6) M 1H-[1,2,4]oxadiazol [4,3,-alpha]quinoxalin-1-one (ODQ)), removal of the superoxide anion (100 U/ml superoxide dismutase (SOD) plus 1200 U/ml catalase) or hydroxyl radical (10(-4) M deferoxamine), or specific alpha1 - (10(-6) M prazosin) or endothelin (10(-5) M bosentan) receptor antagonism. In contrast, adenylate cyclase activation (3 x 10(-8) M forskolin) reduced the contractile response to AVP, while prostanoid synthesis (3 x 10(-6) M indomethacin) inhibition and blockade of Ca2+ -activated potassium channels (KCa) (10(-3) M tetraethylammonium (TEA)) enhanced AVP contraction. Age, gender and smoking also modified the AVP response. CONCLUSION: Our findings suggest a role for AVP as a modulator of vascular tone in human IMA. The effect of AVP is dependent on prostanoids and Ca2+ -activated K+ channels, so its dysfunction in pathophysiological cardiovascular processes could mean that AVP, among other factors, produces vasospasm in IMA grafts.     

Intrathecal synthesis of anti-myelin basic protein IgG in HIV-1+ patients

Human immunodeficiency virus type 1 (HIV-1)-infected individuals frequently develop a broad spectrum of neurological syndromes, classified as HIV-1-associated cognitive/motor complex. Diffuse demyelination of hemispheric white matter is a commonly observed in HIV-1 infected brain, but the events leading to myelin destruction are still obscure. Since oligodendrocyte infection by HIV-1 is not proven as yet, myelin damage in HIV-1 infection may result from indirect mechanisms such as the excessive release of myelinotoxic substances or the triggering of autoimmune responses directed to myelin constituents. To verify the latter hypothesis, we searched for elevated anti-myelin basic protein (MBP) IgG levels in the cerebrospinal fluid (CSF) and serum of 25 patients with HIV-1 infection, 12 with multiple sclerosis (MS), and 9 with non-inflammatory neurological diseases (NIND). CSF, but not serum, anti-MBP IgG levels were more frequently elevated in HIV-1⁺ (16/25, 64%) than in MS (3/12, 25%) or NIND (0/9) patients. By using the anti-MBP IgG index, the anti-MBP IgG antibody specificity index (ASI), and the search for anti-MBP oligoclonal IgG, we ascertained that anti-MBP IgG were produced within the CNS in 13 of 25 (52%) HIV-1⁺, in 6 of 12 (50%) MS, and in none of NIND patients. The incidence of increased CSF anti-MBP IgG levels was higher among HIV-1⁺ patients at stage II–III (4/4, 100%) or at stage IV B (7/9, 78%) than among those at stage IV C–IV D (5/12, 42%). Although our data indicate that intrathecal anti-MBP IgG may occur early during HIV-1 infection and that they are more common in patients with HIV-1-associated cognitive/motor complex, the possible demyelinating role of these antibodies remains to be demonstrated.     

Analysis of aberrant somatic hypermutation (SHM) in non-Hodgkin's lymphomas of patients with chronic HCV infection

Hepatitis C virus (HCV) and aberrant somatic hypermutation (SHM) have each been suggested to contribute to the development of B-cell non-Hodgkin's lymphoma (NHL). The incidence of PIM-1, PAX-5, RhoH/TTF, and c-MYC mutations in tumour biopsy specimens from 32 HCV-infected B-cell NHL patients was analysed to determine whether the extent of aberrant SHM among these patients differed from that previously reported for HCV-negative B-cell NHL patients. Mutation of PIM-1, PAX-5, RhoH/TTF, and c-MYC was detected in 4 (13%), 5 (16%), 4 (13%), and 4 (13%) of 32 samples, respectively. In HCV-positive B-cell NHL patients, the frequency of aberrant SHM was lower than that already found in HCV-negative B-cell NHL patients. This indicates that, unlike B-cell lymphomas from HCV-negative patients, aberrant SHM may not contribute significantly to malignant transformation in HCV-associated B-cell lymphomas.     

Co-expression of Epstein-Barr virus latent membrane protein and vimentin in “aggressive” histological subtypes of Hodgkin's disease

Summary The presence of Epstein-Barr virus (EBV) genome in Hodgkin's and Reed-Sternberg (HRS) cells, as detected using in situ hybridization (ISH) with biotinylatedBamHI V probes, along with the expression of EBV-encoded latent membrane protein (LMP) and vimentin was examined in paraffin-embedded sections of 39 immunomorphologically characterized cases of Hodgkin's disease (HD). ISH demonstrated EBV in HRS cells in 15 of 39 cases, whereas LMP expression was detected in 11 of 39 cases, only in the presence of EBV genome detection. With the exception of 1 case, in which HRS cells expressed B-cell-associated antigens, the LMP-positive cases included specimens in which HRS cells were of non-B, non-T phenotype. LMP expression showed a stronger association with lymphocyte depletion (LD) (3/3) and mixed cellularity (MC) (6/11) than with lymphocyte predominance (0/5) or nodular sclerosis (2/20) subtypes. Vimentin expression on HRS cells was found in all the LMP-expressing cases and only in a fraction (13/28) of LMP-negative cases. This study supports the view that HD represents a heterogeneous group of diseases also in terms of EBV association, LMP expression being strongly related to the aggressive LD and MC histological subtypes. In light of the supposed interactions between vimentin and LMP, their coexpression on HRS cells, as detected in this study, provides further evidence for a significant role of EBV in the development of a proportion of HD cases.     

Mapping of MRX81 in Xp11.2-Xq12 suggests the presence of a new gene involved in nonspecific X-linked mental retardation

X-linked nonspecific mental retardation (MRX) accounts for approximately 25% of mental retardation in males. A number of MRX loci have been mapped on the X chromosome, reflecting the complexity of gene action in central nervous system (CNS) specification and function. Eleven MRX genes have been identified, but many other causative loci remain to be refined to the single gene level. In 21 MRX families, the causative gene is located in the pericentromeric region; and we report here the identification by linkage analysis of a further such locus, MRX81. The new MRX locus was identified by two- and multi-point parametric analysis carried out on a large Italian family. Tight linkage of MRX81 to DNA markers ALAS2, DXS991, and DXS7132 was observed with a maximum LOD score of 3.43. Haplotype construction delineates an MRX81 critical region of 8 cM, the smallest MRX pericentromeric interval so far described, between DXS1039 and DXS1216, and placing it in Xp11.2-Xq12. So far, automated sequencing of two candidates in the region, the MRX gene oligophrenin (OPHN1) and the brain-specific ephrinB1 (EFNB1) gene, in DNA from affected males excluded their candidacy for MRX81, suggesting a novel disease gene.     

CD10 is expressed in a subset of chromophobe renal cell carcinomas.

CD10 has been considered a useful marker in the diagnosis of renal carcinomas, because of its expression in clear cell and papillary renal cell carcinomas and its absence in chromophobe renal cell carcinomas. On the other hand, chromophobe renal cell carcinoma expresses parvalbumin, which is absent in clear cell and papillary renal cell carcinomas. To further address the relevance of these markers, we studied the expression of CD10 and parvalbumin in 42 samples of chromophobe renal cell carcinoma (seven of which had aggressive features, including invasion beyond the renal capsule, renal vein invasion, metastases, or sarcomatoid transformation), 75 clear cell renal cell carcinomas (eight metastatic) and 51 papillary renal cell carcinomas (two metastatic). CD10 was found in 100% of clear cell renal cell carcinomas, 63% of papillary renal cell carcinomas and in all metastatic cases of both types. At variance with previous studies, we found CD10 expression in from 30 to 90% of the neoplastic cells, in 11 of 42 (26%) chromophobe renal cell carcinomas. The CD10-positive cases included five of the seven (71%) chromophobe renal cell carcinoma with aggressive features. Statistical analysis showed significant association of CD10-positive tumors with clinicopathologic aggressiveness (P=0.003) and mitotic figures (P=0.04). Parvalbumin was strongly expressed in all primary and metastatic chromophobe renal cell carcinomas. Western blot analysis was utilized to confirm the expression of both CD10 and parvalbumin in chromophobe renal cell carcinomas.     

Dendritic reticulum cell-related immunostaining for laminin in follicular and diffuse B-cell lymphomas

Summary We performed a comparative immunohisto-cytochemical study of the distribution patterns of laminin and follicular dendritic reticulum cells (DRCs) within their follicular microenvironment in both nodular or diffuse B-cell non Hodgkin's lymphomas (NHLs). Twenty nine cases of immunophenotypically diagnosed B-cell NHLs (19 of follicular center cell origin-FCCL- and 10 of the diffuse well differentiated lymphocytic type-WDLL-) and five reactive lymph nodes with follicular hyperplasia were analyzed by immunoperoxidase and immunofluorescence techniques. Serial frozen sections and cytospin preparations were tested either with single antibodies anti laminin and DRC-1, or paired reagents in double labeling immunofluorescence. Our results indicated consistently that within both the reactive germinal centers and the neoplastic nodules of FCCL laminin immunostaining visualized a punctate-granular pattern apart from the linear vascular basement membrane positivity. Double immunofluorescence assay demonstrated that there was a close parallelism between this laminin staining pattern and DRC-1 distribution showing a well developed DRCs meshwork; in the diffuse tumour areas of both FCCL and WDLL, laminin immunoreactivity was found only in those cases in which nests of DRCs were observed. Double immunofluorescence studies performed on cytospin preparations demonstrated that the groups of cells containing DRC-1 positive cells, contained a positivity for laminin, although within the cell the staining for DRC-1 was intense and diffuse, while that for laminin was granular and more sparse. Our results suggested that these laminin and DRC-1 positive reactive sites may be present on the same cells. Since the reduction in number or loss of both DRCs and their related immunostaining for laminin within the microenvironment was consistently associated with a loss of nodularity by lymphoma cells, whereas nodularity in reactive and neoplastic conditions was associated with a rich DRCs meshwork and the related laminin immunostaining, a trapping function of DRCs exercised in the presence of laminin should be considered.This work was supported in part by a Grant N 87.02799.44 from the Consiglio Nazionale delle Ricerche, Progetto Finalizzato Oncologia, Rome, and by the Associazione Italiana per la Ricerca sul Cancro, Milan, Italy     

Increase of predominantly k-type light chains in the CSF of a case of subacute sclerosing panencephalitis treated with interferon

The results of a study of the CSF protein pattern in a case of SSPE treated with interferon are reported. An increase in the IgG, IgG index and CNS IgG synthesis values was found during and after the period of treatment. The electrophoretic and IEF patterns show a predominant increase in the L-chain bands, principally k-type, which are anti-measles antibodies. It is suggested that interferon could stimulate some cell clones to synthesize a particular type of L-chains.

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Sommario Sono riportati i risultati dello studio delle proteine del liquor cefalo-rachidiano in un caso di Panencefalite Sclerosante Subacuta trattato con interferon. È evidenziato un aumento dei valori di IgG, IgG index e delle IgG sintetizzate nel S.N.C. nelle 24 ore durante il periodo di trattamento. I quadri elettroforetico e dell'isoelectrofocusing dimostrano un aumento prevalente delle catene leggere delle IgG di tipo k che sono anticorpi anti-morbillo. È avanzata l'ipotesi che l'interferon possa aver stimolato la sintesi di un particolare tipo di catene leggere da parte di qualche clone cellulare.

     

Vascular Effects of the Polyphenolic Nutraceutical Supplement Taurisolo®: Focus on the Protection of the Endothelial Function

Preservation of vascular endothelium integrity and functionality represents an unmet medical need. Indeed, endothelial dysfunction leads to decreased nitric oxide biosynthesis, which is prodromic of hypertension and hypercoagulability. In this panorama, the nutraceutical supplement Taurisolo^®, a polyphenolic extract from Aglianico cultivar grape, rich in catechin and procyanidins, was evaluated as a vasoprotective, vasorelaxing, anti-hypertensive and anti-coagulant agent in: cell lines, isolated vessels, in vivo models of chronic hypertension and hypercoagulability, and in clinical tests of endothelial reactivity. Taurisolo^® demonstrated to fully protect vascular cell viability from oxidative stimulus at 100 µg/mL and evoke vasorelaxing effects (Emax = 80.6% ± 1.9 and pEC50 = 1.19 ± 0.03) by activation of the Sirtuins-AMPK-pathway. Moreover, Taurisolo^®, chronically administered at 20 mg/Kg/die in in vivo experiments, inhibited the onset of cardiac hypertrophy (heart weight/rat weight = 3.96 ± 0.09 vs. 4.30 ± 0.03), hypercoagulability (decrease of fibrinogen vs. control: p < 0.01) and hypertension (mean of Psys: 200 ± 2 vs. control 234 ± 2 mmHg) and improved endothelial function (Emax = 88.9% ± 1.5 vs. control 59.6% ± 3.6; flow-mediated dilation in healthy volunteers after 400 mg twice daily for 8 weeks vs. baseline: p = 0.019). In conclusion, Taurisolo^® preserves the vascular function against ox-inflamm-ageing process and the consequent cardiovascular accidents.     

Transclavicular approach for delivery of intrathoracic giant goiter. An alternative surgical option

To remove the immerse portion of a cervical goitre it is necessary to treat preventively the cervical thyroid arteries. In most cases it is afterwards it is easy the blunt finger dissection of the mediastinal bulk following the correct cleavage plane and its dislodging in the cervical area. But in very rare instances, according also to the personal experience, remains some difficulty for the passage of a too bulky and hard mediastinal mass through the rigid limits of the upper thoracic outlet, or the immerse struma is too fragile for pulling it by transfixion threads. Therefore, traditionally arises the opportunity of an additional surgical access, through the breastbone or through the thoracic wall, according to the circumstances. Our experience, completely occasional but extremely positive of two of such cases, induces us to advance a proved alternative surgical proposal. When the difficulty of the removal of the immerse portion of the goitre comes only from the incongruence of the immerse volume and the rigid limits of the upper thoracic outlet, our proposal is that to obtain an amplification of the narrow passage breaking the continuity of the clavicle, by its section beneath the periostium near the breastbone and removing this sternal stump from the joint. The result is that of an widening of the upper thoracic outlet, no more rigid, and making easy the transit of the immerse portion from anterior mediastinum so dislodged in the neck. The rationale of this choice is that all is requested in such cases is only to overcome the obstacle of the incongruence among volume and bulk of the immerse portion and the bone limits fixed from the narrow upper thoracic outlet. Both the traditional sternotomy and the thoracotomy seems disproportional for this purpose, moreover with additional problems during the operation. The true advantage of these classical solutions is in treating under direct vision the anomalous arteries of the mediastinal goitre in cases of ectopic localization. But this is not the case of an immerse cervical goitre. It is therefore essential to note that this proposal applies only to the migrated goitre and not to the ectopic ones. The recovery is extremely simple, and both the aesthetics and the static of the scapular joint are not substantially compromised.