Hypophyseal Non-Hodgkin's Lymphoma Presenting with Diabetes Insipidus: A Case Report

We report the case of a 64 year old male patient with a history of ischemic heart disease who underwent surgery for an abdominal mass. The histological diagnosis was highly malignant non-Hodgkin's lymphoma. After surgery the patient was admitted to our Department and received 6 courses of chemotherapy according to the COP schedule, followed by radiotherapy to the left upper abdominal region and ipsilateral lung base. The patient achieved partial remission. One month later he began to complain of left axillary lymphadenomegaly, polydipsia and polyuria. A NMR brain scan showed a hypophyseal mass. The patient was treated with DDAVP and chemotherapy with the PRO-MACE protocol; the polyuria and lymphadenomegaly disappeared and the size of the hypophyseal mass reduced markedly. The clinical picture was, therefore, attributed to a hypophyseal localization of the non-Hodgkin's lymphoma, which is a very rare manifestation of lymphomatous spread to the central nervous system. Our case is also interesting because it shows that a favorable outcome can be obtained with chemotherapy, provided that the latter is sufficiently aggressive. This is not necessarily the case with radiotherapy which may also be followed by late and severe neurologic sequelae.     

Platelet derived growth factor and subarachnoid haemorrage: A study on cisternal cerebrospinal fluid

Summary Platelet derived growth factor (PDGF) was identified as a powerful mitogenic growth factor which is released from activated platelets and has a marked activity as vasoconstrictor agent. In the present study we have measured cisternal cerebrospinal fluid (CSF) levels of PDGF in 72 patients operated on for intracranial aneurysm in order to verify whether it might be related to the clinical aspects of SAH with special regard to symptomatic vasospasm.CSF samples were obtained at surgery by cisternal puncture of the subarachnoid cistern the nearest to the aneurysm before aneurysm isolation and exclusion. The specimen were frozen in liquid nitrogen and stored at-80 ° C until analysis. PDGF was measured using a commercially available reagent. Values are expressed as pg/ml of CSF.In 18 cases no radiological and clinical signs of SAH were detected and the mean cisternal CSF level of PDGF was 885.0±104.5 pg/ml; 20 patients were operated on between day 1 and 3 from the last SAH episode: mean cisternal CSF level of PDGF was 1917.5±459.4 pg/ml. In 34 patients treated with delayed surgery protocol, mean cisternal CSF level of PDGF was 995.3±73.8 pg/ml. Statistical analysis showed significant differences between groups (P: 0.011). In the subgroup of patients operated on within day 3 after SAH, 6 presented vasospasm and had mean cisternal CSF PDGF level which was significantly higher (P<0.01) than in 14 patients without vasospasm. In the delayed surgical patients there was no significant difference in cisternal CSF levels of PDGF considering the occurrence of vasospasm.The results of the present study suggest that (a) after SAH there is a significant release of PDGF early after SAH and (b) higher levels of PDGF found in cisternal CSF of patients operated on within 72 hours after SAH may be predictive of symptomatic vasospasm.     

Platelet activation by cells isolated from human tumor tissues: effect of cyclooxygenase blockade

We have studied in a homologous system the effect on different platelet functions of cells isolated from 26 human tumor tissues (11 breast carcinomas, 11 colon carcinomas, 2 pancreatic carcinomas, 1 gastric carcinoma and 1 esophageal carcinoma). Tumor cells (10(5)/ml) significantly increased platelet adhesion to glass beads; they were also found to possess a potent platelet aggregating activity and aggregation was accompanied by significant release of ATP and platelet derived growth factor (PDGF) and by production of TXB(2). Preincubation of platelets with a low concentration (1 μM) of indobufen, a cyclooxygenase inhibitor, significantly reduced tumor cell induced TXB(2) production and ATP release, while the other platelet functions were not modified. Higher concentrations of the drug (10 or 100 μM) were also able to inhibit tumor cell-induced platelet aggregation and PDGF release, while platelet adhesion to glass beads was unchanged even at these doses. Finally, preincubation of neoplastic cells with indobufen (400μM) had no effect on their ability to induce platelet aggregation, TXB(2) production and ATP release. These data demonstrate that cyclooxygenase blockade in platelets has different effects on several platelet functions activated by the tumor cells that were investigated.     

Distinguishing features of delta-proteobacterial genomes

We analyzed several features of five currently available delta-proteobacterial genomes, including two aerobic bacteria exhibiting predatory behavior and three anaerobic sulfate-reducing bacteria. The delta genomes are distinguished from other bacteria by several properties: (i) The delta genomes contain two "giant" S1 ribosomal protein genes in contrast to all other bacterial types, which encode a single or no S1; (ii) in most delta-proteobacterial genomes the major ribosomal protein (RP) gene cluster is near the replication terminus whereas most bacterial genomes place the major RP cluster near the origin of replication; (iii) the delta genomes possess the rare combination of discriminating asparaginyl and glutaminyl tRNA synthetase (AARS) together with the amido-transferase complex (Gat CAB) genes that modify Asp-tRNA(Asn) into Asn-tRNA(Asn) and Glu-tRNA(Gln) into Gln-tRNA(Gln); (iv) the TonB receptors and ferric siderophore receptors that facilitate uptake and removal of complex metals are common among delta genomes; (v) the anaerobic delta genomes encode multiple copies of the anaerobic detoxification protein rubrerythrin that can neutralize hydrogen peroxide; and (vi) sigma(54) activators play a more important role in the delta genomes than in other bacteria. delta genomes have a plethora of enhancer binding proteins that respond to environmental and intracellular cues, often as part of two-component systems; (vii) delta genomes encode multiple copies of metallo-beta-lactamase enzymes; (viii) a host of secretion proteins emphasizing SecA, SecB, and SecY may be especially useful in the predatory activities of Myxococcus xanthus; (ix) delta proteobacteria drive many multiprotein machines in their periplasms and outer membrane, including chaperone-feeding machines, jets for slime secretion, and type IV pili. Bdellovibrio replicates in the periplasm of prey cells. The sulfate-reducing delta proteobacteria metabolize hydrogen and generate a proton gradient by electron transport. The predicted highly expressed genes from delta genomes reflect their different ecologies, metabolic strategies, and adaptations.     

New category of probable invasive pulmonary aspergillosis in haematological patients

The European Organization for Research and Treatment of Cancer and the Mycosis Study Group (EORTC-MSG) radiological definitions of invasive pulmonary aspergillosis (IPA) may lack diagnostic sensitivity. We evaluated applying less restrictive radiological criteria, when supported by specific microbiological findings, to define IPA in acute myeloid leukaemia (AML), lymphoproliferative diseases (LD) and allogeneic stem cell transplant (allo-SCT) patients. Overall, 109 consecutive episodes of proven/probable IPA in 56 AML, 31 LD and 22 allo-SCT patients diagnosed from February 2006 through to January 2011 were considered. IPA was diagnosed with EORTC-MSG criteria (control group, 76 patients) or without prespecified radiological criteria (study group, 33 patients). The latter differed from the former by the inclusion of patients with pulmonary infiltrates not fulfilling the three EORTC-MSG IPA specific findings of dense, well-circumscribed lesions with or without halo sign, air crescent sign or cavity. All the analysed clinical and mycological characteristics, 3-month response to antifungal therapy and 1- and 3-month cumulative survival were comparable in the control and study groups in AML, LD and allo-SCT patients. Seventeen of 33 (51.5%) patients of the study group fulfilled EORTC-MSG radiological criteria at subsequent imaging performed a median of 15 days (range, 6-40 days) after documentation of the pulmonary infection. Our study seems to confirm the possibility of revising the EORTC-MSG criteria by extending the radiological suspicion of IPA to less specific chest computerized tomography scan findings when supported by microbiological evidence of Aspergillus infection in high-risk haematological patients.     

In vitro Effect of Verapamil on Platelet Activation Induced by ADP, Collagen or Thrombin

We studied the effects in Vitro of the calcium channel blocker verapamil (0.1, 0.2 or 0.3 mM) on platelet aggregation, on cytoplasmic Ca(+ +) levels and on TxB(2) production after activation of platelets with adenosine diphosphate (ADP) (100 μM), collagen (20 μg/ml) or thrombin (1 U/ml). A Platelet Ionized Calcium Aggregometer was used and washed, aequorin loaded platelets were employed. The drug was able to inhibit similarly and always significantly aggregation, Ca(+ +) fluxes and TxB(2) production when collagen was the agonist. Furthermore, inhibition of aggregation and TxB(2) production was significant at all the concentrations tested when platelets were activated by ADP or thrombin, but in this case inhibition of Ca (+ +) fluxes was observed only with the higher concentrations of the drug (0.2 or 0.3 mM). Hence, with these two last agonists inhibition of Ca(+ +) movements was less pronounced than inhibition of aggregation or TxB(2) production. These data suggest that platelet activation by collagen depends directly and almost exclusively on Ca(+ +) fluxes through biological membranes, while activation by ADP or thrombin is less strictly related to Ca(+ +) movements. Indeed, with these last two agonists verapamil may inhibit platelet activation also by calcium-independent mechanism(s).     

Geometry of interplanar residue contacts in protein structures.

The relative spatial disposition of interacting side-chain planar groups (aromatic, guanidinium, amide, carboxyl, imidazole) is analyzed for 186 non-homologous well-resolved protein structures. The dihedral angle of amide or carboxyl planar groups with other planar groups accords with a random distribution of planes. By contrast, the dihedral angle of the planes between close aromatic rings or of the histidine ring interacting with aromatic residues is significantly nonrandom, showing an approximately uniform distribution. Our results indicate that edge-to-edge and edge-to-center spatial dispositions of residue planar sections are prevalent, while complete stacking configurations are uncommon. The hypothesis that electrostatic forces are a major determinant of the geometry of interactions between side-chain planar groups is discussed.     

Genomic and proteomic comparisons between bacterial and archaeal genomes and related comparisons with the yeast and fly genomes

Bacterial, archaeal, yeast, and fly genomes are compared with respect to predicted highly expressed (PHX) genes and several genomic properties. There is a striking difference in the status of PHX ribosomal protein (RP) genes where the archaeal genome generally encodes more RP genes and fewer PHX RPs compared with bacterial genomes. The increase in RPs in archaea and eukaryotes compared with that in bacteria may reflect a more complex set of interactions in archaea and eukaryotes in regulating translation, e.g., differences in structure requiring scaffolding of longer rRNA molecules, expanded interactions with the chaperone machinery, and, in eukaryotic interactions with endoplasmic reticulum components. The yeast genome is similar to fast-growing bacteria in PHX genes but also features several cytoskeletal genes, including actin and tropomyosin, and several signal transduction regulatory proteins from the 14.3.3 family. The most PHX genes of Drosophila encode cytoskeletal and exoskeletal proteins. We found that the preference of a microorganism for an anaerobic metabolism correlates with the number of PHX enzymes of the glycolysis pathway that well exceeds the number of PHX enzymes acting in the tricarboxylic acid cycle. Conversely, if the number of PHX enzymes of the tricarboxylic acid cycle well exceeds the PHX enzymes of glycolysis, an aerobic metabolism is preferred. Where the numbers are approximately commensurate, a facultative growth behavior prevails.