[Successful treatment for cryptococcal meningoencephalitis complicated by cerebral salt-wasting syndrome in a patient with chronic lymphocytic leukemia: A clinical case].

Cryptococcus neoformans is a common agent of fungal meningoencephalitis in immunocompromised patients. Cerebral salt-wasting syndrome is one of the rare causes of severe hyponatremia in patients with CNS diseases. The paper describes the first clinical case of a patient, whose onset of chronic lymphocytic leukemia was complicated by cryptococcal meningoencephalitis presenting with mental disorders and severe electrolytic imbalance. Antifungal treatment with amphotericin B and fluconazole could alleviate an infectious process and metabolic disturbances.

[Autologous hematopoietic stem cell transplantation as late high-dose consolidation in adult patients with T-cell lymphoblastic leukemias: Results of a Russian multicenter study].

AIM: To analyze the efficiency of the ALL-2009 protocol (ClinicalTrials.gov NCT01 193933) in patients with T-cell leukemias, particularly the role of autologous hematopoietic stem cell transplantation (auto-HSCT) after non-myeloablative BEAM conditioning, followed by maintenance therapy. SUBJECTS AND METHODS: Since 2009, the ALL-2009 study has enrolled 90 patients with T-cell acute lymphoblastic leukemia (T-ALL), the treatment results were assessed in 86 patients: 6 and 28 patients underwent allogeneic HSCT and auto-HSCT, respectively. A landmark analysis was used to compare survival rates in patients who had undergone auto-HSCT and in those who had not. For this, the median time from complete remission to the date of auto-HSCT was determined (the median was 6 months). Then to compare with the auto-HSCT group, only 27 patients who had been in complete remission for 6 months or more were included in a chemotherapy group. RESULTS: The achievement of complete remission in patients with thymic T-ALL (100%) was significantly higher than in those with early (85.7%) or mature (70%) variants. The patients with early and mature T-ALL as compared to those with thymic T-ALL showed high death rates in the remission induction (7.4 and 10% versus 0) and the patients with mature T-ALL had a.higher proportion of refractory forms (20% versus 0). The 5-year overall and relapse-free survival rates in all the T-ALL patients were 66 and 76%, respectively. After auto-HSCT, the risk of recurrence was 0% versus 21% after chemotherapy (p=0.03). The relapse-free survival rates significantly differed in the auto-HSCT and non-auto-HSCT groups: 100 and 66%, respectively (p=0.047). CONCLUSION: The long-term survival rates obtained during this multicenter study in the T-ALL patients treated according to the ALL-2009 protocol, the basis for which is the principle of continuity of cytostatic effects, are exclusively optimistic. Late consolidation with auto-HSCT following non-myeloablative BEAM conditioning, followed by maintenance therapy, considerably reduces the risk of recurrence.

[Invasive mucormycosis in patients with hemoblastosis in St.-Petersburg].

Thirty four patients with mucormycosis in 10 hospitals of St. Petersburg were observed in 2004-2013. The most frequent underlying diseases of mucormycosis were acute leukoses (64%). In 100% of the patients mucormycosis developed as a nosocomial infection. The risk factors, etiology, basic clinical signs and strategy in the treatment of mucormycosis were analyzed.

[Development and characterization of Helicobacter pylori CagA recombinant fragments].

AIM: The goal of the work was to produce, purify and characterize recombinant fragments of Helicobacter pylori CagA protein. MATERIALS AND METHODS: The methods of molecular cloning, recombinant protein expression in Escherichia coli, affinity chromatography, gel electrophoresis and western-blotting as well as several in silico algorithms of nucleotide and aminoacid sequence analysis were used. RESULTS: Four N-terminal His6-tagged recombinant fragments of CagA protein were produced. Protein rCagAfr.1 (65 kDa) represents the most conserved N-terminal part of the cytotoxin. Fragment rCagAfr.2 (44 kDa) corresponds to the central conserved region of CagA whereas rCagAfr.3 (39 kDa) represents the highly variable C-terminal part of CagA. Finally, the protein rCagAfr.4 (75 kDa) incorporates the sequences of rCagAfr.2 and rCagAfr.3. In silico analysis of fragments' sequences allowed to suppose that rCagAfr.2 and rCagAfr.4 are highly immunogenic proteins. By means of chromatographic purification, high levels of purity (up to 97%) and yield (about 15 mg per L of culture) of recombinant proteins were achieved. CONCLUSION: Use of recombinant proteins technology allowed to solve the problem of producing the CagA pure protein of H. pylori, which open new perspectives for the development of immunodiagnostic assays for detection of CagA protein or antibodies to this cytotoxin.

[Development of panel of monoclonal antibodies for detection of CagA cytotoxin of Helicobacter pylori].

AIM: To obtain and study of immunochemical characteristics of monoclonal antibodies (MAbs) to CagA cytotoxin of Helicobacter pylori employing recombinant fragments of CagA protein. MATERIALS AND METHODS: Standard methods of construction and selection of hybridomas, different variants of immunoenzyme analysis and immunoblotting were used. Molecular genotyping of H. pylori cultures by amplification of cagA gene fragments was performed. RESULTS: Panel of MAbs recognizing 4 different linear epitopes on the CagA molecule, three of which are localized in conservative parts of cytotoxin and one--in variable region of CagA, was developed. On the basis of two obtained antibodies, system of two-center immunoenzyme assay for quantitative detection of CagA protein which is characterized by high sensitivity and specificity, was developed. Obtained MAbs allow to differentiate CagA-positive and CagA-negative strains of H. pylori by immunochemical methods. CONCLUSION: Employing pure recombinant fragments of CagA protein, first panel of MAbs to CagA cytotoxin of H. pylori was developed and characterized. Obtained MAbs open perspectives for study of the H. pylori cytotoxin molecule and construction of immunodiagnostic assays aimed on detection of CagA antigen.

Himasthla elongata: effect of infection on expression of the LUSTR-like receptor mRNA in common periwinkle haemocytes.

The first mollusc mRNA coding G-protein-coupled transmembrane receptor (GPcapital ES, CyrillicR), homologous to human receptors LUSTR 1 (GPR107) and LUSTR 2 (GPR108), was isolated from haemocytes of common periwinkle Littorina littorea. The analyses showed that the full-length cDNA is 1935 bp long and is predicted to encode a 614 amino acid protein (named Lit-LUSTR) with a calculated molecular mass of 69.6 kDa and theoretical isoelectric point 7.59. Pair-wise comparisons between Lit-LUSTR and LUSTR proteins from human or mouse have approximately 38% identity and 56% similarity. Lit-LUSTR clusters with LUSTR-A sub-family proteins and is a first characterization of proteins containing Lung7TM-R domain in Mollusca. Significant differences were found between the Lit-LUSTR mRNA levels in haemocytes of healthy periwinkles and those naturally infected with the echinostome trematode Himasthla elongata. Down regulated expression of the LUSTR-like receptor caused by infection illustrates modification of the haemocyte receptor system and may be attributed to the previously demonstrated greater numbers of "immature" haemocytes in the circulation of infected snails.

[Spinal stroke in the acute myeloblast leucosis].

Data of literature on the frequency of the nervous system lesions in different variants of leucosis are analyzed. A case of a man with petechial skin rash and bruises on the body, gingival hemorrhage and general sickness is described in details. The hematologic tests revealed acute myeloblast leucosis. A lumbar puncture revealed blood in the cerebrospinal fluid and MRI showed an epidural hematoma in lumbar segments 3 and 4. At this level, the hematoma compressed the dural bag and roots of the horse tail with accompanying vessels (the radicular medullar artery and large radicular veins). A paracentetic removal of the hematoma with the decompression of spinal roots was carried out. The blasts in the cerebrospinal fluid and symptoms of the left facial nerve lesion allowed to diagnose neuroleucosis. This case presented the mixed pathogenesis of myeloischemia. The epidural hematoma compressed not only the roots of the horse tail but the accompanying vessels (arteries and veins). The venous outflow obstruction along radicular veins worsened the microcirculation in the cross-sectional area of the spinal cord. Complex polychemotherapy in the combination with neuroprotectors (cortexin, gliatiline), antiaggregants and vitamins is recommended.