Regulation of AE2-mediated Cl− Transport by Intracellular or by Extracellular pH Requires Highly Conserved Amino Acid Residues of the AE2 NH2-terminal Cytoplasmic Domain

We reported recently that regulation by intracellular pH (pHi) of the murine Cl−/HCO3− exchanger AE2 requires amino acid residues 310–347 of the polypeptide's NH2-terminal cytoplasmic domain. We have now identified individual amino acid residues within this region whose integrity is required for regulation of AE2 by pH. 36Cl− efflux from AE2-expressing Xenopus oocytes was monitored during variation of extracellular pH (pHo) with unclamped or clamped pHi, or during variation of pHi at constant pHo. Wild-type AE2–mediated 36Cl− efflux was profoundly inhibited by acid pHo, with a value of pHo(50) = 6.87 ± 0.05, and was stimulated up to 10-fold by the intracellular alkalinization produced by bath removal of the preequilibrated weak acid, butyrate. Systematic hexa-alanine [(A)6]bloc substitutions between aa 312–347 identified the greatest acid shift in pHo(50) value, ∼0.8 pH units in the mutant (A)6342–347, but only a modest acid-shift in the mutant (A)6336–341. Two of the six (A)6 mutants retained normal pHi sensitivity of 36Cl− efflux, whereas the (A)6 mutants 318–323, 336–341, and 342–347 were not stimulated by intracellular alkalinization. We further evaluated the highly conserved region between aa 336–347 by alanine scan and other mutagenesis of single residues. Significant changes in AE2 sensitivity to pHo and to pHi were found independently and in concert. The E346A mutation acid-shifted the pHo(50) value to the same extent whether pHi was unclamped or held constant during variation of pHo. Alanine substitution of the corresponding glutamate residues in the cytoplasmic domains of related AE anion exchanger polypeptides confirmed the general importance of these residues in regulation of anion exchange by pH. Conserved, individual amino acid residues of the AE2 cytoplasmic domain contribute to independent regulation of anion exchange activity by pHo as well as pHi

КОЖНЫЕ ПРОЯВЛЕНИЯ АНГИОИММУНОБЛАСТНОЙ Т-КЛЕТОЧНОЙ ЛИМФОМЫ

Background: Angioimmunoblast T-cell lymphoma (AITL) is a rare T-cell lymphoproliferative disease that is accompanied by generalized lymphadenopathy, hepatosplenomegaly, intoxication symptoms and extranodal lesions. The extranodal manifestations of the disease frequently involve various skin changes. One of the first such manifestations is maculopapular rashes observed in about half of AITL patients and usually preceding the appearance of lymphadenopathy. Other forms of skin lesions accompany the disease considerably less frequently.Aim: To characterize the range of skin changes in patients suffering from AITL, to establish a correspondence between the nature of skin changes and their histological picture.Materials and methods: 54 AITL patients were being treated at the National Research Centre for Hematology from 2000 to 2017, with the male/female ratio being 30/24. The median age was 61 (29–81) years.Results: Changes in the skin were observed in 24 (44.4 %) of 54 AITL patients, out of whom 18 (75 %) and 6 (25 %) were male and female patients, respectively. Maculopapular rash was observed in 22 (91.7 %) out of 24 patients. The morphological and molecular investigations of skin biopsy specimens exhibiting maculopapular rash demonstrated nonspecific reactive changes. Patients with maculopapular rash demonstrated an increase in the level of total (polyclonal) IgE. Specific skin lesions detected in 8 (14.8 %) cases were represented by a ‘livedo reticularis’, focal skin hyperpigmentation, erythroderma, left eyelid tumour and tumour in 3, 2, 1, 1 and 1 cases, respectively.Conclusion: Maculopapular rash frequently observed in AITL patients is a reactive process not associated with a specific skin lesion. Specific skin lesions in AITL are much less common and can be represented by various forms. In some AITL cases, skin changes of the reactive and tumour nature can be simultaneously observed. Введение. Ангиоиммунобластная Т-клеточная лимфома (АИТЛ) — редкое Т-клеточное лимфопролиферативное заболевание, протекающее с генерализованной лимфаденопатией, гепатоспленомегалией, симптомами интоксикации и экстранодальными поражениями. Изменение кожных покровов — одно из наиболее частых экстранодальных проявлений заболевания. Макулопапулезная сыпь, наблюдающаяся приблизительно у половины больных АИТЛ, обычно предшествует появлению лимфаденопатии и является одним из первых проявлений заболевания. Значительно реже поражение кожи представлено другими кожными элементами.Цель: охарактеризовать спектр изменений кожных покровов у больных АИТЛ, установить соответствие между характером изменений кожи и гистологической картиной.Материалы и методы. В Национальном медицинском исследовательском центре гематологии Минздрава России с 2000 по 2017 г. наблюдалось 54 больных АИТЛ, соотношение м/ж — 30/24. Медиана возраста составила 61 (29–81) год.Результаты. Изменение кожных покровов наблюдали у 24 (44,4 %) из 54 больных АИТЛ, у мужчин в 18 (75 %), у женщин в 6 (25 %) случаях. Макулопапулезная сыпь наблюдалась у 22 (91,7 %) из 24 случаев больных. Морфологическое и молекулярное исследования биоптатов кожи с элементами макулопапулезной сыпи демонстрировали неспецифические реактивные изменения. У больных с макулопапулезной сыпью наблюдалось повышение уровня общего (поликлонального) IgЕ. Специфическое поражение кожи было выявлено в 8 (14,8 %) случаях и было представлено livedo reticularis в 3 случаях, очаговой гиперпигментацией кожи — в 2, эритродермией — в 1, опухолевидным образованием на коже левого века — в 1 и опухолевыми образованиями — в 1 случае.Заключение. Макулопапулезная сыпь, часто наблюдающаяся при АИТЛ, является реактивным процессом и не ассоциирована со специфическим поражением кожи. Специфическое поражение кожи при АИТЛ встречается значительно реже и может быть представлено различными кожными элементами. В некоторых случаях АИТЛ одновременно может наблюдаться изменение кожных покровов реактивного и опухолевого генеза.

Успешный опыт лечения первичной кожной анапластической крупноклеточной лимфомы, протекающей с распространенным поражением кожного покрова и легочной ткани

The aim of the study is to present a successful case in treating primary cutaneous anaplastic large cell lymphoma (PCALCL) occurring with common lesions of the skin and lung tissue.Materials and methods. For the verification of the diagnosis in a patient with three types of skin elements (spot, thin plaque with and without ulceration), differential diagnosis was performed between ulcerative pyoderma gangrenosum, PCALCL, large-cell transformation of mycosis fungoides, and secondary skin lesions under the nodal ALK-negtaive ALCL. A complex of studies, including histological, immunohisto - chemical, cytogenetic studies of skin tumor biopsy, allowed the verification of the PCALCL diagnosis. For the treatment of the patient, intensive induction chemotherapy was used followed by high-dose consolidation and autologous transplantation of hematopoietic stem cells.Results. The selected treatment tactics allowed a long-term complete remission of the disease to be achieved in a patient from the poor prognosis group.Conclusion. An algorithm for the differential diagnosis and tactics of treating is presented for a patient with primary anaplastic large cell lymphoma with a widespread skin lesion and extradermal foci.Цель: демонстрация успешного опыта лечения первичной кожной анапластической крупноклеточной лимфомы (пкАККЛ), протекающей с распространенным поражением кожного покрова и легочной ткани.Материалы и методы. Для верификации диагноза у больного с тремя видами кожных элементов (пятно, тонкая бляшка с изъязвлением и без него) проводилась дифференциальная диагностика между язвенно-гангренозной пиодермией, пкАККЛ, крупноклеточной трансформацией грибовидного микоза и вторичным поражением кожи при нодальной АККЛ, ALK-. Проведенный комплекс исследований, включающий гистологическое, иммуногистохимическое, цитогенетическое исследования биоптата опухоли кожи, позволил верифицировать диагноз пкАККЛ. Для лечения больного была применена интенсивная индукционная химиотерапия с последующей высокодозной консолидацией и аутологичной трансплантацией гемопоэтических стволовых клеток.Результаты. Выбранная тактика лечения позволила достигнуть продолжительной полной ремиссии заболевания у больного из группы неблагоприятного прогноза.Заключение. Представлены алгоритм дифференциальной диагностики и определение тактики лечения больного первичной кожной анапластической крупноклеточной лимфомой с распространенным поражением кожного покрова и экстрадермальными очагами

2-METHYLPYRIDINIUM SALT OF PENTAIODOBENZOIC ACID: ROLE OF THE HALOGEN BOND IN THE FORMATION OF A CRYSTAL PACKING

Abstract: In the reaction of pentaiodobenzoic acid (PIBA) and 2-methylpyridine in N,N′-dimethylformamide (2-MePyH)PIBA·DMF salt (1) is formed, whose structure is studied by X-ray crystallography. The structure of 1 contains noncovalent interactions of the I⋯O type of the halogen bond, whose energies are estimated by quantum chemical calculations

Adaptation of Mycoplasmas to Fluoroquinolones: Modulation of Proteome and Genotoxicity of Extracellular Vesicles of Acholeplasma laidlawii

The paper is devoted to the comparative analysis of proteomic profiles and genotoxicity of extracellular vesicles produced by cells that differ in sensitivity to ciprofloxacin of Acholeplasma laidlawii strains – the mycoplasma, being a causative agent of mycoplasmoses of plants and animals, as well as the main contaminant of cell cultures. The relevance of the study is determined by the fact that extracellular vesicles – nanostructures surrounded by a membrane mediating intercellular communication and pathogenesis in bacteria are involved in adaptation of A. laidlawii to antimicrobials and present a new type of infects, the study of which is associated with the prospects of determining the mechanisms of host-parasite systems and solution of problems of pathogen control. The present study has been performed with a view of elucidation of the proteome profile features and assessment of the genotoxicity of extracellular vesicles of A. laidlawii in the development of resistance of the mycoplasma to ciprofloxacin – a drug of fluoroquinolone group which is widely used for inhibiting mycoplasmas. To achieve this goal, we have used the standard microbiological methods, as well as the modern physical and chemical methods, including proteomic profiling with help of 1D-LC-ESI-MS/MS, PCR, automatic scanning, and karyotyping system for assessment of the genotoxicity of vesicles. It has been shown that a significant part of vesicular proteome of A. laidlawii strains with differential sensitivity to ciprofloxacin represents the bacterial virulence factors, as well as that the vesicles of all strains exhibit genotoxicity to lymphocytes of human peripheral blood in vitro. The most important of these results is the fact that the development of resistance of A. laidlawii to ciprofloxacin is accompanied by a significant modulation of vesicular proteome and the increase of mitotoxicity to eukaryotic cells. The obtained data are essential for fundamental research and applied works in the control system of socially significant infections, contaminations of cell cultures and vaccines. The results of the study provide fundamentally new notions about the processes of adaptation of A. laidlawii to antimicrobial drugs and pathogenicity of extracellular vesicles of mycoplasma, as well as suggest the necessity for correction of the control system of mycoplasmas with a view of bacterial vesicles as a new type of infects

Halogen···halogen contacts in triiodide salts of pyridinium-derived cations: Theoretical and spectroscopic studies

© 2020 Elsevier B.V. Triiodide salts of pyridinium-type cations CatI3 (cat = 1,2-MePy (1), 1,2,6-MePy (2) and 1,2,4,6-MePy (3) were prepared and characterized by X-ray diffractometry. In the cases of 1 and 2, formation of supramolecular anionic dimers {(I3)2}2- was observed in solid state (I⋯I = 3.685 and 3.912 Å, respectively), while in 3 triiodides remain isolated. The features of I⋯I contacts were studied by theoretical methods and Raman spectroscopy

Heteroleptic copper(II) complexes with 2-bromo-5-methylpyridine: Structures, features of non-covalent interactions and magnetic behavior

© 2019 Elsevier B.V. Isostructural complexes [Cu(2-Br-5-MePy)2X2] (2-Br-5-MePy = 2-bromo-5-methylpyridine, X = Cl (1), Br (2) were prepared and structurally characterized. Magnetic measurements reveal that both complexes demonstrate paramagnetic behavior

The Effect of Helicobacter pylori Eradication on Human Microbiota: Metagenome Analysis of the Human Gut Microbiome

A total of 152 stool samples from 76 patients with symptoms of gastrointestinal diseases have been analyzed using metagenomic shotgun sequencing technology to assess the effect of Helicobacter pylori eradication therapy on Bifidobacterium, Lactobacillus, Escherichia, and Clostridium genera. The relative abundance of bacteria representing these genera in the intestinal microflora of patients before and after antibiotic therapy has been evaluated. It has been shown that the therapy did not have any critical effect in the majority of cases on the number of Lactobacillus, Escherichia and Clostridium genera in the microbial community. Their abundance varied within 0.5% in 76.5%, 51.3%, and 55.2% of patients, respectively. The Bifidobacterium genus has been found to be more susceptible to antibiotics (their number decreased significantly in 60.5% of cases). However, 9.2% of patients have shown the opposite effect. Thus, the obtained data demonstrate that Helicobacter pylori eradication therapy does not have uniform effects on the key members of human intestinal microbiota. This fact should be taken into account when predicting the risks of side effects of antibiotics