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The diagnosis of necrobiosis lipoidica is gaining significance owing to the increase in the incidence of diabetes mellitus. Several theories regarding the etiopathogenesis of necrobiosis lipoidica indicate the distinctive role of transport proteins of the Glut family, as well as the role of matrix metalloproteinase in the development of this dermatosis.

The results of clinical observation of a rare dermatosis, pyoderma gangrenosum, and results of successful complex treatment of the disease with systemic GCS, and cytostatic drugs are shown. The review of the literature on the etiology, pathogenesis, and diagnosis of GP is presented.

To determine the frequency, clinical and morphological features of a nephropathy with C1q deposits in chronic glomerulonephritis adult patients.296 specimens of kidneys of patients with a chronic glomerulonephritis (CGN) from 2014 for 2018 were analyzed. At the first step, specimens with C1q deposits in glomeruli revealed by immunofluorescent method were chosen. Lupus nephritis and primary membranoproliferative glomerulonephritis were exclusion criteria. At the second step, the retrospective analysis of the clinical characteristics was carried out.Deposits of C1q in kidneys at 12 of 296 (4.05%) CGN were revealed, m:f ratio 2:1. Average age of the beginning of a disease was 32.1±14.7 years. At a morphological research in 8 membranous nephropathy (MN), in 2 mesangioproliferative glomerulonephritis (MesPGN), in 2 - nephrosclerosis was revealed. Among 12 patients in 5 the disease debuted a nephrotic syndrome, at the others - a proteinuria from 0.5 to 4.0 g/days with the subsequent formation of a nephrotic syndrome. In 5 of 12 patients the disease was characterized by a favor course with preserved kidney function. At 7 patients at the time of inspection decrease in function of kidneys [glomerular filtration rate (eGFR) 31 (30-34) ml/min] was noted. 5 had slow progressing of a renal failure. 2 of 12 progressed to renal failure (eGFR to 19 and 24 ml/min) within a year.Deposits of C1q in kidney were revealed in 4.05% of biopsy specimens in CGN. The most frequent morphological form was the membranous nephropathy. The clinical course was characterized by a nephrotic syndrome, more than at a half of patients - with renal dysfunction.Цель исследования. Определить частоту выявления, клинические и морфологические особенности нефропатии с C1q депозитами среди взрослых больных хроническим гломерулонефритом (ХГН). Материалы и методы. Проанализировано 296 биоптатов почек больных ХГН, которым проведена биопсия почки за период с 2014 по 2018 г. На первом этапе были выделены биоптаты больных ХГН с отложениями C1q в клубочках почек, выявленными с помощью иммунофлюоресцентного метода. Критериями исключения были диагнозы системной красной волчанки с поражением почек (волчаночный нефрит) и первичного мембранопролиферативного гломерулонефрита. На втором этапе проведен ретроспективный анализ данных клинического обследования пациентов. Результаты и обсуждение. Отложения C1q в клубочках почек выявлены у 12 из 296 (4,05%) больных ХГН, соотношение мужчины : женщины составило 2:1. Средний возраст начала заболевания - 32,1±14,7 года. При морфологическом исследовании биоптатов почек на светооптическом уровне у 8 пациентов обнаружена мембранозная нефропатия (МН), у двух выявлен мезангиопролиферативный гломерулонефрит (МезГН), у двух - нефросклероз в исходе мезангиальных форм нефрита. Среди 12 больных у 5 заболевание дебютировало нефротическим синдромом, у остальных - протеинурией от 0,5 до 4,0 г/сут с последующим формированием нефротического синдрома. У 5 из 12 обследованных пациентов заболевание характеризовалось длительным течением с сохранной функцией почек. У 7 пациентов на момент обследования отмечалось снижение функции почек [скорость клубочковой фильтрации (СКФ) - 31 (30-34) мл/мин]. Из них у 5 отмечалось длительное течение до 6 лет и медленное прогрессирование почечной недостаточности. У двоих наблюдалось быстрое, в течение года, прогрессирование почечной недостаточности со снижением СКФ до 19 и 24 мл/мин (МПГН и МН). Заключение. Отложения C1q в клубочках почек выявлены в 4,05% биоптатов почек больных ХГН, наиболее частым морфологическим вариантом являлась МН. Клиническое течение характеризовалось нефротическим синдромом, более чем у половины больных - с нарушением функции почек.

BACKGROUND. Мonoclonal gammopathy (MG) is not only the state preceding of hematological neoplasms, but also associated with non- hematological diseases, in particular damage of kidneys. Earlier diagnosis of MG represents an important area in treating patients with renal diseases associated with MG. THE AIM: To determine the frequency of MG among therapeutic and nephrological patients for optimization of methods of their diagnosis and treatment. PATIENTS AND METHODS: In common, 11392 patients were analyzed within 4 years (2013-2016). The standard clinical examination was conducted. Method of an electrophoresis of proteins of serum of blood and the 24-hour urine, method of immunofixation of proteins of serum and urine, and method of free light chains definition in serum (Freelite) were used for MG identification. RESULTS: MG is diagnosed in 174 of 11392 patients: 49 % of men and 51 % of women aged from 18 up to 85 years. MG was found 2.1 times more often in nephrological patient than in patients of therapeutic departments. Among patients of this group, AL-amyloidosis with kidney involvement was diagnosed in 41 %, cryoglobulinemic glomerulonephritis – in 18 %, chronic glomerulonephritis – in 35 %, also there was small number of patients with light chain disease and cast-nephropathy. 86 % of nephrological patients had less than 5 g/l of monoclonal protein that corresponds oligo secretory MG, and at 46 % from them – less than 1 g/l, other 10 % had MG of 5-10 g/l, and only in 4.42 % of patients MG more 10g/l was defined. CONCLUSION: We conclude that MG, especially oligo secretory form, play a significant role in pathogenesis of renal damage. It is important to apply sensitive methods – immunofixation of proteins and method «Freelite» for nephrological patients.

Renal cell carcinoma (RCC) is the second-most common uronephrological cancer. In the absence of specific symptoms, early diagnosis of RCC is challenging. Monitoring of the aberrant expression of tumour-associated antigens (TAAs) and related autoantibody response is considered as a novel approach of RCC diagnostics. The aim of this study was to examine the aberrant expression of arrestin-1 in renal tumours, to investigate the possible epigenetic mechanism underlying arrestin-1 expression, and to assess the frequency of anti-arrestin-1 autoantibody response. Immunohistochemistry was used to assess the presence of arrestin-1 in primary tumours and metastases of 39 patients with RCC and renal oncocytoma. Bisulfite sequencing was employed to analyse the methylation status of the promoter of the SAG gene encoding arrestin-1. Western blot analysis was performed to detect autoantibodies against arrestin-1 in serum samples of 36 RCC and oncocytoma patients. Arrestin-1 was found to be expressed in RCC (58.7% of cases) and renal oncocytoma (90% of cases) cells, while being absent in healthy kidney. The expression of arrestin-1 in RCC metastases was more prominent than in primary tumours. Hypomethylation of the SAG gene promoter is unlikely to be the mechanism for the aberrant expression of arrestin-1. Autoantibodies against arrestin-1 were detected in sera of 75% of RCC patients. Taken together, our findings suggest employment of autoantibody against arrestin-1 as biomarker of RCC.

To discuss the possibilities and prospects of using artificial intelligence (AI) in the diagnosis of prostate cancer (PC). The laboratory diagnosis of PC is considered and prostate images are analyzed according to transrectal ultrasound and magnetic resonance imaging using AI algorithms. Particular emphasis is placed on prostate histologic evaluation.Обсуждение возможностей и перспектив применения искусственного интеллекта (ИИ) в диагностике рака предстательной железы (РПЖ). Рассмотрены лабораторная диагностика РПЖ, анализ изображений предстательной железы (ТРУЗИ, МРТ) с помощью алгоритмов ИИ. Особое внимание уделено оценке гистологии предстательной железы.

Patient K., 44 years old, has been ill since November 2018, when for the first time, for no apparent reason, noted the appearance of a painful pustule in the anterior surface of the left leg. After spontaneous opening of the element, an ulcer was formed, characterized by rapid growth (in 14 days up to 8-9 cm in diameter). I turned to a dermatologist, after consultation, treatment was carried out (prednisolone 30 mg per day, antibacterial drugs, vascular therapy, non-steroidal anti-inflammatory drugs) with a positive effect in the form of a gradual, complete scarring of the ulcer.

Mycosis fungoides (MF) is the most common primary cutaneous epidermotropic T-cell lymphoma (80%). The accurate diagnosis of MF confirmed only by clinical, histological and immunohistochemical signs amounts to 50-75%.To investigate genetic markers (FOXP3, STAT4, IL-12B) for the early diagnosis of MF, to estimate the informative value of used diagnostic techniques (histology, immunophenotyping), and to determine clonality by the T-cell receptor γ-chain genes.Fifty patients with MF and plaque parapsoriasis (PP) who had been treated at the V.A. Rakhmanov Clinic of Skin and Venereal Diseases and at the National Medical Research Center for Hematology were followed up. A MF group consisted of 27 patients; a PP group included 23 patients, and a control group comprised 10 healthy individuals. The expression of the FOXP3, STAT4, and IL-12B genes was analyzed by TaqMan real time-PCR. The objectives of the study were affected skin portions from patients with MF or PP and healthy individuals.The investigation revealed a increase in the expression level of STAT4 mRNA transcripts by 9 times in patients with MF compared with those with PP and by 553 times in healthy individuals. There was also a statistically significant predominance of the expression level of STAT4 mRNA transcripts in patients with spotted and plaque stages of MF (180; 318) compared with those with PP and healthy individuals, as well as a sharp decrease in those with erythrodermic MF, which was statistically significant.MF cannot be diagnosed without comprehensively assessing the clinical, anamnestic, histological, immunophenotypic, and molecular genetic data. The expression level of STAT4 mRNA transcripts is of great importance for the early diagnosis of MF. Inclusion of the level of STAT4 expression in the list of diagnostic signs increases the accuracy of differential diagnosis of MF and PP from 59.1 to 81.8%, respectively.Грибовидный микоз (ГМ) является наиболее распространенной первичной эпидермотропной Т-клеточной лимфомой кожи (80%). Достоверность диагноза ГМ, подтвержденного только клиническими, гистологическими и иммуногистохимическими признаками, составляет 50-75%. Цель исследования - изучить генетические маркеры (FOXP3, STAT4, IL-12B) для ранней диагностики ГМ, а также оценить информативность используемых методов диагностики (гистологического, иммунофенотипического) и определить клональности по генам γ-цепи Т-клеточного рецептора. Материал и методы. Под наблюдением находились 50 пациентов с ГМ и бляшечным парапсориазом (БП), леченных на базе Клиники кожных и венерических болезней им. В.А. Рахманова и ФГБУ 'НМИЦ гематологии'. Группу ГМ составили 27 пациентов, группу БП - 23, группу контроля - 10 здоровых лиц. Анализ экспрессии генов FOXP3, STAT4, IL-12B проводили методом TaqMan Real time-ПЦР. Объектами исследования были пораженные участки кожи больных ГМ, БП и здоровых лиц. Результаты. В ходе исследования выявлено повышение уровня экспрессии мРНК транскриптов STAT4 у пациентов ГМ в 9 раз по сравнению с больными БП и в 553 раза - со здоровыми лицами. Также было отмечено статистически значимое преобладание уровня экспрессии мРНК транскриптов STAT4 у пациентов с пятнистой и бляшечной стадиями ГМ по сравнению с больными БП и здоровыми лицами, а также его резкое снижение у пациентов с эритродермической формой ГМ, что является статистически достоверным. Заключение. Диагностика ГМ невозможна без комплексной оценки клинико-анамнестических, гистологических, иммунофенотипических и молекулярно-генетических данных. Для ранней диагностики ГМ приобретает большое значение уровень экспрессии мРНК транскриптов STAT4. Включение уровня экспрессии STAT4 в список диагностических признаков повышает точность дифференциальной диагностики ГМ и БП с 59,1 до 81,8% соответственно.

C1q glomerulopathy is a rare variety of chronic glomerulonephritis manifested as C1q deposition revealed by immunofluorescence microscopy. The pathogenesis and etiology of the disease have not been studied. The paper deals with the results of clinical, morphological, immunofluorescence, and electron microscopic examinations in 13 patients with C1q glomerulopathy. Light microscopy more commonly revealed membranous nephropathy, mesangioproliferative glomerulonephritis, and nephrosclerosis. Immunofluorescence microscopy detected a C1q fraction in association with other deposits, more frequently IgM and IgG ones. A correlation was found between the clinical presentation and morphological form of chronic glomerulonephritis.C1q-гломерулопатия - редко встречающаяся разновидность хронического гломерулонефрита, при которой выявляется отложение C1q в депозитах при иммунофлюоресцентной микроскопии. Патогенез и этиология заболевания не изучены. Приведены результаты клинико-морфологического, иммунофлюоресцентного и электронно-микроскопического исследований у 13 пациентов с C1q-гломерулопатией. При световой микроскопии чаще выявлялись мембранозная нефропатия, мезангиопролиферативный гломерулонефрит, нефросклероз. При иммунофлюоресцентной микроскопии C1q-фракция обнаруживалась в ассоциации с другими компонентами депозитов, чаще IgM и IgG. Выявлена связь при сравнении клинических проявлений заболевания и морфологической формы хронического гломерулонефрита.

Renal cell carcinoma (RCC) ranks the first death rate among the urogenital tumors, whereas its incidence follows the incidences of prostate and bladder cancer. The diagnosis of RCC at early stages allows immediately undertaking appropriate treatment, which significantly increases patients' survival rate. Early and accurate diagnosis avoids inadequate treatment, provides the disease progression forecast, and permits to apply more efficient therapy. Unfortunately, the small renal tumors are usually asymptomatic resulting in the late diagnosis and, therefore, low efficacy of treatment. Thus, sensible and preventive biomarkers are essential for early RCC detection and monitoring of its progression. So far, many attempts were performed aimed at recognizing novel informative kidney tumor biomarkers applicable for early detection of the disease and possessing prognostic and predictive capabilities. This review summarizes recent advances in renal tumor biomarkers recognition, their diagnostic and prognostic values, and clinical feasibility.

BACKGROUND Early diagnosis of prostate cancer (CaP) can be addressed by studying prostatic intraepithelial neoplasia (PIN) as precancer (high-grade PIN or HGPIN). This article attempts to analyze the diagnostic role of telomerase as an early marker of carcinogenesis. METHODS Complex urological patient evaluation and assessment of telomerase activity. RESULTS Out of 92 patients 44% were diagnosed with CaP, 49% with low-grade PIN (LGPIN) in association with benign prostatic hyperplasia (BPH), and 7% with HGPIN in association with BPH. Active telomerase (AT) in prostate biopsy specimens was detected in 98% of patients with CaP, in 33% of patients with HGPIN, and in 20% of patients with LGPIN. In the event of simultaneous detection of AT and PIN in initial prostate biopsy specimens, further monitoring for 0.5–4.0 years revealed CaP development in 50–56% of cases. Further follow-up of patients with PIN and absent telomerase activity in initial biopsy specimens did not demonstrate the development of CaP. The PSA level was significantly higher in patients with active telomerase in the prostate tissue than in telomerase negative patients. CONCLUSIONS Telomerase activity in the prostate tissue increases the risk of CaP development in patients with PIN. Detection of telomerase activity in prostate biopsy specimens from patients with PIN enables selection of a group of patients with high risk of CaP development and reduction of the number of prostate biopsies performed in other patients. Prostate 74:1043–1051, 2014. © 2014 Wiley Periodicals, Inc.

The authors characterized a heterogeneous group of a rare disease - Langerhans and non-Langerhans cell histiocytosis, and analyzed key differential and diagnostic differences between these forms of the disease. A very rare case of non- Langerhans cell histiocytosis (Rosai-Dorfman disease) in a female patient aged 63 with the subsequent spontaneous regression of eruptions was described. Key skin manifestations of the Rosai-Dorfman disease included papular eruptions of the typical intense pink color with a yellowish and brown tint. Morphologic changes were characterized by proliferation of histiocytes and accumulation of different lipids and pentalamellar markers (S-100 protein, СD 14, СD 68, lysozyme) in their cytoplasm. Though the Rosai-Dorfman disease usually involves lymph nodes, this case was characterized by unaffected nodular structures.

A case of the immunoglobuline deposit disease diagnosis in MM patient having the symptoms of intensive proteinuria, macrohematuria and terminal renal failure is reported. The disease was diagnosed by the evidence from electron microscopy of the kidney and liver biopsies.

The renal cell carcinoma is the ninth most common cancer with an increasing occurrence and mortality. Recoverin is the first retina-specific photoreceptor protein that was shown to undergo aberrant expression, due to its promoter demethylation, as a cancer-retina antigen in a number of malignant tumors. In this work, we demonstrated that recoverin is indeed expressed in 68.4 % of patients with different subtypes of renal cell carcinoma, and this expression has tendency to correlate with tumor size. Interestingly, 91.7 % of patients with the benign renal tumor, oncocytoma, express recoverin as well in their tumor. Epigenetic analysis of the recoverin gene promoter revealed a stable mosaic methylation pattern with the predominance of the methylated state, with the exception of -80 and 56 CpG dinucleotides (CpGs). While the recoverin expression does not correlate withoverall survival of the tumor patients, the methylation of the recoverin gene promoter at -80 position is associated with better overall survival of the patients. This work is the first report pointing towards the association of overall survival of renal cell carcinoma (RCC) patients with promoter methylation of a cancer-retina antigen. Taken together, these data allow to consider recoverin as a potential therapeutic target and/or marker for renal tumors.

Local processes in massively parallel computing systems can be coordinated by asynchronous system of global synchronization via handshake using current sensors for detection of the transient processes completion. The known current sensors are considered, the best one is analyzed, and its shortcomings are revealed. Current sensor with wide range of the measured current is suggested. The principles of control in circuits with current sensors are developed. Self-timed data exchange between local processes of the system is discussed. Transmission/reception circuits with single-wire bit handshake are demonstrated. Their transmission rate is no worse than that of double-wire circuits. They allow one to transmit combinations of n-bit code by n + 2 communication lines. © 1997 John Wiley & Sons, Inc. Integrated Computer-Aided Engineering, Vol. 4( I ), 47-65, January 1997.

Early diagnosis of prostate cancer (CaP) can be addressed by studying prostatic intraepithelial neoplasia (PIN) as precancer (high-grade PIN or HGPIN). This article attempts to analyze the diagnostic role of telomerase as an early marker of carcinogenesis.Complex urological patient evaluation and assessment of telomerase activity.Out of 92 patients 44% were diagnosed with CaP, 49% with low-grade PIN (LGPIN) in association with benign prostatic hyperplasia (BPH), and 7% with HGPIN in association with BPH. Active telomerase (AT) in prostate biopsy specimens was detected in 98% of patients with CaP, in 33% of patients with HGPIN, and in 20% of patients with LGPIN. In the event of simultaneous detection of AT and PIN in initial prostate biopsy specimens, further monitoring for 0.5-4.0 years revealed CaP development in 50-56% of cases. Further follow-up of patients with PIN and absent telomerase activity in initial biopsy specimens did not demonstrate the development of CaP. The PSA level was significantly higher in patients with active telomerase in the prostate tissue than in telomerase negative patients.Telomerase activity in the prostate tissue increases the risk of CaP development in patients with PIN. Detection of telomerase activity in prostate biopsy specimens from patients with PIN enables selection of a group of patients with high risk of CaP development and reduction of the number of prostate biopsies performed in other patients.

This paper deals with the kinetics of tint transfer in soft contact lenses. A mathematical model taking into account both diffusion and chemical reactions is proposed and physicochemical parameters are determined. It is shown that bulk tinting is more effective in practice than surface tinting.

The problems are discussed that arise when designing massively parallel computer systems. The transition from globally synchronized working of such systems to globally asynchronous behavior resolves most of them. This transition implies that all the local processes in the system should interact between each other on the base of asynchronous interfaces. The problems of asynchronous interaction of local processes with the system of their global coordination on the base of handshake are considered as well as the problems of self-timed data transmission between processes. If the system modules that realize local processes are not asynchronous and implemented in CMOS-technology, then, to detect the moments of the transient processes completion in them, the idea of current indication is used. A circuit of a current sensor is suggested with wide range of permissible changes of the measured current and with admissible characteristics. Two ways of organizing the interaction between circuits with current sensors are developed. The principles of self-timed data exchange between local processes of the system and data transmission by means of a dual-rail code and binary code with handshake for every bit are considered. The possibility of organizing single-wire bit handshake is demonstrated and its self-timed implementation is developed with the transmission rate no worse than that of double-wire bit handshake. >

We discuss the problem of designing asynchronous control devices for discrete event coordination specified by a Petri net model. The design is based on the compilation of standard circuit modules corresponding to PN fragments into a net modeling PN behavior and on the semantic interpretation of the modeling circuit. The impossibility of asynchronous implementation of the indivisible operation of marking change at the circuit level leads to the necessity of modeling PN with modified rules of marking change. Modifications of the known modules, a number of new module types, the rules of the module connections, and the procedures of minimization are given that considerably improve the quality of the obtained solutions in terms of both speed and area. The design “reefs” are fixed. The minimization procedures are usually associated with a change of marking change rules producing the problems of providing the equivalence of the initial and modified PNs.

A concept of the pathogenesis of tubular interstitial nephritis (TIN) is presented, based on histologic, immunohistologic and electromicroscopic investigations on 61 patients with glomerulonephritis, lupus erythematodes and rheumatoid arthritis. The pathogenic model is a hypersensitivity reaction which leads to alterations in the tubular basement membrane (TBM) and results in changes in the TBM and secondary damage to stroma, vessels and tubular cells. The findings change depending on the stage, reflecting the transition from an acute to a chronic process. In acute TIN which is generally a drug allergy, the dominant characteristic of the inflammatory process allows the reaction to be categorized in edematous (72%), cellular (23%) and tubular necrotic (5%) types. The cellular types show 4 subdivisions: plasma cellular, eosinophil-granulocytic, lymphohistiocytic and granulomatous. Chronic TIN is in particular characterized through the destruction of the TBM, dystrophy and atrophy of the tubules as well as their degeneration, lymphohistiocytic infiltrates and sclerotic stroma reactions. A distinction is made between cellular destructive and atrophic-sclerotic types. At view of the etiology and pathogenesis a distinction should be made between an infectious and non-infectious TIN and further by the character of the immunoreaction, into a primary and secondary form. If there glomerular changes are present and there is evidence of an immune phenomenon in the glomeruli and TBM we recommend the use of the term glomerulo-tubulo-interstitial nephritis.

A total of 1,308 renal biopsies performed during the years 1978 to 1983 in Moscow (M, 852 cases) and Rostock (R, 456 cases) showed that 685 (80.4%) and 346 (75.9%), in the two cities respectively, had glomerular disorders when classified according to WHO nosology (Churg and Sobin 1982). Among the 1,031 glomerulopathies from the two cities there were 121 with minor glomerular abnormalities (M: 49 = 7.1%; R: 72 = 20.8%), 145 with focal segmental glomerulopathies (M: 76 = 11.1%; R: 69 = 20.0%), and 765 with diffuse glomerulopathies (M: 560 = 81.6%; R: 205 = 59.3%). The 765 diffuse glomerulopathies from the two series were distributed according to the WHO classification into 77 membranous (M: 63 = 9.25%; R: 14 = 4.1%), 519 mesangioproliferative (M: 380 = 55.5%; R: 139 = 40.2%), 11 endocapillary proliferative (M: 5, R: 6), 99 mesangiocapillary (M: 65 = 9.5%; R: 34 = 10.4%), 2 dense deposit (in R), 4 extracapillary (M: 1, R: 3) and 53 sclerosing glomerulonephritides (M: 46 = 6.7%; R: 7 = 2.0%). Utilization of the WHO classification of glomerular diseases proved to be a useful compromise, allowing two different schools of nephropathology to agree on classification of renal biopsy material. The group of minimal change abnormalities and the focal segmental lesions should be subclassified further according to the clinical and morphologic findings.

The development of cell-sensitization to renal antigen in rats with experimental Heymann's glomerulonephritis and the effect of levamisole on cell sensitivity have been studied. Morphologic changes in GN rats appeared after 14 days and were most pronounced on days 21-28, with focal proliferation of glomerular cells, an increase of mesangium, a focal increase of the basal membrane material. After day 49 the changes improved slightly and were still the same on day 147 when a location of IgG to the glomerular basal membrane was detected. In every GN rat, cell-sensitivity to renal antigen was revealed from day 21 of the experiment till its end. Levamisole treatment decreased renal morphologic changes and abolished cell-sensitivity to renal antigen. The possible mechanisms of preventing the development of cell-sensitization in rats treated with levamisole are discussed.