Pilot Experiment on Non-Invasive Non-Thermal Disintegration of Human Mucinous Breast Carcinoma Ex Vivo Using Boiling Histotripsy.

We present the results of a pilot study demonstrating the feasibility of non-invasive non-thermal disintegration of human mucinous carcinoma of the breast ex vivo using sequences of high-intensity focused ultrasound pulses in boiling histotripsy regimen. The target volume was sonicated by focusing ultrasound pulses (n=20) of 1.5 MHz frequency, 10-msec duration and 1-sec pulse repetition period, 517 W acoustic power within the pulse, and 103 MPa shock front amplitude at the focus into each node of a volumetric grid 4×4×1 mm. Sonication was visualized and controlled using B-mode ultrasound imaging, total time of the treatment was 21 min. Histological hematoxylin and eosin and Masson's trichrome staining revealed the absence of tumor elements in the treated region confirming destruction of cancer cells and their nuclei after boiling histotripsy procedure.

[Morphology of hypersensitivity pneumonitis]. / Morfologiya giperchuvstvitel'nogo pnevmonita.

Hypersensitivity pneumonitis (HP) is one of the most common interstitial lung diseases, the manifestations of which are diverse, and the diagnosis is complex and requires a multidisciplinary approach. HP is an immunologically determined disease in response to inhaled antigens. The main feature of the disease is terminal bronchiole's involvement accompanied by interstitial inflammation and/or fibrosis together with the presence of non-necrotizing granulomas in the interalveolar septa and bronchioles. The article presents the histological features of non-fibrous and fibrotic variants of the disease. Well-defined diagnostic criteria were formulated on the basis of published international recommendations and the authors' own experience.

[Clinical and morphological features of lung injury long-term after SARS-CoV-2 recovery].

AIM: To study the clinical and histological profile of lung tissue in patients with persistent pulmonary disease, respiratory symptoms and CT findings after SARS-CoV-2 infection. MATERIALS AND METHODS: The study included 15 patients (7 females and 8 males) with a mean age of 57.7 years. All patients underwent laboratory tests, chest computed tomography, echocardiography, and pulmonary function tests. Pulmonary tissue and bronchoalveolar lavage samples were obtained by fibrobronchoscopy, transbronchial forceps (2 patients), and lung cryobiopsy (11 patients); open biopsy was performed in 2 patients. Cellular composition, herpesvirus DNA, SARS-CoV-2, Mycobacterium tuberculosis complex, galactomannan optical density index, and bacterial and fungal microflora growth were determined in bronchoalveolar lavage. SARS-CoV-2 was also identified in samples from the nasal mucosa, throat and feces using a polymerase chain reaction. RESULTS: The results showed no true pulmonary fibrosis in patients recovered from SARS-CoV-2 infection with persistent respiratory symptoms, functional impairment, and CT findings after SARS-CoV-2 infection. The observed changes comply with the current and/or resolving infection and inflammatory process. CONCLUSION: Thus, no true pulmonary fibrosis was found in patients after SARS-CoV-2 infection with persistent respiratory symptoms, functional impairment, and CT findings. The observed changes comply with the current and/or resolving infection and inflammatory process.

Pilot ex vivo study on non-thermal ablation of human prostate adenocarcinoma tissue using boiling histotripsy.

Focused ultrasound technologies are of growing interest for noninvasive ablation of localized prostate cancer (PCa). Here we present the results of the first case study evaluating the feasibility of non-thermal mechanical ablation of human prostate adenocarcinoma tissue using the boiling histotripsy (BH) method on ex vivo tissue. High intensity focused ultrasound field was generated using a 1.5-MHz custom-made transducer with nominal F#=0.75. A sonication protocol of 734 W acoustic power, 10-ms long BH-pulses, 30 pulses per focal spot, 1 % duty cycle, and 1 mm distance between single foci was tested in an ex vivo human prostate tissue sample containing PCa. The protocol used here has been successfully applied in the previous BH studies for mechanical disintegration of ex vivo prostatic human tissue with benign hyperplasia. BH treatment was monitored using B-mode ultrasound. Post-treatment histologic analysis demonstrated BH produced liquefaction of the targeted tissue volume. BH treated benign prostate parenchyma and PCa had similar tissue fractionation into subcellular fragments. The results of the study demonstrated that PCa tumor tissue can be mechanically ablated using the BH method. Further studies will aim on optimizing protocol parameters to accelerate treatment while maintaining complete destruction of the targeted tissue volume into subcellular debris.

[Comparative pathomorphological characteristics of idiopathic pulmonary fibrosis and fibrotic hypersensitivity pneumonitis]. / Sravnitel'naya patomorfologicheskaya kharakteristika idiopaticheskogo legochnogo fibroza i fibroznogo giperchuvstvitel'nogo pnevmonita.

The paper presents an X-ray morphological differential diagnosis of idiopathic pulmonary fibrosis (IPF) and fibrotic hypersensitivity pneumonitis (FHP). It describes the etiology, pathogenesis, radiological signs, and pathoanatomy of IPF and FHP. For differential diagnosis, radiological and morphological signs were studied in 105 patients with IPF and in 111 patients with FHP. The mean ages of patients with IPF or FHP were 65.0±8.9 and 48.9±12.3 years, respectively. The history of IPF to the moment of its diagnosis ranged from 1 to 18 months, while that of FHP was 35 to 79 days. The authors describe the additional morphological signs of FHP: delicate collagen fibrosis; smooth muscle metaplasia in the interalveolar septa and fibrotic areas; fibroblastic foci mainly in the walls of bronchioles; plasma cell infiltration of interalveolar septa with a touch of neutrophils and eosinophils. A table has been compiled for differential diagnosis according to the morphological signs of IPF and FHP.

Telocytes in the Myocardium of Children with Congenital Heart Disease Tetralogy of Fallot.

Telocytes, a new type of interstitial stem cells with long thin processes that form a three-dimensional network around cardiomyocytes, vessels, and nerve fibers were described in the myocardium of children with tetralogy of Fallot. Two types of morphologically different telocytes, spindle-shaped and rounded, were identified. Contacts of telocytes with stem cells and interstitial macrophages were found. Telocytes were more common in the immature myocardium, where the assembly of myofibrils in cardiomyocytes was not completed and small Ki-67+ cardiomyocyte progenitor cells were present. Telocytes expressed immunohistochemical markers CD117, vimentin, CD34, and CD44. Localization and ultrastructural characteristics of telocytes suggested their participation in stem cell differentiation, coordination of neoangiogenesis, and paracrine regulation of all components of the interstitium.

[Histological differential diagnosis of granulomatous lung diseases (Part II)]. / Gistologicheskaia differentsial'naia diagnostika granulematoznykh boleznei legkikh (chast' II).

Granulomatous diseases are a heterogeneous group of the diseases of different etiology, which are manifested by a variety of clinical syndromes and variants of tissue changes, by non-uniform sensitivity to therapy and by the predominance of the common dominant histologic sign - the presence of granulomas that determine the clinical and morphological essence of each disease. Granuloma is a chronic inflammatory response, which involves macrophages and other inflammatory cells. After antigen exposure, the activation of T lymphocytes, macrophages, epithelioid cells, and multinucleated giant cells results in granuloma formation. Granuloma also contains the extracellular matrix produced by fibroblasts, which can demarcate and isolate the antigen. Granulomatous diseases are classified by their etiology as infectious and non-infectious. However, recent investigations demonstrate that pathogenic microorganisms can cause granulomas in the diseases previously considered non-infectious. In some cases, it is very difficult to classify a granulomatous process as infectious and non-infectious. The aim of this paper is to draw the attention of readers to the diversity of granulomatous diseases, to describe the key points of pathological and anatomical manifestations of various infectious diseases, and to determine an approach to the differential diagnosis of granulomatoses.

[Histological differential diagnosis of granulomatous lung diseases (part I)]. / Gistologicheskaia differentsial'naia diagnostika granulematoznykh boleznei legkikh (chast' I).

Granulomatous diseases are a heterogeneous group of the diseases of different etiology, which are manifested by a variety of clinical syndromes and variants of tissue changes, by non-uniform sensitivity to therapy, and by the predominance of the common dominant histologic sign - the presence of granulomas that determine the clinical and morphological essence of each disease. Granuloma is a chronic inflammatory response, which involves macrophages and other inflammatory cells. After exposure to an antigen, T-lymphocytes, macrophages, epithelioid cells, and multinucleated giant cells are activated, resulting in the formation of granulomas. Granuloma also includes the extracellular matrix produced by fibroblasts, which can demarcate and isolate the antigen. According to etiology, granulomatous diseases are classified as infectious and non-infectious. However, recent investigations demonstrate that pathogenic microorganisms can cause granulomas in diseases previously considered non-infectious. In some cases, it is very difficult to classify a granulomatous process as infectious and non-infectious. The aim of this paper is to draw the attention of readers to the diversity of granulomatous diseases, to describe the key points of pathological and anatomical manifestations of various non-infectious diseases, as well as to determine an approach to the differential diagnosis of granulomatoses.

[Kaposi's sarcoma in the grafted lung]. / Sarkoma Kaposhi v transplantirovannykh legkikh.

The paper provides a clinical note. A 45-year-old patient suffered from severe primary emphysema and underwent bilateral lung transplantation. A year after surgery, exercise dyspnea again appeared in the patient. Lung computed tomography revealed multiple rounded soft tissue masses; thoracoscopic biopsy and further histological examination proved the development of Kaposi's sarcoma in the patient. The tumor disappeared completely following corrected immunosuppressive therapy. After 22 months of transplantation, the patient died from gastrointestinal bleeding. This case is of interest due to that Kaposi's sarcoma develops extremely rarely in the allogeneic lung after its transplantation.

Resident stem cells in the myocardium of patients with obstructive hypertrophic cardiomyopathy.

Interventricular septum myocardium was studied in 40 patients with obstructive hypertrophic cardiomyopathy. Immunohistochemical assay revealed c-kit-positive resident cardiac stem cells in 82.5% patients. The content of the connective tissue and myofibrillar disarray zones and the degree of cardiomyocyte hypertrophy and myolysis were determined. In 30% cases, cardiomyocytes containing atrial natriuretic peptide were detected in the interventricular septum myocardium. The data were compared with clinical and functional parameters of patients. It was found that cardiac stem cells are present in patients, whose myocardium was characterized by increased density of the connective tissue, hypertrophy of mature cardiomyocytes, medium degree of myolysis in them, and accumulation of natriuretic peptide, a cardiac failure marker, in cardiomyocytes.

Resident cardiomyocyte precursor stem cells in the myocardium of infants of the first two years of life with tetralogy of Fallot.

We studied the content of resident myocardial stem cells, cardiomyocyte precursors, in myocardial biopsy specimens from the right ventricular outflow tract of patients of the first two years of life with tetralogy of Fallot. Myocardial resident stem cells were detected by the method of confocal immunohistochemistry using antibodies to c-kit and sarcomeric α-actin. The diameter of right ventricular cardiomyocytes was measured; the presence of myolysis zones was semiquantitatively evaluated. Electron microscopic analysis of right ventricular cardiomyocytes was performed. The data on the content of resident myocardial stem cells were compared with clinical and functional parameters of the patients and morphological peculiarities of the myocardium. C-kit-positive resident myocardial stem cells were detected in the right ventricle of 17.4% patients with tetralogy of Fallot. The content of resident myocardial stem cells in these patients varied from 4 to 45 (median 11) per 1 mln cardiomyocytes; this parameter was higher in patients with high content of small cardiomyocytes (diameter <10 µ) and cardiomyocytes with incomplete myofibril assembly in the right ventricular myocardium.

Pathomorphological peculiarities of microcirculatory bed in bronchial wall in workers employed in mining and chemical industry.

Morphological alterations of microvessels in bronchial mucosa and blood capillaries of alveolar septa during endobronchitis were examined in workers employed at a plutonium plant and not employed residents (Zheleznogorsk, Krasnoyarsk Region). Alterative, destructive, and dysadaptive changes in pulmonary vessels of workers were paralleled by developing reparative and adaptive processes in neighboring capillaries.

Wall thickness and constrictive responses of the caudal artery in rats with renovascular hypertension.

In rats with hypertension modeled by the one kidney-one clamp method, constrictory responses of the isolated caudal artery to norepinephrine differed under various perfusion conditions. Vascular reactions in hypertensive rats were more potent at a constant flow rate, and less potent at a constant pressure compared to those in normotensive rats. Previous experiments demonstrated similar changes in constrictory responses of the caudal artery in spontaneously hypertensive rats. It is assumed that these peculiarities of the vascular reactivity during hypertension are determined by thickening of the smooth muscle layer of the vascular wall.

Variability of the cardiomyocyte ploidy in normal human hearts.

We have performed cytophotometry for DNA in isolated myocytes of the left ventricle from 16 men, aged 19-39 years, who died from various non-cardiac or pulmonary causes. The mean ploidy of myocytes varied from 3.2-3.9 c to 6.6-7.3 c in different layers of the anterior wall of the left ventricle (where c is the haploid DNA content measured by cytophotometry in Feulgen-stained preparations). There was no correlation between the layers. The percentage of binuclear cells varied from 25 to 86% and correlated in every layer with the mean ploidy value of the whole myocyte population. Approximate calculation of total ploidy revealed low values in the ventricles of some individuals, and high values in others. Averaging the values for all the hearts studied obscures this variation. Mean myocyte ploidy in different layers of the anterior wall was similar: in the external layer it was 5.1 +/- 0.3 c, in the middle layer 5.5 +/- 0.3 c and in the inner layer 4.8 +/- 0.4 c. The mean percentage of binuclear myocytes in these three layers was also similar, being 61 +/- 3%, 63 +/- 4% and 54 +/- 5%, respectively. Myocyte ploidy in tissue from the posterior wall of the left ventricle also varied, but was always higher than for the same layer of the anterior wall in the same ventricle. We propose that high or low myocyte ploidy, as well as different proportions of mono- and binucleate cells, can be a factor affecting the course and result of cardiac pathology in the absence of any changes of myocyte genome determined during early ontogenesis and representing a stable characteristic of the individual.