Accumulation Of Acid Mucopolysaccharides Research Articles

Cellular/intercellular interrelations in various parts of aorta after reconstructive treatment of aortic stenosis in infants

Aim. The article focuses on the evaluation of cellular/intercellular relationships in various parts of the aorta after reconstructive treatment of aortic stenosis in infants.Methods. Medical histories and protocols of autopsies of three newborns were studied after surgical treatment of aortic coarctation. The operations were performed in children at 8th, 10th and 15th day after birth. In two cases, resection of the aortic lumen narrowing, botulinum duct ligation and formation of a direct aortic anastomosis were performed. In one observation, a closed balloon dilatation of the aorta in the area of constriction was used. When performing autopsy, the size of the heart, the perimeter of the aorta at the surgical sites and various parts of the aorta were examined. The fragments of the wall of the aortic sections were cut out and fixed in 10% neutral formalin. Histologic sections were prepared in a conventional way followed by staining them with hematoxylin-eosin or picrofuxin by Van Gieson, while elastic fibers were stained with rezorcin-fuchsin by Hotchkiss and Periodic acid–Schiff (PAS) in order to detect mucopolysaccharides.Results. Cellular/intercellular relationships in various parts of the aorta following aortic coarctation in infants have some morphological features. Morphometric examination of the heart and aorta showed a significant increase in the volume and mass of the heart compared with the normal values due to myocardial hypertrophy of the right and left ventricles of the heart. An uneven narrowing of the aortic lumens was most pronounced in the arch and isthmus as compared to the ascending and thoracic parts of aorta. Morphological examination of the aortic wall in the constriction zones demonstrated the presence of coagulation necrosis, lysis of elastic, collagen fibers with surrounding hyperplasia of smooth myocytes, newly formed thin-walled capillary vessels. Outside the coarctation zone, the most significant changes characterized by the development of hypoelastosis, non-uniform accumulation of acid mucopolysaccharides were observed in the walls of the arch and the ascending aorta. Conclusion. In infants with coarctation of the aorta, dilatation of the ascending aorta with compensatory hypertrophy of the heart is observed, and a muscle-fibrous tissue, rich in smooth myocytes and newly formed thin-walled vessels, tends to develop in stenotic zones. The risk of restenosis development is believed to depend on the prevalence and severity of proliferative processes of the cellular elements of the aorta, which allows us to consider early surgical interventions to prevent irreversible destructive changes as justifiable.Received 2 February 2017. Accepted 27 May 2017.Funding: The study required no additional funding and sponsorship.Conflict of interest: The author declares no conflict of interest.AcknowledgementsThe author expresses his gratitude towards Professor S.V. Shlyk, Dr. Sci. (Medicine), Rector of Rostov State Medical University, Professor N.I. Volkova, Dr. Sci. (Medicine), Pro-Rector for Research of Rostov State Medical University and the researchers of the Molecular/Biological & Optical Research Methods Department.

Scleromyxedema (Arndt-Gottron Syndrome): a Case Report

Abstract Lichen myxedematosus, also known as papular mucinosis, is a primary diffuse cutaneous mucinosis. It is a rare cutaneous myxedematous condition characterized by formation of numerous lichenoid papules. Scleromyxedema, also known as Arndt–Gottron syndrome, is a rare, confluent, papular and sclerotic variant of lichen myxedematosus, characterized by diffuse thickening of the skin underlying the papules. The condition is associated with systemic, even lethal manifestations, fibroblast proliferation and accumulation of acid mucopolysaccharides of the hyaluronic acid. Serum IgG class paraproteinemia is always present and it can be detected in all patients if appropriate or even repeat testing is used. Herein, we present a 67-year-old patient with a 2-year history of skin problems. He had no health problems other than hypertension and diabetes, wich were both diagnosed 15 years before. On examination, the patient exhibited sclerodermoid lesions with diffuse pseudo-sclerodermatous thickening of the exposed skin, microstomia and sclerodactyly-like changes; on the face, there were numerous solid, shiny 2 - 4 mm in diameter skin-coloured lichenoid papules, scattered across the forehead, glabellar area, nasolabial folds, perioral region, ear lobes and the neck. Histopathological examination revealed: highly distinctive collagenosis and fibrosis in the middle dermis, increased fibroblasts; collagen bundles with irregular arrangement and fragmentation; alcian blue-positive deposits with appearance consistent with acid mucins. Serum protein electrophoresis detected IgG lambda paraproteinemia. The patient was treated with systematic corticosteroids during 9 months with subsequent introduction of methotrexate and showed satisfactory results. The etiology of scleromyxedema remains unknown, since the purified IgG paraprotein itself has no direct effects on fibroblast proliferation. In scleromyxedema, numerous therapeutic modalities are proposed, unfortunatelly with limited effects. In colclusion, we report a case of an adult male with lichenoid papules; after a two-year progression, they evolved into scleromyxedema and exhibited well response to conventional therapy.

Transforming growth factor-beta signaling pathway in Marfan’s syndrome: a preliminary histopathological study

Marfan's syndrome is an inherited disorder that affects the connective tissue. It has been proposed that mutations of FBN1 gene or of transforming growth factor (TGF)-beta type II receptor may be responsible for its pathogenesis. However, the role of TGF-beta signaling pathway in the development of Marfan's syndrome has not been comprehensively investigated. Surgical specimens of the aorta were obtained from two female Marfan patients, and the control aortic tissue was taken from an autopsy of a healthy individual. The aortic specimens were examined with hematoxylin-eosin, Masson's trichrome, von Gieson/victoria blue-van Gieson bichrome, and immunohistochemical stainings of TGF-beta1, TGF-beta type I receptor, Smad2/3, Smad4 and Smad7. Hematoxylin-eosin staining demonstrated severe elastic lamellar disruption and patchy vascular smooth muscle dissolution in the aortic media of the Marfan patients. Collagen deposition, interlamilar elastic fiber fragmentation, loss or proliferation, and acid mucopolysaccharide accumulation were observed in the disarrayed aortic wall structures of Marfan patients by Masson's trichrome, victoria blue-van Gieson bichrome, and Alcian blue and periodic schiff's (AB-PAS) stainings, respectively. By immunohistochemistry, structural disruptions with enhanced TGF-beta;1 in the cytoplasm, Smad2/3 in the interstices, Smad4 in the cytoplasm, nuclei or interstices, and OOO Smad7, in the nucleus along with attenuated TGF-beta type I receptor in the aortic tissues of Marfan patients in comparison to the healthy control. Marfan patients may have aberrant TGF-beta signaling pathway associated with increased collagen deposition, interlamilar elastic fiber degenerative changes, and acid mucopolysaccharide accumulation. The signaling dysregulation may play an important role in the pathogenesis of this genetic disorder.

Early detection of left ventricular dysfunction in patients with mitral regurgitation due to flail leaflet is still a challenge

This editorial refers to ‘Prognostic and therapeutic implications of pulmonary hypertension complicating degenerative mitral regurgitation due to flail leaflet: A Multicentre Long-term International Study’ by A. Barbieri et al., doi:10.1093/eurheartj/ehq294 Lack of normal mitral leaflet apposition and abnormal pointing of the flail component into the left atrium (LA) during systole are typical features of mitral leaflet flail which generate haemodynamically relevant mitral regurgitation (MR). The most common reason for mitral leaflet flail is chord rupture.1 Rarely, severe prolapse with the leaflet tip bulging into the LA causing severe MR can also occur without chord rupture.2 The flow direction impacting the mitral leaflets and anatomical features of the leaflets in patients with mitral valve prolapse (MVP) may facilitate chord rupture. Rupture of the chord or papillary muscle is the major cause of acute severe MR due to mitral leaflet flail. Flail mitral leaflet is associated with significant risk of developing left ventricular (LV) dysfunction, atrial fibrillation, pulmonary hypertension, tricuspid regurgitation (TR), heart failure, and sudden death.1–3 Although MVP has a higher prevalence in younger women, mitral leaflet flail often affects males >50 years of age.1,2 The aetiology of mitral leaflet flail is complex. Prolapsed myxomatous mitral valves show collagen and elastic tissue alterations, and in spontaneously ruptured mitral chords the myxomatous process often involves mitral chords and papillary muscles. In spontaneously ruptured chords, collagen types III and AB are often absent. Impaired mechanical properties due to collagen alterations and acid mucopolysaccharide accumulation in the mitral leaflets and chords may lead to spontaneous chord rupture. Myxoid chords are more extensible and weaker than normal chords and the failure resistance is more likely to be compromised in the chord than in the leaflet.2,4 Relevant fibrosis of the myxoid chords, particularly near their …

Dissecting aneurysms involving both anterior cerebral artery and aorta

Non-traumatic intracranial dissecting aneurysm (IDA) has been recently reported with increasing frequency and is recognized as a possible cause of subarachnoid hemorrhage. However, the pathogenesis of this disease is still unclear. Cystic medial necrosis (CMN) is known to be a cause of aortic dissection, especially in Marfan's syndrome. Presented herein is the case of a 49-year-old man who had IDA of the right anterior cerebral artery and abdominal aortic dissection without Marfan's syndrome. Histological examination showed medial degenerative changes with the accumulation of acid mucopolysaccharides in various intra- and extracranial arteries. Coexistence of dissecting aneurysms in the anterior cerebral artery and aorta suggests the presence of underlying pathogenesis that is common to these two dissection processes.

Adenosquamous carcinoma of the tongue: Report of a case with histochemical, immunohistochemical, and ultrastructural study and review of the literature

A rare case of oral adenosquamous carcinoma in a 78-year-old woman is reported. The tumor occurred in her tongue and metastasized to the submandibular and cervical lymph nodes. Histologically, the tumor showed invasive growth involving the submucosal and muscle layers. Its solid carcinomatous nests exhibited ductal differentiation in the deeper aspects and squamous differentiation toward the surface. Histochemical examination revealed an accumulation of acid mucopolysaccharide in the ductal lumina, and the ductal cells were immunohistochemically positive for carcinoembryonic antigen, epithelial membrane antigen, cancer antigen 15-3 and Ulex europaeus agglutinin I. Ultrastructurally, tonofibrils, desmosomes and numerous cytoplasmic processes were common features of the tumor cells. In addition, true glandular structures and pseudocysts were seen in areas. Clinical features of 13 adenosquamous carcinomas in the literature were analyzed.

Toxic effects of solanum malacoxylon on sheep bone

Solanum malacoxylon (Sm), a calcinogenic plant that contains 1,25-(OH) 2D 3 glycoside, was administered orally to sheep. Fifty milligrams of air-dried leaves three times a week caused an increased volume density of cancellous bone within lumbar vertebrae and an increased trabecular thickness. There was little remodeling activity at the end of a 180-day treatment period, and few trabecular bone surfaces had let-racycline double labels at this time. Bone biopsies taken at the end of a 1-month treatment demonstrated increased extent of bone-forming surfaces and osteoid volume. Sm caused a mineralization defect that was transitory but resulted in unmineralized lines and foci in osteones. These remaining foci of unmineralized bone were associated with the deposition of acid mucopolysaccharide, and acid mucopolysaccharide accumulation could be identified on all bone envelopes in 30-day biopsy specimens. A similar hyperostosis in the metaphyses of rats was produced by parenteral administration of 1,25-(OH) 2D 3 for 10 days.

Toxic effects of solanum malacoxylon on sheep bone

Solanum malacoxylon (Sm), a calcinogenic plant that contains 1,25-(OH) 2D 3 glycoside, was administered orally to sheep. Fifty milligrams of air-dried leaves three times a week caused an increased volume density of cancellous bone within lumbar vertebrae and an increased trabecular thickness. There was little remodeling activity at the end of a 180-day treatment period, and few trabecular bone surfaces had tetracycline double labels at this time. Bone biopsies taken at the end of a 1-month treatment demonstrated increased extent of bone-forming surfaces and osteoid volume. Sm caused a mineralization defect that was transitory but resulted in unmineralized lines and foci in osteones. These remaining foci of unmineralized bone were associated with the deposition of acid mucopolysaccharide, and acid mucopolysaccharide accumulation could be identified on all bone envelopes in 30-day biopsy specimens. A similar hyperostosis in the metaphyses of rats was produced by parenteral administration of 1,25-(OH) 2D 3 for 10 days.

Floppy mitral valve chordae tendineae: histopathologic alterations.

Pathologic studies of floppy or myxomatous mitral valves have focused primarily on changes in the valve cusps, with little attention given to the chordae tendineae. In a systematic study of the histopathology of floppy mitral valve chordae tendineae, 128 nonruptured chordae from 8 severely regurgitant floppy mitral valves were compared to 152 chordae from 10 normal control mitral valves and to 152 chordae from 8 control mitral valves with severe regurgitation due to ischemic heart disease. Collagen alterations were observed in 2% of normal mitral valve chordae and 3% of control regurgitant mitral valve chordae compared to 38% of floppy mitral valve chordae. Moderate or severe acid mucopolysaccharide accumulation was observed in 2% of normal mitral valve chordae and 3% of control regurgitant mitral valve chordae compared to 39% of floppy mitral valve chordae. Nonuniform histopathologic alterations, rare in normal and control regurgitant mitral valve chordae tendineae, were frequent in floppy mitral valve chordae tendineae (p less than 0.001). Histopathologic alterations provide the basis for abnormal physical properties previously demonstrated in floppy mitral valve chordae tendineae and may predispose to chordal elongation and rupture.

Corneal Manifestations of Scleromyxedema

Bilateral superficial corneal deposits and scleromyxedema, an uncommon dermatosis caused by the accumulation of acid mucopolysaccharide in the skin often associated with a benign monoclonal gammopathy developed in a 71-year-old man. A biopsy specimen of the cornea showed that the deposits stained strongly positive for IgG and lambda chains. Ultrastructurally, the deposits consisted of amorphous granular material. Scleromyxedema should be considered in the differential diagnosis of noninflammatory superficial keratopathies associated with benign gammopathies.

Microlaryngoscopic and histopathological studies in hypothyroidism and goitres

Microlaryngoscopic studies were conducted in 7 cases of hypothyroidism and 18 cases of benign goitres. Histopathological observations were made in all hypothyroid cases and 17 goitres. Pale and thickened vocal cords with sub-epithelial oedema were found in all cases and mild to moderate accumulation of mucopolysaccharides in the subepithelial stroma of vocal cords in 71% of the cases of Hypothyroidism. In cases of goitres, oedematous vocal cords were detected in 28%, pale irregularly thickened vocal cords in 33% and vocal nodules in 11% of the cases. Acid mucopolysaccharide accumulation in the vocal cords was noted in 2 cases of diffuse goitres. Left vocal cord palsy in one case of solitary nodular goitre was also noted.

Correlation of two-dimensional echocardiography and pathologic findings in porcine valve dysfunction

Two-dimensional echocardiographic findings in porcine valve dysfunction were compared with pathologic findings in 10 patients (12 valves). Three specific echocardiographic findings were identified in patients with regurgitant lesions: prolapse, fracture and flail leaflets. Prolapse was associated pathologically with thinning of the leaflets, longitudinal tears close to the ring margin and acid mucopolysaccharide accumulation. Valve fracture was seen with and without prolapse and was accompanied pathologically by small pinpoint perforations or tears of the leaflet. A flail leaflet was seen with a linear tear of the free margin and was associated with calcific deposits. Mild degrees of fracture seen pathologically were missed on the echocardiographic study in five patients. Thickening or calcification, when present in moderate or severe amounts, was correctly identified by echocardiography. When all abnormal features were considered collectively, two-dimensional echocardiography correctly identified at least one of them in all patients. Therefore, two-dimensional echocardiography may prove useful in assessing the source of valvular regurgitation in patients with bioprosthetic valves.

Histopathological changes of the retina and optic nerve in the albino mutant quail ( Coturnix coturnix japonica)

Histopathological changes in the retina and optic nerve in imperfect albino mutant quails with a sex-linked recessive gene were studied ontogenetically. The mutant quail showed eye enlargement 3 months after hatching. The eyes exhibited hazy corneas, lens opacities and deep anterior chambers at 18 months of age. Some ganglion cells in the retina and axons in the optic disc began to degenerate 6 months after hatching. There were many deformed or fragmented ganglion cells at 12 months of age, and axonal degeneration was observed in the optic disc. The optic disc and the retina around it became excavated. At this time, hydropic degeneration was found in the ganglion nerve fibre layer and optic nerve and a small accumulation of acid mucopolysaccharide, which was sensitive to hyaluronidase, was present in the optic disc and optic nerve. The excavation was found to be fully developed around the optic disc at 18 months and most ganglion cells showed degenerative changes. During this period, the inner plexiform and inner nuclear layers showed hydropic degeneration. At 24 months the ganglion cell and ganglion nerve fibre layers had disappeared, the thickness of the inner nuclear layer was reduced and many photoreceptor cells were totally degenerated. The optic nerve was occupied by glial cells, blood vessels and cavernous spaces in which acid mucopolysaccharide accumulated. These histopathological retinal changes in the mutant quail are very similar to those reported in experimentally induced glaucoma of other animal species and to those in human glaucoma. The usefulness of this mutant quail as an animal model for the human disease is discussed.

Dyssegmental dwarfism: A histologic study of osseous and nonosseous cartilage

Dyssegmental dwarfism is probably an autosomal recessive, lethal, generalized chondrodysplasia; it is characterized by anisospondyly , shortening of long bones, and narrow chest. Maturation of chondrocytes at the epiphyseal plates is disturbed. The pathologic features of osseous and nonosseous cartilage in a stillborn female infant with dyssegmental dwarfism are described. The cartilage matrix of tubular bones, vertebrae, ilia , ribs, nose, larynx, and trachea showed acellular areas with accumulation of acid mucopolysaccharides and no increase in collagen fibers. The findings, although not pathognomonic, suggest that this type of dwarfism may be a generalized connective tissue disorder. The abnormal synthesis, structure, or secretion of the components of the cartilaginous matrix may lead to accumulation of acellular material in both skeletal and respiratory tract cartilage.

Familial amyloid polyneuropathy with marked hypertrophy of the peripheral nerves.

Autopsy findings in a 40-year-old male with heredofamilial amyloidosis and polyneuropathy are reported. He had been suffering from progressive autonomic as well as sensorimotor dysfunctions. Prominent amyloid deposit was found in the kidney, heart, thyroid, and testis, and less in the interstitium and small vessels of almost all organs. The peripheral nerves, some showing prominent hypertrophy, were most severely involved by amyloid deposit in a form of stellate mass, which ultrastructurally consisted of radially arranged amyloid filaments. In the hypertrophied nerves and ganglia, in addition to amyloid, massive accumulation of acid mucopolysaccharide (AMPS) was seen filling up the interstitial space, which was the cause of hypertrophy. Ultrastructurally, AMPS was seen as finely granular substance. An extracted amyloid from the kidney showed 8 nm filament on negative staining and was estimated of having a molecular weight of 14,000.

Chondromatous metaplasia in the human larynx.

The finding of metaplastic fibroelastic cartilage in both vestibular folds of the larynx of an Orang-utan (Pongo pygmaeus) prompted the search for similar tissue in the same situation in 111 unselected human larynges removed at autopsy. Fibroelastic cartilage was found in both vestibular folds in three cases, being unilateral in a further four instances. The formation of this cartilage was preceded by the accumulation of acid mucopolysaccharide between fine collagen bundles within the vestibular fold followed by enlargement and alteration of the fibrocytes to resemble chondrocytes. These changes were found in 43 vestibular folds, and were bilateral in 10 cases.

Ocular changes in rabbits with corticosteroid-induced ocular hypertension.

Rabbit eyes with steroid-induced ocular hypertension were investigated in order to evaluate the histochemical abnormalities in the chamber angle region. The right eye of 14 rabbits was treated by dexamethasone 1% 3 times daily for 3 to 5 weeks. The eyes were stained by haematoxylin-eosin, periodic acid Schiff, fibrin, colloidal iron, and alcian blue with and without hyaluronidase. All treated eyes developed elevated intraocular pressure up to 4 weeks after treatment. These globes showed alcian-blue-positive hyaluronidase-sensitive staining in the amorphous material adjacent to Schlemm's canal and in the cytoplasmic granules of trabecular endothelial cells. There was no increase in incorporation of radioactive thymidine into nuclei of endothelial cells as seen by autoradiography. These results provide further support for the idea that there is abnormal accumulation of acid mucopolysaccharides in the chamber angle in steroid-induced ocular hypertension.

Local responses in primary and secondary human lung cancers. I. Patterns of cellular (eosinophils and macrophages) and extracellular (acid mucopolysaccharide) reactions

Local free cell (eosinophils and macrophages) and extracellular (acid mucopolysaccharides) reactions were studied by histochemical techniques in 72 primary lung cancers (Group A), 17 pulmonary metastases and 5 lung tumours of unknown origin (Group B). Strong cellular reactions were more frequent in Group A than in Group B, whereas extracellular reactions were more frequent in Group B than in Group A. In both groups the degrees of eosinophilic infiltration and accumulation of acid mucopolysaccharides tended to be negatively correlated. In contrast, macrophages and eosinophils showed a positive correlation in the primary cancers, but none in the other tumours. The extracellular material had physical and chemical properties (solubility, affinity to stains and degradability by enzymes) of the sulphated acid mucopolysaccharides. From its distribution it appeared to be derived from fibroblasts and/or tumour cells.

CHILDHOOD CORONARY SCLEROSIS

Childhood coronary sclerosis was studied histologically, histochemically immunohistochemically and biochemically on 60 autopsy cases aged from new-born to 20 years. Intimal thickening often started even in the newborn babies particularly at branching or bending points of the arteries, where fibrocellular proliferation with acid mucopolysaccharide accumulation was the main histological feature. Microthrombi were occasionally demonstrated even in infants, and fatty streaks appeared generally in the second decade. Microthrombi were usually smaller and fewer than fatty streaks. Beta-lipoprotein and fibrinogen infiltrations into intima were proven in some cases. Mural vascularization was occasionally observed especially in the areas beneath intimal thickening. Pressure effect of the blood stream and anatomically specific points in the arteries seemed to be important as initial factors of coronary sclerosis, where plasma constituents might pass in an easier manner into intimas by increased permeability. Secondarily mural capillaries might play some role in developing atheromas which would produce an eccentrically located luminal obstruction later in adulthood, by local circulatory disturbances within the arterial walls.

Cysts of the semilunar cartilage of the knee. A light and electron microscopic study.

The semilunar cartilages of the knee of six cases showing various degrees of mucoid degeneration with cyst formation were studied with the light microscope. Three cases were selected for electron microscopic observation which revealed that some of the cystic spaces filled with mucoid material were lined by synovial cells. Masses of mucinous, alcian bluc positive material (acid mucopolysaccharides) were observed also among degenerated and intact bundles of collagen. It is concluded that the accumulation of acid mucopolysaccharides in meniscial cysts is at least in part a product of secretion of synovial cells. This observation explains the high incidence of recurrence of meniscial cysts after incomplete surgical excision and supports the concept that it is an active rather than a degenerative process.