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Histochemical localization of glycoconjugates in the palmar aponeurosis of Dupuytren's patients.

Acridine orange added to the primary fixative or reduced osmium tetroxide as postfixative have been used in order to localize by thin section electron microscopy glycoconjugates in the extracellular matrix of the normal palmar aponeurosis as well as in tissues at different stages of Dupuytren's contracture. After use of acridine orange or reduced osmium tetroxide, in the nodule of the active stage an extensive network of fine filaments separated single or small bundles of collagen fibrils from each other. In the cord of the residual stage fixed in presence of acridine orange, the tightly packed collagen fibrils in the central region of the specimens were swollen and had stained material interposed between the single microfibrils. In specimens of the same cord first fixed with glutaraldehyde alone, followed by reduced osmium tetroxide, the disaggregation of collagen fibrils could be seen only occasionally and the intrafibrillar stained glycoconjugates were less evident. Comparable alterations were absent from the normal tissue. The possible reasons of these differences are discussed.

Acridine Orange↗

Detrusor morphology and pathology in relation to bladder outflow obstruction in bilharzial patients.

The light and electron microscopic structure of detrusor muscle of trabeculated urinary bladder from patients with urodynamically proved bilharzial outflow obstruction had been compared with normal detrusor muscle. In bilharzial outflow obstruction, the detrusor muscle bundles were formed of relatively smaller smooth muscle cells widely separated by dense connective tissue, fatty infiltration, bilharzial ova, inflammatory cells and hyalinosis. No evidence of smooth muscle hyperplasia, mitosis, or fibroblastic proliferation. At the level of electron microscopy. The connective tissue infiltration was proved to be microfibriles apparently in continuity of the basal lamina of the smooth muscle. These pathological changes can explain both the morphological and urodynamic changes in bilharzial urinary bladder outflow obstruction.

Adult↗

Tight-skin, a new mutation of the mouse causing excessive growth of connective tissue and skeleton.

A new dominant mutation, tight-skin (Tsk), is located on Chromosome 2, two recombination units distal to pallid (pa). Heterozygotes (Tsk/+) have tight skins with marked hyperplasia of the subcutaneous loose connective tissues, increased growth of cartilage and bone, and small tendons with hyperplasia of the tendon sheaths. In the loose connective tissue there are large accumulations of microfibrils in the intercellular space. In spite of the increased skeletal size, body weight is not increased. Increase in size of the thoracic skeleton is especially pronounced and leads to pathologic distentsion of the hollow thoracic viscera. Concentration of growth hormone in the pituitary and plasma is normal. Homozygotes (Tsk/TSK) die in utero at 7 to 8 days of gestation. We propose the hypothesis that Tsk might act by causing defective cell receptors with high affinity for a somatomedin-like factor promoting growth of cartilage, bone, and connective tissue and low affinity for a multiplication-stimulating factor promoting embryonic growth.

Animals↗

Nodular cutaneous mucinosis--an unusual multiple type of euthyreotic focal mucinosis.

A 32-year-old Turkish man with a progressive appearance of indolent, skin-colored nodules on the trunk and proximal extremities is presented. Clinical and laboratory examinations did not reveal any other relevant abnormalities. Histological specimens showed focal, ill-defined depositions of acid mucopolysaccharides mainly in the reticular dermis. Collagen fibers were split up and separated. Ultrastructurally, activated fibroblasts and an increased synthesis of collagen fibrils and elastic microfibrils as well as numerous macrophages were noticed. Diagnostically, an unusual multiple type of cutaneous focal mucinosis is most likely.

Adult↗

The induction of emphysema with elastase. II. Changes in connective tissue.

Both clinical and experimental evidence implicate proteolytic enzymes active against elastin in the pathogenesis of emphysema. Paradoxically, however, the elastin content of emphysematous human lungs at autopsy has been normal. When emphysema was produced in hamsters by a single intratracheal injection of 25 units of porcine pancreatic elastase, the elastin content of the lungs was reduced from 1.40 +/- 0.22 mg. in controls to 0.43 +/- 0.10 mg. 24 hours after injection, and histologic sections showed that many elastic fibers had disappeared. The elastin content of the lungs gradually increased, approaching normal values by 2 months after injection. The incorporation of 14C-proline into elastin was markedly elevated during the first 2 weeks after injection, decreasing nearly to normal by 2 months. The synthesis of collagen was also increased, indicated by an increase in the collagen content of the lung, an increase in the prolyl hydroxylase activity, and an increase in incorporation of labeled proline into collagen. During the period of active resynthesis of elastin, small clumps of microfibrils and elastic fibrils were visible by electron microscopy within grooves on the surface of septal connective tissue cells in the lungs. Many elastic fibers seen in histologic sections up to 4 months after injection were of abnormal configuration and disorganized.

Animals↗

[Giardia intestinalis: transmission electron microscopy study of in vitro excystation].

The in vitro excystation process in Giardia intestinalis was studied by transmission electron microscopy (TEM). Untreated cysts served as controls. The excystation process was monitored by examination of organisms after the in vitro induction and at several times during the incubation phase. The control cyts had a thick wall, made of microfibrils, that appeared not to contain any weak areas. The peritrophic space extended between the cyst wall and the organism peripherally, the space was delimited by a thin cytoplasmic layer, "the outer cytoplasmic envelope" that subtended the cyst wall. During the in vitro incubation, the trophozoite cytoplasm retracted from the wall; thus, the peritrophic space became progressively larger. The outer cytoplasmic envelope detached from the cyst wall, then broke up forming numerous small vesicles lodged between the wall and the organism. The tight arrangement of the wall microfibirils was lost. Electron-dense vacuoles appeared in the peripheral cytoplasm of the trophozoite. The organism emerged through the posterior end of the cyst, leaving behind the empty husk. Emergence was followed by cell division. The possible interrelationships of biochemical and mechanical factors affecting the process of excystation are discussed in light of the present TEM findings.

Animals↗

Venous microvasculature of the pineal body and choroid plexus in the rat.

Rats were perfused from aorta with Ringer's solution and with Karnovsky's fixative, and injected from the right atrium with Mercox resin. Specimens were properly taken, observed under LM, TEM, SEM, and stereo-photographed. Fenestrated endothelial cells of the pineal capillary were observed to contain plenty of microtubules running parallel to the long axis of the vessel. The endothelial basal lamina appeared anchored by microfibrils onto fine collagen fibrils and onto the basal lamina of the perivascular cells. These findings indicate resistance of the capillary endothelium against compression by perivascular hydrostatic pressure, and strongly suggest that the perivascular cerebrospinal fluid is absorbed into the capillary lumen. Resin cast of the pineal venous system looked like a glomerule with two longer collecting veins on the ventral surface and with shorter ones on the dorsal side all emptying into the straight sinus and the confluence of sinuses. Resin cast of the choroid plexus venous system tended to lobulate and looked like a vine with a spiral collecting vein emptying into the great vein. Two veins were found connecting the great vein to the confluence and to the transverse sinuses. These could be effective collaterals in case of occlusion of Galen's vein.

Animals↗

Monoclonal antibodies to human tumor nucleolar antigens: probes for studying biological function and determining clinical significance.

Using novel strategies, monoclonal antibodies (MAbs) were developed to two proliferation-associated nucleolar antigens. These two new antigens, termed P145 and P120, according to their molecular weights, were found in a broad range of tumor tissues. Overall, P120 was more restricted in its distribution than P145 because it was absent from many benign tumors and some malignant tumors. Using the MAbs as probes, antigens P145 and P120 were localized to separate nucleolar components. P145 was mainly associated with high molecular weight nucleolar RNPs. Antigen P120 was localized to a novel beaded microfibril found in a nucleolar residue fraction. DNAse and high salt treatment of this fraction provided optimal extraction of the P120 antigen. P145 and P120 differed from other proliferation-associated nuclear/nucleolar antigens identified by autoimmune sera and by other MAbs. In PHA stimulated lymphocytes, both antigens were expressed in early G1 prior to or concurrent with increased RNA Pol I transcription. Microinjection of tumor cells with the P120 MAb inhibited cell proliferation and blocked the appearance of nucleolar pleomorphism that is characteristic of tumor cells. Clinical studies showed that P145 was not detected in normal bone marrow but was expressed in leukemic marrows (AML); the percentage of P145 positive cells correlated with percentage of malignant blasts (Raza et al., Am. Soc. Hematology, 1990). Antigen P145 was detected in 10 of 39 marrows from patients in complete remission. This result suggested that these cells have a higher proliferative potential than normal stem cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Histologic signs of cutaneous aging].

The changes induced by ageing of the skin are particularly visible in photo-exposed areas, indicating the interaction between actinic factors and factors specific to the ageing process itself. The corresponding histological signs affect various structures: epidermis (thinning of the epidermis, reduced cell proliferation...), dermis-epidermis junction (disappearance of the microvilli with defective adhesion of the epidermis to the dermis), dermis (degeneration of elastin and collagen, which is photoinduced, and a moth-eaten appearance with loss of microfibrils as a result of time-related ageing), microcirculation (reduced vascularization, particularly visible in photo-exposed areas...) appendages.

Epidermis↗

Linear focal elastosis. An ultrastructural study.

We studied an 86-year-old Japanese man with linear focal elastosis. The lesions were asymptomatic yellow striae in the lumbar region, histologically composed of massive, well-demarcated basophilic fibers that stained positively with elastic tissue stains. Electron microscopy revealed fine, reticular or granular electron-dense materials, and elastic fiber microfibril-like materials in the matrix, in addition to numerous mature and immature elastic fibers. These findings suggest that active elastogenesis was occurring in the lesions. The four cases reported so far have the three common features of age, sex, and lesion location.

Actin Cytoskeleton↗

[Morton's disease: optic and electron microscopy observations].

The authors performed an optic and electron-microscope investigation above the common digital nerve of the foot, whose fragments had been surgically removed from patients suffering from "Morton metatarsalgia" (neuroma). Histological sections were taken from pre-stenotic swelling in patients with clinical symptoms persisting for one year; perineural thickening without evidence of fibroblastic proliferation could be demonstrated, together with an intraneural deposition of an amorphous substance. In other patients suffering from Morton's disease for a longer time, a more pronounced epineural thickening in the pre-stenotic zone could be shown, with partial replacement of nerve fibers by amorphous substance. In the same patients endoneural fibrositis was seen at the level of the stenosis. Electron-microscopy in patients after one year showed an increase in collagenous endoneural fibers and microfibrils. These histopathological findings suggest a compressive mechanism in the pathogenesis of the damage to the common interdigital nerve in Morton's disease, caused by the extrinsic anatomical structures surrounding the nerve. The so-called "neuroma" can be identified with the pre-stenotic swelling.

Adult↗

Posterior attachment of ciliary muscle in young, accommodating old, presbyopic monkeys.

The authors studied the posterior attachment of the ciliary muscle in seven young (3-10 yr) and five old (26-34 yr) rhesus monkeys by light microscopy and electron microscopy. Posterior attachment of the muscle bundles consisted of elastic tendons, exclusively. The elastic tendons were continuous with the elastic lamina of Bruch's membrane and were also connected by smaller elastic fibers to an elastic meshwork that surrounds the pars plana vessels. In some areas, the tendons formed focal contacts with the endothelial cells. The authors found that in old eyes, the tendons and the elastic fibers of the posterior ciliary body showed pronounced structural changes. The tendons appeared thickened, showed increased amounts of associated microfibrils, and were surrounded by dense layers of thick collagen fibrils. An increased amount of collagen fibrils was also seen between the elastic layer of Bruch's membrane and the pigmented epithelium. A mechanical link between those collagen fibrils and the elastic fibers is suggested by the presence of osmiophilic points of contact. The age-related increase in elastic fibrillar material could cause decreased compliance of the posterior insertion of ciliary muscle and could be an essential factor for presbyopia in rhesus monkeys.

Accommodation, Ocular↗

Ultrastructure of bone marrow tissue in so-called primary (idiopathic) myelofibrosis-osteomyelosclerosis (agnogenic myeloid metaplasia). II. The myeloid stroma (hematopoietic microenvironment).

An ultrastructural study was performed on bone marrow tissue in 8 patients revealing early and late stages of so-called primary (idiopathic) myelofibrosis - osteomyelosclerosis (agnogenic myeloid metaplasia) to evaluate the constituents of the hematopoietic microenvironment (myeloid stroma). A survey of the stroma cells disclosed an overall increase, particularly in so-called undifferentiated (primitive - pluripotent), but also in transitional (fibroblastic) reticular cells and myofibroblasts. The most primitive reticular cells were characterized by their stellate aspect with elongated slender cytoplasmic processes traversing the interstitial space, and by the scarcity of organelles. The transition into a fibroblast was preceded by the appearance of branching cisternal structures of the rough endoplasmic reticulum, extensively developed Golgi fields and an abundance in mitochondria. Frequently, so-called myofibroblasts were encountered displaying bundles of filaments along the subplasmalemmal region. Extracellularly fibrillar material with an irregular cross-banding as well as microfibrils could be observed. The many vascular structures (sinusoids and capillaries) exhibited a multilayered basement membrane-like material including many fibrils and adventitial cells (pericytes, smooth muscle and transitional reticular cells) with numerous cytoplasmic processes. Undifferentiated and transitional reticular cells as well as myofibroblasts seem to form an integral part of the hematopoietic microenvironment in OMF and are assumed to play an important role for the evolution of the disease-specific myelofibrosis in this disorder.

Bone Marrow↗

Dermatitis herpetiformis bodies. Ultrastructural study on the skin of patients using direct preembedding immunogold labeling.

Skin samples from three adult patients with dermatitis herpetiformis (DH) and granular IgA deposits in the papillary tips were studied using ultrastructural immunogold technique. IgA positive, so-called DH bodies were identified as amorphous clumps--most probably immunocomplex aggregates--scattered throughout the upper papillary dermis. Dermatitis herpetiformis bodies were seen underneath the basement membrane, sometimes along microfibrillar bundles, as well as adjacent to the papillary collagen fibers and within the surface (microfibrillar) region of elastic tissue. Some DH bodies, however, were not related to any fibrillar components. The collagen and elastic fibers, microfibrillar bundles, anchoring fibrils, and elastic microfibrils themselves were unlabeled. Dermatitis herpetiformis bodies were not found in normal human skin. The results of our ultrastructural study indicate that DH bodies either are bound to a nonfibrillar component of dermal connective tissue or represent deposits of immune complexes trapped in DH skin.

Actin Cytoskeleton↗

[Exfoliative materials in the skin of patients with exfoliation syndrome].

The iris and the skin of the lateral canthus of patients with exfoliation syndrome were studied by light and electron microscopy. The materials were surgically obtained from 9 patients of cataract and/or glaucoma associated with exfoliation syndrome. For the control study, we prepared the iris and the skin of 6 patients without exfoliation syndrome. In all 9 cases of exfoliation syndrome, exfoliative materials were observed in the pigment epithelium of the iris. In 3 of 9 cases, exfoliative materials were found in the dermis. In 6 other cases, microfibrils and immature forms of exfoliative materials were observed, but not typical forms. Neither in the iris nor in the skin of the control cases were exfoliative materials detected. Exfoliative materials in the dermis seen in the patients with exfoliation syndrome were morphologically similar to those in the iris. This is the first report of demonstration of exfoliative materials in the skin. These observations suggest that exfoliation syndrome may be a systemic degenerative disorder of the body.

Aged↗

[New morphologico-functional concepts of sensory structures].

The author analyzes the terminology of sensory nerve structures serving mechanoreception, nociception, thermoreception, chemoreception and baroreception which is not only very varied but also inaccurate, as it reflected so far only some morphological or functional phenomena. The author considers particularly inapt to use the term "receptor" for so-called nerve endings, as at present the term receptor stands for the specific binding capacity of protein molecules in particular in cell membranes, the transmission of information into the cell and evoking of a biological response. From the aspect of the contemporary concept the so-called nerve endings must be considered systems formed by a different number of sub-systems which participate in a certain way in the activity of the structure as a whole. This system is formed by the dendritic zone with the ability to form a generating potential, by modified Schwann cells, Grandry's on Merkel's modified fibrocytes, in corpuscles by fluid, a system of cellular lamellae and microfibrils and in Pacini's corpuscles also by a network of capillaries. Every sensory structure is associated metabolically with surrounding tissue. The author defines sensitive nervous formations as basic special sensory systems which serve the receipt of information and their transmission to the CNS and complex sensitive nervous formations which are systems of a higher order with an adaptive graded sensitivity. The author submits then his own classification of sensory nervous formations which respects morphological and functional phenomena which can be essentially summarized in two basic and one transient class.

Animals↗

Structure of the glomerular mesangium: a biomechanical interpretation.

This paper summarizes our current knowledge of the structural details and probable functional significance of the system of contractile filaments in the glomerular mesangium. The description is based mainly on studies of superficial glomeruli of the rat kidney. The contractile apparatus of mesangial cells consists of microfilament bundles located predominantly within mesangial cell processes. The thickest microfilament bundles occur in the juxtacapillary mesangial cell processes, which directly abut the glomerular capillaries. The effector structure of mesangial cell contractility is the GBM. Mesangial cell processes are connected to the GBM either directly or through the interposition of extracellular microfibrils. In general, the contractile system of the mesangium interconnects opposing parts of the GBM. This arrangement is particularly obvious in the juxtacapillary processes, which underlie a mechanical connection between the GBM at the two opposing mesangial angles of a single capillary. The geometry and structural composition of the contractile apparatus of the mesangium indeed suggest a static rather than a dynamic function. In conjunction with the GBM, the mesangial contractile apparatus seems capable of supporting sufficient wall tension to counteract the distending forces acting across the capillary walls; the apparatus also seems capable of directly balancing the distending forces on the perimesangial walls. Assuming that mesangial cells are capable of isotonic contractions, the effect of such a contraction on capillary diameter and, consequently, on filtration area would be small.

Actin Cytoskeleton↗

Chick tropoelastin isoforms. From the gene to the extracellular matrix.

Studies from several laboratories have demonstrated the existence of multiple tropoelasting mRNAs and protein isoforms. The present study was designed to examine the developmental expression of a specific tropoelastin mRNA, its encoded isoform, and the fate of that isoform in the extracellular matrix. A chick genomic DNA library was screened with a chick tropoelastin cDNA. Seven unique, overlapping clones spanning 39 kilobases were isolated. A synthetic oligonucleotide complementary to a variable tropoelastin mRNA sequence was used to identify a 1.5-kilobase PstI-BamHI genomic fragment. Nucleotide sequence data revealed that the putative exon was surrounded by intron sequences possessing canonical splice sites at the exon/intron borders. Using both immunologic and molecular probes specific to the tropoelastin isoform and mRNA, quantitative protein and RNA analyses were performed. Results demonstrate that total tropoelastin mRNAs increased significantly during aortic embryogenesis whereas the amount of mRNA containing the variable exon remained relatively constant. The amount of total tropoelastins within the same developmental period reflect the level of total tropoelastin mRNA. The amount of the tropoelastin isoform containing the variable exon essentially mirrored the corresponding mRNA with the exception that a decrease in the isoform at day 15 was not seen in the mRNA level. Immunoelectron micrographs of 13-day chick aortic tissue using both total and isoform-specific antisera showed ultrastructural localization to definable elastic fibers. Antibodies to the variable tropoelastin isoform occurred preferentially at sites where elastic fiber microfibril structures were evident.

Amino Acid Sequence↗