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ABSTRACT: Keratinocyte growth factor (KGF) is involved in the control of proliferation and differentiation of human keratinocytes. It binds to, and activates, the tyrosine kinase KGF receptor (KGFR), a splicing transcript variant of the fibroblast growth factor receptor 2. We have previously shown (C. Marchese et al., Cell Growth Differ., 8: 989-997, 1997) that differentiation of primary cultured keratinocytes triggered by high Ca2+ concentrations in the growing medium induced up-regulation of KGFR expression, which suggested that KGFR may play a crucial role in the control of the proliferative/differentiative program during transition from basal to suprabasal cells. Here we analyzed the process of modulation of the expression of KGFRs in the human keratinocyte cell line HaCaT, widely used as a model to study keratinocyte differentiation. Western blot and double immunofluorescence for KGFR and the K1 differentiation marker showed that cell differentiation and stratification induced by confluence and high cell density correlated with an increase in KGFR expression. KGFRs, present on suprabasal differentiated cells, appeared to be efficiently tyrosine-phosphorylated by KGF, which indicated that the receptors up-regulated by differentiation can be functionally activated by ligand binding. Bromodeoxyuridine incorporation assay revealed that a significant portion of suprabasal differentiated cells expressing KGFR seemed to be still able to synthesize DNA and to proliferate in response to KGF, which suggested that increased KGFR expression may be required for retention of the proliferative activity.
Cell growth & differentiation: the molecular biology journal of the American Association for Cancer Research 12/2000; 11(11):607-14.
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ABSTRACT: The effects of lengthening of the metacarpal bone on peripheral nerves and blood vessels were studied in 8 calves. Specimens for light and electron microscopy were obtained from the palmar neurovascular bundle at 1 cm (8% of the initial length), 2.5 cm (20% of the initial length), and 4 cm (33% of the initial length) of metacarpal lengthening. In 2 calves, specimens were studied 2 months after the end of the lengthening procedure. At 8% of lengthening, myelinated fibers of the palmar nerve showed moderate degenerative changes in the myelin sheath. This became severe at 20% and 33% of lengthening, and affected the axoplasm as well. At 20% of lengthening, the palmar vein started to show fibrous metaplasia of the smooth muscle tissue of the tunica media. This became much thinner than normal. The palmar artery showed moderate alterations of the inner part of the tunica media and the intima. The palmar nerve and blood vessels recovered their normal structure almost completely 2 months after the end of the lengthening procedure. The morphologic alterations of peripheral nerves and vessels may constitute the pathophysiologic basis of the nervous and circulatory disturbance observed in clinical practice.
Clinical Orthopaedics and Related Research 12/1994; · 2.53 Impact Factor
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ABSTRACT: Two cases of Ledderhose's disease (plantar fibromatosis) are described with emphasis on histologic features. This disorder has three histologic stages: in the first, or proliferative, stage, numerous fibroblasts associated with a small amount of collagen are observed; in the second, or active, stage, the cells are more mature and the collagen is more evident; in the third, or maturation, stage, the extracellular matrix is composed of dense bundles of collagen fibers with few fibroblasts. Ultrastructural analysis revealed filamentous aggregation of an unknown nature among the collagen fiber bundles. The authors discuss some clinical, physiological, and pathologic aspects of a disorder which is similar to Dupuytren's disease but does not involve retraction of the surrounding anatomical structures.
Italian journal of orthopaedics and traumatology 02/1992; 18(1):129-33.
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ABSTRACT: Two normal proximal femoral growth plates and core biopsies from six patients with slipped capital femoral epiphysis (SCFE) were studied by electron microscopy. In these SCFE patients, chondrocytes from all the zones of the plate were frequently smaller than normal, more irregular in shape, and many of them were degenerating, with formation of matrix vesicles and cellular debris. Floccular electron-dense material, most likely abnormal proteoglycan, was present in the hypertrophic rough-surfaced endoplasmic reticulum and Golgi apparatus as well as in the extracellular matrix, intermingled with collagen fibrils thinner than normal and loosely arranged. Mineralization of the abnormal matrix of the longitudinal septa of the degenerating zone was either scanty or absent, with scanty formation of irregular and thin bone trabeculae. The abnormalities observed in SCFE seem to be caused by a change in chondrocyte metabolism with consequent altered synthesis and/or extracellular aggregation of both collagen and proteoglycan, and scanty mineralization of the abnormal cartilage matrix.
Journal of Orthopaedic Research 02/1989; 7(2):252-9. · 2.81 Impact Factor
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Progress in clinical and biological research 02/1989; 296:153-8.
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ABSTRACT: Core biopsies obtained from the articular cartilage of the femoral head of a 16-year-old girl with idiopathic chondrolysis of the hip were subjected to an ultrastructural study. Zone I was missing and zone II was the most superficial layer present in the articular cartilage of our patient. Collagen fibrils were thinner than normal and more uniform in diameter, and proteoglycans were normally distributed among them. Degenerating chondrocytes were found, as well as debris of dead cells, but many chondrocytes were still vital and engaged in active synthesis. Most of the chronic degenerative changes observed in ultrastructural studies on osteoarthritis were not observed in this case of idiopathic chondrolysis which seems to be, on the basis of our findings, a pathological process which develops and runs its course very quickly.
Orthopedics 11/1986; 9(10):1383-7. · 2.66 Impact Factor
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ABSTRACT: The tendon sheaths of extensor pollicis brevis (EPB) and abductor pollicis longus (APL), obtained from four patients with de Quervain's disease were studied by light and electron microscopy. Three different layers were identified in the sheath which was much thicker than normal. Both the outer and the middle layers had thick bundles of collagen fibres with scattered fibroblasts.The inner layer was mainly formed by chondroid and myxomatous tissue. Collagen fibrils were thicker than normal, reaching 2100 nm in diameter. Numerous cells which resembled myofibroblasts were scattered throughout the whole thickness of the sheath.The results seem to indicate that thickening and hardening of the EPB and APL tendon sheaths in de Quervain's disease is caused by increased synthesis of the extracellular matrix, increased thickness of the collagen fibrils and areas of myxomatous and chondroid metaplasia.Les gaines tendineuses du court extenseur et du long abducteur du pouce ont t tudies du point de vue histologique et ultrastructural chez quatre patients atteints de maladie de de Quervain. Dans les gaines tendineuses, beaucoup plus paisses que normalement, ont t identifies trois couches diffrentes. La couche externe et la couche intermdiaire sont formes d'pais faisceaux de fibres collagnes qui contiennent peu de fibroblastes.La couche interne est forme principalement d'un tissu myxode et chondrode; les fibrilles collagnes sont plus paisses que la normale, atteignant le diamtre de 2100 nanomtres. De nombreuses cellules semblables des myofibroblastes sont prsentes dans toutes les couches de la gaine.Nos rsultats semblent indiquer que l'augmentation d'paisseur et de consistance de la gaine tendineuse du court extenseur et du long abducteur du pouce dans la maladie de de Quervain, est cause par l'augmentation de la synthse de la matrice extra-cellulaire, par l'augmentation d'paisseur des fibrilles collagnes et par des aires de mtaplasie myxode et chondrode.
International Orthopaedics 05/1985; 9(1):41-47. · 2.03 Impact Factor
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ABSTRACT: Using antisera for two specific basement membrane (b.m.) antigens such as laminin and collagen type-IV, together with electron microscopy, we have shown that fully antigenic b.m. and morphologically typical basal lamina (b.l.) are associated with normal and transformed cells of the melanocyte lineage in different ways. Thus, while b.m. and b.l. surround individual choroidal melanocytes, intradermal nevus cells and cells of blue nevi are not detectable at the periphery of resting and proliferating epidermal melanocytes. They have a low degree of expression with a heterogeneous pattern of distribution in primary and metastatic melanoma. This heterogeneity is present within single metastases and among autologous metastases. These findings indicate that the presence of b.m. can be an additional marker for cells of the melanocyte lineage and should be considered when applying serological means for the detection and control of neoplasms of melanocytic origin.
International Journal of Cancer 05/1985; 35(4):461-7. · 5.44 Impact Factor
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ABSTRACT: The tendon sheaths of extensor pollicis brevis (EPB) and abductor pollicis longus (APL), obtained from four patients with de Quervain's disease were studied by light and electron microscopy. Three different layers were identified in the sheath which was much thicker than normal. Both the outer and the middle layers had thick bundles of collagen fibres with scattered fibroblasts. The inner layer was mainly formed by chondroid and myxomatous tissue. Collagen fibrils were thicker than normal, reaching 2100 nm in diameter. Numerous cells which resembled "myofibroblasts" were scattered throughout the whole thickness of the sheath. The results seem to indicate that thickening and hardening of the EPB and APL tendon sheaths in de Quervain's disease is caused by increased synthesis of the extracellular matrix, increased thickness of the collagen fibrils and areas of myxomatous and chondroid metaplasia.
International Orthopaedics 02/1985; 9(1):41-7. · 2.03 Impact Factor
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ABSTRACT: Morphologic studies of annulus fibrosus of newborn, young, and old rats were carried out to determine the tissue changes occurring with aging. Newborn annulus consists of an inner portion containing chondroblast-like cells, a middle portion showing cells with intermediate features between chondroblasts and fibroblasts, and an outer portion containing fibroblast-like cells. The cells, arranged in rows, show a prominent ergastoplasm and are surrounded by pericellular lucunae. In the inner portion, the collagen fibers in the matrix are oriented randomly; in the middle and outer portions, the fibers between adjacent cell rows are arranged parallel, forming fibrous lamellae. The collagen fibers have fairly uniform diameters (average 510 nm), are strongly positive to the PASM reaction, and are surrounded by small proteoglycan granules. Both immature and mature elastic fibers are present. Young annulus consists of a transition zone, composed of large cells with no definite arrangement and bundles of collagen fibers oriented in various directions, and a lamellar zone consisting of fibrous lamellae separated by interlamellar septa containing the cells. These show intermediate features between chondrocytes and fibrocytes and well-developed ergastoplasm. The interlamellar septa consist of collagen fibrils and proteoglycans and contain few aggregates of electron dense material. The collagen fibers have highly variable diameters (average 740 nm). The larger fibers are scarcely periodate-silver-methenamine (PASM) positive. The proteoglycans are similar in size to those in the newborn. Few, mature elastic fibers are present. In old annulus, the transition zone is larger than in the young tissue. The cells are less numerous, and most of them show a sparse ergastoplasm.(ABSTRACT TRUNCATED AT 250 WORDS)
Spine 10/1984; 9(6):596-603. · 2.08 Impact Factor
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ABSTRACT: This is an ultrastructural study of disc material obtained from two patients subjected to operation two weeks after an unsuccessful chymonucleolysis. It confirms that the "in vivo" effects of chymopapain are similar to those observed "in vitro", namely that it is ineffective in large contained hernias and in extruded hernias.
Italian journal of orthopaedics and traumatology 10/1984; 10(3):385-91.
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ABSTRACT: The effect of the association of gossypol and Lonidamine on the electron transport in Ehrlich ascites tumor mitochondria has been investigated by addition of drugs to isolated mitochondria. The results may be summarized as follows. (1) Low concentrations of gossypol increase the rate of oxygen consumption at the level of three energy-conserving sites of the respiratory chain. Higher concentrations result in an inhibition of oxygen consumption at (or near) both energy-conserving sites 1 and 2, while energy-conserving site 3 is unaffected. (2) Gossypol, at concentrations at which it exerts its uncoupling effect, stimulates ATPase activity. Higher concentrations inhibit the enzyme activity. (3) The addition of gossypol to mitochondria respiring on pyruvate plus malate or succinate induces a more oxidized state of NAD+ and cytochrome b, respectively. (4) Gossypol enhances the effect of Lonidamine on oxygen consumption. Lonidamine does not affect state 4 respiration, but in the presence of gossypol, it determines a marked decrease in the rate of oxygen consumption. The inhibition of oxidation of NAD-linked substrates is greater than that of FAD-linked substrates. (5) It may be concluded that gossypol is very effective in potentiating the effect of Lonidamine. Moreover, it may be suggested that the antitumor activity of Lonidamine is enhanced if it is used in combination with other drugs and/or treatments, such as hyperthermia, which modify the energy status of mitochondria.
Experimental and Molecular Pathology 05/1984; 40(2):246-61. · 2.42 Impact Factor
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ABSTRACT: Lonidamine was given to several patients affected with different types of neoplasias growing as metastases both in ascites and pleural effusion, and solid cutaneous metastases. The patients with tumor cells in ascites and pleural effusion were treated with Lonidamine per os or in loco injections. In cutaneous metastases, Lonidamine was administered by different routes: (1) per os; (2) local endoarterial; and (3) in association with hyperthermic perfusion with or without antiblastic drugs.
Oncology 02/1984; 41 Suppl 1:94-103. · 2.27 Impact Factor
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ABSTRACT: The distribution of actin, myosin, fibronectin and basement membrane antigens has been studied by indirect immunofluorescence in benign and malignant human breast lesions. While benign tumors showed only minor differences from normal mammary tissue, tumors of different histological types displayed a heterogeneous distribution of the antigens studied. Heterogeneity was observed within the same tumor, among different neoplasms and between primary tumors and autologous metastases. As a common characteristic, most of the tumors did not stain for actin and myosin, the pattern being similar to that found in myoepithelial cell distribution. In transformed epithelia there was often a lack of detectable actin with a myosin-positive fluorescence. Staining for both proteins was diffused to most of the cell cytoplasm. Staining for fibronectin was seen in only a minority of the cases, with medullary tumors being the most positive. Basement membrane stain was either absent or decreased and fragmented, except in rare ductal, i.e. papillary, carcinomas. Medullary tumors displayed an almost continuous, though fragmented basement membrane in approximately 70% of cases.
Virchows Archiv. A, Pathological anatomy and histopathology 02/1984; 405(1):69-83.
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ABSTRACT: A direct ultrastructural study was carried out with a view to determining the changes brought about in vitro by chymopapain on the intervertebral disc and the vertebral growth plate. The tissues studied were: (A) fragments of protruded nucleus pulposus and extruded disc tissue; (B) portions of human and rabbit annulus fibrous; (C) fragments of rabbit vertebral growth plate. The fragments of tissue were incubated with chymopapain for three, six and twenty-four hours and were then fixed. In the protruded nucleus pulposus and extruded disc tissue, chymopapain produced disappearance of the electron-dense granules (which are presumably proteoglycans) and of the electron-dense granular material of the intercellular matrix. The enzyme probably also has an injurious action on the chondrocytes, but does not affect the fibrils and collagen fibres. Its action is also conditioned by the dimensions of the fragment of tissue incubated. If this is large, only the peripheral portion is completely digested. The action of the enzyme on the annulus fibrosus and the vertebral growth plate is similar to that on the nucleus pulposus. The present study indicates that the clinical effects of chymopapain are due to digestion of the proteoglycan granules and the electron-dense granular material of the herniated nucleus pulposus. These effects appear to be correlated with the collagen fibre content of the tissue, in the sense that the greater the collagen content, the more tissue mass remains unaffected.
Italian journal of orthopaedics and traumatology 01/1983; 8(4):445-55.
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ABSTRACT: The ultrastructural aspects of the germinal epithelium of 10 infertile men affected by maturative arrest of spermatogenesis were studied. We noted an increased number of malformed germinal cells. Marginal nuclear vescicles were present in spermatogonia of patients affected by spermatogonial arrest. The few spermatid present in the germinal epithelium of the patients affected by a spermatidic arrest presented changes of the nuclear condensation, the acrosome, and the tail. The Sertoli cells presented an immature aspect of the nucleus and changes of the "mantle". A possible correlation between the Sertoli cells changes and the altered spermatogenesis was proposed.
Bollettino della Società italiana di biologia sperimentale 08/1982; 58(14):907-13.
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Chemotherapy 02/1981; 27 Suppl 2:50-60. · 1.82 Impact Factor
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Chemotherapy 02/1981; 27 Suppl 2:27-42. · 1.82 Impact Factor
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ABSTRACT: Morphological changes in rat germ cell mitochondria are described. In diplotene and secondary spermatocytes and in the spermatids of the Golgi, cap and acrosomal phases, the mitochondria take on a rounded appearance with the inner space containing the matrix flattened against the outer membrane and the intracristal spaces considerably swollen ("condensed" mitochondria). Functional studies on "condensed" mitochondria isolated from the germ cells of normal rats have been performed. The following parameters have been evaluated: ADP/O ratio, respiratory control ratio (RCR) and ADP affinity. The ADP/O values found in the presence of various substrates are in agreement with the theoretical figures. The RCR is remarkably high. Moreover, the ADP affinity of these mitochondria is very high, as demonstrated by the low values of the "apparent Km". These biochemical findings, which demonstrate a high oxidative capacity coupled with a marked phosphorylation, suggest that the "condensed" appearance of germ cell mitochondria is the expression of an active functional state.
Cell and Tissue Research 02/1979; 196(1):1-22. · 3.11 Impact Factor
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Bollettino della Società italiana di biologia sperimentale 02/1978; 54(2):154-60.
