Charcot-Marie-Tooth disease: an intermediate form.
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Adult↗
Biomedical subjects
M Villanova
Publications and source records attributed to M Villanova.
Altered expression of the alpha2 laminin chain in psoriatic skin: the effect of treatment with cyclosporin.
The histopathological pattern of psoriasis is characterized by dermal inflammatory reaction and hyperproliferation of the epidermis. The mechanism of the epidermal hyperproliferation is not completely understood, but it is probably modulated by the basal lamina (BL), the alterations of which have not been described. We performed the present study to evaluate the expression of the alpha1, alpha2, beta1 and gamma1 laminin chains and collagen IV in the BL of active psoriasis vulgaris before and after cyclosporin treatment administered until the psoriasis was in remission. The results showed that the alpha2 chain is weak and irregular in the lesions, while the alpha1, beta1 and gamma1 chains and collagen IV are normal, with intense and continuous reaction. In the same subjects, this alteration was absent in skin that was clinically unaffected. After treatment with cyclosporin, the altered expression of the alpha2 chain returned to normal in the healing lesions.
Adult↗
CAG repeat expansion in an italian family with spinocerebellar ataxia type 2 (SCA2): a clinical and genetic study.
We report an Italian family in which molecular genetic analysis showed expansion of CAG repeats indicative of the SCA2 genotype. This family confirms that ataxia, ophthalmoparesis and sensory peripheral neuropathy are the salient features of the SCA2 phenotype. In the present cases, early onset and mental deterioration were important additional findings. Nerve biopsy findings were compatible with a chronic axonopathy. We found a direct correlation between length of triplet expansion and severity of the clinical symptoms. Of particular interest is the late-onset phenotypical expression in a patient with 34 repeats.
Adult↗
Inflammatory pathogenesis of cortical polymicrogyria: an autopsy study.
Polymicrogyria, a cortical abnormality usually classified among neuron migration disorders, is characterized by different etiologies and pathogeneses. Recently, it has been proposed that polymicrogyria could be acquired as a consequence of a lasting damage to the developing brain. In this study, we test the hypothesis that an infection in the fetal adnexa may give rise to distant brain defects and eventually polymicrogyria. Thirty-two fetuses spontaneously aborted for extensive ascending chorioamnionitis at 15-26 wk of gestation were evaluated. Control subjects were represented by 8 fetuses aborted at 15-24 wk of gestation. A complete autopsy was carried out between 4 and 12 h after fetal expulsion. We found different histologic alterations in the primitive cortical architecture, both isolated and combined (undulation of the cortical ribbon, untimely cortical folding/molecular layer fusion, and neuronal loss). A total of 25 cases presented one or more of the above-described morphologic alterations in the brain (78%). On the contrary, similar alterations were never observed in any of the control brains (p=0.019). Our findings indicate that chorioamnionitis significantly impairs brain cortex morphogenesis. Such neuron damage may be caused by an unspecific, indirect mechanism of injury to the developing cortex involving hypoxia and free radical generation. The reported brain abnormalities may even evolve into polymicrogyria in surviving fetuses.
Abortion, Spontaneous↗
Expression of laminin 1 and 2 in brain tumor vessels. An immunohistochemical study.
Components of the blood-brain barrier (BBB) include capillary endothelial cells, the vessel basement membrane (BM) and glial cell interface. While endothelial cell peculiarities are well known and thoroughly studied, BM morphology and functional properties are not. Vessel BM throughout the body is composed of laminin 1, the most common variant of laminin, which is made up of alpha 1, beta 1, and gamma 1 laminin chains, while cerebral vessel BM has been reported to also express the alpha 2 chain. In the present study, we show that the BM of newly formed vessels in brain tumors presents the same immunohistochemical structure as normal brain vessel BM, expressing alpha 1, alpha 2, beta 1, and gamma 1 laminin chains. The function of this particular vessel structure in the central nervous system is not yet completely understood; however, we hypothesize that vessel BM could play a role in impeding the extraneural spreading of brain tumors.
Adult↗
Polymyositis associated with simvastatin.
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Adult↗
Expression of CD59, a regulator of the membrane attack complex of complement, on human skeletal muscle fibers.
Control of complement deposition on autologous cells is mediated by a group of complement regulatory membrane proteins acting at different levels of the complement cascade. Decay accelerating factor (CD55) prevents the assembly of C3 convertases and CD59 membrane inhibitor of reactive lysis (MIRL) restricts homologous complement lysis by the membrane attack complex of complement (MAC) by inhibition of C5b-8 catalyzed insertion of C9. The aim of this work was to study the eventual expression of CD55 and CD59 on human skeletal muscle fibers. Highly sensitive immunoblotting using murine monoclonal antibodies showed that CD59, but not CD55, was present in skeletal muscle fibers. Immunocytochemistry with a monoclonal antibody against CD59 demonstrated a dense granular immunostaining mainly localized at the level of the sarcolemma. Thus, CD59, but not CD55, is expressed on normal skeletal muscle fibers. CD59 may play a prominent role in preventing MAC deposition and subsequent complement-mediated damage in myopathies where the complement system activation is involved.
CD55 Antigens↗
Detection of Borrelia burgdorferi DNA and complement membrane attack complex deposits in the sural nerve of a patient with chronic polyneuropathy and tertiary Lyme disease.
We report a patient who developed a chronic sensory-motor polyneuropathy and a progressive myelopathy 4 years after a tick bite. An increased serum antibody titer to Borrelia burgdorferi suggested a diagnosis of Lyme neuroborreliosis, although a concomitant cervical spondylosis probably contributed to spinal cord damage. Treatment with ceftriaxone resulted in a marked improvement of neuropathic symptoms, providing indirect evidence of spirochetal infection. Search for B. burgdorferi DNA by polymerase chain reaction amplification on sural nerve confirmed the diagnosis, demonstrating that the spirochete localized in the peripheral nervous system. The presence of complement membrane attack complex deposits and macrophage infiltrates around epineurial vessels and within the endoneurium suggests that the neuropathy in our patient was immune-mediated.
Aged↗
Selective bilateral amyotrophy of the anterior tibial muscle: a case report.
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Adult↗
X-linked vacuolated myopathy: membrane attack complex deposition on muscle fiber membranes with calcium accumulation on sarcolemma.
Cytochemical localization of calcium on muscle fibers from patients with X-linked vacuolated myopathy demonstrated strong sarcolemmal or vacuolar calcium deposits in histologically abnormal muscle fibers. All membrane attack complex-positive fibers demonstrated such calcium accumulation. Total content of calcium was significantly elevated in muscles from patients with X-linked vacuolated myopathy compared to control muscles. Taken together, these results suggest that calcium accumulation on sarcolemma could be probably secondary to membrane attack complex deposition on the cell surface.
Calcium↗
Localization of the laminin alpha 2 chain in normal human skeletal muscle and peripheral nerve: an ultrastructural immunolabeling study.
A particular form of congenital muscular dystrophy is associated with a deficiency of the tissue-specific basement membrane protein laminin alpha 2. A more precise knowledge of the normal distribution and localization of laminin alpha 2 would be useful in further elucidating the development of this disorder. In this study we used specific electron microscopic techniques, i.e., thin-section fracture labeling and cryoultramicrotomy in combination with immunogold labeling for laminin alpha 2, to determine its ultrastructural localization in normal human muscle and peripheral nerve. Both in muscle and in peripheral nerve, laminin alpha 2 is found to be associated solely with the basal lamina of myofibers and Schwann cells, respectively. Of special interest is the finding that in peripheral nerve, laminin alpha 2 is associated only with myelinated and not with unmyelinated nerve fibers.
Humans↗
Localization of laminin alpha 2 chain in normal human central nervous system: an immunofluorescence and ultrastructural study.
Recently, a rare form of congenital muscular dystrophy has been shown to be associated with a deficiency of laminin alpha 2 chain, a tissue-specific component of the basal lamina. Besides muscular dystrophy, children affected with this disorder also show electrophysiological and magnetic resonance imaging evidence of white matter involvement in the central nervous system (CNS). We have studied the precise localization of laminin alpha 2 chain in normal human brain, using specific electron microscopic techniques including thin-section fracture labeling and cryoultramicrotomy, in parallel with immunohistochemical techniques. We found that this laminin chain was localized to the basal lamina of all cerebral blood vessels, whereas blood vessels of the choroid plexus did not show any reaction. No positive reaction was found in meningeal blood vessels either. We hypothesize that in normal brain, laminin alpha 2 may be important for the selective filtration capability of the blood-brain barrier. The lack of laminin alpha 2 in cerebral vessels of children with laminin alpha 2-deficient congenital muscular dystrophy may cause impaired selective filtration, leading to leakage of plasma components and damage to the CNS. Further studies should be performed on patients affected by congenital muscular dystrophy associated with laminin alpha 2 deficiency to test this hypothesis.
Adult↗
Focal myositis: a polymerase chain reaction analysis for a viral etiology.
Focal myositis (FM) is a benign inflammatory condition that may clinically simulate a soft tissue sarcoma. It was first described in 1977, and only approximately 30 cases have been reported to date, yet this entity is probably more frequent. The pathogenesis of FM is totally unknown. It has been proposed that it represents a nodular form of myositis, which can evolve into polymyositis, but this hypothesis has not been confirmed by follow-up studies. We describe seven cases of FM, five of which have never been reported before. Histology of the lesions was very similar, showing a destructive inflammatory myopathy with evidence of regeneration. Our study attempted to better understand the pathogenesis of this focal inflammatory myopathy. We performed a polymerase chain reaction study to explore the presence of a number of viral infectious agents in the inflammed tissue. The present study failed to show the presence of a known viral agent with a recognized tropism for myofibers. With a panel of lymphoid cell markers, we also characterized the phenotype of the inflammatory infiltrate that was composed of many T-lymphocytes with few CD4+ cells. Lastly, we reviewed the published cases and discuss the possible pathogenesis.
Adult↗
A syndrome of autosomal recessive pontocerebellar hypoplasia with white matter abnormalities and protracted course in two brothers.
We describe two brothers with an autosomal recessive syndrome characterized by neonatal onset, severe impairment of cognitive and motor functions, abnormal ocular movements and slight dystonic postures. Brain MR and CT scan showed a reduction in size of the cerebellum and to a lesser extent pons, accompanied by cerebral and cerebellar white matter abnormalities. These data suggest that they have a particular phenotype of pontocerebellar hypoplasia. Extensive laboratory investigation excluded known metabolic causes of pontocerebellar hypoplasia. We discuss the nosological status of pontocerebellar hypoplasia in relation to other early-onset pontocerebellar disorders.
Adolescent↗
Localization of laminin chains in the human retina: possible implications for congenital muscular dystrophy associated with alpha 2-chain of laminin deficiency.
One recently described form of congenital muscular dystrophy (CMD) is associated with deficiency of the alpha 2-chain of laminin, an extracellular matrix protein that is specifically located in the basement membrane of placental villi, Schwann cells and skeletal muscle in healthy humans. This laminin is also normally present in the skin, kidney and basement membrane of blood vessels of the CNS, though it is absent from the blood vessel walls in other tissues. In this immunohistochemical study, we have explored the presence of the alpha 1, alpha 2, beta 1 and gamma 1 chains of laminin in the normal human retina, which are all localized in the basement membrane of blood vessels. This study adds to the growing evidence that the alpha 2-chain of laminin is selectively expressed in certain tissues, and suggests that CMD associated with a lack of this protein may be a multisystem disorder, with possible direct involvement of the visual system.
Adult↗
Intracellular detection of laminin alpha 2 chain in skin by electron microscopy immunocytochemistry: comparison between normal and laminin alpha 2 chain deficient subjects.
The aim of this study is to localize the alpha 2 laminin chain in normal human skin. The methods used were immuno-gold cytochemistry on cryo-ultramicrotomy sections and thin-section-fracture-label, together with electron microscopy observation. Results were compared with light microscopy peroxidase immuno-staining. Both normal skin samples and skin biopsies from laminin alpha 2 chain deficient congenital muscular dystrophy affected patients were studied. The results show that, in normal skin, the laminin alpha 2 chain is spread throughout the cytoplasm of basal keratinocytes, while it appears associated with desmosomal tonofilaments in the spinous and granular epidermal layers; in skin samples from dystrophic patients the laminin alpha 2 chain was not detectable. These data suggest that the function of the laminin alpha 2 chain is different in the epidermis as compared to that in muscle and peripheral nerve, where it is localized in the basement membrane.
Humans↗
Unusual clinical features and early brain MRI lesions in a family with cerebral autosomal dominant arteriopathy.
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a recently described inherited disorder. The pathologic gene maps on chromosome 19. The clinical spectrum of the disease consists of recurrent strokes, migraine, transient ischemic attacks, mood changes, and dementia. We report a genetically assessed CADASIL family with atypical clinical presentations of epileptic seizures. In two asymptomatic family members there were early brain abnormalities on MRI. Our report expands the clinical spectrum of CADASIL and suggests that it is possibly an undiagnosed disorder.
Adult↗
Immunolocalization of several laminin chains in the normal human central and peripheral nervous system.
Using specific monoclonal antibodies against different subunits of laminin, we studied the differential distribution pattern of several laminin chains in the central (CNS) and peripheral (PNS) nervous system. Laminin chains alpha 1, beta 1 and gamma 1, were found in the basement membrane (BM) of blood vessels in both CNS and PNS. In contrast, laminin alpha 2 though present in the BM of capillaries in the CNS, was completely absent from PNS capillaries. Laminins alpha 2, beta 1, gamma 1 could be detected in peripheral nerve, in the BM of Schwann cells, which did not contain Laminin alpha 1. The possible importance of laminin alpha 2 for myelination in the PNS as well as in the function of the blood-brain barrier in the CNS, and its potential relevance to the pathology of congenital muscular dystrophy associated with deficiency of this laminin chain, is discussed.
Antibodies, Monoclonal↗