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Biomedical subjects

R Martini

Publications and source records attributed to R Martini.

At least 73 records · Page 4Linked to original sources
PubMed1996

Onion bulb cells in mice deficient for myelin genes share molecular properties with immature, differentiated non-myelinating, and denervated Schwann cells.

Onion bulb formation is a pathological feature observed in peripheral nerves of patients suffering from inherited peripheral neuropathies such as Charcot-Marie-Tooth and Déjérine-Sottas diseases. An onion bulb consists of small circumferentially oriented (supernumerary) cells and their processes surrounding a large caliber axon. In the present study, we investigated the molecular phenotype of supernumerary cells at the light and electron microscopic levels. The major motor (quadriceps muscle) branch of the femoral nerve from 16- to 24-month-old mice with an inactivated allele of the myelin protein zero gene or deficient for myelin-associated glycoprotein (MAG; P0(+)- and MAG--mice, respectively), which have numerous onion bulbs, was teased to obtain single nerve fibers, which were then processed for immunocytochemistry. Corresponding nerves from wild-type mice served as controls. In both P0(+)- and MAG--mice, supernumerary cells expressed S-100, the low-affinity nerve growth factor receptor (p75, NGFr), the cell adhesion molecule L1, the neural cell adhesion molecule (N-CAM), and glial fibrillary acidic protein (GFAP). At the electron microscopic level, the cell surface of supernumerary cells was NGFr immunoreactive and L1 and N-CAM were expressed at points of contact between supernumerary cells. NGFr, L1, and N-CAM were also present in the basal lamina surrounding myelinated axons associated with onion bulbs. Both S-100 and GFAP immunoreactivities were seen in the cytoplasm of supernumerary cells. In contrast, in wild-type mice myelinating Schwann cells only expressed S-100 intracellularly and L1 and N-CAM in their basal lamina, whereas non-myelinating Schwann cells expressed all five molecules investigated. The present study indicates that supernumerary cells in onion bulbs have a molecular phenotype characteristic of immature, differentiated non-myelinating, and denervated Schwann cells, thus excluding the possibility that supernumerary cells are perineurial cells.

Animals↗
PubMed1996

Disruption of the gene for the myelin-associated glycoprotein improves axonal regrowth along myelin in C57BL/Wlds mice.

The myelin-associated glycoprotein (MAG) has been shown to be inhibitory for certain neurons in vitro (Mukhopadhyay et al., 1994; McKerracher et al., 1994). To investigate whether MAG is an inhibitory component in peripheral myelin in vivo, MAG-deficient mutant mice were cross-bred with C57BL/Wlds mice that have delayed lesion-induced myelin degeneration and axon regrowth. While in crushed nerves of C57BL/Wlds mice expressing MAG, only 16% of myelin sheaths were associated with regrowing axons, this number was doubled in MAG-deficient C57BL/Wlds mice. These observations suggest that the absence of MAG may contribute to the improved axonal regrowth in the double mutants. Therefore, degeneration of MAG-containing myelin might be an important prerequisite to optimize axonal regrowth after peripheral nerve injury.

Animals↗
PubMed1996

Tolerability and clinical efficacy of desmin in the treatment of superficial thrombovaricophlebitis.

Fifty-six patients with superficial thrombovaricophlebitis of the lower limbs were enrolled in an open and multicenter (4 centers) trial for a period of thirty days. Patients were randomly allocated to three treatment groups to receive a new low-molecular-weight dermatan sulfate (Desmin) at the dose, respectively, of 100 mg once daily by subcutaneous (SC) route, 100 mg twice a day SC, and 200 mg once daily by intramuscular (IM) route. The general and local tolerability and the clinical efficacy of the drug were evaluated by means of clinical, instrumental, and laboratory parameters. Desmin proved capable of effectively improving the symptoms of patients affected by thrombovaricophlebitis, inducing rapid regression by the tenth day of treatment. The daily dose of 200 mg (either SC or IM) was more effective than the 100 mg dose. The systemic tolerability of the drug, administered for the first time for one month, was extremely good, without significant variations in the relevant laboratory tests. Local tolerance (at the site of injection) of the drug was also good.

Adult↗
PubMed1996

IgD multiple myeloma. A report of three cases.

Three patients suffering from IgD myeloma, which a rare variant of multiple myeloma which often has an aggressive course, were studied retrospectively in order to elucidate the existence of clinical or laboratory features in relationship to survival time. The patients were monitored in follow-up for a time variable for 8 to 52 months. All patients received courses of chemotherapy using an association of Melphalan and Prednisone (MP); one patient also received recombinant interferon alpha in association. Response to chemotherapy, with a > 50% reduction of serum M component, disappearance of Bence Jones proteinuria and permanent control of the disease was achieved in all patients. The median duration of survival in IgD myeloma is shorter than that currently observed in patients with other myeloma types: in our series one patient died 8 months after diagnosis but other two patients are still alive 8 and 52 months after diagnosis, respectively. Great difficulty was encountered in analysis of unfavourable prognostic clinical and laboratory data: in our series, in spite of the small number of cases, the Authors observe that only the relief of increased serum levels of Lactate Dehydrogenase (LDH) seem to be in relationship with a trend of shorter survival. The authors, confirming the particular clinical and laboratory aspects of this myeloma, stress that there may coexist cases in which standard chemotherapy failed to control the diseases: these seem to indicate neoplasia with fast growth kinetics. Further studies are necessary in order to identify new prognostic index which allows the identification of selected groups of patients who can profit from a combination chemotherapy regimen other than the standard MP association.

Aged↗
PubMed1996

[Changes in cerebral vasomotor reactivity in relation to respiratory and metabolic stimuli: an analysis of its behavior in hypertensive and normotensive subjects].

We know that increases in the arterial blood pressure determines changes in the behaviour of the cerebrovascular resistance and also the possible lack of vasomotor reactivity. In order to clarify the pathway of circulatory vasomotor reactivity in arterial hypertension, we carried out a study on a group of hypertensive subjects (20 patients) who were compared to a group of normotensive controls (18 patients). A transcranial doppler (TCD) study was performed with rebreathing tests (apnea and hyperventilation) and it was carried out in both groups of subjects. The TCD was repeated after an administration of sublingual pill of nitroglycerin. In both groups the hyperventilation caused a significant reduction in the velocity peak in the middle cerebral artery (norm.: 84.88 +/- 4.86 cm/sec 60 +/- 5.2 cm/sec; hyperten. 84.50 +/- 7.1 cm/sec 58.80 +/- 5.47 cm/sec) in contrast apnea induced a major increase in the velocities (norm.: 84.88 +/- 4.86 cm/sec 102.50 +/- 4.89 cm/sec; hyperten.: 84.50 +/- 7.1 cm/sec 101.59 +/- 10.6 cm/sec). We noticed a statistical significant difference between the velocities recorded in the different tests (Anova test p < 0.0001). The behaviour of the velocities in the rebreathing tests after nitroglycerin was similar when compared to the same test were performed without the drug. This study suggests that there is no difference in the behaviour of the cerebral reactivity between normotensives and the hypertensive subjects without vascular or cardiac compliance. Finally we would emphasize the role of TCD in the recording changes of cerebrovascular resistances due to pressure or metabolic causes.

Adult↗
PubMed1995

Molecular basis of interactions between regenerating adult rat thalamic axons and Schwann cells in peripheral nerve grafts I. Neural cell adhesion molecules.

To gain insight into the possible molecular mechanisms underlying axonal regeneration of neurons of the adult central nervous system (CNS), we have investigated, by in situ hybridization and by immunocytochemistry, the localization and sites of synthesis of the neurite outgrowth-promoting cell surface molecules L1, N-CAM and its highly sialylated form, N-CAM-PSA, in and around peripheral nerve grafts implanted into the thalamus of adult rats. Normal unoperated adult rat thalamus contains N-CAM and L1 but no N-CAM-PSA immunoreactive axons. Between 7 days and 13 weeks after graft implantation, L1, N-CAM and N-CAM-PSA were all present at the surface of axonal sprouts in the brain parenchyma close to grafts and in the central parts of Schwann cell columns within grafts. Schwann cell membranes were L1 and N-CAM positive at all postgraft survival times, more strongly at 2-4 weeks than other times, but were associated with N-CAM-PSA reaction product only where they abutted N-CAM-PSA positive axons. Schwann cell membranes apposed to basal laminae (which were avoided by regenerating CNS axons) were L1, N-CAM and N-CAM-PSA negative. Between 3 days and 8 weeks after grafting, N-CAM and L1 mRNA were generally weakly upregulated in neurons of the ipsilateral thalamus, but, most conspicuously, L1 mRNA was strongly upregulated in the neurons of the thalamic reticular nucleus; these neurons are known to regenerate axons very effectively into peripheral nerve grafts and are the probable source of most of the axons which enter thalamic grafts. N-CAM and L1 mRNA were also strongly upregulated in presumptive Schwann cells in the graft. These results show that regenerating CNS axons (re)express N-CAM-PSA and upregulate L1 and N-CAM, suggesting that all of these molecules may play a role in cellular interactions during the regeneration of CNS axons. Furthermore L1 synthesis appears to be particularly well correlated with the ability of CNS neurons to regenerate axons into peripheral nerve grafts.

Animals↗
PubMed1995

Molecular basis of interactions between regenerating adult rat thalamic axons and Schwann cells in peripheral nerve grafts. II. Tenascin-C.

Tenascin-C is a developmentally regulated extracellular matrix component. There is evidence that it may be involved in axon growth and regeneration in peripheral nerves. We have used in situ hybridization and immunocytochemistry to investigate the association of tenascin-C with central nervous system axons regenerating through a peripheral nerve autograft inserted into the thalamus of adult rats. Between 3 days and 4 weeks after implantation, tenascin-C immunoreactivity was increased in the grafts, first at the graft/brain interface, then in the endoneurium of the graft, and finally within the Schwann cell columns of the graft. By electron microscopy, reaction product was present around collagen fibrils and basal laminae in the endoneurium, but the heaviest deposits were found at the surface of regenerating thalamic axons within Schwann cell columns. Schwann cell surfaces were not associated with tenascin-C reaction product except where they faced the tenascin-rich basal lamina or were immediately opposite axons surrounded by tenascin-C. By 8 weeks after graft implantation tenascin-C in the endoneurium and around axons of the graft was decreased. In the brain parenchyma around the proximal part of the graft, axonal sprouts associated with tenascin-C could not be identified earlier than 2 weeks after grafting and were sparse at this stage. Larger numbers of such axons were present at 8-13 weeks after grafting and were located predominantly where the glia limitans between brain and graft appeared to be incomplete, suggesting that the tenascin-C may have penetrated the brain parenchyma from the graft. By in situ hybridization, cells expressing tenascin-C mRNA (probably Schwann cells) appeared first at the brain/graft interface 3 days after grafting and thereafter were mainly located within the grafts. Lightly labelled cells containing tenascin-C mRNA (probably glial cells) were scattered in the thalamic parenchyma both ipsilateral and contralateral to the graft and a few heavily labelled cells were located very close to the tip of the graft. These results show that regenerating adult thalamic axons, unlike regenerating peripheral axons, become intimately associated with peripheral nerve graft-derived tenascin-C, suggesting that they express a tenascin-C receptor, as many neurons do during development, and that tenascin-C derived from Schwann cells may play a role in the regenerative growth of such axons through the grafts.

Animals↗
PubMed1995

Up-regulation of a chondroitin sulphate epitope during regeneration of mouse sciatic nerve: evidence that the immunoreactive molecules are related to the chondroitin sulphate proteoglycans decorin and versican.

After transection of adult mouse sciatic nerve, the expression of a chondroitin sulphate epitope recognized by the monoclonal antibody 473-HD (mAb 473-HD) was found to be up-regulated. The epitope was localized immunocytochemically mainly in Schwann cell basal laminae and, more weakly, also in the endoneurium. In cultures of mouse dorsal root ganglion cells, Schwann cells expressed high levels but fibroblasts only low levels of the epitope. To identify the molecule(s) carrying this chondroitin sulphate epitope, human sciatic nerves were extracted with phosphate-buffered saline and shown to contain two chondroitin sulphate proteoglycans of apparent molecular weights of 130 and 900 kDa. The 900 kDa and, more weakly, the 130 kDa proteoglycan were reactive with mAb 473-HD, which was found to recognize chondroitin-6-sulphate as epitope. Following chondroitinase ABC treatment of the 130 kDa proteoglycan, a core protein of approximately 45 kDa was seen and shown to react with polyclonal antibodies against the chondroitin-dermatan sulphate proteoglycan decorin from human fibroblasts. Chondroitinase ABC treatment of the 900 kDa proteoglycan yielded a core protein with a molecular weight of approximately 400 kDa that was recognized by polyclonal antibodies against recombinantly expressed fusion proteins from human versican. After transection of adult mouse sciatic nerves, the distal nerve stumps showed up-regulation of the chondroitin-6-sulphate epitope of the 900 kDa proteoglycan, whereas the core protein of this proteoglycan did not show any detectable change in the level of expression. In contrast, the core protein of the 130 kDa proteoglycan was up-regulated in expression. These observations suggest that versican- and decorin-like molecules may contribute to successful regeneration in the peripheral nervous system of mammals.

Animals↗
PubMed1995

Crucial role for the myelin-associated glycoprotein in the maintenance of axon-myelin integrity.

It has recently been shown that mice deficient in the gene for myelin-associated glycoprotein develop normal myelin sheaths in the peripheral nervous system. Here we report that in mutant mice older than 8 months the maintenance of axon-myelin units is disturbed, resulting in both axon and myelin degeneration. Morphological features include those typically seen in human peripheral neuropathies, where demyelination-induced Schwann cell proliferation and remyelination lead to the formation of so-called onion bulbs. Expression of tenascin-C, a molecule indicative of peripheral nerve degeneration, was up-regulated by axon-deprived Schwann cells and regenerating axons were occasionally seen. Myelin-associated glycoprotein thus appears to play a crucial role in the long-term maintenance of the integrity of both myelin and axons.

Animals↗
PubMed1995

Tenascin-C expression during wallerian degeneration in C57BL/Wlds mice: possible implications for axonal regeneration.

Schwann cells in the distal stumps of lesioned peripheral nerves strongly express the extracellular matrix glycoprotein tenascin-C. To gain insights into the relationship between Wallerian degeneration, lesion induced tenascin-C upregulation and regrowth of axons we have investigated C57BL/Wlds (C57BL/Ola) mice, a mutant in which Wallerian degeneration is considerably delayed. Since we found a distinct difference in the speed of Wallerian degeneration between muscle nerves and cutaneous nerves in 16-week-old C57BL/Wlds mice, as opposed to 6-week-old animals in which Wallerian degeneration is delayed in both, we chose the older animals for closer investigation. Five days post lesion tenascin-C was upregulated in the muscle branch (quadriceps) but not in the cutaneous branch (saphenous) of the femoral nerve in 16-week-old animals. In addition myelomonocytic cells displaying endogenous peroxidase activity invaded the muscle branch readily whereas they were absent from the cutaneous branch at this time. We could further show that it is only a subpopulation of axon-Schwann cell units (mainly muscle efferents) in the muscle branch which undergo Wallerian degeneration and upregulate tenascin-C at normal speed and that the remaining axon-Schwann cell units (mainly afferents) displayed delayed Wallerian degeneration and no tenascin-C expression. Regrowing axons could only be found in the tenascin-C-positive muscle branch where they always grew in association with axon-Schwann cell units undergoing Wallerian degeneration. These observations indicate a tight relationship between Wallerian degeneration, upregulation of tenascin-C expression and regrowth of axons, suggesting an involvement of tenascin-C in peripheral nerve regeneration.

Animals↗
PubMed1995

Pediatric otolaryngology: a psychosocial perspective.

Physical illness in children is affected by a variety of factors unique to pediatrics. They include a child's developmental level, family environment and the presence of premorbid behavior patterns. Therefore, pediatric care requires special considerations pertaining to the patient-physician relationship and the potential for psychosocial dysfunction. Three case reports are presented to illustrate these concerns in treating children within the specialty of otolaryngology. Prompt identification of these factors and effective intervention in cases of psychosocial disturbance are challenging facets of the practice of pediatric otolaryngology.

Adolescent↗
PubMed1995

Glycans and the modulation of neural-recognition molecule function.

Neural-recognition molecules are carbohydrate-bearing glycoproteins, glycolipids or proteoglycans that are found at the cell surface or in the extracellular matrix that regulate cell interactions during development, modification of synaptic activity and regeneration of nerve connections after damage in the adult. The expression of the carbohydrates appears to be fine tuned to these functions. Among the identified carbohydrates are polysialic acid, a 3'-sulfated glucuronic acid, and oligomannosidic residues. They act not only between apposing partner cell surfaces (trans-interaction) but also between recognition molecules within the surface membrane of one cell (cis-interaction), thereby forming complexes that influence transduction of signals to the cell interior.

Animals↗
PubMed1995

Ethanol-related liver injury in the rat: a model of steatosis, inflammation and pericentral fibrosis.

BACKGROUND/AIMS: While several animal models exist for the study of ethanol heptotoxicity, they are limited in their applicability. This paper describes a relatively simple rat model of alcohol-related liver injury. METHODS: Ethanol was supplied in the drinking water in a concentration of 40% v/v for up to 29 weeks. Animals are concurrently supplied a chow diet which provides adequate protein and choline for normal growth. Total fat intake is low (7% of consumed calories). RESULTS: Histological changes of steatosis, inflammation, hepatocyte necrosis and pericentral sclerosis were evident in ethanol-treated rat livers. Littermate controls with and without pair-feeding had normal livers. Electron microscopy revealed abnormal mitochondria and a marked proliferation of smooth endoplasmic reticulum in livers of animals fed ethanol. Biochemical analysis revealed that levels of hepatic-free choline were similar in treated and pair-fed control rats. There was an expected increase in the activity of the microsomal enzyme cytochrome P450 2E1 in ethanol-fed rats. CONCLUSIONS: The model provides a convenient method for the production of alcoholic liver injury, and it may be useful for the study of the pathogenesis of ethanol-related liver disease.

Alcohol Drinking↗
PubMed1995

Hypermyelination and demyelinating peripheral neuropathy in Pmp22-deficient mice.

Peripheral myelin protein PMP22 has been suggested to have a role in peripheral nerve myelination and cell proliferation. Defects at the PMP22 locus are associated with peripheral neuropathies such as Charcot-Marie-Tooth disease type 1A. We now demonstrate that mice devoid of Pmp22 are retarded in the onset of myelination and develop abundant sausage-like hypermyelination structures (tomacula) at a young age followed by severe demyelination, axonal loss and functional impairment. Mice carrying one functional copy of Pmp22 are less affected but they also exhibit focal tomacula comparable to the morphological features in hereditary neuropathy with liability to pressure palsies (HNPP). We conclude that Pmp22 is required for the correct development of peripheral nerves, the maintenance of axons and the determination of myelin thickness and stability.

Animals↗
PubMed1995

Protein zero (P0)-deficient mice show myelin degeneration in peripheral nerves characteristic of inherited human neuropathies.

Mutations in the human gene for the myelin recognition molecule protein zero (P0) give rise to severe and progressive forms of dominantly inherited peripheral neuropathies. We have previously reported that mice homozygous for a null mutation in P0 have severely hypomyelinated nerves ten weeks after birth. Here we show hypomyelination already exists at day four with subsequent demyelination and impaired nerve conduction. Furthermore, heterozygous mutants show normal myelination, but develop progressive demyelination after four months of age. Thus, the pathology of homo- and heterozygous P0 mutants resembles that of the severely affected Déjérine-Sottas and the more mildly affected Charcot-Marie-Tooth type 1B patients, respectively.

Animals↗
PubMed1995

Transcutaneous PCO2 level as an index of tissue resistance to ischemia.

The authors performed a retrospective study on a data base of 525 patients with peripheral arterial disease, to analyze the pathophysiologic meaning of resting transcutaneous pressure of carbon dioxide (PCO2) and of CO2 production during three minutes of local ischemia. The resting and postischemic PCO2 and its maximum increase related to rest (PCO2 production) were measured with Kontron 7640 equipment. The results show a significant increase of PCO2 production in the Fontaine stage 2A (183 patients, 4.61 mmHg, P < 0.0001), in stage 2B (194 patients, 5.22 mmHg, P < 0.0001), in the third stage (83 patients, 6.10 mmHg, P < 0.0001), and in the fourth stage (53 patients, 8.66 mmHg, P < 0.0001). Only the patients at the first stage showed an insignificant increase, perhaps because of the small number (12) in this group. The authors feel that the measurement of tcPCO2 production during local ischemic stress can be a very important parameter for evaluating peripheral arterial disease as an expression of metabolic tissue performance and, overall, of the tissue resistance to ischemia.

Arterial Occlusive Diseases↗
PubMed1995

Mice doubly deficient in the genes for P0 and myelin basic protein show that both proteins contribute to the formation of the major dense line in peripheral nerve myelin.

In search for the molecular mechanisms underlying the formation of the major dense line in peripheral nerve myelin we investigated mice deficient in the myelin proteins P0 and MBP. In mice lacking both molecules axons were enwrapped by myelin-like processes devoid of the major dense line, while mice deficient in either protein showed, respectively, partial and normal compaction. Mice heterozygous for P0 but devoid of MBP showed myelin of reduced thickness around axons of normal caliber. Both molecules thus contribute to the formation of the major dense line and to the determination of myelin thickness. Furthermore, our observations modify the view that axon caliber is dependent on normal myelin.

Animals↗