RESUMO
This study examined CD200 expression in different peripheral nerves and ganglia. Intense CD200 immunoreactivity was consistently localized in unmyelinated nerve fibers as opposed to a faint immunostaining in the myelinated nerve fibers. By light microscopy, structures resembling the node of Ranvier and Schmidt-Lanterman incisures in the myelinated nerve fibers displayed CD200 immunoreactivity. Ultrastructural study revealed CD200 expression on the neurilemma of Schwann cells whose microvilli and paranodal loops at the node of Ranvier were immunoreactive. The CD200 immunoexpression was also localized in the satellite glial cells of sensory and autonomic ganglia and in the enteric glial cells. Double labeling of CD200 with specific antigens of satellite glia or Schwann cells in the primary cultures of dorsal root ganglia had shown a differential expression of CD200 in the peripheral glial cells. The existence of CD200 in glial cells in the peripheral nervous system (PNS) was corroborated by the expression of CD200 mRNA and protein in a rat Schwann cell line RSC96. Using the model of crush or transected sciatic nerve, it was found that CD200 expression was attenuated or diminished at the site of lesion. A remarkable feature, however, was an increase in incidence of CD200-labelled Schmidt-Lanterman incisures proximal to the injured site at 7 days postlesion. Because CD200 has been reported to impart immunosuppressive signal, we suggest that its localization in PNS glial cells may play a novel inhibitory role in immune homeostasis in both normal and pathological conditions.
Assuntos
Antígenos CD/metabolismo , Regulação da Expressão Gênica/fisiologia , Neuroglia/metabolismo , Neuropatia Ciática/patologia , Animais , Axotomia/métodos , Células Cultivadas , Gânglios Espinais/citologia , Proteína Glial Fibrilar Ácida/metabolismo , Masculino , Microscopia Eletrônica de Transmissão , Neuroglia/ultraestrutura , Ratos , Ratos Wistar , Células de Schwann/metabolismo , Células de Schwann/ultraestrutura , Ubiquitina Tiolesterase/metabolismoRESUMO
OBJECTIVE: To assess the prevalence, nature, and associated phenotypes of ATP13A2 gene mutations among patients with juvenile parkinsonism (onset <21 years) or young onset (between 21 and 40 years) Parkinson disease (YOPD). METHODS: We studied 46 patients, mostly from Italy or Brazil, including 11 with juvenile parkinsonism and 35 with YOPD. Thirty-three cases were sporadic and 13 had positive family history compatible with autosomal recessive inheritance. Forty-two had only parkinsonian signs, while four (all juvenile-onset) had multisystemic involvement. The whole ATP13A2 coding region (29 exons) and exon-intron boundaries were sequenced from genomic DNA. RESULTS: A novel homozygous missense mutation (Gly504Arg) was identified in one sporadic case from Brazil with juvenile parkinsonism. This patient had symptoms onset at age 12, levodopa-responsive severe akinetic-rigid parkinsonism, levodopa-induced motor fluctuations and dyskinesias, severe visual hallucinations, and supranuclear vertical gaze paresis, but no pyramidal deficit nor dementia. Brain CT scan showed moderate diffuse atrophy. Furthermore, two Italian cases with YOPD without atypical features carried a novel missense mutation (Thr12Met, Gly533Arg) in single heterozygous state. CONCLUSIONS: We confirm that ATP13A2 homozygous mutations are associated with human parkinsonism, and expand the associated genotypic and clinical spectrum, by describing a homozygous missense mutation in this gene in a patient with a phenotype milder than that initially associated with ATP13A2 mutations (Kufor-Rakeb syndrome). Our data also suggest that ATP13A2 single heterozygous mutations might be etiologically relevant for patients with YOPD and further studies of this gene in Parkinson disease are warranted.
Assuntos
Predisposição Genética para Doença/genética , Mutação de Sentido Incorreto/genética , Doença de Parkinson/genética , Transtornos Parkinsonianos/genética , ATPases Translocadoras de Prótons/genética , Adolescente , Adulto , Idade de Início , Encéfalo/patologia , Encéfalo/fisiopatologia , Brasil/epidemiologia , Criança , Estudos de Coortes , Análise Mutacional de DNA , Diagnóstico Diferencial , Feminino , Testes Genéticos , Genótipo , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/epidemiologia , Transtornos Parkinsonianos/epidemiologia , Fenótipo , PrevalênciaRESUMO
BACKGROUND: Mutations in the gene Leucine-Rich Repeat Kinase 2 (LRRK2) were recently identified as the cause of PARK8 linked autosomal dominant Parkinson's disease. OBJECTIVE: To study recurrent LRRK2 mutations in a large sample of patients from Italy, including early (<50 years) and late onset familial and sporadic Parkinson's disease. RESULTS: Among 629 probands, 13 (2.1%) were heterozygous carriers of the G2019S mutation. The mutation frequency was higher among familial (5.1%, 9/177) than among sporadic probands (0.9%, 4/452) (p<0.002), and highest among probands with one affected parent (8.7%, 6/69) (p<0.001). There was no difference in the frequency of the G2019S mutation in probands with early v late onset disease. Among 600 probands, one heterozygous R1441C but no R1441G or Y1699C mutations were detected. None of the four mutations was found in Italian controls. Haplotype analysis in families from five countries suggested that the G2019S mutation originated from a single ancient founder. The G2019S mutation was associated with the classical Parkinson's disease phenotype and a broad range of onset age (34 to 73 years). CONCLUSIONS: G2019S is the most common genetic determinant of Parkinson's disease identified so far. It is especially frequent among cases with familial Parkinson's disease of both early and late onset, but less common among sporadic cases. These findings have important implications for diagnosis and genetic counselling in Parkinson's disease.
Assuntos
Mutação , Doença de Parkinson/genética , Proteínas Serina-Treonina Quinases/genética , Adulto , Idoso , Alelos , Sequência de Bases , Feminino , Efeito Fundador , Heterozigoto , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Masculino , Pessoa de Meia-Idade , Dados de Sequência MolecularRESUMO
OBJECTIVE: To assess the prevalence, nature, and associated phenotypes of PINK1 gene mutations in a large series of patients with early-onset (<50 years) parkinsonism. METHODS: The authors studied 134 patients (116 sporadic and 18 familial; 77% Italian) and 90 Italian controls. The whole PINK1 coding region was sequenced from genomic DNA; cDNA was analyzed in selected cases. RESULTS: Homozygous pathogenic mutations were identified in 4 of 90 Italian sporadic cases, including the novel Gln456Stop mutation; single heterozygous truncating or missense mutations were found in another 4 Italian sporadic cases, including two novel mutations, Pro196Leu and Gln456Stop. Pathogenic mutations were not identified in the familial cases. Novel (Gln115Leu) and known polymorphisms were identified with similar frequency in cases and controls. In cases carrying single heterozygous mutation, cDNA analysis detected no additional mutations, and revealed a major pathogenic effect at mRNA level for the mutant C1366T/Gln456Stop allele. All patients with homozygous mutations had very early disease onset, slow progression, and excellent response to l-dopa, including, in some, symmetric onset, dystonia at onset, and sleep benefit, resembling parkin-related disease. Phenotype in patients with single heterozygous mutation was similar, but onset was later. CONCLUSIONS: PINK1 homozygous mutations are a relevant cause of disease among Italian sporadic patients with early-onset parkinsonism. The role of mutations found in single heterozygous state is difficult to interpret. Our study suggests that, at least in some patients, these mutations are disease causing, in combination with additional, still unknown factors.
Assuntos
Predisposição Genética para Doença/genética , Mutação/genética , Doença de Parkinson/genética , Proteínas Quinases/genética , Adolescente , Adulto , Idade de Início , Criança , Análise Mutacional de DNA , DNA Complementar/análise , DNA Complementar/genética , Feminino , Frequência do Gene , Testes Genéticos , Genoma/genética , Genótipo , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Doença de Parkinson/epidemiologia , Doença de Parkinson/fisiopatologia , Fenótipo , Polimorfismo Genético/genética , Homologia de Sequência de AminoácidosRESUMO
Between one-third and one-half of all cases of sepsis are known to be caused by gram-positive microorganisms through the cell wall component, e.g. lipoteichoic acid (LTA). Gram-positive bacteria are also known to induce encephalomyelitis and meningeal inflammation, and enhance the production of nitric oxide (NO) via expression of inducible nitric oxide synthase (iNOS) in murine tissue macrophages. It remains to be explored if LTA could activate microglia considered to be resident brain macrophages. We report here that LTA derived from gram-positive bacteria (Staphylococcus aureus) significantly induces NO release and iNOS expression in primary microglia. LTA-induced NO accumulation was detected at 2 h in microglial culture and was significantly attenuated by pretreatment with anti-CD14, complement receptor type 3 (CR3) or scavenger receptor (SR) antibodies. LTA activated mitogen-activated protein kinases (MAPKs) such as extracellular signal-regulated kinase, p38 MAPK or c-Jun N-terminal kinase in cultured microglia. LTA-elicited microglial NO production was also drastically suppressed by SB203580 (p38 MAPK inhibitor) or pyrrolidine dithiocarbamate (an inhibitor of nuclear factor kappaB), indicating that p38 MAPK and nuclear factor kappaB were involved in microglial NO release after LTA challenge. These results suggest that gram-positive bacterial product such as LTA can activate microglia to release NO via the signal transduction pathway involving multiple LTA receptors (e.g. CD14, CR3 or SR), p38 MAPK and nuclear factor kappaB. The in vivo study further confirmed that administered intracerebrally LTA induced considerable noticeable iNOS, phospho-IkappaB and phospho-p38 MAPK expression in microglia/macrophages.
Assuntos
Lipopolissacarídeos/farmacologia , Microglia/efeitos dos fármacos , Óxido Nítrico/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ácidos Teicoicos/farmacologia , Animais , Anticorpos/farmacologia , Western Blotting/métodos , Carbidopa/imunologia , Células Cultivadas , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Proteínas do Olho/imunologia , Imunofluorescência/métodos , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas I-kappa B/metabolismo , Indóis , Lectinas/metabolismo , Levodopa/imunologia , Receptores de Lipopolissacarídeos/imunologia , Microglia/enzimologia , Proteínas do Tecido Nervoso/imunologia , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo II , Nitritos/metabolismo , Ratos , Ratos Wistar , Fatores de Tempo , gama-Sinucleína , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Using isolectin (GSA I-B4) as a marker, this study examined the possible alterations of lectin-labeled membranous glycoproteins in microglial cells in the olfactory bulb of normal development and under experimentally induced degeneration. In light microscopy, several morphological types of microglial cells representing different degrees of cell differentiation were distributed in the bulb laminae. A gradient of microglial differentiation extending from the intermediate to superficial and intermediate to deep occurs in the bulb layers. The differentiation gradient and lectin labeling pattern of microglial cells in the developing bulb resembled those in other areas of the brain tissues. Differentiating microglia showed a gradual diminution of lectin staining when the nascent round cells transformed into the mature ramified cells. Microglia in the external plexiform layer of the olfactory bulb were the first to mature and the cells expressed very weak lectin reactivity. In mature or adult rats, some microglial cells showing intense lectin labeling were observed in the olfactory nerve layer, granule cell layer and subependymal layer. Ultrastructurally, lectin labeling was localized at the trans saccules of the Golgi apparatus. Microglial cells in other bulb laminae, however, exhibited a negative reaction for the isolectin at the Golgi apparatus. Following intranasal irrigation of zinc sulfate, some microglial cells in the olfactory nerve layer and glomerular layer were activated to become phagocytic cells with increased lectin labeling at their ramified processes. GSA I-B4 staining was also localized at their trans saccules of the Golgi apparatus. The lectin labeling pattern of these phagocytic cells resembled that of differentiating microglia in postnatal bulbs, suggesting that bulb microglia in the lesioned sites were activated through cell dedifferentiation into macrophages.
Assuntos
Microglia/química , Bulbo Olfatório/química , Traumatismos do Nervo Olfatório , Nervo Olfatório/química , Sulfato de Zinco/toxicidade , Animais , Imunoquímica , Lectinas/análise , Microglia/ultraestrutura , Bulbo Olfatório/crescimento & desenvolvimento , Bulbo Olfatório/ultraestrutura , Nervo Olfatório/crescimento & desenvolvimento , Nervo Olfatório/ultraestrutura , Ratos , Ratos WistarRESUMO
Pathological diagnosis of neuropathy has traditionally depended on ultrastructural examinations of nerve biopsy specimens, particularly for sensory neuropathies affecting unmyelinated and small-myelinated nociceptive nerves. These sensory nerves terminate in the epidermis of the skin, and the pathology of neuropathy usually begins from nerve terminals. We investigated the feasibility of diagnosing small-fiber sensory neuropathy by evaluating cutaneous innervation. Skin biopsy specimens of 3-mm in diameter were obtained from the distal leg and the distal forearm of 55 healthy controls and 35 patients with sensory neuropathy. In the healthy controls, conventional intraepidermal nerve fiber densities (IENF densities) as measured using the image analysis system in the distal forearm and in the distal leg were correlated (r=0.55, P<0.0001), with significantly higher values in the distal forearm than in the distal leg (17.07+/-6.51 vs 12.92+/-5.33 fibers/mm, P<0.001). Compared to IENF densities of healthy controls, these values of neuropathic patients were significantly reduced in the distal forearm (5.82+/-6.50 fibers/mm, P<0.01) and in the distal leg (2.40+/-2.30, P<0.001). We further explored the possibility of quantifying skin innervation by counting "ocular intraepidermal nerve fiber density" (ocular nerve fiber density) with no aid of an image analysis system. This was based on the fact that the epidermal length on specifically defined sections was very close to the predicted epidermal length of 3 mm, the diameter of skin punches (P=0.14). Ocular nerve fiber densities were significantly correlated with IENF densities as measured by the image analysis system (r=0.99, P<0.0001). Dermal nerve fibers of neuropathic patients either disappeared or became degenerated. These findings were consistent with the notion of early terminal degeneration in neuropathy, and will facilitate quantitative interpretation of epidermal innervation in human neuropathy.
Assuntos
Epiderme/inervação , Epiderme/patologia , Degeneração Neural/patologia , Doenças do Sistema Nervoso Periférico/patologia , Células Receptoras Sensoriais/patologia , Adulto , Idoso , Biópsia , Contagem de Células , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
After glucocorticoid injection(s), the number of amoeboid microglial cells (AMC) in the corpus callosum labelled by lectin was markedly reduced when compared with the corresponding control rats. In rats killed at the age of 7 days, all the labeled cells differentiated to become ramified microglia. Ultrastructurally, the AMC in glucocorticoid-injected rats were extremely vacuolated and showed increased lipid droplets. Furthermore, the cells displayed varied lectin labelling patterns especially at both the trans saccules of the Golgi apparatus and lysosomes. In differentiating ramified microglia, massive cellular debris and lectin-stained vesicles or vacuoles were observed; some of the latter appeared to fuse with the plasma membrane. The most striking feature after glucocorticoid (GCC) treatment was the complete diminution of lectin labelling at the Golgi saccules in some differentiating ramified microglia. The present results have demonstrated different effects of glucocorticoids on AMC and differentiating ramified microglia. The differential response of AMC and differentiating ramified microglia to the immunosuppressive drugs may be attributed to the fact that these cells in the postnatal brains subserve different functions or that they are at different differentiation stages. In other words, the sensitivity of microglial cells to the immunosuppressive drugs is dependent upon the stage of cell maturation/differentiation.
Assuntos
Animais Recém-Nascidos/crescimento & desenvolvimento , Diferenciação Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Corpo Caloso/efeitos dos fármacos , Glucocorticoides/farmacologia , Lectinas/farmacocinética , Microglia/efeitos dos fármacos , Animais , Animais Recém-Nascidos/anatomia & histologia , Animais Recém-Nascidos/metabolismo , Contagem de Células , Diferenciação Celular/fisiologia , Movimento Celular/fisiologia , Tamanho Celular/efeitos dos fármacos , Tamanho Celular/fisiologia , Corpo Caloso/crescimento & desenvolvimento , Corpo Caloso/ultraestrutura , Cortisona/farmacologia , Dexametasona/farmacologia , Histocitoquímica , Membranas Intracelulares/efeitos dos fármacos , Membranas Intracelulares/metabolismo , Membranas Intracelulares/ultraestrutura , Microglia/metabolismo , Microglia/ultraestrutura , Microscopia Eletrônica , Organelas/efeitos dos fármacos , Organelas/metabolismo , Organelas/ultraestrutura , Ratos , Ratos Wistar , Vacúolos/efeitos dos fármacos , Vacúolos/metabolismo , Vacúolos/ultraestruturaRESUMO
BACKGROUND AND PURPOSE: Although orbital fractures are common, orbital cellulitis rarely develops following orbital fracture. We hypothesized that compromise of the blood supply to the intraorbital fat during orbital floor fracture is responsible for this condition. The purpose of this study was to determine whether or not the lower intraorbital fat is supplied by a branch of the infraorbital artery along the orbital groove or canal on the orbital floor. MATERIALS AND METHODS: We dissected 14 orbits from seven fixed human cadavers and 12 orbits from six fresh cadaver heads following dye injection into the maxillary artery. The sites of dye-filled vessels branching from the infraorbital artery supplying the lower intraorbital fat were measured and plotted on a two-dimensional orbital floor graph. RESULTS: A main branch of the infraorbital artery rose through the medial orbital floor to supply the lower intraorbital fat in all of the cadaver orbits. The sites of the branching point of the vessel ranged from 0 to 5 mm (mean, 2.2 mm; n = 14) medial to the line connecting the infraorbital foramen and the infraorbital groove. The shortest distance measured from the branching point to the orbital rim ranged from 3 to 20 mm (mean, 14.1 mm; n = 14). This suggests that if orbital fracture were to occur around the infraorbital groove or canal, this vascular pedicle would be in danger of being incarcerated by bone fragments. CONCLUSION: Our cadaveric investigation revealed that the lower intraorbital fat is supplied by a branch of the infraorbital artery along the infraorbital groove or canal on the orbital floor. This finding suggests that compromised blood supply to the intraorbital fat may cause anaerobic cellulitis or enophthalmos.
Assuntos
Tecido Adiposo/irrigação sanguínea , Celulite (Flegmão)/etiologia , Órbita/irrigação sanguínea , Doenças Orbitárias/etiologia , Fraturas Orbitárias/complicações , Adulto , Bactérias Anaeróbias , Cadáver , Feminino , Humanos , MasculinoRESUMO
We have established a QCM immunoassay system which allows on-line and quantitative monitoring throughout the entire detection procedure and provides information on the surface coverage and the binding ratio of antibody to antigen. Compared to conventional immunoassay systems the QCM system offers advantages of short response times, obviates the need for additive labeling reagents, and permits direct conversion of a frequency signal into mass accumulation.
Assuntos
Imunoensaio/métodos , Quartzo , Cristalização , Humanos , Albumina Sérica/imunologiaRESUMO
UNLABELLED: Renal afferent signaling diuretic response is impaired in streptozotocin-induced diabetic rats. BACKGROUND: Renal insufficiency develops in diabetes and shows structural and functional abnormalities. Renal afferents, including chemoreceptors and mechanoreceptors located in the vascular and ureteropelvic portions of the kidney, may reflect changes in the environment and trigger an afferent nerve-mediated regulatory function that is known as the renorenal reflex. In this study, the involvement of these renal sensory receptors during the early diabetic state is defined. METHODS: Diabetes was induced in rats after a tail vein injection of streptozotocin (STZ; 60 mg/kg intravenously). Four groups of rats, control (C), diabetic (DM), diabetic with acute insulin treatment (DMAI, 9 U/rat, subcutaneously, on the experimental day), and chronic insulin treatment (DMCI, 9 U/rat, subcutaneously, daily) were studied. Spontaneous firing type 2-renal chemoreceptor (CR2), arterial mechanoreceptor (MRa), ureteropelvic mechanoreceptor (MRu), and venous mechanoreceptor (MRv) were identified by single-unit analysis of renal afferent nervous activity. The receptor activities were confirmed by their response patterns to stimuli elicited by renal arterial occlusion (RAO), backflow of urine, increasing arterial pressure, increasing ureteropelvic pressure (UP), or renal venous occlusion (RVO). The response of these afferent receptors to a challenge of volume expansion and their functional activities on renorenal reflexes were also examined. Immunostaining with PGP 9.5 was applied for examination of the nerve distribution in the diabetic kidney. The tissue level of histamine in the renal pelvis was determined. We explored the effect of histamine on renal receptor activity in these animals to address the possible role of histamine in MRu receptor activity. RESULTS: In early diabetics, signaling activities in MRa and MRv were maintained; however, activity in CR2 and MRu was depressed. For CR2, the reduced basal discharge and the repressed responses to RAO, backflow of urine, and volume expansion found in DM rats were recovered by acute insulin treatment to restore glucose levels to near normal. For MRu, the depressed response to increasing UP and volume expansion was not restored by acute correction of hyperglycemia in DMAI rats. However, antihistamine treatment or chronic insulin treatment recovered the MRu response to mechanical stimuli in DM rats. Because of the desensitized CR2 and MRu activity, renorenal reflexes elicited by backflow of urine and increasing UP were depressed in DM rats. CONCLUSION: Despite a lack of structural changes, the operating system, signaling ability, and renorenal reflex regulatory function of two renal afferent nerve receptors, CR2 and MRu, are altered in the early diabetic state.
Assuntos
Diabetes Mellitus Experimental/metabolismo , Diurese , Transdução de Sinais , Animais , Diabetes Mellitus Experimental/fisiopatologia , Feminino , Liberação de Histamina , Rim/inervação , Rim/metabolismo , Rim/fisiopatologia , Neurônios Aferentes/fisiologia , Ratos , Ratos Wistar , EstreptozocinaRESUMO
We investigated whether uninjured cutaneous C-fiber nociceptors in primates develop abnormal responses after partial denervation of the skin. Partial denervation was induced by tightly ligating spinal nerve L6 that innervates the dorsum of the foot. Using an in vitro skin-nerve preparation, we recorded from uninjured single afferent nerve fibers in the superficial peroneal nerve. Recordings were made from 32 C-fiber nociceptors 2-3 wk after ligation and from 29 C-fiber nociceptors in control animals. Phenylephrine, a selective alpha1-adrenergic agonist, and UK14304 (UK), a selective alpha2-adrenergic agonist, were applied to the receptive field for 5 min in increasing concentrations from 0.1 to 100 microM. Nociceptors from in vitro control experiments were not significantly different from nociceptors recorded by us previously in in vivo experiments. In comparison to in vitro control animals, the afferents found in lesioned animals had 1) a significantly higher incidence of spontaneous activity, 2) a significantly higher incidence of response to phenylephrine, and 3) a higher incidence of response to UK. In lesioned animals, the peak response to phenylephrine was significantly greater than to UK, and the mechanical threshold of phenylephrine-sensitive afferents was significantly lower than for phenylephrine-insensitive afferents. Staining with protein gene product 9.5 revealed an approximately 55% reduction in the number of unmyelinated terminals in the epidermis of the lesioned limb compared with the contralateral limb. Thus uninjured cutaneous C-fiber nociceptors that innervate skin partially denervated by ligation of a spinal nerve acquire two abnormal properties: spontaneous activity and alpha-adrenergic sensitivity. These abnormalities in nociceptor function may contribute to neuropathic pain.
Assuntos
Agonistas alfa-Adrenérgicos/farmacologia , Fibras Nervosas/fisiologia , Nociceptores/fisiologia , Nervos Espinhais/fisiologia , Animais , Tartarato de Brimonidina , Relação Dose-Resposta a Droga , Epiderme/inervação , Pé/inervação , Pé/fisiologia , Técnicas In Vitro , Ligadura , Região Lombossacral , Macaca fascicularis , Fibras Nervosas/efeitos dos fármacos , Nociceptores/efeitos dos fármacos , Nervo Fibular/efeitos dos fármacos , Nervo Fibular/fisiologia , Fenilefrina/farmacologia , Quinoxalinas/farmacologia , Limiar Sensorial/efeitos dos fármacosRESUMO
Denervation of skin has a profound influence on epidermis; epidermal thinning was a consistent finding in rats. However, it is not clear whether the degree of epidermal thinning was similar in the region receiving the same innervation. In mice, how early epidermal nerves were degenerated after nerve injury remained unknown. To address these issues, we transected the sciatic nerve in mice and compared the changes of epidermal thickness in different areas of the hind foot skin. Epidermal nerves degenerated within 48 h after nerve transection, similar to what was observed in rats. Seven days after nerve transection, there was differential thinning of epidermis. The interpad area, in the center of the sciatic nerve-innervated region, exhibited the most profound degree of epidermal thinning (34.6 +/- 3.1 vs 47.8 +/- 2.4 microns, P < 0.01). The heel area, in the periphery of the sciatic nerve-innervated zone, did not show significant thinning of epidermis after denervation (37.3 +/- 4.8 vs 41.5 +/- 5.1 microns, P > 0.05). The degree of epidermal thinning after denervation in the pad area was the intermediate one: with 98.8 +/- 4.8 vs 120.1 +/- 7.3 microns, P < 0.02, in the rete pegs, and 51.1 +/- 4.1 vs 62.1 +/- 6.0 microns, P < 0.02, in the dermal papilla. The differential thinning was obvious when the thickness of the denervated epidermis was normalized to that of the control epidermis with the ratios of 0.73 +/- 0.03 in the interpad area, 0.83 +/- 0.04 in the rete peg, 0.85 +/- 0.05 in the dermal papilla, and 0.92 +/- 0.05 in the heel. Epidermal thinning was reversed by reinnervation of the epidermis after sciatic nerve crush (41.5 +/- 1.5 vs 45.0 +/- 2.0 microns in the interpad area, P > 0.05). These findings suggest that sensory nerves exhibit trophic influences on the epidermis presumably through the effects of diffusible factors.
Assuntos
Epiderme/anatomia & histologia , Pele/inervação , Animais , Peptídeo Relacionado com Gene de Calcitonina/análise , Denervação , Epiderme/química , Epiderme/fisiologia , Pé/anatomia & histologia , Pé/inervação , Pé/fisiologia , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos ICR , Compressão Nervosa , Regeneração Nervosa , Proteínas do Tecido Nervoso/análise , Pele/anatomia & histologia , Pele/química , Fenômenos Fisiológicos da Pele , Tioléster Hidrolases/análise , Fatores de Tempo , Ubiquitina TiolesteraseRESUMO
Denervation in man often results in shiny, dry, thin skin. A previous study has shown that the epidermis of glabrous skin in the rat becomes approximately 40% thinner within 1 week following sciatic nerve transection, but which nerve fiber type or types influence epidermal thickness is unknown. In this study, we compared the effects on the epidermis of selective sensory, motor, and sympathetic denervation. Protein gene product 9.5 and calcitonin gene-related peptide immunocytochemical staining were used to determine the extent of denervation of epidermis, dermis, and sweat glands in the footpads. Epidermal thickness of the glabrous plantar skin of the foot was measured. To verify the specificity and reliability of each animal model, the relevant regions of the peripheral nervous system were examined by light or electron microscopy or both. Epidermal thickness decreased significantly following sciatic nerve transection (58% of control, P < 0.05) and dorsal root ganglionectomy (59%; P < 0.05). The thickness also decreased following lumbar ventral rhizotomy (61%; P < 0.01), destruction of lumbar spinal motor neurons (66%; P < 0.05), and botulinum toxin-induced paralysis of the tibialis anterior and gastrocnemius muscles (70%; P < 0.05). A slight decrease followed dorsal rhizotomy (84%; P < 0.01). In contrast, no significant alterations in epidermal thickness were detected following sham operation and sympathectomy. Epidermal thinning was paralleled by reductions in the amounts of transcripts for glyceraldehyde-3-phosphate dehydrogenase and beta-actin. These results suggest that selective loss of both sensory and motor fibers to the hind limb can contribute to reducing epidermal thickness in rat foot glabrous skin.
Assuntos
Denervação , Epiderme/patologia , Hipestesia/fisiopatologia , Paralisia/fisiopatologia , Actinas/biossíntese , Actinas/genética , Animais , Toxinas Botulínicas/toxicidade , Denervação/métodos , Epiderme/inervação , Epiderme/metabolismo , Gânglios Espinais/cirurgia , Ganglionectomia , Regulação da Expressão Gênica , Gliceraldeído-3-Fosfato Desidrogenases/biossíntese , Gliceraldeído-3-Fosfato Desidrogenases/genética , Peróxido de Hidrogênio/toxicidade , Hipertrofia , Hipestesia/etiologia , Queratinócitos/patologia , Laminectomia , Masculino , Neurônios Motores/fisiologia , Denervação Muscular , Músculo Esquelético/inervação , Neurônios Aferentes/fisiologia , Paralisia/induzido quimicamente , Paralisia/etiologia , Fragmentos de Peptídeos/biossíntese , Fragmentos de Peptídeos/genética , Reação em Cadeia da Polimerase , Ratos , Ratos Sprague-Dawley , Rizotomia , Nervo Isquiático/lesões , Traumatismos da Medula Espinal/induzido quimicamente , SimpatectomiaRESUMO
Microglia in different layers of the rat olfactory bulb expressed a variety of membrane antigens except for CD4 (OX-35). Bulb microglial cells bearing complement receptor type 3 (OX-42) were ubiquitous and their immunoreactivity varied considerably in different bulb layers. Although very few in number, labeled microglia in all layers also expressed major histocompatibility complex class I antigen (OX-18), leukocyte common antigen (OX-1) and unknown macrophage antigen (ED-2). The latter was localized in cells distributed almost exclusively in the perivascular spaces. The immunoreactivity of ED-1, an unknown cytoplasmic or lysosomal membrane antigen in macrophages, was localized in labeled microglia which were concentrated mainly in the granule cell layer and periglomerular zone of the bulb. A variable number of microglial cells were stained with OX-6 (major histocompatibility complex class II antigen) and they were located predominantly in the periglomerular zone and at the junction between the granule cell layer and the subependymal layer. Ultrastructural study using GSA I-B4 lectin labeling showed that microglia in different layers of the bulb exhibited similar labeling patterns in their subcellular structures. A remarkable feature was the occurrence of some microglia in the olfactory nerve layer, subependymal layer and granule cell layer adjacent to the subependymal layer in which the cells showed intense lectin labeling at their Golgi apparatus, a feature which was absent in microglia of other bulb layers. Present results showed the regional differences in microglial antigen expressions and lectin labeling within the olfactory bulb. It is therefore suggested that the cells subserve very different specific functions depending on their ambient microenvironments. The heterogeneity of microglial functions in the olfactory bulb may be related to the progressive regeneration and degeneration of its containing neurons.
Assuntos
Antígenos/biossíntese , Lectinas , Microglia/imunologia , Bulbo Olfatório/imunologia , Animais , Antígenos CD4/biossíntese , Antígenos de Histocompatibilidade Classe I/biossíntese , Antígenos de Histocompatibilidade Classe II/biossíntese , Histocitoquímica , Antígenos Comuns de Leucócito/biossíntese , Macrófagos/imunologia , Masculino , Microglia/química , Bulbo Olfatório/química , Bulbo Olfatório/citologia , Ratos , Ratos Wistar , Receptores de Complemento/imunologiaAssuntos
Quimiocinas/análise , Doenças do Sistema Nervoso/imunologia , Sistema Nervoso/imunologia , Receptores de Quimiocinas/análise , Animais , Northern Blotting , Quimiocinas/genética , Quimiocinas/imunologia , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/imunologia , Imunofluorescência , Regulação da Expressão Gênica , Imuno-Histoquímica , Hibridização In Situ , Magnésio/farmacologia , Doenças do Sistema Nervoso/metabolismo , Reação em Cadeia da Polimerase , RNA Mensageiro/análise , Receptores de Quimiocinas/imunologia , Ribonucleases/metabolismo , RoedoresRESUMO
A case of malignant chondroid syringoma on a foot with multiple bone metastases is presented. An 18-year-old male patient first noticed a protruding mass on the plantar surface of his right foot at 9 years of age. A sweat gland tumor of a benign nature was diagnosed and excised at that time. The tumor recurred three times during the 10 years after surgery and was finally diagnosed as malignant chondroid syringoma. Multiple bone metastases involving the calcaneus, talus and fibula of the lesion side were found after extensive radiologic survey. The patient underwent below-knee amputation with total removal of the fibula. However, pelvic bone metastasis developed 1 year after the amputation. He died of this disease due to brain and diffuse bony metastasis 36 months after the amputation. This is a rare case of malignant chondroid syringoma with a long history but ominous outcome. We recommend that sweat gland tumors be carefully examined and treated more radically when there is a suspicion of malignancy.
Assuntos
Adenoma Pleomorfo/patologia , Neoplasias das Glândulas Sudoríparas/patologia , Adenoma Pleomorfo/cirurgia , Adolescente , Humanos , Masculino , Neoplasias das Glândulas Sudoríparas/cirurgiaRESUMO
A patient with Marfan syndrome with ascending aortic aneurysm, aortic regurgitation and pectus excavatum was treated with simultaneous Bentall's procedure and sternal turnover. Partial sternal necrosis and mediastinitis developed 12 days after surgery. After debridement of about one-third of turnovered sterno-costal complex (SC), successful salvage of the remaining two-thirds of SC and sterilization of the infected aortic Dacron graft were accomplished with pedicled omental flap. The 7 previously published cases of simultaneous Bentall's procedure and sternal turnover are reviewed.