RESUMO
1. The E3 ubiquitin protein ligase 1 (WWP1) gene, the mutation of which causes muscular dystrophy in chickens, is expressed not only in the pectoral muscle, but also in a number of tissues such as the kidney. Therefore, this study examined some parameters related to kidney function in muscular dystrophic (MD) chickens. 2. Plasma osmolality, Na+ and K+ concentrations, aldosterone levels, and the expression of aquaporin (AQP) 2, AQP3, and α subunits of the amiloride-sensitive epithelial sodium channel (αENaC) were analysed in the kidneys of 5-week-old MD chickens and White Leghorn (WL) chickens under physiological conditions or after one day of water deprivation. 3. Plasma osmolality, Na+ concentrations, and plasma aldosterone levels were significantly higher in MD chickens than in WL chickens. αENaC mRNA expression levels were lower in MD chickens than in WL chickens. AQP2 and AQP3 mRNA expression levels were similar in the two strains of chickens. 4. Plasma osmolality correlated with aldosterone levels and AQP2 and αENaC mRNA levels in WL chickens. In MD chickens, plasma osmolality correlated with AQP2 mRNA levels, but not with plasma aldosterone or αENaC mRNA levels. 5. These results suggest that neither water reabsorption nor the expression of AQP2 and AQP3 is impaired in MD chickens and that a WWP1 gene mutation may or may not directly induce an abnormality in Na+-reabsorption in the kidneys of MD chickens, potentially through αENaC.
Assuntos
Galinhas , Expressão Gênica , Hipernatremia/veterinária , Distrofia Muscular Animal/fisiopatologia , Concentração Osmolar , Doenças das Aves Domésticas/fisiopatologia , Animais , Proteínas Aviárias/genética , Proteínas Aviárias/metabolismo , Eletrólitos/sangue , Hipernatremia/genética , Hipernatremia/metabolismo , Hipernatremia/fisiopatologia , Rim/metabolismo , Masculino , Distrofia Muscular Animal/genética , Distrofia Muscular Animal/metabolismo , Potássio/sangue , Doenças das Aves Domésticas/genética , Doenças das Aves Domésticas/metabolismo , Sódio/sangueRESUMO
BACKGROUND: Insulinoma is a tumour of insulin-producing cells of the pancreas and is known to be one of the causes of hypoglycaemia. Usually, appropriate removal of the insulinoma results in normalization of blood glucose levels. However, we found novel cases of insulinoma, in which hyperglycaemia developed soon after resection of the insulinoma. CASE REPORT: We encountered two patients with repeated hypoglycaemia caused by insulinoma. Following removal of the insulinoma, unanticipated hyperglycaemia was observed in both patients. Thereafter, their blood tests revealed low levels of serum C-peptide and high titres of anti-glutamic acid decarboxylase antibody, indicating concomitant Type 1 diabetes. Indeed, histological examination of the resected specimen revealed that one patient showed insulitis in non-tumorous pancreatic tissue in which ß-cells had already disappeared. Moreover, inflammatory cells infiltrated the insulinoma, as if it were insulitis of Type 1 diabetes, suggesting the existence of anti-islet autoimmunity. CONCLUSION: These are first cases of insulinoma associated with underlying Type 1 diabetes. Physicians should be aware of the possibility that insulinoma may mask Type 1 diabetes, and measurement of anti-islet autoantibodies may be helpful to find underlying Type 1 diabetes, such as in these cases. It is pathologically interesting that the immune cell infiltration into insulinoma may be suggestive of anti-islet autoimmunity.
Assuntos
Autoanticorpos/sangue , Diabetes Mellitus Tipo 1/diagnóstico , Hiperglicemia/diagnóstico , Insulinoma/diagnóstico , Ilhotas Pancreáticas/imunologia , Neoplasias Pancreáticas/diagnóstico , Adulto , Idoso , Peptídeo C/sangue , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/imunologia , Diagnóstico Diferencial , Feminino , Humanos , Hiperglicemia/sangue , Hiperglicemia/imunologia , Insulinoma/sangue , Insulinoma/imunologia , Masculino , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/imunologiaRESUMO
AIMS: The long-term efficacy of epalrestat, an aldose reductase inhibitor, in improving subjective symptoms and nerve function was comprehensively assessed to identify patients with diabetic peripheral neuropathy who responded to epalrestat treatment. METHODS: Stratified analyses were conducted on data from patients in the Aldose Reductase Inhibitor-Diabetes Complications Trial (ADCT). The ADCT included patients with diabetic peripheral neuropathy, median motor nerve conduction velocity > or = 40 m/s and with glycated haemoglobin (HbA(1c)) < or = 9.0%. Longitudinal data on HbA(1c) and subjective symptoms of the patients for 3 years were analysed (epalrestat n = 231, control subjects n = 273). Stratified analyses based on background variables (glycaemic control, grades of retinopathy or proteinuria) were performed to examine the relationship between subjective symptoms and nerve function. Multiple logistic regression analyses were conducted. RESULTS: Stratified subgroup analyses revealed significantly better efficacy of epalrestat in patients with good glycaemic control and less severe diabetic complications. In the control group, no improvement in nerve function was seen regardless of whether symptomatic benefit was obtained. In the epalrestat group, nerve function deteriorated less or improved in patients whose symptoms improved. The odds ratio of the efficacy of epalrestat vs. control subjects was approximately 2 : 1 (4 : 1 in patients with HbA(1c) < or = 7.0%). CONCLUSION: Our results suggest that epalrestat, an aldose reductase inhibitor, will provide a clinically significant means of preventing and treating diabetic neuropathy if used in appropriate patients.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Neuropatias Diabéticas/tratamento farmacológico , Inibidores Enzimáticos/administração & dosagem , Rodanina/análogos & derivados , Tiazolidinas/administração & dosagem , Administração Oral , Idoso , Retinopatia Diabética/tratamento farmacológico , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Assistência de Longa Duração , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Proteinúria/etiologia , Rodanina/administração & dosagem , Resultado do TratamentoRESUMO
Our previous study demonstrated that elongated spermatids and sperm carrying the female-specific W-chromosome of the sex-reversed domestic fowl can activate the mouse oocyte, but whether they can fertilize the avian oocyte and lead to a developing zygote remains undetermined. A single sperm isolated from the semen and testis of normal rooster and from a testis of sex-reversed hen was microinjected into a quail oocyte and cultured for 20 to 24 h. Blastoderms were fixed, cleaved, nuclei stained by 4',6'-diamidino-2-phenylin-dole, and developmental stages were assessed. In the normal rooster group, ejaculated and testicular sperm induced blastodermal development in 22.6 and 20% of the quail oocytes, respectively. The developmental stages ranged from IV to VII. In the sex-reversal group, 20% of injected testicular sperm induced blastodermal development. The blastodermal stages varied from stage III to VI. Blastoderms after 4',6'-diamidino-2-phenylindole staining were assayed by PCR to identify the W chromosome of either chicken sperm or quail oocyte. The PCR assay results showed that 2 out of 9 developed blastoderms microinjected with sperm of sex-reversed hen were identified containing the female-specific W chromosome derived from sex-reversed hen. From these results, it is concluded that chicken sperm bearing the W chromosome possess fertilizing ability and can function to stimulate blastoderm development similar to that of normal chicken sperm carrying the Z chromosome.
Assuntos
Blastoderma/fisiologia , Galinhas , Oócitos/fisiologia , Codorniz/fisiologia , Cromossomos Sexuais/fisiologia , Injeções de Esperma Intracitoplásmicas/veterinária , Espermatozoides/fisiologia , Animais , Embrião não Mamífero , Feminino , Fertilização , Masculino , Codorniz/embriologia , Cromossomos Sexuais/genéticaRESUMO
OBJECTIVES: We studied the association of diabetes transmission with left ventricular hypertrophy (LVH) in patients with non-insulin-dependent diabetes mellitus (NIDDM). BACKGROUND: It is suggested that NIDDM has a strong genetic basis and that maternally transmitted NIDDM is associated with mitochondrial deoxyribonucleic acid (DNA) mutations. However, genetic factors for LVH in NIDDM are unknown. METHODS: We investigated the family history of diabetes and the prevalence of LVH using electrocardiography in 834 patients with NIDDM, of whom 199 also underwent echocardiography. RESULTS: Of the 834 patients, 121 had diabetic mothers, 122 had diabetic fathers and 30 had both. The LVH criterion of S(v1) + R(V5) or R(v6) >35 mm was met in 148 patients. The percentage of patients having diabetic mothers was higher in those with LVH criterion (29%) than without it (16%) (p < 0.001), but the percentage of patients having diabetic fathers was similar in those with LVH (18%) and without it (18%). Compared with the 683 patients with nondiabetic mothers, the 151 patients with diabetic mothers were younger and had earlier onset of diabetes. The percentage of patients having diabetic siblings was also higher in those with diabetic mothers (31%) than in those with nondiabetic mothers (18%) (p < 0.001). On electrocardiograms, the prevalence of LVH was higher in patients with diabetic mothers (28%) than in those with nondiabetic mothers (15%) (p < 0.001). Echocardiograms showed that patients with diabetic mothers had greater left ventricular wall thickness and mass than those with nondiabetic mothers. In multivariate analysis, the family history of diabetes in mothers was an independent factor to LVH, but the family history of diabetes in fathers was not. CONCLUSIONS: Maternal transmission of diabetes was associated with LVH in patients with NIDDM. Some genetic factors of diabetes, such as mitochondrial DNA abnormalities, may contribute to the development of LVH in maternally transmitted NIDDM.
Assuntos
Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Hipertrofia Ventricular Esquerda/genética , Adulto , Idoso , DNA Mitocondrial/genética , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Ecocardiografia , Eletrocardiografia , Feminino , Seguimentos , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Humanos , Hipertrofia Ventricular Esquerda/complicações , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Pessoa de Meia-Idade , Mutação , Contração Miocárdica , Núcleo Familiar , Prognóstico , Estudos RetrospectivosRESUMO
OBJECTIVE: To investigate the role of glycemic control and blood pressure in the development and progression of nephropathy and to suggest goals for glycemic control and blood pressure for the prevention of nephropathy in elderly Japanese NIDDM patients. RESEARCH DESIGN AND METHODS: A total of 123 age- and diabetes duration-matched elderly Japanese NIDDM patients (aged 60-75 years; 74 normoalbuminuric and 49 microalbuminuric) were retrospectively studied for 6 years. RESULTS: The group that developed microalbuminuria from normoalbuminuria (group NM: n = 24) showed a higher 6-year mean HbA1c than the group that remained normoalbuminuric (group NN: n = 50; 9.0 +/- 0.8 vs. 8.1 +/- 0.8%, P < 0.01) in spite of no significant difference in 6-year mean blood pressure (MBP). On the other hand, the group that progressed from microalbuminuria to overt proteinuria (group MP: n = 26) showed a higher 6-year MBP than the group that remained microalbuminuric (group MM: n = 23; 106 +/- 5 vs. 95 +/- 6 mmHg, P < 0.01) in spite of no significant difference in 6-year mean HbA1c. The cutoff level of HbA1c separating group NN from group NM was 8.5% (normal range < or = 6.5%), and that of MBP separating group MM from group MP was 100 mmHg. CONCLUSIONS: Glycemic control is a more potent factor than blood pressure level on the development of microalbuminuria. However, as far as the progression of microalbuminuria to overt proteinuria is concerned, hypertension is the most crucial factor in elderly NIDDM patients. Suggested goals for glycemic control and blood pressure level for the prevention of nephropathy in elderly Japanese patients are an HbA1c of < or = 8.5% (equivalent to 7.8% in the current measurement of stable HbA1c; normal range < or = 5.8%) and an MBP of < or = 100 mmHg.
Assuntos
Glicemia/análise , Pressão Sanguínea , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/fisiopatologia , Idoso , Albuminúria , Anti-Hipertensivos/uso terapêutico , Transtornos Cerebrovasculares/epidemiologia , Diabetes Mellitus Tipo 2/sangue , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/epidemiologia , Retinopatia Diabética/epidemiologia , Progressão da Doença , Feminino , Hemoglobinas Glicadas/análise , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Japão , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/epidemiologia , Valor Preditivo dos Testes , Prognóstico , Proteinúria , Fatores de Risco , Fatores de TempoRESUMO
OBJECTIVE: To examine the usefulness of the revised criterion for fasting plasma glucose (FPG) in the diagnosis of diabetes recommended by the American Diabetic Association (ADA) (126 mg/dl, 7 mmol/l), and to characterize insulin response during the 75-g oral glucose tolerance test (OGTT) in newly diagnosed Japanese diabetic subjects. RESEARCH DESIGN AND METHODS: A series of 2,121 Japanese subjects underwent a 75-g OGTT (0-3 h) and were divided into three groups (normal glucose tolerance [NGT], impaired glucose tolerance [IGT], and diabetes mellitus [DM] according to the current World Health Organization criteria. After the cutoff values of FPG that distinguish NGT and IGT from diabetes were analyzed, the usefulness of the ADA criterion for FPG was examined by comparing diagnostic parameters (sensitivity, specificity, and accuracy) with those for the cutoff value of 140 mg/dl. To assess insulin response, both the insulinogenic index (IsIx), a marker of early secretion, and the area under the insulin response curve (AUCins), a marker of total secretion, were compared between the DM, NGT, and IGT groups. RESULTS: First, the FPG cutoff value distinguishing NGT from diabetes was 109 mg/dl. An FPG of 126 mg/dl showed a higher sensitivity (0.52 vs. 0.31), the same specificity (1.00), and a higher accuracy (0.82 vs. 0.74) than an FPG of 140 mg/dl, and it had a higher specificity (1.00 vs. 0.86) with a slightly lower accuracy (0.82 vs. 0.85) than an FPG of 109 mg/dl. Second, the FPG cutoff value differentiating IGT from diabetes was 113 mg/dl. An FPG of 126 mg/dl showed a higher sensitivity (0.52 vs. 0.31) and accuracy (0.80 vs. 0.74) and a similar specificity (0.97 vs. 1.00) compared with an FPG of 140 mg/dl, and it had a higher specificity (0.97 vs. 0.82) with the same accuracy (0.80) as an FPG of 113 mg/dl. Third, the DM group showed the lowest IsIx among the three groups at all FPG values. The AUCIns in the DM group increased along with FPG, reached the maximum level at an FPG of 110 mg/dl, and declined thereafter. AUCIns was higher in the DM group than in the NGT group at FPG values > or = 100 mg/dl. CONCLUSIONS: The revised ADA criterion for FPG of 126 mg/dl may improve diagnostic sensitivity without loss of specificity in Japanese diabetic subjects when compared with an FPG criterion of 140 mg/dl. Although early insulin secretion was impaired, total insulin secretion did not seem to be reduced in newly diagnosed Japanese diabetic subjects.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus/sangue , Insulina/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Jejum , Feminino , Glucose/administração & dosagem , Glucose/metabolismo , Teste de Tolerância a Glucose , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
CASE HISTORY: We recently encountered a 65-year-old anti-GAD+ diabetic woman with residual beta-cell function who was proved to have T-cell insulitis. The proportion of CD4+ and CD8+ cells varied among individual islets, although CD4+ cells tended to be the predominant T-cell type in the islets examined. All of the islets examined still contained insulin, suggesting that beta-cell mass may have been preserved. DISCUSSION: It is well known that lymphocytic infiltration of pancreatic islets, a condition referred to as "insulitis," is seen in acute-onset type 1 diabetes at autopsy and in biopsy specimens. However, there have been no proven cases of insulitis in type 1 diabetes with residual beta-cell function. We believe that this is the first type 1 diabetic patient with residual beta-cell function who was proven to have T-cell insulitis. This novel evidence will contribute to the proper classification and treatment of diabetes and to a better understanding of the pathophysiology of type 1 diabetes.
Assuntos
Autoanticorpos/análise , Diabetes Mellitus Tipo 1/imunologia , Glutamato Descarboxilase/imunologia , Ilhotas Pancreáticas/fisiologia , Linfócitos T/imunologia , Idoso , Relação CD4-CD8 , Diabetes Mellitus Tipo 1/patologia , Feminino , Hemoglobinas Glicadas/análise , Humanos , Ilhotas Pancreáticas/patologiaRESUMO
OBJECTIVE: To present a novel mitochondrial DNA mutation in a diabetic family RESEARCH DESIGN AND METHODS: The proband was a 64-year-old man. In the family, diabetes was maternally inherited. He had diabetes, cerebellar ataxia, cervical lipoma, hearing loss, olfactory dysfunction, ophthalmoplegia, and facial nerve bilateral palsy. On examination, early insulin secretion was blunted, and the M value on glucose clamp test was low. In muscle, ragged red fibers were not found. T-to-C mutation at position 3264 was detected in the proband (0.5% mutant DNAs in leukocyte and 30% in muscle), but was not detected in 201 normal individuals. RESULTS: Heteroplasmy of mutation, maternal inheritance of diabetes, and symptoms related to mitochondrial dysfunction suggest the pathogenecity of this 3264 mutation. As for diabetes etiology, both impaired insulin secretion and decreased insulin sensitivity seem to be important. In phenotypic characteristics, the combination of cerebellar ataxia and lipoma is a symptom sometimes found in myoclonic epilepsy and ragged red fibers (MERRFs). Ophthamoplegia is a symptom of chronic progressive external ophthalmoplegia (CPEO). These suggest that our proband had phenotypic overlap with MERRF and CPEO. Conversely, facial nerve bilateral palsy is a rare finding. The pictures that focused on his cranial nerves were thus unique, suggesting the heterogeneity of mitochondrial DNA (mtDNA)-related diabetes. CONCLUSIONS: A novel 3264 mitochondrial DNA mutation in diabetes gives new insight to the etiology of mitochondrial diabetes. Its pathogenecity supports the belief that the tRNA(Leu)(UUR) gene is an etiological hot spot of mitochondrial diseases.
Assuntos
DNA Mitocondrial/genética , Diabetes Mellitus Tipo 2/genética , Mutação Puntual/genética , RNA de Transferência de Leucina/genética , DNA Mitocondrial/análise , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Humanos , Leucócitos/química , Masculino , Pessoa de Meia-Idade , Músculos/química , Linhagem , Reação em Cadeia da PolimeraseRESUMO
OBJECTIVE: To investigate the basis of central nervous system dysfunction in diabetes associated with the 3243 mitochondrial tRNA mutation, we studied neuroimaging findings in patients with this disease. RESEARCH DESIGN AND METHODS: We screened 205 diabetic patients. Those patients who had the 3243 mutation in leukocytes or muscle were enrolled. All the subjects underwent computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), and N-isopropyl-p-[123I]iodoamphetamine ([123I]IMP) single-photon emission computed tomography (SPECT) of the brain. RESULTS: None of the nine subjects with the 3243 mutation had the typical clinical picture of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes, and none had neurological focal signs. CT or MRI revealed diffuse brain atrophy in three patients (33%) and cerebellar atrophy in one (11%). Abnormal high intensity areas were observed on MRI in five patients (56%). The overall prevalence of brain abnormalities was 56% (5 of 9) on CT and 78% (7 of 9) on MRI scans. MRA revealed no stenotic lesions. SPECT showed reduced accumulation of [123I]IMP in the right or left parieto-occipital region in eight patients (89%). CONCLUSIONS: Reduced accumulation of [123I]IMP in the parieto-occipital cortex was found in a high proportion of our subjects on SPECT. This imaging finding might be characteristic of diabetes associated with the 3243 mitochondrial tRNA mutation and may be a sign of latent central nervous system dysfunction.
Assuntos
Doenças do Sistema Nervoso Central/genética , DNA Mitocondrial/genética , Diabetes Mellitus/genética , Neuropatias Diabéticas/genética , Mutação Puntual , RNA de Transferência de Leucina/genética , Adulto , Idoso , Encéfalo/patologia , Doenças do Sistema Nervoso Central/fisiopatologia , Diabetes Mellitus/fisiopatologia , Neuropatias Diabéticas/fisiopatologia , Feminino , Humanos , Leucócitos/metabolismo , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Músculos/metabolismo , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
OBJECTIVE: To ascertain why alcohol is prone to manifest unpleasant effects in diabetes associated with mitochondrial tRNA(Leu(UUR) mutation at position 3243 (DM-Mt3243), we investigated the genotype of aldehyde dehydrogenase (ALDH) 2 and alcohol dehydrogenase 2 (ADH2) in DM-Mt3243. RESEARCH DESIGN AND METHODS: Nineteen unrelated patients with DM-Mt3243 were included in the study (12 men and 7 women). They were recruited from approximately 700 diabetic patients at three different institutes, without prior information of alcohol habit. ALDH2, ADH2, and 3243 mutation were genotyped by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) methods. There were 461 unrelated Japanese individuals and 170 non-3243 mutant NIDDM patients enrolled as control subjects. RESULTS: In the DM-Mt3243 group, 15 (79%) patients had inactive ALDH2 and 18 (95%) had atypical ADH2. The frequency of the inactive ALDH2 genotype was higher than that in the normal control subjects (P < 0.002) and that in the NIDDM control subjects (P < 0.003). However, the frequencies of ADH2 genotype in the DM-Mt3243 group, the normal control subjects, and the NIDDM control subjects were not different. CONCLUSIONS: Inactive ALDH2 genotype was frequently observed in DM-Mt3243. It suggests that DM-Mt3243 is associated with ALDH2 inactivity. We speculate the trait of acetaldehyde accumulation on ALDH2 inactivity may favor mitochondrial DNA abnormalities, thereby worsening ATP production and impairing insulin secretion. In addition, the interaction of ALDH1 and ALDH2 may alter the retinoid metabolism in the pancreas, thereby influencing insulin secretion and precipitating diabetes. Thus, this association of ALDH2 genotype with DM-Mt3243 provides insight into the etiology of diabetes in the mitochondrial diseases.
Assuntos
Aldeído Desidrogenase/genética , Diabetes Mellitus/genética , Mitocôndrias/enzimologia , Mutação Puntual , RNA de Transferência de Leucina/genética , RNA/genética , Adulto , Idoso , Alelos , Diabetes Mellitus/enzimologia , Feminino , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mitocondrial , Valores de ReferênciaRESUMO
Diabetes mellitus associated with mitochondrial tRNA mutation at position 3243(DM-Mt3243) is a new disease. Patients have a distinctly different picture from MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). During observations at the Saiseikai Central Hospital, the following findings were noted in DM-Mt3243 patients: DM-Mt3243 patients are diagnosed earlier with diabetes, compared to NIDDM (non-insulin dependent diabetes mellitus) controls without family history. DM-Mt3243 patients often need insulin more often than NIDDM controls without family history. Post-treatment neuropathy and insulin edema are often found in DM-Mt3243, and the two phenomena possibly have a similar pathophysiology related to mitochondrial dysfunction. Ambiguous psychiatric disorders of functional psychosis are observed frequently in DM-Mt3243. Mild headache is common in DM-Mt3243 cases. Ambiguous neuromuscular abnormalities such as sleep disturbance, paresthesia of the legs, edema of the legs, and palpitation may be symptoms associated with mitochondrial dysfunction in DM-Mt3243. Coenzyme Q may be effective in the relief of these neuromuscular symptoms.
Assuntos
DNA Mitocondrial/genética , Diabetes Mellitus/genética , Encefalomiopatias Mitocondriais/genética , Mutação Puntual , RNA de Transferência de Leucina/genética , Ubiquinona/análogos & derivados , Adulto , Idoso , Ensaios Clínicos como Assunto , Coenzimas , Depressão/diagnóstico , Diabetes Mellitus/classificação , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/psicologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/genética , Diagnóstico Diferencial , Edema/etiologia , Feminino , Humanos , Insulina/efeitos adversos , Insulina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Encefalomiopatias Mitocondriais/tratamento farmacológico , Encefalomiopatias Mitocondriais/psicologia , Doenças do Sistema Nervoso Periférico/etiologia , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/etiologia , Ubiquinona/uso terapêuticoRESUMO
An automated analyzer for individual eye movements (EMs) has been developed that enables precise analyses of their incidence. Three new parameters for each EM are obtained: EM magnitude, the angle and speed of eyeball rotation, and the energy of each EM. All rapid eye movement (REM) sleep EMs from 40 nights of polysomnography for 20 healthy young men were analyzed. The mean frequency of eye movement (EM frequency) was 15.9 per minute. Compared to conventionally analyzed rapid eye movement (REM) density, EM frequency was more sensitive to differences among sleep cycles, nights, and individuals. The mean EM rotation was 6.27 +/- 0.021 degrees, the mean speed of rotation was 58.73 +/- 0.18 degrees/second, and mean energy was 525.85 +/- 3.82 degrees2/second. The distribution of changes in these new parameters differed from conventional measures across REM episodes. The conventional measures, REM episode duration, and REM density increased progressively in successive REM episodes in an ascent-to-right pattern. However, the new parameters peaked in the second, followed by relatively low values, producing an inverted V pattern. This discrepancy could indicate physiological mechanisms of EM that are not revealed in conventional measures of REM sleep intensity.
Assuntos
Polissonografia/métodos , Sono REM/fisiologia , Adulto , Humanos , MasculinoRESUMO
The aim of this study was to clarify whether amniotic fluid macrophage colony-stimulating factor (M-CSF) is related to placental development and fetal growth. Maternal serum and amniotic fluid M-CSF levels were analyzed in 22 pregnant women (seven intrauterine growth retardation (IUGR) complicated and 15 normal pregnancies) at 33-40 weeks' gestation. Amniotic fluid was obtained by transabdominal amniocentesis performed under ultrasonographic guidance. The mean amniotic fluid M-CSF level of the IUGR-complicated pregnancy group (5.0 +/- 1.4 ng/ml) was significantly lower (P < 0.05) than that of the normal pregnancy group (7.4 +/- 1.6 ng/ml). All the IUGR-complicated pregnant women subsequently delivered small-for-gestational-age (SGA) infants with significantly lower placental weights than those of the normal infants. There was no significant correlation between amniotic fluid M-CSF levels and gestational age in the normal pregnancy group. The same scattergram showed the amniotic fluid M-CSF levels of the IUGR-complicated pregnancy group tended to be lower than those of the normal pregnancy group at 33-40 weeks' gestation. The results suggested that amniotic fluid M-CSF was one of the regulators of human placental development and was related to fetal growth.
Assuntos
Retardo do Crescimento Fetal/etiologia , Fator Estimulador de Colônias de Macrófagos/análise , Adulto , Líquido Amniótico/química , Feminino , Humanos , Recém-Nascido , Fator Estimulador de Colônias de Macrófagos/sangue , GravidezRESUMO
A surgical case of teratoma with malignant transformation (TMT) of the mediastinum in a 66-year-old man is reported. The unilocular, cystic, mediastinal mass, which had been seen in a chest radiograph 7 years earlier, was extirpated. The mass was histologically revealed to be a mature cystic teratoma containing skin and respiratory epithelial tissues, with some areas of well-differentiated adenocarcinoma. Surgical cases of TMT in the mediastinum, which have not received any preoperative chemotherapy or radiation therapy, are rare. By reviewing the previous literature on TMT in various organs, the authors distinguished two types of TMT, chemotherapy- or radiotherapy-induced TMT and naturally occurring TMT. The pathogenesis of these two types are discussed.
Assuntos
Adenocarcinoma/patologia , Neoplasias do Mediastino/patologia , Neoplasias Primárias Múltiplas/patologia , Teratoma/patologia , Adenocarcinoma/diagnóstico por imagem , Humanos , Masculino , Neoplasias do Mediastino/diagnóstico por imagem , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Radiografia , Teratoma/diagnóstico por imagemRESUMO
To investigate the pathophysiology of diabetes mellitus associated with the 3243 mitochondrial tRNA(Leu)(UUR) mutation (DM-Mt3243), insulin secretion and sensitivity were studied using the 75-g oral glucose tolerance test (oGTT), 1-mg intravenous glucagon test, and euglycemic glucose clamp test. Twelve DM-Mt3243 patients were investigated (seven men and five women). Their ages ranged from 36 to 74 years, and the onset of diabetes occurred at 44.5 +/- 9.5 years (mean +/- SD). In the glucose tolerance test, nine patients (75.0%) showed lower C-peptide reactivity (CPR) than normal at 30 minutes, suggesting blunted insulin secretion. Three patients showed an impaired glucose tolerance (IGT) pattern, although they had absolute hyperglycemia at the onset of diabetes. In the glucagon test, 10 patients (76.3%) had CPR within the normal range at 6 minutes, indicating an adequate response. In the glucose clamp test, the M value was 8.70 +/- 2.35 mg/kg/min and was within normal limits in all patients. The glucose metabolized (M value) was negatively correlated with 24-hour urinary C-peptide excretion (r = .696, P < .05). Thus, plasma CPR to glucose loading was blunted in many DM-Mt3243 patients, but CPR to glucagon was relatively well preserved. This difference in the intrinsic insulin response to the two stimuli may be characteristic of DM-Mt3243. Although M values were normal in all subjects, the correlation with 24-hour urinary C-peptide excretion suggests a relationship between insulin sensitivity and insulin secretion. These two mechanisms may cooperate to maintain homeostasis in this disease. Since three patients did not progress with aging, this mutation may not always cause gradual beta-cell destruction.
Assuntos
Diabetes Mellitus/genética , Insulina/metabolismo , Mitocôndrias/fisiologia , Mutação , RNA de Transferência de Leucina/genética , Adulto , Idoso , Proteína C-Reativa/análise , Diabetes Mellitus/diagnóstico , Feminino , Glucagon , Técnica Clamp de Glucose , Teste de Tolerância a Glucose , Humanos , Secreção de Insulina , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
The present study was carried out to examine the occurrence of heme oxygenase-2 (HO-2) in the periodontal ligament of the rat incisor. HO-2-like immunoreactive (-IR) structures showed dendritic profiles, resembling the Ruffini endings, in the alveolar half of the ligament of rat incisor. Neither thin nerve fibers nor perivascular nerve fibers displayed HO-2-like immunoreactivity (-LI). No non-neural elements exhibited HO-2-LI. Electron microscopy revealed that immunoreactions were diffusely observed in the axon terminals of the Ruffini endings, but neither terminal Schwann cells nor Schwann sheaths contained immunoreactions for HO-2. Both most neurons in the trigeminal ganglion and trigeminal mesencephalic nucleus showed HO-2-LI. The presence of HO-2 in the periodontal Ruffini endings and its absence in the periodontal thin nerve fibers suggest the involvement of carbon monoxide produced by HO-2 in mechanoreception in the periodontal ligament.
Assuntos
Axônios/enzimologia , Dendritos/enzimologia , Heme Oxigenase (Desciclizante)/análise , Terminações Nervosas/enzimologia , Periodonto/inervação , Animais , Axônios/ultraestrutura , Dendritos/ultraestrutura , Imuno-Histoquímica , Incisivo , Masculino , Terminações Nervosas/ultraestrutura , Fibras Nervosas/ultraestrutura , Neurônios/enzimologia , Ratos , Ratos Sprague-Dawley , Células de Schwann/citologia , Gânglio Trigeminal/enzimologia , Núcleos do Trigêmeo/enzimologiaRESUMO
The present study was undertaken to reveal whether S-100alpha or S-100beta or both are present in the nerve fibers in the rat molar tooth pulp. No immunoreactivity for S-100alpha was observed in the molar pulp. In the root pulp, thick smooth-surfaced structures accompanying the blood vessel showed S-100beta-like immunoreactivity (-LI), and occasionally a very few thin beaded elements exhibited S-100beta-LI. In the coronal pulp, S-100beta-like immunoreactive (-IR) structures arborized repeatedly and extensively; they had a predominantly thick, smooth-surfaced appearance, though parts appeared thin and beaded. Numerous thin varicose S-100beta-IR structures ran through the odontoblast cell layer, and further penetrated into the predentin alongside the dentinal tubules. They could be traced for approximately 10-20 micrometers into the predentin from the pulp-predentin border. Immunoelectron microscopy revealed that the Schwann cells in the root pulp showed S-100beta-LI, and that S-100beta-LI was present in the axoplasm as well as Schwann cells in the coronal pulp. The S-100beta-IR axons were rarely surrounded by S-100beta-IR Schwann cells. In the predentin, S-100beta-IR nerve fibers terminated in a position close to the odontoblast processes. The present findings indicate that S-100beta, not S-100alpha, is present in the axon in the dental pulp and predentin as well as in the Schwann cells.
Assuntos
Proteínas de Ligação ao Cálcio/análise , Polpa Dentária/química , Dente Molar/química , Fatores de Crescimento Neural/análise , Proteínas S100 , Animais , Imuno-Histoquímica , Masculino , Microscopia Imunoeletrônica , Ratos , Ratos Sprague-Dawley , Subunidade beta da Proteína Ligante de Cálcio S100RESUMO
Our previous study showed that the migration of terminal Schwann cells occurred in the periodontal ligament of the rat lower incisor following transection of the inferior alveolar nerve (IAN) in the adult animals [Y. Atsumi, K. Matsumoto, M. Sakuda, T. Maeda, K. Kurisu, S. Wakisaka, Altered distribution of Schwann cells in the periodontal ligament of the rat incisor following resection of the inferior alveolar nerve: An immunohistochemical study on S-100 proteins, Brain Res. 849 (1999) 187-195]. The aim of the present study was to investigate the effects of neonatal transection of the IAN on the regeneration of axon elements and Schwann cells in the periodontal ligament of the rat lower incisor. Following transection of IAN at post-natal day 5 (PN 5d), when the numbers of both axon elements and the terminal Schwann cells were very small, regenerating nerve fibers appeared between post-injured days 7 (PO 7d) and PO 14d, and increased in number thereafter gradually. Although the terminal morphologies of regenerated Ruffini endings became identical to those of the adult animals by PO 54d, the number of regenerated PGP 9.5-IR nerve fibers did not recover the adult levels even by PO 56d. A small number of Schwann cells migrated into the shear zone, the border between the alveolus-related part (ARP) and the tooth-related part (TRP), but did not enter into the TRP. Following transection of the IAN at PN 14d or PN 28d, when clusters of apparent terminal Schwann cells could be recognized, axon regeneration started around PO 5d. Individual axon terminals of the regenerating Ruffini endings ramified and became identical to those of the adult animals around PO 28d, but the number of regenerated Ruffini endings was smaller than that of the adult animals. Similar to the adult animals, the migration of Schwann cells into the shear zone and TRP occurred, and disappeared prior to the completion of the axonal regeneration. The present results indicate that the migration of the Schwann cells into TRP during the regeneration of the periodontal nerve fibers following nerve injury to the IAN depends on the maturation of the terminal Schwann cells of the periodontal Ruffini endings, not on post-operative time.
Assuntos
Incisivo/inervação , Mecanorreceptores/crescimento & desenvolvimento , Regeneração Nervosa/fisiologia , Ligamento Periodontal/inervação , Células de Schwann/metabolismo , Traumatismos do Nervo Trigêmeo , Fatores Etários , Animais , Animais Recém-Nascidos , Movimento Celular/fisiologia , Incisivo/citologia , Incisivo/crescimento & desenvolvimento , Masculino , Nervo Mandibular/citologia , Nervo Mandibular/crescimento & desenvolvimento , Mecanorreceptores/citologia , Mecanorreceptores/metabolismo , Ligamento Periodontal/citologia , Ligamento Periodontal/crescimento & desenvolvimento , Ratos , Ratos Sprague-Dawley , Proteínas S100/metabolismo , Células de Schwann/citologia , Tioléster Hidrolases/metabolismo , Ubiquitina TiolesteraseRESUMO
The present study employed immunohistochemistry for the detection of S-100 proteins to reveal the alteration in the distribution of Schwann cells in the periodontal ligament of the rat incisor following resection of the inferior alveolar nerve (IAN). In normal animals, S-100-immunostaining demonstrated the profiles of Ruffini endings, primary mechanoreceptors in the periodontal ligament, in the alveolus-related part of the ligament. Under the electron microscope, S-100-like immunoreactivity (-LI) was observed in the cytoplasm of the terminal Schwann cell elements and in some axon profiles of the Ruffini endings. During the regeneration, S-100-like immunoreactive (-IR) terminal Schwann cells in the alveolus-related part of the ligament gradually decreased in number. In contrast, S-100-LI was found in the spindle-shaped cells at the shear zone (the border between alveolus-related and tooth-related parts) and in the tooth-related part, where S-100-LI was rarely detected in normal animals. Immunoelectron microscopic observations revealed that some S-100-IR spindle-shaped cells contained fibrous long spacing (FLS) fibers, suggesting that they were Schwann cells. Some regenerating axons were observed at the shear zone, but were rarely found in the tooth-related part. With the progress of the regeneration of the periodontal Ruffini endings, S-100-IR terminal Schwann cells became rearranged in the alveolus-related part by 42-56 days post injury, whereas the S-100-IR spindle-shaped Schwann cells in the shear zone and tooth-related part disappeared when the regeneration was complete.