RESUMO
PURPOSE: Neurodegeneration of the nucleus ambiguus and the dorsal vagal motor nucleus has been implicated in cardiac parasympathetic dysfunction in multiple system atrophy (MSA). The nucleus ambiguus and the dorsal vagal motor nucleus, which are located in the medulla oblongata (MO), control the autonomic-specifically, the parasympathetic-functions of the body. The aim of our study was to investigate the relationship between cardiac parasympathetic dysfunction and the anteroposterior diameter of the MO in MSA by quantitatively analyzing magnetic resonance imaging (MRI) outcome measures. METHODS: We retrospectively assessed 40 consecutive patients with probable MSA and 25 age- and sex-matched controls. The anteroposterior diameter of the MO at two locations (MO diameter-A and -B) and the diameters of the midbrain and pons were measured by conventional MRI. A cardiac parasympathetic function score (CP-score) and cardiac sympathetic function score (CS-score) were generated by calculating the z-scores of multiple autonomic function tests. The relationship between the scores and the measured diameters of the brainstem was also investigated. RESULTS: The CP-score and CS-score were significantly lower in the patients with MSA than in the controls (CP-score: 0.61 ± 0.75 vs. - 0.38 ± 0.52, p < 0.001; CS-score: 0.91 ± 1.06 vs. - 0.57 ± 1.07, p < 0.001). Also, in the patients with MSA, the CP-score was significantly correlated with MO diameter-A (r = 0.40, p = 0.010), and the CS-score was significantly correlated with the diameter of the midbrain (r = 0.33, p = 0.038). CONCLUSION: The anteroposterior diameter of the MO is a potential imaging marker of parasympathetic dysfunction in MSA.
Assuntos
Cardiopatias , Atrofia de Múltiplos Sistemas , Sistema Nervoso Autônomo , Humanos , Bulbo/diagnóstico por imagem , Atrofia de Múltiplos Sistemas/diagnóstico por imagem , Estudos RetrospectivosRESUMO
Radish (Raphanus sativus L. var. sativus), a widely cultivated root vegetable crop, possesses a large sink organ (the root), implying that photosynthetic activity in radish can be enhanced by altering both the source and sink capacity of the plant. However, since radish is a self-incompatible plant, improved mutation-breeding strategies are needed for this crop. TILLING (Targeting Induced Local Lesions IN Genomes) is a powerful method used for reverse genetics. In this study, we developed a new TILLING strategy involving a two-step mutant selection process for mutagenized radish plants: the first selection is performed to identify a BC1M1 line, that is, progenies of M1 plants crossed with wild-type, and the second step is performed to identify BC1M1 individuals with mutations. We focused on Rubisco as a target, since Rubisco is the most abundant plant protein and a key photosynthetic enzyme. We found that the radish genome contains six RBCS genes and one pseudogene encoding small Rubisco subunits. We screened 955 EMS-induced BC1M1 lines using our newly developed TILLING strategy and obtained six mutant lines for the six RsRBCS genes, encoding proteins with four different types of amino acid substitutions. Finally, we selected a homozygous mutant and subjected it to physiological measurements.
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BACKGROUND AND AIMS: The rising atmospheric CO2 concentration ([CO2]) is a ubiquitous selective force that may strongly impact species distribution and vegetation functioning. Plant-plant interactions could mediate the trajectory of vegetation responses to elevated [CO2], because some plants may benefit more from [CO2] elevation than others. The relative contribution of plastic (within the plant's lifetime) and genotypic (over several generations) responses to elevated [CO2] on plant performance was investigated and how these patterns are modified by plant-plant interactions was analysed. METHODS: Plantago asiatica seeds originating from natural CO2 springs and from ambient [CO2] sites were grown in mono stands of each one of the two origins as well as mixtures of both origins. In total, 1944 plants were grown in [CO2]-controlled walk-in climate rooms, under a [CO2] of 270, 450 and 750 ppm. A model was used for upscaling from leaf to whole-plant photosynthesis and for quantifying the influence of plastic and genotypic responses. KEY RESULTS: It was shown that changes in canopy photosynthesis, specific leaf area (SLA) and stomatal conductance in response to changes in growth [CO2] were mainly determined by plastic and not by genotypic responses. We further found that plants originating from high [CO2] habitats performed better in terms of whole-plant photosynthesis, biomass and leaf area, than those from ambient [CO2] habitats at elevated [CO2] only when both genotypes competed. Similarly, plants from ambient [CO2] habitats performed better at low [CO2], also only when both genotypes competed. No difference in performance was found in mono stands. CONCLUSION: The results indicate that natural selection under increasing [CO2] will be mainly driven by competitive interactions. This supports the notion that plant-plant interactions have an important influence on future vegetation functioning and species distribution. Furthermore, plant performance was mainly driven by plastic and not by genotypic responses to changes in atmospheric [CO2].
Assuntos
Dióxido de Carbono/metabolismo , Plantago/fisiologia , Genótipo , Japão , Modelos Biológicos , Fotossíntese/fisiologia , Folhas de Planta/fisiologia , Plantago/genética , Plantago/crescimento & desenvolvimentoRESUMO
We previously reported that camostat mesilate (CM) had renoprotective and antihypertensive effects in rat CKD models. In this study, we examined if CM has a distinct renoprotective effect from telmisartan (TE), a renin-angiotensin-aldosterone system (RAS) inhibitor, on the progression of CKD. We evaluated the effect of CM (400 mg/kg/day) and/or TE (10 mg/kg/day) on renal function, oxidative stress, renal fibrosis, and RAS components in the adenine-induced rat CKD model following 5-weeks treatment period. The combination therapy with CM and TE significantly decreased the adenine-induced increase in serum creatinine levels compared with each monotherapy, although all treatment groups showed similar reduction in blood pressure. Similarly, adenine-induced elevation in oxidative stress markers and renal fibrosis markers were significantly reduced by the combination therapy relative to each monotherapy. Furthermore, the effect of the combination therapy on plasma renin activity (PRA) and plasma aldosterone concentration (PAC) was similar to that of TE monotherapy, and CM had no effect on both PRA and PAC, suggesting that CM has a distinct pharmacological property from RAS inhibition. Our findings indicate that CM could be a candidate drug for an add-on therapy for CKD patients who had been treated with RAS inhibitors.
Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Benzimidazóis/administração & dosagem , Benzoatos/administração & dosagem , Gabexato/análogos & derivados , Insuficiência Renal Crônica/tratamento farmacológico , Inibidores de Serina Proteinase/administração & dosagem , Aldosterona/sangue , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Animais , Anti-Hipertensivos/farmacologia , Benzimidazóis/farmacologia , Benzoatos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Creatinina/sangue , Modelos Animais de Doenças , Quimioterapia Combinada , Ésteres , Fibrose/tratamento farmacológico , Gabexato/administração & dosagem , Gabexato/farmacologia , Guanidinas , Rim/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Renina/sangue , Sistema Renina-Angiotensina/efeitos dos fármacos , Inibidores de Serina Proteinase/farmacologia , TelmisartanRESUMO
Talaromyces stipitatus ATCC 10500 possesses 17 non-reducing polyketide synthase (NR-PKS) genes. During the course of our functional analysis of PKS genes with a C-terminus methyltransferase domain from T. stipitatus, we expressed tspks2, tspks3 and tspks4 genes in the heterologous host Aspergillus oryzae, respectively. Although the tspks4 transformant gave no apparent product in HPLC analysis, a novel azaphilone pentaketide (3) was identified along with two known related products from the tspks2 transformant. Of four hexaketide products from the tspks3 transformant, two new compounds were identified to be 2-acetyl-7-methyl-3,6,8-trihydroxynaphthalene (4) and its derivative fused with α-methyl-α,ß-unsaturated γ-lactone (7).
Assuntos
Aspergillus oryzae/genética , Regulação Enzimológica da Expressão Gênica/genética , Metiltransferases/metabolismo , Policetídeo Sintases/metabolismo , Talaromyces/enzimologia , Benzopiranos/análise , Estrutura Molecular , Pigmentos Biológicos/análise , Policetídeo Sintases/genéticaRESUMO
The aim of this study was to assess the efficacy, safety, and concentration of meropenem in cerebrospinal fluid when meropenem (2 g every 8 h) was administered to Japanese adult patients with bacterial meningitis. Five Japanese patients (mean age 60.6 years [range 35-71]) were enrolled. Infection with Streptococcus pneumoniae (three patients), Streptococcus salivarius (one patient), and Staphylococcus aureus (one patient) was confirmed by cerebrospinal fluid culture. Meropenem (2 g every 8 h) was administered to all five patients. Treatment duration ranged from 14 to 28 days (mean 22.6 days). All the patients were successfully treated. The concentration of meropenem in cerebrospinal fluid ranged from 0.27 to 6.40 µg/ml up to 8.47 h and was over 1 µg/ml 3 h after starting meropenem infusion. In each patient, the present study confirmed for the first time that the concentration of meropenem in cerebrospinal fluid exceeded the minimal inhibitory concentration for these pathogens. Eleven clinical and laboratory adverse events considered to be related to meropenem were observed in all patients, but no serious adverse event and no discontinuance of treatment due to adverse events occurred. Thus meropenem appeared to be a well-tolerated and effective agent for Japanese adult patients with bacterial meningitis. 2 g every 8 h of meropenem was delivered to CSF and its concentration was exceed in MICs for the detected pathogens.
Assuntos
Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Meningites Bacterianas/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus/efeitos dos fármacos , Tienamicinas/efeitos adversos , Tienamicinas/uso terapêutico , Adulto , Idoso , Feminino , Humanos , Japão , Masculino , Meningites Bacterianas/líquido cefalorraquidiano , Meningites Bacterianas/microbiologia , Meropeném , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Infecções Estafilocócicas/líquido cefalorraquidiano , Infecções Estafilocócicas/microbiologia , Resultado do TratamentoRESUMO
We report a case of numb chin syndrome caused by a small cortical infarction in the postcentral gyrus. A 67-year-old man suddenly developed numbness in his right lower lip and the chin. There were no apparent abnormal neurological symptoms other than numbness. MRI revealed a fresh small infarction in the left postcentral gyrus, which corresponds with the somatosensory area of the lower lip and the chin drawn by Penfield and Rasmussen. MRA showed no significant stenosis in the main trunk of the cerebral arteries. A soft plaque with irregular wall was detected in the left carotid bifurcation on carotid ultrasonography. Based on these findings, we diagnosed him with arteriogenic cerebral embolism, and started antiplatelet therapy. A small infarction in the postcentral gyrus can cause numbness in the lower lip and the chin, which can be considered numb chin syndrome. Numb chin syndrome due to thalamic infarction has been reported previously. The present case is the first numb chin syndrome caused by a small cortical infarction in the postcentral gyrus.
RESUMO
Interstitial fibrosis is a final common pathway for the progression of chronic kidney diseases. Activated fibroblasts have an extremely important role in the progression of renal fibrosis, and transforming growth factor (TGF)-ß1 is a major activator of fibroblasts. Since previous reports have indicated that serine protease inhibitors have a potential to inhibit TGF-ß1 signaling in vitro, we hypothesized that a synthetic serine protease inhibitor, camostat mesilate (CM), could slow the progression of renal fibrosis. TGF-ß1 markedly increased the phosphorylation of TGF-ß type I receptor, ERK 1/2, and Smad2/3 and the levels of profibrotic markers, such as α-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF), and plasminogen activator inhibitor-1, in renal fibroblasts (NRK-49F cells), and they were all significantly reduced by CM. In protocol 1, 8-wk-old male Sprague-Dawley rats were subjected to unilateral ureteral obstruction (UUO) and were concurrently treated with a slow-release pellet of CM or vehicle for 14 days. Protocol 2 was similar to protocol 1 except that CM was administered 7 days after UUO. CM substantially improved renal fibrosis as determined by sirius red staining, collagen expression, and hydroxyproline levels. The phosphorylation of ERK1/2 and Smad2/3 and the levels of α-SMA, CTGF, promatrix metalloproteinase-2, and matrix metalloproteinase-2 were substantially increased by UUO, and they were all significantly attenuated by CM. These antifibrotic effects of CM were also observed in protocol 2. Our present results suggest the possibility that CM might represent a new class of therapeutic drugs for the treatment of renal fibrosis through the suppression of TGF-ß1 signaling.
Assuntos
Fibroblastos/metabolismo , Gabexato/análogos & derivados , Nefroesclerose/terapia , Inibidores de Serina Proteinase/uso terapêutico , Fator de Crescimento Transformador beta1/metabolismo , Animais , Linhagem Celular , Quimiocina CCL2/metabolismo , Ésteres , Gabexato/farmacologia , Gabexato/uso terapêutico , Guanidinas , Macrófagos/efeitos dos fármacos , Nefroesclerose/etiologia , Nefroesclerose/metabolismo , Fosforilação/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Inibidores de Serina Proteinase/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Obstrução Ureteral/complicaçõesRESUMO
Aldosterone plays an important role in the regulation of blood pressure by modulating the activity of the epithelial sodium channel (ENaC) that consists of α-, ß-, and γ-subunits. Aldosterone induces a molecular weight shift of γENaC from 85 to 70 kDa that is necessary for the channel activation. In vitro experiments demonstrated that a dual cleavage mechanism is responsible for this shift. It has been postulated that furin executes the primary cleavage in the Golgi and that the second cleavage is provided by other serine proteases such as prostasin or plasmin at the plasma membrane. However, the in vivo contribution of serine proteases to this cleavage remains unclear. To address this issue, we administered the synthetic serine protease inhibitor camostat mesilate (CM) to aldosterone-infused rats. CM decreased the abundance of the 70-kDa form of ENaC and led to a new 75-kDa form with a concomitant increase in the urinary Na-to-K ratio. Because CM inhibits the protease activity of serine proteases such as prostasin and plasmin, but not furin, our findings strongly indicate that CM inhibited the second cleavage of γENaC and subsequently suppressed ENaC activity. The results of our current studies also suggest the possibility that the synthetic serine protease inhibitor CM might represent a new strategy for the treatment of salt-sensitive hypertension in humans.
Assuntos
Aldosterona/farmacologia , Pressão Sanguínea/fisiologia , Canais Epiteliais de Sódio/metabolismo , Serina Proteases/metabolismo , Animais , Pressão Sanguínea/efeitos dos fármacos , Cloretos/metabolismo , Ésteres , Gabexato/análogos & derivados , Gabexato/farmacologia , Guanidinas , Masculino , Potássio/metabolismo , Ratos , Ratos Sprague-Dawley , Inibidores de Serina Proteinase/farmacologia , Sódio/metabolismoRESUMO
The number of the chronic renal failure (CRF) patients is increasing explosively. Hypertension, proteinuria, inflammation, fibrosis, and oxidative stress are intertwined in a complicated manner that leads to the progression of CRF. However, the therapeutic strategies to delay its progression are limited. Since serine proteases are involved in many processes that contribute to these risk factors, we investigated the effects of a synthetic serine protease inhibitor, camostat mesilate (CM), on the progression of CRF in 5/6 nephrectomized (Nx) rats. Eighteen male Sprague-Dawley rats were divided into three groups: a sham-operated group (n = 6), a vehicle-treated Nx group (n = 6), and a CM-treated Nx group (n = 6). Following the 9-wk study period, both proteinuria and serum creatinine levels were substantially increased in the vehicle-treated Nx group, and treatment with CM significantly reduced proteinuria and serum creatinine levels. The levels of podocyte-associated proteins in glomeruli, such as nephrin and synaptopodin, were markedly decreased by 5/6 nephrectomy, and this was significantly ameliorated by CM. CM also suppressed the levels of inflammatory and fibrotic marker mRNAs including transforming growth factor-ß1, TNF-α, collagen types I, III, and IV, and reduced glomerulosclerosis, glomerular hypertrophy, and interstitial fibrosis in histological studies. Furthermore, CM decreased the expression of NADPH oxidase component mRNAs, as well as reactive oxygen species generation and advanced oxidative protein product levels. Our present results strongly suggest the possibility that CM could be a useful therapeutic agent against the progression of CRF.
Assuntos
Gabexato/análogos & derivados , Falência Renal Crônica/tratamento farmacológico , Rim/efeitos dos fármacos , Proteinúria/tratamento farmacológico , Inibidores de Serina Proteinase/uso terapêutico , Animais , Creatinina/sangue , Progressão da Doença , Ésteres , Gabexato/farmacologia , Gabexato/uso terapêutico , Guanidinas , Rim/metabolismo , Rim/patologia , Falência Renal Crônica/metabolismo , Falência Renal Crônica/patologia , Masculino , Proteínas de Membrana/metabolismo , Proteínas dos Microfilamentos/metabolismo , Nefrectomia , Estresse Oxidativo/efeitos dos fármacos , Proteinúria/metabolismo , Proteinúria/patologia , Ratos , Ratos Sprague-Dawley , Inibidores de Serina Proteinase/farmacologia , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: Nitrogen turnover within plants has been intensively studied to better understand nitrogen use strategies. However, differences among the nitrogen absorbed at different times are not completely understood and the fate of nitrogen absorbed during winter is largely uncharacterized. In the present study, nitrogen absorbed at different times of the year (growing season, winter and previous growing season) was traced, and the within-leaf nitrogen turnover of a temperate deciduous oak Quercus serrata was investigated. METHODS: The contributions of nitrogen absorbed at the three different times to leaf construction, translocation during the growing season, and the leaf-level resorption efficiency during leaf senescence were compared using (15)N. KEY RESULTS: Winter- and previous growing season-absorbed nitrogen significantly contributed to leaf construction, although the contribution was smaller than that of growing season-absorbed nitrogen. On the other hand, the leaf-level resorption efficiency of winter- and previous growing season-absorbed nitrogen was higher than that of growing season-absorbed nitrogen, suggesting that older nitrogen is better retained in leaves than recently absorbed nitrogen. CONCLUSIONS: The results demonstrate that nitrogen turnover in leaves varies with nitrogen absorption times. These findings are important for understanding plant nitrogen use strategies and nitrogen cycles in forest ecosystems.
Assuntos
Nitrogênio/metabolismo , Folhas de Planta/metabolismo , Quercus/metabolismo , Absorção , Transporte Biológico , Parede Celular/química , Parede Celular/metabolismo , Nitrogênio/análise , Ciclo do Nitrogênio , Isótopos de Nitrogênio/análise , Folhas de Planta/crescimento & desenvolvimento , Quercus/crescimento & desenvolvimento , Estações do Ano , Árvores/metabolismoRESUMO
According to the guideline issued by the Japan Thyroid Association in 2006 for treatment of Graves' disease, discontinuing antithyroid drug (ATD) therapy is recommended when serum free thyroxine (FT4) and thyroid stimulating hormone (TSH) concentrations have been maintained within the reference range for a certain period after treatment with one ATD tablet every other day (minimum maintenance dose therapy, MMDT). In this retrospective study, the relationship between MMDT duration and remission rate was investigated. The participants were 107 consecutive patients with Graves' disease whose ATD therapy was stopped according to the guideline. Serum FT4, TSH, and TSH receptor antibody (TRAb) levels were measured when ATD was discontinued and every 3 months thereafter. The percentage of patients in remission was 86.9% at 6 months, 73.8% at 1 year, and 68.2% at 2 years after ATD discontinuation. The remission rate increased with MMDT duration, being significantly higher in patients with MMDT durations of 19 months or more than those with MMDT durations of 6 months or less. In patients with MMDT durations of 6 months or less, the remission rate was significantly lower in TRAb-positive patients than in TRAb-negative patients at the time of withdrawal of ATD; however, this was not observed in patients with MMDT durations of 7 months or more. These findings suggest that in patients who discontinue ATD after a certain MMDT duration, the remission rate increases as the MMDT duration increases, and ATD should not be discontinued in TRAb-positive patients with MMDT durations of 6 months or less.
Assuntos
Antitireóideos/administração & dosagem , Doença de Graves/tratamento farmacológico , Adolescente , Idoso , Feminino , Doença de Graves/sangue , Doença de Graves/patologia , Humanos , Imunoglobulinas Estimuladoras da Glândula Tireoide/sangue , Japão , Masculino , Metimazol/administração & dosagem , Pessoa de Meia-Idade , Propiltiouracila/administração & dosagem , Recidiva , Indução de Remissão/métodos , Estudos Retrospectivos , Glândula Tireoide/patologia , Tireotropina/sangue , Tiroxina/sangue , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: Knowledge gaps exist in the use of biologics for pregnant patients with Crohn's disease (CD), especially the usage of ustekinumab (UST) and infliximab (IFX) infusion during the late gestation period. In this case series, we investigated perinatal and neonatal outcomes and pharmacokinetics of these biologics in pregnant CD patients. METHODS: Pregnant CD patients under treatment with IFX or UST during January 2017 to December 2019 were monitored. Growth and development of their babies were followed up to six months. Drug concentrations were measured in maternal peripheral and cord blood at delivery and infants' blood at six months of age. RESULTS: Four cases were kept IFX treatment until late gestation (median last dose: 31.2 weeks). One case received UST until 23 weeks of gestation. All cases were in clinical remission but moderately undernourished. Babies were delivered by cesarean section at full term without any complications or congenital abnormalities. No growth or developmental defects and no susceptibility to infections were observed by six months. However, two babies whose mothers received IFX after 30 weeks of gestation were detected IFX in their blood at six months of age (0.94 and 0.24 pg/ml). Concentrations of UST in maternal and cord blood were 267.7 and 756.5 ng/ml, respectively. UST was not detected in the infant at six months of age. CONCLUSIONS: Administration of UST or IFX to pregnant patients with CD is safe, particularly IFX to be given in the late gestation period. Understanding of the pharmacokinetics of biologics in maternal-infant interactions may improve the management of pregnant CD patients.
RESUMO
Molluscan smooth muscles exhibit a low energy cost contraction called catch. Catch is regulated by twitchin phosphorylation and dephosphorylation. Recently, we found that the D2 fragment of twitchin containing the D2 site (Ser-4316) and flanking immunoglobulin motifs (TWD2-S) formed a heterotrimeric complex with myosin and with actin in the region that interacts with myosin loop 2 (Funabara, D., Hamamoto, C., Yamamoto, K., Inoue, A., Ueda, M., Osawa, R., Kanoh, S., Hartshorne, D. J., Suzuki, S., and Watabe, S. (2007) J. Exp. Biol. 210, 4399-4410). Here, we show that TWD2-S interacts directly with myosin loop 2 in a phosphorylation-sensitive manner. A synthesized peptide, CAQNKEAETTGTHKKRKSSA, based on the myosin loop 2 sequence (loop 2 peptide), competitively inhibited the formation of the trimeric complex. Isothermal titration calorimetry showed that TWD2-S binds to the loop 2 peptide with a K(a) of (2.44 +/- 0.09) x 10(5) m(-1) with two binding sites. The twitchin-binding peptide of actin, AGFAGDDAP, which also inhibited formation of the trimeric complex, bound to TWD2-S with a K(a) of (5.83 +/- 0.05) x 10(4) m(-1) with two binding sites. The affinity of TWD2-S to actin and myosin was slightly decreased with an increase of pH, but this effect could not account for the marked pH dependence of catch in permeabilized fibers. The complex formation also showed a moderate Ca(2+) sensitivity in that in the presence of Ca(2+) complex formation was reduced.
Assuntos
Actinas/metabolismo , Proteínas Musculares/metabolismo , Músculo Liso/fisiologia , Miosinas/metabolismo , Mytilus/metabolismo , Animais , Ligação Competitiva , Cálcio/metabolismo , Calorimetria , Concentração de Íons de Hidrogênio , Complexos Multiproteicos/metabolismo , Contração Muscular/fisiologiaRESUMO
There is some debate over the clinical utility of measuring serum TgAb to assess the presence of thyroid autoimmunity. To clarify the relationship between TgAb levels and thyroid autoimmunity, a histological examination of thyroid tissue was carried out on unselected living individuals with detectable serum TgAb. 146 patients with a pathological diagnosis of follicular adenoma were selected as subjects. Focal lymphocytic infiltration (FLI) was defined as lymphocytic aggregates of more than 200 in number. A thyroid gland in which 0-1 FLI was observed in a few visual fields of low magnification (20 x 4) in thyroid tissue adjacent to a tumor was judged to be normal and a thyroid gland in which 2 or more FLI were observed was diagnosed as focal lymphocytic thyroiditis (FLT). Serum levels of TgAb and TPOAb were measured by radioimmunoassay. Out of the 146 patients, 18 had detectable serum TgAb and 16 had detectable serum TPOAb. All but one (i.e. 94%) of the 18 TgAb positive patients had FLT and 14 out of the 16 TPOAb positive patients had FLT. The sensitivity (17/32; 53.1%) and specificity (113/114; 99.1%) of TgAb for detecting FLT were higher than those (14/32; 43.7% and 112/114; 98.2%) of TPOAb, but the differences were not significant. In 9 patients who were TgAb positive (but TPOAb negative), 8 (88.9%) had FLT. These results throw doubt on the Laboratory medicine practice guidelines published in Thyroid 2003, in which measuring TgAb is not usually necessary for detecting autoimmune thyroid disease. At least measuring TgAb by sensitive assay is useful for assessing the presence of thyroid autoimmunity in Japan, an area with high iodine intakes.
Assuntos
Autoanticorpos/análise , Iodo/provisão & distribuição , Tireoglobulina/imunologia , Tireoidite Autoimune/diagnóstico , Adulto , Autoanticorpos/sangue , Autoimunidade/imunologia , Ingestão de Alimentos/fisiologia , Feminino , Geografia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Radioimunoensaio/métodos , Radioimunoensaio/normas , Sensibilidade e Especificidade , Tireoidite Autoimune/sangue , Tireoidite Autoimune/imunologiaRESUMO
The degree and frequency of orthostatic hypotension (OH) are high in patients with multiple system atrophy (MSA); however, the association of orthostatic blood pressure (BP) with the symptoms of OH and cognitive impairment in these patients remains unclear. The aim of this study was to clarify whether absolute BP and/or changes in BP during standing are related to OH symptoms and cognitive impairment in patients with MSA. Thirty-two patients with MSA were examined using the head-up tilt and cognitive function tests. OH symptoms were evaluated using a patient-reported scale. The results were compared with those for 15 age- and sex-matched healthy controls. Seventeen of the 32 (53.1%) patients had OH, with eight of them exhibiting OH symptoms, which were related to the absolute BP value at 60° tilt. However, OH symptoms were not related to the degree of decrease in BP during the tilt test, and they were frequently observed in patients with a mean BP of <80 mmHg at 60° tilt (sensitivity, 67%; specificity, 91%). Cognitive dysfunction assessed by the Mini-Mental State Examination (MMSE; ≤ 26) was also associated with a low mean BP at 60° tilt (odds ratio, 1.32; 95% confidence interval, 1.04-1.67; p = 0.02). The upright BP value is associated with OH symptoms and the MMSE score in patients with MSA. Thus, careful observation of OH symptoms can enable early management of BP and the detection of cognitive impairment in these patients.
Assuntos
Disfunção Cognitiva/etiologia , Hipotensão Ortostática/complicações , Atrofia de Múltiplos Sistemas/complicações , Idoso , Pressão Sanguínea/fisiologia , Encéfalo/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atrofia de Múltiplos Sistemas/patologia , Teste da Mesa Inclinada , Substância Branca/patologiaRESUMO
Early season leaf growth requires a large amount of nitrogen, and the amount of N provided for new leaf development has been well tested. Although shoot position within the crown strongly influences leaf properties, little is known about absorbed and remobilized nitrogen allocation in the tree crown. Thus, we investigated differences in the allocation of recently absorbed nitrogen in the tree crown. To quantify nitrogen allocation, we conducted 15N tracer experiments using potted saplings of the temperate deciduous oak (Quercus serrata Thunb. ex. Murray). Allocation of 15N within the crown varied significantly: the top leaves received more remobilized nitrogen than did the lateral leaves, suggesting that remobilized nitrogen is predominantly allocated to the top shoots, which are important for height growth. On the other hand, the proportion of currently-absorbed nitrogen to total nitrogen in the lateral leaves was more than twice that in the top leaves. We also detected the input and the output of nitrogen in the top leaves after the completion of leaf expansion, indicating that significant nitrogen cycling occurs even after full leaf expansion.
Assuntos
Nitrogênio/metabolismo , Folhas de Planta/metabolismo , Quercus/metabolismo , Folhas de Planta/crescimento & desenvolvimento , Quercus/crescimento & desenvolvimento , Estações do Ano , Árvores/metabolismoRESUMO
Cardiac parasympathetic function is strongly affected by aging. Although sympathetic dysfunction has been well documented in Parkinson's disease (PD), cardiac parasympathetic dysfunction has not been well studied. The objective of this study was to clarify the development of cardiac parasympathetic dysfunction in the early phase of PD and to explore the age-corrected correlation between cardiac parasympathetic dysfunction and cardiac sympathetic dysfunction. We reviewed 25 healthy controls and 56 patients with idiopathic PD of Hoehn and Yahr stages I-III. We evaluated cardiac parasympathetic function using the Valsalva ratio, the baroreflex sensitivity (BRS) and the coefficient of variation of RR intervals in the resting state (resting-CVRR) and during deep breathing (DB-CVRR). In addition, we measured cardiac 123I-metaiodobenzylguanidine (MIBG) uptake to investigate the relationship between cardiac sympathetic and parasympathetic dysfunction in PD. Compared with healthy controls, patients with PD showed significantly decreased cardiac parasympathetic parameters (resting-CVRR 2.8 ± 1.3 vs. 1.7 ± 0.6%, p < 0.001; DB-CVRR 5.8 ± 2.3 vs. 3.8 ± 1.7%, p < 0.001; Valsalva ratio 1.52 ± 0.26 vs. 1.34 ± 0.17, p < 0.01; BRS 10.6 ± 9.5 vs. 5.0 ± 5.4 ms/mmHg, p < 0.01). In particular, resting-CVRR and DB-CVRR were significantly decreased in the early phase of PD. In age-corrected analyses, none of the parasympathetic indices correlated with the delayed cardiac 123I-MIBG uptake. These observations indicate that cardiac parasympathetic dysfunction occurs in the early phase of PD, but not necessarily in parallel with cardiac sympathetic dysfunction.
Assuntos
Doenças do Sistema Nervoso Autônomo/fisiopatologia , Doença de Parkinson/fisiopatologia , 3-Iodobenzilguanidina , Idoso , Envelhecimento/fisiologia , Doenças do Sistema Nervoso Autônomo/tratamento farmacológico , Doenças do Sistema Nervoso Autônomo/etiologia , Pressão Sanguínea , Determinação da Pressão Arterial , Progressão da Doença , Feminino , Coração/diagnóstico por imagem , Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Imagem de Perfusão do Miocárdio , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/tratamento farmacológico , Compostos Radiofarmacêuticos , Índice de Gravidade de Doença , Teste da Mesa Inclinada , Manobra de ValsalvaRESUMO
INTRODUCTION: Lower body mass index (BMI) is associated with orthostatic hypotension (OH) in the general population, especially in the elderly; however, no studies have addressed this issue in Parkinson's disease (PD). METHODS: We investigated the results of the head-up tilt test and BMI of patients with PD, and evaluated whether BMI is related to orthostatic systolic blood pressure (SBP) change during the head-up tilt test. PD patients were divided into male and female groups, and further divided into middle-aged (age<65years) and elderly (age≥65years) subgroups in each sex. RESULTS: OH was observed in 13 of 64 male and 12 of 75 female patients with PD. BMI was lower in patients with OH than in those without, in both men and women. In the elderly group, a significant correlation between BMI and orthostatic SBP change was found (men, r=0.47, p=0.006; women, r=0.43, p=0.005), and a BMI below mean-0.5 standard deviation increased OH odds (men: BMI<20.5; odds ratio, 6.79; 95% CI, 1.06-43.36; women: BMI<18.5; odds ratio, 5.11; 95% CI, 1.05-24.96). CONCLUSION: Lower BMI is a predisposing factor of OH in elderly patients with PD.