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1.
Clin Exp Nephrol ; 22(3): 597-602, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29071504

RESUMO

OBJECTIVE: Using a single-center cohort of Japanese patients with SLE, we attempted to clarify the long-term outcome and factors associated with damage accrual using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). METHODS: We examined a cohort of 557 patients who had been referred to Niigata University Hospital and diagnosed as having SLE between 1961 and 2013. The patients' data at the latest visit were collected from their clinical records, and causes of death were defined on the basis of those data. Survival from the time of diagnosis was calculated by the Kaplan-Meier method. The SDI was calculated and analyzed using Spearman's correlation coefficient and stepwise multiple regression analysis to reveal the factors associated with any organ damage. RESULTS: Data from 458 of the patients were successfully obtained. The overall 5-year survival rate was 92.2%, and patients diagnosed after 2000 had a significantly high 5-year survival rate of 96.4%. Stepwise multiple regression analysis selected serum creatinine levels (B = 0.6051, p < 0.0001), age (standardized beta = 0.2762, p < 0.001), hypertension (standardized beta = 0.2267, p < 0.001), and antiphospholipid antibody syndrome (standardized beta = 0.1533, p = 0.005) as positive independent variables, whereas administration of bisphosphonate (standardized beta = - 0.1295, p = 0.016) was selected as a negative independent variable. CONCLUSION: These results suggest that Japanese patients with SLE have a favorable long-term prognosis, and also indicate that disease control as well as management of chronic complications such as hypertension and osteoporosis has possible effects for prevention of organ damage.


Assuntos
Lúpus Eritematoso Sistêmico/mortalidade , Adulto , Idoso , Causas de Morte , Feminino , Humanos , Japão/epidemiologia , Lúpus Eritematoso Sistêmico/complicações , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Adulto Jovem
2.
BMC Cancer ; 17(1): 381, 2017 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-28549422

RESUMO

BACKGROUND: Patients with tongue cancer frequently show loss of heterozygosity (LOH) of the von Hippel-Lindau (VHL) tumor suppressor gene. However, expression of VHL protein (pVHL) in tongue cancer has rarely been investigated and remains largely unknown. We performed immunohistochemical staining of pVHL in tongue tissues and dysplasia, and examined the association with LOH and its clinical significance. METHODS: Immunohistochemical staining of pVHL in formalin-fixed, paraffin-embedded sections of cancerous and other tissues from 19 tongue cancer patients showed positivity for LOH of VHL in four samples, negativity in four samples, and was non-informative in 11 samples. The staining pattern of pVHL was also compared with those of cytokeratin (CK) 13 and CK17. RESULTS: In normal tongue tissues, pVHL staining was localized to the cytoplasm of cells in the basal layer and the area of the spinous layer adjacent to the basal layer of stratified squamous epithelium. Positive staining for pVHL was observed in the cytoplasm of cancer cells from all 19 tongue cancer patients. No differences as a result of the presence or absence of LOH were found. Notably, cytoplasm of poorly differentiated invasive cancer cells was less intensely stained than that of well and moderately differentiated invasive cancer cells. pVHL staining was also evident in epithelial dysplasia lesions with pVHL-positive cells expanding from the basal layer to the middle of the spinous layer. However, no CK13 staining was noted in regions of the epithelium, which were positive for pVHL. In contrast, regions with positive staining for CK17 closely coincided with those positive for pVHL. CONCLUSIONS: Positive staining for pVHL was observed in cancerous areas but not in normal tissues. pVHL expression was also detected in lesions of epithelial dysplasia. These findings suggest that pVHL may be a useful marker for proliferative lesions.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias da Língua/patologia , Proteína Supressora de Tumor Von Hippel-Lindau/biossíntese , Adulto , Idoso , Carcinoma de Células Escamosas/metabolismo , Epitélio/metabolismo , Epitélio/patologia , Feminino , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas de Cabeça e Pescoço , Língua/metabolismo , Língua/patologia , Neoplasias da Língua/metabolismo , Proteína Supressora de Tumor Von Hippel-Lindau/análise , Adulto Jovem
3.
Breast Cancer Res ; 15(1): R12, 2013 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-23407024

RESUMO

INTRODUCTION: Despite continued improvements in diagnosis, surgical techniques, and chemotherapy, breast cancer patients are still overcome by cancer metastasis. Tumor cell proliferation, invasion and metastasis are mediated, at least in part, through degradation of basement membrane by neutral matrix metalloproteinases (MMP) produced by tumor and stromal cells. Evidence suggests that MMP-9 plays a significant role in breast tumor cell invasion and metastasis. DNAzymes or catalytic oligonucleotides are new classes of gene targeting molecules that bind and cleave a specific mRNA, resulting in decreased protein expression. METHODS: The application of anti-MMP-9 DNAzyme (AM9D) for the treatment of primary and metastatic breast cancer was evaluated in vitro and in vivo using MDA-MB-231 cells and the MMTV-PyMT transgenic breast cancer mouse model. Spontaneously developed mammary tumors in MMTV-PyMT transgenic mice were treated intratumorally with naked AM9D, once a week for 4 weeks. The stability of DNAzyme was determined in vitro and in vivo using fluorescently labeled DNAzyme. RESULTS: AM9D specifically inhibited expression of MMP-9 in MDA-MB-231 cells resulting in reduced invasive property of these cells by 43%. Weekly intratumoral treatment of spontaneously developed mammary tumors in MMTV-PyMT transgenic mice was sufficient to significantly reduce the rate of tumor growth and final tumor load in a dose dependent and statistically significant manner (P < 0.05). This decrease in tumor growth was correlated with decreased MMP-9 protein production within the treated tumor tissues. Tumors treated with AM9D were also less vascularized and contained more apoptotic cells compared to control and untreated tumors. CONCLUSIONS: These results show that targeting and down regulation of MMP-9 by AM9D could prove useful as a therapy against breast carcinoma tumor growth and invasion.


Assuntos
Neoplasias da Mama/tratamento farmacológico , DNA Catalítico/administração & dosagem , Neoplasias Mamárias Animais/tratamento farmacológico , Metaloproteinase 9 da Matriz/biossíntese , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Mamárias Animais/genética , Neoplasias Mamárias Animais/patologia , Metaloproteinase 9 da Matriz/genética , Camundongos , Invasividade Neoplásica/genética , Metástase Neoplásica
4.
Ear Nose Throat J ; 102(3): 170-174, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33559492

RESUMO

OBJECTIVES: This study aimed to identify vocal fold leukoplakia (VFL) lesions on the inferior surface as a risk factor for recurrence. METHODS: This was a retrospective study with data collected from 2001 to 2018. The study comprised 37 patients with VFL, divided into the nonrecurrent and recurrent groups. We examined the clinicopathological characteristics and the surgical procedures performed in each patient. RESULTS: Among the 37 patients, 15 (40.5%) had residual (3) or recurrent (12) VFL. Of those patients with and without recurrence, 8 of 12 (66.7%) and 6 of 22 (27.3%), respectively, had inferior surface lesions of the vocal fold at the initial operation (P = .036). Recurrences were significantly higher in patients with inferior surface lesions. Other evaluated factors did not show significance for recurrence. CONCLUSION: The presence of VFL lesions on the inferior surface is a significant risk factor for recurrence.


Assuntos
Doenças da Laringe , Prega Vocal , Humanos , Prega Vocal/patologia , Estudos Retrospectivos , Doenças da Laringe/cirurgia , Doenças da Laringe/patologia , Leucoplasia/cirurgia , Leucoplasia/patologia , Fatores de Risco , Laringoscopia/métodos
5.
Nature ; 444(7120): 770-4, 2006 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-17086194

RESUMO

FGF23 is a unique member of the fibroblast growth factor (FGF) family because it acts as a hormone that derives from bone and regulates kidney functions, whereas most other family members are thought to regulate various cell functions at a local level. The renotropic activity of circulating FGF23 indicates the possible presence of an FGF23-specific receptor in the kidney. Here we show that a previously undescribed receptor conversion by Klotho, a senescence-related molecule, generates the FGF23 receptor. Using a renal homogenate, we found that Klotho binds to FGF23. Forced expression of Klotho enabled the high-affinity binding of FGF23 to the cell surface and restored the ability of a renal cell line to respond to FGF23 treatment. Moreover, FGF23 incompetence was induced by injecting wild-type mice with an anti-Klotho monoclonal antibody. Thus, Klotho is essential for endogenous FGF23 function. Because Klotho alone seemed to be incapable of intracellular signalling, we searched for other components of the FGF23 receptor and found FGFR1(IIIc), which was directly converted by Klotho into the FGF23 receptor. Thus, the concerted action of Klotho and FGFR1(IIIc) reconstitutes the FGF23 receptor. These findings provide insights into the diversity and specificity of interactions between FGF and FGF receptors.


Assuntos
Fatores de Crescimento de Fibroblastos/metabolismo , Glucuronidase/metabolismo , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais , Animais , Linhagem Celular , Proteína 1 de Resposta de Crescimento Precoce/genética , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/antagonistas & inibidores , Fatores de Crescimento de Fibroblastos/genética , Glucuronidase/antagonistas & inibidores , Glucuronidase/genética , Humanos , Proteínas Klotho , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosforilação , Ligação Proteica , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Receptores de Fatores de Crescimento de Fibroblastos/genética , Especificidade por Substrato
6.
Clin Nephrol ; 77(5): 347-51, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22551879

RESUMO

BACKGROUND: The extracellular domain of klotho is cleaved and released into various extracellular fluids, such as blood, urine, and cerebrospinal fluid, as soluble α-klotho (sαKl). METHODS: We measured sαKl in 53 hemodialysis patients and 20 healthy controls to examine its role in mineral metabolism. RESULTS: The sαKl level of the hemodialysis patients was 430 pg/ml (386 - 540 pg/ml, which was lower than that of healthy controls 740 pg/ml (550 - 913 pg/ml, p < 0.01). The serum sαKl level showed a positive correlation with serum phosphorus (P) (σ = 0.33, p = 0.014), while serum corrected Ca tended to be negatively correlated with sαKl (σ = -0.26, p = 0.06). Both parameters showed the same trends in healthy subjects. However, there was no significant association between serum sαKl and age (σ= 0.21, p = 0.14), intact PTH (σ = -0.08, p= 0.55), whole PTH (σ = -0.08, p = 0.59), or FGF23 (σ = -0.07, p = 0.62). Multiple regression analysis showed that P was independently associated with the serum sαKl levels (total adjusted R2 = 0.18, p = 0.02). CONCLUSIONS: The sαKl level was lower in hemodialysis patients than in healthy persons. Serum P level was independently associated with the serum sαKl level.


Assuntos
Glucuronidase/sangue , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Diálise Renal , Adulto , Idoso , Biomarcadores/sangue , Cálcio/sangue , Estudos de Casos e Controles , Regulação para Baixo , Feminino , Fator de Crescimento de Fibroblastos 23 , Humanos , Japão , Proteínas Klotho , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fósforo/sangue , Análise de Regressão
7.
Eur Arch Otorhinolaryngol ; 269(10): 2271-6, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22215212

RESUMO

A number of reports have investigated the relationship between laryngeal papilloma and human papilloma virus (HPV) infection. On the other hand, it is unclear whether the HPV infection is involved in the occurrence of pharyngeal papilloma. We hypothesized that HPV infection was involved in the occurrence of pharyngeal papilloma similarly to laryngeal papilloma. To verify this hypothesis, we investigated the presence of HPV infection. Furthermore, clinical manifestations of pharyngeal papilloma, which had rarely been reported, were discussed. A male-to-female ratio, solitary or multiple occurrences, and koilocytosis were examined in cases with pharyngeal papilloma. HPV DNA was examined with unfixed surgically resected specimens of pharyngeal papilloma. A screening test by the liquid-phase hybridization method was carried out for the HPV high-risk group (16, 18, 31, 33, 35, 39, 45, 51, 56, 58, 59, and 68) and HPV low-risk group (6, 11, 42, 43, 44). As a control, 15 cases with laryngeal papilloma for which the same screening test was carried out were employed. Pharyngeal papilloma occurred as a solitary lesion more often, whereas laryngeal papilloma occurred as multiple tumors more frequently. The HPV infection rate was 0% in pharyngeal papilloma cases, which was in stark contrast with 66.7% in the HPV low-risk group in laryngeal papilloma cases. Pharyngeal papilloma occurred as a solitary lesion in females more frequently. Contrary to our hypothesis, the involvement of HPV infection was unlikely in the occurrence of pharyngeal papilloma.


Assuntos
Carcinoma de Células Escamosas/virologia , Neoplasias de Cabeça e Pescoço/virologia , Papiloma/virologia , Infecções por Papillomavirus/epidemiologia , Neoplasias Faríngeas/virologia , Adulto , Idoso , Carcinoma de Células Escamosas/diagnóstico , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico , Humanos , Neoplasias Hipofaríngeas/diagnóstico , Neoplasias Hipofaríngeas/virologia , Japão , Neoplasias Laríngeas/diagnóstico , Neoplasias Laríngeas/virologia , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/diagnóstico , Neoplasias Orofaríngeas/virologia , Papiloma/diagnóstico , Infecções por Papillomavirus/virologia , Neoplasias Faríngeas/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço , Prega Vocal/virologia , Adulto Jovem
8.
Turk Arch Otorhinolaryngol ; 60(2): 105-108, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36105531

RESUMO

Schwannomas are benign soft tissue tumors derived from the Schwann cells of the peripheral nerves. An intramuscular schwannoma arising within the trapezius muscle in the posterior neck is rare. We report a case of a 31-year-old woman with an intramuscular schwannoma in the trapezius muscle. A painless and smooth-surfaced mass from 10 years ago was evident on palpation in the right posterior neck. Ultrasonography revealed an oval mass with clear borders and slight internal blood flow. No continuous hypoechoic lesions were noted at the tip of the mass. Magnetic resonance imaging of the neck revealed a mass in the right posterior cervical trapezius muscle with isointensity on T1-weighted imaging and heterointensity on T2-weighted imaging. Based on these findings, a schwannoma was suspected. Ultrasonography guided fine needle aspiration cytology revealed no significant findings. During surgery, a white-colored, encapsulated-tumor mass was found in the trapezius muscle. Histopathologically, hypocellular and hypercellular areas of fusiform cells were conspicuous, and nuclear palisading was observed in a part of the hypercellular region, confirming the diagnosis of schwannoma. To our knowledge, this is an extremely rare report of an intramuscular schwannoma within the trapezius muscle; herein, we report its clinical, radiological, and pathological features.

9.
Endocr J ; 58(8): 647-55, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21597229

RESUMO

X-linked hypophosphatemic rickets (XLH) is caused by inactivating mutations in the phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) gene. Deletion of Phex leads to increased serum fibroblast growth factor23 (FGF23) levels in mouse. The aim is to assure the clinical usefulness of FGF23 determination in the diagnosis of XLH. Participants were 21 patients with XLH having abnormalities in PHEX from 13 kindred (PtPHEX: 1 to 42 years old; 10 males, 11 females) and 55 healthy controls (1 month to 18 years old; 27 males, 28 females). Temporal changes in FGF23 were determined by a single oral phosphate administration in PtPHEX and an ad lib diet in controls. Reference ranges of intact FGF23 (iFGF23) for children were determined. iFGF23 level which distinguish between controls and PtPHEX were validated. Correlations between iFGF23 and the severity of XLH (gender, age of onset, bone deformity, The ratio of maximum rate of renal tubular reabsorption of phosphate to glomerular filtration rate (TmPO(4)/GFR), inorganic phosphate (IP), Alkaline Phosphatase (ALP), therapeutic dose) were investigated. Increasing tendency after phosphate administration and no general tendency after breakfast in iFGF23 were observed. Reference range (5(th) and 95(th) percentiles) of iFGF23 for children (12.9 and 51.2 pg/mL) was similar to that for adults. iFGF23 were above the reference range in 19 of 21 PtPHEX (40 to 4710 pg/mL). iFGF23 did not correlate with any index of severity of XLH. Relatively high iFGF23 despite hypophosphatemia is one of the clinical indicators to diagnose XLH.


Assuntos
Raquitismo Hipofosfatêmico Familiar/diagnóstico , Fatores de Crescimento de Fibroblastos/sangue , Doenças Genéticas Ligadas ao Cromossomo X , Hipofosfatemia/sangue , Adolescente , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Diagnóstico Diferencial , Raquitismo Hipofosfatêmico Familiar/sangue , Raquitismo Hipofosfatêmico Familiar/genética , Feminino , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/fisiologia , Humanos , Hipofosfatemia/diagnóstico , Hipofosfatemia/genética , Lactente , Masculino , Concentração Osmolar , Endopeptidase Neutra Reguladora de Fosfato PHEX/genética , Prognóstico , Adulto Jovem
10.
J Surg Case Rep ; 2021(7): rjab324, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34345405

RESUMO

Thyroid hyalinizing trabecular adenoma (HTA) is a rare and borderline tumor of follicular origin. It is characterized by a trabecular growth pattern and marked intratrabecular hyalinization. Excessively elevated thyroglobulin levels have not been reported previously in cases without bilateral lung metastases. Here, we present a case of a 54-year-old woman with chronic thyroiditis with a 50-mm tumor in the left lobe of the thyroid gland, which was observed on ultrasonography. Her thyroglobulin level was found to be elevated at 684 ng/ml. Since fine needle aspiration cytology could not exclude possible malignancy, she underwent thyroid lobectomy; the final diagnosis was thyroid HTA. Two weeks after resection, her thyroglobulin level showed negative conversion. To our knowledge, this is the first report of a patient with a thyroid HTA exhibiting a thyroglobulin level as high as that for a patient with hyalinizing trabecular carcinoma.

11.
J Voice ; 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34600799

RESUMO

Prevention of the recurrence of recurrent respiratory papillomatosis (RRP), a neoplasm of the respiratory tract, is a challenge. Human papillomavirus (HPV) vaccine has been expected to suppress the aggressiveness of RRP. However, there has been insufficient data to verify whether HPV vaccination can serve as an adjuvant therapy option for RRP. The aim of this study was to add our data on the efficacy of HPV vaccination for RRP to the academic discipline. Twenty-four RRP patients were treated with a combination therapy of surgery and three sessions of quadrivalent HPV vaccine. The patients' clinical courses, which were HPV infection status changes, intersurgical interval, and disease severity score (Derkay's site score), were statistically analyzed before and after combination therapy. Twelve of the 24 (52.5%) RRP patients who were HPV-DNA positive turned negative after the combination therapy. The mean of intersurgical interval was significantly extended from 6.85 ± 4.49 months to 30.5 ± 27.6 months after the therapy (P <0.01). The median of Derkay's score of the participants also significantly decreased from 7.5 (interquartile range, 5-12) to 1 (interquartile range, 0-4.25) after the therapy (P <0.01). Thus, combination therapy comprising of surgery and HPV vaccination can postpone the recurrence and lessen the severity of RRP.

12.
Kidney Int ; 78(10): 975-80, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20844473

RESUMO

Circulating levels of fibroblast growth factor 23 (FGF23) are elevated in patients with early chronic kidney disease (CKD) and are postulated to cause low blood levels of 1,25-dihydroxyvitamin D, as well as normal phosphate levels. In order to provide more direct evidence for the pathophysiological role of FGF23 in the settings of mineral ion homeostasis typically seen in early CKD, we studied rats with progressive CKD treated with anti-FGF23 neutralizing antibody. Without antibody treatment, rats with CKD exhibited high circulating levels of FGF23 and parathyroid hormone, low 1,25-dihydroxyvitamin D, and normal serum phosphate levels, accompanied by increased fractional excretion of phosphate. Antibody treatment, however, lessened fractional excretion of phosphate, thus increasing serum phosphate levels, and normalized serum 1,25-dihydroxyvitamin D by increased 1α-OHase and decreased 24-OHase expressions in the kidney. These antibody-induced changes were followed by increased serum calcium levels, leading to decreased serum parathyroid hormone. Hence, our study shows that FGF23 normalizes serum phosphate and decreases 1,25-dihydroxyvitamin D levels in early-stage CKD, and suggests a pathological sequence of events for the development of secondary hyperparathyroidism triggered by increased FGF23, followed by a reduction of 1,25-dihydroxyvitamin D and calcium levels, thereby increasing parathyroid hormone secretion.


Assuntos
Fatores de Crescimento de Fibroblastos/metabolismo , Nefropatias/metabolismo , Rim/metabolismo , Fosfatos/metabolismo , Vitamina D/metabolismo , Animais , Anticorpos Monoclonais/farmacologia , Autoanticorpos/efeitos adversos , Cálcio/metabolismo , Doença Crônica , Modelos Animais de Doenças , Fatores de Crescimento de Fibroblastos/imunologia , Homeostase , Rim/fisiopatologia , Nefropatias/induzido quimicamente , Nefropatias/fisiopatologia , Masculino , Minerais/metabolismo , Hormônio Paratireóideo/metabolismo , Ratos , Ratos Endogâmicos WKY , Vitamina D/análogos & derivados
13.
Biochem Biophys Res Commun ; 398(3): 513-8, 2010 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-20599764

RESUMO

BACKGROUND: Alpha-Klotho (alphaKl) regulates mineral metabolism such as calcium ion (Ca(2+)) and inorganic phosphate (Pi) in circulation. Defects in mice result in clinical features resembling disorders found in human aging. Although the importance of transmembrane-type alphaKl has been demonstrated, less is known regarding the physiological importance of soluble-type alphaKl (salphaKl) in circulation. OBJECTIVES: The aims of this study were: (1) to establish a sandwich ELISA system enabling detection of circulating serum salphaKl, and (2) to determine reference values for salphaKl serum levels and relationship to indices of renal function, mineral metabolism, age and sex in healthy subjects. RESULTS: We successively developed an ELISA to measure serum salphaKl in healthy volunteers (n=142, males 66) of ages (61.1+/-18.5year). The levels (mean+/-SD) in these healthy control adults were as follows: total calcium (Ca; 9.46+/-0.41mg/dL), Pi (3.63+/-0.51mg/dL), blood urea nitrogen (BUN; 15.7+/-4.3mg/dL), creatinine (Cre; 0.69+/-0.14mg/dL), 1,25 dihydroxyvitamin D (1,25(OH)(2)D; 54.8+/-17.7pg/mL), intact parathyroid hormone (iPTH; 49.2+/-20.6pg/mL), calcitonin (26.0+/-12.3pg/mL) and intact fibroblast growth factor (FGF23; 43.8+/-17.6pg/mL). Serum levels of salphaKl ranged from 239 to 1266pg/mL (mean+/-SD; 562+/-146pg/mL) in normal adults. Although salphaKl levels were not modified by gender or indices of mineral metabolism, salphaKl levels were inversely related to Cre and age. However, salphaKl levels in normal children (n=39, males 23, mean+/-SD; 7.1+/-4.8years) were significantly higher (mean+/-SD; 952+/-282pg/mL) than those in adults (mean+/-SD; 562+/-146, P<0.001). A multivariate linear regression analysis including children and adults in this study demonstrated that salphaKl correlated negatively with age and Ca, and positively with Pi. Finally, we measured a serum salphaKl from a patient with severe tumoral calcinosis derived from a homozygous missense mutation of alpha-klotho gene. In this patient, salphaKl level was notably lower than those of age-matched controls. CONCLUSION: We established a detection system to measure human serum salphaKl for the first time. Age, Ca and Pi seem to influence serum salphaKl levels in a normal population. This detection system should be an excellent tool for investigating salphaKl functions in mineral metabolism.


Assuntos
Envelhecimento/sangue , Ensaio de Imunoadsorção Enzimática , Glucuronidase/sangue , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Animais , Anticorpos Monoclonais/imunologia , Cálcio/sangue , Criança , Feminino , Fator de Crescimento de Fibroblastos 23 , Glucuronidase/genética , Glucuronidase/imunologia , Humanos , Proteínas Klotho , Masculino , Camundongos , Pessoa de Meia-Idade , Mutação
14.
Circ J ; 74(12): 2734-40, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21041973

RESUMO

BACKGROUND: Fibroblast growth factor 23 (FGF-23) is a novel bone-derived phosphate-regulating hormone, and serum FGF-23 levels are associated with mortality among hemodialysis (HD) patients. However, the pathophysiological role of FGF-23 in those patients remains unclear, so the association between serum FGF-23 levels and known cardiac biomarkers or echocardiographic measurements were investigated in long-term HD patients without cardiac symptoms. METHODS AND RESULTS: The 87 consecutive patients treated in a single HD center (51 males, 36 females; mean age 64 years, mean HD duration 5.8 years) were included in this study. Comprehensive echocardiography was performed after HD. Blood samples were obtained before HD. Serum FGF-23 levels in dialysis patients were 1,171±553pg/ml. In univariate analysis, serum phosphate (r=0.443, P<0.001) and calcium levels (r=0.256, P=0.04), left ventricular mass index (LVMI) (r=0.268, P=0.039) were significantly associated with FGF-23 levels. Neither the B-type natriuretic peptide (BNP) nor the cardiac troponin T level was correlated with FGF-23. In multivariate regression analysis, only LVMI (ß=0.287, P=0.031, confidence interval (CI) 0.390-8.040) and phosphate levels (ß=0.419, P=0.001, CI 57.12-207.7) and calcium levels (ß=0.277, P=0.025, CI 24.95-360.1) remained significantly correlated with FGF-23. CONCLUSIONS: Beside BNP, FGF-23 was identified as a factor that is significantly associated with LVMI. FGF-23 could be a novel biomarker of left ventricular overload, which is closely associated with the increased risk of death in HD patients.


Assuntos
Fatores de Crescimento de Fibroblastos/sangue , Hipertrofia Ventricular Esquerda/sangue , Hipertrofia Ventricular Esquerda/terapia , Peptídeo Natriurético Encefálico/sangue , Diálise Renal , Troponina T/sangue , Idoso , Biomarcadores/sangue , Feminino , Fator de Crescimento de Fibroblastos 23 , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
15.
Turk Arch Otorhinolaryngol ; 57(1): 42-45, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31049253

RESUMO

We here report a rare salivary gland tumor, a non-sebaceous lymphadenoma (NSLA), in the parotid gland with positive technetium-99m (99mTc) pertechnetate scintigraphy and cervical masses that was difficult to distinguish from malignant lymphoma preoperatively. A 65-year-old Japanese woman presented to our institution with a painless left parotid mass that had been gradually enlarging for three months. Computed tomography and magnetic resonance imaging showed a solid mass (30 mm) in the tail of the left parotid gland with three swellings (each 10 mm) on the periphery of the parotid gland. A low grade malignant lymphoma was diagnosed by fine needle aspiration cytology. Gallium-67 scintigraphy showed mild positivity. On 99mTc pertechnetate scintigraphy, the mild accumulation remained after oral stimulation with a mixture of ascorbic acid and calcium pantothenate. The patient underwent superficial parotidectomy with removal of the cervical masses. Our findings in this patient suggest that 99mTc positivity may constitute a clue to the preoperative diagnosis of NSLA that has pathologically overlapping sites with Warthin tumor.

16.
Laryngoscope Investig Otolaryngol ; 3(3): 191-197, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30062134

RESUMO

BACKGROUND: A malfunction or impairment of swallow function can potentiate aspiration events and interfere with both quality of life and survival. Establishing an animal model for swallow research would provide a better understanding of its pathophysiology and would also allow for the development and validation of physiologically based clinical interventions to improve swallow function. Two requirements define the ideal model for longitudinal exploration: 1) identification of species similar to human in form and function; and 2) provision for reliable and reproducible evoked swallow under general anesthesia and one that would also support a longitudinal study design. OBJECTIVE: We hypothesize that an anesthetized porcine model under dexmedetomidine-based or ketamine-based anesthesia will support a reproducible and stable evoked swallow response. METHODS: Seven neutered male Yorkshire pigs were anesthetized using combinations of dexmedetomidine-based or ketamine-based anesthesia for induction and maintenance of anesthesia during the experimental portion of our study. Single stimulation of iSLN or vagus nerve, bilateral simultaneous single stimulation of iSLN or vagus nerve, and stimulus trains applied to afferent nerves were performed. RESULTS: None of the seven pigs demonstrated evoked swallow events, both during inhalational anesthesia (1.0 MAC) or during post-washout intravenous anesthesia (dexmedetomidine, ketamine/fentanyl or ketamine alone). CONCLUSION: Our results support a high degree of organizational neurophysiologic complexity characterizing the swallow reflex and highlight the challenges and limitations of intraoperative study in survival models. LEVEL OF EVIDENCE: NA Laryngoscope, 2018.

17.
J Clin Invest ; 113(4): 561-8, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14966565

RESUMO

Inorganic phosphate is essential for ECM mineralization and also as a constituent of important molecules in cellular metabolism. Investigations of several hypophosphatemic diseases indicated that a hormone-like molecule probably regulates serum phosphate concentration. FGF23 has recently been recognized as playing important pathophysiological roles in several hypophosphatemic diseases. We present here the evidence that FGF23 is a physiological regulator of serum phosphate and 1,25-dihydroxyvitamin D (1,25[OH]2D) by generating FGF23-null mice. Disruption of the Fgf23 gene did not result in embryonic lethality, although homozygous mice showed severe growth retardation with abnormal bone phenotype and markedly short life span. The Fgf23(-/-) mice displayed significantly high serum phosphate with increased renal phosphate reabsorption. They also showed an elevation in serum 1,25(OH)2D that was due to the enhanced expression of renal 25-hydroxyvitamin D-1alpha-hydroxylase (1alpha-OHase) from 10 days of age. These phenotypes could not be explained by currently known regulators of mineral homeostasis, indicating that FGF23 is essential for normal phosphate and vitamin D metabolism.


Assuntos
Fatores de Crescimento de Fibroblastos/metabolismo , Fosfatos/sangue , Vitamina D/sangue , Animais , Cálcio/sangue , Feminino , Fêmur/citologia , Fêmur/metabolismo , Fêmur/patologia , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/genética , Marcação de Genes , Túbulos Renais/citologia , Túbulos Renais/metabolismo , Masculino , Camundongos , Camundongos Knockout , Hormônio Paratireóideo/sangue
18.
Clin Chim Acta ; 385(1-2): 35-42, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17644082

RESUMO

BACKGROUND: It is uncertain whether atherosclerosis is accelerated in premenopausal and postmenopausal patients with long-term well-controlled systemic lupus erythematosus (SLE). METHODS: We measured the intima-media thickness (IMT) of the carotid arteries and the cardio-ankle vascular index (CAVI) in 39 women with SLE and in age- and sex-matched controls. RESULTS: In the premenopausal state, carotid plaque was detected only in SLE patients (36%). In the postmenopausal state, the maximum IMT was about 2-fold greater in SLE patients than in control subjects (1.3+/-0.7 vs. 0.7+/-0.2 mm, p<0.001). CAVI was higher in both the premenopausal and postmenopausal SLE patients. The serum amyloid A protein (SAA) was higher in SLE patients in the premenopausal state (p=0.025), while remnant like particle-cholesterol (RLP-C), the homeostasis model assessment of insulin resistance (HOMA-IR), and SAA were significantly increased in postmenopausal SLE patients (p=0.001, p<0.001 and p<0.05, respectively). Multiple regression analysis revealed that the maximum IMT was associated with cumulative PSL dosage (p=0.027) and SAA (p=0.074) in the premenopausal SLE patients, and with HOMA-IR (p<0.001) in the postmenopausal SLE patients. CONCLUSION: Atherosclerosis is accelerated in long-term well-controlled SLE. More attention should be given to subclinical inflammation and insulin resistance in the management of SLE patients.


Assuntos
Aterosclerose/complicações , Aterosclerose/patologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/terapia , Adulto , Aterosclerose/sangue , Biomarcadores , Coagulação Sanguínea , Doenças das Artérias Carótidas/patologia , Doença Crônica/terapia , Feminino , Humanos , Inflamação/patologia , Resistência à Insulina , Lipoproteínas/sangue , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/patologia , Menopausa , Análise de Regressão , Fatores de Tempo
19.
Clin Rheumatol ; 26(1): 101-4, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16391894

RESUMO

Thrombotic thrombocytopenic purpura (TTP) is a rare complication of mixed connective tissue disease (MCTD). In this report, we describe the case of a 73-year-old Japanese woman with MCTD who developed fever, thrombocytopenia, and microangiopathic hemolytic anemia and was diagnosed with MCTD together with TTP. The activity of von Willebrand factor (vWF) cleaving metalloprotease ADAMTS13 was low and considered to have contributed to the disease activity of TTP. The patient died despite intensive treatment of plasma exchange (PEX) and steroid pulse therapy. Autopsy results revealed that the kidneys had platelet and fibrin thrombi, which occluded capillaries and arterioles. These findings were compatible with TTP and the decreased activity of ADAMTS13 was considered to be associated with the disease activity of TTP.


Assuntos
Doença Mista do Tecido Conjuntivo/complicações , Púrpura Trombocitopênica Trombótica/complicações , Proteínas ADAM/sangue , Proteínas ADAM/deficiência , Proteína ADAMTS13 , Idoso , Evolução Fatal , Feminino , Humanos , Doença Mista do Tecido Conjuntivo/sangue , Troca Plasmática , Púrpura Trombocitopênica Trombótica/sangue
20.
Ann Otol Rhinol Laryngol ; 126(2): 152-158, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27913709

RESUMO

OBJECTIVES: Human papillomavirus (HPV) has emerged as a driving cause of head and neck cancer, but investigations outside the West are limited. A p16 immunohistochemistry is a commonly used biomarker for HPV cancers. We sought to investigate the pathology and rates of HPV head and neck oropharyngeal cancer in Japan via p16 immunohistochemistry at 2 institutions in Japan. METHODS: Fifty-nine oropharyngeal specimens from 2 university hospitals in Japan were examined for morphology and p16 immunohistochemistry. The rate of p16 positivity was then determined, and the 2 groups were compared for differences in age, smoking history, gender, and stage of presentation and mortality. RESULTS: The rate of p16 positivity among the oropharyngeal specimens was 29.5%. There were important differences in the pathology compared to morphology usually seen in the US. The patients with p16+ cancer tended to be younger. There was no significant difference in smoking status. Patients with p16+ cancers trended toward better survival. CONCLUSION: There appears to be a geographical difference in HPV rates of oropharyngeal cancers with persistently lower rates in Asian countries when compared to Western Europe and the US. Conclusions about HPV head and neck squamous cell carcinoma (HNSCC) in Western countries may not be generalizable across the globe at this time.


Assuntos
Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/virologia , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/virologia , Neoplasias Orofaríngeas/epidemiologia , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/epidemiologia , Idoso , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Feminino , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Imuno-Histoquímica , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/metabolismo , Neoplasias Orofaríngeas/mortalidade , Infecções por Papillomavirus/metabolismo , Distribuição por Sexo , Fumar/epidemiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço
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