Papel do Receptor Lgr5 no Prognóstico e na Biologia de Sarcomas de Partes Moles / Role of the Lgr5 Receptor in the Prognosis and Biology of Soft Tissue Sarcomas

INTRODUÇÃO: Os sarcomas de partes moles (SPM) de alto grau são neoplasias heterogêneas, de prognóstico ruim e que apresentam poucas alternativas de tratamento. A identificação de marcadores de resposta tumoral ao tratamento, prognóstico, e até ao desenvolvimento de novas drogas, é uma busca incessante para um melhor tratamento dos sarcomas. Neste aspecto, o receptor Lgr5 tem um grande potencial em ser um novo alvo molecular, sendo um marcador de células-tronco das criptas intestinais e glândulas mamárias que também atua como um modulador negativo da sinalização da via Wnt/ß-catenina, uma das mais importantes na biologia de sarcomas emerge como um promissor candidato para estudos pré-clínicos, uma vez que já foi demonstrada sua importância em tumores do trato gastrointestinal. Para isso, os modelos de tumor de xenoenxerto derivado do paciente (PDX) representam uma plataforma valiosa para identificar novos biomarcadores e novos alvos, assim como o Lgr5 para avaliar a resposta à terapia e os mecanismos de resistência. OBJETIVO: Este estudo teve como objetivo estabelecer, caracterizar e testar a proteína Lgr5 através de ensaios in vitro e in vivo para desvendar a importância de Lgr5 na biologia de SPM e estabelecer uma estrutura integrada, convergente e translacional para o estudo deste tipo de tumor. MATERIAIS E MÉTODOS: Para a determinação da expressão de Lgr5 foi estabelecida duas coortes de estudo, uma retrospectiva oriunda do Registro Institucional de Sarcomas e uma prospectiva, onde foram convidados pacientes operados na Instituição com o intuito de gerar Patient-derived xenografts (PDX), um modelo-pré-clínico que possui a capacidade de manter as características moleculares dos tumores dos pacientes. Para isso, foram utilizados fragmentos implantados em camundongos imunossuprimidos para gerar esses modelos tumorais derivados de pacientes, além dos estudos funcionais in vitro utilizando linhagens de SPM para análise de perfil de expressão da proteína Lgr5 através de ensaios com imunofluorescência para verificar a capacidade de expressão de Lgr5, citometria de fluxo para verificar o padrão e quantidade de proteína nas amostras analisadas e western blotting para obter um padrão de marcação da proteína Lgr5. Além dos ensaios funcionais para avaliar a participação da proteína na proliferação, se a expressão da proteína interfere no poder migratório das células e tumores de SPM e capacidade de auto renovação, bem como sua associação com os dados clínicos e dados de sobrevida. RESULTADOS: O Registro Institucional retrospectivo conta com mais de 300 pacientes, já o Registro prospectivo com 70 pacientes que derivaram a geração de 33 PDX. Foi observado que pacientes com H-score superior a 20 apresentaram sobrevida global menor em 5 anos em comparação com o H-score de pacientes com valores inferiores a 20. Agora na outra análise feita, o H-score de pacientes com valores superiores a 25 é pior em comparação com os que apresentaram valores inferiores a 25 nos dados de sobrevida livre de doença. Além disso, células que superexpressam a proteína Lgr5 tem maior capacidade migratória (p= 0.02) e uma tendência de aumento na proliferação e auto renovação. Realizamos o teste de implante dessas populações positivas e negativas de Lgr5, separadas previamente por cell sorting. Para isso foram utilizados animais Balb/c Nude. Sugerindo que a expressão da proteína transduzida pode ser modulada por mecanismos compensatórios que precisam ser explorados. CONCLUSÃO: A construção do Registro Institucional de SPM é um grande passo para o melhor compreendimento da biologia dos Sarcomas, além da possibilidade de estudar novos alvos terapêuticos desse tumor raro, uma vez que os estudos e artigos científicos ainda são muito escassos. A geração dos modelos PDX também foi uma estratégia implantada muito bem executada com a geração de 33 PDX de diversos subtipos histológicos. Além da proteína Lgr5 induzir a migração celular a sua expressão está relacionada a um pior prognóstico, uma vez que, quanto maior a expressão de Lgr5 menor é a sobrevida global do paciente.

INTRODUCTION: High-grade soft tissue sarcomas (STS) are heterogeneous neoplasms with a poor prognosis and few treatment alternatives. The identification of tumor response markers to treatment, prognosis, and even the development of new drugs, is an incessant search for a better treatment of sarcomas. In this aspect, the Lgr5 receptor has great potential to be a new molecular target, being a marker of stem cells of the intestinal crypts and mammary glands that also acts as a negative modulator of the signaling of the Wnt/ß-catenin pathway, one of the most important in the biology of sarcomas emerges as a promising candidate for preclinical studies, since its importance in tumors of the gastrointestinal tract has already been demonstrated. To that end, patient-derived xenograft (PDX) tumor models represent a valuable platform to identify new biomarkers and new targets, as does Lgr5 to assess therapy response and resistance mechanisms. OBJECTIVE: This study aimed to establish, characterize, and test the Lgr5 protein through in vitro and in vivo assays to unravel the importance of Lgr5 in the biology of PMS and to establish an integrated, convergent and translational framework for the study of this type of tumor. MATERIALS AND METHODS: To determine the expression of Lgr5, two study cohorts were established, a retrospective one from the Institutional Registry of Sarcomas and a prospective one, in which patients operated on at the Institution were invited to generate Patient-derived xenografts (PDX), a pre-model -clinical that has the ability to maintain the molecular characteristics of patients' tumors. For this, fragments implanted in immunosuppressed mice were used to generate these tumor models derived from patients, in addition to in vitro functional studies using SPM strains to analyze the expression profile of the Lgr5 protein through immunofluorescence assays to verify the ability to express Lgr5, flow cytometry to verify the pattern and amount of protein in the analyzed samples and western blotting to obtain a pattern of labeling of the Lgr5 protein. In addition to functional assays to assess the protein's participation in proliferation, whether protein expression interferes with the migratory power of SPM cells and tumors and self-renewal capacity, as well as its association with clinical data and survival data. RESULTS: The Institutional Retrospective Registry has more than 300 patients, while the Prospective Registry has 70 patients who derived the generation of 33 PDX. It was observed that patients with an H-score greater than 20 had a lower overall survival at 5 years compared to the H-score of patients with values below 20. Now in the other analysis performed, the H-score of patients with values greater than 25 it is worse compared to those who had values less than 25 in the disease-free survival data. Furthermore, cells that overexpress the Lgr5 protein have greater migratory capacity (p=0.02) and a tendency to increase proliferation and self-renewal. We performed the implant test of these positive and negative populations of Lgr5, previously separated by cell sorting. For this, Balb/c Nude animals were used. Suggesting that the expression of the transduced protein can be modulated by compensatory mechanisms that need to be explored. CONCLUSION: The construction of the Institutional Registry of PMS is a big step towards a better understanding of the biology of Sarcomas, in addition to the possibility of studying new therapeutic targets for this rare tumor, since studies and scientific articles are still very scarce. The generation of PDX models was also an implemented strategy very well executed with the generation of 33 PDX of several histological subtypes. In addition to the Lgr5 protein inducing cell migration, its expression is related to a worse prognosis, since the higher the Lgr5 expression, the lower the overall survival of the patient

Clinical characteristics and outcomes of thrombotic microangiopathy in Malaysia

BACKGROUND: Thrombotic microangiopathy (TMA) with non-deficient ADAMTS-13 (a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13) outcome is unknown hence the survival analysis correlating with ADAMTS-13 activity is conducted in Malaysia. METHODS: This was a retrospective epidemiological study involving all cases of TMA from 2012–2016. RESULTS: We evaluated 243 patients with a median age of 34.2 years; 57.6% were female. Majority of the patients were Malay (62.5%), followed by Chinese (23.5%) and Indian (8.6%). The proportion of patients with thrombotic thrombocytopenic purpura (TTP) was 20.9%, 72.2% of which were acquired while 27.8% were congenital. Patients with ADAMTS-13 activity ≥5% had a four-fold higher odds of mortality compared to those with ADAMTS-13 activity <5% (odds ratio: 4.133, P=0.0425). The mortality rate was 22.6% (N=55). Most cases had secondary etiologies (42.5%), followed by acquired TTP (16.6%), atypical hemolytic uremic syndrome (HUS) or HUS (12.8%) and congenital TTP (6.4%). Patients with secondary TMA had inferior overall survival (P=0.0387). The secondary causes comprised systemic lupus erythematosus (30%), infection (29%), pregnancy (10%), transplant (8%), malignancy (6%), and drugs (3%). Transplant-associated TMA had the worst OS (P=0.0016) among the secondary causes. Plasma exchange, methylprednisolone and intravenous immunoglobulin were recorded as first-line treatments in 162 patients, while rituximab, bortezomib, vincristine, azathioprine, cyclophosphamide, cyclosporine, and tacrolimus were described in 78 patients as second-line treatment. CONCLUSION: This study showed that TMA without ADAMTS-13 deficiency yielded inferior outcomes compared to TMA with severeADAMTS-13 deficiency, although this difference was not statistically significant.

Nefropatía por IgA y microangiopatía trombótica / IgA Nephropathy and Thrombotic Microangiopathy

INTRODUCCIÓN: La asociación de microangiopatía trombótica (MAT) y nefropatía por IgA (N.IgA) resulta un hecho conocido, aunque su prevalencia, patogénesis y evolución aún no se han esclarecido. MATERIAL Y MÉTODOS: Se realizó un estudio descriptivo y retrospectivo de 12 pacientes con N.IgA y MAT (N.IgA-MAT), diagnosticadas por biopsia renal en nuestro hospital, para analizar las características clinicopatológicas. Todas las biopsias renales se procesaron para microscopía óptica e inmunofluorescencia. RESULTADOS: La prevalencia de pacientes con N.IgA-MAT fue del 4.4% (12/274). La edad media fue de 33 años y 58.3% eran hombres, con tensión arterial sistólica y diastólica media al momento del diagnóstico de 171.3±53mmHg y 97.5±19.8mmHg respectivamente. La proteinuria promedio resultó 5.3 ± 3.7g/24hs y en 8 pacientes estuvo en rango nefrótico. Se constató deterioro de la función renal en 11 pacientes, con una creatinina sérica media de 7.2±4.7mg/dl. Ningún paciente presentó hallazgos clínicos o de laboratorio sugestivos de microangiopatía trombótica. La biopsia renal mostró MAT aguda con trombos de fibrina arteriolares en el 75% y lesiones crónicas con hiperplasia intimal concéntrica y aspecto de "catáfilas de cebolla" en 83.3%, que se asociaron con un elevado porcentaje de esclerosis glomerular global (72%), atrofia tubular moderada (38.6%) y/o fibrosis intersticial (31.3%). En 91.7% de los casos, la MAT se asoció con grado histológico V. CONCLUSIÓN: La prevalencia y significado de la asociación de N.IgA-MAT nos plantea si la MAT es causa o consecuencia de estadios avanzados de N.IgA. Distintos estudios clinicopatológicos han demostrado que la MAT juega un rol importante en la progresión de la N.IgA. La relación de MAT con los niveles de creatinina sérica y proteinuria apoya su rol en la progresión de la N.IgA. Mientras que las MAT sistémicas cursan con afección de múltiples órganos, en estos casos el riñón fue el único órgano comprometido. La injuria endotelial y subsecuente trombosis microvascular conducen a la isquemia y disfunción renal. El hallazgo de MAT-N.IgA en pacientes con presión arterial normal al momento de la biopsia sugiere que ni la hipertensión ni las lesiones parenquimatosas avanzadas son prerrequisitos para el desarrollo de MAT. Los mecanismos fisiopatológicos que conducen a la injuria endotelial son aún desconocidos, pero parecerían ser distintos a los de la nefropatía hipertensiva maligna

INTRODUCTION: Although the association between thrombotic microangiopathy (TMA) and IgA nephropathy (IgAN) is a known fact, its prevalence, pathogenesis and progression are not clear yet. METHODS: A descriptive, retrospective study involving 12 patients with IgAN and TMA (IgAN-TMA) was carried out; patients were diagnosed by a renal biopsy performed in our hospital in order to analyze clinicopathologic features. All the biopsy samples were processed for light microscopy and immunofluorescence. RESULTS: The prevalence of patients with IgAN-TMA was 4.4% (12/274). The mean age was 33 and 58.3% of the subjects were men, showing, during diagnosis, mean systolic and diastolic blood pressure values of 171.3±53 mmHg and 97.5±19.8 mmHg, respectively. The average amount of protein in urine was 5.3 ± 3.7g/24 h and 8 patients had nephrotic-range proteinuria. Impairment of renal function was found in 11 patients, with a mean serum creatinine level of 7.2±4.7 mg/dL. No clinical or laboratory findings suggested thrombotic microangiopathy in any of the patients. The renal biopsy showed acute TMA with arteriolar fibrin thrombi in 75% of the subjects and 'onion-skin-like' chronic lesions with concentric intimal hyperplasia in 83.3% of them, which were associated with a high percentage of global glomerulosclerosis (72%), moderate tubular atrophy (38.6%) and/or interstitial fibrosis (31.3%). In 91.7% of the cases, TMA was related to histological grade 5. CONCLUSIONS: The prevalence and significance of the relationship between IgAN and TMA pose the question of whether TMA is the cause or consequence of advanced stage IgAN. Several clinicopathologic studies have proved that TMA plays a major role in IgAN progression. The connection of TMA with creatinine serum and proteinuria levels seems to support this conclusion. While systemic TMA usually affects multiple organs, in these cases, the kidney was the only one compromised. Endothelial injury and the subsequent microvascular thrombosis lead to ischaemia and kidney failure. The TMA-IgAN finding in patients with normal blood pressure at the time of the biopsy suggests that neither hypertension nor advanced parenchymal lesions are a prerequisite for the development of TMA. The physiopathological mechanisms leading to endothelial injury are still unknown, but appear to be different from those of malignant nephrosclerosis

Effects of VEGF-C, VEGFR-3 and LYVE-1 on Lymphangiogenesis and Prognosis in Gastric Cancer / 天津医药

Objective To study the role of expressions of vascular endothelial growth factor C (VEGF-C), vascular endothelial growth factor receptor-3 (VEGFR-3) and lymphatic vessel hyaluronan receptor-1(LYVE-1) on the lymphangio-genesis and prognosis in gastric cancer. Methods The tissue microarray technology was used to detect the expressions of VEGF-C, VEGFR-3 and LYVE-1 in 125 gastric cancer specimens, 96 adjacent normal tissues and 20 benign gastric lesion samples. The lymphatic vessel density (LVD) marked by Podoplanin was detected as well. Results The positive rates of VEGF-C, VEGFR-3 and LYVE-1 in gastric cancer tissues were 62.4%, 56.0%and 58.4%, which were significantly higher than those in adjacent normal tissues (10.4%,12.5%and 9.4%) and benign gastric lesion tissues (20%, 30%and 25%, P<0.05). The LVD score was significantly higher in gastric intra-tumoral and peri-tumoral samples (2.98±0.81 and 4.22±1.09) than that in adjacent normal tissues or benign gastric lesion samples (1.82±0.63 or 0.89±0.45, P<0.01). The LVD score was significantly higher in peri-tumoral samples than that of intra-tumoral samples (P<0.01). There was a positive relationship between expression levels of VEGF-C,VEGFR-3 and LYVE-1 with LVD (P<0.05). The positive expressions of the three indexes were the risk factors of lymph node metastasis and distant metastasis (P<0.05). There was a significantly longer 5-year survival rate in patients with negative expression of the three indexes (P<0.05). Conclusion VEGF-C, VEGFR-3 and LYVE-1 proteins were positively highly expressed in gastric cancer tissues, which were risk factors affecting the progno-sis of gastric cancer. The expression levels of the three indexes can be used to predict the prognosis and lymphangiogenesis of gastric cancer.

A Case of Atypical Thrombotic Microangiopathy

We report the case of a 14-year-old girl, diagnosed with atypical thrombotic microangiopathy (TMA). The patient presented with persistent fever, nausea, and newly developed peripheral edema. Her laboratory findings indicated chronic anemia with no evidence of hemolysis, thrombocytopenia, or elevated serum creatinine level. A few days after hospitalization, acute renal failure and fever worsened, and proteinuria developed. On day 40 of hospitalization, she experienced a generalized tonic seizure for 5 min, accompanied by renal hypertension. Brain magnetic resonance imaging revealed posterior reversible leukoencephalopathy syndrome. After steroid pulse therapy, a renal biopsy was performed because of delayed recovery from thrombocytopenia. The biopsy findings showed features of thrombotic microangiopathic hemolysis with fibrinoid change restricted. Current diagnostic criteria for TMA have focused on thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, and diagnosis is based on the clinical presentation and etiology, with the consequence that idiopathic and atypical forms of TMA can be overlooked. Developing effective tools to diagnose TMA, such as studying levels of ADAMTS13 or testing for abnormalities in the complement system, will be the first step to improving patient outcomes.

A Case of Atypical Thrombotic Microangiopathy

We report the case of a 14-year-old girl, diagnosed with atypical thrombotic microangiopathy (TMA). The patient presented with persistent fever, nausea, and newly developed peripheral edema. Her laboratory findings indicated chronic anemia with no evidence of hemolysis, thrombocytopenia, or elevated serum creatinine level. A few days after hospitalization, acute renal failure and fever worsened, and proteinuria developed. On day 40 of hospitalization, she experienced a generalized tonic seizure for 5 min, accompanied by renal hypertension. Brain magnetic resonance imaging revealed posterior reversible leukoencephalopathy syndrome. After steroid pulse therapy, a renal biopsy was performed because of delayed recovery from thrombocytopenia. The biopsy findings showed features of thrombotic microangiopathic hemolysis with fibrinoid change restricted. Current diagnostic criteria for TMA have focused on thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, and diagnosis is based on the clinical presentation and etiology, with the consequence that idiopathic and atypical forms of TMA can be overlooked. Developing effective tools to diagnose TMA, such as studying levels of ADAMTS13 or testing for abnormalities in the complement system, will be the first step to improving patient outcomes.

An evaluation of p16INK4a expression in cervical intraepithelial neoplasia specimens, including women with HIV-1

Although several studies have evaluated the role of p16INK4a as a diagnostic marker of cervical intraepithelial neoplasia (CIN) and its association with disease progression, studies regarding the role of p16INK4a in human immunodeficiency virus (HIV)-infected patients remain scarce. The present study was designed to determine the potential utility of p16INK4a as a diagnostic marker for CIN and invasive cervical cancer in HIV-positive and negative cervical specimens. An immunohistochemical analysis of p16INK4a was performed in 326 cervical tissue microarray specimens. Performance indicators were calculated and compared using receiving operating characteristics curve (ROC)/area under the curve. In HIV-1-negative women, the percentage of cells that was positive for p16INK4a expression was significantly correlated with the severity of CIN (p < 0.0001). A ROC curve with a cut-off value of 55.28% resulted in a sensitivity of 89%, a specificity of 81%, a positive predictive value of 91% and a negative predictive value of 78%. HIV-seropositive women exhibited decreased expression of p16INK4a in CIN2-3 specimens compared with HIV-negative specimens (p = 0.031). The ROC data underscore the potential utility of p16INK4a under defined conditions as a diagnostic marker for CIN 2-3 staging and invasive cervical cancer. HIV-1 infection, however, is associated with relatively reduced p16INK4a expression in CIN 2-3.

Tracionamento de incisivo central permanente superior impactado com fio de beta-titânio (TMA) durante a dentadura mista / Impacted incisor traction with beta-titanium wire during the mixed dentition

A localização intraóssea de um incisivo central superior, e o consequente atraso de sua irrupção, é um problema que afeta a autoestima das crianças. além disso, a falta de função mastigatória localizada, associada à migração dos dentes vizinhos, revela a importância do tratamento interceptivo nesses casos. A escolha da liga de beta-tirânio para o tratamento do incisivo foi fundamental na fórmula de Bustone (1981): rigidez do aparelho = rigidez do fio X desenho do aparelho. A combinação do módulo de elasticidade dessa liga ortodôntica com a configuração das alças de nivelamento permitiu a aplicação de forças leves e controle do movimento extrusivo.

Perda de amostras em tissue microarray: comparação entre técnicas com uso de fita adesiva comercial, lâminas silanizadas pelo método tradicional ou por método modificado / Loss of tissue samples in the tissue microarray: comparison between techniques using commercial adhesive tape, silane-coated microslides by the conventional method and by a modified technique

Introdução/objetivo: O microarranjo tecidual, ou tissue microarray (TMA), permite avaliar múltiplas amostrasde tecido em um único bloco. Um dos problemas do TMA é o descolamento dos cortes teciduais, por isso, para reduzir essa perda, tem-se utilizado fita adesiva especial comercial. Não há relatos comparando o uso dessas fitas adesivas com a técnica de silanização modificada. O objetivo desse estudo foi comparar as perdas de cortes entre lâminas usando fitas adesivas comerciais, lâminas silanizadas por técnica convencional elâminas silanizadas por técnica modificada, com menor consumo de acetona. Material e método: O TMA foiconstruído com blocos de tecido hepático, em dispositivo de base fixa, colocando-se 32 cilindros de 2 mmde diâmetro em duplicata e espaçamento de 2,2 mm. Quinze secções de 4 μm foram colocadas em lâminas silanizadas a 4% por técnica convencional (grupo 1), 15 em lâminas silanizadas com técnica modificada (6%de silano e com uso mínimo de acetona) (grupo 2) e 15 em lâminas com fita adesiva comercial de acordo comas recomendações do fabricante (grupo 3). Todas as lâminas foram processadas por imuno-histoquímica para citoqueratina 18, com recuperação antigênica em tampão citrato pH 6, em microondas. As perdas de amostrasforam quantificadas e expressas como: perda total (≥ 80%), quase total (75% a 79%) ou parcial (50% a 74%).Resultados: A perda de tecidos foi semelhante nos três grupos: com silanização tradicional, modificada oufita adesiva comercial (4,9 vs. 3,1 vs. 8,1, respectivamente) (análise de variância [ANOVA], p = 0,3654). Umadas lâminas com a fita adesiva apresentou descolamento artefatual de todos os tecidos e outra de 20 tecidosem um dos lados. Nenhuma das lâminas silanizadas apresentou tal artefato. Conclusão: Lâminas silanizadas têm resultados satisfatórios, requerem menos treinamento técnico e reduzem os custos da utilização do TMA justificando seu uso em pesquisa...

Introduction/objective: The tissue microarray (TMA) technique allows the evaluation of multiple tissue samplesin a single block. One of the problems of TMA is the ungluing of tissue sections, thus commercial adhesive tape has been used to reduce this loss. There are no reports comparing the use of the commercial adhesive tape with the use of the modified silane-coated technique. The objective of this study was to compare section loss in slides using commercial adhesive tape, silane-coated microslides with the conventional technique or with the modified technique. Material and method: The TMA was constructed with hepatic tissue blocks embedded in paraffin, using a fixed base device, placing 32 cylinders of 2 mm in diameter in duplicate and 2.2 mm apart from each other. Fifteen 4-μm sections were placed on conventional silane-coated microslides at 4% (Group 1), 15 on silane-coated microslides with a modified technique (6% of silane and minimum use of acetone) (Group 2), and 15 on slides using commercial adhesive tape, according to the manufacturer's recommendations (Group 3). All microslides were processed by immunohistochemistry for cytokeratin 18, with antigen retrieval accomplished by incubation with citrate buffer pH 6.0 with microwave enhancement. Samples loss was quantified and expressed as: total (≥ 80%), almost complete (75% to 79%) or partial (50% to 74%). Results: The loss of sections was similar in all three groups (4.9 vs. 3.1 vs. 8.1, respectively) (analysis of variance [ANOVA], p = 0.3654). One slide usingcommercial adhesive tape showed artifactual ungluing of all sections and another one showed loss of 20 sampleson one side of the slide. None of the silane-coated microslides showed such artifact. Conclusions: Silane-coated microslides show adequate results, require less technical training and reduce the cost of TMA procedure, whatjustifies their use in research...

ADAMTS13 Activity in Childhood Hemolytic Uremic Syndrome(HUS)

PURPOSE: HUS usually occurs in children after infection with shiga toxin-producing microorganism(D+HUS). In contrast, non-postdiarrheal(D-) HUS occurs at any age and has a high rate of relapse and a poor prognosis. The clinical presentation of D-HUS is similar to that of thrombotic thrombocytopenic purpura(TTP). Recently severe deficiencies of ADAMTS13 were reported not only in TTP and D- HUS but also in D+ HUS during their acute phase. The purpose of the study is to evaluate the plasma ADAMTS13 activity in D+ and D-HUS. METHODS: Nineteen children with HUS(D+ HUS 12 and D- HUS 7) were enrolled. The assays of plasma ADAMTS13 activity were performed during the acute stage in the D+ HUS and at various stages of relapsing courses in the D- HUS patients by multimer assay, based on electrophoresis. RESULTS: The median plasma activity of ADAMTS13 in D+ HUS and D- HUS were 80.9%(37.8-132.4%) and 53.9%(1.0-94.1%), respectively, which were not statistically significantly different from control(86.4%, 34.2-112.3%)(P>0.05). One boy with D- HUS had severe deficiency of ADAMTS13(1.0%). His platelet count was normalized temporarily by fresh frozen plasma infusion. CONCLUSION: We have demonstrated that there is no significant difference of the plasma ADAMTS13 activity between D+ HUS, D- HUS and control. We detected severe deficiency of ADAMTS13 in one boy who presented with relapsing episodes of D- HUS. ADAMTS13 deficiency should be considered in the subgroup of D- HUS especially with early onset and recurrent courses. Plasma therapy can be beneficial in this subgroup.

A photoelastic study of the stress distribution on canine retraction by segmented TMA T-loop spring / 대한치과교정학회지

The segmented TMA T-loop spring, used for reciprocal space closure and described by Burstone, was used to achievebodily movement of canine. Photoelastic analysis is a technique for the transformation of internal stress into visible light patterns. The two-dimensional photoelastic stress analysis was performed, and stress distribution was recorded by photography. The purpose of this study was to visualize photoelastically the distribution of forces transmitted to the alveolus and surrounding structures using new segmented TMA T-loop spring for canine retraction. The results were as follows: 1. Decreased activation produced decreased stress of upper 1st. premolar extraction site and increased intrusive stress of upper 1st. molar, regardless of T-loop position. 2. At 5mm activation, More posterior positioning of T-loop produced an increased stress in upper 1st. premolar extraction site. 3. At 3mm activation, More posterior positioning of T-loop produced an increased stress in upper 1st. premolar extraction site and mesial lower half of upper 1st. molar mesio-buccal root. 4. At 1mm activation, More anterior positioning of T-loop produced an increased stress in upper mesial and blew apex area of upper canine root. 5. 0.25 B/L ratio and 3mm activation produced bodily movement of canine. To summarize, desired tooth movement and anchorage requirement is possible by altering the activation and mesio-distal position of the T-loop spring.

A FEM study about the initial stress distribution on canine altered by the application point of preangulated TMA T-loop spring / 대한치과교정학회지

The purpose of this study was to find the difference of stress distribution on canine altered by the application point of preangulated T-loop spring T-loop spring. For this study, the finite element models of upper left canine, upper left second premolar and upper left first molar were made. Also, the finite element models of 0.017X0.025 inch preangulated, preactivated T-loop spring and 0.018X0.025 inch stainless steel wire were made. Three types of T-loop spring were made : the middle of activated T-loop is positioned in accordance with the middle position of distance of bracket position of both the canine and first molar, 2mm anterior, 2mm posterior. We compared the forces and the distribution of stress that were generated by the difference of position of T-loop spring. The results were as follows. 1. All of the 3 types of T-loop spring showed the similar retraction forces. 2. All showed the similar amount & pattern of stress distribution. 3. The centers of rotation of canine in 3 types of T-loop spring were same and were positioned between C and D plane. 4. The canine showed the intrusive force by 2mm anterior positioned T-loop spring, but the extrusive force by 2mm posterior positioned T-loop spring. Neverthless, because of the small amount of the forces, the effect of vertical force was not significant.

Regional load deflection rate of multiloop edgewise archwire / 대한치과교정학회지

This study was conducted in order to analyze the mechanical characteristics of multiloop edgewise archwire(MEAW). The purposes were 1) to compare load deflection rate(LDR) of MEAW with that of various other archwires in the individual interbracket span, 2)to compare the wire stiffness in the interbracket span with that in the multi-L-loop region (the span from distal border of the bracket of the lateral incisor to the mesial border of the buccal tube of second molar), and 3) to verify the experimental results with theoretically derived formula. The single L-loops five different horizontal lengths and multi-L-loops for the upper and lower arches were made out of .016 X .022 permachrome stainless steel wire. Straight segment of plain stainless steel, TMA and NiTi wire of the same dimension were prepared. The LDR was measured using Instron model 4466 with the load cell of 50N capacity at cross head speed of 1.0mm/min, and maximum deflection of 1.0mm. Five specimens were tested under each experimental condition. The wire stiffness number for each interbracket region and multi-L-loop region was calculated from the LDR and the interbracket spans. By dividing the theoretical model of multi-L-loop into 35 linear segments, the energy stored in each segment was obtained. Then the LDR and wire stiffness of single L-loop and multi-L-loop were calculated and compared. The findings were as follows : 1) The average LDR of MEAW in the individual interbracket region was 1/1.53 of that of the NiTi, 1/247 of TMA and 1/5.16 of the plain stainless steel wire. 2) The wire stiffness of MEAW in the multi-L-loop region was 1.53 times larger than that in the interbracket region, and the LDR was almost twice as large as that of NiTi in that region. 3) According to the theoretically derived equation, the wire stiffness of the single L-loop was lower than that of multi-L-loop. The results of this study suggest that MEAW has the unique mechanical property which could allow individual tooth movement and transmit elastic force effectively through the entire arch wire.

A photoelastic study on the stress distribution in bone by the transpalatal lingual arch / 대한치과교정학회지

The purpose of this study was to investigate the stress distribution and intensity derived from the transpalatal lingual arch in the investing bone composed of photoelastic material(PL-3). The transpalatal lingual arch wire was deflected in the horizontal and vertical direction to give the various conditions. The two-dimensional photoelastic stress analysis was performed, and the stress distrebution was recored by photofraphy. The results were as follows: 1. In bilateral expansion, as horizontal deflection was singly applied, the stress was more concentrated on the root apex in square free end than round. In square free end, as vertical deflection was increased gradually, the black line meaning center of rotation moced inferiorly togerher with the increment of whole fringes. 2. In application of vertical deflection on anchorage side for unilateral expansion, the stress distribution that expansive force leaned to expansion side was observed. As vertical deflection increased, the extruding stress was obesrved on molar of expansion side. And as horisontal deflection increased, the tipping stress on the molar of anchorage side was observed. 3. In unilateral rotation with the asymmetric toe-in, the fringe appeared on the distal aspect of root apex.

A photoelastic study on the initial stress distribution of 3 types TMA multi-vertical loop arch wire / 대한치과교정학회지

Multi -Vertical Loop Arch Wire(MVLAW) is a kind of appliance for uprighting the mesially inclined posterior teeth axes simultaneously. In this study MVLAW was classified as 3 types by modifing the vertical loop design and named type A, B and C. Each MVLAW was fabricated from .017" x .025" TMA wire and preactivated at the distal end of the open vertical loop with 10 degree tip-back bend(type B has an electric welding stop at the distal end of each loop and type C has no electric welding stop). Type A MVLAW was preactivated at the apex of each open vertical loop with 10 degree tip-back bend(the electric welding stop of type A is positioned at the mesial side of each loop). The aim of the present study was to identify when and which MVLAW is more effective to correct the buccal segment axes simultaneously. The photoelastic overview of the upper and lower right quadrant showed that stress concentrations were observed in its photoelastic model. The obtained results were as follows: 1. Higher level compression can be seen clearly at the distal curvature of the lower 1st and 2nd molar when A type MVLAW was applied without short class III elastic, but mild compression cannot be seen at the distal curvature of lower anterior teeth using the class III elastic. 2. Higher concentration was presented at the mesial curvature from the lower 1st premolar to the 2nd molar than the anterior teeth when B type MVLAW without short class III elastic was applied, but using the short class III elastic, higher concentration of compression was presented in the anterior teeth area. 3. Areas of higher compression and tension were not observed at the mesial and distal curvature of the entire lower teeth except lower central and lateral incisors in C type MVLAW without short class III elastic, but using the short class III elastic, higher concentration was seen at the mesial curvature of the lower 1st premolar and lower anterior teeth.

A photoelastic study on the initial stress distribution by 3 types of molar uprighitng spring / 대한치과교정학회지

The aim of this investigation was to identify which spring is more suitable for uprighting of the 30 degree inclined lower second molar in different situations. Between four different molar uprighting springs which were A, B, C type and T-Ioop spring, the author tested T-loop spring as a control material and the other springs were experimental group, Each spring was fabricated from .017" X .025" TMA wire and preactivated with 40 degree tip-back bend. Stabilizing unit included from the lower right central incisor to the lower right second premolar which were made by acrylic resin. The photoelastic overview of the lower right quadrant showed that stress concentrations were observed in its photoelastic model. The obtained results were as follows. 1. Higher concentration of compression can be seen clearly at the distal curvature than the mesial of the lower second molar when A type uprighting spring was applied, which can be used as a space regainer. 2. Higher level compression was presented at the mesial root apex area than the distal of the lower second molar in B type uprighting spring, which can be used as a space closer. 3. Areas of higher compression and tension were observed about the mesial and distal root of the lower second molar than A and B type in C type uprighting spring, which can be used as a partial space regainer.

Positive Criterion And Clinical Significance of Serum TGA TMA Titers in Patients with Chronic Lymphocytic Thyroiditis / 昆明医科大学学报

Serum TGA TMA titers were determined by a radioimmunoassay in 117 patients divided into five groups whose diagnoses of various thyroid diseases were confirmed with thyroid biopsy and 80 normal subjects. The serum TGA, TMA titers of the chronic lymphocytic thyroiditis (CLT) group was Statistically higher than those of other groups (P