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  • 1
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Multiple endocrine neoplasia type 2A (MEN2A) is a dominantly inherited cancer syndrome characterized by medullary thyroid carcinoma, pheochromocytoma, and parathyroid hyperplasia. The gene responsible for MEN2A was localized by linkage analysis to chromosome 10q11.2 in 1987, and recently mutations in RET, a proto-oncogene in the candidate region, were discovered in patients with MEN. The majority of mutations found so far in MEN2A patients have been located in nucleotide sequences encoding cysteine residues in the extracellular domain of RET. To characterize MEN2A germline alterations in the Japanese population, we screened DNA from eight unrelated patients for mutations in exons 10 and 11 of the RET proto-oncogene and found mutations in all eight patients, at codons 618, 620, or 634; each of these sites encodes a cysteine residue in the extracellular domain of RET. The mutations were confirmed in other affected individuals in the respective families by digestion of polymerase chain reaction (PCR) products containing the mutated codons with restriction enzymes (RsaI, CfoI, or AluI) for which cleavage sites had been generated by the specific genetic alteration. These PCR-restriction enzyme systems will be useful for genetic diagnosis in members of families carrying these mutations.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    World journal of surgery 14 (1990), S. 431-435 
    ISSN: 1432-2323
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé La protéine BGP (bone Gla protein) est une protéine dépendante de la vitamine K, marqueur de renouvellement osseux. Pour savoir si la BGP était un indicateur utile de parathyroïdectomie chez les patients ayant une hyperparathyroïdie secondaire (HP II), nous avons mesuré les niveaux sériques de BGP. Trente-sept patients ayant une HP II suivis un an au moins après leur parathyroïdectomie ont été étudiés. Tous les patients ont eu une parathyroïdectomie totale avec réimplantation. Nous avons également mesuré la BGP chez 46 patients hémodialysés chroniques depuis au moins 3 ans comme témoins. Le taux sérique de BGP (normal: 〈6.5 ng/ml) étaient très augmentés chez 37 patients parathyroïdectomisés, leurs valeurs allant de 4.2 ng/ml à 645 ng/ml, la moyenne étant 278.8±159.8 ng/ml (moyenne±écart type) comparée à 65.0±85.2 ng/ml chez les 46 témoins (p〈0.001). Les patients ayant une BGP élevée se plaignaient de douleurs osseuses et articulaires sévères. La BGP sérique des patients ayant eu une parathyroïdectomie était en corrélation significative avec les phosphatases alcalines sériques et la mPTH (p〈0.001 pour les deux). Le poids total des tumeurs parathyroïdes réséquées était de 2,152±1,368 mg, le poids tumoral extrême allant de 200 à 5,600 mg. Le taux de BGP était en corrélation significative avec le poids tumoral (r=0.656,p〈0.001). Les 2 patients qui avaient des niveaux BGP au-dessous de 10 ng/ml avaient des poids tumoraux de seulement 470 mg et 240 mg, respectivement, et leur Symptomatologie douloureuse n'a pas changé en postopératoire, même si leur taux de mPTH a augmenté.Ces résultats suggèrent que le mesure de BGP est une méthode sensible pour détecter le renouvellement osseux augmenté et est une méthode utile dans l'indication d'une parathyroïdectomie pour HP II.
    Abstract: Resumen La proteína Gla ósea (PGO) es una proteína vitamina K-dependiente que es marcador del recambio óseo. Con el objeto de determinar si la PGO sérica es un indicador útil del resultado de la paratiroidectomía en pacientes con hiperparatiroidismo secundario, procedimos a medir los niveles séricos de PGO. Treinta y siete pacientes con hiperparatiroidismo seguidos por más de un año fueron estudiados; todos los pacientes fueron sometidos a paratiroidectomía y autotrasplante de glándula paratiroides. Cuarenta y seis pacientes tratados con hemodiálisis crónica por más de 3 años fueron utilizados como controles. Los niveles séricos de PGO (normal: 〈6.5 ng/ml) aparecieron marcadamente elevados en 37 de los pacientes sometidos a paratiroidectomía, con un rango de 4.2 ng/ml a 645 ng/ml y un valor promedio de 278.8±159.8 ng/ml, versus 65.0±85.2 ng/ml en los 64 pacientes control (p〈0.001). Los pacientes con niveles altos de PGO sufrían de severos dolores óseos y articulares. Los niveles séricos de PGO en los pacientes sometidos a paratiroidectomía aparecieron significativamente correlacionados con los niveles de fosfatasa alcalina sérica y de mPTH (p〈0.001 para ambos). El peso total de los tumores paratiroideos resecados fue 2,152±1,368 mg, con un rango de 200 mg a 5,600 mg. Se observó una correlación altamente significativa entre el nivel de PGO y el peso del tumor (r=0.656,p〈0.001). Los 2 pacientes que exhibieron niveles de PGO inferiores a 10 ng/ml tuvieron tumores con pesos de sólo 470 mg y 240 mg, respectivamente, y no mejoraron de su dolor en el postoperatorio, aunque sus niveles de mPTH ascendieron. Estos resultados sugieren que las determinaciones de PGO representan un método sensible para detectar recambio óseo incrementado y que es de posible utilidad como indicador de paratiroidectomía en pacientes con hiperparatiroidismo secundario.
    Notes: Abstract Bone Gla protein (BGP) is a vitamin K-dependent protein which is a marker of bone turnover. To determine whether serum BGP is a useful indicator for parathyroidectomy in patients with secondary hyperparathyroidism, we measured serum BGP levels. Thirty-seven patients with secondary hyperparathyroidism who were followed up for more than 1 year after parathyroidectomy were studied. All patients underwent total parathyroidectomy and autotransplantation. Controls were 46 patients who were treated by chronic hemodialysis for more than 3 years. Serum BGP levels (normal: 〈6.5 ng/ml) were markedly increased in 37 patients with parathyroidectomy, ranging from 4.2 ng/ml to 645 ng/ml, with a mean value of 278.8±159.8 ng/ml (mean±standard deviation) versus 65.0±85.2 ng/ml in the 46 controls (p〈0.001). Patients with a high BGP level had severe bone and joint pain. Serum BGP in patients with parathyroidectomy was significantly correlated with serum alkaline phosphatase and mPTH (p〈0.001 for both). The total weight of resected parathyroid tumors was 2,152±1,368 mg, and tumor weights ranged from 200 mg to 5,600 mg. There was a highly significant correlation between BGP level and tumor weight (r=0.656,p〈0.001). The 2 patients who showed BGP levels below 10 ng/ml had tumor weights of only 470 mg and 240 mg, respectively, and revealed no improvement of pain postoperatively, although their mPTH levels were increased. These results suggested that BGP measurement is a sensitive method for detecting increased bone turnover and is possibly useful as an indicator for parathyroidectomy in patients with secondary hyperparathyroidism.
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  • 3
    ISSN: 1432-2323
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Cette étude a été élaborée pour identifier 11 antigènes différents, y compris la calcitonine (CT), la peptide codée par le gène calcitonine (PCGC), la peptide de stimulation de la gastrine (PSG), et ACE dans les tumeurs de 36 patients ayant un cancer médullaire de la thyroïde (CMT) avec la technique de coloration immunopéroxidase. La clinique des patients ayant un CMT a été comparée aux données immunohistochimiques pour établir des facteurs influençant le pronostic. Les CMT contenaient de nombreuse substances chimiques chez la plupart des patients. La CT et ACE étaient positifs chez tous les patients. La PCGC et la PSG se coloraient positivement chez 96.6 et 82.9% des patients à CMT, respectivement, suggérant que la PCGC et la PSG sont des marqueurs tumoraux potentiels pour le CMT. Dans les cellules tumorales, CT, PSGC., et PSG ont été souvent identifiées dans les mêmes cellules. En général on a trouvé plus d'antigènes chez les patients à CMT familiaux que chez les patients à CMT sporadiques. Chez les 2 patients inopérables chez qui l'évolution était extrêmement agressive, ces tumeurs étaient histologiquement indifférenciéés et la coloration pour ces hormones, pauvres, suggèrant une perte des caractères spécifiques neurendocrines de la tumeur. Chez ces 2 patients, la distribution de CT et d'ACE était inversement proportionnelle l'une par rapport à l'autre: la quantité de CT était réduite dans les cellules alors que la coloration pour l'ACE était homogène. Les résultats de cette étude suggèrent que la PCGC et la PSG, comme le sont déjà la CT et l'ACE, sont peut-être des marqueurs tumoraux pour le CMT. Il est possible que la CT et l'ACE puissent être utilisés pour différencier les patients à haut degré de malignité.
    Abstract: Resumen Este estudio fue diseñado con el fín de identificar 11 antígenos diferentes, incluyendo calcitonina (CT), péptido calcitonina gen-relacionada (PCGR), péptido liberador de gastrina (PLG), y antígeno carcinoembriónico (ACE), en los tumores de 36 pacientes con carcinoma medular de tiroides (CMT) utilizando técnicas de coloración con inmunoperoxidasa. Además, se compararon las características clínicas del CMT con los hallazgos inmunohistoqufmicos para definir factores que tengan influencia sobre el pronóstico. Se encontró que el CMT contiene una variedad de productos en muchos de los pacientes y que la CT y el ACE fueron positivos en la totalidad de los pacientes. El PCGR y PLG mostraron coloración positiva en 96.6% y 82.9% de los pacientes, respectivamente, lo cual sugiere que el PCGR y el PLG son noveles marcadores tumorales del CMT. En las células tumorales comparadas en secciones adyacentes apareadas, las 3 hormonas, CT, PCGR, y PLG fueron frecuentemente demostrados en células idénticas. Los pacientes con enfermedad de tipo familiar exhibieron mayor número de sustancias múltiples que los pacientes con enfermedad esporádica. En los 2 pacientes inoperables con progresión tumoral de extrema agresividad, los tumores mostraron indiferenciación en la histología y pobre coloración para las hormonas péptidos, lo cual sugiere que se habían perdido sus cualidades específicas como tumores neuroendocrinos. Estos 2 pacientes, en particular, revelaron una relación inversa entre la distribución de CT y de ACE, tal que pequeñas cantidades de CT estaban presentes en células que exhibían coloración homogénica para ACE. Este estudio sugiere que el PCGR y el PLG, además de la CT y el ACE, pueden ser potenciales marcadores tumorales para CMT. La CT y el ACE pueden ser posibles marcadores para diferenciar los pacientes con severo grado de malignidad de aquellos con malignidad ordinaria.
    Notes: Abstract This study was designed to identify 11 different antigens including calcitonin (CT), calcitonin gene-related peptide (CGRP), gastrin-releasing peptide (GRP), and carcinoembryonic antigen (CEA), in the tumors of 36 patients with medullary thyroid carcinoma (MTC) using immunoperoxidase staining techniques. In addition, clinical features of MTC patients were compared with the immunohistochemical findings to establish factors influencing prognosis. MTC was found to contain various products in many patients and CT and CEA were positive in all patients. CGRP and GRP showed positive staining in 96.6% and 82.9% of MTC patients, respectively, suggesting that CGRP and GRP are novel tumor markers for MTC. In tumor cells, CT, CGRP, and GRP were often revealed in identical cells. Familial patients showed more multiple substances than sporadic patients. In the 2 inoperable patients with extremely aggressive progression, tumors showed undifferentiated histology and poor staining for peptide hormones, suggesting that specific qualities such as neuroendocrine tumor had been lost. These 2 patients particularly revealed an inverse relationship between CT and CEA distribution such that small amounts of CT were present in cells which have homogenous staining for CEA. This study suggests that CGRP and GRP, in addition to CT and CEA, may be a histologically potential tumor marker for MTC. CT and CEA may be possible markers for differentiating patients with high malignancy from those with ordinary malignancy.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Archives of orthopaedic and trauma surgery 102 (1984), S. 203-205 
    ISSN: 1434-3916
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die erfolgreiche Rekonstruktion eines ausgedehnten Tibiadefektes mit einem freien, vaskularisierten Fibulaspan wird vorgestellt. Der Fibulaspan zeigte 2 Jahre nach der Operation eine eindeutige Hypertrophie.
    Notes: Summary A successful reconstruction of a large tibial defect with a free vascularized fibular graft is presented. The fibular graft demonstrated a significant hypertrophy 2 years postoperatively.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1436-2813
    Keywords: Graves’ disease ; subtotal thyroidectomy ; endocrine response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Changes in the serum levels of anterior pituitary, thyroid, parathyroid, and adrenal hormones following subtotal thyroidectomy in 31 patients with Graves’ disease were investigated. In 14 patients, rapid ACTH tests were performed on the preoperative and the first, third, and seventh postoperative days. Remarkable differences were not seen with regard to the changes in anterior pituitary hormones or cortisol, compared to those seen during general surgery. As to the thyroid hormones, the serum level of triioodothyronine (T3) decreased markedly after surgery and fell to half that of the preoperative value on the first postoperative day. Thereafter, a low value of T3 was maintained during the early postoperative period. Unlike T3, the serum level of thyroxine (T4) decreased gradually until the 7th post-operative day. The levels of both epinephrine and norepinephrine increased transiently during surgery, but the serum level of norepinephrine increased again on the third postoperative day. In the postoperative period, almost half the number of patients showed an inadequate cortisol response to rapid ACTH tests. It is suggested that the unique responses, such as the rise in serum norepinephrine or an inadequate response of cortisol to ACTH, or hypocalcemia, after subtotal thyroidectomy in patients with Graves’ disease is largely due to the rapid decrease of T3 in the hypothyroid state, as was noted during the postoperative period.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Journal of hepato-biliary-pancreatic surgery 2 (1995), S. 395-400 
    ISSN: 1436-0691
    Keywords: tumor marker ; hepatocellular caroinoma ; α-fetoprotein ; PIVKA-II ; pancreatic carcinoma ; carbohydrate antigen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Because they show high levels in hepatocellular carcinoma, α-fetoprotein and des-γ-carboxyprothrombin are clinically useful tumor markers for differentiating hepatocellular carcinoma from other hepatic diseases. The two are useful complementary markers of hepatocellular carcinoma because they do not correlate with each other. A typical marker of pancreatic cancer is carbohydrate antigen (CA)19-9. Over a period of more than 10 years, many markers resembling CA19-9 have been identified, but none are markedly superior to CA19-9, and the sensitivity of these markers in pancreatic cancer is only 65%–80%. Tumor markers are not useful for the early diagnosis of either hepatocellular carcinoma or pancreatic cancer. They are, however, considered to be useful for monitoring after treatment.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1534-4681
    Keywords: Parathyroid carcinoma ; PCNA ; Ki-67 ; Labeling index.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: It is widely accepted that histological diagnosis of parathyroid tumors is established with great difficulty. Carcinomas cannot be reliably separated from adenomas by histology alone. In this study, immunohistochemical staining for proliferating cell nuclear antigen (PCNA) and Ki-67 was determined in 10 cases of parathyroid carcinomas, labeling indices (LIs) were calculated, and the results were correlated with the clinical outcomes. Methods: Ten cases of formalin-fixed, paraffin-embedded tissue with surgically resected parathyroid carcinoma were used. Immunohistochemical staining for PCNA and Ki-67 was performed and the LIs were calculated. We also examined whether LI could become a useful marker for parathyroid carcinomas. Results: Although nine patients with minimally invasive growth without recurrence of the tumor showed a low LI for both markers, one patient with a widely invasive neoplasm, and who died, had a high LI. Conclusions: These results suggested that the LI of PCNA and Ki-67, in addition to the histological appearance, may be markers of the biological behavior of parathyroid carcinomas. However, this study was on a small scale, so it may be valuable to repeat these studies in a larger group of patients with better defined histological criteria.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1435-232X
    Keywords: Key words Multiple endocrine neoplasia type 2 (MEN2) ; Familial medullary thyroid carcinoma (FMTC) ; Sporadic medullary thyroid carcinoma (MTC) ; RET proto-oncogene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Multiple endocrine neoplasia types 2A and 2B (MEN2A and MEN2B) and familial medullary thyroid carcinomas (FMTC) are caused by germline mutations in the RET proto-oncogene. To investigate the spectrum of RET mutations among Japanese patients, we screened the RET gene in 71 patients with thyroid carcinomas. The panel included representatives of 44 families carrying FMTC or MEN2, 22 sporadic medullary thyroid carcinomas (MTCs), and five MTCs without familial information. Mutations in nucleotide sequences encoding one of three specific cysteine residues in the extracellular domain of the RET protein were found in 33 of the 34 MEN2A patients and in five of the six FMTC patients examined. A mutation at codon 918, causing the substitution of threonine for methionine in the tyrosine kinase domain of the protein, was found in germline DNAs of all four patients with MEN2B and in two of the 22 patients with sporadic MTCs; codon 918 was mutated somatically in tumor DNAs from three other sporadic cases. Germline mutations of codon 768, GAG to GAC (Glu to Asp), were detected in one FMTC, in one patient with sporadic MTC, and in one of the patients without familial information. Two somatic mutations, an Asp to Gly substitution at codon 631 and a Cys to Arg substitution at codon 634, had not been reported previously. Of five germline mutations found among the 22 sporadic cases, four were confirmed as de novo mutations since in each case neither parent carried the mutation. As nearly one-fourth of the patients with sporadic MTCs carried germline mutations and 50% of their children are expected to develop MTC and other endocrine tumors, these results indicated the importance of careful clinical surveillance of family members of any patient with MTC.
    Type of Medium: Electronic Resource
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