Identification of a Sgo2-Dependent but Mad2-Independent Pathway Controlling Anaphase Onset in Fission Yeast.

The onset of anaphase is triggered by activation of the anaphase-promoting complex/cyclosome (APC/C) following silencing of the spindle assembly checkpoint (SAC). APC/C triggers ubiquitination of Securin and Cyclin B, which leads to loss of sister chromatid cohesion and inactivation of Cyclin B/Cdk1, respectively. This promotes relocalization of Aurora B kinase and other components of the chromosome passenger complex (CPC) from centromeres to the spindle midzone. In fission yeast, this is mediated by Clp1 phosphatase-dependent interaction of CPC with Klp9/MKLP2 (kinesin-6). When this interaction is disrupted, kinetochores bi-orient normally, but APC/C activation is delayed via a mechanism that requires Sgo2 and some (Bub1, Mph1/Mps1, and Mad3), but not all (Mad1 and Mad2), components of the SAC and the first, but not second, lysine, glutamic acid, glutamine (KEN) box in Mad3. These data indicate that interaction of CPC with Klp9 terminates a Sgo2-dependent, but Mad2-independent, APC/C-inhibitory pathway that is distinct from the canonical SAC.

Bub3-Bub1 Binding to Spc7/KNL1 Toggles the Spindle Checkpoint Switch by Licensing the Interaction of Bub1 with Mad1-Mad2.

The spindle assembly checkpoint (SAC) ensures that sister chromatids do not separate until all chromosomes are attached to spindle microtubules and bi-oriented. Spindle checkpoint proteins, including Mad1, Mad2, Mad3 (BubR1), Bub1, Bub3, and Mph1 (Mps1), are recruited to unattached and/or tensionless kinetochores. SAC activation catalyzes the conversion of soluble Mad2 (O-Mad2) into a form (C-Mad2) that binds Cdc20, BubR1, and Bub3 to form the mitotic checkpoint complex (MCC), a potent inhibitor of the anaphase-promoting complex (APC/C). SAC silencing de-represses Cdc20-APC/C activity allowing poly-ubiquitination of Securin and Cyclin B, leading to the dissolution of sister chromatids and anaphase onset [1]. Understanding how microtubule interaction at kinetochores influences the timing of anaphase requires an understanding of how spindle checkpoint protein interaction with the kinetochore influences spindle checkpoint signaling. We, and others, recently showed that Mph1 (Mps1) phosphorylates multiple conserved MELT motifs in the Spc7 (Spc105/KNL1) protein to recruit Bub1, Bub3, and Mad3 (BubR1) to kinetochores [2-4]. In budding yeast, Mps1 phosphorylation of a central non-catalytic region of Bub1 promotes its association with the Mad1-Mad2 complex, although this association has not yet been detected in other organisms [5]. Here we report that multisite binding of Bub3 to the Spc7 MELT array toggles the spindle checkpoint switch by permitting Mph1 (Mps1)-dependent interaction of Bub1 with Mad1-Mad2.

Checkpoint proteins come under scrutiny.

Details are emerging of the interactions between the kinetochore and various spindle checkpoint proteins that ensure that sister chromatids are equally divided between daughter cells during cell division.

[Pre-operative symptoms and post-operative improvement in patients diagnosed with hyperparathyroidism. Analysis of 120 consecutive cases]. / Clínica preoperatoria y mejoría postoperatoria en pacientes con diagnóstico de hiperparatiroidismo. Análisis de 120 casos consecutivos.

OBJECTIVE: To compare the pre-operative and post-operative clinical symptoms in patients diagnosed as having hyperparathyroidism and given surgical treatment, in order to prove the existence of statistically significant improvement. MATERIAL AND METHOD: We report here a retrospective study performed on 120 consecutive patients operated on following diagnosis of hyperparathyroidism between 1990 and 2003. RESULTS: Nephrolithiasis, generalized bone pain and HBP were the most common clinical manifestations. Primary hyperparathyroidisms represented 76.7 %, while secondary ones were 20.8 % and 2.5 % were tertiary. We carried out 85 adenoma removals, 30 sub-total and 5 total parathyroidectomies. We only encountered one case of recurrent palsy and about 25 % of hypocalcemias (2 of them permanent). Osteoarticular pathology and nephrolithiasis suffered by our patients clearly improved after surgery (P< .01) after 2 years of follow-up. There was no significant improvement in HBP, digestive and psychiatric pathology or pruritus. CONCLUSIONS: The improvement in quality of life for most of the patients operated on for this condition amply justifies parathyroidectomy by an experienced otolaryngology team.

Clínica preoperatoria y mejoría postoperatoria en pacientes con diagnóstico de hiperparatiroidismo. Análisis de 120 casos consecutivos / Pre-operative symptoms and post-operative improvement in patients diagnosed with hyperparathyroidism. Analysis of 120 consecutive cases

Objetivo: Comparar los síntomas clínicos preoperatorios y postoperatorios en pacientes diagnosticados de hiperparatiroidismo y sometidos a tratamiento quirúrgico, para comprobar si se produce mejoría estadísticamente significativa. Material y método: Estudio retrospectivo realizado sobre 120 pacientes consecutivos intervenidos con diagnóstico de hiperparatiroidismo entre 1990 y 2003. Resultados: La litiasis renal, los dolores óseos generalizados y la hipertensión fueron las manifestaciones clínicas más frecuentes. El 76,7 % eran hiperparatiroidismos primarios; el 20,8 %, secundarios y el 2,5 %, terciarios. Se practicaron 85 resecciones de adenoma, 30 paratiroidectomías subtotales y 5 paratiroidectomías totales. Sólo hemos constatado 1 caso de parálisis recurrencial y un 25 % de hipocalcemias (2 definitivas). Mejoraron significativamente tras la cirugía (p < 0,01) la afección osteo articular y la litiasis renal que presentaban los pacientes tras 2 años de seguimiento. No mejoraron de forma significativa la hipertensión, las enfermedades digestivas y psiquiátricas y elprurito. Conclusiones: La mejoría en la calidad de vida de la mayoría de los pacientes operados por esta enfermedad justifica sobradamente la paratiroidectomía por un equipo otorrinolaringológico experimentado (AU)

Objective: To compare the pre-operative and post-operative clinical symptoms in patients diagnosed as having hyperparathyroidism and given surgical treatment, in order to prove the existence of statistically significant improvement. Material and method: We report here a retrospective study performed on 120 consecutive patients operated on following diagnosis of hyperparathyroidism between 1990 and 2003. Results: Nephrolithiasis, generalized bone pain and HBP were the most common clinical manifestations. Primary hyperparathyroidisms represented 76.7 %, while secondary ones were 20.8% and 2.5 % were tertiary. We carried out85 adenoma removals, 30 sub-total and 5 total parathyroidectomies. We only encountered one case of recurrent palsy and about 25 % of hypocalcemias (2 of them permanent). Osteoarticular pathology and nephrolithiasis suffered by our patients clearly improved after surgery (P<0.01) after 2 years of follow-up. There was no significant improvement in HBP, digestive and psychiatric pathology or pruritus. Conclusions: The improvement in quality of life for most of the patients operated on for this condition amply justifies parathyroidectomy by an experienced otolaryngology team (AU)

[Acute epiglottitis in adults. Diagnosis and treatment in our experience of 30 cases]. / Epiglotitis aguda en adultos. Nuestra experiencia clínica en 30 casos.

OBJECTIVE: We present the 15-year-long experience of 2 hospitals in our region regarding the therapeutic management of acute epiglottitis in adults. PATIENTS AND METHOD: Thirty patients with an average age of 46 years were diagnosed as having acute epiglottitis, either by indirect laryngoscopy or fibroscopy, and studied through a series of clinical parameters: age, sex, personal history, complementary tests, clinical symptoms, treatment, evolution, and average stay in hospital. RESULTS: We found an obvious predominance of this urgent pathology in males, with most patients reporting dysphagia or odynophagia (90 %). Dyspnoea was confirmed in 40 % of the cases but only 7 required intubation, coniotomy, or tracheotomy. The complications recorded include one case of mediastinitis and another of death due to sudden cardiorespiratory arrest. CONCLUSIONS: We feel that a specific protocol must be established to take into account, apart from admission to hospital, personal contact with an intensive care unit (ICU) even though in most cases it is ultimately unnecessary to ensure airway patency as seen in the various case series published.

Epiglotitis aguda en adultos. Nuestra experiencia clínica en 30 casos / Acute epiglottitis in adults. Diagnosis and treatment in our experience of 30 cases

Objetivo: Dar a conocer la experiencia conjunta de 2 hospitales de nuestra región en los últimos 15 años sobre el manejo terapéutico de los casos de epiglotitis aguda en adultos. Pacientes y método: Se incluye a 30 pacientes con una media de edad de 46 años, diagnosticados de epiglotitis aguda mediante laringoscopia indirecta o fibroscopia, de los que se recogió una serie de parámetros clínicos: edad, sexo, antecedentes personales, estudios complementarios, síntomas clínicos, tratamiento, evolución y estancia hospitalaria. Resultados: Encontramos un claro predominio de esta enfermedad urgente en varones, que en su mayoría referían disfagia u odinofagia (90 %). Se constató disnea en un 40 % de los casos, de los que sólo 7 requirieron intubación, coniotomía o traqueotomía. Entre las complicaciones registramos un caso de mediastinitis y una muerte por parada cardiorrespiratoria súbita. Conclusiones: Creemos que se debe establecer un protocolo de actuación que incluya, aparte del ingreso hospitalario, un contacto personal con una unidad de cuidados intensivos (UCI) aunque en la mayoría de los casos finalmente no sea necesario asegurar la vía respiratoria, como se comprueba en las diferentes casuísticas publicadas

Objective: We present the 15-year-long experience of 2 hospitals in our region regarding the therapeutic management of acute epiglottitis in adults. Patients and method: Thirty patients with an average age of 46 years were diagnosed as having acute epiglottitis, either by indirect laryngoscopy or fibroscopy, and studied through a series of clinical parameters: age, sex, personal history, complementary tests, clinical symptoms, treatment, evolution, and average stay in hospital. Results: We found an obvious predominance of this urgent pathology in males, with most patients reporting dysphagia or odynophagia (90 %). Dyspnoea was confirmed in 40 % of the cases but only 7 required intubation, coniotomy, or tracheotomy. The complications recorded include one case of mediastinitis and another of death due to sudden cardiorespiratory arrest. Conclusions: We feel that a specific protocol must be established to take into account, apart from admission to hospital, personal contact with an intensive care unit (ICU) even though in most cases it is ultimately unnecessary to ensure airway patency as seen in the various case series published

[Surgical treatment of refractory hyperparathyroidism and usefulness of the intraoperative PTH]. / Tratamiento quirúrgico del hiperparatiroidismo refractario y utilidad de la paratirina intraoperatoria.

OBJECTIVE: To share our experience in the surgery of so-called refractory hyperparathyroidism (secondary and tertiary without response to therapy with calcitriol). MATERIAL AND METHODS: Retrospective study based on 41 patients-5 with secondary and 6 with tertiary hyperparathyroidism-referred by nephrology for surgical evaluation of their illness because of poor response to the medical treatment given. RESULTS: In 18 of the 41 cases we used the fast or turbo intra-operative PTH with reduction of more than 60 % in all patients. In the group in whom normal PTH was performed, we registered 2 secondary hyperparathyroidisms with no significant decrease and persistence of symptoms. One of them was reoperated successfully. DISCUSSION: Subtotal or total parathyroidectomy with reimplant represents the treatment of choice in refractory hyperparathyroidism with good results in most of the series reviewed.

[Contralateral hemithyroidectomy due to carcinoma of the thyroid. Our cases reviewed and updated]. / Hemitiroidectomía contralateral por carcinoma de tiroides. Nuestra casuística revisada y actualizada.

OBJECTIVE: We are reporting our 14 years' experience with prior hemithyroidectomies or contralateral hemithyroidectomies after a pathology result reporting malignancy (thyroid carcinoma) in the first surgery. MATERIAL AND METHOD: Twenty female patients with an average age of 45 years old have been studied and we have analyzed the initial symptoms, results of complementary tests, pathology diagnosis following initial surgery, and final outcome after a second intervention. RESULTS: The incidence of malignancy shown in our series after secondary surgery was 40 % and the percentage of hemithyroidectomy on hemithyroidectomy was 3 % after operating on 650 thyroid glands. CONCLUSIONS: Though opinions differ in the medical literature, we feel a total thyroidectomy must be performed after a casual finding of thyroid carcinoma because of the oncologically safer outcome and the better control of the patient.

Hemitiroidectomía contralateral por carcinoma de tiroides. Nuestra casuística revisada y actualizada / Contralateral hemithyroidectomy due to carcinoma of the thyroid. Our cases reviewed and updated

Objetivo: Se presenta nuestra experiencia de 14 años en hemitiroidectomías sobre hemitiroidectomías previas o hemitiroidectomías contralaterales tras un resultado anatomopatológico de malignidad (carcinoma de tiroides) en la primera cirugía. Material y método: Hemos incluido a 20 pacientes, todas ellas mujeres, con una media de edad de 45 años. Se analizan los síntomas clínicos iniciales, los resultados de las exploraciones complementarias, el diagnóstico anatomopatológico de la primera intervención y el resultado final tras la segunda cirugía. Resultados: En nuestra serie la segunda hemitiroidectomía resultó positiva en un 40 % y el porcentaje de hemitiroidectomías sobre hemitiroidectomías de 650 tiroides operados fue del 3 %. Conclusiones: Aunque hay diferentes opiniones en la literatura médica, nosotros creemos que ante el hallazgo casual de un carcinoma tiroideo se debe completar una tiroidectomía total, por su mayor seguridad oncológica y mejor control del paciente

Objective: We are reporting our 14 years' experience with prior hemithyroidectomies or contralateral hemithyroidectomies after a pathology result reporting malignancy (thyroid carcinoma) in the first surgery. Material and method: Twenty female patients with an average age of 45 years old have been studied and we have analyzed the initial symptoms, results of complementary tests, pathology diagnosis following initial surgery, and final outcome after a second intervention. Results: The incidence of malignancy shown in our series after secondary surgery was 40 % and the percentage of hemithyroidectomy on hemithyroidectomy was 3 % after operating on 650 thyroid glands. Conclusions: Though opinions differ in the medical literature, we feel a total thyroidectomy must be performed after a casual finding of thyroid carcinoma because of the oncologically safer outcome and the better control of the patient

Tratamiento quirúrgico del hiperparatiroidismo refractario y utilidad de la paratirina intraoperatoria / Surgical treatment of refractory hyperparathyroidism and usefulness of the intraoperative PTH

Objetivo: Dar a conocer nuestra experiencia en la cirugía del denominado hiperparatiroidismo refractario (secundario y terciario sin respuesta al tratamiento con calcitriol). Material y métodos: Estudio retrospectivo con revisión de 41 pacientes (35 con hiperparatiroidismos secundarios y 6 terciarios) remitidos por nefrología para valoración quirúrgica de su enfermedad ante la mala respuesta al tratamiento médico. Resultados: En 18 de los 41 casos se utilizó la determinación de paratirina rápida o turbo intraoperatoria, con descenso superior al 60 % en todos los pacientes. En el grupo en que se empleó paratirina normal registramos 2 hiperparatiroidismos secundarios en los que la citada hormona no descendió significativamente y los síntomas persistieron, uno de los cuales fue reintervenido con éxito. Conclusiones: La paratiroidectomía subtotal o total con autotrasplante es el tratamiento de elección en el hiperparatiroidismo refractario, con buenos resultados en la mayoría de las series consultadas

Objective: To share our experience in the surgery of so-called refractory hyperparathyroidism (secondary and tertiary without response to therapy with calcitriol). Material and methods: Retrospective study based on 41 patients­5 with secondary and 6 with tertiary hyperparathyroidism­referred by nephrology for surgical evaluation of their illness because of poor response to the medical treatment given. Results: In 18 of the 41 cases we used the fast or turbo intra-operative PTH with reduction of more than 60 % in all patients. In the group in whom normal PTH was performed, we registered 2 secondary hyperparathyroidisms with no significant decrease and persistence of symptoms. One of them was reoperated successfully. Discussion: Subtotal or total parathyroidectomy with reimplant represents the treatment of choice in refractory hyperparathyroidism with good results in most of the series reviewed