IgG4-related disease and B-cell malignancy due to an IKZF1 gain-of-function variant.

BACKGROUND: Monoallelic loss-of-function IKZF1 (IKAROS) variants cause B-cell deficiency or combined immunodeficiency, whereas monoallelic gain-of-function (GOF) IKZF1 variants have recently been reported to cause hypergammaglobulinemia, abnormal plasma cell differentiation, autoimmune and allergic manifestations, and infections. OBJECTIVE: We studied 7 relatives with autoimmune/inflammatory and lymphoproliferative manifestations to identify the immunologic disturbances and the genetic cause of their disease. METHODS: We analyzed biopsy results and performed whole-exome sequencing and immunologic studies. RESULTS: Disease onset occurred at a mean age of 25.2 years (range, 10-64, years). Six patients suffered from autoimmune/inflammatory diseases, 4 had confirmed IG4-related disease (IgG4-RD), and 5 developed B-cell malignancies: lymphoma in 4 and multiple myeloma in the remaining patient. Patients without immunosuppression were not particularly prone to infectious diseases. Three patients suffered from life-threatening coronavirus disease 2019 pneumonia, of whom 1 had autoantibodies neutralizing IFN-α. The recently described IKZF1 GOF p.R183H variant was found in the 5 affected relatives tested and in a 6-year-old asymptomatic girl. Immunologic analysis revealed hypergammaglobulinemia and high frequencies of certain lymphocyte subsets (exhausted B cells, effector memory CD4 T cells, effector memory CD4 T cells that have regained surface expression of CD45RA and CD28-CD57+ CD4+ and CD8+ T cells, TH2, and Tfh2 cells) attesting to immune dysregulation. Partial clinical responses to rituximab and corticosteroids were observed, and treatment with lenalidomide, which promotes IKAROS degradation, was initiated in 3 patients. CONCLUSIONS: Heterozygosity for GOF IKZF1 variants underlies autoimmunity/inflammatory diseases, IgG4-RD, and B-cell malignancies, the onset of which may occur in adulthood. Clinical and immunologic data are similar to those for patients with unexplained IgG4-RD. Patients may therefore benefit from treatments inhibiting pathways displaying IKAROS-mediated overactivity.

High genetic diversity on a sample of pre-Columbian bone remains from Guane territories in northwestern Colombia.

Ancient DNA was recovered from 17 individuals found in a rock shelter in the district of "La Purnia" (Santander, Colombia). This region is the homeland of pre-Columbian Guane, whom spread over the "Río Suarez" to the "Río de Oro", and were surrounded to the west by the Central Andes, south and east by foothills of Eastern Andes, and north by the "Chicamocha" river canyon. Guanes established in a region that straddles the Andes and the northern Amazon basin, possibly making it an unavoidable conduit for people moving to and from South America. We amplified mtDNA hypervariable region I (HVI) segments from ancient bone remains, and the resulting sequences were compared with both ancient and modern mitochondrial haplogroups from American and non-American populations. Samples showed a distribution of 35% for haplogroup A, 41% for haplogroup B and 24% for haplogroup D. Nine haplotypes were found in 17 samples, indicating an unusually high genetic diversity on a single site ancient population. Among them, three haplotypes have not been previously found in America, two are shared in Asia, and one is a private haplotype. Despite geographical barriers that eventually isolated them, an important influence of gene flow from neighboring pre-Columbian communities, mainly Muiscas, could explain the high genetic polymorphism of this community before the Spanish conquest, and argues against Guanes as being a genetic isolate.

[Mitochondrial DNA analysis on pre-Columbian bone remains of the Herrera period]. / Análisis de ADN mitocondrial en una muestra de restos óseos arcaicos del periodo Herrera en la sabana de Bogotá.

INTRODUCTION: Ancient bone remains constitute an important source of biological information, and their genetic characterization allows the confirmation or rebuttal of human affiliations proposed on the basis of non-molecular approaches. Pre-Columbian history of the Eastern Andes in Colombia has been divided into three main periods: (i) an early colonization by groups of hunter-gatherers, (ii) an intermediate period "Herrera" characterized by primitive agriculture and (iii) a late stage of Chibcha-speaking groups, with agriculture and ceramics ("agroalfarero"). OBJECTIVE: The mitochondrial DNA on ancient bone remains of the Herrera period were analyzed for comparison with modern and other ancient DNAs. MATERIALS AND METHODS: Mitochondrial DNA was extracted from 11 Herrera individuals [approximately 2,000 years before present (YBP)] found in the Madrid 2-41 archaeological site near Bogotá, Colombia. A 192 bp segment of the hypervariable segment I was amplified and sequenced, following stringent archaic DNA authenticity criteria. The sequences were compared with those in American and European databases using bioinformatics tools. RESULTS: All individuals had identical sequences and were classified as haplogroup B. This identity may be related to the type of ritual burial performed in the site, probably exclusively for members of a hierarchically important family of the ancient Herrera society. The search for homologous sequences in the American and European mtDNA data bases produced no identical coincidences, although a Brazilian Amazonic individual (approximately 4,000 YBP) was recorded with a matching sequence. CONCLUSION: Individuals buried in the Madrid 2-41 site were maternally closely related and showed a mtDNA sequence that is apparently absent in contemporary populations.

[Mitochondrial DNA diversity in prehispanic bone remains on the eastern Colombian Andes].

INTRODUCTION: DNA extracted from ancient human bones allows to analyze the genetic makeup of pre-Columbian populations and to determine the dynamics that gave rise to the diversity of contemporary populations. OBJECTIVE: To determine the genetic diversity of skeletal remains associated with the Templo del Sol (Sun Temple) and their relationship with other contemporary and ancient communities of America. MATERIALS AND METHODS: We analyzed 13 individuals belonging to the pre-Columbian Muisca Period (IX-XVI centuries AD) from the vicinities of the Templo del Sol (Sun Temple) (Sogamoso, Boyacá) in the eastern Colombian Andes. Mitochondrial DNA was amplified and RFLPs were performed in order to type the four traditional Amerindian haplogroups (A, B, C and D). In addition, autosomal markers including amelogenin and Y-chromosome STRs were amplified. RESULTS: Among the observed mitochondrial lineages, haplogroup A was the most frequent, followed by haplogroups B and C; no evidence of haplogroup D was found. The genetic variation analysis indicated a similar diversity of pre-ColumbianMuiscas to that of contemporary populations belonging to the Chibcha linguistic family from Colombia and Central America. Molecular sexing was accomplished and it was compared to osteological data. With only one exception, anthropological and molecular data were consistent. CONCLUSIONS: Our results contribute new genetic elements supporting the hypothesis of Central American origin of the Chibcha groups of the Cundiboyacense plateau, and allowed sex typing and kinship evaluations.

Mitochondrial DNA Analysis of a Sample of Pre-Columbian Acient Remains from Norte de Santander, Colombia (Chitarera Cultural Area) / Análisis de adn mitocondrial en una muestra de restos óseos precolombinos de norte de santander, colombia (área cultural chitarera)

RESUMEN Los análisis de ADN antiguo (ADNa) han incrementado en los últimos años permitiendo conocer la diversidad genética de las poblaciones precolombinas. En Colombia, existen pocos registros arqueológicos de la población prehispánica del Norte de Santander habitada en el siglo XVI por el grupo Chitarero. Por este motivo, nos propusimos analizar la diversidad genética a partir de secuencias de la región HVRI del ADNmt y determinar sus posibles relaciones con otras comunidades tanto antiguas como contemporáneas. Se analizaron siete individuos precolombinos asociados a este grupo prehispánico, recuperados en los municipios de Cácota y Silos en el departamento de Norte de Santander de los Andes Orientales colombianos, siguiendo criterios estrictos de autenticidad para el ADNa. En todos los individuos se logró identificar el haplogrupo B caracterizado por el polimorfismo en la posición 16217C, siendo éste uno de los más frecuentes en comunidades precolombinas y contemporáneas de los Andes Suramericanos. Este hallazgo indica que este grupo poblacional se encuentra estrechamente emparentado por línea materna, con posibles índices de endogamia, con una probable densidad demográfica baja y una baja diversidad genética, similares a lo observado en comunidades pertenecientes a periodos anteriores como el Formativo. Este grupo precolombino exhibe una de las diversidades genéticas más bajas reportadas en las poblaciones pertenecientes a la familia lingüistica Chibcha. Estos resultados genéticos coinciden con los planteamientos sobre el grupo Chitarero de pertenecer a comunidades pequeñas independientes, con asentamientos dispersos, apartados unos de otros.

ABSTRACT In the last few years there has been an increase in ancient DNA (aDNA) analyses that has allowed shedding light on the diversity of pre-Columbian populations. In Colombia, there are few archaeological records belonging to the prehispanic population from Norte de Santander inhabited in the XVI century by the Chitarero. For this reason, we performed a genetic diversity analysis of the HVRI region of mtDNA in order to determine their possible relationships with other communities both ancient and contemporary. We analyzed seven pre-Columbian individuals belonging to this pre-Hispanic group, recovered from the municipalities of Cácota and Silos in the department of Norte de Santander located at the Colombian Andes, following strict authenticity criteria for aDNA. All individuals were identified as belonging to haplogroup B, characterized by the polymorphism found at position 16217C which is one of the most frequent haplogroups in pre-Columbian and contemporary communities of the South American Andes. This finding suggests that this population group was closely related through its maternal lineage, with possible inbreeding indexes, low population density and therefore low genetic diversity, similar to what is observed in communities belonging to previous periods such as the Formative period. This pre-Columbian group exhibits one of the lowest genetic diversities reported in populations belonging to the Chibcha linguistic family. These genetic results coincide with the views on the Chitarero group as belonging to small independent communities, with dispersed settlements separated among them.

Diversidad del ADN mitocondrial en restos óseos prehispánicos / Mitochondrial DNA diversity in prehispanic bone remains on the eastern Colombian Andes

Resumen Introducción. El ADN antiguo que se extrae de los restos óseos humanos permite analizar la composición genética de las poblaciones precolombinas y determinar las dinámicas poblacionales que dieron origen a la diversidad de las poblaciones contemporáneas. Objetivo. Determinar la diversidad genética y la relación con otras comunidades contemporáneas y antiguas de América, de los restos óseos asociados al Templo del Sol en Sogamoso, Colombia. Materiales y métodos. Se analizaron 13 individuos pertenecientes al periodo precolombino muisca (siglos IX-XVI d. C.), provenientes de los alrededores del Templo del Sol en Sogamoso, Boyacá, Andes orientales colombianos. Se amplificó el ADN mitocondrial (ADNmt) y se determinaron los polimorfismos de la longitud de los fragmentos de restricción (Restriction Fragment Length Polymorphism, RFLP) para los cuatro haplogrupos amerindios (A, B, C y D). Además, se amplificaron y analizaron los marcadores autosómicos, incluida la amelogenina, y los marcadores de los polimorfismos de repeticiones cortas en tándem (Short Tandem Repeat, STR) del cromosoma Y. Resultados. El haplogrupo A fue el linaje mitocondrial más frecuente en esta población, seguido de los haplogrupos B y C; no se detectó el haplogrupo D. Los análisis de variación genética indicaron una diversidad semejante a la de las poblaciones pertenecientes a la familia lingüística chibcha, contemporánea en Colombia y Centroamérica. Se logró hacer la determinación molecular del sexo de los individuos estudiados y compararla con los datos osteológicos. Con una sola excepción, los datos bioantropológicos y moleculares concordaron. Conclusiones. Estos resultados aportan nuevos elementos a la hipótesis del origen centroamericano de los grupos chibchas del altiplano cundiboyacense con base en marcadores genéticos, y permitieron establecer el sexo y las relaciones de parentesco.

Abstract Introduction: DNA extracted from ancient human bones allows to analyze the genetic makeup of preColumbian populations and to determine the dynamics that gave rise to the diversity of contemporary populations. Objective: To determine the genetic diversity of skeletal remains associated with the Templo del Sol (Sun Temple) and their relationship with other contemporary and ancient communities of America. Materials and methods: We analyzed 13 individuals belonging to the pre-Columbian Muisca Period (IX-XVI centuries AD) from the vicinities of the Templo del Sol (Sun Temple) (Sogamoso, Boyacá) in the eastern Colombian Andes. Mitochondrial DNA was amplified and RFLPs were performed in order to type the four traditional Amerindian haplogroups (A, B, C and D). In addition, autosomal markers including amelogenin and Y-chromosome STRs were amplified. Results: Among the observed mitochondrial lineages, haplogroup A was the most frequent, followed by haplogroups B and C; no evidence of haplogroup D was found. The genetic variation analysis indicated a similar diversity of pre-Columbian Muiscas to that of contemporary populations belonging to the Chibcha linguistic family from Colombia and Central America. Molecular sexing was accomplished and it was compared to osteological data. With only one exception, anthropological and molecular data were consistent. Conclusions: Our results contribute new genetic elements supporting the hypothesis of Central American origin of the Chibcha groups of the Cundiboyacense plateau, and allowed sex typing and kinship evaluations.

[Current view and critic of alternatives to transurethral surgery of prostatic benign prostate]. / Visión actual y crítica de las alternativas a la cirugía transuretral de la hiperplasia benigna de próstata.

OBJECTIVES: Critical update of transurethral surgery options based on the last decade most relevant bibliography. METHODS: Comparative study between Incision/TUR of the prostate and alternative techniques, accordingly to data from 30 randomized studies and 28 clinical studies. We evaluate efficiency, retreatment index, morbidity, post operative number of days with catheter, anesthetic requirements, and cost. Data are expressed as percentages resulting from a differential formula in randomized studies and simple percentages or numeric expression for relevant clinical data. RESULTS: Efficiency: all alternative treatments show a symptomatic improvement (> 50%) similar to that achieved by transurethral surgery; post treatment flowmetry percentage increase is inferior in all alternatives except vaporization, holmium laser and prosthesis. Re-Treatment requirements: they were higher in all alternatives except the ablative ones (vaporization and holmium laser). Morbidity: all of them had an operative estimated blood loss inferior to TUR and similar to prostatic incision; contact laser and vaporization had more irritative symptoms than incision, and VLAP and TUMT more than TUR; TUMT and interstitial laser have a higher rate of post operative infection; all alternatives except the ablative ones had lower percentages of urethral stenosis and retrograde ejaculation. Number of days of catheter post operative: it was comparatively longer after vaporization and very long after VLAP, interstitial laser and TUMT. All treatments except TUNA and TUMT require the same anesthesia than transurethral surgery. The cost/benefit has not been sufficiently evaluated, but it is superior with holmium laser, contact laser and vaporization than with transurethral surgery. CONCLUSIONS: Based on study data we can accept holmium laser as a real alternative, TUMT in cases when surgery is questioned and intraprostatic prosthesis when it is not possible.

[Radical cystectomy for superficial tumors in the BCG era]. / Cistectomía radical en tumores superficiales en la era de la BCG.

OBJECTIVE: To analyze the indications and outcome of cystectomy for superficial bladder cancer since the introduction of BCG therapy. METHODS: From June 1990 to December 1996, 384 patients underwent cystectomy for transitional cell bladder tumor. A retrospective study was carried out on 43 cases (11.1%) that underwent cystectomy for Tis, Ta, T1 tumors. The characteristics of patients with superficial bladder cancer, correlation between the clinical stage (determined after TUR) and pathological findings (cystectomy specimen) and outcome were analyzed. RESULTS: 36 patients were male and 7 were female; mean age 63 years (range 39-79). Mean follow-up was 48 months (8-120). Twenty-nine patients received BCG therapy prior to surgery. No response to BCG was the main indication for cystectomy. By clinical stage, 79% were high grade, 65% T1 and 65% CIS. A correlation between the clinical stage and the pathological findings was found in 32.5%, overstaging in 28% and understaging in 39.5%. The increase in stage after analysis of the surgical specimen in 13 patients (30%) was due to progression of the superficial bladder tumor to infiltrating or metastatic tumor. Urinary tract tumor was found during follow-up in 8 patients (18.6%). Eleven patients died of bladder cancer, 3 of other causes and 29 (67%) are free of disease. Seven of the 13 patients (53%) that were clinically understaged and had infiltrating tumor or metastasis died. CONCLUSIONS: No response to BCG therapy was the main indication for cystectomy. Before starting conservative treatment for high risk superficial bladder cancer, the possibility of endoscopic understaging should be taken into account. Patients undergoing cystectomy for superficial bladder cancer have a high risk of developing urinary tract tumor.

Análisis de ADN mitocondrial en una muestra de restos óseos arcaicos del periodo Herrera en la sabana de Bogotá / Mitochondrial DNA analysis on pre-Columbian bone remains of the Herrera period

Introducción. Los restos óseos arcaicos son fuente privilegiada de información biológica y su caracterización genética permite confirmar o descartar filiaciones propuestas por otras aproximaciones científicas. La historia precolombina de los Andes orientales se divide en tres periodos principales: I) un poblamiento temprano por parte de grupos cazadores-recolectores; II) un periodo intermedio (Herrera) de pueblos con agricultura incipiente, y III) un periodo tardío de pueblos chibchas, agrícolas y alfareros (agroalfarero). Objetivo. Analizar el ADN mitocondrial de restos óseos del periodo Herrera. Materiales y métodos. Se analizaron 11 individuos pertenecientes al yacimiento arqueológico Madrid 2-41, con una edad aproximada de 2.000 años. Un fragmento (192 pb) del segmento hipervariable I fue amplificado y secuenciado, siguiendo criterios estrictos de autenticidad deADN arcaico. Las secuencias se compararon con las existentes en bases de datos de Norteamérica y Europa usando herramientas bioinformáticas. Resultados. Todas las secuencias resultaron idénticas y fueron clasificadas como haplogrupo B. Esto puede relacionarse con el tipo de entierro ritual practicado en Madrid 2-41, es decir, probablemente los individuos analizados hagan parte de una familia jerárquicamente importanteen la antigua sociedad Herrera. La búsqueda de secuencias homólogas en las bases de datos estadounidense y europea no arrojó coincidencias exactas, aunque existe el reporte de un individuo amazónico de ~4.000 años de antigüedad (Brasil) cuya secuencia coincide con la hallada en Madrid 2-41.Conclusión. Los individuos del yacimiento arqueológico Madrid 2-41 están estrechamente emparentados entre sí por línea materna y presentan una secuencia aparentemente ausente en poblaciones actuales.

Prevalencia y variabilidad de ocho rasgos morfológicos dentales en jóvenes de tres colegios de Cali, 2002 / Prevalence and variability of eight dental morphologic characteristics in young people of three schools of Cali, 2002

Objetivos: Determinar la prevalencia y variabilidad de ocho rasgos morfológicos dentales: incisivos en pala (UI1), cúspide de Carabelli (UM1), reducción del hipocono (UM2), cresta distal del trigónido (LM1), cúspide sexta TAPI (LM1), cúspide séptima TAMI (LM1), pliegue acodado (LM1) y protostílido (LM1). Materiales y métodos: Se realizó un estudio descriptivo transversal cuantitativo para caracterizar la morfología dental mediante el sistema de placas ASU, en 100 jóvenes de ambos sexos pertenecientes al grupo poblacional mestizo, estudiantes de tres colegios de Cali y con edades comprendidas entre los 10 y 18 años. Resultados: Los rasgos de mayor prevalencia fueron la reducción del hipocono y el pliegue acodado. Se apreciaron frecuencias bajas de los incisivos en pala, cúspide de Carabelli, protostílido, cúspide 6, cúspide 7. No se observó en la muestra la cresta distal del trigónido. Los resultados indican que existe bilateralidad en la expresión de los rasgos y que estos no presentan dimorfismo sexual; además la prevalencia de algunos de ellos sugiere que la muestra observada tiene semejanza con el patrón dental caucasoide y preserva algún tipo de influencia del complejo dental mongoloide

Microendoscopia y la coloracion vital en tumores del esofago y estomago y enfermedades asociadas / Microendoscopy and vital stain in tumors of the esophagus, stomach and associated diseases

Demostracion de los cambios malignos mediante la tecnica de magnificacion y coloracion vital y tambien de los aspectos importantes de lesiones consideradas premalignas

Diagnostico de lesiones de vias digestivas superiores por biopsia y citologia por puncion / Diagnosis of the upper digestive tract injuries using biopsy and citology by punction

Determinacion de la seguridad de la citologia mediante un metodo por puncion para obtener las muestras y comparar los resultados con el diagnostico histologico en 85 pacientes seleccionados al azar

Morbilidad oral en esqueletos de una comunidad indígena prehispánica soacha-cundinamarca-colombia II Parte / Oral morbidity in skeletons of a prehispanic indian colombian community (Soacha, Cundinamarca, Colombia)

El Instituto Colombiano de Antropología y el Departamento de Antropología de la Facultad de Ciencias Humanas de la Universidad Nacional de Colombia están investigando unos esqueletos de una comunidad indígena prehispánica que una empresa privada de construcciones encontró en unas excavaciones para urbanizar unos lotes, en Soacha, Cundinamarca, Colombia en 1988.

Electro-reseccion endoscopica de heterotopias y tumores submucosos del tracto digestivo superior: presentacion de cuatro casos / Endoscopic technique for electro resection of upper gastrointestinal tract wall heterotopias and submucosal tumors: report of 4 cases

Se presentaron las indicaciones y la tecnica endoscopica para la electroreseccion de heterotopias y tumores submucosos localizados en la pared del tracto digestivo superior, como un avance adicional al de la polipectomia. Se describen cuatro casos de pacientes tratados con este procedimiento lograndose el diagnostico y el tratamiento definitivo sin complicaciones inmediatas ni tardias. Se propone el empleo de esta tecnica como tratamiento de eleccion en este tipo de patologia