The role of HLA variation in lymphoma aetiology and survival.

Epidemiologic and laboratory evidence has consistently supported a strong inflammatory and immune component for lymphoma aetiology. These studies have consistently implicated variation in the immune gene, human leucocyte antigen (HLA), to be associated with lymphoma risk. In this review, we summarize the historical and recent evidence of HLA in both lymphoma aetiology and survival. The recent momentum in uncovering HLA associations has been propelled by the conduct of genome-wide association studies (GWAS), which has permitted the evaluation of imputed HLA alleles in much larger sample sizes than historically feasible with allelotyping studies. Based on the culmination of smaller HLA typing studies and larger GWAS, we now recognize several HLA associations with Hodgkin (HL) and non-Hodgkin lymphomas (NHLs) and their subtypes. Although other genetic variants have also been implicated with lymphoma risk, it is notable that HLA associations have been reported in every NHL and HL subtype evaluated to date. Both HLA class I and class II alleles have been linked with NHL and HL risk. It is notable that the associations identified are largely specific to each lymphoma subtype. However, pleiotropic HLA associations have also been observed. For example, rs10484561, which is in linkage disequilibrium with HLA-DRB1*01:01˜DQA1*01:01˜DQB1*05:01, has been implicated in increased FL and DLBCL risk. Opposing HLA associations across subtypes have also been reported, such as for HLA-A*01:01 which is associated with increased risk of EBV-positive cHL but decreased risk of EBV-negative cHL and chronic lymphocytic leukaemia/small cell lymphoma. Due to extensive linkage disequilibrium and allele/haplotypic variation across race/ethnicities, identification of causal alleles/haplotypes remains challenging. Follow-up functional studies are needed to identify the specific immunological pathways responsible in the multifactorial aetiology of HL and NHL. Correlative studies linking HLA alleles with known molecular subtypes and HLA expression in the tumours are also needed. Finally, additional association studies investigating HLA diversity and lymphoma survival are also required to replicate initial associations reported to date.

The use of a cartilage decellularized matrix scaffold for the repair of osteochondral defects: the importance of long-term studies in a large animal model.

OBJECTIVE: To investigate the effect of decellularized cartilage-derived matrix (CDM) scaffolds, by itself and as a composite scaffold with a calcium phosphate (CaP) base, for the repair of osteochondral defects. It was hypothesized that the chondral defects would heal with fibrocartilaginous tissue and that the composite scaffold would result in better bone formation. METHODS: After an 8-week pilot experiment in a single horse, scaffolds were implanted in eight healthy horses in osteochondral defects on the medial trochlear ridge of the femur. In one joint a composite CDM-CaP scaffold was implanted (+P), in the contralateral joint a CDM only (-P) scaffold. After euthanasia at 6 months, tissues were analysed by histology, immunohistochemistry, micro-CT, biochemistry and biomechanical evaluation. RESULTS: The 8-week pilot showed encouraging formation of bone and cartilage, but incomplete defect filling. At 6 months, micro-CT and histology showed much more limited filling of the defect, but the CaP component of the +P scaffolds was well integrated with the surrounding bone. The repair tissue was fibrotic with high collagen type I and low type II content and with no differences between the groups. There were also no biochemical differences between the groups and repair tissue was much less stiff than normal tissue (P < 0.0001). CONCLUSIONS: The implants failed to produce reasonable repair tissue in this osteochondral defect model, although the CaP base in the -P group integrated well with the recipient bone. The study stresses the importance of long-term in vivo studies to assess the efficacy of cartilage repair techniques.

BREMSO: a simple score to predict early the natural course of multiple sclerosis.

BACKGROUND AND PURPOSE: Early prediction of long-term disease evolution is a major challenge in the management of multiple sclerosis (MS). Our aim was to predict the natural course of MS using the Bayesian Risk Estimate for MS at Onset (BREMSO), which gives an individual risk score calculated from demographic and clinical variables collected at disease onset. METHODS: An observational study was carried out collecting data from MS patients included in MSBase, an international registry. Disease impact was studied using the Multiple Sclerosis Severity Score (MSSS) and time to secondary progression (SP). To evaluate the natural history of the disease, patients were analysed only if they did not receive immune therapies or only up to the time of starting these therapies. RESULTS: Data from 14 211 patients were analysed. The median BREMSO score was significantly higher in the subgroups of patients whose disease had a major clinical impact (MSSS≥ third quartile vs. ≤ first quartile, P < 0.00001) and who reached SP (P < 0.00001). The BREMSO showed good specificity (79%) as a tool for predicting the clinical impact of MS. CONCLUSIONS: BREMSO is a simple tool which can be used in the early stages of MS to predict its evolution, supporting therapeutic decisions in an observational setting.

Enfermedad por Staphylococcus aureus resistente a meticilina en Panamá / Methicillin-resistant Staphylococcus aureus disease in Panama

Introducción: A nivel mundial se describe un incremento de las infecciones por Staphylococcus aureus (S. aureus) resistente a meticilina (SARM). El espectro clínico de la enfermedad incluye desde colonización nasal hasta infecciones superficiales e invasoras. Objetivo: Describir la frecuencia, características clínicas y factores de riesgo asociados a la enfermedad por SARM en menores de 15 años, establecer la prevalencia de colonización y la susceptibilidad a antimicrobianos de las cepas aisladas. Materiales y métodos: Estudio descriptivo. Se incluyó a sujetos con edades comprendidas entre 1 mes a 15 años de edad atendidos en el Hospital del Niño de Panamá con infección invasora o superficial por S. aureus entre el 1 de junio de 2009 al 30 de junio de 2010. El estado de portador fue evaluado a través de la realización de muestra nasal. Se analizaron variables epidemiológicas, clínicas, tratamiento de la enfermedad y patrones de resistencia antimicrobiana. Resultados: Cohorte constituida por 146 sujetos con infecciones por S. aureus, de los cuales el 8,9% (13/146) presentaron infección por SARM, 38,5% de los cuales fueron adquiridos en la comunidad. El 53,8% de los sujetos con SARM presentó infección invasora. No se identificaron factores de riesgo para el desarrollo de infecciones por SARM. La prevalencia de portador nasal fue del 8,3%. Las tasas de resistencia a eritromicina y clindamicina fueron de 15,4%. Conclusiones: La incidencia de infecciones por SARM fue baja comparada con otras regiones. Se recomienda la vigilancia epidemiológica activa a fin de establecer guías de tratamiento basadas en criterios epidemiológicos locales (AU)

Introduction: Infections due to methicillin-resistant Staphylococcus aureus (MRSA) are increasing worldwide. The clinical spectrum of the disease ranges from nasal colonization to superficial and invasive infections. Objectives: To describe the frequency, clinical characteristics and risk factors associated with MRSA disease in children under 15years old. To establish the prevalence of colonization and antimicrobial susceptibility of isolates. Material and methods: Retrospective study. Included subjects; aged 1 month to 15years old treated in the Hospital del Niño in Panama with invasive or superficial infection by S. aureus in the period from June 1, 2009 to June 30, 2010. Carrier status was assessed by performing nasal swabs. Demographic, clinical features, treatment of disease and antimicrobial resistance patterns. Results: A total of 146 subjects were collected with S.aureus infections, of which 8.9% (13/146) were infected by MRSA. Community-acquired MRSA accounted for 38.5% of the isolates. We did not identify any risk factors for developing MRSA infections. The prevalence of nasal carriage was 8.3%. The resistance rates to erythromycin and clindamycin were 15.4%. Conclusions: The incidence of MRSA infections was low compared with other regions. We recommend active surveillance in order to establish measures to prevent nosocomial infections and treatment guidelines based on local epidemiological criteria (AU)

[Methicillin-resistant Staphylococcus aureus disease in Panama]. / Enfermedad por Staphylococcus aureus resistente a meticilina en Panamá

INTRODUCTION: Infections due to methicillin-resistant Staphylococcus aureus (MRSA) are increasing worldwide. The clinical spectrum of the disease ranges from nasal colonization to superficial and invasive infections. OBJECTIVES: To describe the frequency, clinical characteristics and risk factors associated with MRSA disease in children under 15 years old. To establish the prevalence of colonization and antimicrobial susceptibility of isolates. MATERIAL AND METHODS: Retrospective study. Included subjects; aged 1 month to 15 years old treated in the Hospital del Niño in Panama with invasive or superficial infection by S. aureus in the period from June 1, 2009 to June 30, 2010. Carrier status was assessed by performing nasal swabs. Demographic, clinical features, treatment of disease and antimicrobial resistance patterns. RESULTS: A total of 146 subjects were collected with S.aureus infections, of which 8.9% (13/146) were infected by MRSA. Community-acquired MRSA accounted for 38.5% of the isolates. We did not identify any risk factors for developing MRSA infections. The prevalence of nasal carriage was 8.3%. The resistance rates to erythromycin and clindamycin were 15.4%. CONCLUSIONS: The incidence of MRSA infections was low compared with other regions. We recommend active surveillance in order to establish measures to prevent nosocomial infections and treatment guidelines based on local epidemiological criteria.

Sobrepeso y obesidad en los trastornos de la conducta alimentaria / Overweight and obesity in eating disorders

Fundamentos: El sobrepeso y la obesidad, habituales en algunos trastornos de la conducta alimentaria (TCA), influyen en su pron¨®stico. El objetivo fue analizar la prevalencia de sobrepeso y obesidad en TCA y los factores diet¨¦ticos responsables del aumento de peso, as¨ª como proporcionar unas pautas diet¨¦ticas para dichos pacientes. M¨¦todos: Revisadas las historias cl¨ªnicas de 1.005 pacientes con TCA se seleccionaron los 192 con un ¨ªndice de masa corporal (IMC) ¡Ý 25 kg/m2, de los que se recogieron datos cl¨ªnicos, antropom¨¦tricos y diet¨¦tico-nutricionales durante el tratamiento. Resultados: El IMC ¡Ý 25 se asoci¨® a bulimia nerviosa (BN) (33,33%) y al trastorno por atrac¨®n (TA) (58,85%), influyendo en el IMC m¨¢ximo alcanzado el tipo de TCA (p < 0,01), el picoteo (p < 0,001), la toma de ¡Ü 3 ingestas al d¨ªa (p < 0,05) y la ausencia de ejercicio regular (p < 0,05). En relaci¨®n con el TA, los pacientes con BN picotean menos (51,56%), no comen habitualmente pan (67,56%), no toman dos platos en cada comida (70,27%) y habitualmente no realizan ejercicio f¨ªsico (70,56%). Conclusiones: En el tratamiento de los TCA con sobrepeso y obesidad es especialmente necesaria la intervenci¨®n diet¨¦tica, promocionando h¨¢bitos saludables mediante una actuaci¨®n que, m¨¢s all¨¢ de la informaci¨®n, pretenda modificar conductas hacia patrones alimentarios m¨¢s saludables(AU)

Backgrounds: Overweight and obesity related to some eating disorders (ED) may influence in the prognostic. The aim was to analyze the prevalence of overweight and obesity in ED, and the dietetic factors which are related to weight gain. Moreover to give some dietetic rules for those patients. Methods: A total of 1005 medical histories were analyzed, and a sample of 192 patients with a BMI ¡Ý 25 kg/m2 was collected. Their clinical data, anthropometric measures, and dietetic data during the period of treatment were analyzed. Results: A BMI ¡Ý 25 was related to bulimia nervosa (BN) (33.33%) and overeating disorder (OD) (58.85%). The highest BMI was associated with the type of ED (p<0.01), taking snacks (p<0.001), the intake of ¡Ü 3 meals/day (p<0.05), and the absence of regular exercise (p<0.05). Comparing with OD, patients with BN have less snacks (51.56%), they don't eat bread with their meals (67.56%), they use to eat only one plate of food (70.27%) in their main meals, and they don't practice exercise (70.56%). Conclusions: The dietetic treatment in ED is necessary, especially in cases with overweight/ obesity associated. Healthy habits should be promoted not only giving information, but trying to change behaviors into more healthy eating habits(AU)

[Design and implementation of a national serum bank for the surveillance of exotic animal diseases in the Republic of Cuba]. / Diseño e instauración de un banco nacional de sueros para la vigilancia de enfermedades exóticas de los animales en la República de Cuba.

A serum bank for the surveillance of exotic diseases was designed in accordance with the provisions of the Information and Epizootiological Surveillance System in the Republic of Cuba. Sera were collected from imported animals, from sentinel animals used for monitoring target areas at biological risk and from animals located in high animal-density areas. Methodologies were developed for the selection and characterisation of target areas at biological risk and sentinel animal points, the collection and storage of serum samples and the management of the national animal serum bank. After developing the methodologies, the serum bank was established throughout Cuba. The national animal serum bank operates using a quality management system based on the recommendations of the World Organisation for Animal Health and the International Organization for Standardization.

Response to host volatiles by native and introduced populations of Dendroctonus valens (Coleoptera: Curculionidae, Scolytinae) in North America and China.

Bark beetles (Coleoptera: Curculionidae, Scolytinae) have specialized feeding habits, and commonly colonize only one or a few closely related host genera in their geographical ranges. The red turpentine beetle, Dendroctonus valens LeConte, has a broad geographic distribution in North America and exploits volatile cues from a wide variety of pines in selecting hosts. Semiochemicals have been investigated for D. valens in North America and in its introduced range in China, yielding apparent regional differences in response to various host volatiles. Testing volatiles as attractants for D. valens in its native and introduced ranges provides an opportunity to determine whether geographic separation promotes local adaptation to host compounds and to explore potential behavioral divergence in native and introduced regions. Furthermore, understanding the chemical ecology of host selection facilitates development of semiochemicals for monitoring and controlling bark beetles, especially during the process of expansion into new geographic ranges. We investigated the responses of D. valens to various monoterpenes across a wide range of sites across North America and one site in China, and used the resulting information to develop an optimal lure for monitoring populations of D. valens throughout its Holarctic range. Semiochemicals were selected based on previous work with D. valens: (R)-(+)-alpha-pinene, (S)-(-)-alpha-pinene, (S)-(-)-beta-pinene, (S)-(+)-3-carene, a commercially available lure [1:1:1 ratio of (R)-(+)-alpha-pinene:(S)-(-)-beta-pinene:(S)-(+)-3-carene], and a blank control. At the release rates used, (+)-3-carene was the most attractive monoterpene tested throughout the native range in North America and introduced range in China, confirming results from Chinese studies. In addition to reporting a more effective lure for D. valens, we present a straightforward statistical procedure for analysis of insect trap count data yielding cells with zero counts, an outcome that is common but makes the estimation of the variance with a Generalized Linear Model unreliable because of the variability/mean count dependency.

Biologic and genetic characteristics of Toxoplasma gondii isolates in free-range chickens from Costa Rica, Central America.

The prevalence of Toxoplasma gondii in free-ranging chickens is a good indicator of the prevalence of T. gondii oocysts in the soil because chickens feed from the ground. The prevalence of T. gondii in 144 free-range chickens (Gallus domesticus) from Costa Rica was determined. Antibodies to T. gondii were assayed by the modified agglutination test (MAT), and found in 60 (40.1%) of 144 chickens with titers of 1:5 in 16, 1:10 in 5, 1:20 in 2, 1:40 in 3, 1:80 in 5, and 1:160 or higher in 29. Tissues of all chickens were bioassayed for T. gondii in mice or cats. Hearts and brains of 52 chickens with titers of 1:5 or higher and 16 chickens with doubtful titers were pooled and bioassayed in mice. Tissues from 76 chickens with MAT titers of 1:10 or less were pooled and fed to three T. gondii-free cats. Fecal floats of cats were bioassayed orally in mice but were negative for T. gondii oocysts. T. gondii was isolated by bioassay in mice from 32 chickens with MAT titers of 1:10 or higher. All infected mice from 4 of the 32 isolates died of toxoplasmosis. Genotyping of these 32 isolates using polymorphisms at the loci SAG1, SAG2, SAG3, BTUB and GRA6 revealed five genotypes. Five isolates had type I alleles and one isolate had type III alleles at all loci. The rest 26 isolates contained the combination of type I and II or I and III alleles and were divided into three genotypes. None was found to have genotype II alleles at all five loci. This is the first report of genetic characterization of T. gondii isolates from Costa Rica, Central America.

[Hyperhomocysteinemia-related cerebral venous thrombosis]. / Trombosis venosa cerebral en relación con la hiperhomocisteinemia.

INTRODUCTION: Moderate hyperhomocysteinemia is a causal risk factor for atherosclerosis and venous thromboembolism. Recent researches have tried to find out a causal relationship. However, only a small number of cases have been reported on hyperhomocysteinemia and cerebral venous thrombosis in the world medical literature. CASE REPORT: We present the case of a 21 years old woman, and oral contraceptives taker, who consulted for a one week clinical picture of biparietal headache, nausea and vomiting. Examination revealed bilateral papilledema, and subsequent CT scan, MRI and MR angiography showed thrombosis of the left lateral sinus. Immunologic tests (antinuclear antibodies, antiphospholipid antibodies) were negative. Hypercoagulability studies showed persistent homocysteine high levels. The patient improved and was discharged after treatment with anticoagulants and therapeutic measures against brain edema. DISCUSSION: The 70 percent of the patients with thrombosis of the cerebral venous sinuses present hypercoagulable states, including moderate hyperhomocysteinemia. Several mechanisms are proposed for venous thrombosis in hyperhomocysteinemia, homocysteine induced endothelial dysfunction between others. Otherwise, oral contraceptives can increase the risk of venous thrombosis in other prothrombotic conditions. Folic acid and vitamins supplementation therapy are commented.

Trombosis venosa cerebral en relación con la hiperhomocisteinemia / Hyperhomocysteinemia related cerebral venous trombosis

Introducción. La hiperhomocisteinemia moderada es un factor de riesgo independiente para la arteriosclerosis y la enfermedad tromboembólica. En los últimos años existe un interés creciente por determinar su relación causal; sin embargo, se recogen pocos casos en la literatura asociados a la trombosis venosa cerebral. Caso clínico. Mujer de 21 años que toma anticonceptivos orales. Una semana antes del ingreso, comienza con cefalea opresiva biparietal continua que interfiere el sueño, acompañada de nausea y vómitos, y que empeora con las maniobras de Valsalva. En la exploración neurológica destaca un papiledema bilateral de predominio izquierdo. El resto de la exploración fue normal. En distintas pruebas de neuroimagen –tomografía computarizada (TAC), resonancia magnética (RM) y angiorresonancia magnética– se objetiva una trombosis de seno transverso izquierdo. Se realizó un estudio inmunológico (ANA, ANCA y anticuerpos antifosfolípidos), que fue normal. En el estudio de hipercoagulabilidad, la concentración de homocisteína resultó elevada de forma repetida. Tras un tratamiento anticoagulante, y medidas antiedema, evolucionó satisfactoriamente. Discusión. El 70% de las trombosis de seno venoso se deben a estados protrombóticos, entre ellos la hiperhomocisteinemia moderada. Su patogénesis parece ser multifactorial, incluido el daño endotelial directo. Por otra parte, se comenta el papel facilitador de los anticonceptivos orales sobre estados protrombóticos subclínicos, además de discutirse las posibilidades terapéuticas con ácido fólico (AU)

Introduction. Moderate hyperhomocystinemia is a causal risk factor for atherosclerosis and venous thromboembolism. Recent researches have tried to find out a causal relationship. However, only a small number of cases have been reported on hyperhomocysteinemia and cerebral venous thrombosis in the world medical literature. Case report. We present the case of a 21 years old woman, and oral contraceptives taker, who consulted for a one week clinical picture of biparietal headache, nausea and vomiting. Examination revealed bilateral papilledema, and subsequent CT scan, MRI and MR angiography showed thrombosis of the left lateral sinus. Immunologic tests (antinuclear antibodies, antiphospholipid antibodies) were negative. Hypercoagulability studies showed persistent homocysteine high levels. The patient improved and was discharged after treatment with anticoagulants and therapeutic measures against brain edema. Discussion. The 70 percent of the patients with thrombosis of the cerebral venous sinuses present hypercoagulable states, including moderate hyperhomocysteinemia. Several mechanisms are proposed for venous thrombosis in hyperhomocysteinemia, homocysteine induced endothelial dysfunction between others. Otherwise, oral contraceptives can increase the risk of venous thrombosis in other prothrombotic conditions. Folic acid and vitamins supplementation therapy are commented (AU)

Phenol degradation in horizontal-flow anaerobic immobilized biomass (HAIB) reactor under mesophilic conditions.

A bench-scale horizontal-flow anaerobic immobilized biomass (HAIB) reactor was assayed aiming to verify its potential use for phenol degradation. The HAIB reactor consisted of a bore-silicate tube (100 cm long; 5.04 cm diameter) filled with polyurethane foam matrices containing immobilized anaerobic sludge. Before being subjected to phenol, the reactor was fed with synthetic substrate at the influent chemical oxygen demand (COD) of 1,028 mg.l-1 achieving 98% of COD removal efficiency. Thereafter, phenol as the sole carbon source was added under step-increasing concentrations from 50 to 1,200 mg.l-1. Phenol degradation was evaluated by gas chromatographic analysis of influent and effluent samples. Process monitoring included determinations of pH, volatile acids, alkalinity and COD. The HAIB reactor was operated at a constant hydraulic detention time (HDT) of 12 hours. After 33 days with 50 mg/l of phenol in the influent, the reactor achieved 98% of COD removal efficiency. Successful phenol degradation (efficiency removal of 99%) occurred for influent concentrations of 100, 300, 600, 900 and 1,200 mg.l-1 after 148, 58, 47, 29 and 7 days, respectively. The predominance of Methanosaeta-like, rods and methanogenic cocci could be observed in all the operating conditions, besides the presence of phenol oxidizing microorganisms as irregular rods. The results indicate that phenol degradation at very high rates can be accomplished in HAIB reactors containing acclimatized biomass.

The sequence of the human genome.

A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge.

Cochlear implantation in patients with compromised healing.

BACKGROUND: The indications for cochlear implantation (CI) are continually evolving and, as experience accumulates, the relative contraindications for CI continue to decrease. However, there is little information regarding CI in patients who may be considered to be at risk for poor wound healing due to immunosuppression or intercurrent disease. OBJECTIVE: To assess and report the complication rates, postoperative course, postimplant rehabilitation, and long-term performance of patients considered at risk due to presumably impaired healing capability. We hypothesized that these patients had outcomes similar to other implanted patients. METHODS: This is a retrospective chart review of 277 patients who have received CI at the University of Miami Ear Institute between 1990 and 1999. The clinical courses of 6 patients on immunosuppressive medications and 7 patients with diseases believed to be associated with poor healing are reported. RESULTS: Long-term follow-up (mean, 33 months) showed postoperative complication rates, performance, and rehabilitation compliance that were similar to published reports of noncompromised patients. CONCLUSION: CI of selected patients with potentially reduced healing capabilities is safe and effective.

A whole-genome assembly of Drosophila.

We report on the quality of a whole-genome assembly of Drosophila melanogaster and the nature of the computer algorithms that accomplished it. Three independent external data sources essentially agree with and support the assembly's sequence and ordering of contigs across the euchromatic portion of the genome. In addition, there are isolated contigs that we believe represent nonrepetitive pockets within the heterochromatin of the centromeres. Comparison with a previously sequenced 2.9- megabase region indicates that sequencing accuracy within nonrepetitive segments is greater than 99. 99% without manual curation. As such, this initial reconstruction of the Drosophila sequence should be of substantial value to the scientific community.

Class II major histocompatibility complex typing across the ethnic barrier in pemphigoid gestationis. A study in Mexicans.

BACKGROUND: Pemphigoid gestationis (PG), also called herpes gestationis, is a rare autoimmune disease of pregnancy or puerperium (estimated 1 out of 50,000 pregnancies among Caucasians). A previous series has demonstrated an association of PG with human leukocyte antigen (HLA)-DR3 or HLA-DR4 haplotypes. While these haplotypes are most commonly found in individuals of European ancestry, they have also been found in African-American patients affected with PG. PG has rarely been reported in other ethnic groups, and the HLA association in non-Europeans has not been examined. METHODS: We have characterized eight patients of Mexican ancestry who have PG by clinical, histologic, and immunofluorescence criteria. Class I and class II major histocompatibility complex (MHC) antigens were studied by standard microlymphocytotoxicity assays. Class II MHC antigens were further studied by polymerase chain reaction (PCR) amplification of HLA-DRB1, DQA, and DQB genes and allele-specific oligonucleotide hybridization. For comparison purposes, we used results obtained from a group of 100 ethnically matched healthy individuals. RESULTS: We found that all eight patients had the HLA-DR3/DR4 phenotype; all HLA-DR3 haplotypes were HLA-DRB1*0301, DQA1*0501, and DQB1*0201, whereas half of the HLA-DR4 haplotypes were from the DRB1*0401 subtype and the other half were DRB1 *0407. CONCLUSIONS: These results suggest that, in Mexicans, the genetic susceptibility for the development of PG is strongly influenced by the genetic admixture of Caucasian origin, and the role of class II MHC antigens in the pathophysiology of this disease is confirmed.