GS-9857 in patients with chronic hepatitis C virus genotype 1-4 infection: a randomized, double-blind, dose-ranging phase 1 study.

GS-9857, an inhibitor of the hepatitis C virus (HCV) nonstructural protein (NS) 3/4A, demonstrates potent activity against HCV genotypes 1-6 and improved coverage against commonly encountered NS3 resistance-associated variants (RAVs). In this study, the safety, tolerability, antiviral activity and pharmacokinetics (PK) of GS-9857 were evaluated in patients with chronic HCV genotype 1-4 infection. Patients with genotype 1-4 infection received placebo or once-daily GS-9857 at doses ranging from 50 to 300 mg for 3 days under fasting conditions. GS-9857 was well tolerated; all reported adverse events (AEs) were mild or moderate in severity. Diarrhoea and headache were the most commonly reported AEs. Grade 3 or 4 laboratory abnormalities were observed in 17% of patients receiving GS-9857; there were no Grade 3 or 4 abnormalities in alanine aminotransferase, aspartate aminotransferase or alkaline phosphatase levels. GS-9857 demonstrated potent antiviral activity in patients with chronic HCV infection, achieving mean and median maximum reductions in HCV RNA of ≥3 log10 IU/mL following administration of a 100-mg dose in patients with HCV genotype 1a, 1b, 2, 3 or 4 infection. The antiviral activity of GS-9857 was unaffected by the presence of pretreatment NS3 RAVs. In patients with genotype 1-4 infection, GS-9857 exhibited linear PK and was associated with a median half-life of 29-42 h, supporting once-daily dosing. Thus, the tolerability, efficacy and pharmacokinetic profile of GS-9857 support its further evaluation for treatment of patients with chronic HCV infection.

A randomized, double-blind, placebo-controlled phase II study to assess the efficacy and safety of mapatumumab with sorafenib in patients with advanced hepatocellular carcinoma.

BACKGROUND: This randomized, double-blind, placebo-controlled, phase II study evaluated the efficacy and safety of mapatumumab (a human agonistic monoclonal antibody against tumor necrosis factor-related apoptosis-inducing ligand receptor 1) in combination with sorafenib in patients with advanced hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Patients with advanced HCC (stratified by Barcelona Clinic Liver Cancer stage and Eastern Cooperative Oncology Group performance status) were randomized 1:1 to receive sorafenib (400 mg, twice daily per 21-day cycle) and either placebo (placebo-sorafenib arm) or mapatumumab (30 mg/kg on day 1 per 21-day cycle; mapatumumab-sorafenib arm). The primary end point was time to (radiologic) progression (TTP), assessed by blinded independent central review. Key secondary end points included progression-free survival, overall survival, and objective response. RESULTS: In total, 101 patients were randomized (placebo-sorafenib arm: N = 51; mapatumumab-sorafenib arm: N = 50). There was no significant difference in median TTP between both arms [5.6 versus 4.1 months, respectively; adjusted hazard ratio (one-sided 90% confidence interval) 1.192 (0-1.737)]. No mapatumumab-related benefit was identified when TTP was evaluated in the stratified subgroups. The addition of mapatumumab to sorafenib did not demonstrate improvement in the secondary efficacy end points. The reported frequency of adverse events (AEs) and serious AEs was comparable in both treatment arms. CONCLUSIONS: The addition of mapatumumab to sorafenib did not improve TTP or other efficacy end points, nor did it substantially change the toxicity profile of sorafenib in patients with advanced HCC. Based on these results, further development of the combination of mapatumumab and sorafenib in HCC is not planned.

A phase 1, randomized, dose-ranging study of GS-5816, a once-daily NS5A inhibitor, in patients with genotype 1-4 hepatitis C virus.

GS-5816 is an inhibitor of the hepatitis C virus (HCV) NS5A protein that has demonstrated pan-genotypic activity and a high barrier to resistance in HCV replicon assays. The aim of this study was to evaluate the safety, antiviral activity and pharmacokinetics of once-daily doses of GS-5816 in patients with genotype 1-4 HCV infection. Patients with genotype 1-4 HCV infection were randomized to 3 days of GS-5816 at doses ranging from 5 to 150 mg or placebo. Adverse events were recorded, and plasma samples obtained for analysis of pharmacokinetics, HCV RNA and NS5A sequencing studies. GS-5816 5-150 mg for 3 days was well tolerated and resulted in rapid declines in HCV RNA that were sustained over the dosing period. In patients treated with the 150 mg dose of GS-5816, the mean maximal HCV RNA declines were 4.0, 4.0, 4.4, 3.3 and 3.5 log10 IU/mL in patients with genotype 1a, 1b, 2, 3 and 4 HCV infection, respectively. Pretreatment NS5A resistance-associated polymorphisms were detected in 31% (22/70) of patients. Genotype 1 and 3 HCV-infected patients without pretreatment NS5A resistance-associated polymorphisms had greater declines in HCV RNA than patients with resistance-associated polymorphisms. Plasma pharmacokinetics were supportive of once-daily dosing. GS-5816 demonstrated pangenotypic antiviral activity in patients with genotype 1-4 HCV infection. It will be further evaluated in combination with other pangenotypic direct-acting antivirals to achieve the goal of developing a well-tolerated, highly effective treatment for all HCV genotypes.

All-oral therapy with nucleotide inhibitors sofosbuvir and GS-0938 for 14 days in treatment-naive genotype 1 hepatitis C (nuclear).

Sofosbuvir and GS-0938 are distinct nucleotide analogues with activity against hepatitis C virus (HCV) in vitro. We evaluated the antiviral activity and safety of sofosbuvir and GS-0938 alone and in combination in HCV genotype 1 patients. In this double-blind study, 40 treatment-naïve patients were randomly assigned to 4 treatment cohorts: (i) GS-0938 for 14 days, (ii) GS-0938 for 7 days followed by GS-0938 plus sofosbuvir for 7 days, (iii) sofosbuvir for 7 days followed by GS-0938 plus sofosbuvir for 7 days and (iv) GS-0938 plus sofosbuvir for 14 days. In each arm, 8 patients received active drug and 2 placebo. After 7 days of dosing, patients in all 4 dose groups experienced substantial reductions in HCV RNA, with median declines (Q1, Q3) of -4.50 (-4.66, -4.24) in Cohort 1, -4.55 (-4.97, -4.13) in Cohort 2, -4.65 (-4.78, -4.17) in Cohort 3 and -4.43 (-4.81, -4.13) in Cohort 4; patients receiving placebo had essentially no change in HCV RNA (+0.07 log(10) IU/mL). Seven days after the end of treatment, the proportions of patients with HCV RNA <15 IU/mL were 4 (50%), 8 (100%), 7 (88%) and 5 (63%) for Cohorts 1-4, respectively, vs 0 for placebo. No viral breakthrough or resistance mutations were observed. No serious adverse events or Grade 3 or 4 adverse events were reported. Sofosbuvir and GS-0938-alone and in combination--were well tolerated and led to substantial reductions in viral load. Sofosbuvir is undergoing further investigation as a possible backbone of an all-oral regimen for chronic HCV.

Valoración del riesgo de desarrollar úlceras por presión en unidades de cuidados críticos: revisión sistemática con metaanálisis / Risk assessment scales for pressure ulcer in intensive care units: a systematic review with metaanalysis

OBJETIVOS: identificar las escalas de valoración del riesgo de desarrollar úlceras por presión que han sido utilizadas en el contexto de los cuidados críticos. Determinar cuáles de ellas han sido validadas en función de los criterios de validez predictiva, capacidad predictiva y fiabilidad, elaborando, cuando sea posible, indicadores agregados. MÉTODOS: revisión sistemática de la literatura científica. Se realizo una búsqueda en las 14 principales bases de datos bibliográficas internacionales de ciencias de la salud. Se incluyeron los estudios publicados entre 1962 y 2009, sin restricción idiomática, que fueran prospectivos, con pérdidas < 25%, con seguimiento sistemático y que aportaran datos de validez y/o capacidad predictiva y/o fiabilidad. Se ha excluido la literatura gris, los estudios de revisión, retrospectivos y transversales. La valoración de la calidad metodológica de los estudios se ha realizado mediante el Critical Appraisae Skills Programme (CASP). Los indicadores analizados han sido validez, magnitud de efecto (RR) y fiabilidad. RESULTADOS: se han identificado un total de 255 artículos que identifican 16 escalas de valoración del riesgo diseñadas específicamente para las UCI. Existen 26 estudios que miden la validez de las mismas. Solo tres escalas tienen más de un estudio de validación (NM Bienstein, Cubbin-Jackson, Jackson-Cubbin). Cuatro escalas generalistas también han sido validadas en UCI (Braden, Norton, BM Song-Choi y Waterlow). NM Bienstein y Waterlow no son válidas por baja sensibilidad. Cubbin-Jackson, Jackson-Cubbin y Norton presentan datos muy similares de validez y capacidad predictiva, pero con muestra muy pequeña. Braden es la escala mejor testada en las UCI, con adecuados parámetros de validez y capacidad predictiva. CONCLUSIONES: recomendamos el uso de la escala de Braden para valorar el riesgo de desarrollar úlceras por presión en las unidades de cuidados críticos. Otras escalas como Cubbin-Jackson, Jackson-Cubing, Norton o BM Song-Choi, pueden ser útiles, pero precisan ser probadas en un mayor número de pacientes

AIMS: To identify risk assessment scales for pressure ulcers that have been used in the critical care units. Determine which of them have been validated according to the criteria of validity, predictive capacity and reliability, developing, where possible, aggregate indicators. METHODS: Systematic review of the clinical literature with meta-analysis. The main international health science databases were searched for prospective studies on the validity and/or predictive capacity of pressure ulcers risk assessment scales published between 1962 and 2009 in any language and with a loss to follow-up of less than 25%. We excluded the grey literature, reviews, and retrospective and cross-sectional studies. The methodological quality of the studies was assessed according to the guidelines of the Critical Appraisal Skills Program. The indicators analyzed were validity, effect size (RR) and reliability. When two or more valid original studies were found, a meta-analysis was conducted using the random-effect model followed by a sensitivity analysis. RESULTS: We have identified a total of 255 articles identified 16 risk assessment scales designed specifically for UCI. There are 26 studies that measure the validity of the same. Only three scales have more of a validation study (NM Bienstein, Cubbin-Jackson, Jackson-Cubbin). Four general scales have also been validated in ICU (Braden, Norton, BM Choi Song-and Waterlow). Waterlow and NM Bienstein are not valid for low sensitivity. Cubbin-Jackson, Jackson-Cubbin and Norton have very similar predictive validity data, but with very small sample. Braden scale is best tested in the ICU, with appropriate parameters and predictive validity. CONCLUSIONS: We recommend the use of the Braden Scale to assess the risk of developing pressure ulcers in critical care units. Other scales as Cubbin-Jackson, Jackson-Cubing, Norton or BM Choi-Song can be useful, but need to be tested in a larger number of patients

Optimized threshold for serum HCV RNA to predict treatment outcomes in hepatitis C patients receiving peginterferon alfa-2a/ribavirin.

It is unclear whether the current threshold for 'high' hepatitis C virus (HCV) RNA level (800,000 IU/mL) is optimal for predicting sustained virological response (SVR). We retrospectively analysed pretreatment HCV RNA levels and SVR rates in 1529 mono-infected and 176 HIV-HCV co-infected patients treated with peginterferon alfa-2a (40 kD) plus ribavirin. We improved the threshold for differentiating low and high viral load by fitting semiparametric generalized additive logistic regression models to the data and constructing receiver operating characteristics curves. Among HCV genotype 1 mono-infected patients, the difference in SVR rates between those with low and high baseline HCV RNA levels was 27% (70%vs 43%) when 400,000 IU/mL was used and 16% (59%vs 43%) when 800,000 IU/mL was used. In HIV-HCV genotype 1 co-infected patients, the difference was 51% (71%vs 20%) when 400,000 IU/mL was used and 43% (61%vs 18%) when 800,000 IU/mL was used. A lower threshold (200,000 IU/mL) was identified for genotype 1 mono-infected patients with 'normal' alanine aminotransferase (ALT) levels. No threshold could be identified in HCV genotype 2 or 3 patients. A threshold HCV RNA level of 400,000 IU/mL is optimal for differentiating high and low probability of SVR in genotype 1-infected individuals with elevated ALT.

Degree of viral decline early in treatment predicts sustained virological response in HCV-HIV coinfected patients treated with peginterferon alfa-2a and ribavirin.

BACKGROUND: In hepatitis C virus (HCV) monoinfection, the on-treatment virological response at Weeks 4 and 12 is a strong predictor of treatment outcomes. METHODS: In a retrospective analysis, we examined these responses in 289 HIV-HCV coinfected patients treated with Peg-IFN alfa-2a /ribavirin for 48 weeks in a large randomized, multinational trial (APRICOT). RESULTS: Overall, 21% of patients achieved a rapid virological response at Week 4 and, of these, 88% achieved a sustained virological response. An early virological response at Week 12 was achieved in 71% of patients, and 56% of these patients achieved a sustained virological response. These results are similar to the sustained virological response rates obtained in monoinfected patients who achieve a rapid or early virological response. Patients who did not achieve a rapid virological response but who had unquantifiable HCV RNA or > 3 log10 drop over baseline also had high sustained virological response rates. A total of 46% of patients achieved undetectable HCV RNA (<50 IU/mL) at Week 12. Multiple logistic regression analysis showed that infection with HCV genotype 2/3, low baseline HCV RNA level, and lower age predicted rapid virological response. Infection with HCV genotype 2/3 and low baseline HCV RNA level predicted early virological response. CONCLUSION: A rapid virological response is the best predictor of a sustained virological response, and lack of an early virological response is the best predictor of no sustained virological response. Such results are consistent with findings in HCV monoinfected patients.

Factors associated with rapid and early virologic response to peginterferon alfa-2a/ribavirin treatment in HCV genotype 1 patients representative of the general chronic hepatitis C population.

Rapid virologic response (RVR) and complete early virologic response (cEVR) are associated with sustained virologic response to hepatitis C virus (HCV) therapy. We retrospectively examined baseline and on-treatment factors associated with RVR (HCV RNA undetectable at week 4) and cEVR (HCV RNA undetectable at week 12, regardless of week 4 response). The analysis comprised 1550 HCV genotype-1 patients from five clinical trials, including three enriched with difficult-to-treat populations, randomized to peginterferon alfa-2a 180 microg/week plus ribavirin 1000-1200 mg/day. Overall, 15.6% achieved RVR and 54.0% achieved cEVR. Baseline factors predictive of RVR were serum HCV RNA 3 x ULN (OR: 2.01; P < 0.0001), non-cirrhotic status (OR: 1.92; P = 0.0087), age 13 mg/kg/day was predictive of RVR (OR: 1.69; P = 0.005) and cEVR (OR: 1.24; P = 0.09), whereas peginterferon alfa-2a dose reduction was not. Greater decreases in haematologic parameters were observed in patients who achieved cEVR compared with patients who did not. In conclusion, several baseline and on-treatment factors were associated with RVR and cEVR to peginterferon alfa-2a plus ribavirin in difficult-to-treat HCV genotype-1 patients, providing important prognostic information on the antiviral response in a patient cohort that is reflective of the general chronic hepatitis C population.

Strong association of socioeconomic status with genetic ancestry in Latinos: implications for admixture studies of type 2 diabetes.

AIMS/HYPOTHESIS: Type 2 diabetes is more prevalent in US American minority populations of African or Native American descent than it is in European Americans. However, the proportion of this epidemiological difference that can be ascribed to genetic or environmental factors is unknown. To determine whether genetic ancestry is correlated with diabetes risk in Latinos, we estimated the proportion of European ancestry in case-control samples from Mexico and Colombia in whom socioeconomic status had been carefully ascertained. METHODS: We genotyped 67 ancestry-informative markers in 499 participants with type 2 diabetes and 197 controls from Medellín (Colombia), as well as in 163 participants with type 2 diabetes and 72 controls from central Mexico. Each participant was assigned a socioeconomic status scale via various measures. RESULTS: Although European ancestry was associated with lower diabetes risk in Mexicans (OR [95% CI] 0.06 [0.02-0.21], p = 2.0 x 10(-5)) and Colombians (OR 0.26 [0.08-0.78], p = 0.02), adjustment for socioeconomic status eliminated the association in the Colombian sample (OR 0.64 [0.19-2.12], p = 0.46) and significantly attenuated it in the Mexican sample (OR 0.17 [0.04-0.71], p = 0.02). Adjustment for BMI did not change the results. CONCLUSIONS/INTERPRETATION: The proportion of non-European ancestry is associated with both type 2 diabetes and lower socioeconomic status in admixed Latino populations from North and South America. We conclude that ancestry-directed search for genetic markers associated with type 2 diabetes in Latinos may benefit from information involving social factors, as these factors have a quantitatively important effect on type 2 diabetes risk relative to ancestry effects.

Conocimientos y creencias de las enfermeras sobre el cuidado de las úlceras por presión: revision sistemática de la literatura / Nurses’ knowledge and beliefs about pressure ulcers care: a systematic review of literature

Objetivos: Determinar el estado actual del conocimiento sobre las medidasde prevención y tratamiento de las upp en los profesionales de enfermería.Diseño: Revisión sistemática. Fuentes de datos: Se han utilizado 14 bases dedatos bibliográficas. Database of Abstracts of Reviews of Effectiveness (DARE);Cinahl; Medline; Currents Contents: Clinical Medicine, Social and BehavioralSciences, Life Sciences; Índice médico español (IME); Cuiden; CentroLatinoamericano y del Caribe de Información en Ciencias de la Salud (LILACS);Cochrane Library; EBSCO; ScienceDirect; Springer; InterSciencia;ProQuest y Pascal. Métodos de revisión: Se han incluido artículos de encuestasde conocimientos sobre úlceras por presión que estuvieran publicadosen español, inglés, francés y portugués, y un estudio cuasi-experimental,para ver la influencia en los conocimientos de una sesión educativa específicasobre upp. Se han excluido aquellos estudios sobre conocimientos que utilizanmetodologías que impiden su comparación. Resultados: Se han incluido18 artículos. La mayoría utilizaron un muestreo por conveniencia. Losparticipantes de los estudios eran enfermeras tituladas, auxiliares de enfermeríay estudiantes. El índice global de conocimientos se sitúa en un 70%como media; con un rango entre 73 y 85% para la prevención y de 56 a 78%para tratamiento. El nivel de formación influye sobre el índice de conocimientos.Los factores de riesgo mejor conocidos son la incontinencia, la inmovilidad,presión mantenida o la desnutrición. Las intervenciones de enfermeríamejor conocidas son cuidados de la piel, mantener la cama limpia y los cambios posturales. El uso de superficies de alivio de la presión, la educaciónal paciente y la clasificación de la upp están entre las intervenciones enfermerasconocidas por un menor número de profesionales. Conclusiones:Existe un aceptable nivel de conocimientos de las recomendaciones para laprevención y cuidados de las upp, siendo superior el índice de conocimientosde factores de riesgo y prevención al de tratamiento. La formación específicasobre upp mejora este índice de conocimientos

Aim: To determine the current knowledge about prevention and treatment ofpressure ulcers (PU) in nurses. Design: Systematic review. Data source: Fourteenbibliographic databases: Database of Abstracts of Reviews of Effectiveness (DARE);Cinahl; Medline; Currents Contents: Clinical Medicine, Social and BehavioralSciences, Life Sciences; Índice médico español (IME); Cuiden; Centro Latinoamericanoy del Caribe de Información en Ciencias de la Salud (LILACS);Cochrane Library; EBSCO; ScienceDirect; Springer; InterSciencia; ProQuest yPascal. Methods: Papers about surveys of knowledge on PU published in Spanish,English, French and Portuguese were included. Also a quasi-experimentalstudy about the effect of a formation session on PU knowledge was included. Studiesabout knowledge using non comparable methodology were excluded. Results:Eighteen papers were included in the review. Most of them have used a conveniencesample. Participants were registered nurses, licensed nurses and nurse students.As average, the overall index of knowledge was 70%; with a range between73 and 85% for prevention, and between 56 and 78% for treatment. Risk factorsbest known were: incontinence, immobility, pressure or malnutrition. Thenursing interventions best known were: skin care, maintain clean the bed and repositioning.On contrary, the use of pressure-relief surfaces, patient education andPU classification were the nursing interventions kwon by a fewer number of nurses.Conclusions: Overall the level of knowledge about PU care is acceptable.The knowledge about risk factors and prevention measures is better than that oneabout treatment. Education and specific training about PU improve the knowledge index

Occult hepatitis B virus infection in the setting of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection: clinically relevant or a diagnostic problem?

The clinical relevance of occult hepatitis B virus (HBV) infection, defined as detectable HBV DNA serum/liver, in the absence of hepatitis B surface antigen (HBsAg), is unclear. We determined the prevalence of serum occult HBV infection in HIV/HCV co-infected patients enrolled in APRICOT, a randomized multinational trial that investigated the efficacy and safety of peginterferon alfa-2a (40 kDa) plus ribavirin for treatment of HCV. We also examined the effect of prior HBV exposure to liver histology at baseline. Only HBsAg-negative patients were eligible. At screening, serum HBV DNA was assessed by commercial assay (detection limit = 200 copies/mL). Patients were divided into four serological groups: anti-HBs+/anti-HBc+; anti-HBs-/anti-HBc+; anti-HBs+/ anti-HBc-; anti-HBs-/anti-HBc-. Baseline liver biopsy grade and stage were compared among groups. Serum HBV DNA was undetectable in all patients, (n = 866). Results of anti-HBs and anti-HBc was available for 176 patients: 60 (34.1%) anti-HBs+/anti-HBc+; 60 (34.1%) anti-HBs-/anti-HBc+; 11 (6.3%) anti-HBs+/anti-HBc-; 45 (25.6%) anti-HBs-/anti-HBc-. There were no differences among the groups in the histological grade or stage at baseline liver biopsies. Occult HBV infection in serum was not detected in this large immunocompetent cohort. Moreover, prior exposure to HBV did not appear to have any affect on baseline liver histology.

Effect of ribavirin on intracellular and plasma pharmacokinetics of nucleoside reverse transcriptase inhibitors in patients with human immunodeficiency virus-hepatitis C virus coinfection: results of a randomized clinical study.

The intracellular triphosphorylation and plasma pharmacokinetics of lamivudine (3TC), stavudine (d4T), and zidovudine (ZDV) were assessed in a pharmacokinetic substudy, in 56 human immunodeficiency virus-hepatitis C virus (HIV-HCV) coinfected patients receiving peginterferon alfa-2a (40KD) 180 microg/week plus either placebo or ribavirin (RBV) 800 mg/day in the AIDS PEGASYS Ribavirin International Coinfection Trial. There were no significant differences between patients treated with RBV and placebo in plasma pharmacokinetics parameters for the nucleoside reverse transcriptase inhibitors (NRTIs) at steady state (weeks 8 to 12): ratios of least squares mean of area under the plasma concentration-time curve (AUC(0-12 h)) were 1.17 (95% confidence interval, 0.91 to 1.51) for 3TC, 1.44 (95% confidence interval, 0.58 to 3.60) for d4T and 0.85 (95% confidence interval, 0.50 to 1.45) for ZDV, and ratios of least squares mean plasma C(max) were 1.33 (95% confidence interval, 0.99 to 1.78), 1.06 (95% confidence interval, 0.68 to 1.65), and 0.84 (95% confidence interval, 0.46 to 1.53), respectively. Concentrations of NRTI triphosphate (TP) metabolites in relation to those of the triphosphates of endogenous deoxythymidine-triphosphate (dTTP) and deoxcytidine-triphosphate (dCTP) were similar in the RBV and placebo groups. Differences (RBV to placebo) in least squares mean ratios of AUC(0-12 h) at steady state were 0.274 (95% confidence interval, -0.37 to 0.91) for 3TC-TP:dCTP, 0.009 (95% confidence interval, -0.06 to 0.08) for d4T-TP:dTTP, and -0.081 (95% confidence interval, -0.40 to 0.24) for ZDV-TP:dTTP. RBV did not adversely affect HIV-1 replication. In summary, RBV 800 mg/day administered in combination with peginterferon alfa-2a (40KD) does not significantly affect the intracellular phosphorylation or plasma pharmacokinetics of 3TC, d4T, and ZDV in HIV-HCV-coinfected patients.

Identification of a putative methylenetetrahydrofolate reductase by sequence analysis of a 6.8 kb DNA fragment of yeast chromosome VII.

We report the sequence analysis of a 6.8 kb DNA fragment from Saccharomyces cerevisiae chromosome VII. This sequence contains five open reading frames (ORFs) greater than 100 amino acids. There is also an incomplete ORF flanking one of the extremes, G2868, which is the 3' end of the SCS3 gene (Hosaka et al., 1994). The translated sequence of ORF G2882 shows similarity to the human methylenetetrahydrofolate reductase (Goyette et al., 1994). ORF G2889 shows no significant homologies with the sequences compiled in databases. ORF G2893 corresponds to the gene SUP44, coding for the yeast ribosomal protein S4 (All-Robin et al., 1990). G2873 and G2896 are internal ORFs.