构建及鉴定表达胃泌酸调节素的乳酸乳球菌

目的:构建食品级表达胃泌酸调节素(oxyntomodulin,OXM)的乳酸乳球菌,鉴定其在体外?体内的表达水平?方法:构建重组质粒pNZ8149-OXM电转至乳酸乳球菌中,用Western blot检测重组乳酸乳球菌OXM表达水平?给小鼠喂食表达OXM的乳酸乳球菌后,用液质联用质谱检测小鼠血清OXM的含量?结果:重组质粒经测序鉴定正确,制备的重组乳酸乳球菌在nisin诱导5 h后OXM表达量最高,食用后小鼠血清OXM含量是对照组的2.5倍左右?结论:成功构建了表达胃泌酸调节素的乳酸乳球菌,为进一步探讨其减肥降脂效应提供了基础?     

The presence of citrulline in salivary glands is evidence that nitric oxide is mediator of inflammation in Sjögren acinar epithelia

Aim: The present study addresses the question whether nitric oxide (NO) plays a role in inflammation of salivary glands in Sjögren's syndrome. Methods: The expression of inducible nitric oxide synthase (iNOS) and the presence of citrulline, as a monitor of NO activity were studied by immunohistochemistry, in minor salivary glands from 24 patients with primary Sjögren syndrome. An equal number of control tissues were included. The presence of mRNA of eNOS (endothelial NOS) and iNOS in tissues was studied by fluorescent in situ hybridization. Results: All salivary glands displayed eNOS along the ductal epithelia, blood vessels and acini. In Sjögren disease iNOS enzyme was widely expressed along ductal epithelia, acini and in foci of lymphocyte infiltration; therefore by the extensive citrulline presence and iNOS, we infer that NO is related to inflammation. Control biopsies were negative for iNOS and citrulline. Conclusion: The present data suggest that local production of NO should contribute to salivary gland inflammation in Sjögren disease.     

Treatment of acute lymphoblastic leukaemia in adults

Between 1972 and 1982, 112 consecutive previously untreated adults (aged 15-69 years, median 26) commenced therapy for acute lymphoblastic leukaemia (ALL) at St Bartholomew's Hospital. The first 63 patients entered into the study received initial treatment which comprised four cycles of adriamycin and vincristine, prednisolone and L-asparaginase with the first cycle (OPAL). In 1978, six cycles were given, with escalating doses of adriamycin and cyclophosphamide from cycle 3 (HEAV'D). Central nervous system (CNS) prophylaxis incorporated intrathecal methotrexate and cytosine arabinoside with cranial irradiation. Maintenance chemotherapy consisted of 6-mercaptopurine, cyclophosphamide and methotrexate for 3 years. Results obtained with the OPAL and HEAV'D regimens were not significantly different. The overall complete remission (CR) rate was 66% (73/111), factors correlating unfavourably with achievement of CR being advanced age (P less than 0.001) and L3 morphology/B-ALL immunophenotype (P less than 0.01). Fifty-three patients have relapsed, the bone marrow being the primary site in 43. Extramedullary relapse alone occurred in 10 (seven CNS, two testicular and one skin). Only three of the 64 patients who had complete CNS prophylaxis subsequently relapsed in the CNS as an isolated site. One patient died in CR, 19 remain in continuous CR between 2.5 and 10.5 years. The median duration of remission of the 73 patients who achieved CR was 18.5 months, factors correlating favourably with duration of CR being low blast cell count at presentation (P less than 0.002) and common ALL immunophenotype (P less than 0.04). Twenty-four patients remain alive, with a median survival of all patients of 18 months. Long-term survival is possible for approximately 20% of adults with ALL treated relatively intensively.     

Mitoxantrone and cytosine arabinoside as treatment for acute myeloblastic leukemia in older patients

The majority of patients with acute myeloid leukemia (AML) are elderly, and their response to chemotherapy is poorer than that of younger patients. The combination of mitoxantrone (MTN) and cytosine arabinoside (Ara-C) is a possible alternative to an anthracycline/Ara-C combination for the treatment of AML in these patients. Of 52 older patients (> 59 years) referred over a 3.5-year period, 33 patients (age range 60–78 years, median 67 years) received MTN and Ara-C as therapy for newly diagnosed AML. MTN was administered at a dose of 12 mg/m²/day, intravenously, for 3 days (23 patients), or 10 mg/m²/day for 5 days (10 patients), and Ara-C at a dose of 100 mg/m² twice daily, intravenously, for 7 days. Complete remission (CR) was achieved in 16/33 patients (48%). The median remission duration was 6 months (range 1–37 months). The median survival was 14 months for those who achieved CR compared with 9 months for those with resistant disease. Two patients remain in first CR after 13 and 37 months, but three patients died whilst receiving consolidation therapy. In selected elderly patients with AML, the combination of MTN and Ara-C provides an acceptable alternative to an anthracycline/ Ara-C regimen, with a higher CR rate than historical controls. However, the CR rate and remission duration remain low compared with those of younger patients, supporting the need to investigate new approaches to treatment in this population.     

Hematopoietic stem cells express multiple myeloid markers: implications for the origin and targeted therapy of acute myeloid leukemia

Human hematopoietic stem cells (HSCs) are generally regarded as being devoid of the markers expressed by differentiated blood cells, the lineage-specific antigens. However, recent work suggests that genes associated with the myeloid lineage are transcribed in mouse HSCs. Here, we explore whether myeloid genes are actually translated in human HSCs. We show that CD33, CD13, and CD123, well-established myeloid markers, are expressed on human long-term repopulating cells from cord blood and bone marrow. In addition, we demonstrate that nonobese diabetic/severe combined immunodeficiency (NOD/SCID) leukemia-initiating cells (SL-ICs) are restricted to the CD33+ fraction in 11 of 12 acute myeloid leukemia (AML) samples studied, indicating that leukemic stem cells (LSCs) express this antigen. This study changes our view of HSCs and the process of differentiation. Furthermore, based on the phenotypic similarity of HSCs and LSCs, our data provide support for the hypothesis that AML derives from an HSC. Our findings also provide a challenge to contemporary attempts to improve the outcome of AML using myeloid antigen-targeted therapies, given the potential for HSC killing.     

Acute lymphangitic nocardiasis

The third case of lymphangitic nocardiasis caused by Nocardia brasiliensis to be recorded in Uruguay is presented. The clinical picture showed some of the features of sporotrichosis, but it was more acute, the nodules developing rapidly into abscesses. A review of eight similar cases, reported previously, reveals that N. brasiliensis was properly identified in five of them. All cases were localized on the upper limbs, and granules were not seen on direct examination. Mycetomas caused by N. brasiliensis have not been observed in Uruguay.     

IDENTIFICATION OF Leishmania infantum IN PUERTO IGUAZú, MISIONES,ARGENTINA

 The emergence of zoonotic visceral leishmaniasis (ZVL) in Latin America is a growing public health problem. The urbanization of ZVL has been observed in different countries around the world, and there are a growing number of reports drawing attention to the emergence of this infection in new locations, as well as its increase in previously established areas of endemicity. In the city of Posadas, Misiones province, Northeastern Argentina, the transmission of ZVL associated with canines and Lutzomyia longipalpis was first reported in 2006. In the city of Puerto Iguazú, also in Misiones province, the first human case of ZVL was reported in February 2014. From 209 surveyed dogs, 15 (7.17%) were identified as positive by serological and/or parasitological methods. Amplification was observed in 14 samples and in all cases the species implicated was Leishmania infantum. To the authors’ knowledge, this is the first molecular characterization of L. infantum from dogs in this area.     

Pulmonary Embolism Severity Index and troponin testing for the selection of low‐risk patients with acute symptomatic pulmonary embolism

Summary. Background: The combination of the Pulmonary Embolism Severity Index (PESI) and troponin testing could help physicians identify appropriate patients with acute pulmonary embolism (PE) for early hospital discharge. Methods: This prospective cohort study included a total of 567 patients from a single center registry with objectively confirmed acute symptomatic PE. On the basis of the PESI, each patient was classified into one of five classes (I–V). At the time of hospital admission, patients had troponin I (cTnI) levels measured. The endpoint of the study was all‐cause mortality within 30 days after diagnosis. We calculated the mortality rates in four patient groups: group 1, PESI class I–II plus cTnI < 0.1 ng mL^?1; group 2, PESI classes III–V plus cTnI < 0.1 ng mL^?1; group 3, PESI classes I–II plus cTnI ≥ 0.1 ng mL^?1; and group 4, PESI classes III–V plus cTnI ≥ 0.1 ng mL^?1. Results: The study cohort had a 30‐day mortality of 10% [95% confidence interval (CI), 7.6–12.5%]. Mortality rates in the four groups were 1.3%, 14.2%, 0% and 15.4%, respectively. Compared with non‐elevated cTnl, the low‐risk PESI had a higher negative predictive value (NPV) (98.9% vs. 90.8%) and negative likelihood ratio (NLR) (0.1 vs. 0.9) for predicting mortality. The addition of non‐elevated cTnI to low‐risk PESI did not improve the NPV or the NLR compared with either test alone. Conclusions: Compared with cTnl testing, PESI classification more accurately identified patients with PE who are at low risk of all‐cause death within 30 days of presentation.