Molecular cloning and characterization of a novel gene of Candida albicans,CDR1, conferring multiple resistance to drugs and antifungals

By functional complementation of a PDR5 null mutant of Saccharomyces cervisiae, we have cloned and sequenced the multidrug-resistance gene CDR1 of Candida albicans. Transformation by CDR1 of a PDR5-disrupted host hypersensitive to cycloheximide and chloramphenicol resulted in resistance to cycloheximide, chloramphenicol and other drugs, such as the antifungal miconazole, with collateral hypersensitivity to oligomycin, nystatin and 2,4 dinitrophenol. Our results also demonstrate the presence of several PDR5 complementing genes in C. albicans, displaying multidrug-resistance patterns different from PDR5 and CDR1. The nucleotide sequence of CDR1 revealed that, like PDR5, it encodes a putative membrane pump belonging to the ABC (ATP-binding cassette) superfamily. CDR1 encodes a 1501-residue protein of 169.9 kDa whose predicted structural organization is characterized by two homologous halves, each comprising a hydrophobic region with a set of six transmembrane stretches, preceded by a hydrophilic nucleotide binding fold.     

Susceptibility pattern and molecular type of species-specific Candida in oropharyngeal lesions of Indian human immunodeficiency virus-positive patients

A study of oropharyngeal candidiasis (OPC) in Indian human immunodeficiency virus (HIV)/AIDS patients was conducted over a period of 15 months. This study revealed that 75% of the HIV/AIDS patients had OPC. MIC testing revealed that 5% of the Candida isolates were fluconazole resistant. A correlation between CD4(+)-T-cell counts and development of OPC in HIV/AIDS patients was also observed. Molecular typing of C. albicans isolates showed that all were genetically unrelated.     

Multiple cerebral metastases: detectability with Gd-DTPA-enhanced MR imaging

Sixteen patients with suspected cerebral metastases were studied with magnetic resonance (MR) imaging before and after the intravenous administration of 0.1 mmol/kg of gadolinium diethylenetriaminepenta-acetic acid. The images were interpreted blindly by two neuroradiologists; all clinical, radiologic (computed tomographic and MR imaging), and pathologic data were reviewed to arrive at a final "best diagnosis," which was then compared with the prior blinded interpretations. Of seven patients found to have multiple metastases, six (86%) had at least one tumor nodule depicted by postinfusion MR imaging that was missed by one or both observers on review of preinfusion images alone. Lesions missed on preinfusion studies were usually small nodules hidden by or not detected next to regions of high-signal edema thought to be related to the adjacent tumor nodule. The authors believe that contrast enhancement improves detection of metastatic foci with MR imaging and that the findings indicate broader implications for the detection of multiple lesions from other causes.     

Osteopetrosis: MR characteristics at 1.5 T

Four patients with proved osteopetrosis (three with the infantile malignant form and one with the benign form) were examined with magnetic resonance imaging at 1.5 T. All patients were studied in the coronal and sagittal planes using both short and long repetition time/echo time sequences. The infantile malignant form was characterized by a complete lack of signal from the marrow alternating with a signal intensity equivalent to that of the intervertebral disks, resulting in a "stepladder" appearance. In the benign form or after successful marrow transplantation in the infantile malignant form, intermediate or high signal intensity in the vertebrae was noted, suggesting the presence of some marrow elements.     

A Cross-Sectional Study on Novel-Risk Factors Associated with Supraspinatus Tendon Tear

Background and AimSeveral patient-related factors have been identified which are responsible for the development of rotator cuff tears. The purpose of the study was to assess various parameters which can be risk factors for the development of supraspinatus tendon tear.MethodsA total of 100 patients with symptomatic rotator cuff tear, aged > 18 years, of either gender, presenting to the outpatient department were included in this cross-sectional study. Magnetic resonance imaging was done and based on its results; patients were identified for the type of tear. Demographic, clinical, and biochemical factors affecting the tears were assessed using logistic regression analysis.ResultsFactors such as age, gender, pain radiation, night pain, and analgesic intake had significant association with supraspinatus tendon tears.Conclusion“Pain radiation” and “Analgesic intake” were two new parameters found associated with the supraspinatus tendon tears. New parameters that have been assessed as risk factors will help in better understanding of supraspinatus tendon tears.     

Comparison of functional outcomes among subtypes of Fraser’s typeⅡfloating knee

Purpose The poor prognosis in patients with floating knee injuries is mainly contributed to articular involvement(Fraser’s typeⅡ).This study aims to evaluate and compare the functional outcomes among different Fraser’s typeⅡfloating knee injuries after surgical management.Methods Twenty-seven patients with Fraser’s typeⅡfloating knee injuries(54 fractures)between September 2014 and December 2015 were enrolled prospectively in this study and were distributed according to Fraser’s floating knee classification into three different groups as typeⅡA(ipsilateral femoral shaft and tibial intra-articular involvement,n=11),typeⅡB(ipsilateral tibial shaft and femoral intra-articular involvement,n=9)and typeⅡC(both femoral and tibial intra-articular involvement,n=7).The differences among the groups were evaluated and compared.The functional outcomes of these injuries at one year were analyzed using Knee Injury and Osteoarthritis Outcome Score(KOOS)which covers 5 subscales of pain,other symptoms,activities of daily living,sports and recreation,and quality of life.The result was also compared with standardized age-sex matched healthy population using paired samples t-test.Results All the patients were male,and the injury mechanism was solely roadside accident.The mean age was 29.8 years and injury severity score 17.9(comparable in all the three groups).Most injuries were observed on the right side(20 cases,74.1%).Based on paired samples t-test,the KOOS score of patients with Fraser’s typeⅡA was found to be better than that of typeⅡB and typeⅡC.Compared with the reference age-sex matched control group,patients with Fraser’s typeⅡB andⅡC fractures had significantly lower mean score in all KOOS subscales(all p<0.01).However,Fraser’s typeⅡA only revealed significant difference regarding the subscales of activities of daily living(p<0.0001),sports and recreation(p<0.0001),and quality of life(p<0.0001).Conclusion The results of this study show that patients with Fraser’s typeⅡA fractures had a better functional outcome as compared to those with typeⅡB andⅡC fractures.This might be due to the open intra-articular involvement of the distal femur of the latter two fracture types.     

Small renal carcinoma with large retroperitoneal hemorrhage: Diagnostic considerations

Two cases of small peripheral papillary renal carcinoma causing large spontaneous perirenal hemorrhages are presented. The value and limitations of computerized tomography, ultrasonography, arteriography, and percutaneous aspiration biopsy in these cases are discussed. The need for careful explorative surgery and dissection of the specimen is emphasized. Excretory urography should be the first examination in all patients with renal pain and signs of internal bleeding. Arteriography should be done when the diagnosis is not evident.     

Ewing’s肉瘤细胞X-射线照射后TNF-α和TGF-β mRNA表达的研究

 目的　研究Ewing’s肉瘤细胞系 (RM 82 )X 射线外照射后肿瘤坏死因子 (TNF α)和转化生长因子 (TGF β)mRNA表达水平的变化 ,探讨X 射线诱导内源性TNF α和TGF β产生的可能性及意义。 方法　应用实时荧光RT PCR ,检测接受不同剂量X 线照射 (2Gy ,5Gy ,10Gy ,2 0Gy ,30Gy ,4 0Gy)和受照后不同时间 (1h ,3h ,6h ,12h ,2 4h ,4 8h ,72h)。TNF α和TGF βmRNA表达水平的变化。 结果　RM 82细胞TNF αmRNA表达水平较外照射前显著升高。一方面受照后TNF αmRNA表达逐渐升高 ,照射剂量达 4 0Gy时TNF αmRNA表达水平达高峰 ,为正常对照组的 10 8倍 ;另一方面 ,照射后 3h后TNF αmRNA表达逐渐升高 ,6h达高峰 ,为正常对照组的 18倍。相反 ,TGF βmRNA表达水平X 射线照射前后无显著变化。结论　Ewing’s肉瘤细胞系 (RM 82 )接受X 线照射后TNF αmRNA表达明显升高 ,且呈现时间、剂量依赖性。放射治疗可诱导Ewing’s肉瘤细胞系 (RM 82...     

Fat gram target to achieve high energy intake in cystic fibrosis

Higher fat and energy intakes confer a survival advantage in cystic fibrosis (CF). There is a need to develop effective nutrition programmes that ensure optimal energy intake in CF.

Methodology:

A cross-sectional measurement of clinical characteristics and energy and fat intakes in patients attending the CF outpatients clinic of the John Hunter Hospital, Newcastle was undertaken. Twenty-nine subjects, mean age 12 years (range 4.3–20.2), completed weighed food records to determine the contribution of fat to the percentage of the recommended energy intake obtained and to document use of pancreatic enzyme replacement therapy.

Results:

Diets with a high percentage of energy derived from fat did not guarantee that individuals with CF met their energy requirements. Subjects with total fat intakes of 100 g per day or greater, however, achieved in excess of 110% recommended daily intake (RDI) for energy. Up to 47% of subjects consumed more pancreatic enzyme replacement capsules than shown to give maximum effectiveness.

Conclusion:

Setting a 100 g daily fat target is a realistic way of ensuring high energy intakes in CF. Fat ready reckoners would identify the fat content of food and prescribe specific numbers of pancreatic enzyme replacement capsules to be consumed with each meal or food item.     

Evaluation of cytotoxic, oxidative stress, proinflammatory and genotoxic responses of micro- and nano-particles of dolomite on human lung epithelial cells A(549)

Dolomite is a natural mineral of great industrial importance and used worldwide, thus millions of workers are at risk of occupational exposure. Its toxicity is however, meagerly documented. In the present investigation, a dolomite powder obtained from its milling unit was analyzed by some standard methods namely, optical microscopy, transmission electron microscopy and dynamic light scattering. Results showed that dolomite powder contained particles of different shapes and size both microparticles (MPs) and nanoparticles (NPs), suggesting potential occupational exposure of these particles. An attempt was therefore, made to investigate dolomite toxicity in a particle size-dependent manner in human lung epithelial cells A(549). The comparative toxicity evaluation of MPs and NPs was carried out by assessing their effects on cell viability, membrane damage, glutathione, reactive oxygen species (ROS), lipid peroxidation (LPO), micronucleus (MN) and proinflammatory cytokines, namely tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). These markers of cytotoxicity, genotoxicity and inflammation were assayed in cells exposed to MPs and NPs in a dose-and time-dependent manner. Invariably, their toxic effects were dose-and time-dependent while NPs in general were significantly more toxic. Notably, NPs caused oxidative stress, genotoxicity and inflammatory responses, as seen by significant induction of ROS, LPO, MN, TNF-α, IL-1β and IL-6. Thus, the study tends to suggest that separate health safety standards would be required for micrometer and nanometer scale particles of dolomite.