The timing and frequency of hybrid formation in African trypanosomes during cyclical transmission

The frequency of hybrid formation between twoTrypanosoma brucei clones during cyclical transmission throughGlossina morsitans centralis was analyzed. In two independent experiments, teneralG. m. centralis were infected with an equal mixture of twoT. brucei clones showing different homozygous isoenzyme patterns for isocitrate dehydrogenase (ICD; E.C. 1.1.1.42) and alkaline phosphatase (AP; E.C. 3.1.3.1). Trypanosomes were cyclically transmitted to mice from 23 infective flies and the subsequent blodstream-form populations were characterized by isoenzyme electrophoresis. Heterozygous patterns for ICD and AP indicated that hybrid formation occurred in at least 9 of the 23 vectors. There was further evidence that extrusion of hybrid parasites with saliva from a single fly was not necessarily continuous but could alter over time with the occurrence of either of both of the homozygous parental clones.     

A comparison of cupola-free perimetry with conventional perimetry: preliminary results

In the comparison of ten normal and two pathological visual fields, excellent agreement was found between examinations made with Octopus perimeters (types 201 and 500) and a prototype version of a new cupola-free perimeter (CFPP). The examination of a single glaucomatous visual field, however, exhibited an elevated mean defect value with the prototype instrument in comparison with Octopus 201 examinations of the same visual field. Although this difference may be easily explained by long-term fluctuation effects, further investigations based on a broader empirical basis will be required. Based on the results of this preliminary work the following remarks can be made with respect to the cupola-free perimeter: provided that the zero point of the dB scale is chosen appropriately, ie, with a stimulus luminance of about 4,000 asb used as the 0 dB level, the same differential light sensitivity (DLS) values for normal visual fields can be obtained with the CFPP as with all Octopus models (201, 500, 2000). Within the limits of measurement error, the same decrease of DLS was found with the CFPP as obtained using the other perimeters for test locations (of the G1 program), ranging from the center out to an eccentricity of 30 degrees. Thus it appears that the normal values as used in the other Octopus perimeters can also be utilized in this cupola-free instrument within this range.     

Studies on antigenic variation of cyclically transmitted Trypanosoma congolense.

Antigenic variants of T. congolense transmitted by G. m. morsitans through normal and X-irradiated mice were investigated by means of the neutralization test and IFAT. Clones of a cyclically passaged derivative strain were isolated from irradiated and normal mice. The IFAT revealed cross immunofluorescent reactions between most of the stabilates, whereas only the two clones obtained from irradiated mice were totally neutralized by their homologous antisera. These two antisera showed no cross neutralizing activity. The results indicate a possible antigenic heterogeneity of the extruded metacyclic forms.     

A primary cardiac sarcoma with unusual histology and clinical course

A left atrial tumor, in which radical resection was impossible, demonstrated two processes: An inflammatory pseudotumor and cellular atypia suggestive of a sarcoma. Immunohistochemistry (proliferating cell nuclear antigen [PCNA], MIB-1 [Ki-67 antibody], bcl-2 positive; p53 negative, focal loss of nm23) was supportive for a malignant tumor. Despite no further therapy because of uncertainty in tumor classification, the patient remained in remission for 28 months. Thereafter, spine metastases and local regrowth were found, and the patient died 15 months later, after temporary remission by radiotherapy. This case stresses the impact immunohistochemistry may have on diagnosis of malignancy and the difficulty in predicting the biological behavior of cardiac sarcomas.     

Double-blind,placebo-controlled,randomized phase III trial of darbepoetin alfa in lung cancer patients receiving chemotherapy

BACKGROUND: Patients receiving chemotherapy often develop anemia. Darbepoetin alfa (Aranesp(TM)) is an erythropoiesis-stimulating glycoprotein that has been shown, in dose-finding studies, to be safe and clinically active when administered to patients with cancer every 1, 2, or 3 weeks. This phase III study compared the safety and efficacy of darbepoetin alfa with placebo in patients with lung cancer receiving chemotherapy. METHODS: In this multicenter, double-blind, placebo-controlled study, 320 anemic patients (hemoglobin or=25% improvement; mean difference = 13%; 95% CI = 2% to 23%, P =.019) than patients receiving placebo. Patients receiving darbepoetin alfa did not appear to have any untoward effect in disease outcome and did not develop antibodies to the drug. Adverse events were similar between the groups. CONCLUSIONS: Patients with chemotherapy-associated anemia can safely and effectively be treated with weekly darbepoetin alfa therapy. Darbepoetin alfa decreased blood transfusion requirements, increased hemoglobin concentration, and decreased fatigue. Although no conclusions can be drawn about survival from this study, the potential salutary effect on disease outcome warrants further investigation in a prospectively designed study.     

Dose-dependent cysteine-mediated protection of insulin-producing cells from damage by hydrogen peroxide

AIMS/HYPOTHESIS: Oxidative damage is believed to play a key role in the process of pancreatic beta cell destruction leading to type 1 diabetes. The beta cells are sensitive to oxidative stress because their intracellular anti-oxidative defence mechanisms are weak. The defence mechanisms depend heavily on glutathione, the synthesis of which is dependent on the availability of cysteine. We investigated whether an increased amount of cysteine available could protect beta cells from oxidative damage. METHODS: Rat insulinoma cells (RINm5F) were exposed to 50 or 100 microM hydrogen peroxide in the presence of three different cysteine concentrations (0.1, 1 and 5mM). Cell viability was analyzed by vital staining and the cellular metabolic status by C,N-diphenyl-N'-4,5-dimethyl thiazol-2-yl tetrazolium bromide (MTT) analysis. Intracellular insulin, DNA and glutathione contents were measured. The mechanism of death was further clarified by gel electrophoretic DNA fragmentation analysis. RESULTS: Hydrogen peroxide decreased cell viability and induced functional impairment. Vital staining indicated that 1mM cysteine effectively protected the cells. The protective effect was confirmed by the MTT assay showing preserved metabolic integrity, and by measurements of intact intracellular insulin and DNA content. Cysteine increased intracellular glutathione. Gel electrophoretic analysis of DNA revealed hydrogen peroxide-induced apoptotic fragmentation. This was also abolished by 1mM cysteine. The therapeutic window of cysteine was narrow: 0.1mM cysteine provided inadequate protection, and 5mM cysteine was already toxic in this setting. CONCLUSION: A proper dose of cysteine could provide a safe and effective means to protect beta cells from oxidative damage.     

ECG-gated multi-detector row CT for assessment of mitral valve disease: initial experience

Our objective was to evaluate applicability and image quality of contrast-enhanced, retrospectively ECG-gated multi-detector row CT (MDCT) for visualization of anatomical details of the mitral valve and its apparatus, and to determine the value of MDCT for diagnosing abnormal findings of the mitral valve. Twenty consecutive patients with mitral valve disease underwent MDCT preoperatively. Two readers assessed visibility of the mitral valve annulus, mitral valve leaflets, tendinous cords, and papillary muscles by using a four-point Likert grading scale. Abnormal mitral valve findings [thickening of the mitral valve leaflets, presence of mitral annulus calcification (MAC), and calcification of the valvular leaflets] were compared with preoperative echocardiography and intraoperative findings. Visibility of the mitral valve annulus and mitral valve leaflets was good or excellent in 15 patients (75%) and in 19 patients (95%) for papillary muscles. The MDCT yielded a 95–100% agreement compared with echocardiography and surgery with regard to the assessment of mitral valve leaflet thickening and the presence of calcifications of the mitral valve annulus or mitral valve leaflets. Intermodality agreement between MDCT and echocardiography was excellent with regard to classification of mitral valve leaflet thickness (κ=1.00) and good regarding classification of MAC thickness (κ=0.73). Contrast-enhanced, retrospectively ECG-gated MDCT allows good to excellent visualization of anatomical details of the mitral valve and its apparatus, and demonstrates good agreement with echocardiography and surgery in diagnosing mitral valve abnormalities. Electronic Publication