Phlebotomus papatasi sand fly salivary gland lysate down-regulates a Th1, but up-regulates a Th2, response in mice infected with Leishmania major

A vertebrate host becomes infected with Leishmania major when the sand fly vector injects parasites into skin along with saliva. Previous studies showed that salivary gland lysate of the New World sand fly Lutzomyia longipalpis markedly enhanced L. major infection in CBA mice. However, L. major is an Old World parasite transmitted in nature by the Old World sand fly Phlebotomus papatasi. Here we examine the ability of P. papatasi salivary gland lysate to enhance infection (lesion size and parasite burden) by L. major. In addition, we examine the effects of salivary gland lysate on the immune response to L. major by monitoring the levels of cytokine mRNA from the lymph nodes draining cutaneous lesions. We found that P. papatasi salivary gland lysate dramatically exacerbated lesion development in disease-resistant CBA mice. This exacerbation of disease correlated with inhibition of the production of Thl cytokines and associated factors (IFN-gamma, IL-12, and inducible nitric oxide synthase), but with enhancement of the Th2 cytokine IL-4, whereas no changes in the levels of IL-10 and TGF-beta were noted. Importantly, salivary gland lysate directly up-regulated expression of IL-4 mRNA in mice in the absence of infection with L. major.     

Trends in mortality of childhood-onset insulin-dependent diabetes mellitus in Leicestershire: 1940-1991

The relative risk of death by calendar date of diagnosis was investigated in a population-based incident cohort of 845 (463 males:382 females) IDDM diagnosed in Leicestershire before the age of 17 years between 1940 and 1989. The mortality status of 844 (99.9%) patients was determined as of the 31 December 1991, representing 14,346 person-years of risk. Trends in relative risk of death were investigated using Cox proportional hazards modelling for within cohort comparisons and age/sex and calendar time adjusted standardized mortality ratios (SMR) using generalized linear modelling for external comparisons. Median age at diagnosis was 10 years (range 3 months to 16 years); median duration of diabetes 15 years (range 1-51 years). Forty-four patients had died (5.2%; median age at death 31 years, range 11-51 years). A further four patients died at presentation (within 24 h) from ketoacidosis and are excluded from all analyses. Calendar date of diagnosis was found to be an important predictor of mortality. Adjusting for attained age there was evidence of a decline in relative risk of death with calendar date of diagnosis of 3.4% (95% CI, 0.005-6.9%) per annum, equivalent to a 32% fall per decade (95% CI, 5-51%), or 84% (95% CI, 21-97) from 1940 to 1989. The data are consistent with a large fall in mortality between the 1940s and 1950s representing over 50% of the total reduction in mortality between 1940 and 1991. Neither sex nor age at diagnosis were significant predictors of mortality. Over the study period 1940-89 the SMR (male and female combined) fell from 981 (541-1556) to 238 (60-953) relative to the general population. This population-based study shows that the prognosis for Type 1 (insulin-dependent) diabetes mellitus has improved markedly over the period 1940-1991.     

Reduced skin tumor development in cyclin D1-deficient mice highlights the oncogenic ras pathway in vivo

Cyclin D1 is part of a cell cycle control node consistently deregulated in most human cancers. However, studies with cyclin D1-null mice indicate that it is dispensable for normal mouse development as well as cell growth in culture. Here, we provide evidence that ras-mediated tumorigenesis depends on signaling pathways that act preferentially through cyclin D1. Cyclin D1 expression and the activity of its associated kinase are up-regulated in keratinocytes in response to oncogenic ras. Furthermore, cyclin D1 deficiency results in up to an 80% decrease in the development of squamous tumors generated through either grafting of retroviral ras-transduced keratinocytes, phorbol ester treatment of ras transgenic mice, or two-stage carcinogenesis.     

Synthesis of corneal keratan sulfate proteoglycans by bovine keratocytes in vitro

Keratan sulfate proteoglycans (KSPGs) are the major proteoglycans of the cornea and are secreted by keratocytes in the corneal stroma. Previous studies have been able to show only transient secretion of KSPG in cell culture. In this study, cultures of bovine keratocytes were found to secrete the three previously characterized KSPG proteins into culture medium. Reactivity with monoclonal antibody I22 demonstrated substitution of these proteins with keratan sulfate chains. KSPG constituted 15% of the proteoglycan metabolically labeled with [35S]sulfate in keratocyte culture medium. This labeled KSPG contained keratan sulfate chains of 4700 Da compared to 21,000 Da for bovine corneal keratan sulfate. Labeled keratan sulfate from cultures contained nonsulfated, monosulfated, and disulfated disaccharides that were released by digestion with endo-beta-galactosidase or keratanase II. Nonsulfated disaccharides were relatively more abundant in keratan sulfate from culture than in corneal keratan sulfate. These results show that cultured bovine keratocytes maintain the ability to express all three of the known KSPG proteins, modified with keratan sulfate chains and sulfated on both N-acetylglucosamine and galactose moieties. KSPG made in vitro differs from that found in vivo in the length and sulfation of its keratan sulfate chains. The availability of cell cultures secreting corneal keratan sulfate proteoglycans provides an opportunity to examine biosynthesis and control of this important class of molecules.     

The role of the surface free energy in the selection of a suitable excipient in the course of a wet-granulation method

Pellets containing metronidazole were produced in a centrifugal granulator, with hydroxypropylcellulose (Klucel LF®) as binding agent, and corn starch, microcrystalline cellulose (Vivapur 101®) and lactose as excipients. The wettability of the pharmaceutical powders was assessed by means of contact angle measurements, and the dispersive and polar surface energies were determined. The spreading coefficients, the work of adhesion and the work of cohesion were calculated and correlated with the pellet properties (friability, bulk and tapped density, and porosity). The aim was to investigate the role of the surface free energy of one- and two-component powder compositions in pellet production. The interactions between the particles were found to be connected with the measured pellet parameters. It was concluded that, in the course of the growth of the pellets, the particle sizes of the pharmaceutical powders and the interactions between them are important. If the work of cohesion of the binder is lower than the work of cohesion of the substrate and the work of adhesion, then the optimal amount of the binding agent is that which coats the particles uniformly in minimal quantity and in continuous layer.     

On Efficiency of Multi-job Grid Allocation Based on Statistical Trace Data

The ever growing number of computation-intensive applications calls for utilizing large-scale, potentially interoperable distributed infrastructures. Nowadays, such distributed systems enable the management of heterogeneous scientific workflows of considerable sizes, where job scheduling and resource management is a crucial issue. In this paper we focus on the challenges of scheduling parameter sweep applications, a specific and commonly used type of workflows where ordering of job executions is irrelevant. A parameter sweep has a large set of independent job instances, called a multi-job, submitted for execution in a single step. In order to cope with the high uncertainty and unpredictable load of resources, and the simultaneous submissions of multi-job instances, we propose a statistics-based brokering approach for allocating jobs to resources so that the makespan is minimised. Earlier studies claim that users’ predictions on job runtime are inaccurate and unusable for scheduling. Our aim is to examine, whether statistical trace data for the same purpose is efficient compared to randomized allocation.     

The biological properties of Aerococcus antagonists, representatives of human microbiocenoses

The paper deals with the data on biology of Aerococcus, a slightly studied group of microorganisms. Physiological-biochemical properties of Aerococcus are described, data of their distribution in nature are given. Peculiar attention is paid to the estimate of the role of Aerococcus in human microbiocenoses. As a result of the profound and all-round study of this group of microorganisms the authors have developed new bacterial drug "A-bakterin" based on the aerococcus strain. Data presented about the results of clinical tests of "A-bakterin" are presented, a possibility to use Aerococcus lysate in the elaboration of new drugs is discussed.     

The effect of combined antenatal vitamin K and phenobarbital therapy on umbilical blood coagulation studies in infants less than 34 weeks' gestation

OBJECTIVE: To determine if antenatal vitamin K and phenobarbital therapy affect coagulation studies in umbilical blood at birth, and to provide 95% reference ranges for umbilical blood coagulation parameters in premature gestations. METHODS: Patients at imminent risk for spontaneous or indicated premature delivery less than 34 weeks' gestation were randomized to receive either placebo or vitamin K and phenobarbital. Prothrombin time (PT), activated partial thromboplastin time (PTT), functional coagulation factors, and decarboxylated prothrombin assays were performed on umbilical blood specimens. Decarboxylated prothrombin, also known as "protein induced by vitamin K absence-factor II" or precursor prothrombin, is a sensitive marker for vitamin K deficiency. Standardized values of PT and PTT are reported in seconds and standardized values of factor assays in percentage of normal adult functional activity (mean +/- one standard deviation). RESULTS: Newborns in the placebo and treatment groups had similar umbilical blood PT (12.6 +/- 1.2 versus 12.7 +/- 1.4 seconds), PTT (48.8 +/- 13.4 versus 49.6 +/- 13.8 seconds), and functional activity of factor II (40.3 +/- 12.5 versus 42.0 +/- 12.1%), factor VII (67.0 +/- 20.9 versus 66.8 +/- 18.9%), factor IX (27.4 +/- 12.8 versus 25.8 +/- 8.9%), and factor X (47.0 +/- 12.8 versus 49.2 +/- 11.6%). Newborns in the treatment group were about half as likely as those in the placebo group to have detectable decarboxylated prothrombin levels in umbilical blood at birth (gestational age-adjusted odds ratio 0.47, 95% confidence interval 0.22-1.01; P = .05). CONCLUSIONS: Combined maternal therapy with vitamin K and phenobarbital before premature delivery does not affect umbilical blood PT, PTT, or functional activity of vitamin K-dependent coagulation factors II, VII, IX, and X. However, it is associated with the reduced presence of decarboxylated prothrombin in umbilical blood at birth. There is significant improvement in umbilical blood coagulation tests as gestational age advances from 24 to 34 weeks.