Early septal lesion: Effect on the development of the cholinergic system in rat hippocampus

The development of the cholinergic system in the rat hippocampal formation was studied following lesion of the septal region at an age of 2–4 days postnatal (i.e. the lesion was performed prior to the establishment of the septohippocampal connections). The steep increase in acetylcholinesterase (AChE) level, that under normal conditions take place during the second and the third week postnatal, was not observed in early lesioned animals, and AChE level at maturity was about 30% of control. AChE level of adult-lesioned animals was about 15% of control, suggesting an age-dependent plasticity in response to the lesion. Early deafferentation did not seem to alter the pattern of development of muscarinic binding sites as measured by specific binding of [³H]quinuclidinyl benzilate ([³H]QNB). Total [³H]QNB bound per hippocampus of adult, early-lesioned animals was about 70% of control, but this reduction could be accounted for by the atrophy observed in the hippocampal formation following early lesion. Binding of [³H]QNB per protein in early lesioned animals did not differ from normal. Thus the development and the level of muscarinic binding sites in the hippocampal formation do not seem to depend upon normal establishment of presynaptic contacts.     

Genes and learning in Drosophila

To survive, every animal needs appropriate behavior patterns. Evolution has provided simple creatures with the necessary behavioral repertoire in the form o f fixed action patterns — programmed reactions to external stimuli, coded by the genes and ‘hard-wired’ into the nervous system. More complex organisms require more versatility to cope with unusual situations and to occupy new niches. They need to learn. For this they also rely on genes to specify components of the neural machinery that makes learning and memory possible. By studying the learning behavior of normal and mutant flies it may be possible to isolate and identify some of these mechanisms.     

Spray vaccination of turkeys against Newcastle disease

Turkeys poults were vaccinated against Newcastle disease by spray vaccination using Hitchner B1 and La Sota vaccines. Turkeys with maternally derived immunity vaccinated at 7, 35 and 63 days of age developed an active immunity. Each revaccination resulted in higher levels of haemagglutination-inhibiting and neutralising antibodies. Challenge with virulent virus showed that turkeys, serologically free from antibodies against Newcastle disease were less sensitive than specific pathogen free chicks to Newcastle disease.     

Should chloroquine be laid to rest?

Chloroquine (CQ) has been the front line antimalarial drug due to its efficacy, low cost and scanty side effects, until resistance has evolved. Although its use has been officially discontinued in most malaria-affected countries, it is still widely used. Practical and pharmacological considerations indicate that it could be still used in semi-immune adults and that more efficient treatment protocols could be devised to treat even patients infected with CQ-resistant parasite strains. Since its antimalarial activity is pleiotropic, drug resistance may be due to different mechanisms, each amenable to reversal by drug combination.     

Type III mixed cryoglobulinemia and antiphospholipid syndrome in a patient with partial DiGeorge syndrome

We studied a 14 year-old boy with partial DiGeorge syndrome (DGS), status post complete repair of Tetralogy of Fallot, who developed antiphospholipid syndrome (APS) and type III mixed cryoglobulinemia. He presented with recurrent fever and dyspnea upon exertion secondary to right pulmonary embolus on chest computed tomography (CT). Coagulation studies revealed homozygous methylene tetrahydrofolate reductase 677TT mutations, elevated cardiolipin IgM antibodies, and elevated beta(2)-glycoprotein I IgM antibodies. Infectious work-up revealed only positive anti-streptolysin O (ASO) and anti-DNAse B titers. Autoimmune studies showed strongly positive anti-platelet IgM, elevated rheumatoid factor (RF), and positive cryocrit. Renal biopsy for evaluation of proteinuria and hematuria showed diffuse proliferative glomerulonephritis (DPGN) with membranoproliferative features consistent with cryoglobulinemia. Immunofixation showed polyclonal bands. Our patient was treated successfully with antibiotics, prednisone, and mycophenolate mofetil (MMF). This is the first report of a patient with partial DGS presenting with APS and type III mixed cryoglobulinemia possibly due to Streptococcal infection.     

Cellular senescence-like features of lung fibroblasts derived from idiopathic pulmonary fibrosis patients

Idiopathic pulmonary fibrosis (IPF) is an age-related fatal disease with unknown etiology and no effective treatment. In this study, we show that primary cultures of fibroblasts derived from lung biopsies of IPF patients exhibited (i) accelerated replicative cellular senescence (CS); (ii) high resistance to oxidative-stress-induced cytotoxicity or CS; (iii) a CS-like morphology (even at the proliferative phase); and (iv) rapid accumulation of senescent cells expressing the myofibroblast marker α-SMA. Our findings suggest that CS could serve as a bridge connecting lung aging and its quite frequent outcome -- pulmonary fibrosis, and be an important player in the disease progression. Consequently, targeting senescent cells offers the potential of being a promising therapeutic approach.     

Adolescent obesity and adult male breast cancer in a cohort of 1,382,093 men

Male breast cancer (MBC) accounts for 1% of all breast cancer. Adult obesity and tallness are risk factors for MBC, but the role of adolescent fatness is largely unknown. We aimed to assess the association between body mass index (BMI) in adolescence and the incidence of MBC in a large cohort of 16‐ to 19‐year‐old Israeli males. 1,382,093 Jewish Israeli males aged 16–19 who underwent anthropometric measurements, a general intelligence test (GIT) and other examinations during 1967–2011, were followed up to December 31, 2012 for MBC incidence. Cox proportional hazards models assessed the association between adolescent BMI (as WHO BMI categories and as age‐specific CDC percentiles) and time to MBC diagnosis, adjusting for sociodemographic covariates. Of 100 MBC cases diagnosed during 29,386,233 person‐years of follow‐up, 97 were included in multivariable analyses. Compared to “healthy” BMI (18.5–24.9 kg/m²) and adjusted for year of birth, country of origin and GIT score, higher adolescent BMI was associated with higher MBC risk: hazard ratio (HR) = 2.01 (95% confidence interval [CI] 1.14–3.55, p = 0.015) in overweight (25.0 ≤ BMI < 30.0 kg/m²) adolescents; and HR = 4.97 (95%CI 2.14–11.53, p = 0.0002) in obese (BMI ≥ 30.0 kg/m²) adolescents. When CDC age‐specific BMI percentiles were assessed results were similar and statistically significant for obesity. In addition, low (vs. high) GIT score (HR = 4.76, 95%CI 1.96–12.50, p = 0.001) and European (vs. west‐Asian) origin (HR = 1.99, 95%CI 1.19–3.34, p = 0.009) were independent predictors of MBC. Measured adolescent overweight and obesity are associated with increased risk of MBC, suggesting a modifiable risk factor potentially allowing for early intervention. The novel association with cognitive function should be further explored.     

Killing of intraerythrocytic<Emphasis Type="Italic"> Plasmodium falciparum</Emphasis> by lysosomotropic amino acid esters

Esters of amino acids are known to penetrate into cells by simple diffusion. Subsequently, they are hydrolyzed by hydrolases to release the parent amino acid. Due to the abundance of hydrolases in phagolysosomes, amino acids accumulate, there because the rate of influx and hydrolysis exceed the rate of amino acid efflux through specific carriers. The osmotic effect of this accumulation results in the disruption of the organelles. This mechanism has been demonstrated to be responsible for the killing of Leishmania amastigotes by amino acid esters. In this investigation, it is shown that all esters tested, including alcohol esters, N-acetyl esters and the esters of some dipeptides, inhibit the growth of Plasmodium falciparum in culture. Inhibition is time-dependent and, in some cases, ring-stage parasites are more sensitive than trophozoites. Similar to the findings with Leishmania, alcohol esters of Glu, Leu, Met, Phe and Trp are more toxic to Plasmodium whereas Ala, Gly, His and Ile are much less noxious. Esters caused the release of acridine orange that selectively accumulates in the phagolysosome-like food vacuole of the parasite, attesting the ostensible destruction of this organelle by osmotic lysis. The toxicity of the N-acetyl esters is probably associated in part to their ability to inhibit cytosolic proteases. Since excess of amino acids can also inhibit proteolysis, the effect of free amino acids on parasite growth was also tested. Of the 19 odd amino acids tested, only three, namely Cys, His and Trp, were found to be toxic to the parasites at millimolar concentrations and the reasons for their possible specific toxicity are discussed.     

Phylogenetic Relationships of West Nile Viruses Isolated from Birds and Horses in Israel from 1997 to 2001

In November 1997, an outbreak of a neuroparalytic disease caused by West Nile (WN) virus was diagnosed in young goose flocks. Domestic geese were similarly affected in the late summer and fall of 1998, 1999, 2000 and 2001. WN viruses were also isolated from migratory and wild birds and horses in 1998–2001. A 1278 bp sequence of the envelope gene of 24 Israeli WN virus isolates was compared with those of seven isolates from Africa, Europe and New York. As a result, the Israeli isolates could then be grouped into two clusters. The 15 avian and three equine from 1997–2001 in the first cluster of viruses were shown to be identical to WN-NY99, while the second cluster comprised one goose isolate from 1998 and two goose and two pigeon isolates from 2000. These closely resembled the most recent Old World isolates, and indicate that at least two WN genotypes were co-circulating in the region during this time.