<Emphasis Type="Italic">Balamuthia mandrillaris</Emphasis>, an opportunistic agent of granulomatous amebic encephalitis,infects the brain via the olfactory nerve pathway

Balamuthia mandrillaris is a free-living ameba and an opportunistic agent of lethal granulomatous amebic encephalitis (GAE) in humans and other mammals. Its supposed routes of infection have been largely assumed from what is known about Acanthamoeba spp. and Naegleria fowleri, other free-living amebae and opportunistic encephalitis agents. However, formal proof for any migratory pathway, from GAE patients or from animal models, has been lacking. Here, immunodeficient mice were infected with B. mandrillaris amebae by intranasal instillation, the most likely natural portal of entry. By means of classical and immunohistology, the amebae are shown to adhere to the nasal epithelium, progress along the olfactory nerves, traverse the cribriform plate of the ethmoid bone, and finally infect the brain. A similar invasion pathway has been described for N. fowleri. The data suggest that the olfactory nerve pathway is a likely route for natural infection of the brain by B. mandrillaris amebae.     

A new CARD15 mutation in Blau syndrome

The caspase recruitment domain gene CARD15/NOD2, encoding a cellular receptor involved in an NF-kappaB-mediated pathway of innate immunity, was first identified as a major susceptibility gene for Crohn's disease (CD), and more recently, as responsible for Blau syndrome (BS), a rare autosomal-dominant trait characterized by arthritis, uveitis, skin rash and granulomatous inflammation. While CARD15 variants associated with CD are located within or near the C-terminal leucine-rich repeat domain and cause decreased NF-kappaB activation, BS mutations affect the central nucleotide-binding NACHT domain and result in increased NF-kappaB activation. In an Italian family with BS, we detected a novel mutation E383K, whose pathogenicity is strongly supported by cosegregation with the disease in the family and absence in controls, and by the evolutionary conservation and structural role of the affected glutamate close to the Walker B motif of the nucleotide-binding site in the NACHT domain. Interestingly, substitutions at corresponding positions in another NACHT family member cause similar autoinflammatory phenotypes.     

Antiplatelet Drugs Plus Thrombolysis in Myocardial Infarction

A breakthrough in platelet inhibition was achieved with the advent of antagonists of the glycoprotein (GP) IIb/IIIa receptors. These receptors are essential to platelet aggregation triggered by any of several different mechanisms. GP IIb/IIIa receptor antagonists, especially the monoclonal antibody abciximab, have been established as adjuncts to angioplasty in acute coronary syndromes. Conjunctive treatment with thrombolysis in myocardial infarction has been studied less extensively. GP IIb/IIIa receptor antagonists appear to be a feasible adjunct to thrombolysis. In particular, the use of abciximab in conjunction with reduced doses of thrombolytics is an attractive approach to achieve early coronary reperfusion with probably acceptable bleeding risk. The eventual role of this combined treatment can only be defined by the large-scale clinical trials that will be performed in the near future.     

Syncytial organization of acanthors of Polymorphus minutus (Palaeacanthocephala), Neoechinorhynchusrutili (Eoacanthocephala), and Moniliformis moniliformis (Archiacanthocephala) (Acanthocephala)

The fine structures of immature and of developed shelled acanthors of three species belonging to the three subgroups of the Acanthocephala were investigated. Acanthors are surrounded by four eggshells (embryonic envelopes) and are composed of three syncytia: a frontal syncytium, a central syncytium, and an epidermal syncytium. Neither a sense organ nor a nervous system has been found. The central syncytium shows a mass of condensed nuclei and 12 decondensed nuclei and gives rise to 10 anterior/posterior subepidermal myofibrillar systems and 2 oblique retractor muscles. Circular muscles are missing. A single decondensed nucleus can be assigned to each of the 12 muscular systems. The epidermal syncytium embeds the other two syncytia and forms the wrinkled epidermis, which shows an extracellular glycocalyx and intrasyncytial condensations. Prominent recurved hooks, which mark the anterior end of each acanthor, and body spines are intraepidermal differentiations. Partly branched tubular infoldings of the epidermal plasma membrane of the acanthor exist and represent precursors of the pore ducts typical of the adult epidermis. Autapomorphies in the ground pattern of the monophylum Acanthocephala are the four eggshells, the early development of three syncytia, the condensed nuclei in the central syncytium, and the differentiation of ten longitudinal muscle bands and two muscle retractors and of intraepidermal hooks and spines. The syncytial organization of the epidermis with intraepidermal skeletal condensations and infoldings of the apical plasma membrane are characteristics inherited from a stem species common to Acanthocephala, Seison, and Rotifera. Received: 25 September 1996 / Accepted: 10 October 1996     

Flexible versus rigid endoscopes for outpatient hysteroscopy: a prospective randomized clinical trial

To evaluate patient acceptance, optical properties and the clinical feasibility of flexible compared with rigid hysteroscopes, 142 patients undergoing outpatient hysteroscopy were included in a prospective, randomized clinical trial. The flexible hysteroscope was used in 70 patients, and the rigid instrument in 72. At different stages of the hysteroscopy the level of pain experienced by the women was assessed using a 10 cm visual analogue scale. Optical properties characterized by the parameters intrauterine visibility, hysteroscopic view and diagnostic accuracy were ranked by the surgeons using a 5-point scale (1 = excellent to 5 = insufficient), and duration of the hysteroscopy was measured. Hysteroscopy was successful in 87.5 and 100% of patients in the flexible and rigid groups respectively. With the use of rigid telescopes, discomfort at introduction and during the hysteroscopy was significantly greater (median 1.7 versus 0.7, P = 0.003; 3.1 versus 1.2, P < 0.001 respectively), but optical properties were judged to be far superior (P < 0.001 for all three comparisons) and procedure time was significantly shorter (median 70 versus 120 s, P = 0.003). In conclusion, outpatient hysteroscopy seems to be less painful when using flexible telescopes. However, rigid hysteroscopes provide superior optical qualities and permit a more rapid performance with higher success rates at much lower cost.     

Polarized ion transport during migration of transformed Madin-Darby canine kidney cells

Epithelial cells lose their usual polarization during carcinogenesis. Although most malignant tumours are of epithelial origin little is known about ion channels in carcinoma cells. Previously, we observed that migration of transformed Madin-Darby canine kidney (MDCK-F) cells depended on oscillating K⁺ channel activity. In the present study we examined whether periodic K⁺ channel activity may cause changes of cell volume, and whether K⁺ channel activity is distributed in a uniform way in MDCK-F cells. After determining the average volume of MDCK-F cells (2013±270 m³; n=8) by means of atomic force microscopy we deduced volume changes by calculating the K⁺ efflux during bursts of K⁺ channel activity. Therefore, we measured the membrane conductance of MDCK-F cells which periodically rose by 22.3±2.5 nS from a resting level of 6.5±1.4 nS (n=12), and we measured the membrane potential which hyperpolarized in parallel from –35.4±1.2 mV to –71.6±1.8 mV (n=11). The distribution of K⁺ channel activity was assessed by locally superfusing the front or rear end of migrating MDCK-F cells with the K⁺ channel blocker charybdotoxin (CTX). Only exposure of the rear end to CTX inhibited migration providing evidence for horizontal polarization of K⁺ channel activity in transformed MDCK-F cells. This is in contrast to the vertical polarization in parent MDCK cells. We propose that the asymmetrical distribution of K⁺ channel activity is a prerequisite for migration of MDCK-F cells.     

Quantitative histologic studies of the gonads of sand rats (Psammomys obesus) during the development of diabetes mellitus]

Quantitative-histological investigations (point counting method) are pointed out in 27 male and 15 female sand rats. The animals are divided in the IGT (impaired glucose tolerance), the diabetic and the control group. The LEYDIG cells are in the IGT-group increased, and in the diabetic group decreased. The female sand rats are characterized by the tendency of increase of size and number of follicles in the IGT-group. Corpora lutea are reduced but atretic follicles are increased in the diabetic group. The ovaries are greater in diabetic sand rats.     

Protective role of endothelial nitric oxide synthase

Nitric oxide is a versatile molecule, with its actions ranging from haemodynamic regulation to anti-proliferative effects on vascular smooth muscle cells. Nitric oxide is produced by the nitric oxide synthases, endothelial NOS (eNOS), neural NOS (nNOS), and inducible NOS (iNOS). Constitutively expressed eNOS produces low concentrations of NO, which is necessary for a good endothelial function and integrity. Endothelial derived NO is often seen as a protective agent in a variety of diseases.This review will focus on the potential protective role of eNOS. We will discuss recent data derived from studies in eNOS knockout mice and other experimental models. Furthermore, the role of eNOS in human diseases is described and possible therapeutic intervention strategies will be discussed.     

Induction of chromosome aberrations and mitotic arrest by cytomegalovirus in human cells

Human cytomegalovirus (CMV) is potentially an effective but often overlooked genotoxic agent in humans. We report here evidence that indicates that infection by CMV can induce chromosome alterations and mitotic inhibition. The frequency of chromosome aberrations induced was dependent on the input multiplicity of infection (m.o.i.) for human lung fibroblasts (LU), but not for human peripheral blood lymphocytes (PBLs) when both cell types were infected at the GO phase of the cell cycle. The aberrations induced by CMV were mostly chromatid breaks and chromosome pulverizations that resembled prematurely condensed S-phase chromatin. Pulverized chromosomes were not observed in LU cells infected with virus stocks that had been rendered nonlytic by UV-irradiation at 24,000 ergs/mm2 or from infection of human lymphocytes. In LU cells infected with UV-irradiated CMV, the frequency of aberrations induced was inversely dependent on the extent of the exposure of the CMV stock to the UV-light. In permissive CMV infection of proliferating LU cells at 24 hr after subculture, a high percentage (greater than 40%) of the metaphase cells were arrested at their first metaphase and displayed severely condensed chromosomes when harvested 48 hr later. A significant increase (p less than 0.05) in the chromosome aberration frequency was also observed. Our study shows that CMV infection is genotoxic to host cells. The types and extent of damage are dependent on the viral genome expression and on the cell cycle stage of the cells at the time of infection. The possible mechanisms for induction of chromosome damage by CMV are discussed.