Modifiers of ochre suppressors in Saccharomyces cerevisiae that exhibit ochre suppressor-dependent amber suppression

Summary Mutants of Saccharomyces cerevisiae were selected that would interact with ochre (UAA) suppressors so as to allow ochre -suppressor dependant amber (UAG) suppression, but which do not exhibit opal (UGA) suppression. Strains mutant at four distinct loci were isolated, and two of these are recessive mutations while the other two behave as dominants or semidominants. MOS3 has some suppressor activity in the absence of a resident SUP4-o gene and shares other characteristics with previously described omnipotent suppressors. MOS4, mos1 and mos2, on the other hand, exhibit no suppressor activity in the absence of a resident SUP4-o gene but do exhibit suppression of UAG alleles when there is a resident SUP4-o gene. These latter modifier strains do not interact with a SUP4-o gene to suppress UGA alleles. By genetic and physiological criteria the MOS4, mosl, and most mutations appear to be different than previously described allosuppressors or modifiers of suppression.     

Role of NK cells and gamma interferon in transplacental passage of Toxoplasma gondii in a mouse model of primary infection

Protective immunity in mice infected with Toxoplasma gondii is mainly mediated by NK cells, CD4 and CD8 T cells, and type 1 cytokines, such as gamma interferon (IFN-gamma). To clarify the roles of NK cells and IFN-gamma in protection against primary congenital toxoplasmosis, we used recombination activating gene 2 knockout (RAG-2(-/-)) mice, which lack T and B lymphocytes, in comparison with the wild-type BALB/c model. RAG-2(-/-) mice had a significantly lower risk of fetal toxoplasmosis than BALB/c mice (25 versus 63.9%; P = 0.003). This protection was associated with an increased number of maternal NK cells, IFN-gamma secretion by spleen cells, and decreased parasitemia. In the RAG-2(-/-) mice, NK cell depletion increased both the rate of fetal infection, to 56.5% (P = 0.02), and the blood parasite burden. Conversely, in the BALB/c mice, this treatment did not modify maternofetal transmission or the blood parasite burden. Neutralization of IFN-gamma in both infected RAG-2(-/-) and BALB/c mice decreased congenital Toxoplasma transmission, contrasting with an exacerbation of maternal infection. These data suggest that a partially protective immunity against congenital toxoplasmosis is achieved due to the increased number of NK cells in RAG-2(-/-) mice. However, it seems that IFN-gamma enhances, directly or indirectly, the transplacental transmission.     

Mechanisms of peptide YY release induced by an intraduodenal meal in rats: neural regulation by proximal gut

 Peptide YY (PYY) release in anaesthetized rats was studied during the 2 h following the intraduodenal administration of a semi-liquid meal of 21 kJ. Surgical and pharmacological manipulations were performed in order to analyse the mechanisms of PYY release. Postprandial PYY release was suppressed or strongly decreased by caecocolonectomy, truncal vagotomy, tetrodotoxin, hexamethonium, sensory denervation by perivagal capsaicin, and by the NO-synthase inhibitor L-N-arginine methyl ester, while atropine, adrenergic blockers, antagonists of type-A or type-B cholecystokinin (CCK) receptors or bombesin receptors had no effect. Comparing the digestive transit of the semi-liquid meal with the amount of PYY contained in the small bowel wall showed that nutrients had not reached the area rich in cells containing PYY by 30 min, the time at which there was a large PYY release in plasma. By 120 min, the meal front had travelled 72% of the small intestine length, just beginning to reach the PYY-rich part of the ileum. We conclude that the main postprandial PYY release studied in this model comes from ileal and colonic L-cells indirectly stimulated through a neural mechanism originating in the proximal gut and involving sensory vagal fibres, nicotinic synapses and NO release, while CCK and bombesin do not seem to be physiologically involved. Received: 17 July 1996 / Received after revision: 11 October 1996 / Accepted: 18 October 1996     

Fucosidosis revisited: a review of 77 patients

Fucosidosis is a rare, autosomal recessive, lysosomal storage disorder caused by a severe deficiency of alpha-L-fucosidase in all tissues. We have conducted a review of fucosidosis, compiling data from published reports and an international questionnaire survey. Seventy-seven patients affected with fucosidosis of which 19 had not been reported before have been identified. A major aim of the present study was to define the natural history of fucosidosis. The clinical picture of fucosidosis consists of progressive mental (95%) and motor (87%) deterioration, coarse facies (79%), growth retardation (78%), recurrent infections (78%), dysostosis multiplex (58%), angiokeratoma corporis diffusum (52%), visceromegaly (44%), and seizures (38%). Whereas the original fucosidosis patients described by Durand et al. (J. Pediatr 75:665-674, 1969) were decerebrate and died before age 5 years, most fucosidosis patients have a slower course of degeneration. Mortality before age 5 years was observed in only 7 patients (9%), whereas 36 patients (64%) reached the second decade. We did not find evidence for the existence of clinical heterogeneity with a rapidly progressive type I and a slowly progressive type II fucosidosis as suggested in the literature. Instead, there seems to exist a wide continuous clinical spectrum. At the biochemical level no heterogeneity in residual fucosidase enzyme activity or cross-reacting immunoreactive fucosidase protein was observed. At the DNA level at least 4 different mutations must be responsible for fucosidosis. These genotypic differences however do not explain the observed phenotypic differences.     

Lamellar cells of sensory receptors and perineural cells of nerve endings of pig skin contain cytokeratins

Summary The lamellar cells of the sensory corpuscles of the pig dermis must be considered to be epithelial cells as they contain cytokeratins. The cytokeratins detected are similar to those found in simple epithelia. Moreover, lamellar cells are embedded in an extracellular matrix reminiscent of the basement membrane of epithelium since it contains laminin and collagen IV. The perineural cells surrounding the nerves of pig dermis present the same features.These results suggest that lamellar cells and perineural cells have the same origin. The nature of the lamellar and perineural cells of the rabbit or human dermis is not as clear since cytokeratins were not detected in those cells. These results, together with recent observations on Merkel cells, may indicate that epithelio-neuronal junctions are a general feature of cutaneous sensory receptors.     

Proliferation and differentiation of human CD5+ and CD5- B cell subsets activated through their antigen receptors or CD40 antigens.

The pan-T cell antigen CD5 has been shown to delineate two different mouse B cell subsets, originating from distinct progenitors. In man, on average, 30% of the tonsillar B cell pool expresses this antigen. In the present report, a detailed comparison of the CD5+ and CD5- B cell response to cytokines, following activation via surface immunoglobulins (sIg) or CD40 antigen, was undertaken. CD5+ B cells were positively selected by panning or by sorting from tonsils. Two-color immunofluorescence analysis performed on tonsillar B cell populations showed that CD5+ B cells displayed most of the phenotypic features of mantle zone B cells. CD5+ B cells could be stimulated for DNA synthesis by mitogenic concentrations of Staphylococcus aureus, Cowan I strain (SAC), insolubilized anti-IgM antibodies, immobilized anti-CD40 antibodies and phorbol 12-myristate 13-acetate (PMA). The growth-response of small dense CD5- B cells to these T cell-independent mitogens was comparable to that of CD5+ B cells, whereas the low-density, in vivo-activated, CD5- B cells were only marginally stimulated by Ig-cross-linking agents and PMA. Following ligation of sIg, both B cell subsets proliferated essentially in response to interleukin (IL)-2 and IL-4. When used in co-stimulation with immobilized anti-CD40 antibodies, IL-4 promoted growth of CD5+ and CD5- B cells, whereas IL-2 displayed only moderate stimulatory effects. CD5+ and CD5- B cells differentiated into Ig-secreting cells when they were co-cultured with SAC or cross-linked anti-CD40 antibodies and IL-2. However, IgM constituted the major component of the Ig response of CD5+ B cells, whereas high levels of IgG were secreted by CD5- B cells.     

Electrotonic parameters of neurons following chronic ethanol consumption

The electronic parameters of nerve cells in the dentate gyrus following long-term ingestion of ethanol were studied in vitro. The ethanol was administered in a liquid diet for a period of 20 wk followed by a 3-wk withdrawal period. A control group received a similar diet with the ethanol replaced by maltose-dextrins. Intracellular recordings were obtained from 44 neurons, and the voltage decays following current injections were analyzed with a recent electrical model of granule cells to take into account a somatic shunt already detected in previous studies. The new model accurately accounted for the fast voltage transients and showed that the membrane time constant in the dendrites is, on average, five times larger than the somatic time constant. Injection of horseradish peroxidase into the neurons for the morphological analysis showed that neurons in the ethanol group have a longer dendritic tree than neurons in the control group. Estimation of the membrane surface area showed that the membrane area in the dendrites is at least 60% greater (in both control and ethanol groups) when the membrane foldings and irregularities are taken into account. The results of the modeling analysis showed that the membrane time constant and the input resistance are not affected by ethanol. However, the membrane resistance is significantly increased in the ethanol group (6,632 versus 18,460 omega X cm2), and the capacitance is significantly decreased (4.48 versus 1.71 microF/cm2). The electrotonic length is also increased by chronic ethanol treatment (0.85 versus 0.94). Higher values of membrane specific resistance (Rm) mean larger transmission coefficients. However, since the neurons from the ethanol group are on average longer than neurons in the control group, it is suggested that the change in Rm compensates for the increase in the length of the dendrites, thereby maintaining a value of the electrotonic length under 1.0. The observed changes in the passive parameters are in opposite direction from the recently measured effect of acute doses of ethanol on hippocampal neurons. These results support a model of chronic alcohol intake where homeostatic adaptive changes lead to the development of long-term changes in cellular physiology.     

First record of the Indo-Pacific Cymothoa indica (Crustacea, Isopoda, Cymothoidae), a Lessepsian species in the Mediterranean Sea

Cymothoa indica, a typical Indo-Pacific genus and species, is reported for the first time in the eastern Mediterranean Sea. Specimens were found parasitizing mainly barracudas (Sphyraenidae) from Lebanon. Female and male specimens are described on collected materials. To date, the genus Cymothoa has not been reported in the Mediterranean Sea although it is widely represented in other areas of the world. It is suggested that C. indica should be added to the list of exotic species introduced from the Red Sea and known as Lessepsian migrants.