Target cells for the activity of a synthetic adjuvant: muramyl dipeptide.

Muramyl dipeptide (MDP), a synthetic adjuvant, increased the primary response of CBA mice to sheep red blood cells (SRBC). In reconstituted irradiated recipients, cooperation between T and B lymphocytes was required for the expression of adjuvant activity and MDP increased the efficiency of SRBC-educated T cells. The role of T-derived lymphocytes in mediating the MDP adjuvant activity was also demonstrated in irradiated mice and in mice reconstituted with various splenic cellular types of donors which had received SRBC and MDP 24 hr earlier. In our experiments, the macrophage did not seem to be involved, since MDP did not increase the phagocytic capacity of peritoneal exudate cells and MDP- and SRBC-pretreated macrophages had no increased ability to induce an anti-SRBC immune response. These results demonstrate the importance of T lymphocytes as mediators of the adjuvant activity of MDP.     

Influence of dicarboxylic phosphatidylcholines on phosphatidylcholine liposomes as revealed by gel chromatography and electron microscopy

The effect of dicarboxylic phosphatidylcholines (glutarylphosphatidylcholine) on the structural changes of phosphatidylcholine liposomes is examined by using multilamellar liposomes prepared with egg phosphatidylcholine or dipalmitoylphosphatidylcholine and by varying the surface charge by addition of dicetyl phosphate. Investigations are performed by gel chromatography and electron microscopy. Glutarylphosphatidylcholine is in micellar form (rod-like micelles or globular micelles). The structures obtained depend on the fatty acid saturation of liposomes and on the charge of liposome (addition or not of dicetyl phosphate). With egg phosphatidylcholine/glutarylphosphatidylcholine dispersions, an aspect more similar to myelinic figures than liposomes is observed, while in the presence of dicetyl phosphate, liposomes similar to control egg phosphatidylcholine liposomes are obtained. Gel chromatography on Sepharose 4B and turbidity measurements prove that dicetyl phosphate increases the stability of egg phosphatidylcholine/glutarylphosphatidylcholine mixtures. On the other hand, in dipalmitoylphosphatidylcholine/glutarylphosphatidylcholine dispersions, incorporation of dicetyl phosphate destabilizes bilayer structure and the formation of mixed micelles occurs. Viscosity measurement shows, in the presence of dicetyl phosphate, an increased fluidity for dipalmitoylphosphatidylcholine/glutarylphosphatidylcholine dispersions, in agreement with the micellar organization. These data confirm that the disorganization of liposomal membranes by dicarboxylic phosphatidylcholine depends on the fatty acid composition of phosphatidylcholine and on the presence of dicetyl phosphate.     

Image cytometry of progesterone receptor expression during the cell cycle in the MCF-7 cell line

Progesterone receptors (PR) appear to be distributed in a heterogeneous way in mammary tumor cells. The study presented here was designed to examine if heterogeneity of PR expression is cell-cycle dependent. Immunofluorescence techniques were used to label PR on the MCF-7 human breast cancer cell line and image cytometry was used to analyze the PR expression during G0 (Ki-67 antigen-negative cells), G1, S, and G2/M cell-cycle phases. A second PR, BrdU, and DNA analysis was performed to study PR expression in the S-phase (BrdU-positive cells). Our results show that PR synthesis occurs preferentially during the G0-G1 transition and that PR levels are constant during the G1-G2 transition. The PR expression appears to be cell-cycle related and may therefore explain the heterogeneity of PR expression. However, the possibility that PR heterogeneity may be linked to the existence of PR-negative subclones cannot be ruled out.     

Cerebral Metabolic Effects of Monoamine Oxidase Inhibition in Normal and 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Acutely Treated Monkeys

The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces dopaminergic cell death in the substantia nigra pars compacta (SNpc) and clinical parkinsonism in humans and experimental animals. Pretreatment with monoamine oxidase inhibitors prevents this cell death and associated parkinsonism by blocking the oxidation of MPTP to a toxic intermediate. The 2-deoxyglucose method was used to study the acute effects of MPTP in the monkey brain and the effects of monoamine oxidase inhibition on local cerebral glucose utilization in both normal and MPTP-treated monkeys. MPTP administration alone caused a major increase in glucose utilization in the SNpc and smaller increases in some subnuclei within the ventral tegmental area in which eventual dopaminergic cell loss also occurs. Pretreatment with pargyline abolished these metabolic increases, a finding suggesting both that the oxidized product of MPTP generates the metabolic increases and that the increased glucose consumption may contribute to cell toxicity. On the other hand, in most cortical, thalamic, striatal, brainstem, and cerebellar areas MPTP alone caused reductions in glucose utilization, and pargyline failed to prevent these effects. Pargyline alone depressed metabolism in the locus coeruleus and a few other monoaminergic structures.     

Iodine intakes assessed by urinary iodine concentrations in healthy children aged ten months,two years,and four years

Urinary iodine excretion was assessed in 642 healthy children aged 10 mo (n=243), 2 yr (n=183), and 4 yr (n=216) living in the Paris area and originating from continental France (60.3%), North Africa (13.8%), the West Indies (9.1%), West Africa (8.3%), Southeast Asia (4.8%), and southern Europe (3.8%). Mild impairment of neurological (reflexes, tone, audiometry) and intellectual development (Brunet-Lézine scale) was assessed in relation to iodine status. Iodine excretions (median values) were 18.4, 11.9, and 10.9 μg/100 mL at 10 mo, 2 yr, and 4 yr, respectively, and risk of mild iodine deficiency (5–10 μg/100 mL) was 18.1%, 34.8%, and 38.3% for the same age groups. No relationship was found between anthropometry, global development quotient, and iodine status. High hearing thresholds were more commonly associated with lower iodine excretion, suggesting mild hearing defects. In spite of iodine prophylaxis, the risk of mild to moderate iodine deficiency still exists in France and in a number of European countries. Evaluation of neurological sequels of borderline iodine status is a major public health problem in European communities.     

In situ spectroradiometric estimation of microalgal biomass in first-year sea ice

Summary First- and multi-year sea ice are colonized by microalgae, whose biomass modifies the spectral distribution of underice downwelling irradiance. It is proposed that an index of algal biomass in the first-year ice may be derived from the ratio of underice irradiance at a wavelength where absorption by chlorophyll a is high to a wavelength where absorption by the photosynthetic pigments is low and transmission through the ice is high. In southeastern Hudson Bay (Canadian Arctic), the irradiance ratio (671540 nm) accounts for 55% of the variance in chlorophyll a, indicating that the in situ biomass of algae in first-year ice can be estimated from spectral measurements of underice downwelling irradiance.Contribution to the programme of GIROQ (Groupe interuniversitaire de recherches océanographiques du Québec)     

Morphology and morphodynamics of the stenotele nematocyst of Hydra attenuata Pall. (Hydrozoa,Cnidaria)

This light- and electron-microscopic study has investigated the structure, the morphodynamics of discharge, and the impact of the stenotele cyst of Hydra attenuata (Hydrozoa, Cnidaria) on the prey's integument. The triggered capsule, which is ejected from the cell, discharges its tubular content (shaft, stylets and tubule) by a process of evagination. In doing so the three joined stylets punch a hole into the cuticle of the prey through which the long evaginating tubule penetrates into the interior of the target. The behaviour of the tubule is described in detail and the functional significances of the various parts of the capsule are discussed.     

Effect of the natural ATPase inhibitor on the binding of adenine nucleotides and inorganic phosphate to mitochondrial F1-ATPase

(1) Incubation of the beef heart mitochondrial ATPase, F₁ with Mg-ATP was required for the binding of the natural inhibitor, IF₁, to F₁ to form the inactive F₁-IF₁ complex. When F₁ was incubated in the presence of [¹⁴C]ATP and MgCl₂, about 2 mol ¹⁴C-labeled adenine nucleotides were found to bind per mol of F₁; the bound ¹⁴C-labeled nucleotides consisted of [¹⁴C]ADP arising from [¹⁴C]ATP hydrolysis and [¹⁴C]ATP. The ¹⁴C-labeled nucleotide binding was not prevented by IF₁. These data are in agreement with the idea that the formation of the F₁-IF₁ complex requires an appropriate conformation of F₁. (2) The ¹⁴C-labeled adenine nucleotides bound to F₁ following preincubation of F₁ with Mg-[¹⁴C]ATP could be exchanged with added [³H]ADP or [³H]ATP. No exchange occurred between added [³H]ADP or [³H]ATP and the ¹⁴C-labeled adenine nucleotides bound to the F₁-IF₁ complex. These data suggest that the conformation of F₁ in the isolated F₁-IF₁ complex is further modified in such a way that the bound ¹⁴C-labeled nucleotides are no longer available for exchange. (3) ³²P_i was able to bind to isolated F₁ with a stoichiometry of about 1 mol of P_i per mol of F₁ (Penefsky, H.S. (1977) J. Biol. Chem. 252, 2891–2899). There was no binding of ³²P_i to the F₁-IF₁ complex. Thus, not only the nucleotides sites, but also the P_i site, are masked from interaction with external ligands in the isolated F₁-IF₁ complex.