Tomoscintigraphy for detecting gastrointestinal and medullary thyroid cancers: first clinical results using radiolabelled monoclonal antibodies against carcinoembryonic antigen.

Transaxial tomoscintigraphy (or single-photon emission computerised tomography) was used to detect secondary deposits of carcinoma in 17 patients who had been injected with iodine-131-labelled monoclonal antibodies against carcinoembryonic antigen. Of 17 tumor sites studied by tomoscintigraphy 16 were detected (sensitivity 94%); five sites had a volume smaller than 10 cm3. Tomoscintigraphy also detected three unknown tumour deposits later confirmed by surgery or radiology. In contrast, when 21 tumour sites in the same patients were studied by rectilinear scintigraphy, only nine tumour sites were detected (sensitivity 43%), of which eight had a volume larger than 50 cm3.     

B cell growth-promoting activity of recombinant human interleukin 4

Human interleukin 4 (IL-4), also known as B cell stimulatory factor 1, is a T cell-derived glycoprotein consisting of 129 amino acids for which a cDNA has been recently isolated. IL-4 displays little or no B cell growth factor (BCGF) activity in the standard anti-IgM costimulatory assay using suboptimal concentrations of soluble anti-IgM antibody whereas the low m.w. BCGF is very active. When insolubilized anti-IgM was used as the costimulating agent, both IL-4 and the low m.w. BCGF were found to promote B cell proliferation. Human IL-4 is able to induce the proliferation of B lymphocytes preactivated for either 1 day with insolubilized anti-IgM antibody or for 3 days with Staphylococcus aureus strain Cowan I. However, IL-4 is poorly mitogenic for B cells preactivated for 1 day with the Staphylococcus strain whereas the low m.w. BCGF strongly enhances the proliferation of these B cells. These two findings demonstrate that the preactivation signal necessary to induce human B cells to proliferate in response to IL-4 is critical. The increased tritiated thymidine ([3H]dThd) uptake in preactivated B cell cultures with IL-4 reflects cel proliferation because cell cycle analysis demonstrates that IL-4 induces activated B cells to enter the S and G2/M phases of the cell cycle and the addition of IL-4 to preactivated B cell cultures permits the recovery of three- to fourfold more B cells after 4 days of culture. IL-4 and the low m.w. BCGF act in concert to induce the proliferation of anti-IgM-preactivated B cells as demonstrated by [3H]dThd uptake and cell cycle analysis. In striking contrast to the demonstrated antagonistic effect of interferon-gamma on the IL-4-induced expression of the low affinity receptor for IgE (Fc epsilon RL/CD23), on B cells, it was found that interferon-gamma enhanced the IL-4-induced proliferation of anti-IgM-preactivated B cells. Finally, it was found that IL-4 had to be present continuously during the culture period to exert an optimal growth-promoting effect on B cell blasts. As a conclusion, IL-4 is able to induce the proliferation of an appropriately activated subpopulation of human B cells.     

Backbone side-chain interactions in peptides

IR, ¹H-NMR and X-ray experiments have been carried out on dipeptides with the Pro-Asp and Pro-Asn sequences protected on both ends by amide groups. The Pro-Asp dipeptide was investigated for the carboxylic, methyl ester and carboxylate forms of the Asp residue.In solution, all dipeptides are found to accommodate almost exclusively the I-turn conformation stabilized by an interaction between the Asp or Asn-NH and CO bonds. The I-turn percentage roughly parallels the basicity of the Asp or Asn side substituent, and decreases from Asp^- to Asn, and to Asp or Asp (OMe).The I-turn, stabilized by the interaction involving the Asp-CO site, is retained in the crystal structure of the Pro-Asp(OMe) dipeptide. The Pro-Asp and Pro-Asn dipeptides assume a II-turn conformation in the solid state and the polar Asp or Asn side-groups are involved in a complex network of intermolecular interactions.     

Crystal state conformation of three azapeptides containing the Azaproline residue,a β-turn regulator

The molecular structure of three protected AzaPro-containing peptides have been determined by x-ray diffraction: Z-AzaPro-NHiPr ( 1 ; Z: benzyloxycarbonyl), Z-AzaPro-L -Ala-NHiPr ( 2 ), and Boc-L -Ala-AzaPro-NHiPr ( 3 ; Boc: tert-butyloxycarbonyl). Starting from the key synthon benzyl-azaprolinate, compounds 1 , 2 , and 3 have been prepared by combined use of liquid phase peptide synthesis method and adequate isocyanates. In all peptides, the following geometric characteristics are retained: (a) pyramidal character of the two nitrogen atoms of the pyrazolidine ring; (b) pseudo cis conformation of the urethane ( 1 , 2 ) or tertiary amide ( 3 ) function preceding the AzaPro residue; (c) identical absolute values of the Azaproline residue torsion angles “?, ψ” respectively 111° and 23°. In compound 2 , the two nitrogen atoms of the pyrazolidine ring are R, R but the opposite S, S absolute configurations are observed in compound 3 . In the crystal, compound 3 adopts a folded structure similar to a type VI β-turn with a weak intramolecular i + 3 → i hydrogen bond, while an extended structure is observed in compound 2 . In the light of our findings, in a peptide chain and contrary to the Pro residue, an AzaPro residue should prevent the formation of any type of any type of β-turn with the residue following it but could accommodate a folded structure with a pseudo type VI βturn with the preceding residue. If confirmed, this would be of tremendous importance in the design of biologically active peptides and drugs. © 1993 John Wiley & Sons, Inc.     

Folded Structures in Protonated Reduced Dipeptides

Reduced dipeptides with the general formula RCO-Xaa- rXbb-N⁺HR′R′′ (rXbb, reduced analogue of residue Xbb: NH-C^α HR¹ -C_r H₂) are shown to adopt a folded conformation in solution and in the solid state. The protonated reduced amide bond is an active proton donor capable of interacting with a peptide carbonyl to give a strong hydrogen bond topologically equivalent to the i+2 or i+3? i interaction. The resulting conformation is similar to the γ- or β-turn structure found in peptides and proteins.     

Modelling of fluid-phase endocytosis kinetics in the amoebae of the cellular slime mouldDictyostelium discoideum. A multicompartmental approach

Fluid-phase endocytosis (pinocytosis) kinetics were studied inDictyostelium discoideum amoebae from the axenic strain Ax-2 that exhibits high rates of fluid-phase endocytosis when cultured in liquid nutrient media. Fluorescein-labelled dextran (FITC-dextran) was used as a marker in continuous uptake- and in pulse-chase exocytosis experiments. In the latter case, efflux of the marker was monitored on cells loaded for short periods of time and resuspended in marker-free medium. A multicompartmental model was developed which describes satisfactorily fluid-phase endocytosis kinetics. In particular, it accounts correctly for the extended latency period before exocytosis in pulse-chase experiments and it suggests the existence of some sorts of maturation stages in the pathway.     

Excess of deletions of maternal origin in the DiGeorge/Velo-cardio-facial syndromes. A study of 22 new patients and review of the literature

We have determined the parental origin of the deleted chromosome 22 in 29 cases of DiGeorge syndrome (DGS) using a CA-repeat mapping within the commonly deleted region, and in one other case by using a chromosome 22 short arm heteromorphism. The CA-repeat was informative in 21 out of 29 families studied and the deleted chromosome was of maternal origin in 16 cases (72%). When these data are pooled with recent results from the literature, 24 de novo DGS, velo-cardio-facial syndrome (VCFS) and isolated conotruncal cardiac disease deletions are found to be of maternal origin and 8 of paternal origin, yielding a ² of 8 with a probability level lower than 0.01. These data, and review of the literature on familial DGS/VCFS and isolated conotruncal cardiopathies suggest that there is a strong tendency for the 22q11.2 deletions to be of maternal origin.