A report from Poland: treatment and non-treatment of defective newborns

The author and his colleagues surveyed pediatricians in Warsaw, Poland, to determine the doctors' attitudes toward treating infants with severe handicaps. They used a questionnaire originally designed by Australian researchers to survey pediatricians and compared their findings with those of the Australian study. Szawarski notes important differences between the approaches of Australian and Polish doctors to the treatment of handicapped newborns. Polish physicians tend to display an unconditional respect for life, a paternalistic attitude toward decision making, and an unwillingness to distinguish between ordinary and extraordinary means of prolonging life. Half the Polish respondents would be willing to preserve the lives of severely handicapped infants at all costs. Szawarski discusses six factors that may help to explain why Polish physicians have a different approach from that of their Western colleagues to the question of selective treatment of handicapped newborns.     

Peptides related to the active fragment of "proline rich polypeptide", an immunoregulatory protein of the ovine colostrum. Spectroscopic and computer modeling studies

The preferred solution conformation of the PRP-hexapeptide (Tyr-Val-Pro-Leu-Phe-Pro) and of some of its structural analogues was investigated by NMR-spectroscopy, spectrofluorimetry and computer simulation technic. It was found that the preferred conformation is characterized by cis'-conformation of Pro3 and the gamma-turn on the Leu4-residue: for Val2 and Phe5 a beta-structure seems to be privileged. In such a conformation Val2 and Leu4 residues occupy exactly the same positions in space as residues i and i + 3 in an alpha-helix. It suggests that the PRP-hexapeptide can interact with receptor protein inducing or stabilizing its helical conformation by "knobs into holes" packing.     

Immunosuppressive activity of antamanide and some of its analogues

In connection with our discovery of a strong immunosuppressive activity of cyclolinopeptide A (CLA), we investigated immunosuppressive properties of antamanide and a number of its analogues, including symmetrical antamanide, and compared them with the activities of cyclosporin A and CLA. The peptides were investigated by using plaque forming cell (PFC), graft-versus-host (GvH), delayed type hypersensitivity (DTH), and autologous rosette formation cell (ARFC) tests. Antamanide and symmetrical antamanide exhibit an immunosuppressive activity lower than CLA. Linear antamanide fragments are also active. At higher concentrations of the latter peptides, toxic effects occur.     

Natural killer cell activity in murine muscular dystrophy. III. NK-sensitive myoblast cells and lack of NK activity in beige/dystrophic hybrid mice

The NK-susceptibility of dystrophic mouse myoblast cells was investigated. Spleen cells from 8- to 10-week-old normal (+/+) and dystrophic (dy2J/dy2J) male C57BL/6J mice were fractionated on Percoll density gradients and the cells at each density interface were incubated with either 51Cr-labeled YAC-1 or myoblast cells in a 6 hr 51Cr-release assay. Myoblast target cells were obtained from either heterozygous (+/dy2J) or homozygous (dy2J/dy2J) muscle cultures or a transformed tetraploid myoblast line (M14D2). The data indicate that the interface between the 50 and 60% (1.060-1.075 g/ml) Percoll density fractions of spleen cells from either normal or dystrophic mice contains the largest proportion of asialo GM-1 positive and NK-1 positive cells displaying NK activity. Myoblast cells from either heterozygous (phenotypically normal) or homozygous dystrophic mice were not significantly different in susceptibility to NK-mediated lysis by Percoll enriched normal or dystrophic mouse NK cells. However, dystrophic mouse spleen cells had the highest NK activity against both myoblast targets as compared with normal mouse spleen cells. The transformed myoblast cell line, M14D2, was significantly less susceptible to NK-mediated lysis by dystrophic mouse spleen cells when compared with freshly cultured myoblast target cells. Target cell binding studies revealed that conjugate forming cells from the 50% Percoll density interface of dystrophic mouse spleen cells were approximately twofold greater than that of normal mouse spleen cells against either heterozygous or homozygous dystrophic mouse myoblast targets. Cold target inhibition studies revealed that the natural killing of dystrophic mouse myoblast cells was due to a YAC-1 reactive NK cell. Breeding experiments between C57BL/6J homozygous "beige" (bgJ/bgJ) mutant mice and dystrophic (dy2J/dy2J) mice produced beige/dystrophic hybrid mice which displayed clinical symptoms of the dystrophy process by 3 to 4 weeks of age. Spleen cells from these hybrid mice showed no significant differences in NK activity against YAC-1 target cells when compared with homozygous beige mice. Taken together, these results demonstrate the first reported evidence that murine myoblasts are susceptible to NK-mediated lysis. In addition, the data indicate that although dystrophic mouse NK cells recognize myoblast cells as targets, the NK cell studies with the beige/dystrophic hybrid mice do not indicate a direct in vivo role for NK cells in the dystrophy process.     

Analysis of a cell cycle model based on unequal division of metabolic constituents to daughter cells during cytokinesis

We demonstrate that the unequal division of RNA during cytokinesis explains the dispersion of cell generation times in CHO cell cultures. Experimental cytometric results reported previously serve as a basis for a probabilistic model of cytokinesis. Unequal RNA division to daughter cells, together with two simple laws of RNA production, are used as a source of randomness within the cell cycle. The model reproduces the experimental growth of the CHO cell population, including the observed variability in RNA content. The model has stabilizing properties which explain why a cell population with increased RNA content characteristics, a few cell cycles, to the original pattern. Other cell cycle characteristics, like sister-to-sister and mother-to-daughter generation time correlations implied by the model, are close to their experimental analogs. The conceptual basis of the model is general enough to include unequal division of factors other than RNA (cell mass, cell proteins, etc.) as sources of generation time variability. It seems that the observed dispersion of cell generation times, explained previously in the terms of random transitions in some part of the cell cycle (the Smith & Martin A and B state hypothesis), can be reduced to the single random event of unequal division. This supplies a new convenient tool in the investigation of cell cycle kinetics.     

Removal of239Pu from mice with 3,4,3 LICAM(C) or N,N′, N″, N‴-tetra-(2,3-dihydroxybenzoyl)-spermine

Summary Male mice SAS/4 were injected i.v. with²³⁹Pu citr(IV) 0.27 µCikg^–1–9.99 kBqkg^–1. After 1 h 30 µmol kg^–1 of 3,4,3 LICAM(C), N, N, N, N-tetra-(2,3-dihydroxybenzoyl)-spermine or Na₃CaDTPA as a reference compound was given intraperitoneally. After 4 days the animals were sacrified and the Pu content in livers, kidneys, femurs and carcasses was determined by the liquid scintillation method. It was found that, as compared with the control, 3,4,3 LICAM(C) removed 83% of the Pu activity deposited in the liver, 71% of that in the femur and 79% of the Pu in the whole body. The Pu content in the kidneys exceeded the control value by about 50%. Na₃CaDTPA removed 96, 86, 40 and 72% of plutonium from the liver, kidneys, femurs and carcasses respectively.Tetra-DHB-spermine caused the excretion of 50, 57 and 39% of Pu from liver, bone and whole body respectively. The retention of Pu in the kidneys was increased to 400% of the control value.     

Stathmokinetic Analysis of Human Epidermal Cells in vitro

Proliferation kinetics of cultured human epidermal cells is characterized in quantitative terms. Three distinct subpopulations of keratinocytes, two of which are cycling have been discriminated by two parameter DNA/RNA flow cytometry. Based on mathematical modelling, the cell cycle parameters of the cycling subpopulations have been assessed from stathmokinetic data collected at different time points after initiation of cultures (7–15 days). the first subpopulation is composed of low-RNA cells which resemble basal keratinocytes of epidermis and which show some characteristics of stem cells; these cells have a mean generation time of approximately 100 hr. the second subpopulation consists of high-RNA cells, resembling stratum spinosum cells of epidermis, which have an average generation time of approximately 40 hr. the third subpopulation consists of non-cycling cells with G_o/G₁ DNA content, with cytochemical features similar to those of cells in granular layer of epidermis. The results based on modelling can reproduce with acceptable accuracy the actual growth curve of the cultured cell population. Analysis of kinetics and differentiation of human keratinocytes is of interest in view of the recent application of cultured epidermal cell sheets for transplantation onto burn wounds. the results of this study also reveal the existence of regulatory mechanisms associated with proliferation and differentiation in the cultured epidermal cell population.