The 4p- syndrome,with a report of two new cases

Summary This report illustrates the typical clinical and cytogenetic findings in two children with the Wolf syndrome (4p- syndrome). The literature of previously published cases is reviewed.

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Zusammenfassung In diesem Bericht werden die typischen klinischen und cytogenetischen Befunde bei zwei Kindern mit Wolf-Syndrom (4p--Syndrom) dargestellt. Bei dieser Gelegen-heit wird eine Übersicht über die bisher publizierten Fälle gegeben.

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Supported by contract No. 20.122 F.W.G.O., Belgium

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Bevoegd Navorser N.F.W.O., Belgium     

Representation of time-dependent correlation and recurrence time functions

Correlation functions based on time averaging are not suited to study non-stationary point processes (e.g. the electric organ discharge activity of weakly-electric pulse fish). To overcome this problem, we present here a time-dependent correlation method, which can also be applied to study complicated correlations of moderately non-stationary point processes (e.g. neuronal spike trains). Indication of recurrence time aspects of the point processes provides a more complete representation of the correlation functions. In addition higher order correlations between two point processes are represented.     

Heterogeneous binding of high mobility group chromosomal proteins to nuclei

A dramatic difference is observed in the intracellular distribution of the high mobility group (HMG) proteins when chicken embryo fibroblasts are fractionated into nucleus and cytoplasm by either mass enucleation of cytochalasin-B-treated cells or by differential centrifugation of mechanically disrupted cells. Nuclei (karyoplasts) obtained by cytochalasin B treatment of cells contain more than 90 percent of the HMG 1, while enucleated cytoplasts contain the remainder. A similar distribution between karyoplasts and cytoplasts is observed for the H1 histones and the nucleosomal core histones as anticipated. The presence of these proteins, in low amounts, in the cytoplast preparation can be accounted for by the small percentage of unenucleated cells present. In contrast, the nuclei isolated from mechanically disrupted cells contain only 30-40 percent of the total HMGs 1 and 2, the remainder being recovered in the cytosol fraction. No histone is observed in the cytosol fraction. Unike the higher molecular weight HMGs, most of the HMGs 14 and 17 sediment with the nuclei after cell lysis by mechanical disruption. The distribution of HMGs is unaffected by incubating cells with cytochalasin B and mechanically fractionating rather than enucleating them. Therefore, the dramatic difference in HMG 1 distribution observed using the two fractionation techniques cannot be explained by a cytochalasin-B-induced redistribution. On reextraction and sedimentation of isolated nuclei obtained by mechanical cell disruption, only 8 percent of the HMG 1 is released to the supernate. Thus, the majority of the HMG 1 originally isolated with these nuclei, representing 35 percent of the total HMG 1, is stably bound, as is all the HMGs 14 and 17. The remaining 65 percent of the HMGs 1 and 2 is unstably bound and leaks to the cytosol fraction under the conditions of mechanical disruption. It is suggested that the unstably bound HMGs form a protein pool capable of equilibrating between cytoplasm and stably bound HMGs.     

Synergistic antitumor activity of cyclophosphamide and ABPP in the treatment of established and advanced tumors in murine tumor models

Summary We have previously shown that the in vivo administration of ABPP, an interferon inducing pyrimidinone, generates activated killer cells that can lyse fresh tumor cells in vitro in 4-h ⁵¹chromium release assays. The administration of this agent however has no effect on established tumor. In this communication we show that ABPP, when used in combination with low or moderate doses of cyclophosphamide, can be quite effective against early established (day 3) tumor as well as against advanced, grossly visible (day 8–10) tumor in both the i.p. and pulmonary metastasis model. The synergistic antitumor activity of this cheoimmunotherapeutic regimen was very strong against immunogenic tumors but rather weak against nonimmunogenic tumors. Two treatment cycles were significantly more effective than one and multiple cycles even cured the majority of mice with established i.p. tumor. These experiments demonstrate the potential of chemoimmunotherapeutic regimens and highlight the efficacy of multiple treatment cycles.     

Molecular evolution of rodent insulins

Several trees of amino acid sequences of rodent insulins were derived with the maximum-parsimony procedure. Possible orthologous and paralogous relationships were investigated. Except for a recent gene duplication in the ancestor of rat and mouse, there are no strong arguments for other paralogous relationships. Therefore, a tree in agreement with other biological data is the most reasonable one. According to this tree, the capacity to form zinc-binding hexamers was lost once in the ancestor of the hystricomorph rodents, followed by moderately increased evolutionary rates in the lineages to African porcupine and chinchilla but highly increased rates in at least three independent lines to other taxa of this suborder: guinea pig, cuis, and Octodontoidea (coypu and casiragua).      

In vivo generation of lymphokine activated killer cell activity by ABPP and interleukin-2 and their antitumor effects against immunogenic and nonimmunogenic tumors in murine tumor models

Summary The capacity of the interferon inducer ABPP and recombinant interleukin-2 (IL-2) to generate lymphokine activated killer (LAK) cell activity in vivo was examined and compared to the cytolysis of fresh tumor cells by in vitro generated LAK cells. Various tumors differing in histology and immunogenicity were used in in vitro and in vivo experiments. The i.p. administration of ABPP or IL-2 generated much higher levels of LAK cell activity in the peritoneal exudate than in the spleen. Administration of 2 injections of ABPP was as effective as a 3-day course of moderate doses of IL-2. Generation of LAK cell activity by IL-2 was dose dependent. ABPP had significant antitumor activity in vivo in both the i.p. tumor model and the pulmonary metastasis model when administered early (24–48 h after tumor inoculation), but was ineffective against established (day 3) tumor or advanced grossly visible i.p. (day 8) tumor. Treatment of established tumor with IL-2 and LAK cells was not more effective when ABPP was given concurrently. In contrast when ABPP preceded IL-2 and LAK treatment an additional antitumor effect was seen. Immunogenic tumors were more sensitive to treatment with ABPP than nonimmunogenic tumors. Only a marginal difference in lysability in vitro existed. The antitumor effects of ABPP in vivo may therefore be mediated by mechanisms other than cytolysis by activated killer cells alone. These data taken together suggest that ABPP and IL-2 induce discernable levels of LAK cell activity, but do not synergize when combined