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Biomedical subjects

P Gottlieb

Publications and source records attributed to P Gottlieb.

At least 55 records · Page 3Linked to original sources
PubMed1987

Psychotic homicides in Copenhagen from 1959 to 1983.

During the years from 1959 to 1983, 263 Copenhagen defendants of homicide underwent a psychiatric examination for the court. Twenty-three percent of the defendants were held to be psychotic at the time of the crime. The psychotic defendants differed from the non-psychotic by being older, less often substance abusing and by choosing victims inside their families. It is discussed whether a reduction in the available number of psychiatric beds could be a contributional reason for the increase in especially the number of schizophrenic defendants. About one third of all defendants were by the examining psychiatrists found in need of a sanction different from ordinary punishment; furthermore, a tendency towards sanctions of treatment instead of just placement in a psychiatric hospital was documented and is discussed. The increasing demand of capacity for forensic, psychiatric patients is mentioned.

Adult↗
PubMed1987

The practice of forensic psychiatry in cases of homicide in Copenhagen, 1959 to 1983.

During the years 1959 to 1983 a doubling in the rate of homicide took place in Copenhagen. This increase was exclusively due to an increasing number of male offenders. By comparing with another Danish material, the frequency of female homicide as well as that of homicide combined with suicide was found practically unchanged since 1946, indicating that both of these kinds of homicides seem to have a background different from those of other offences of fatal violence. During the years 1959 to 1983, the criteria of selection of the defendants for a psychiatric examination for the court were fairly consistent. Examinations were performed in practically all cases, where a charge of murder raised by the police was followed by a legal trial for homicide. Less and less of the defendants, however, were hospitalized for the examination, while more were examined in The Clinic of Forensic Psychiatry in Copenhagen.

Denmark↗
PubMed1986

Tuftsin analogues: synthesis, structure-function relationships, and implications for specificity of tuftsin's bioactivity.

Thirteen analogues of the natural macrophage activator peptide tuftsin, ten of which are novel, were synthesized with the aim of exploring the relation between their biological potency and their capacity to attach specifically to cellular tuftsin's receptors. The analogues representing modifications and chain extensions at various parts of the parent tuftsin molecule can be classified as N-terminal analogues, C-terminal analogues, "within-chain" derivatives, or dimers of tuftsin and retrotuftsin. The various synthetic routes employed to prepare the analogues are described. A direct correlation was found between the ability of analogues to inhibit [3H-Arg4]tuftsin specific binding to mice peritoneal macrophages and their capacity to enhance phagocytosis or to inhibit tuftsin-mediated phagocytosis by the cells and to potentiate the cell's immune response.

Animals↗
PubMed1985

Binding studies of SV40 T-antigen to SV40 binding site II.

SV40 T-Antigen binding site II was synthesized, cloned and analyzed for its ability to bind purified SV40 T-antigen. We report the binding constant of T-antigen for isolated site II. Using a filter binding assay the calculated binding constant was 6-8 fold less efficient than site I previously reported. Binding constants were calculated using two methods. The first was a direct calculation using a protein titration curve (KD). The second was by the ratio of measured association and dissociation rates. Both methods gave similar constants. Protection studies with SV40 T-antigen on the T-antigen binding sites in the wild-type array demonstrated that the binding constants of site I and site II are similar to those calculated for the individual sites. These results demonstrate that SV40 T-antigen does not bind cooperatively to sites one and two as earlier believed and are in agreement with recent observations emanating from several laboratories.

Antigens, Polyomavirus Transforming↗
PubMed1985

Alterations in the number of rRNA operons within the Bacillus subtilis genome.

Deletions and additions of rRNA gene sets in Bacillus subtilis were observed by Southern hybridizations using cloned radiolabeled rDNA sequences. Of the ten rRNA gene sets found in B. subtilis 168M or NCTC3610, one was deleted in strains possessing the leuB1, ilvC1, argA2 and pheA1 mutations. Among EcoRI restriction fragments of genomic DNA products, a 2.9-kb 23S rRNA homolog was missing. In HindIII digest, both 5.5- and 5.1-kb hybrid bands were lost with 16S and 23S probes, respectively. Similarly, genomic DNAs digested with SmaI showed the absence of both 2.1- and 2.0-kb fragments that hybridized to 16S and 5S sequences, respectively, in wild-type genomes. In contrast, B. subtilis strain 166 and its derivatives displayed a gain of a 3.3-kb HindIII fragment homologous to 16S rRNA. Transforming the ilvC1 and leuB1 mutations into new genetic backgrounds revealed in some clones the concomitant introduction of the ribosomal defect. Transformations with the slightly heterologous donor DNA from strain W23 yielded some Leu+ and Arg+ transformants with altered hybridization patterns when probed with cloned sequences. We propose that the deletion of the rRNA operon occurred in the ilv-leu gene cluster of the B. subtilis genome as a result of unequal recombination between redundant sequences.

Bacillus subtilis↗
PubMed1984

Receptor-mediated endocytosis of tuftsin by macrophage cells.

A fluorescent analog of the phagocytosis stimulating peptide tuftsin was prepared by coupling tetramethyl rhodamine isothiocyanate to a C-terminal elongated derivative of tuftsin. This analog, Thr-Lys-Pro-Arg-Gly-Lys(N epsilon-tetramethyl rhodamine)-OH, was used to visualize tuftsin receptors on mice macrophage cells by fluorescent image intensification. Fluorescent labelling was carried out at 37 degrees C, using a concentration of 200 nM and 2 microM of the fluorescent tuftsin derivative. The formation of peptide-receptor clusters and their subsequent internalization, as discerned by image intensification, were rapid processes, 5 min and 5-30 min, respectively. Preincubation of macrophages with tuftsin for various time intervals, followed by quantification of the tuftsin receptor using radiolabelled tuftsin, suggest that tuftsin receptors are initially increased in amount (5-7 min) and subsequently reduced (after 10-15 min) as judged by sites available for tritiated tuftsin. The binding studies are rather complementary to the fluorescence observations and support the assumption that the tuftsin receptor on the membrane of the mice macrophage cell is rapidly mobilized.

Animals↗
PubMed1983

Peptide fragments from the tuftsin containing domain of immunoglobulin G synthesis and biological activity.

Peptides corresponding to sequences of the Fc-portion of immunoglobulin G (IgG) surrounding and containing the tuftsin molecule were synthesized. The compounds were assayed for their ability to compete with [3H-Arg4]tuftsin in binding to mouse peritoneal macrophages and to stimulate the cell's capacity to phagocytize. Despite the sensitivity that tuftsin has demonstrated to various chemical modifications and structural alterations which usually cause reduction or total loss of biological activity, IgG-related analogs possess potent tuftsin-like activity. The activity is not caused by enzymatic breakdown and release of tuftsin. The fact that the elongated tuftsin analogs can specifically be attached to and activate macrophages may indicate a possible connection between Fc and tuftsin's receptors.

Amino Acid Sequence↗
PubMed1983

Inhibition by tuftsin of Rauscher virus leukemia development in mice.

The antitumor effect of tuftsin, the natural phagocytosis-stimulating peptide, on leukemia induced by Rauscher murine leukemia virus (R-MuLV) was studied in vivo in SWR inbred mice. Tuftsin was found capable of significantly increasing the survival of R-MuLV-infected mice. The peptide, when injected both ip and iv into mice, exerted its activity in a dose- and time-dependent manner. Optimal antitumor activity was achieved upon administration of 25 micrograms tuftsin 4 days before R-MuLV inoculation.

Animals↗
PubMed1982

Tuftsin analogs for probing its specific receptor site on phagocytic cells.

Six new analogs of the phagocytosis-stimulating peptide tuftsin were synthesized with the eventual aim of characterizing and isolating the tuftsin receptor. These analogs can be classified as follows: (a) photoaffinity labelling analogs for the specific covalent attachment to the tuftsin receptor: (b) fluorescent analogs containing either rhodamine or dansyl fluorescent probes for microscopic visualization of the tuftsin receptor; (c) biotin analog for separation and purification of the receptor by affinity methods. In this paper we describe the various synthetic pathways employed to introduce sensitive prosthetic groups into the tuftsin molecule while preserving its biological activity. Activities of the various analogs synthesized as compared to tuftsin in biological and receptor-binding assays are described. All analogs are able to stimulate phagocytosis of the macrophage cell as well as complete specifically for tuftsin binding sites on these cells.

Affinity Labels↗
PubMed1981

Tuftsin, Thr-Lys-Pro-Arg. Anatomy of an immunologically active peptide.

Tuftsin, a natural occurring tetrapeptide, has been found to exhibit several biological activities connected with immune system function. Although little is known about tuftsin's 'biogenesis', much information has been gleaned about its structure-function relationships, which have shown that several features of the molecule are essential for expression of full biological activity. Furthermore, specific receptor sites for tuftsin have been found to exist exclusively on phagocytic cells. Research indicates that tuftsin binding to target cells effect intracellular calcium and cyclic nucleotide levels. Implication of these facts on tuftsin's mode of action are discussed. Basic peptidic segments resembling tuftsin are found in a variety of regulatory peptides. Questions are, therefore, raised as to the biospecificity an cross-reactivity of these sequences. Substance P, one such peptide, which binds with and activates tuftsin receptors, is described. In light of tuftsin's therapeutic potential, assays for its determination have been introduced. When applied to analyze human blood serum of normal as well as of various pathological origins, direct correlation was found between tuftsin levels and susceptibility to bacterial infections.

Amino Acid Sequence↗
PubMed1980

The phagocytosis stimulating peptide tuftsin: further look into structure-function relationships.

Sixteen new analogs of the phagocytosis-stimulating peptide tuftsin have been synthesized. The biological activities of these synthetic peptides, in which either the C-terminal or both C- and N-terminals are chemically altered, were evaluated by studying their effects on the phagocytosis of heat-killed yeasts and on the reduction of the dye nitroblue tetrazolium by normal human polymorphonuclear leukocytes. The results demonstrate that the integrity of the guanidine side chain of arginine at position four of tuftsin is crucial for maximal activity. Modification, even in side chain length, of the guanidine leads to decreasing activity. Preservation of the positive charge of position four of tuftsin yields analogs possessing considerable activity. Simultaneous alterations of both C- and N-terminal results in diminishing activities. The results of this study are discussed in relation to the structural features of tuftsin. It appears that interaction between the carboxyl of Arg4 and the amino group of Thr1 which would indicate a specific conformation such as a 4 leads to 1 beta-turn are not favored.

Arginine↗