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Biomedical subjects

V Simon

Publications and source records attributed to V Simon.

At least 55 records · Page 3Linked to original sources

Depressed immune response in malnourished rats correlates with increased thymic noradrenaline level.

Depressed immune response is well documented in protein-calorie malnutrition (PCM). Also, central and peripheral noradrenaline (NA) activities have been reported to be increased in malnourished animals. Since increases in central and peripheral NA may inhibit immune function, it is possible that malnutrition-induced immunodepression could be mediated by noradrenergic hyperactivity. To address this hypothesis the effect of malnutrition on cell-mediated immune response, as well as on NA levels of the median eminence, spleen and thymus was studied in PCM rats. Decreased lymphoproliferative response and IL-1 production by mononuclear macrophages was observed in PCM. Besides, increased NA concentration was detected in thymuses of PCM rats, while unchanged levels of this neurotransmitter were observed in median eminence and spleen. These data suggest a positive correlation between malnutrition-induced immunodepression and sympathetic noradrenergic activity in thymus, an organ implicated in immune cell differentiation during early development.

Animals↗

Triplicity of the malignant tumor of the urinary bladder.

Described report case of the patient after left nephrectomy, performed 18 years ago, for adenocarcinoma. Recently he has a simultaneous carcinoma of the bladder and the left ureter. Carcinoma of the bladder was treated with transurethral resection and electrocoagulation. Once checked, the hemorrhage was found from the left ureter, later, papilocarcinoma was diagnosed and the urethrectomy with the resection of the part of the wall of the bladder in the region of the estuary. Patient was in good condition 5 months after the operation. There is a review of others report cases.

Adenocarcinoma↗

Rat endopeptidase-24.18 alpha subunit is secreted into the culture medium as a zymogen when expressed by COS-1 cells.

Endopeptidase-24.18 (EC 3.4.24.18, E-24.18) is an oligomeric Zn-ectoenzyme. The alpha and beta subunits have been cloned from both rat and mouse kidneys. The primary structure of these subunits revealed that they both contain the consensus Zn binding site and that they are members of the astacin family. Analysis of the hydropathy plot also suggested that they are anchored by a C-terminal hydrophobic domain. In order to verify the mode of anchoring of the rat E-24.18 alpha subunit and to test the functionality of the astacin-like domain in the alpha subunit when expressed alone, COS-1 cells were transfected with a cloned cDNA for rat alpha subunit. Despite the presence of its putative transmembrane domain, the alpha subunit was not anchored in the plasma membrane but rather secreted as a dimer into the culture medium. When the enzymatic activity of the secreted recombinant protein was tested in the azocasein degradation assay, the alpha subunit was found to be inactive. Activity could, however, be revealed after mild trypsin digestion. This activity was abolished by replacing the Glu-157 in the active site by Val. Taken together our results suggest that the alpha subunit of Endopeptidase-24.18 contains a latent astacin-like Zn metallopeptidase activity which could be secreted as a soluble enzyme by kidney and intestine.

Animals↗

Effects of two selective dopaminergic antagonists on ethologically-assessed encounters in male mice.

1. Although it is accepted that dopaminergic antagonists suppress aggressive behaviour, the drugs used have been relatively non-selective or specific to the D2 receptor. 2. The selective D1 antagonist, SCH 23390, makes it possible to evaluate the impact of this receptor on aggressive behaviour. 3. The effects of SCH 23390 and Spiperone (a D2 antagonist) on the aggressive behaviour of mice were assessed employing a "standard opponent" test. 4. Both drugs markedly decreased aggressive behaviour whilst increasing immobility. However, whilst SCH 23390 increased immobility to a small extent, Spiperone, produced a general decline in active behaviours. 5. It appears that the D1 receptor inhibition of aggression is the more specific.

Aggression↗

DNA-drug recognition and effects on topoisomerase II-mediated cytotoxicity. A three-mode binding model for ellipticine derivatives.

Cytotoxic effects and topoisomerase II-mediated DNA breaks induced in vitro by ellipticine derivatives were examined in connection with 1H NMR and circular dichroism (CD) studies on molecular structures and interactions of drugs with DNA. The compounds included four 9-hydroxyellipticine and two 7-hydroxyisoellipticine derivatives. Structure-activity relationships indicated that a change in nitrogen atom position in the pyridinic ring greatly affected drug effects both on topoisomerase II action and cytotoxicity to L1210 cells. The four 9-hydroxyellipticine derivatives yielded bell-shaped curves in in vitro topoisomerase II-mediated DNA break assays, whereas the two 7-hydroxyisoellipticine derivatives demonstrated an almost linear increase at the same concentration (0-10 microM). In both cases, the intensity of cleavage was modulated by the position and the degree of methylation on the pyridinic ring, and results were correlated with cytotoxic activity expressed as the in vitro ID50 values for L1210 leukemia cells. 1H NMR experiments performed on free drug molecules in solution revealed that the two protons (alpha and beta) contiguous to the biologically important hydroxy group were sensitive to changes in electron distribution produced by the distant chemical modifications and methylations of the pyridinic ring. A linear relationship was observed between the differences in chemical shifts of alpha and beta protons (delta delta alpha-beta) versus ID50 values. CD experiments indicated that, at weak ionic strength I = 0.02 and at pH 7, drugs interact with the poly[d(A-T)] duplex according to a "three-mode binding model" which is governed by the drug structure and the drug to DNA ratio. The intercalation mode was related to the induction of topoisomerase II-mediated DNA cleavage, while the external binding mode consecutive to intercalation was related to cleavage suppression. These two modes concerned the good intercalators 9-hydroxyellipticines. The third was found for the weak intercalators 7-hydroxyisoellipticines and was characterized by self-stacked molecules bound "outside" DNA, presumably in the minor groove. Ligands either could be intercalated partially or linked at the edge of bases with a small number of molecules filling intercalation sites, for the second alternative. In addition to having different binding modes, 9-hydroxyellipticines were better inducers of DNA distortions than 7-hydroxyisoellipticines. The incidence of the drug binding modes on DNA-topoisomerase II recognition was discussed in connection with the in vitro cytotoxic activity exhibited by the drugs.

Animals↗

[Treatment of kidney stones using shock-wave lithotripsy with sonographic control].

Lithotripsy by means of an extracorporeal shock-wave was performed in 128 patients with urolithiasis. In this group for the first time in Czechoslovakia ultrasound control of kidney stones was used in 44 patients; in the remainder X-ray control was used. The authors used equipment designed and manufactured locally. The ultrasonic probe is laterally connected with the shock-wave applicator. Disappearance of the fragments after lithotripsy was achieved in 39 patients where ultrasonic control was used. The paper presents the results, discusses the advantages and limitations of ultrasonic control in extracorporeal lithotripsy of urolithiasis.

Adult↗

A CD study of interactions of ellipticine derivatives with DNA. Relations with the in vitro cytotoxicity.

UV-absorption and circular dichroism (CD) experiments showed that ellipticine derivatives may interact with DNA according to 3 possible binding modes depending on their structure and concentration. The first mode concerned intercalation of 1-methyl-9-hydroxyellipticine (1-Me-HE) with its long axis perpendicular to the long axis of base pairs. The same drug was able to bind to external sites (second mode) once the intercalation sites were saturated at high concentration. The third mode illustrated by 1,2-dimethyl-9-hydroxyisoellipticinium (1-Me-isoNMHE), concerned self-stacked molecules interacting at the surface of DNA. Biological significance of these different binding modes was then discussed in connection with in vitro cytotoxic activity of compounds.

Animals↗

Blocking of human T lymphocyte activation by channel antagonists.

It has been established that early events in lymphocyte activation involve a rise in intracellular Ca++ as well as changes in the flux of other ions. Although a Ca++ channel has been postulated to participate in the early Ca++ rise, its presence in lymphocytes remains controversial. Also although yet undetected, electrophysiological data suggest the presence of a Ca++ activated K+ channel on human peripheral blood lymphocytes (HPBL). Here we report on the effect of specific channel blockers as an approach to the identification of these channels on HPBL. At 40 nM nifedipine, an inhibitor of voltage-gated Ca++ channels, fully inhibits the PHA-promoted activation of HPBL. This effect is concentration dependent with a half maximum effect at approximately 10 nM and is demonstrable whether the drug is added at the same time as or up to 18 h after the addition of the mitogen. This inhibition of activation is not seen if the lymphocytes are activated using IL-2 instead of PHA. Charybdotoxin a toxin which blocks a Ca++ activated K+ channel of muscle cells also blocks to almost 100 per cent the PHA-induced activation of HPBL. This inhibition can be demonstrated regardless of whether the blocker is added together with or up to 4 h after PHA. As opposed to nifedipine charybdotoxin shows no effect if added 18 h after the initiation of the activation process. When nifedipine and charybdotoxin were tested on mice splenocytes we found that nifedipine fully inhibits the LPS-promoted activation of these cells while charybdotoxin has no effect on their activation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Suppressive effects of dehydroepiandrosterone and 3-beta-methylandrost-5-en-17-one on attack towards lactating female intruders by castrated male mice.

Three experiments were performed. In Experiment I, triads of adult castrated male mice were chronically administered with either oil-vehicle or 80 micrograms/day of dehydroepiandrosterone (D) or 3-beta-methylandrost-5-en-17-one (D-CH3). They were subsequently tested for their attack on a lactating intruder female introduced for 15 min in their home-cage, 2 hr after their last injection. Both D and D-CH3 significantly reduced male aggressive responses (cf. oil-injected category). In Experiment II the effects of D-CH3 dosed at 20, 40 or 80 micrograms/day were measured in the same testing situation. D-CH3 dose-dependently reduced the mice attack probability on lactating intruders with the highest dose being the most effective. Finally, to test in Experiment III that D-CH3 was not demonstrably androgenic, castrated males received daily injections of 20, 40 or 80 micrograms of this synthetic steroid for 4, 8, 16 or 32 days before tissue sampling. At all doses and whatever treatment duration, D-CH3 did not significantly increase the weights of the accessory sex organs.

Aggression↗

[Diagnosis and treatment of benign subvesicular obstruction in benign prostatic hyperplasia without enlargement].

At the urological department of the First Surgical Clinic, Faculty of general Medicine Charles University in Prague from January 1977 to December 1986 922 men were operated on account of benign obstruction of the cervix. Ninety-one patients, i.e. 9.8%, with some common signs were subjected to clinical analysis. The criterium for inclusion in the group was the finding of a not enlarged, through on palpation frequently altered prostate, the finding of a histological, endoscopic, X-ray and urodynamic examination. The common sign of these patients was the presence of the disease in young age, a prolonged persistence (up to 20 years) and the frequent presence of supravesical congestion, sometimes with a diverticulum of the urinary bladder. The cause of the disease was dyssynergy, urethrovesical hypertrophy of the poesterior commissure, atrophy of the prostate, subtrigonal hyperplasia of the prostate and a secondary contracture. A transurethral operation was performed in 64 patients, a transvesicalar one in 24 and in three a XY plastic operation was made.

Humans↗

[Pepsinogen C in the human prostate].

The authors investigated the proteolytic activity of the normal prostate, the prostate with benign hypertrophy and with cancer. Pepsinogen obtained from the normal prostate was isolated on DEAHP pearl cellulose and purified by means of affinite chromatography. Separation on affinite chromatography and by electrophoresis on agar confirmed that the pepsinogen is identical with gastric progastricsin. The proteolytic activity was examined by a modified method of Anson and Mirsky, and with the aid of synthetic substrates it was assessed quantitatively in all three examined groups. The enzyme activity of the carcinomatous tissue practically did not differ from the activity of the normal prostate. In beniming hypertrophy of the prostate the proteolytic activity assessed by the breakdown of haemoglobin is markedly reduced and when tested on the breakdown of synthetic substrates [For-Tyr-Tyr- and Ac-Phe- Tyr (I2)] it is practically zero.

Humans↗

The potential of antiestrogens as centrally-acting antihostility agents: recent animal data.

Recent studies suggest that motivations for certain forms of masculine behavior including social aggression are mediated by central estrogen receptors. Two studies using antiestrogens in rodent species were performed. Intact male LH rats were given Tamoxifen or vehicle for 4 or 8 days. The three possible pairings were videotaped for 60 min. Intact male OF1 mice were given CI-680 or vehicle over 25 days. Similar pairings were carried out but some CI-680 or vehicle animals were paired with anosmic opponents. Encounters were videotaped for 10 min. In both experiments evidence was obtained that the antiestrogen markedly reduced time allocated to offense. Any variations in defense were a consequence of the level of attack to which animals were subjected. Neither compound greatly influenced the androgen-dependent sex accessory glands. Antiestrogens consequently have potential as antihostility agents in some forms of attack.

Aggression↗

Characterization of the submerged growth of Moraxella bovis.

A submerged batch cultivation of Moraxella bovis in a medium containing enzymic casein hydrolyzate and supplemented with dialyzed ram blood was described. Up to the growth limitation the bacteria grew exponentially without a lag phase and with a doubling period of 64 min. During the exponential phase no significant decrease of viable cells and cell autolysis were observed. Amino acids were the limiting factor. At the end of growth glutamic acid, threonine and serine were detected at the lowest concentrations. Substrate limitation led to an irreversible decrease of the metabolic activity. Growth yield on oxygen was 2.3 X 10(9) cells per mg O2. The fraction of respiration required for growth-uncoupled processes was negligible. During the cultivation ammonia was produced and the pH increased but it was not the inhibitory factor. Respiration was not limited by oxygen at concentrations higher than 0.63 mumol O2 per L. Sufficient pili were produced.

Culture Media↗

In vivo formation of gene fusions in Pseudomonas putida and construction of versatile broad-host-range vectors for direct subcloning of Mu d1 and Mu d2 fusions.

The Mu d1 and Mu d2 prophages were integrated into the conjugative broad-host-range plasmid R751. The two plasmids were then transferred into Pseudomonas putida, and derivatives carrying intact Mu prophages were recovered. After induction of Mu at 42 degrees C, both operon and gene fusions were observed on 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-Gal) plates. Broad-host-range vectors were constructed which allow direct cloning of both operon or gene fusions and their analysis in Escherichia coli and P. putida. By using one of these vectors, two operon fusions were isolated from the P. putida chromosome and comparatively analyzed in E. coli and P. putida.

Bacteriophages↗