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J Svoboda

Publications and source records attributed to J Svoboda.

At least 55 records · Page 3Linked to original sources
PubMed1994

src-specific immunity in inbred chickens bearing v-src DNA- and RSV-induced tumors.

The growth pattern (progression/regression) of v-src DNA- and Rous sarcoma virus (RSV)-induced tumors was analogous on a panel of inbred chicken lines. The decisive role of the major histocompatibility complex [Mhc(B)] alleles in resistance to the progression of these tumors was formally proved in segregating backcross populations. The immune mechanism of tumor regression was demonstrated by both in vivo and in vitro assays. A protective effect of v-src-specific immunity against RSV challenge was shown in Rous sarcoma regressor, line CB (B12/B12). Immune cells from regressors of v-src DNA-induced tumors can protect syngeneic hosts from the development of tumor after challenge with both v-src DNA and RSV. Suppression of RSV-induced tumor cell growth in vitro was also achieved by the use of cocultivation with spleen cells from chickens in which v-src DNA-induced tumors had regressed. This in vitro sarcoma-specific response was Mhc(B)-restricted. Chickens of the congenic Rous sarcoma progressor line CC (B4/B4) are sometimes able to regress v-src DNA-induced tumors, but immune cells can only slow the growth of v-src DNA-induced tumors in syngeneic hosts. This suggests that the primary reason for the susceptibility of CC chickens is a weak v-src-specific immune response. Furthermore, some of the v-src DNA-induced tumors were transplantable across the Mhc(B) barrier. The growth of tumor allografts was able to be facilitated when immunological tolerance to the B-F/L region antigens (class I and class II) had been established. This demonstrated that a high tumorigenicity of the transplantable tumor was not due to the lack of Mhc(B) antigens on tumor cells.

Animals↗
PubMed1994

Extracellular volume fraction and diffusion characteristics during progressive ischemia and terminal anoxia in the spinal cord of the rat.

Extracellular space (ECS) volume fraction (alpha), ECS tortuosity (lambda), and nonspecific uptake (k'), three parameters affecting the diffusion of substances in nervous tissue, were studied during ischemia and anoxia in the rat spinal cord gray matter in vivo. Progressive ischemia evoked by exsanguination, as well as anoxia evoked by respiratory or cardiac arrest, produced prominent extracellular K+ and pH changes closely related to a decrease in blood pressure and amplitude of field potentials. With use of ion-selective microelectrodes, the changes in the diffusion parameters were measured by quantitative analysis of concentration-time profiles of tetramethylammonium (TMA+) applied by iontophoresis concomitantly with ionic shifts. Under normoxic conditions (in rats with blood pressure of 80-110 mm Hg) diffusion parameters in the dorsal horn gray matter at depth 500-900 microns were as follows: alpha = 0.20 +/- 0.019, lambda = 1.62 +/- 0.12, k' = 4.6 +/- 2.5 x 10(-3) s-1 (mean +/- SD, n = 39). Extracellular K+, pH, and diffusion properties gradually changed during progressive ischemia. As the blood pressure fell to 50-60 mm Hg and field potential amplitude to 20-60%, K+ rose to 6-12 mM, pHe fell by approximately 0.05-0.1 pH unit, and volume fraction of the ECS significantly decreased, to alpha = 0.16 +/- 0.019 (n = 22). Even though the tortuosity remained virtually constant, the nonspecific uptake significantly decreased to k' = 3.4 +/- 1.8 x 10(-3) s-1. As the blood pressure fell to 20-30 mm Hg and field potential amplitude to 0-6%, K+ rose to 60-70 mM, pHe fell by approximately 0.6-0.8 pH unit, and all three diffusion parameters significantly changed. The ECS volume fraction decreased to alpha = 0.05 +/- 0.021, tortuosity increased to lambda = 2.00 +/- 0.24, and TMA+ uptake decreased to k' = 1.5 +/- 1.6 x 10(-3) s-1 (n = 12). No further increase in extracellular K+ or changes in the alpha were found during and up to 120 min after the death of the animal. However, there was a further significant increase in lambda = 2.20 +/- 0.14 and decrease in k' = 0.4 +/- 0.3 x 10(-3) s-1 (n = 24). The acid shift reached its maximum level at approximately 5-10 min after respiratory arrest and then the pHe gradually increased by approximately 0.2 unit. Full recovery to "normoxic" diffusion parameters was achieved after reinjection of the blood or after an injection of noradrenaline during severe ischemia, if this resulted in a rise in blood pressure above 80 mm Hg and a decrease in extracellular K+ below 12 mM.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Origin and evolution of the c-src-transducing avian sarcoma virus PR2257.

Avian sarcoma virus PR2257 transduced de novo the c-src gene and about 900 bp of 3' non-coding sequences belonging to the src locus. This virus contains only one mutation in the c-src coding sequence causing a reading frame shift after Pro-525. The molecular clone studied was derived from a cell line of transformed quail fibroblasts, C7. It contains endogenous virus (ev) derived sequences in the U5 and 3' non-coding regions, indicating that multiple recombination occurred with endogenous virus. Here we investigated the possible evolution of PR2257 when the original tumour was repeatedly passaged in vivo. After 16 passages a new virus, designated PR2257/16, appeared with a tenfold higher titre. The sequence of PR2257/16 was determined and showed that PR2257/16 resulted from recombination of PR2257 with the env gene of the helper virus (td daPR-C). This recombination expanded the env gene content in PR2257/16 and, in addition, five point mutations occurred in its genome. Because we thought that an endogenous virus might be involved in the mechanism of c-src transduction, we also reinvestigated the presence of ev sequences in PR2257 proviruses from several early passages of the original tumour. We found that in contrast with the first isolate from the C7 cell line, the provirus in these tumours did not contain such sequences. These results do not support the hypothesis that endogenous sequences were involved in the transduction process.

Animals↗
PubMed1994

High rate of morphological reversion in tumor cell line H-19 associated with permanent transcriptional suppression of the LTR, v-src, LTR provirus.

The highly malignant line of morphologically transformed H-19 hamster tumor cells that harbor a single LTR, v-src, LTR provirus segregates morphologically flat revertants at the rate of 1.4 to 2.4 x 10(-3)/cell/cycle. Revertants behave like almost nonmalignant cells; they keep the provirus within an unaltered junction DNA fragment. However, the provirus is methylated, permanently transcriptionally silent, and not rescuable. Using the polymerase chain reaction, we have synthesized the whole proviral structure from two revertants and established that the left-hand long terminal repeats assuring transcription remained structurally intact. Moreover, the cloned proviral DNAs from three revertants were shown to produce tumors in chickens. The unusually high reversion rate together with the finding of structural integrity of proviral transcriptional signals in revertants indicate strongly that the reversion has been mediated by cell-regulatory mechanisms.

Animals↗
PubMed1993

Extracellular space parameters in the rat neocortex and subcortical white matter during postnatal development determined by diffusion analysis.

Extracellular space volume fraction, tortuosity and nonspecific uptake of tetramethylammonium--three diffusion parameters of brain tissue--were measured in gray matter of the somatosensory neocortex and subcortical white matter of the rat during postnatal development. The three parameters were determined from concentration-time profiles of tetramethylammonium in postnatal days 2-120 in vivo. Tetramethylammonium concentration was measured with ion-selective microelectrodes positioned 130-200 microns from an iontophoretic source. Data were correlated with cytoarchitectonic structure and average thickness of the regions in 0-90-day-old rats using rapidly frozen tissue. Extracellular space volume fraction was largest in the newborn rats and diminished with age. In two-to three-day-old animals, volume fraction (mean +/- S.E.) was 0.36 +/- 0.04 in layers III and IV, 0.38 +/- 0.02 in layer V, 0.41 +/- 0.01 in layer VI and 0.46 +/- 0.01 in white matter. The earliest decrease in volume fraction was found in layers V and VI at postnatal days 6-7 followed by a decrease in layer III and IV at postnatal days 8-9 and in white matter at postnatal days 10-11. A further dramatic reduction in volume fraction occurred in all cortical layers and especially in the white matter between postnatal days 10 and 21. There was no further decrease in volume fraction between postnatal day 21 and adults (90-120 days old). The adult volume fraction values were: layer II, 0.19 +/- 0.002; III, 0.20 +/- 0.004; IV, 0.21 +/- 0.003; V, 0.22 +/- 0.003; VI, 0.23 +/- 0.007; white matter, 0.20 +/- 0.008. Values of tortuosity ranged between 1.51 and 1.65, nonspecific cellular uptake varied from 3.3 x 10(-3)/s to 6.3 x 10(-3)/s. The variations in each parameter were not statistically significant at any age. These data represent the first characterization of diffusion parameters in a developing brain. They confirm previous histological indications of a relatively large extracellular volume fraction during early postnatal development. The constancy of the tortuosity shows that diffusion of small molecules is no more hindered in the developing brain than in the adult. The large extracellular space volume fraction of the neonatal brain could significantly dilute ions, metabolites and neuroactive substances released from cells, relative to release in adults, and may be a factor in preventing anoxia, seizure and spreading depression in young animals. The diffusion characteristics could also play an important role in the developmental process itself.

Aging↗
PubMed1992

Tumor induction by the LTR, v-src, LTR DNA in four B (MHC) congenic lines of chickens.

We report that the cloned DNA harboring the long terminal repeat (LTR), v-src, LTR proviral structure is tumorigenic in chickens of the Prague congenic lines. The growth rate of these tumors is by far the highest in the recombinant CC.R1 line, the B haplotype of which is composed of the B-F/L4 and B-G12 subregions originating from different naturally occurring haplotypes. Some of the tumors induced by the LTR, v-src, LTR DNA are repeatedly transplantable in syngeneic chickens, maintain unaltered provirus, and express v-src mRNA. Differences in the response to challenge with Rous sarcoma virus (RSV) and LTR, v-src, LTR DNA on a given experimental model are compared and possible involvement of an interaction between B-F/L and B-G region genes is considered. Regression of the LTR, v-src, LTR DNA-induced tumors did not prevent the formation and growth of tumors induced subsequently by RSV.

Animals↗
PubMed1992

Extracellular K+, pH, and volume changes in spinal cord of adult rats and during postnatal development.

Activity-related transient changes in extracellular K+ concentration ([K+]c), extracellular pH (pHc), and extracellular volume (EC volume) were studied by means of ion-selective microelectrodes in the adult rat spinal cord in vivo and in neonatal rat spinal cords isolated from pups 3-14 days of age. Repetitive electrical nerve stimulation (10-100 Hz) in adults elicited increases in [K+]c by about 2.0-3.5 mM, followed by a poststimulation K+ undershoot and triphasic alkaline-acid-alkaline changes in pHc. In 3- to 6-day-old pups, the [K+]c increased by as much as 6.5 mM at a stimulation frequency of 10 Hz, and this was accompanied by an alkaline shift. Increases in [K+]c as large as 1.3-2.5 mM accompanied by an alkaline shift were evoked by a single electrical stimulus. Stimulation in 10- to 13-day-old pups produced smaller [K+]c change and an acid shift, which was preceded by a small initial alkaline shift, as in adult rats. We conclude that glial cells buffer the activity-related [K+]c increase and alkaline pHc shifts. Mg2+ blocked the alkaline but not the acid shift. Acetazolamide had no effect on the alkaline shift but blocked the acid shift. The alkaline shift was enhanced and the acid shift blocked by Ba2+, amiloride, 4-acetamido-4'-isothiocyanotostilbene-2,2'-disulfonic acid (SITS), and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). Activity-related acid shifts therefore have a complex mechanism, which includes Na+H+ exchange, Cl-/HCO3- exchange, or Na+/Cl-/H+/HCO3- antiport, Na(+)-HCO3- cotransport, and H+ efflux through voltage-sensitive H+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

[Relapsing polychondritis--ultrastructure in 2 additional cases].

A 37-year-old woman and a 74-year-old man with typical clinical history of relapsing polychondritis enabled electron microscopical analysis of various cartilages (ear, nasal septum, rib). Apoptotic lesion and degradation of chondrocytes combined not always with changes of their lacunae prevailed in both patients, fragmentation of elastic tissue in the man. Lesions of chondrocytes, a bit varied and asynchronous in intensity were observed as everywhere in a single cartilage as in cartilages from different sites.

Adult↗
PubMed1992

[Treatment of chronic uveitis with long-term administration of penicillin].

The authors followed up a group of 20 patients with chronic uveitis (10 men and 10 women), mean age 36.5 years. Despite treatment of the foci, they suffered on average from seven relapses of the disease, frequently several times in the course of one year. From the anamnestic aspect there was a significantly high number of spells of tonsillitis, respiratory infections and arthralgia. Half the cases of uveitis, mainly anterior, were bilateral. The patients suffered from dysimmunoglobulinaemia with low values of FW, ASLO, Latex. HLA B 27 was positive in five subjects. After one-year of Pendepon or Penclen administration (in half the patients with NORG) 18 patients did not develop a relapse for a period of 2-3 years. The method is simple, cheap, easy to use in field practice, in particular in junior patients. The clinical effect of treatment justifies the use of this method as an alternative of intermittent immunosuppression.

Adult↗
PubMed1991

The isopycnic, compartmentalized integration of Rous sarcoma virus sequences.

Rous sarcoma virus (RSV) can cause tumors in hamsters, which harbor complete or partially deleted RSV sequences, in their genomes. Here we have studied the localization of RSV sequences integrated into the genome of cell lines derived from six independent hamster tumors. We have found that integration occurred in the isochores richest in guanine + cytosine, of the host genome, as it had been previously observed for bovine leukemia and hepatitis B viral sequences. The integration of RSV proviral sequences is, therefore, 'isopycnic' (i.e., it takes place in host genome sequences which compositionally match the viral sequences) and compartmentalized (i.e., it occurs in a small compositional compartment of the host genome). The hamster genome compartment hosting RSV sequences precisely corresponds to a compartment of the human genome which is the most active in both transcription and recombination. The notion of a compartmentalized, isopycnic integration of RSV proviral sequences fits, therefore, with the viral integration into transcriptionally active and recombinogenic regions of the host genome observed by other authors, but is broader, in that it includes, in addition, the requirement for a compositional match between host genome sequences and expressed viral sequences.

Animals↗
PubMed1991

Extracellular space volume changes in the rat spinal cord produced by nerve stimulation and peripheral injury.

Double-barrelled potassium and tetramethylammonium-sensitive microelectrodes were used in diffusion studies with tetramethylammonium ions, which remain essentially extracellular during the measurements. Activity-related changes in the extracellular space (ECS) volume fraction (alpha), ECS tortuosity (lambda) and the dynamics of the ECS volume changes were examined in the spinal dorsal horns of rats. The alpha and lambda in L4 and L5 segments of unstimulated rats were alpha = 0.24 +/- 0.01 (i.e. ECS occupied 24 +/- 1% of the total spinal cord volume) and lambda = 1.54 +/- 0.04 (mean +/- S.D. of mean, n = 21). The values were not significantly different throughout the dorsal horn. Repetitive electrical stimulation of peripheral nerves at 3-100 Hz increased extracellular potassium concentration [( K+]e) and ECS volume in Rexed laminae III-V by 15.8 +/- 2.7% (n = 5). After the end of stimulation, when the [K+]e decreased below the original baseline (K+ undershoot), the ECS volume decreased by 20-45%. The magnitude and duration of ECS volume decrease were positively related to the stimulation frequency and duration. The ECS volume decrease was maximal at 2-10 min after the stimulation had been discontinued, and it returned to the prestimulation values in 15-40 min. The ECS volume decreased by 20-50% after injury of the ipsilateral hind paw evoked either by subcutaneous injection of turpentine (n = 5), or by thermal injury (n = 6). The maximal changes were found in Rexed laminae III-V, 5-10 min after injection of turpentine and 10-25 min after thermal injury, and persisted for more than 120 min and 30 min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

[Clinical aspects of the pathophysiology of HIV infection. III. Principles of therapy].

The author analyzes different possible therapeutic approaches to HIV infection in different clinical stages. He draws attention to the fact that antiretroviral therapy has always also a certain immunomodulating effect and vice versa. It is in particular necessary to pay attention to the fact that therapeutic activation of the immune system may be associated with undesirable activation of HIV replication. After giving an account of different theoretical possibilities of the therapeutic influencing of HIV infection the author analyzes hitherto assembled experience with the only treatment which can stabilize the condition in clinical practice for a certain period, i. e. administration of azidothymidine (AZT).

HIV Infections↗
PubMed1991

[Clinical aspects of the pathophysiology of HIV infection. I].

The author analyzes individual pathophysiological mechanisms which play a part in the development and clinical manifestation of HIV infection. He uses as a basis the CDC classification of HIV infections and explains on different models of clinical situations mechanisms which lead to haematological, neurological, immunological, pneumological, gastroenterological, oncological and rheumatological symptomatology.

HIV Infections↗
PubMed1991

[Clinical aspects of the pathophysiology of HIV infection. II].

The author pays attention to interindividual differences in the course of HIV infection and its causes. He emphasizes above all the influence of sex life, herpetic infections and the mental state of the patient. He analyzes also individual clinical and laboratory prognostic factors which can be used in clinical practice. In the conclusion he tries to find a way how to integrate medical care with normal life of the affected subjects and seeks prerequisites of understanding of the HIV infection, i.e. good knowledge of medicine as a whole and oneself.

HIV Infections↗