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Biomedical subjects

R Jung

Publications and source records attributed to R Jung.

At least 73 records · Page 4Linked to original sources
PubMed1996

Lack of bioavailability of dichlorobenzidine form diarylide azo pigments: molecular dosimetry for hemoglobin and DNA adducts.

The hypothetical release of 3,3'-dichlorobenzidine (DCB) from two insoluble azo pigments and from a soluble azo dye was investigated in female Wistar rats for a 4 week treatment with 0.2% (w/w) Colour Index Pigment 13 (PY13) or 0.2% (w/w) Colour Index Pigment Yellow 17 (PY17) in the diet or 0.06% (w/v) Colour Index Direct Red 46 (DR46) in the drinking water. Steady-state DCB-hemoglobin adduct levels were determined by GC/MS with negative chemical ionization as well as DCB-DNA adduct levels in the liver by (32)P-postlabelling and compared with the respective adduct levels obtained in animals after treatment for 4 weeks with 0.00024, 0.0012 or 0.006% (w/v) DCB in the drinking water. A dose-proportional increase in adduct levels from 8.1 ng/g hemoglobin and 2.6 ng/g DNA (relative adduct level, RAL, 3.3x10(-9)) to 160 ng/g hemoglobin and 45.4 ng/g DNA (RAL 56.1x10(-9)) was observed in the DCB-treated rats. In rats treated with DR46 total adduct levels of 17.7 ng/g hemoglobin and 5.2 ng/g DNA (RAL 6.4x10(-9))were determined. No hemoglobin of DNA adducts were found in rats treated with PY17 in the diet, at a limit of detection of 0.1 ng/g hemoglobin and 0.08 ng/g DNA (RAL 0.1x10(-9)). In animals treated with PY13 in the diet no adducts or only minimal amounts slightly above the limit of detection could be identified. Taking into consideration that PY13 was contaminated with 0.02% of the respective soluble monoazo compound, it is concluded that the small amounts of DCB detected have been released from the contaminating soluble monoazo compound and not from insoluble PY13. The results of the present study demonstrate the lack of bioavailability of DCB from the diarylide azo pigments PY17 and PY13.

3,3'-Dichlorobenzidine↗
PubMed1996

Dynamic behavior of a neural network model of locomotor control in the lamprey.

1. Experimental studies have shown that a central pattern generator in the spinal cord of the lamprey can produce the basic rhythm for locomotion. This pattern generator interacts with the reticular neurons forming a spinoreticulospinal loop. To better understand and investigate the mechanisms for locomotor pattern generation in the lamprey, we examine the dynamic behavior of a simplified neural network model representing a unit spinal pattern generator (uPG) and its interaction with the reticular system. We use the techniques of bifurcation analysis and specifically examine the effects on the dynamic behavior of the system of 1) changing tonic drives to the different neurons of the uPG; 2) altering inhibitory and excitatory interconnection strengths among the uPG neurons; and 3) feedforward-feedback interactions between the uPG and the reticular neurons. 2. The model analyzed is a qualitative left-right symmetric network based on proposed functional architecture with one class of phasic reticular neurons and three classes of uPG neurons: excitatory (E), lateral (L), and crossed (C) interneurons. In the model each class is represented by one left and one right neuron. Each neuron has basic passive properties akin to biophysical neurons and receives tonic synaptic drive and weighted synaptic input from other connecting neurons. The neuron's output as a function of voltage is given by a nonlinear function with a strict threshold and saturation. 3. With an appropriate set of parameter values, the voltage of each neuron can oscillate periodically with phase relationships among the different neurons that are qualitatively similar to those observed experimentally. The uPG alone can also oscillate, as observed experimentally in isolated lamprey spinal cords. Varying the parameters can, however, profoundly change the state of the system via different kinds of bifurcations. Change in a single parameter can move the system from nonoscillatory to oscillatory states via different kinds of bifurcations. For some parameter values the system can also exhibit multistable behavior (e.g., an oscillatory state and a nonoscillatory state). The analysis also shows us how the amplitudes of the oscillations vary and the periods of limit cycles change as different bifurcation points are approached. 4. Altering tonic drive to just one class of uPG neurons (without altering the interconnections) can change the state of the system by altering the stability of fixed points, converting fixed points to oscillations, single oscillations to two stable oscillations, etc. Two-parameter bifurcation diagrams show the critical regions in which a balance between the tonic drives is necessary to maintain stable oscillations. A minimum tonic drive is necessary to obtain stable oscillatory output. With appropriate changes in the tonic drives to the L and C neurons, stable oscillatory output can be obtained even after eliminating the E neurons. Indeed, the presence of active E neurons in the biological system does not prove they play a functional role in the system, because tonic drive from other sources can substitute for them. On the other hand, very high excitation of any one class of neurons can terminate oscillations. Appropriate balance of tonic drives to different neuron classes can help sustain stable oscillations for larger tonic drives. Published experimental results concerning changes in amplitude and swimming frequency with increased tonic drives are mimicked by the model's responses to increased tonic drive. 5. Interconnectivity among the neurons plays a crucial role. The analysis indicates that the C and L classes of neurons are essential components of the model network. Sufficient inhibition from the L to C neurons as well as mutual inhibition between the left and right halves is necessary to obtain stable oscillatory output. When the E neurons are present in the model network, they must receive appropriate tonic drive and provide appropriate excitation

Animals↗
PubMed1995

Purification, cDNA cloning and characterization of proteinase B, an asparagine-specific endopeptidase from germinating vetch (Vicia sativa L.) seeds.

Proteinase B, an asparagine-specific endopeptidase, has been purified from germinating vetch (Vicia sativa L.) seeds. The final preparation consists of two enzymically active proteins with molecular masses of approximately 39 kDa and 37 kDa. Synthetic substrates were used to confirm cleavage specificity of the proteinase B preparation. As expected, the enzyme cleaves the substrates at the C-terminal side of Asn residues. The octapeptide ETRNGVEE was digested most efficiently. When Gly was replaced by Ile or Glu, cleavage took place with lower efficiency. Polyclonal antibodies displayed both proteins in cotyledon extracts of germinated vetch seeds. In addition, a strong cross-reacting protein band was found in cotyledon extracts of developing seeds, indicating the presence of a very similar enzyme during seed development. cDNA clones encoding proteinase B precursor have been obtained on the basis of the N-terminal amino acid sequence DDDFEGTRWAILLAGS, by means of the polymerase chain reaction. The cDNA clones contain an open reading frame of 1479 bp encoding a polypeptide of 493 amino acids. The precursor displayed 59% sequence identity to the cDNA-derived amino acid sequence of a vacuolar Asn-specific enzyme from the developing castor beam endosperm which is thought to catalyze the post-translational processing of pro-proteins into the mature forms. Proteinase B is synthesized de novo during seed germination. The results of Southern-blot analyses suggested that there are at least two genes for proteinase B.

Amino Acid Sequence↗
PubMed1995

Cardiorespiratory reflex control in rats with left ventricular dysfunction.

Patients with heart failure exhibit a neurohumoral excitatory state and abnormal baroreflex control of the cardiovascular system. We determined whether arterial baroreflexes are impaired during left ventricular dysfunction (LVD) caused by chronic myocardial infarction in the absence of congestive heart failure and whether abnormal central mechanisms contribute to this impairment. Baroreceptors were stimulated in anesthetized rats with and without LVD by increasing arterial pressure with phenylephrine. Lumbar sympathetic nerve and phrenic nerve activity as well as heart rate were recorded. Rats were divided into different groups based on infarct size. Rats with moderate LVD showed impaired baroreflex control of sympathetic, ventilatory, and heart rate responses. Baroreflex gains were inversely related to the size of the infarct. The central gain for sympathetic nerve activity, obtained by using electrical stimulation of the aortic depressor nerve, also was impaired. Baroreflex control of the cardiorespiratory system is thus impaired in rats with moderate LVD in the absence of congestive heart failure. The attenuated baroreflexes are likely due to abnormal afferent mechanisms, although central mechanisms contribute to the impaired barosympathetic reflex.

Afferent Pathways↗
PubMed1995

Tumour diagnosis by PCR-based detection of tumour cells.

Tumour cells shed from solid primary tumours can be detected by the polymerase chain reaction (PCR) based on the selective amplification of mutated tumour genes or of genes expressed in a tissue specific manner. When tumour specific alterations are amplified, few tumour cells can be detected in excess of normal cells derived from the same tissue. Thus, malignant cells can be detected specifically in pancreatic juice, stool, urine, and sputum. Here we describe the adaptation of the mutant enriched PCR in conjunction with the introduction of artificial primer mediated restriction sites to the selective amplification of mutant K-ras genes in stool samples from patients with colorectal carcinomas. In reconstitution experiments, down to 10 colorectal carcinoma cells could be detected in 100 mg of stool. For the diagnosis of micrometastatic disease, a sensitive and specific technique was established based on the reverse transcription of mRNA specific for the carcinoembryonic antigen followed by the amplification of the cDNA (RT-PCR). Attempts to establish a specific RT-PCR for cytokeratin-18 failed because of the existence of at least one processed pseudogene.

Biomarkers, Tumor↗
PubMed1994

Evaluation of the genotoxicity of 4-diethylamino-4'-nitroazobenzene and seven analogues.

A series of eight nitroaromatic azo compounds based on 4-diethylamino-4'-nitroazobenzene has been examined for genotoxic activity in a collaborative study conducted under the auspices of the Ecological and Toxicological Association of Dyes and Organic Pigments Manufacturers (ETAD). The evaluation has been conducted in two parts, firstly an examination in vitro to assess any intrinsic genotoxic activity of the compound. The chemicals were examined in the Salmonella assay in a standard plate incorporation protocol in both the presence and absence of S9 and in a minimum of the four tester strains recommended in the OECD guideline for this assay, i.e. TA1535, TA1537, TA98 and TA100. All of the compounds were mutagenic in one or more of the Salmonella tester strains, and all were positive in TA98 with S9. A considerable range of potency was seen in this assay. The chemicals were further examined in vitro for mammalian cell gene mutation at either the HGPRT or TK locus in a standard (CHO, V79 or L5178Y) cell system. Only one of the chemicals was mutagenic and only with S9. This chemical also showed the most potent response in the Salmonella assay. The second part of the study was an examination in vivo to see whether any genotoxic activity was expressed in the whole animal. The in vivo rat liver DNA repair (unscheduled DNA synthesis; UDS) assay was chosen as being the most likely to be sensitive to aromatic nitroazo compounds. All of the materials were negative when tested alongside a structurally related positive control. The chemicals were also examined in the mouse bone marrow micronucleus assay in order to provide a second in vivo assessment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Psychiatric manifestations of Pick's disease.

Pick's disease is a rare cause of dementia frequently misdiagnosed as Alzheimer's disease. Because patients with Pick's disease often present with psychiatric symptoms, the psychiatric aspects of this disorder are reviewed, as well as the pathology and epidemiology of the disease. Two case reports illustrate many of the clinical features of PD. A detailed examination of the psychiatric aspects of the disorder is followed by an elucidation of the many clinical differences between Pick's disease and Alzheimer's disease.

Activities of Daily Living↗
PubMed1993

Evaluation of mutagenicity testing with Salmonella typhimurium TA102 in three different laboratories.

Thirty compounds of various chemical classes were investigated for mutagenicity in a collaborative study (three laboratories) using Salmonella typhimurium TA102. With five compounds, hydrazine sulfate, phenylhydrazine, hydralazine, glutardialdehyde, and glyoxal, mutagenicity was detected by all laboratories. Formaldehyde was assessed as weakly mutagenic in only one of three laboratories. The remaining 24 agents were uniformly described as non-genotoxic in TA102. In spite of the overall good qualitative agreement in the mutagenicity results between the three laboratories, some quantitative discrepancies occurred in the dose response of the mutagenic compounds. Varying inter- and intralaboratory differences in the spontaneous rate of revertants were obtained. The usefulness of the tester strain TA102 in routine mutagenicity testing is discussed.

Formaldehyde↗
PubMed1992

A simple and efficient method for the oligodeoxyribonucleotide-directed mutagenesis of double-stranded plasmid DNA.

A method for the oligodeoxyribonucleotide-directed mutagenesis of double-stranded DNA without the necessity for phenotypic selection is described. Plasmids denatured with alkali and purified by adsorption to and elution from nitrocellulose have single-stranded regions where primers can hybridize and serve as templates for a T7 DNA polymerase-catalyzed synthesis of complementary mutant DNA strands. When this procedure was carried out such that the original nonmutant strand contained uracil [method of Kunkel, Proc. Natl. Acad. Sci. USA 82(1985)488-492], mutation frequencies of between 30% and 40% were obtained. The technique has been used to generate mutant genes in plasmids of a wide variety of sizes. The largest plasmid manipulated and successfully mutagenized was 22 kb. The method is rapid and efficient and is not dependent upon either f1 phage vectors or the presence of restriction sites in the vicinity of the sequence targeted for mutation.

Base Sequence↗
PubMed1992

A protease responsible for post-translational cleavage of a conserved Asn-Gly linkage in glycinin, the major seed storage protein of soybean.

The assembly of 11S globulin seed storage proteins in plants is regulated in part by the activity of a protease that cleaves between asparagine and glycine residues. Post-translational cleavage of subunit precursors into acidic and basic polypeptides is associated with the ability of subunits in trimers to aggregate into hexamers in vitro. An activity is present in extracts from immature soybean seeds that specifically cleaves immature 11S seed storage proteins of soybean and Vicia faba into the polypeptides of the mature proteins. Sequence microanalysis has been used to demonstrate that proglycinin and prolegumin are cut at the legitimate site when proteins synthesized in vitro are used as substrates. A single amino acid change in the cleavage site renders the substrate uncleavable. The protease responsible for this activity also hydrolyzes a synthetic octapeptide whose sequence reproduces four amino acids on either side of the glycinin subunit G4 cleavage site. This assay permitted the purification and characterization of the protease. It is a glycosylated enzyme with an acidic pH optimum and a molecular mass of about 45 kDa in solution.

Amino Acid Sequence↗
PubMed1992

Changes in cortical negative DC shifts due to different motor task conditions.

The experiments were performed to study the relationship between motor performance and DC potential curves recorded by scalp electrodes. Accordingly, we studied the influence of different movements (e.g., unilateral versus bilateral, simple versus complex, active versus passive, phasic versus tonic muscle activity) on negative DC potentials. Our results confirm that spatial distributions of DC potential maxima can be used as an indicator of the activation of distinct cortical areas. Furthermore, evidence is presented that some motor tasks have a greater influence on the magnitude of surface electronegativity than others. (1) Phasic muscle activity revealed a significantly larger potential size than tonic. (2) Performance of a complex finger movement task elicited an increased surface electronegativity compared with performance of a simple task. (3) No significant differences in potential size were found between left (untrained) and right (skilled) hand use during the performance of the same complex motor task. (4) This was also true for the performance of an active and a passive finger movement task, indicating that, at least in simple motor tasks, somatosensory afferents significantly contribute to the recorded potential curve.

Adolescent↗
PubMed1992

Evaluation of the genotoxic potential of sorbic acid and potassium sorbate.

The genotoxic potential of sorbic acid and potassium sorbate was investigated in vivo and in vitro. Oral administration of sorbic acid (up to 5000 mg/kg body weight) did not induce sister chromatid exchanges or the formation of micronuclei in bone marrow cells of mice. Intraperitoneal treatment of rats with 400-1200 mg potassium sorbate/kg body weight did not alter the elution profile of DNA from isolated liver cells in the in vivo alkaline elution assay. Sorbic acid did not induce DNA repair in cultured human A549 cells in the unscheduled DNA synthesis (UDS) assay. In vitro incubation of the cells with 1-1000 micrograms potassium sorbate/ml, in the absence or presence of rat liver homogenate, did not result in the formation of DNA single-strand breaks in the alkaline elution assay. These results demonstrate that sorbic acid and its potassium salt are not genotoxic in vivo or in vitro. In contrast to sorbic acid and potassium sorbate, sodium sorbate is very sensitive to oxidative degradation; the main oxidation product was identified to be 4,5-oxohexenoate, which was mutagenic in the Ames test.

Administration, Oral↗
PubMed1992

A compilation of genotoxicity and carcinogenicity data on aromatic aminosulphonic acids.

A review is presented to evaluate existing information on genotoxicity and carcinogenicity testing of various aromatic aminosulphonic acids (AASAs). A great variety of water-soluble azo dyes can form aromatic phenyl- or naphthyl-aminosulphonic acids by chemical and enzymatic reduction. AASAs are also used as intermediates in the synthesis of azo dyes and azo pigments and can arise as contaminants in the final products. Comparisons have been made with the data available on the corresponding unsulphonated analogues, some of which are known to be genotoxic and/or carcinogenic. The vast majority of the AASAs were conclusively non-mutagenic in the Ames test. In most cases the absence of genotoxicity was also demonstrated with a variety of other test systems in vitro and in vivo. It is concluded that AASAs, in contrast with some of their unsulphonated analogues, generally have no or very low genotoxic and tumorigenic potential.

Amines↗
PubMed1992

Collaborative study of mutagenicity with Salmonella typhimurium TA102.

Thirty compounds of various chemical classes were investigated for mutagenicity in a collaborative study (3 laboratories) using Salmonella typhimurium TA102. With 5 compounds, namely hydrazine sulfate, phenylhydrazine, hydralazine, glutardialdehyde and glyoxal, mutagenicity was detected by all laboratories. Formaldehyde was assessed as weakly mutagenic in only 1 of 3 laboratories. The remaining 24 agents were uniformly described as non-genotoxic in TA102. In spite of the overall good qualitative agreement in the mutagenicity results between the 3 laboratories some quantitative discrepancies occurred in the dose response of the mutagenic compounds. Varying inter- and intra-laboratory differences in the spontaneous rate of revertants were obtained. The usefulness of the tester strain TA102 in routine mutagenicity testing is discussed.

Evaluation Studies as Topic↗
PubMed1992

Isoflurane and nitrous oxide: comparative impact on cerebrospinal fluid pressure in patients with brain tumors.

The relative effects on cerebrospinal fluid pressure (CSFP) of equipotent concentrations of isoflurane and N2O were compared in 20 patients with brain tumors who had lumbar subarachnoid catheters in place. Patients were randomly assigned to receive one of two anesthetic sequences: group 1, 0.7% end-tidal isoflurane in O2, which was changed to 70% N2O in O2; or group 2, 70% N2O in O2, which was changed to 0.7% end-tidal isoflurane in O2. End-tidal PCO2 and percent end-tidal N2O and isoflurane were monitored by mass spectrometry from just before changing anesthetics (time = 0 min) until the end of a 20-min observation period (time = 20 min). Ventilation was held constant at PaCO2 = 36 +/- 1 mm Hg (mean +/- SE). The patients in group 1 sustained an increase in CSFP that reached a maximum of 33% above the value at 0 min, despite a 3-mm Hg decrease in PaCO2 (P < 0.05). By contrast, CSFP remained unchanged in group 2. Although the absolute increase in CSFP after replacement of isoflurane/O2 by N2O/O2 anesthesia was relatively small (9 +/- 1 to 12 +/- 2 mm Hg; P < 0.05), the absence of a similar effect in patients where N2O was replaced by isoflurane suggests that replacement of isoflurane by an equipotent concentration of N2O is more likely to lead to an increase in CSFP in patients with altered intracranial dynamics than is replacement of N2O by isoflurane.

Brain Neoplasms↗