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Biomedical subjects

M Jung

Publications and source records attributed to M Jung.

At least 19 recordsLinked to original sources
PubMed1992

Mutations in the p53 gene in radiation-sensitive and -resistant human squamous carcinoma cells.

Five of six human squamous cell carcinoma (SCC) cell lines characterized as radiation sensitive (SQ-38, SCC-9, SQ-9G) or radiation resistant (SQ-20B, SCC-35, JSQ-3) exhibited alterations of the p53 gene. The point mutations and a deletion were detected by using single-stranded conformational polymorphism analysis and polymerase chain reaction-direct sequencing. Interestingly, three of three radiation-sensitive and two of three radiation-resistant cell lines revealed mutations in the p53 gene. Point mutations were located in exons 4, 6, and 8 (at codons 72 and 298 in JSQ-3; 273 in SCC-35; 196 in SQ-38), and deletions consisted of 32 base pairs between codons 274 and 285 in SCC-9 and 1 base pair at codon 271 in SQ-9G. Three mutations resulted in substitutions for an arginine residue. Immunocytochemical analysis confirmed p53 protein overexpression in SCC-35 cells which contained a missense mutation at codon 273. In contrast to previous studies which linked alterations in ras, myc, and raf expression with radiation resistance, this study indicates that mutations in the tumor suppressor gene, p53, do not directly correlate with such resistance.

Carcinoma, Squamous Cell↗
PubMed1992

Absence of interaction between tenoxicam and warfarin.

The influence of tenoxicam on plasma warfarin concentrations and on its anticoagulant effect has been studied in healthy volunteers. Tenoxicam did not alter the plasma warfarin concentration versus time profile. Treatment with it for 14 days had no effect on the average dose of warfarin required to maintain the prothrombin time within a specified range. The coumarin dose index, an indicator of warfarin sensitivity, remained unchanged during tenoxicam administration. The results demonstrate the lack of a clinically relevant effect of tenoxicam on warfarin-induced anticoagulation.

Adult↗
PubMed1992

HIV-1 sensitivity to zidovudine: a consensus culture technique validated by genotypic analysis of the reverse transcriptase.

In order to select and standardize a reliable assay for the analysis of sensitivity of HIV isolates to AZT, we have compared two culture methods. The first assay (Cell-Associated Isolate Sensitivity Assay: CAISA) quantified AZT-resistant HIV isolates by end-point dilution cultures of peripheral blood mononuclear cells (PBMCs) in the presence of various concentrations of AZT. In the second assay (Cell-Free Isolate Sensitivity Assay: CFISA), following a conventional isolation of HIV, dilutions of infected cell-free supernatants were cultivated with fresh normal donor PBMCs in the presence of increasing concentrations of AZT. Samples from 64 untreated and AZT-treated patients were studied by CAISA (41), CFISA (43) or both assays (20). The CFISA, which allows the determination of titration parameters with respect to various kinetics patterns of viral replication was selected, and some of the CFISA phenotypically characterized isolates were further studied by nucleotide sequence analysis of the reverse transcriptase gene. CFISA showed that isolates from untreated patients were susceptible to AZT while the frequency of resistance increased with the duration of therapy. Genotypic analysis of CFISA-resistant isolates exhibited mutations at crucial positions, particularly at residue 215. We consider CFISA as a consensus culture technique for longitudinal studies of isolates from patients receiving AZT or other analogs of nucleosides.

Cell-Free System↗
PubMed1992

Benzodiazepines block long-term potentiation in slices of hippocampus and piriform cortex.

The effects of two benzodiazepines, diazepam and triazolam, on long-term potentiation were tested in slices of hippocampus and piriform cortex. The drugs had little influence on baseline synaptic responses but both were very effective in blocking LTP elicited by theta pattern stimulation. The effects were fully reversible upon washout. Diazepam reduced the increase in burst responses that occurs during theta stimulation and thus appears to interfere with the initial triggering events for long-term potentiation. This may reflect the enhancing action of the drug on GABA-mediated inhibitory potentials. Triazolam did not detectably change the burst responses elicited by theta pattern stimulation. Experiments with slices of piriform cortex indicated that triazolam also failed to disrupt the development of long-term potentiation but instead caused the potentiation to decay back to baseline in 15-30 min. Triazolam thus seems to act on the mechanisms that stabilize long-term potentiation. These results provide a possible explanation for the amnestic effects of benzodiazepines in humans and animals and support the hypothesis that long-term potentiation contributes to memory encoding.

Analysis of Variance↗
PubMed1992

Reliable and efficient direct sequencing of PCR-amplified double-stranded genomic DNA template.

Modified PCR amplification and direct sequencing procedures for the double-stranded genomic DNA template are described. Advantages of the approach we describe are: background artifact bands previously observed using high-molecular-weight DNA as a template were eliminated by this protocol; no gel purification or subcloning of the PCR-amplified double-stranded fragment was required prior to direct sequencing; and sequences of 300 nucleotides can be easily read even after a single loading. The successful use of the modified dideoxynucleotide chain-termination method for direct sequencing of both strands demonstrates the efficiency of this technique for removing sequencing artifacts and for producing reliable sequence data.

Base Sequence↗
PubMed1992

Susceptibility of HIV-1 isolates to zidovudine: correlation between widely applicable culture test and PCR analysis.

Thirteen isolates of human immunodeficiency virus type 1 (HIV-1) obtained in coculture with peripheral blood lymphocytes were tested for in vitro susceptibility to zidovudine (ZDV). Seven isolates were obtained from patients who had never been treated with ZDV and six from patients receiving the drug. The seven isolates from untreated patients and four of six from treated patients were susceptible to ZDV. The two isolates from the patients treated for the longest periods were resistant to the drug. The presence of mutations at critical positions of the reverse transcriptase gene was investigated by direct sequencing of polymerase chain reaction (PCR)-amplified DNA and four isolates were found to be mutants. An isolate from an untreated patient showed a change at residue 70 of the reverse transcriptase and an isolate from a patient treated for 4 months showed a change at residue 67. A change at residue 215 was found only for the two drug-resistant isolates, which correlated with the results obtained by Larder et al. using isolates from MT-2 cell cocultures. These results suggest that any HIV isolate provided by conventional coculture could be confidently tested for ZDV susceptibility in order to study the emergence of resistance during long-term therapy.

Base Sequence↗
PubMed1991

Pacing-induced myocardial ischemia does not affect the endothelial release of coagulant and fibrinolytic factors into the coronary circulation.

The present study addresses the potential effects of pacing-induced myocardial ischemia on the secretion of coagulant and fibrinolytic factors within the coronary circulation. In 6 patients undergoing programmed ventricular stimulation with repeated induction of clinical ventricular tachycardia, the coronary release of tissue-type plasminogen activator (t-PA) antigen, plasminogen activator inhibitor (PAI) capacity, von Willebrand factor antigen (WF:Ag), and prostacyclin (6-keto-PGF 1a) was measured. Blood samples were collected simultaneously from the ascending aorta and the coronary sinus at baseline and immediately after the induction of ventricular tachycardia. The occurrence of pacing-induced myocardial ischemia was established by myocardial net lactate production. Myocardial ischemia was induced in every patient by repeated pacing trials. Pacing-induced ischemia did not affect the coronary release of any of the above factors. Consequently, there was no alteration of transcardiac gradients of thrombin-antithrombin complexes and D-dimer. The present results indicate that pacing-induced myocardial ischemia does not affect the release of coagulant and fibrinolytic endothelial factors or prostacyclin into the coronary circulation.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Genetic variability affects the detection of HIV by polymerase chain reaction.

Nine isolates of HIV-1 obtained from Congolese AIDS patients were amplified by the polymerase chain reaction (PCR) using primer pairs and oligomer probes derived from the HIV-1 LAV-BRU (BRU) sequence. When compared to BRU, two isolates exhibited a significant decrease of PCR efficiency with a given primer pair. Moreover, the DNA amplified from two other isolates did not hybridize with the corresponding probe despite efficient PCR. Base substitutions were detected in the regions of proviral genomes involved in oligonucleotide annealing and were assumed to be responsible for the failure of both amplification and probing. Our data confirm that the genetic variability of HIV-1 may reduce the efficiency of PCR as a diagnostic procedure, especially in the case of African isolates.

Base Sequence↗
PubMed1991

MS-8209, a new Amphotericin B derivative that inhibits HIV-1 replication in vitro and restores T-cell activation via the CD3/TcR in HIV-infected CD4+ cells.

A new Amphotericin B derivative, MS-8209, which retains high antifungal activity with greatly reduced toxicity and improved solubility, has been developed. We investigated the antiviral properties of MS-8209 in Jurkat and CEM T-cell lines and in peripheral blood mononuclear cells infected in vitro with HIV-1BRU. Our results demonstrate, by determination of reverse transcriptase activity and p24 antigen level titration in cell culture supernatants, that MS-8209 inhibits HIV-1 replication in all cell types at concentrations without cytotoxicity. MS-8209 also prevents membrane expression of the HIV-1 large envelope glycoprotein gp120 and the decrease in CD4 level at the surface of infected cells. HIV-1-infected Jurkat cells exhibit a severe signalling defect at CD3 stimulation. Treatment with MS-8209 restores normal responsiveness at CD3 as assessed by measurement of inositol triphosphate accumulation and calcium flux. Finally, our results indicate that MS-8209 inhibits HIV-1BRU replication without preventing virus binding and penetration into target cells.

Amphotericin B↗
PubMed1991

[The effect of diamond grinding instrument of different grit on dental hard tissue].

Under practice-related conditions 100 human molars and premolars were prepared with diamond grinding instruments of different grit. We obtained the smoothest surfaces by using the extra-fine grit at 250,000 rpm, thus indicating the suitability of these instruments for finishing cavity walls especially at high rotating speeds. Only slight differences were found between medium and coarse grit. The time saved by choosing the super-coarse grit for preparation is largely compensated because finishing of rough cavity walls will take longer. No constant effect of the rotating speeds on the depth of roughness of cavity walls was observed.

Carbon↗
PubMed1990

Diagnosis of protein C deficiency in patients on oral anticoagulant treatment: comparison of three different functional protein C assays.

The efficacy of three different protein C activity assays and of protein C antigen determination for the diagnosis of protein C deficiency was studied in 13 protein C deficient patients (11 with type I, 2 with type II deficiency) and in 51 presumably non-deficient patients (control group), both groups being on oral anticoagulant (OAC) treatment. For protein C activity measurement (1) the assay according to Francis (slightly modified) with thrombin activation and measurement of activated protein C in the aPTT system, (2) an assay using Protac activation and chromogenic substrate (Protac-CS) and (3) an assay using Protac activation and the aPTT system (Protac-PTT) were used. Protein C antigen was determined by Laurell immunoelectrophoresis. The three activity assays gave different results, with the highest values obtained by the Protac-CS assay and the lowest values by the Protac-PTT assay. The Francis assay gave intermediate results. Protein C activity and antigen values were significantly lower in protein C deficient patients compared to the control group. Protein C activity tests had a higher discriminative power than the antigen determination. After taking into account the intensity of treatment, by the Francis assay all deficient and non-deficient patients were correctly classified, by the Protac-CS and the Protac-PTT assay 2 and 4 patients, respectively, were misclassified and by the antigen assay 8 patients were misclassified. Calculation of the ratios of protein C activity to factor II activity was of high discriminative power. We conclude that for diagnosis of protein C deficiency protein C activity tests are superior to antigen determination not only in type II but also in type I deficient patients.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Hydroxycoumarins↗
PubMed1990

Electrophysiologic determinants of recurrent atrial flutter after successful termination by overdrive pacing.

The potential ability of electrophysiologic abnormalities to predict recurrence of atrial flutter was evaluated. Twenty-five patients with chronic atrial flutter resistant to combined digitalis and quinidine therapy were studied electrophysiologically after restoration of sinus rhythm by overdrive pacing or by eventual direct current cardioversion. Recurrence of atrial flutter was observed in 12 patients during a mean follow-up period of 17 months (range 3 to 50). Electrophysiologic testing included programmed high right atrial stimulation at a paced drive cycle length of 600 ms and incremental pacing up to 200-ms paced intervals. When coupling intervals of 90% of the drive cycle length were compared to coupling intervals of 48% of the drive cycle length, the increase in S1A1 interval, defined as the interval between the stimulus artifact and the atrial activation near the atrioventricular junction, was greater in patients with subsequent recurrence of atrial flutter (47 +/- 11 vs 21 +/- 18 ms). Stepwise logistic regression analysis identified the S1A1 increase to be the sole independent predictor of recurrence (p = 0.0082) while previous episodes of atrial flutter or the presence of organic heart disease were identified as dependent variables. Reclassification showed a 91% sensitivity and a 92% specificity. Correct classification was achieved in 92% of patients. The initiation of atrial dysrhythmia had no predictive value. The assessment of the S1A1 interval by programmed atrial stimulation appears helpful in delineating the patient risk of recurrent atrial flutter after termination by overdrive pacing.

Atrial Flutter↗
PubMed1990

Hypomorphic C4B* 15 variant of the fourth component of complement.

We report a rare 'hypomorphic' C4 allotype detected during routine screening in controls for the Rogers:1 epitope. C4B* 15 was distinguished by having only faint staining when using polyclonal anti-C4 antibody on agarose immunoelectrophoresis (e.g. hypomorphic), having relatively weak hemolytic activity but being strongly reactive with monoclonal antibody to Rodgers 1. TaqI restriction fragment length polymorphism (RFLP) demonstrated that C4B* 15 segregated with 7 kb and 5.4 kb C4 gene fragments and with the haplotype HLA-A2,C-, B50,BW6,DR7,DQ2,DR52,SO7C2(1,15). The 5.4-kb fragment was more intense than the 7.0-kb fragment, suggesting duplication of the 5.4-kb fragment. This hypomorphic C4 allotype (genotype frequency = 0.0088) has diminished expression of C4 epitopes commonly recognized by polyclonal anti-C4 and may be missed by standard phenotyping methods.

Adult↗
PubMed1990

Long-term results of palliative endoscopic and surgical intubation of benign oesophageal stenoses.

Benign oesophageal stenosis can be treated by different methods. Besides surgical procedures and established conservative treatment (e.g. dilatation), more invasive endoscopic techniques such as cryosurgery and laser therapy have recently been developed. Intubation, which has been used to treat malignant strictures, can also be used in benign oesophageal strictures. Between 1977 and 1989 a total of 43 tubes were implanted in 26 patients (mean age 62.3 years). The mean duration of intubation was 149 days. We report our experience in patients intubated for (1) acid burns, (2) actinic strictures, (3) peptic strictures, (4) postoperative stenosis, (5) postoperative complications and (6) tracheo-oesophageal fistulae. We also discuss the complications (dislocation, disintegration, bleeding, perforation, operative removal) and long-term results. Because of the prolonged survival of patients with benign oesophageal stenosis, follow-up and late complications are of particular importance in this report. Despite drawbacks, intubation is an option in the management of patients with benign oesophageal stenosis.

Adult↗
PubMed1990

Prognostic role of inducible ventricular tachycardia in patients with dilated cardiomyopathy and asymptomatic nonsustained ventricular tachycardia.

We studied the prognostic relevance of inducible ventricular tachycardia in 32 patients with dilated cardiomyopathy and spontaneous nonsustained asymptomatic ventricular tachycardia. Programmed ventricular stimulation included basic drive cycle lengths of 600, 500, 430, 370, 330 and 300 msec at single, double, and triple extrastimuli. Ventricular tachycardia (greater than or equal to 6 beats) was initiated in 7 patients (22%), with sustained monomorphic ventricular tachycardia being seen in 4 of them. During median follow-up of 21 months (13-44), 14 patients died. Sudden cardiac death occurred in two of the seven patients with inducible tachycardia and in only one of the 25 patients in whom it was not possible to induce tachycardia. Although patients with inducible tachycardia did not differ clinically from those in whom tachycardia could not be induced, the projected mean survival time was significantly shorter in those with inducible tachycardia (10 months vs. 32 months, P = 0.04). For late sudden cardiac death, the positive predictive value of inducible tachycardia was 28%. The negative predictive value was 96%. We conclude that induction of ventricular tachycardia by programmed stimulation might indicate poorer prognosis in patients with dilated cardiomyopathy.

Adult↗
PubMed1990

Synthesis and antimalarial activity of (+)-deoxoartemisinin.

(+)-Deoxoartemisinin (2), a new and more active antimalarial agent, was successfully prepared from artemisinin in one step using NaBH4 and BF3.Et2O in THF. (-)-Deoxodeoxyartemisinin (5), a potential metabolite of deoxoartemisinin, was also prepared either from 2 or from artemisinic acid. 2 shows 8-fold increased antimalarial activity in vitro against chloroquine-resistant malaria as compared to artemisinin (1). Compound 2 possesses superior in vivo antimalarial activity to 1.

Animals↗
PubMed1990

Sucralfate in the treatment and prevention of gastric ulcer: multicentre double blind placebo controlled study.

A randomised controlled multicentre trial was performed in 160 patients with gastric ulcer, proved by endoscopy and biopsy, to compare ulcer healing with sucralfate and ranitidine (double blind double dummy design) and to assess the effect of maintenance treatment with sucralfate on ulcer recurrence (double blind placebo controlled design). The healing rates were similar with 4 g sucralfate suspension per day and 300 mg ranitidine per day (82% and 88% after 12 weeks, respectively). Of the 109 patients with healed ulcers, 92 were entered into the maintenance trial and treated with sucralfate tablets (2 g per day) or placebo tablets. Maintenance treatment with sucralfate delayed symptoms of gastric ulcer recurrence. Lifetable analysis showed significant differences between sucralfate and placebo, both after six months (p = 0.018) and after 12 months (p = 0.044). The rates of symptom recurrences were 13% and 34% after six months and 34% and 55% after 12 months for sucralfate and placebo, respectively. The rate of asymptomatic recurrences after 12 months was similar in the two groups (9% and 10%, respectively). The recurrence rate was higher in patients who had never taken non-steroidal anti-inflammatory drugs than in those who had but had stopped on admission to the study. It was also higher in patients with recurrent ulcer and in those with scarring deformation and narrowing of the pylorus. Maintenance treatment with sucralfate slowed the appearance of symptom recurrences of gastric ulcer.

Adult↗