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Biomedical subjects

M Geiser

Publications and source records attributed to M Geiser.

At least 55 records · Page 3Linked to original sources

Early and long-term toxicity in the management of advanced germ cell testicular tumors.

47 patients with advanced germ cell testicular tumors were treated with combination chemotherapy, cis-platinum, vinblastine and bleomycin (PVB). All patients were reexamined on average 2.5 years after the end of treatment. Persistent mild long-term toxicity affecting the lungs, kidneys and peripheral nerve system was found in about one third of the patients. In addition, 32 patients who had received radiation therapy of seminoma were reexamined. Objective long-term toxicity was rare. However, possible damage to chromosomes and spermatogenesis has to be kept in mind.

Adult↗

[Budesonide (Pulmicort) and exertion-induced asthma].

Twelve young adult asthmatic patients were selected in an asthma-free interval to be tested for exercise-induced bronchoconstriction. The degree of bronchoconstriction was estimated indirectly by spirometry, using FEV1 as parameter. Exercise was performed on a 10% steep treadmill for six minutes, leading to a pulse rate of more than 180 beats/min. Spirometry was done before, immediately after, and 10 and 20 min after the work. Only patients with more than a 10% fall in FEV1 during the 20 min period of recovery were selected. In the randomized crossover double blind trial the asthmatic patients received placebo inhalations for one week and budesonide inhalations for another week (2 X 800 micrograms daily). Spirometry was repeated at the end of each week. Under placebo we found a surprisingly high rate of protection against exercise-induced bronchoconstriction (50%, p less than 0.05). With budesonide 8% additional protection (compared to placebo) was achieved (mean of all 12 patients). The patient-drug-interaction was significant at the level of F = 30, p less than 0.05. There are some nonresponders to budesonide. Of the 12 asthmatics, 8 recognized the drug inhalation period. We conclude that one week of high dosage budesonide regimen recudes the tendency to exercise-induced asthma in adults. Budesonide seems to influence and mitigate bronchial hyperreactivity in the responder group.

Adolescent↗

The hypervariable region in the genes coding for entomopathogenic crystal proteins of Bacillus thuringiensis: nucleotide sequence of the kurhd1 gene of subsp. kurstaki HD1.

One of the genes for the entomophatogenic crystal protein of Bacillus thuringiensis (subsp. kurstaki strain HD1) has been cloned in Escherichia coli, and its nucleotide sequence determined completely. The gene is contained within a 4360-bp-long HpaI-PstI DNA restriction fragment and codes for a polypeptide of 1,155 amino acid residues. The protoxin protein has a predicted Mr of 130,625. The E. coli-derived protoxin gene product is biologically active against Heliothis virescens larvae in a biotest assay. Extensive computer comparisons with other published B. thuringiensis subsp. kurstaki strains HD1, HD73, and B. thuringiensis subsp. sotto gene sequences reveal hypervariable regions in the first half of the protoxin coding sequence. These regions are responsible for the biological activity of the protein product of the cloned gene, and may explain the different biological activities of these different protoxins.

Bacillus thuringiensis↗

Specific modulation of the transcription of cloned avian vitellogenin II gene by estradiol-receptor complex in vitro.

Avian vitellogenin-cauliflower mosaic virus hybrid gene is effectively transcribed in vitro in the homologous embryonic liver nuclei system. The transcription of the hybrid gene is modulated by the addition of an estradiol-receptor preparation that has been shown to bind selectively to an upstream region of cloned vitellogenin gene. Stimulation of the transcription of cloned vitellogenin hybrid gene by estradiol receptor is alpha-amanitin sensitive, hormone dependent, and promoter specific. Simian virus 40 and Escherichia coli promoters are not stimulated by the estradiol-receptor complex. The endogenous silent vitellogenin II gene (wild type) present in the nuclei is not turned on by the addition of estradiol-receptor complex. Deletion or inversion of the DNA sequence where the estradiol-receptor complex binds results in the complete suppression of the in vitro stimulation of transcription by estradiol receptor. Correct initiation of the transcription was demonstrated by primer extension studies of the newly synthesized RNA.

Animals↗

Preferential binding of estrogen-receptor complex to a region containing the estrogen-dependent hypomethylation site preceding the chicken vitellogenin II gene.

DNA-cellulose competition binding assays were used to measure the ability of cloned DNA fragments of the chicken vitellogenin II gene to displace the estrogen-receptor complex from total chicken DNA coupled to cellulose. The DNA fragment that gave the highest competition is situated in the upstream region of the gene between nucleotides -458 and -725. This DNA fragment has four small clusters of A + T-rich sequences and contains the estrogen-dependent hypomethylation site. In vitro methylation of the Msp I site does not change the capacity of the DNA fragment to compete for estrogen-receptor complex, whereas cleavage of the C-C-G-G (Msp I site) results in a complete loss of competition of this fragment for estrogen-receptor complex. These results, combined with deoxyribonuclease I protection experiments, suggest that the most probable binding site for estrogen-receptor complex is . . .G-C-G-T-G-A-C-C-G-G-A-G-C-T-G-A-A-A-G-A-A-C-A-C. . . . This sequence has 73% homology with the core enhancer sequence of simian virus 40, . . .G-G-T-G-T-G-G-A-A-A-G. . . (identical bases italicized).

Animals↗

Structure and sequence of the promoter area and of a 5' upstream demethylation site of the estrogen-regulated chicken vitellogenin ii gene.

We sequenced 487 base pairs (bp) covering the 5' end of chicken vitellogenin II gene and 840 bp of its 5' end-flanking region. This region includes a MspI/HpaII restriction site which becomes undermethylated in chicken liver upon estrogen treatment. Southern blot analysis of restriction enzyme digests of total DNA confirms that this undermethylation site is the one situated at -611 bp from the cap sequence. This site is flanked at nucleotides -567, -629, and -667 by stretches of DNA very rich in A + T. We used S1 nuclease mapping as well as a primer extension procedure to map the transcription starting point of the vitellogenin II gene. We found a 5'CATAAAA3' box between nucleotides -32 and -26, and between nucleotides -77 and -69 a sequence (5'TTGAGAATT3') homologous to the bacterial RNA polymerase-binding site. A similar sequence (5'TGTTTACATAAA3') is also found between nucleotides -101 and -90. A comparison of the sequence of the primer-extended DNA with the 5' end of vitellogenin II gene revealed the presence of two small exons of 53 and 21 bp between nucleotides +1 and +53, and +169 and +189, respectively, and two small introns of 115 and 100 bp between nucleotides +54 and +168, and +190 and +290, respectively. The first AUG at nucleotide +14 is in front of an open reading frame. We found that 77% of the amino acids coded by the first exon are hydrophobic, a feature compatible with a signal sequence of a secreted protein such as vitellogenin.

Amino Acid Sequence↗

Genomic clones of a wild-type allele and a transposable element-induced mutant allele of the sucrose synthase gene of Zea mays L.

In an attempt to isolate the transposable genetic element Ds from Zea mays L., we cloned DNA fragments hybridizing to a cDNA clone derived from the sucrose synthase gene in a lambda vector (lambda::Zm Sh). The fragments cloned from wild-type and from the Ds-induced mutant sh-m5933 (lambda::Zm sh-m5933) share a segment 6 kb long while a contiguous segment of 15 kb of lambda::Zm sh-m5933 (mutant-derived DNA) does not hybridize to the DNA segment cloned from the wild-type. Restriction maps are given, and the junction point between the two DNA segments in the mutant clone was determined. Hybridization of DNA fragments, present in the wild-type DNA of lambda::Zm Sh, but not in the mutant clone, lambda::Zm sh-m5933, to genomic DNA of sh-m5933 showed that no part of this DNA is deleted. It cannot be said whether the DNA found in the mutant, but not in the wild-type clone, has been brought there by Ds insertion or by another Ds-dependent DNA rearrangement. The mutant-derived DNA was hybridized to genomic DNA of various maize lines digested by several restriction endonucleases. Approximately 40 bands were detected. The mutant-derived DNA contains two pairs of inverted repeats several hundred nucleotide pairs long, one of which is located at the junction to wild-type-derived DNA.

Journal Article↗

A cDNA clone from Zea mays endosperm sucrose synthetase mRNA.

A cDNA clone for maize endosperm sucrose synthetase of 62o nucleotide pairs length was obtained by cloning double stranded DNA obtained from the total maize endosperm poly(A) RNA in pBR322, and identifying the appropriate clone by hybrid-promoter translation. In Southern blotting to genomic BamHI-digested DNA, a single band only of approximately 20 Kb lights up, indicating that the sucrose synthetase gene is unique, or that closely linked copies are located on this DNA fragment.

Base Composition↗

[Catamnesis of patients with backache from an infantry boot camp].

A follow-up is reported in 58 former infantry recruits whose locomotor system was examined during recruit training in 1964. 35 recruits completed the training period in spite of marked pathological lesions of the spine, and 23 were prematurely discharged from recruit training due to back complaints. Reexamination of these men 7 and 15 years later showed that recruits discharged because of persistent back complaints did not show pathological findings in the spine not also observable in men who remained fit for service for 15 years. One exception was a recruit discharged for herniated lumbar disc. The pathological findings were spondylolisthesis, scoliosis, Scheuermann's disease, straight back and hyperkyphosis, and hyperlordosis. Half of those who remained fit for service, and three quarters of those discharged prematurely, complained of back pain in activities straining the spine. However, only one sixth of those fit for service and a quarter of those discharged prematurely saw a doctor for treatment of these symptoms. The results of these reexaminations may encourage army doctors to declare men fit for service in spite of a pathological back diagnosis, if they show a positive attitude to military service and if the history suggests functional load capacity of the spinal column.

Back Pain↗

Suppression of phosphorylcholine-specific IgE antibody formation in BALB/c mice by isologous anti-T 15 antiserum.

In order to study the regulation of IgE antibody formation, isologous anti-idiotypic antisera against the phosphoryl choline (PC)-specific BALB/c myeloma proteins T 15 and M 167 were passively administered to BALB/c in the course of an anti-PC IgE response. Isologous anti-T 15 antiserum had a long-lasting suppressive effect on the formation of IgE antibodies with PC specificity, whereas administration of anti-M 167 antiserum had no or only little effect, similar to that of normal BALB/c serum. This indicates that anti-PC IgE antibodies consist mainly of the T 15 idiotype or of cross-reacting idiotypes, and that IgE response is accessible to regulation with anti-idiotypic antibodies. This murine model may permit the study of regulation of an IgE response largely restricted to few defined idiotypes characterized as tumor proteins.

Animals↗

Two chromatographically separable forms of Escherichia coli elongation factor Tu.

Two forms of the elongation factor Tu from Escherichia coli have been separated by chromatography on DEAE-Sephadex A50. Obvious chromatographic artifacts have been ruled out by investigation of the elution profile of GDP (a component of the column buffer as well as a ligand of Tu) and by rechromatography of the two components, either separately to give the component peaks or together to give a double peak. The two components have been confirmed as Tu by the poly(uridylic)-dependent polyphenylalanine synthesis and by the distribution of the Tu protein as quantitated from sodium dodecyl sulfate/polyacrylamide gel electrophoresis. Complexes with the elongation factors Ts and G have also been ruled out by activity profiles and by quantitation of the protein distribution, again on gels. The distribution of the two forms between ribosomal and supernatant fractions has been examined: one is bound preferentially to the ribosomal fraction and the other is found in the supernatant fraction. The possible significance of this is discussed.

Bacterial Proteins↗

[Dysplasia and pseudodysplasia of the infantile hip joint (author's transl)].

The natural course of "dysplasia" of the hip diagnosed between the age of two and ten months was followed in 47 children. If the dysplasia diagnosed by radiographs was not combined with a clinical instability of the hip dislocation never occurred although no therapy- except abduction exercise - was given. The radiological signs of dysplasia regularly disappear after the child has learned to walk. Three different kinds of dysplasia are described. Dysplasia may be a residual sign of neonatal instability which became stable with or without treatment. Pseudodysplasia is the effect of faulty X-ray technique or X-ray interpretation. In dysplasia with no known instability in the history it may be the residual sign of a neonatal instability which was not diagnosed or it may be a variation of development of the hip joint during the first year of life. Since dysplasia without clinical instability does not progress and will never end with a dislocation there is no indication for therapeutic measures in a stable hip with radiological signs of dysplasia during the first year of life. The treatment of unstable hips diagnosed between the third and the twelfth month of life may be dangerous due to epiphyseal damage by immobilisation.

Age Factors↗

[Difficulties in the treatment of congenital instability of the hip].

The method of early diagnosis of congenital dislocation of the hip and the results of immediate treatment are described. X-rays are only useful to prove an instability if the hip is dislocated at the moment the X-ray is taken. If the unstable hips are reduced and redislocation is prevented by means of a splint the great majority of the hips show a normal developement. A primarily unstable hip which was stabilised spontaneously or by using a splint for a short time may become unstable again. Nevertheless splinting in the stable positon should not last longer than 1-2 months. The development of a coxa vara in three children rises the question whether the fixation of the hips in a frog position combined with the presence of a contraction of the adductors may impede the blood supply to the epiphysis and metaphysis. Early diagnosis of congenital dislocation of the hip means demonstration of instability of the neontal hip and not diagnosis of "dysplasia" during the first year of life. "Dysplasia" without instability does not mean predislocation. It is either a stable dysplasia or a residual sign of neonatal instability which became stable with or without treatement. Difficulties in diagnosis of neonatal instability are discussed. Etiology, pathogenesis and genetics of congenital dislocation of the hip are mentioned.

Age Factors↗