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Biomedical subjects

J Böhm

Publications and source records attributed to J Böhm.

At least 73 records · Page 4Linked to original sources

Mutational spectrum of the p53 gene in human small-cell lung cancer and relationship to clinicopathological data.

The spectrum of p53 gene mutations was determined in formalin-fixed, paraffin-embedded samples of small-cell lung cancer derived from 28 patients. By direct sequencing of exons 5, 7, and 8, including their flanking intron sequences, 18 mutations were identified in 17 tumors (61%), and in all but two of these the wild type allele was lost. In 8 cases, the mutation detected in the tumor was absent from the corresponding normal tissue, indicating that these mutations were somatically acquired. In two patients, identical mutations were found in the primary tumor and corresponding metastases. In a further case, an intrapulmonary metastasis did not show the mutation detected in the primary tumor. The local distribution of the mutations resembled that reported in non-small cell lung cancer and gave no indication of distinct bot spot regions. G-to-T transversions were the predominant type of mutation, reflecting a possible genotoxic influence of carcinogens contained in tobacco smoke. Mutations were equally distributed among tumors with intermediate and oat cell histology and did not show a significant association to age and gender of the patients. Also, no significant relationship was observed between the presence of a mutation and tumor stage (T, N, M) or survival. However, transitions at CpG dinucleotides were restricted to tumors without detectable metastases at the time of biopsy, whereas all other mutations occurred in metastasizing small cell lung cancer.

Base Sequence↗

[The significance of the mycotoxins desoxynivalenol, zearalenone and ochratoxin A for agricultural domestic animals].

Mycotoxins are metabolic products of mycotoxins which have various chemical structures and show various toxic effects. Deoxynivalenol (vomitoxin) is an important economic factor in pig production due to growth depression and suppression of the immune system. Previous studies have shown that the 1-ppm limit in the sole feed for pigs should not be exceeded. Studies of methods of detoxification have as yet not produced conclusive results. Zearalenone has an tolerable effect and may lead to fertility disturbances on the oestrogen production in pigs and can cause remarkable economic damage even in the ppb range. Recommendations of upper limits cannot be made on the basis of the available results. The kidney toxin ochratoxin A is of importance in pig and poultry breeding and--due to its accumulation in the tissue--represents a possible source of danger to man. Since a possible carcinogenic effect of the toxin cannot be excluded, its content in animal rations should be kept as low as possible. For ruminants mycotoxins as a whole do not represent a particular source of danger as these substances can be degraded or converted by rumen flora.

Animal Feed↗

Carboxy-terminal truncated rhuIFN-gamma with a substitution of Gln133 or Ser132 to leucine leads to higher biological activity than in the wild type.

The biological function of the 20 C-terminal amino acids of human interferon-gamma (IFN-gamma) was examined by recombinant DNA methodology. Six truncated IFN-gamma analogues were produced by modification of the 3' end of the coding sequence of the cloned gene, insertion into a vector with the trc promoter and expression of the recombinant IFN-gamma analogue genes in Escherichia coli strain JM 105. The IFN-gamma analogue proteins were shortened by 10 (C-10L), 11 (C-11, C-11L), 14 (C-14L), 19 (C-19L) and 20 (C-20) amino acid. Four of these constructs were modified to have a C-terminal leucine. The expression rates of precipitating IFN-gamma variants in E. coli cells (wild type, C-10L, C-11, C-11L) amount to 35-40% of the total protein, in contrast to 14-21% for the mainly soluble ones (C-14L, C-20). The variant C-19L has an exceptional position in its solubility behaviour with a nearly 1:1 distribution between its soluble and insoluble form by an expression rate of 8%. The purification protocol of the insoluble variants contains a denaturing and a renaturation step. The characteristic step for purification soluble IFN-gamma is HPLC cation-exchange chromatography. The antiviral activities of the variants lacking 14 or more amino acids are less than 2% of the wild-type activity. The variants C-10L, C-11 and C-11L show higher biological activities than wild-type IFN-gamma. The most active variant, C-10L, with leucine as the last C-terminal amino acid, has a fourfold higher specific antiviral activity (A549 cells, encephalomyocarditis virus). Removal, but not replacement of the leucine, represented by the variant C-11, reduces the biological activity compared with variant C-10L. The activity of C-11 is, nevertheless, higher than in the wild type. Comparing the secondary structures, as judged by CD analyses, no significant differences for C-10L, C-14L and C-20, compared with wild type, are observed. Also, all molecules, including the wild-type protein, exist as dimers under physiological conditions. There is a correlation between the grade of truncation and the pI values, which range from pI = 10.4 (wild type) to pI = 8.0 (C-20). The variant C-10L demonstrates a higher temperature stability (tm = 55 degrees C) compared with wild type (tm = 53 degrees C). Perhaps this higher stability will result in a longer half-life in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

Bilateral stromal Leydig cell tumour of the ovary. Case report and literature review.

The stromal Leydig cell tumour of the ovary is a very rare benign neoplasm which usually occurs in postmenopausal women. Due to a significant production of androgens by the tumour, it is frequently associated with symptoms of virilization. To our knowledge only 7 cases have been reported in the literature, one of them with bilateral manifestation. We report an additional case affecting both ovaries in a 59-year-old nun with long-standing virilism, review the literature, and discuss the histomorphological features for differential diagnosis.

Diagnosis, Differential↗

Removal of 3' nontranslated cDNA sequence improves interferon gamma synthesis in Escherichia coli.

The cDNA coding for human interferon gamma contains approximately 600 basepairs not translated sequence with 4 adenine/thymidine (AT)-rich clusters at its 3'end. The influence of this sequence on the expression of recombinant human Interferon gamma in Escherichia coli was investigated. Removal of the non-translated sequence and especially of the AT-rich clusters yielded an increase in expression of interferon gamma from 10 to 40% of total protein. These results may also be important for the production of other recombinant human proteins with similar 3' sequences in their cDNA.

Bacterial Proteins↗

[Androgenization in postmenopause in rare ovarian tumors--2 case reports].

Androgen-producing tumours of the ovary are uncommon in postmenopausal women. We report on symptoms of two patients with androgenization due to a stromal-Leydig cell tumour and a steroid-cell tumour, respectively. Clinical signs and symptoms, laboratory findings and therapeutic consequences are discussed.

Aged↗

Lead in human bones. Investigations on an occupationally non-exposed population in southern Bavaria (F.R.G.). I. Adults.

The concentration of lead in three different bones (pelvic bone, cortical part of the mid-femur, petrous portion of the temporal bone) of 240 occupationally non-exposed adults who died between October 1983 and February 1985 was determined by electrothermal atomic absorption spectrometry. As far as sex, age and domicile (urban and rural) are concerned, a balanced distribution was achieved (for each age decade 10 urban females, 10 rural females, 10 urban males and 10 rural males). The predominantly cortical femur (geom. mean, 3.86 mg Pb/kg bone wet wt.) and temporal bones (5.59) showed higher Pb concentrations than the trabecular pelvic bone (1.65) (in each case n = 240). For each of the three types of bone, the mean lead content of the males (n = 120) was significantly higher than those of the females (n = 120): e.g. for pelvic bone by 38.3%, mid-femur by 51.3% and temporal bone by 24.8%. No statistically significant difference was obtained when comparing residents of Munich (population greater than 1 X 10(6] (n = 120) with people in the remaining parts of Southern Bavaria (n = 120). The Pb content of the temporal bone increased steadily with age. In contrast, in the mid-femur and the pelvic bone the Pb content reaches a plateau in middle age with a decrease at higher ages; this decline is more distinct for females. The mean lead body burden was calculated to be 41.4 +/- 24.2 mg for all males (n = 120) and 24.1 +/- 12.5 mg for all females (n = 120). We conclude that the lead burden, at least in the area investigated, has been reduced in the last decade, probably because of a reduction in the lead content of petrol.

Adolescent↗

[Animal experiment results with a new vena cava filter].

A new cava filter has been tried in 23 dogs weighing between 16 and 23 kg. The filter consists of a stainless steel basket which can be introduced either antegrade or retrograde through a 10F teflon catheter and which can be removed again within the first four days. The filter was effective in holding back embolising thrombus. In the early stages, even without artificial embolisation, two out of five animals showed clot formation in the basket. After three or four months, all the filters were permeable and on only two occasions was a small amount of thrombus found.

Angioplasty, Balloon↗

The perturbation correction factor of ionisation chambers in beta-radiation fields.

In determining the absorbed dose in a solid medium by means of gas-filled ionisation chambers, the perturbation of the radiation field by the chamber needs to be taken into account. So far, an appropriate correction factor has neither been calculated nor measured for beta-radiation. This work describes its experimental determination for an extrapolation chamber and beta-radiation fields of 147Pm, 204Tl, and 90Sr + 90Y. The results show that the correction factor may be assumed to be the product of a shield factor and a scatter factor the magnitudes of which depend on the chamber geometry and the radiation field. The change of the perturbation correction factor with phantom depth is important for the measurement of depth dose curves. This is demonstrated by an example.

Electrons↗

Ion losses in a plane-parallel ionisation chamber irradiated with a pulsed electron beam.

Saturation curves for a plane-parallel ionisation chamber have been studied in a pulsed electron beam of 5.2 MeV initial energy as a function of chamber voltage, chamber depth and charge density liberated per pulse. It is shown that, if ion losses by diffusion and by initial recombination are appropriately considered, the remaining ion losses by volume recombination can be described by Boag's theory. The constant mu in this theory has been determined to be (2.7 +/- 0.1) x 10(10) V m C-1. This value is consistent with data on charge collection characteristics obtained using the same ionisation chamber exposed to continuous radiation from beta-sources.

Electrons↗

Acetylation of nucleosomal histones in vitro.

A new histone-specific acetyltransferase, which is closely associated with nucleosomes prepared from lymphocyte nuclei by treatment with micrococcal nuclease, is described. The acetylating enzyme transfers [3H]acetyl groups from [3H]acetyl-coenzyme A to the endogenous histones H2A, H2B, H3 and H4 in nucleosomes as well as to free histones added to the reaction mixture. Histone H1 is not acetylated by this enzyme. The acetyltransferase was partially purified by DEAE-Sephadex and DNA-cellulose chromatography. The nucleosome-associated enzyme binds to DNA cellulose at low salt concentrations (DNA-binding acetyltransferase), while the previously described histone-specific acetyltransferases have no affinity to DNA under these conditions. This high affinity for DNA may explain the association of DNA-binding acetyltransferase with nucleosomes.

Acetyl Coenzyme A↗

A histone-specific acetyltransferase is associated with simian-virus-40 chromatin.

[14C]Thymidine-labeled simian virus 40 nucleoprotein complexes were prepared from nuclei of lytically infected African green monkey kidney cells. The nucleoprotein complexes were further purified by sucrose gradient centrifugation and then incubated in the presence of [3H]acetyl-coenzyme A. We observed a transfer of [3H]acetyl groups to the endogenous histones H2B, H3 and H4. The enzyme was solubilized in the presence of 0.5 M NaCl and showed properties described for the DNA-binding acetyltransferase (J. Böhm, E. J. Schlaeger and R. Knippers, preceding paper in this journal).

Acetylation↗

Studies on protein-phosphorylation reactions in isolated chromatin.

The endogenous protein-phosphorylating activity of isolated chromatin was tested. We have found that a group of high-molecular-weight proteins (Mr greater than 50 000) was preferentially phosphorylated when chromatin from mouse ascites cells or from bovine lymphocytes was incubated in the presence of ATP. After disintegration of chromatin by nuclease treatment or by high salt concentration, a larger spectrum of chromatin proteins becomes accessible for phosphorylation by the chromatin-bound protein kinase. Some observations described in this communication may help to partially explain this result. The protein kinase was not found in nucleosomal subunits, indicating a non-random distribution of the enzyme in chromatin. This suggests that enzyme and substrate have to be in close spatial contact for the phosphorylation reaction to occur. Furthermore, we have shown for one protein, histone H1, that phosphorylation sites for the endogenous protein kinase are available on the free but not on the DNA-bound protein, suggesting that phosphate-accepting sites in chromatin proteins may be blocked by protein-DNA or by protein-protein interactions. We also discuss the possibility that chromatin protein kinase occurs in stable complexes with its phosphate-accepting substrates, as has been suggested by the findings of other [Kish, V.M. & Kleinsmith, L.J. (1974) J. Biol. Chem. 249, 750-760].

Animals↗

Saturation corrections for plane-parallel ionization chambers.

Experiments described in the literature lead to different formulae for saturation corrections in ionization chambers. To elucidate the differences, saturation curves of an extrapolation chamber irradiated with beta particles from 90Sr+90Y sources have been studied experimentally. The results could be described by one formula which was a combination of known formulae for charge collection losses due to volume recombination, initial recombination and diffusion.

Mathematics↗