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Biomedical subjects

S Hummel

Publications and source records attributed to S Hummel.

87 records · Page 5Linked to original sources

[Analgesic asthma].

Analgesics-induced asthma (AIA) is quite often unidentified and then is a severe danger to the patients affliced. In a case-control-study 1042 asthmatic patients selected by random were investigated. In 18.9% of patients the presence of AIA was recorded. Woman accounted for 71% of the AIA patients. Coincidence of AIA with nasal polyposis, paranasal sinus diseases, chronic rhinitis, alcohol intolerance and severe bronchial asthma was recorded with high significance. Chronic hyperplastic changes in the upper airways were exhibited by about 64% of the AIA patients. AIA is a non-allergic form of asthma, resembling immediate allergic type I reaction. Analgesics-based acute bronchoconstriction will typically develop within 45 min. following intake of the analgesic. Triggering threshold doses may differ strongly by individuals. Oral exposure test is connected with a high risk of complications. A case history usually is sufficient for save diagnosis. Analgesics without inhibiting action on cyclooxygenase usually are tolerated. The causes of AIA should be ascribed to changes in the release and conversion of arachidonic acid (Aa) from membrane phospholipids. The inhibition of Aa release (phospholipase-A2-reaction) by protease inhibitors or the inhibition of Aa transformation to bronchoconstrictive lipoxygenase products by lipoxygenase inhibitors were shown in vitro (isolated guinea pig lung strips and human bronchi). Paraaminomethylbenzoic acid also was found to be effective in clinical experiments preventing analgesics-induced bronchoconstriction. Both seem to be principal ways for modulation of bronchoconstriction.

Analgesics↗

Inhibition of lecithin: cholesterol acyl transfer by propranolol treatment in man.

The changes in some parameters of plasma lipoprotein metabolism in 25 hypertensive men, caused by a two months lasting oral treatment with 120 mg propranolol/day, were compared to the changes that occur during the same time in the subjects (n = 9) of an untreated control group. Propranolol led to an increase of triglycerides and a decrease of HDL cholesterol in plasma, the latter consisting in a small increase of unesterified cholesterol and a larger decrease of cholesteryl esters. In parallel a decrease in the lecithin:cholesterol acyl transfer, measured as initial rate of cholesterol esterification, was observed. The extent of the plasma lipid and enzyme alterations was shown to be dependent on the patient's pretreatment situation. Changes in lecithin:cholesterol acyl transfer rate after oral treatment correlated significantly with similar changes after propranolol addition in comparable amounts to plasma in vitro. A similarity between propranolol induced alterations in the metabolism of plasma lipoproteins and the situation in hereditary LCAT deficiency is obvious and may be interpreted as a harmful component of propranolol action.

Cholesterol Esters↗

Characterization of highly and moderately repetitive 500 bp Eco RI fragments from Xenopus laevis DNA.

Three different types of repetitive Eco RI fragments, which comigrate within a visible band of approximately 500 bp at gel electrophoresis of Xenopus laevis DNA Eco RI digests have been cloned and sequenced. These sequences are designated as Repetitive Eco RI Monomers: REM 1, REM 2 and REM 3. The sequences contain direct repeats, inverted repeats and palindromic elements. Genomic organization of the most abundant sequence (REM 1; 0.4% of total DNA) is that of an interspersed sequence. REM 2 (0.08%) is partly organized as an interspersed element and partly found in tandem arrangement, whereas REM 3 (0.02%) represents the tandemly repeated monomeric unit of a satellite DNA. In situ hybridization has shown that REM 1 and REM 2 sequences are found on most chromosomes, REM 1 being preferentially located on specific chromosomal loci. REM 3 is located near the centromere region of only one chromosome pair (presumably number 1). Hybridization of Northern blots from RNAs of different developmental stages revealed that REM 1, REM 2 and REM 3 sequences are transcribed and that transcription is under developmental control.

Animals↗

[Types of bronchial reaction to analgesics].

Bronchial reaction of asthma bronchiale patients (n = 102) to analgesics was tested by oral exposure to acetylsalicylic acid. 73 patients produced no changed bronchial response to the exposure test. Ventilation parameters improved in 12 patients. In cases in which analgesics intolerance had been recordable from case histories (n = 17), acetylsalicylic acid doses were carefully increased in a stepwise approach to identify the threshold dose required for inset of bronchoconstriction. The average triggering threshold dose was found to be 200 mg. In patients with normal analgesics tolerance products of arachidonic acid metabolism seem to have no effect on bronchial tonus. The observed dilating effect of analgesics may, possibly, be associated with elimination of a cyclooxygenase metabolite with relevance to bronchoconstriction. Inducer of analgesics intolerance is the shift of arachidonic acid metabolism in favour of the route of lipoxygenase. Of importance is possibly a free proteolytic activity (inhibitor deficiency) with increased basic release of arachidonic acid.

Aspirin↗

Molecular cloning and sequencing of mRNAs coding for minor adult globin polypeptides of Xenopus laevis.

Globin mRNA was isolated from immature red blood cells of an adult Xenopus laevis female. mRNA/cDNA hybrids were integrated in the Pst I cleavage site of pBR 322 by G/C tailing, and cloned in Escherichia coli strain HB 101. By restriction site analysis as well as hybridization behaviour we identified two clones coding for minor adult alpha and beta globin chains. Nucleotide sequence analysis and derived amino acid sequences are presented.

Amino Acid Sequence↗

Modulation of human tumor colony growth in soft agar by serum.

The factors controlling the growth of human tumor cells in soft agar are poorly understood. However, it has been demonstrated that serum provides factors which promote anchorage-independent growth. We tested 58 tumor specimens, which were obtained from patients with adenocarcinoma of the lung, colon, ovary or squamous cell carcinoma, for their ability to form colonies in soft agar in serum-free or serum-supplemented media. The cells were unable to replicate, and none of the hormones or growth factors tested: insulin (I), transferrin (T), selenium (S), estradiol (E), hydrocortisone (H) or epidermal growth factor (EGF) could substitute for serum. Examination of the serum dose-response curves indicated that growth factors reduced the serum concentrations needed to support anchorage-independent growth. The addition of the supplements and the lowering of serum concentrations increased cloning efficiencies (C.E.) in 38/51 trials, when cells were able to grow initially. The addition of ITS increased C.E. in 18/21 cases, HITES in 15/17 cases and EGF in 12/18 cases as compared to controls. ITS and HITES increased the number of colonies only when serum was the limiting factor. EGF, however, increased the number of colonies even when serum was not the limiting factor. The ability of the supplements to enhance growth could not be correlated to tumor type or initial cloning efficiencies. However, in only 1/25 cases were cells that were unable to form colonies under standard conditions induced to form colonies in the presence of the growth factors. Normal and tumor-derived human fibroblasts did not form colonies in soft agar in the presence of these growth factors. The results suggest that human tumor cells may require the presence of serum-derived factors for growth in soft agar.

Adenocarcinoma↗

Measure of blood flow by the multiple radioactive microsphere technique in radiated gastrointestinal tissue.

In this study, two different radioactive microspheres were used to measure blood flow of an irradiated segment of small intestine in four dogs before, and 12 days after, irradiation with 2000 rad. The technique and implications are discussed. Using multiple radioactive microspheres, the study demonstrated an increased blood flow in irradiated tissues twelve days after a single dose of 2000 rad. There was also an increase in blood flow to adjoining nonradiated segments of intestine in the same animal. These observations may be of significance in clinical applications of radiation therapy and surgery. A major surgical concern is the impaired healing of irradiated tissue in the immediate postradiation period. The mechanism of this has generally implicated decreases in the perfusion of irradiated tissue. No decrease in blood flow was shown in this study, suggesting that other mechanisms, e.g., stem cell depletion, should be considered. Further studies of this type are recommended to increase understanding of the blood flow in irradiated tissue.

Animals↗

Lung strips from guinea pigs as test system for lipoxygenase inhibitors. Inhibition of arachidonic acid-induced contractions by 3-t-butyl-4-hydroxyanisole and nordihydroguaiaretic acid.

Lung strips and tracheal spirals from guinea pigs and rats were compared as test systems for lipoxygenase inhibitors. The contraction of the smooth muscle was induced by addition of arachidonic acid. Lung strips of guinea pigs proved to be the most suitable in vitro model. Under basal conditions half-maximal contraction was produced by 13 microM arachidonic acid (AA) which was strongly inhibited by 50 microM nordihydroguaiaretic acid (NDGA) or 100 microM 3-t-butyl-4-hydroxyanisole (BHA). NDGA and BHA caused a shift of response towards higher concentrations of AA. BHA also produced pronounced dilatations of both basal tonus and carbachol-induced contractions of the preparations from the respiratory tract. It is concluded that the actions of NDGA and BHA on the airway preparations are due to inhibition of the lipoxygenase reaction and, therefore, of leukotriene synthesis. The assumption of the lipoxygenase inhibition is supported by their action on purified lipoxygenase from rabbit reticulocytes which was inhibited by 50% by 0.5 microM NDGA and 160 microM BHA. In contrast, the antioxidant 2,6-di-t-butyl-4-hydroxytoluene (BHT) did not inhibit at all at 1 mM. To the knowledge of the authors this is the first evidence so far reported for the bronchodilating action of BHA.

Animals↗

[Salicylamide-- a potential pain-remedy alternative in the analgesic asthma syndrome].

Central pathogenetic mechanism of the analgesics-asthma-syndrome is very probably an analgesics-conditioned inhibition of the prostaglandin-biosynthesis (cyclooxygenase). Salicylamide, an analgesic without effect on the prostaglandin synthesis was in the oral exposition test of 18 patients with proved analgesics-asthma-syndrome in the dosage of 500 mg subjectively and objectively tolerated without reaction. Body-plethysmographically in consistent thoracic gas volume a slight decrease of the airways resistance could be registered. At the model of the isolated trachea of guinea-pigs salicylamide, in contrast to indomethacin and phenazone (prostaglandin-synthesis inhibitory substances) did not lead to an increase of the acetylcholine-induced spasm. Salcylamide can, after a tolerability test, be recommended as alternative analgesic in the analgesics-asthma-syndrome in a dosage of 500 mg.

Analgesics↗

[Alpha rhythm during open eye derivation in infantile brain damaged and normal children].

1. The behavior of the occipital alpha rhythm during open-eye derivation was studied on nine- to twelve-year-old boys of normal intelligence, of whom ten were free from brain injuries and eleven had been suffering from brain injuries in early childhood. 2. There was observed a marked tendency of the alpha index to differ in dependence upon the time of testing, the cause of which was believed to be a weakness of vigilance on the part of brain-injured children. 3. Application of this simple method of examination to group comparisons makes it possible to neurophysiologically determine an important part of chronic cerebropsychic axis syndromes.

Alpha Rhythm↗

The transposable element IS4712 prevents S-layer gene (sbsA) expression in Bacillus stearothermophilus and also affects the synthesis of altered surface layer proteins.

Cell surface (S)-layer protein synthesis in Bacillus stearothermophilus PV72/p6 is blocked when cells are grown at elevated temperature. From a culture exhibiting the S-layer-negative phenotype, the S-layer deficient mutant T5 (SbsA-) was isolated. Genetic analysis of the S-layer-encoding gene (sbsA) of mutant T5 revealed an insertion element (IS4712) integrated into the upstream regulatory region of the S-layer gene, thereby blocking sbsA transcription. The insertion element consists of 1371 base pairs which are flanked by two perfect inverted terminal repeats. Sequence similarity to other transposases of the IS4 family was detected. DNA-DNA hybridizations demonstrated that multiple homologues of IS4712 were also present within the genomes of several other thermophilic bacillus isolates. Attempts to isolate SbsA+ revertants failed. Instead, cells with altered surface proteins were detected. The synthesis of the altered S-layer proteins was correlated with the presence of IS4712 along with the occurrence of deletions in the sbsA coding region. Furthermore imprecise excision of IS4712 was detected. This work demonstrated that B. stearothermophilus is able to express at least four different S-layer proteins and that blocking of sbsA transcription by the insertion element IS4712 is associated with the expression of altered surface proteins.

5' Untranslated Regions↗

Comparison of oral-steroid sparing by high-dose and low-dose inhaled steroid in maintenance treatment of severe asthma.

It is not clear whether high doses of inhaled steroids have a greater sparing effect than low doses on the requirement for systemic steroids. In a randomised, double-blind, multicentre study, we compared the effects of high-dose (1500 micrograms/day) and low-dose (300 micrograms/day) inhaled beclomethasone dipropionate (BDP) in patients with severe asthma requiring a daily oral prednisolone dose of 10-40 mg. During a 3-month run-in period, we tried to achieve optimum asthma control by means of oral steroid and inhaled BDP 300 micrograms/day. The patients were then allocated to high-dose (n = 71) or low-dose (n = 72) treatment by an independent observer who took into account various prognostic factors. BDP was administered by means of an aerosol inhaler with a spacer device. The dose of systemic steroid was reduced as much as possible during the 6-month study period while keeping the peak expiratory flow (PEF) constant and asthma clinically stable. There was no difference between the low-dose and high-dose treatment groups in the mean reduction in oral prednisolone dose achieved by the end of the study (5.2[ SD 7.9] vs 5.0 [9.4] mg/day). The maximum response to inhaled steroid was seen, however, only after several months' therapy in both groups. There were no differences between the groups in use of on-demand beta-agonist inhalations or in asthma symptoms, and PEF values were constant throughout the study. Both doses of BDP were well tolerated. High doses of inhaled steroid offer no further benefit over low doses in the maintenance treatment of severe steroid-dependent asthma when the inhaled steroid is administered with a spacer device.

Administration, Inhalation↗

Reconstruction of a historical genealogy by means of STR analysis and Y-haplotyping of ancient DNA.

Archaeological excavations in St Margaretha's church at Reichersdorf, Germany, in 1993 led to the discovery of eight skeletons, so far assumed to be of the Earls of Königsfeld, who used the church as a family sepulchre over a period of seven generations from 1546 to 1749. DNA-based sex testing and analysis of autosomal short tandem repeat systems (STR) was carried out to confirm the assumption of kinship. Since five of the individuals were determined as males, analysis of Y-specific STRs seemed feasible. A comparison of Y-haplotypes revealed that one individual could not be linked to the Königsfeld patrilineage, an observation supported by autosomal STR evidence. Two individuals typed as females posed an identification problem, since supposedly only male members of the family were buried in St Margaretha's. Nevertheless, these individuals could tentatively be identified as members of the House of Königsfeld through genetic fingerprinting.

Burial↗