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Biomedical subjects

H Müller

Publications and source records attributed to H Müller.

At least 325 records · Page 18Linked to original sources

Hematologic effects of recombinant human interleukin-6 in dogs exposed to a total-body radiation dose of 2.4 Gy.

The hematologic effects of recombinant human interleukin-6 (rhIL-6) were studied in dogs exposed to a total-body irradiation (TBI) of 2.4 Gy. IL-6 was administered over a period of 14 days at a daily dose of 18 micrograms/kg by single subcutaneous injection. Treatment was started 1 day after TBI. The data obtained for the different hematologic parameters of the irradiated IL-6-treated dogs were compared with the data obtained from dogs who received TBI of 2.4 Gy and were treated with the carrier (control). No clear influence of IL-6 treatment on the pattern of recovery of lymphocytes could be detected in comparison to the irradiated control animals. The thrombocyte counts in the period from day 1 to 16 after TBI were similar for both groups of dogs, showing a sharp decrease in counts between days 6 and 12 with a stabilization thereafter at approximately 30 x 10(3)/microL. In three of the four IL-6-treated dogs, however, thrombocyte counts increased at day 18 after the beginning of treatment. This increase occurred 7 days earlier than in the controls. In two of the three dogs showing an accelerated recovery of platelet counts, however, treatment with IL-6 caused a strong decrease in the erythrocyte counts associated with a prolonged depression in reticulocyte concentration. There was no influence on the recovery of blood granulocytes. In one of the animals responding with an accelerated thrombocyte recovery, IL-6 had no adverse effect on erythropoiesis. However, IL-6 forced the recovery of blood granulocytes in the period beyond day 10 after TBI. Another animal showed no influence of IL-6 on thrombocyte recovery but a strong depressive effect on erythrocyte and reticulocyte counts. The results show that for standardized conditions of radiation-induced bone marrow damage, the pattern of response to IL-6 in different hematopoietic lineages may show considerable variations between individuals, in contrast to what has been observed in irradiated animals treated with granulocyte-macrophage or granulocyte colony-stimulating factor (GM- or G-CSF).

Animals↗

[Anemia in puerperium--a retrospective analysis].

In 10,393 patients delivered in our hospital between 4/1986 and 8/1992 prevalence of anemia post partum was determined retrospectively. Post partum anemia was classified according to blood hemoglobin content: mild to moderate anemia (6.0-7.0 mmol/l) and severe anemia (< 6.0 mmol/l). After exclusion of patients with high intrapartal blood loss and/or febrile puerperium overall prevalence of anemia increased from 33.78% in 1986 to 49.46% in 1992 (p < 0.01). The portion of patients with blood hemoglobin < 5.4 mmol/l remained stable with 5.6% during observation period. The presented data stress the need for general iron supplementation during pregnancy and puerperium.

Adult↗

[Intravenous or oral 131I treatment of hyperthyroidism and thyroid cancer?].

The purpose of this study was to determine differences in 131I biokinetics after oral or intravenous treatment of hyperthyroidism (0.81 GBq) or differentiated thyroid cancer (1.85 GBq) following thyroidectomy. 20 patients with differentiated carcinoma and 20 patients with hyperthyroidism were studied. In each group 10 patients were treated perorally and 10 patients intravenously. The integrated whole-body activities during therapy were significantly lower, by an average 23% (cancer) and 45% (hyperthyroidism) than after oral application. It is most likely that these differences between oral and intravenous application are due to the higher serum activity after intravenous therapy. It is concluded that a higher activity dose of 131I must be given orally to achieve the same target dose as after intravenous application.

Administration, Oral↗

[Analysis of 122 twin deliveries with special reference to morbidity and mortality of the second twin].

122 consecutive twin deliveries between 1986-1992 were analysed retrospectively under special consideration of morbidity and mortality of the second twin. 13.9% of the twin deliveries occurred before the 33rd week of gestation. The cesarean section rate amounted to 49.2%, the first twin was delivered in 5.7%, the second twin in 27%, by vaginal operative methods. Perinatal mortality of the first twin was 3.3%, of the second twin 6.6% (p < 0.01); thus resulting in an overall twin mortality rate of 4.9%. The acidosis-rate of 16.4% in the second twin was significantly above the 9.0% in the first twin. The vaginal operative mode delivery especially contributed to the impaired outcome of the second twin. There was no correlation between the morbidity of the second twin and the time interval between the two deliveries.

Adolescent↗

[Estrogen substitution: effects on lipid, eicosanoid and collagen metabolism in menopause].

Biochemical markers of bone metabolism are not well established as diagnostic tools. Recently, a new radioimmunoassay has been described, that specifically detects the carboxyterminal telopeptide of type I collagen (ICTP). We have used this method in our studies. Ten menopausal women, age 49-64, received 1.25 mg conjugated estrogens (Presomen) within three cycles of 20 days and 8 days pause. Before and under therapy following parameters have been estimated: cholesterol, LDL, HDL, triglycerides, estradiol, FSH, prolactin, thromboxane B2- 6-ketoprostaglandin F1 alpha, ICTP, and the carboxyterminal propeptide of type I procollagen (PICP). Administration of Presomen resulted in significantly increased levels of HDL. Hormonal replacement therapy (HRT) also resulted in significantly decreased levels of cholesterol, LDL, triglycerides, FSH, prolactin, ICTP, and thromboxane B2. PICP and 6-ketoprostaglandin F1 alpha were uneffected by HRT. Our studies confirm the favorable effects of HRT on lipoprotein metabolism. In addition to these findings we noted a beneficial effect on the arachidonic acid metabolism and on the bone resorption, this requires confirmation in clinical trials.

Bone Density↗

Identification of differentially expressed mRNA species by an improved display technique (DDRT-PCR).

We have significantly improved a method originally developed by Liang and Pardee [Science 257 (1992) 967-971] to display a broad spectrum of expressed genes and to detect differences in expression between different cell types. We have analysed various aspects of the technique and have modified it for both, the application to fast and efficient identification of genes and the use with automatic analysis systems. Based on the mathematical background we have devised the appropriate number of optimal PCR primers. We have also introduced nondenaturating gels for separating double stranded fragments as single bands. By applying the method to regenerating mouse liver, we have identified, out of a total of 38,000 bands, about 70 fragments where the expression of the corresponding genes seems to be differentially regulated at different time points. Application of the method to an automatic DNA sequencer was successfully done. Thus, we have confirmed the usefulness and increased the power of the RNA display technique, which we named differential display reverse transcription PCR (DDRT-PCR), and have extended the range of its application.

Animals↗

[Hereditary p53 mutation in a patient with multiple tumors: significance for genetic counseling].

We describe molecular genetic findings in a patient who initially presented with an intermediate teratoma of the testis and who many years later presented with an oligodendro-astrocytoma. In addition he developed a malignant histiocytoma over the scapula, an adenocarcinoma of the stomach and a late stage adenoma of the sigmoid colon. Due to the development of several neoplasms the possibility of either ataxia telangiectasia or Li-Fraumeni syndrome was considered in differential diagnosis. A molecular genetic investigation revealed that both he and his brother carried a germline p53 tumor suppressor gene mutation at codon 248. From this result we conclude that this family belongs to the Li-Fraumeni syndrome. Once characterized as belonging to the Li-Fraumeni syndrome, the remaining members of the family were typed to determine if they too carried the same mutation. The two children of the index patient were shown not to carry the mutation and are therefore at no increased risk of developing any of the Li-Fraumeni spectrum of malignancies. A molecular genetic investigation into similar families could help to prevent the development of additional malignancies as seen in the index patient, as radiotherapy may interfere with the normal function of the p53 protein and this may in turn help to orchestrate DNA repair after radiation.

Adult↗

[Pleomorphic T-cell lymphoma. The diagnostic problems, therapeutic possibilities and infection-induced complications].

A 30-year-old man complained of high fever, resistant to antibiotics, and progressive loss of strength for five weeks. The peripheral blood showed pancytopenia (leucocytes 2200/microliters, platelets 45,000/microliters, haemoglobin 10.7 g/dl). There was also hepatosplenomegaly, abdominal lymph node enlargement, pleural and pericardial effusions and slight excess of lymphocytes in the cerebrospinal fluid. Histological examination of the bone marrow suggested a small-cell pleomorphic T-cell lymphoma, but Hodgkin's disease was also considered. Splenectomy was performed to confirm the diagnosis and treat the pancytopenia. The blood count rapidly returned to normal and the suggestion of Hodgkin's disease was excluded. Intensive chemotherapy (BMFT-ALL protocol) was followed by regression of nearly all the abnormalities, but marrow infiltration persisted. This treatment was discontinued after phase II of induction. After an intercurrent cytomegalovirus infection maintenance treatment with alpha-interferon (up to 5 million units daily) was started. The partial remission remained stable for 22 months. The lymphoma then relapsed but was held in check by further chemotherapy (Dexa-PAMB protocol). For the past 11 months the patient has remained in stable partial remission on treatment with alpha-interferon (3 million units every other day). Frequent infections (sinusitis, diarrhoea, abscess) require close supervision.

Adult↗

Molecular analysis of the neutral trehalase gene from Saccharomyces cerevisiae.

Neutral trehalase (EC 3.2.1.28) is a trehalose hydrolyzing enzyme of the yeast Saccharomyces cerevisiae (App, H., and Holzer, H. (1989) J. Biol. Chem. 264, 17583-17588). The gene of neutral trehalase was cloned by complementation of a neutral trehalase-deficient yeast mutant which was obtained by ethylmethanesulfonate mutagenesis. Three mutants without detectable neutral trehalase activity were obtained and characterized by tetrad analysis and found to belong to the same complementation group. The mutants were transformed with a S. cerevisiae genomic library in YEp24. Two overlapping plasmids were isolated, containing the neutral trehalase gene NTH1 with an open reading frame of 2079 base pairs (bp), encoding a protein of 693 amino acids, corresponding to a molecular mass of 79,569 Da. Several putative TATA boxes were found in the 5'-nontranslated region of the NTH1 gene. In positions -652 to -641 a possible binding sequence for the MIG1 protein, a multicopy inhibitor of the GAL1 promotor, which also binds to the promotor sequences of the SUC2 and the FBP1 gene, was found. The start codon of the neutral trehalase is located about 2500 bp upstream of the centromere 4 consensus sequence elements I, II, and III (Mann, C., and Davis, R. W. (1986) Mol. Cell. Biol. 6, 241-245). Vicinity to a centromere is known to have a depressing influence on the number of plasmid copies per cell. This probably explains why transformation with pNTH does not lead to overexpression of neutral trehalase. The four consensus sequences AATAAA contained in the centromeric elements and reconfirmed by our sequencing data might be polyadenylation signals for NTH1-mRNA transcription termination. Northern blot analysis yielded a single mRNA species of approximately 2.3 kilobase(s). The neutral trehalase protein has a putative cAMP-dependent phosphorylation consensus sequence RRGS from amino acid positions 22-25. Therefore, the previously described activation of neutral trehalase by cAMP-dependent phosphorylation is probably due to phosphorylation of serine 25. Three potential N-glycosylation sites (Asn-X-Ser/Thr) occur in the open reading frame of the neutral trehalase gene. However, no evidence for glycosylation could be detected by Western blotting.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

Function tests on the neuroendocrine hypothalamo-pituitary system following acute midbrain syndrome, with special reference to computertomographical and magnetic resonance imaging results.

Seventeen patients underwent a neuroendocrinological function test at a mean 6.3 years following a severe craniocerebral trauma (CCT) accompanied by midbrain syndrome. An insulin hypoglycaemia test (IHT) and the combined pituitary anterior lobe test (CPALT) were applied. Whereas the IHT as maximum stimulator of the hypothalamo-pituitary system (HPS) showed an adequate reserve capacity, the CPALT yielded a partial limitation of the secretion dynamic in the somatotropic, adrenocorticotropic axis as well as a dysfunction in the FSH secretion. Neuroradiological tests could not establish substantial injury in the regio hypothalamica in any patient.

Adolescent↗

[Determination of the folic acid content of vegetables and fruits using high-performance liquid chromatography (HPLC)].

The folic acid content of vegetables (including potatoes) and fruits was determined by means of high-performance liquid chromatography (HPLC). Free folate (monoglutamate forms) and total folate (monoglutamate+polyglutamate forms) are differentiated. Vegetables contained 27-187 micrograms/100 g and fruits 10-80 micrograms/100 g total folate. The free folate portion ranged from 6.3% to 96.8% (mean 35%) in vegetables and from 11.6% to 89.0% (mean 56%) in fruits. In addition, the results of the quantification of the main folate derivatives tetrahydrofolic acid (THF), 5-methyltetrahydrofolic acid (5-CH3-THF) and 5-formyltetrahydrofolic acid (5-CHO-THF) are presented. The mean values were 70% 5-CH3-THF, 20% 5-CHO-THF and 10% THF. Their total, resulting from the addition of pteroylglutamate equivalences, is comparable with the results of microbiological methods reported in the tables of nutritive values.

Chromatography, High Pressure Liquid↗

[Determination of the folic acid content of grain, cereal products, baked goods and legumes using high-performance liquid chromatography (HPLC)].

The folic acid content of grain, cereal products (including beer), bakery products and legumes was determined by means of high-performance liquid chromatography (HPLC). Free folate (monoglutamate forms) and total folate (monoglutamate + polyglutamate forms) were differentiated. Of the grain analysed, rye, with a mean value of 143 micrograms/100 g, contained more total folate than wheat (mean = 91 micrograms/100 g). The total folate content of bakery products ranged from 14 micrograms/100 g (whole grain rye bread) to 88 micrograms/100 g (crispbread). Beer had a very low total folate content (mean = 3 micrograms/100 ml). The mean of the free folate portion was 76.5% in grain and cereal products and 65.6% in bakery products. Of the legumes analysed, beans (mean = 128 micrograms/100 g) had the highest content of total folate, followed by lentils (103 micrograms/100 g) and peas (57 micrograms/100 g). The mean value of the free folate portion in legumes (73.1%) was comparable with the values of grain, cereal products and bakery products. In addition to tetrahydrofolic acid (THF), 5-methyl-THF and 5-formyl-THF, pteroylglutamic acid (PteGlu) and 10-formyl-PteGlu were determined in all products (except beer). Their proportion (PteGlu + 10-formyl-PteGlu) of the total folate content ranged from 23.5% to 44.4%.

Beer↗

[The determination of the folic acid content of foods of animal origin using high performance liquid chromatography (HPLC)].

The folic acid content of food of animal origin was determined by means of high-performance liquid chromatography (HPLC). Free folate (monoglutamate forms) and total folate (monoglutamate + polyglutamate forms) were differentiated. Liver (bovine 963, hog 136 micrograms/100 g) and kidney (bovine 410, hog 93 micrograms/100 g) contained the highest content of total folate, followed by egg (67 micrograms/100 g), soft cheese (44-62 micrograms/100 g), milk and other dairy products (3-28 micrograms/100 g). Chicken, fish, beef and pork contained only a low content of total folate (1-12 micrograms/100 g). The free folate portion ranged from 14.7 to 100% (mean 69.2%). The main folate derivatives tetrahydrofolic acid (THF), 5-methyl-THF and 5-formyl-THF showed the following distribution. In milk and milk products the mean was 70% for 5-formyl-THF, 20% for 5-methyl-THF and 10% for THF; in the other products the three derivatives were distributed about equally but the range of variation was high.

Animals↗

Environmental behaviour of radionuclides deposited after the reactor accident of Chernobyl and related exposures.

Several radioecological experiences with isotopes of ruthenium, iodine, caesium and barium, obtained after the reactor accident of Chernobyl, are reported. It was found that for a wet deposition barium was the element with the highest retention on grass. The retention of caesium was lower by a factor of 1.6, retention of iodine by a factor of 2.4 and retention of ruthenium by a factor of 3.5. Former data on the caesium transport in cereals from leaves to grain were confirmed. Depending on the conditions the iodine transfer factor for milk varied between 0.002 and 0.007 d.kg-1. The caesium transfer factor for milk was (0.003 +/- 0.0006) d.kg-1 and was found to be relatively constant in the years 1986-1988. In 1991, the values were higher by a factor of 2-5. Radioecological model results of whole-body burdens in Southern Bavaria showed a reduction of the caesium ingestion doses due to countermeasures and spontaneous changes of consumption habits in the first 2 months by a factor of 5 and till the end of 1987 by a factor of 1.5. The model results agree well with the range of measured whole-body burdens. One month after the deposition, the external exposures in urban environments due to ruthenium, caesium and barium isotopes were found to be reduced by a factor of 2, compared with open lawns, in the case of iodine the reduction was even a factor of 2.5. External exposures of a population group from the Munich area were determined by thermoluminescence dosimetry. The results are in accordance with the spectral measurements of external dose rates in urban environments.

Accidents↗