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Biomedical subjects

R Lange

Publications and source records attributed to R Lange.

At least 307 records · Page 17Linked to original sources

Isolation and partial characterization of a cytochrome P-450 isoenzyme (cytochrome P-450tu) from mouse liver tumors.

Experimental hepatomas induced with 5,9-dimethyldibenzo[c,g]carbazole in female XVIInc/Z mice display a strong microsomal steroid 15 alpha-hydroxylation activity. A cytochrome P-450 isoenzyme (cytochrome P-450tu), specific for this activity, has been isolated by an HPLC derived method using various Fractogel TSK and hydroxyapatite supports. On SDS polyacrylamide gel electrophoresis the purified protein appeared as one major band with an apparent Mr of 50,000. Its specific cytochrome P-450 content was 7.55 nmol/mg protein. As deduced from the visible spectrum, the heme iron of the isolated P-450tu was to 72% in the high-spin state. The CO-bound reduced form showed an absorption maximum at 450 nm. In addition to the stereospecific 15 alpha-hydroxylation of progesterone (2.3 min-1) and testosterone (2.5 min-1), the enzyme catalyzed also 7-ethoxycoumarin O-deethylation, benzphetamine N-demethylation and aniline 4-hydroxylation. Its N-terminal amino-acid sequence (21 residues) was identical to that of cytochrome P-450(15) alpha, isolated by Harada and Negishi from liver microsomes of 129/J mice. P-450tu differed from P-450(15) alpha by its higher molecular weight, its 40-times lower steroid 15 alpha-hydroxylation and its 4-times higher benzphetamine N-demethylation.

Amino Acid Sequence↗

On the nature of the cytochrome P450scc "ultimate oxidant": characterization of a productive radical intermediate.

The electron paramagnetic (EPR) properties of a transient species detected during a cytochrome P450 (P450)-mediated peroxidative reaction have been compared with those of peroxidases Compound I and model metalloporphyrins. The reaction which was studied with cholesterol-specific P450scc and (20R)-20-hydroperoxycholesterol, occurred without enzyme denaturation. The resulting transient species, which reached its maximum after 50 s reaction, was characterized by a one-line EPR spectrum, g = 2.0035, delta 1/2 = 1.08 mT. The decay of this radical was concomitant with the production of (20R)-20,21-dihydroxycholesterol. The reaction (almost 100% yield) conserved the stereo-specificity of the natural pathway. We suggest this intermediate is a candidate for the in vivo ultimate oxidant in the P450-mediated hydroxylation process. The comparison of the observed EPR spectrum with those of peroxidase Compound I and related synthetic models allows us to propose a FeIV porphyrin II cation radical structure for the intermediate.

Adrenal Cortex↗

[A new mechanical anastomosis technique in deep anterior resection for Hirschsprung's disease in infancy].

Since 1987 we perform a new technique of colorectal anastomosis in 6 babies resected because of severe Hirschsprung's disease. The operation was done electively in the seventh to eight month of age. In the method of the so-called compression anastomosis the instrument is inserted through the anorectal canal at the head fitted with two plastic rings (see illustrations). In the rectal stump the instrument is opened up, the rectal bowel edge is slipped over the distal ring. The prepared proximal bowel edge is slipped over the second white coloured ring. The rings are approached to one another and the instrument is released. The knife on the inside cuts the bowel. The two rings are then joined by means of springs. The compression anastomosis is completed. The two bowel edges are joined by compression via the two intraluminal plastic rings. These rings will pass spontaneously with the faeces days after operation. The diameter of the rings is 18 mm. Different diameters are available. Our good experiences in more than 160 compression anastomoses in colorectal surgery of adults encouraged us to use the method also in children. We saw one complication of a rectovaginal fistula 4 weeks after the operation followed by a severe stenosis of the anastomosis. The passing of the plastic rings was without any problem in all the cases. In the follow-up a bouginage was required only in the case mentioned above.

Anastomosis, Surgical↗

[Testing in swine of meal extracted from winter rapeseed with different glucosinolate content with regard to iodine supply. 1. Characterization of rapeseed extraction particles and fattening results].

In a feeding experiment with 48 growing pigs 16% high glucosinolate rapeseed meal (HGRSM) (136 mumol glucosinolates + aglucones/kg dry matter, DM) or low glucosinolate (LG) RSM (48 mumol glucosinolates + aglucones/kg DM) in the feed were compared with 14% soya-bean meal (SBM) in each case. It were established 24 pairs of animals, which received the same quantity of the isonitrogenous but not isocaloric diets with SBM and the both RSM (pair fed). Four of the 2.12 animal pairs were not given supplementary I, four received 0.25 mg supplementary I/kg feed. Further four animals which were fed on LGRSM or HGRSM were provided with 0.0625 or 1 mg supplementary I/kg feed. In case of high glucosinolate intake (HGRSM) the lacking I supplementation decreased feed intake and growth and led to remarkable I deficiency symptoms from the fifth week onwards. The 2/3 lower glucosinolate dosage of the LGRSM diet also decreased performance and provoked I deficiency, however significantly later. The investigated I dosages (greater than 0.0625 mg/kg feed) did not effect the performance. In the experiment the eight animals which received LGRSM with supplementary I consumed 13% more feed than animals fed on HGRSM (P less than 0.05). The additional weight gain was 20% (P less than 0.05). Comparing the live weight gain of the SBM and RSM fed animals (pair fed) there was a significant increase of 9% versus the HGRSM groups and 5% versus the LGRSM groups.

Animal Feed↗

Subadult Ixodes ricinus (Acari: Ixodidae) on rodents in Berlin, West Germany.

To identify hosts that may serve as reservoirs for the agent of Lyme disease in Central Europe, we determined whether Ixodes ricinus L. feed most frequently on certain rodents and whether the abundance of these hosts corresponds to the season of feeding activity of the tick in four sites in Berlin, Federal Republic of Germany. In addition, we correlated abundance of I. ricinus with that of particular rodent hosts. Two small rodents were more abundant than any others; a mouse, Apodemus flavicollis, predominated in a wooded site and a vole, Clethrionomys glareolus, in three brush- or grass-covered sites. The tick was most abundant in the mouse-infested site. Although A. flavicollis comprised only about a third of rodents collected, nearly 60% of all such rodent parasitizing I. ricinus fed on this mouse. These ticks were more abundant on mice than voles in each of the study sites and throughout the year, and more larvae fed on these rodents than did nymphs. Although larval as well as nymphal I. ricinus are most abundant during midsummer, they feed on rodents from April through October. Taken together, these observations suggest A. flavicollis as a potentially important reservoir host for I. ricinus-borne infections.

Animals↗

Sperm chromosome studies in an infertile man with partial, complete asynapsis of meiotic bivalents.

Meiotic and sperm chromosome studies were carried out in two semen samples from an infertile man with a 46,XY karyotype, oligoasthenoteratozoospermia and abundant exfoliation of spermatogenic cells. Meiotic preparations showed partial, complete asynapsis in a large proportion of metaphase I figures observed, and absence of metaphase II figures, while 24 of the 30 sperm chromosome karyotypes analysed were normal. The remaining sperm karyotypes were as follows: one with structural abnormalities, one with both structural abnormalities and hypohaploidy and four with hypohaploidy. The total frequency of chromosomal abnormalities (6.7%) is similar to that obtained by us in normal men (10.9%). The frequency of spermatozoa with structural abnormalities (6.7%) was not significantly different from that obtained by us in normal men (6.9%). These results suggest that, in some cases, asynaptic spermatogenic cells do not proceed further than metaphase I and only normal germ cells continue spermatogenesis.

Adult↗

Monitoring therapy with a gonadotropin-releasing hormone analog: utility of MR imaging.

The utility of magnetic resonance (MR) imaging in assessing response to therapy with a gonadotropin-releasing hormone (GnRH) analog was assessed in 19 women with uterine leiomyomas and 19 women with endometriosis. There was a significant reduction in individual fibroid volumes at 3 months (P less than .05) and at 6 months (P less than .005) in the drug group, whereas there was no significant change in the placebo group. Vessel conspicuity significantly decreased at 3 months (P less than .02) and at 6 months (P less than .01) in the drug group but not in the placebo group. In the patients with endometriosis, there was a significant decrease (P less than .0006) in the number of endometriomas visualized. Significant changes were also noted in the pelvis in women who were receiving the GnRH analog. After 6 months of therapy, the identifiability of the ovaries was significantly poorer (P less than .05). The authors conclude that the utility of conservative therapy with a GnRH analog can be quantitatively assessed with MR imaging.

Abdominal Neoplasms↗

Meniscal abnormalities in the asymptomatic population at MR imaging.

Two hundred eighty meniscal horns in 64 asymptomatic volunteers in the 2nd to 8th decades of life were analyzed for meniscal abnormalities. Grade 1, 2, and 3 changes were present in essentially all decades. There was at least a 25% prevalence of meniscal signal abnormalities as early as the 2nd decade. The prevalence of meniscal abnormalities increased sharply with age. The prevalence of all signal abnormalities correlated with age, grade 2 changes having the highest correlation coefficient (+.88). The correlation coefficient for grades 1 and 3 changes were +.60 and +.71, respectively. The posterior horn of the medial meniscus had a significantly higher (P less than .02) prevalence of abnormalities than did the other meniscal locations. There was no significant correlation between subject weight or sex and meniscal signal. The authors conclude that there is a baseline prevalence of meniscal signal in the asymptomatic population.

Adolescent↗

Effect of varying glucosinolate and iodine intake via rapeseed meal diets on serum thyroid hormone level and total iodine in the thyroid in growing pigs.

In a trial with 50 fattening pigs (20 kg initial body weight), the effect of untreated rapeseed meal (RSM) (148 mmol glucosinolates and aglucones per kg dry matter) on the thyroid was compared with RSM treated with Cu2+ (9.5 mmol glucosinolates and aglucones per kg dry matter) and soybean meal (SBM). The diets containing 8% RSM were supplemented with 0.0625-1.0 and the SBM diet (control) with 0.125 mg iodine kg-1 (I). In comparison with SBM fed control, RSM treatment with Cu2+ resulted in a complete normalization of feed intake and growth. Only untreated RSM without I supplementation depressed performance and resulted in symptoms of I deficiency, but the thyroid and liver weight were also increased and the serum T4 content was significantly reduced in animals which were given RSM not supplemented with I, but treated with Cu2+. In young pigs (4 weeks) a plateau of the serum T4 content was achieved from 0.5 mg I kg-1 of the RSM diet onwards. In contrast, when the concentration of goitrogens was reduced by the treatment with Cu2+, the serum T4 level was increased significantly in groups fed with 0.125 mg I kg-1 diet and more. In older pigs (15 weeks) neither the content of goitrogens nor the I dosage affected the serum T4 level. On the other hand, the I content in the thyroid was a good indicator of the different goitrogenicity of the diet in the case of a low I supply. The present investigations show that pig diets with RSM (greater than 10 mmol glucosinolates and aglucones kg-1) should contain at least 0.5 mg I kg-1, but 0.1 mg supplementary I per kg is sufficient in diets without or with a low content (less than 1 mmol glucosinolates and aglucones per kg-1) of antithyroid compounds.

Animal Feed↗

Rat liver microsomal progesterone metabolism: evidence for differential troleandomycin and pregnenolone 16 alpha-carbonitrile inductive effects in the cytochrome P-450 III family.

The effect of Troleandomycin (TAO) and pregnenolone 16 alpha-carbonitrile (PCN) on the hepatic microsomal progesterone metabolism in the rat is evaluated. Over thirteen hydroxylated progesterone derivatives are detected, including the novel 6 beta, 21-, 6 beta, 16 alpha-, 6 beta, 16 beta- and 2,21-dihydroxy derivatives, suggesting the induction of several cytochrome P-450 isozymes. PCN treatment results overall in an augmented production of progesterone metabolites whereas TAO treatment both induces and represses specific hydroxylase activities. Progesterone metabolism with purified isozymes isolated from liver microsomes from TAO and PCN treated rats differs significantly from that observed with intact microsomes, reflecting the complexity of the induction pattern of the cytochrome P-450 III family.

Animals↗

Particular cytochrome P-450-dependent steroid metabolism: a new class of mouse liver tumor markers.

An altered pattern of cytochrome P-450-dependent microsomal steroid metabolism was identified in female mouse liver tumors induced by 5,9-dimethyldibenzo[c,g]carbazole, a potent organo-specific liver carcinogen. These tumor tissues were compared to extratumoral liver parenchyme, to normal, fetal and neonatal livers and to spontaneous liver tumors, the frequency of which is very low in the highly hybridized mouse strain (XVIInc/Z) used for liver tumorigenesis. Cytochrome P-450-dependent steroid hydroxylase activities were measured by the identification and quantification of four monohydroxyprogesterone and eight monohydroxytestosterone metabolites. In contrast to a general decrease (50%) of total P-450 in tumor microsomes, the individual steroid hydroxylases were regulated differently. Progesterone 16 alpha- and testosterone 6 alpha-, 6 beta-, 7 alpha- and 16 alpha-hydroxylase activities were decreased 50%, and more, whereas progesterone and testosterone 15 alpha-hydroxylase activities were raised 3-4 times with regard to microsomal protein content and 6-7 times with regard to total P-450. Consequently the most prominent feature of the steroid metabolism by tumor-borne microsomes is the hydroxylation at the 15 alpha-position. Furthermore, minor testosterone 2- and 15 beta-hydroxylase activities showed equally an increase of approximately 4 times (8 times with regard to total P-450). The observed new tumoral pattern of P-450-dependent microsomal steroid metabolism appearing characteristically in spontaneous and chemically induced liver tumors indicates that particular P-450 enzymes are strongly expressed in mouse liver tumors. These enzymes may be used as markers for early stages in liver tumorigenesis.

Aging↗

Chernobyl source term, atmospheric dispersion, and dose estimation.

The Chernobyl source term available for long-range transport was estimated by integration of radiological measurements with atmospheric dispersion modeling and by reactor core radionuclide inventory estimation in conjunction with WASH-1400 release fractions associated with specific chemical groups. These analyses indicated that essentially all of the noble gases, 60% of the radioiodines, 40% of the radiocesium, 10% of the tellurium, and about 1% or less of the more refractory elements were released. Atmospheric dispersion modeling of the radioactive cloud over the Northern Hemisphere revealed that the cloud became segmented during the first day, with the lower section heading toward Scandinavia and the upper part heading in a southeasterly direction with subsequent transport across Asia to Japan, the North Pacific, and the west coast of North America. The inhalation doses due to direct cloud exposure were estimated to exceed 10 mGy near the Chernobyl area, to range between 0.1 and 0.001 mGy within most of Europe, and to be generally less than 0.00001 mGy within the United States. The Chernobyl source term was several orders of magnitude greater than those associated with the Windscale and TMI reactor accidents. However, the 137Cs from the Chernobyl event is about 6% of that released by the U.S. and U.S.S.R. atmospheric nuclear weapon tests, while the 131I and 90Sr released by the Chernobyl accident was only about 0.1% of that released by the weapon tests.

Accidents↗

Uterine junctional zone: MR study of water content and relaxation properties.

Weighted samples of uterine myometrium, junctional zone, and endometrium were excised for determination of T1 and T2 in a 20-MHz spectrometer and then dried for determination of water content. The remainder of each uterus, examined with special histopathologic stains, demonstrated no significant difference in the number of blood vessels, smooth muscle cells, fibroblasts, elastin, iron, collagen, mucin, polysaccharide, or amyloid. The junctional zone water content (79.28%) was significantly lower than that of endometrium (82.88%, P = .004) and myometrium (81.05%, P = .005). The T1 of the junctional zone (ie, 643) was significantly lower than that of endometrium (ie, 836; P = .004) and myometrium (ie, 709; P = .01). The T2 of the junctional zone (ie, 58) was significantly lower than that of endometrium (ie, 87; P = .003) and myometrium (ie, 67; P = .006). The low signal intensity of the junctional zone on T2-weighted MR images is accounted for by its lower water content and T2, while the brightness on T1-weighted images is due to its reduced T1.

Adult↗

[Diagnosis of thyroid function in uterine myomatosis].

A correlation between thyroid disease and uterine myoma has been discussed till the fourth decade of this century. Since then, this possible connection was given no further notice. We examined 79 women needing a hysterectomy for various reasons regarding myometrial histology, thyroid function and thyroid antibodies. The patient group bearing myomas showed significantly more frequent (23%) pathological TRH/TSH stimulation tests results than the control group (3.7%, p = 0.0543). 10 of 22 patients with myomas had microsomal and/or thyroglobin antibodies, compared with none in the control group (n = 17, p = 0.0019). Therefore regarding these results a connection between thyroid disease and uterine myoma should undergo a more detailed examination.

Adult↗