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Biomedical subjects

E Zimmer

Publications and source records attributed to E Zimmer.

At least 19 recordsLinked to original sources

Novel amplification unit at chromosome 3q25-q27 in human prostate cancer.

BACKGROUND: In prostate carcinoma, amplification of the genes c-MYC, Her2/NEU, and the androgen receptor gene has been documented, with gene amplification being related to progressive tumor growth. Recently, using comparative genomic hybridization (CGH), we provided evidence for DNA copy number gains at chromosome 3q25-q26 in prostate cancer [Sattler et al.: Prostate 39:79-86, 1999]. METHODS: In this study, additional prostatic tumors were evaluated by CGH to determine the frequency of DNA overrepresentation at 3q. Comparative PCR and Southern blot analyses were applied to determine whether known genes are involved in DNA copy number gains. RESULTS: By CGH, DNA copy number gains, all of which involved chromosome region 3q25-q26, were disclosed in 50% of the prostate tumors analyzed. There was no evidence for high-level amplification. The analysis of 12 genes from 3q25-q27 by comparative PCR revealed amplification in 6 (35.3%) of 17 tumors tested. Amplification was detected for the genes IL12A, MDS1, SLC2A2, and SOX2, with coamplification of three genes in two tumors. IL12A was amplified as single gene in three tumors and in a subline of the DU145 cell line, SLC2A2 in one tumor. CONCLUSIONS: Our studies revealed a novel amplification unit at 3q25-q27 in prostate carcinoma, with the genes IL12A, MDS1, SLC2A2, and SOX2 being located within the amplification unit. A common region of amplification was evident spanning the IL12A gene locus at 3q25-q26.2. Possibly, IL12A indicates an adjacent, till now unidentified gene which is important in the development of prostate cancer.

Blotting, Southern↗

Cardiac compliance in fetuses of diabetic women.

OBJECTIVE: To examine possible changes in cardiac function in fetuses of pregestational diabetic mothers. METHODS: We conducted a prospective longitudinal study of 31 women whose pregnancies were between 22 weeks' gestation and term, and who had pregestational diabetes. All diabetic women included in the study had glycosylated hemoglobin lower than 6.5%. All patients included in the study had an early ultrasound confirming gestational age. Doppler studies of the blood flow through the mitral and tricuspid valves were done every 4 weeks using a pulsed-wave Doppler ultrasound device with a 3.5- or 5-MHz transducer. The following indices were calculated from the flow velocity waveforms: the peak velocity during the rapid ventricular filling (E wave) and during the atrial systole (A wave), and the ratio between these velocities (E/A ratio); and the velocity time integral of the atrioventricular blood flow (this integral correlates with volume flow). A comparison between the Doppler indices obtained in fetuses of diabetic women and of normal women was made by using the Mann-Whitney test. RESULTS: Each patient had four to five fetal echocardiographic examinations at 22, 26, 30, 34, and 38 weeks' gestation. The E/A ratio of the mitral and tricuspid valves did not increase in fetuses of diabetic women during the third trimester and was significantly higher in fetuses of nondiabetic women compared with fetuses of diabetic women at 34 and 38 weeks' gestation. The velocity time integral of the mitral and tricuspid valves multiplied by heart rate was higher, but not significantly, in fetuses of nondiabetic women compared with fetuses of diabetic women at 34 and 38 weeks' gestation. The E-wave of the mitral and tricuspid valves increased in both groups throughout gestation. The A-wave of the mitral and tricuspid valves increased only in fetuses of diabetic women throughout the third trimester and was significantly higher at 34 and 38 weeks' gestation compared with fetuses of nondiabetic women. CONCLUSION: Differences in atrioventricular blood flow patterns between fetuses of diabetic women and normal fetuses do not necessarily result from differences in cardiac compliance.

Diabetes, Gestational↗

Glucose metabolism in the yeast Schwanniomyces castellii: role of phosphorylation site I and an alternative respiratory pathway.

Glucose metabolism in a Crabtree-negative yeast, Schwanniomyces castellii, and a cytochrome b-deficient mutant of this strain was investigated in chemostat culture. The wild-type and mutant strains exhibited the same behavior. Oxidative metabolism was observed when the substrate uptake rate (qS) was low. Fermentative metabolites were excreted when the qS value was higher than 0.40 g.g-1.h-1, indicating the occurrence of a respirofermentative metabolism; however, the respiratory quotient (RQ) remained near 1. When fermentation occurred, the cytochrome pathway was repressed but not the salicylhydroxamic acid (SHAM)-sensitive pathway. The presence of an alternative SHAM-sensitive respiratory pathway and the presence of phosphorylation site I in all metabolic conditions explained the RQ value of 1 and accounted for high biomass yields in oxidative metabolism conditions (0.62 g.g-1 for the wild-type strain and 0.31 g.g-1 for the cytochrome b-deficient mutant strain).

Biomass↗

The CYP2D6B allele is not overrepresented in a population of German patients with idiopathic Parkinson's disease.

The frequency of the CYP2D6B allele of the gene for debrisoquine 4-hydroxylase was studied in 115 patients with sporadic idiopathic Parkinson's disease, 55 of their healthy siblings, 63 patients with familial Parkinson's disease, 55 unaffected relatives, and 92 patients with Alzheimer's disease and 73 age matched healthy controls. By contrast with several previous studies, no significant variation of allele frequencies could be found between any of the groups studied. The results argue against a significant role of the CYP2D6 gene in the aetiology of sporadic and familial idiopathic parkinsonism in this patient population.

Aged↗

A multidirectional sonographic approach to elevated amniotic alpha-fetoprotein or positive acetylcholinesterase.

OBJECTIVE: To evaluate the combined transvaginal and transumbilical ultrasonographic approach in cases of elevated amniotic fluid (AF) alpha-fetoprotein (AFP) and/or acetylcholinesterase in the second trimester. METHODS: Nine pregnant women with normal sonographic results were referred because of elevated AF AFP and/or acetylcholinesterase and screened using a transvaginal and transumbilical 6.5-MHz ultrasound transducer. All women were at 17-21 weeks' gestation. The fetal skull and the vertebral column were scanned in both perpendicular and tangential planes for maximal exploitation of the axial resolution of the transducer, in both directions and in two to three planes. RESULTS: Despite increased AF AFP and/or present acetylcholinesterase, no fetal malformation was detected in any of the nine cases. Open neural tube defects were not detected by the diagnostic technique. All nine women were delivered of term healthy neonates without malformations. CONCLUSION: Our preliminary data suggest that targeted sonographic screening combining transvaginal and transumbilical approaches may reliably rule out an open neural tube defect larger than 0.3 mm. This may influence the decision-making process when termination of pregnancy is considered in cases of high AF AFP and/or positive acetylcholinesterase.

Acetylcholinesterase↗

Immunonephelometric determination of the C4b-binding protein.

A fully mechanised immunonephelometric method for the rapid and specific determination of C4b-binding protein (C4b-BP) in citrated plasma is described. The method utilizes commercially available rabbit antiserum against human C4b-BP and a nephelometer analyser. A single determination can be performed within 6 min, requiring 80 microliters sample volume. The measuring range is about 10 to 200% of normal C4b-BP. Precision is characterized by intraassay coefficients of variation between 1.5% and 2.8%, and interassay coefficients of variation between 4.0% and 4.6% for the same C4b-BP concentrations. The nephelometry of C4b-BP was correlated with electroimmunodiffusion (Laurell technique; r = 0.863, y = 0.909x+7.091, n = 79). C4b-BP concentrations (143%, 96-223%; median and 2.5th-97.5th percentile) from 83 subjects with increased inflammation markers C-reactive protein (> 10 mg/l), and fibrinogen (> 4.5 g/l) showing significantly higher C4b-BP concentrations compared to 151 obviously healthy subjects (97%, 68-141%; p < 0.001). In contrast to 81 patients with therapeutic heparinisation (90%, 60-131%) significant decreased concentrations were found in 90 subjects under oral anticoagulant therapy (OAT) in the stable state (78%, 44-125%; p < 0.001). Depending on different INR levels (< 2.5, n = 40: 71%, 63-85%; > 2.5, n = 50: 81%, 68-92%; median and 25th-75th percentile) no significant differences of C4b-BP concentrations could be measured.

Administration, Oral↗

The effect of atherogenic infusions of the triglyceride-rich, lipid emulsion, Lipofundin-S, on the in vitro growth characteristics of rat aortic smooth muscle cells.

This study shows that arterial smooth muscle cells (SMC) isolated from rats receiving atherogenic doses of the lipid emulsion, Lipofundin-S, alter their in vitro growth properties. Compared to cells from control animals, SMC isolated from Lipofundin-S-infused rats show a reduction in both saturation density and response to increasing serum concentrations, without a change in the baseline proliferation. Also, SMC isolated from lipid-treated animals and grown for five days in the presence of 30, 150, or 300 pg/ml estradiol show a 30% increase in growth vs. cells from controls. Epinephrine at 1 microM stimulates growth in SMC from control rats, while causing no growth enhancement over five days in cells from lipid-infused animals. Thus, atherogenic infusions of Lipofundin-S into rats cause phenotypic changes in arterial SMC which can be passed to successive cell generations in vitro.

Animals↗

First- and second-trimester diagnosis of fetal ocular defects and associated anomalies: report of eight cases.

Ocular cataract, hypertelorism, hypotelorism, anophthalmos, and microphthalmos are rare malformations commonly associated with other fetal anomalies. Previously, ocular malformations were detected only after mid-gestation. Transvaginal sonography allows the detection of many structural fetal anomalies. We describe the case reports of eight ocular anomalies among 1600 fetal screenings by transvaginal sonography at 12-18 weeks' gestation. Severe cataract was correctly diagnosed by transvaginal sonography. However, transvaginal sonography failed to detect moderate cataract in a case of repeat cataract in a subsequent gestation. Anophthalmia may sometimes be secondary to a degenerative process in middle and late pregnancy. In five of the eight described cases, the eye malformations were associated with defects of the central nervous system.

Adult↗

The molecular through ecological genetics of abnormal abdomen. II. Ribosomal DNA polymorphism is associated with the abnormal abdomen syndrome in Drosophila mercatorum.

Restriction endonuclease cleavage analyses of cloned and genomic DNA samples indicate that the structure of the DNA encoding the large cytoplasmic RNAs (rDNAs) is altered in Drosophila mercatorum lines which exhibit an abnormal abdomen (aa) phenotype. In a majority of the rDNA repeat units from aa flies, the 28S coding sequence is interrupted by a large [5-6 kilobase pairs (kbp)] insert. A subclone containing this inserted DNA (ins 3) hybridizes primarily to rDNA-containing sequences in in situ and genomic blot hybridization experiments. Additionally, genomic nitrocellulose blot hybridization analyses show that ins- containing rDNA repeat units are clustered in a spontaneously arising aa mutant. This rDNA alteration in D. mercatorum flies with the aa phenotype more closely resembles the bobbed (bb) defect of D. hydei than the bb defect of D. melanogaster, which involves alterations in rDNA copy number. By analogy with the other Drosophila systems, we propose that the altered D. mercatorum rDNA repeat units are defective in rRNA production at a critical stage. The lowered levels of rRNA ultimately would limit the concentration of ribosomes needed to produce large quantities of a protein (in these cases, juvenile hormone esterase) needed for normal development.

Abdomen↗

Hyperfibrinolysis and hypercholesterolaemia in salt-intoxication in pigs.

Non-acute salt-intoxication in pigs leads to hyperfibrinolysis and a continuous rise in cholesterol due to an increase in the LDL fraction. Morphologically, spherical microthrombi, vascular wall infiltration and changes to organs have been found, as have also been described in shock or stress situations.

Animals↗

Molecular evidence for genetic exchanges among ribosomal genes on nonhomologous chromosomes in man and apes.

We have found that human and ape ribosomal genes undergo concerted evolution involving genetic exchanges among nucleolus organizers on nonhomologous chromosomes. This conclusion is based upon restriction enzyme analysis of the ribosomal gene families in man and five ape species. Certain structural features were found to differ among (but not within) species even though the ribosomal genes have a multichromosomal distribution. Genetic exchanges among nucleolus organizer regions may be related to the well-known phenomenon of acrocentric chromosome associations observed in man and apes. Length variation in a region of the nontranscribed spacer was found in both chimpanzee species we examined. The nature of this length variation was found to be identical to that previously described in man. The origin of the length variation and its polymorphism within these three species might be explained by unequal alignment and unequal cross-over among the ribosomal genes. An especially surprising finding was a nucleotide sequence polymorphism present in each individual human and ape we examined. Some ribosomal genes of each individual have a HindII site in the 28S gene about 800 base pairs from the EcoRI site in this gene. The remaining 28S genes lack this HindII site. The presence of this polymorphism within individuals of every species we examined suggests that it has been maintained by natural selection.

Animals↗

[Laboratory procedures in adenoviruses. IV. The influence of antiglobulin and complement on neutralization and hemagglutination-inhibition (author's transl)].

The neutralization of adenovirus 3,7, and 19 by rabbit antisera is enhanced by additional application of antirabbit globulin. All sera investigated, obtained early or late after the start of immunization, showed two- to sixfold titer rises. Complement also enhances the neutralization; the titer is raised to a greater extent in early than in late sera. To achieve maximal effects, antiglobulin and complement had to be used in fairly high concentration (ca. 10%). In hemagglutination-inhibition the same set of sera showed a titer increase mediated by anti-rabbit globulin (mostly by the factor 2 to 4), while complement was without influence. The neutralization titer of human sera from patients with adenovirus infections, as opposed to the rabbit antisera, was only slightly increased by addition of anti-human globulin or complement. These reagents had likewise negligible influence on the hemagglutination-inhibition of adenovirus 8 by human sera.

Adenoviridae Infections↗