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H Müller

Publications and source records attributed to H Müller.

At least 127 records · Page 7Linked to original sources
PubMed2000

Three novel paralogs of the rodent prolactin gene family.

The prolactin (PRL) family consists of a collection of genes expressed in the uterus, placenta and anterior pituitary. These cytokines/hormones participate in the control of maternal-fetal adaptations to pregnancy. In this report, we establish the presence of three new members of the PRL family. Novel expressed sequence tags (ESTs) with homology to PRL were isolated from embryonic and placental cDNA libraries. The cDNAs were sequenced and compared with those of other members of the PRL family. The three new cDNAs were assigned to the PRL family on the basis of sequence similarities and were referred to as PRL-like protein-J (PLP-J), PRL-like protein-K (PLP-K) and PRL-like protein-M (PLP-M). Both rat and mouse PLP-J cDNAs were identified. Rat PLP-J cDNA encodes for a predicted 211 amino acid protein containing a 29 amino acid signal peptide and two putative N-linked glycosylation sites, whereas the mouse PLP-J cDNA encodes for a 212 amino acid protein containing a 29 amino acid signal peptide with a single N-linked glycosylation site. Rat and mouse PLP-J proteins share approximately 79% and 70% nucleotide and amino acid sequence identity, respectively. A full-length rat PLP-K cDNA and a partial tentative mouse PLP-K cDNA were identified. The rat PLP-K cDNA encodes for a predicted 228 amino acid protein containing a 31 amino acid signal peptide and one putative N-linked glycosylation site; the mouse PLP-M cDNA encodes for a predicted 228 amino acid protein containing a 28 amino acid signal peptide and one putative N-linked glycosylation site. Genes for PLP-J, PLP-K and PLP-M are situated at the Prl family locus on mouse chromosome 13. PLP-J was exclusively expressed in decidual tissue from both the mouse and rat. PLP-K was expressed in trophoblast cells of the chorioallantoic placenta and showed an apparent species difference. In the mouse, virtually all trophoblast lineages expressed PLP-K, whereas in the rat, PLP-K expression was restricted to the labyrinthine trophoblast cells. Mouse PLP-M expression was restricted to the junctional zone of the chorioallantoic placenta. In summary, we have identified three new members of the rodent PRL gene family that are expressed in uterine and placental structures. Future experimentation is needed to determine the specific roles of each of these ligands in the biology of pregnancy.

Amino Acid Sequence↗
PubMed2000

Eosinophils are cellular targets of the novel uteroplacental heparin-binding cytokine decidual/trophoblast prolactin-related protein.

The uterus and placenta of the mouse and rat produce a member of the prolactin (PRL) family referred to as decidual/trophoblast PRL-related protein (d/tPRP). This cytokine/hormone has been hypothesized to regulate decidual cell activities needed for the establishment and maintenance of gestation. An alkaline phosphatase (AP)-tagging strategy was used to identify d/tPRP target cells. AP-d/tPRP bound to virtually all cells and tissues to which it was exposed, consistent with our earlier evidence that d/tPRP binds to heparin-containing molecules. Moreover, we found that co-incubation with heparin or pretreatment with heparitinase greatly decreased the binding of AP-d/tPRP to tissue sections. In addition, we observed that the AP-d/tPRP probe bound to the surface of Chinese hamster ovary (CHO) cells but not to heparan sulfate-deficient CHO-pgsD-677 cells. Potential unique non-heparin d/tPRP binding sites within mouse and rat uteroplacental tissues were identified by consecutively incubating sections with AP-d/tPRP followed by heparin. This strategy led to the identification of d/tPRP target cells associated with the uterus and the labyrinth zone of the chorioallantoic placenta. Within the uterus, d/tPRP specifically bound to eosinophils. d/tPRP-binding and eosinophil peroxidase activity were co-localized and showed similar patterns of distribution during the estrous cycle, pregnancy, and following hormonal manipulation. d/tPRP interactions with eosinophils were further demonstrated in the lung and intestine, with eosinophils isolated from the peritoneum, and in mice with generalized tissue eosinophilia. Collectively, these findings suggest that intercellular d/tPRP targeting is mediated through associations with heparin-containing molecules which help direct d/tPRP to specific interactions with eosinophils within the uterus and with the labyrinthine compartment of the chorioallantoic placenta.

Animals↗
PubMed2000

Cell cycle-dependent AgNOR analysis in invasive breast cancer.

OBJECTIVE: To investigate to what extent analysis of silver-stained nucleolar organizer regions (AgNORs) is cell cycle dependent in breast cancer and to assess the prognostic value of an AgNOR analysis that takes into consideration the cell cycle status of tumor cells. STUDY DESIGN: In 97 cases of invasive breast carcinoma, morphometric AgNOR analysis was performed in tumor cells with immunohistochemical MIB-1 reactivity (NORcyc analysis) and in MIB-1-negative tumor cells (NORnon analysis). Additionally, conventional (NORconv) analysis without preceding MIB-1 staining was done. Findings were compared with the Nottingham prognostic index (NPI). RESULTS: In comparison to noncycling tumor cells, cycling ones exhibited significantly higher AgNOR numbers (mean values, 3.84 +/- 1.09 vs. 2.40 +/- 0.78 per nucleus), higher total AgNOR areas (5.95 +/- 3.17 vs. 5.62 +/- 3.05 micron 2, NS) and significantly lower mean AgNOR areas (2.08 +/- 1.14 vs. 2.93 +/- 1.69 micron 2). When related to NPI, correlation coefficients of NORnon analysis were higher than those of NORcyc analysis but lower than those of NORconv analysis. Among the different AgNOR parameters, total AgNOR area correlated best with NPI. CONCLUSION: Cell cycle status has a high impact on AgNOR analysis. However, the best prognostic information in breast cancer is derived from an AgNOR analysis that considers both cycling and noncycling tumor cells.

Adult↗
PubMed2000

Correlation and function in Cerec 3.

The Correlation and Function modes are valuable assistants for an anatomical occlusal surface design in the Cerec method. Because of the extensive improvements of the Cerec 3 software, particularly the Correlation mode considerably simplifies the clinical procedure. Correlation works so accurately that even with small restorations, provided that the initial situation is anatomically correct, a second exposure is worthwhile, since the intraoral corrections on the occlusal surface are reduced to a minimum by the use of Correlation. The Correlation algorithm also brings somewhat incongruent exposures into exact alignment. With this principle and the enormous progress made in the hardware, further exceptional development of the Cerec occlusal surface can be expected.

Algorithms↗
PubMed2000

Correlation with Cerec 3 for end teeth: single-side correlation.

Correlation is not necessarily a problem for end teeth any longer. All the advantages of Correlation, anatomical occlusal surfaces, and very slight vertical occlusion adjustment are also available with the described method for end teeth and gaps.

Computer-Aided Design↗
PubMed1999

[Identification and genetic counseling of people with HNPCC (hereditary nonpolyposis colorectal cancer): old and new research goals].

Hereditary non-polyposis colorectal cancer (HNPCC) is a relatively common autosomal dominantly inherited predisposition leading to a familial occurrence of cancer of the colon, rectum, endometrium and some other organs. Cancer mortality can be significantly reduced by appropriate intervention. The diagnosis of HNPCC is suspected on the basis of early onset and multiple foci of colorectal cancer (CRC), in many cases affecting the proximal part of the colon, and of endometrial cancer. It may be confirmed by molecular genetic analysis of the mismatch repair genes, especially hMLH1 and hMSH2. In spite of considerable progress in the understanding of hereditary colon cancer, many questions which are of basic importance for the identification and appropriate genetic counselling of gene carriers remain to be answered. HNPCC defined on clinical and genealogical grounds is by no means identical with the presence of mutated mismatch-repair genes. This impedes the identification of persons/families at increased cancer risk. Mutations of other, mainly as yet unidentified genes may lead to a similar phenotype. Not only heterogeneity of the predispositions underlying CRC, but also penetrance and expressivity of the identifiable mutations of the MMR-genes, have been explored only superficially. The process of carcinogenesis in the colon can follow different routes depending on the genetic background of the patients. Its investigation will open up new possibilities of cancer prevention. In addition, genetic counselling must be developed into a more "evidence"-based medical undertaking. These gaps in the understanding of hereditary CRC and in the care of persons at risk can only be overcome through structured collaboration between family doctors, medical specialists such as gastroenterologists, oncologists and surgeons, medical geneticists and basic researchers.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Effect of plasminogen activators on human recombinant apolipoprotein(a) having the plasminogen activation cleavage site.

The serine-proteinase domain in human apolipoprotein(a) [apo(a)] and plasminogen exhibit 89% sequence identity including the catalytic triad. Cleavage of the Arg(561)-Val(562) activation site in plasminogen by either tissue- or urokinase-type plasminogen activator results in formation of the fibrinolytic enzyme plasmin. Apo(a) does not contain measurable amidolytic activity nor can it be activated by plasminogen activators. It has been suggested that the latter finding might be explained by the substitution of the plasminogen Arg-Val activation site by Ser-Ile in apo(a). To investigate if introduction of the Arg-Val activation site in apo(a) might result in sensitivity towards plasminogen activators, we expressed wild-type and Arg-Val mutant recombinant apo(a) [r-apo(a)] in human embryonic kidney and hepatocyte cell lines. Free r-apo(a) and lipoprotein-like particles [r-Lp(a)] were obtained in the culture supernatants of transfected 293 and HepG2 cells, respectively. Incubation of mutant r-apo(a)/r-Lp(a) with plasminogen activators produced neither plasmin-like activity nor cleavage at the Arg-Val activation site, even in the presence of various stimulators of plasminogen activation. Our data suggest that the high selectivity of activators for plasminogen activation requires interactions with regions in plasminogen distant from the activation disulfide loop which are not present in apo(a).

Amino Acid Sequence↗
PubMed1999

The single-crystal structure of the organic superconductor betaCO-(BEDT-TTF)2I3 from a powder grain.

Synchrotron radiation diffraction data have been collected at 200 K on a microscopic single crystal (dimensions 12 x 10 x 2 µm) of the title compound, where BEDT-TTF is bis(ethylenedithio)tetrathiafulvalene, C(10)H(8)S(8). The quality of the diffraction data allowed a full structure refinement and enabled the determination of structural details such as the conformations of the ethylene groups as well as the occupancy of the triiodide sites. The compound was found to be slightly iodine-deficient and better described as beta(CO)-(BEDT-TTF)(2)I(3-x) [x = 0.014 (3)]. One of the ethylene groups of the BEDT-TTF cation is disordered at this temperature and exists in two distinct conformations with occupancies which are identical within the standard uncertainty.

Journal Article↗
PubMed1999

Functional staging of ADP/ATP carrier translocation across the outer mitochondrial membrane.

The ADP/ATP carrier (AAC) is the major representative of the inner membrane carrier proteins of mitochondria that are synthesized without cleavable presequences. The characterization of the import pathway of AAC into mitochondria has mainly depended on an operational staging system. Here, we introduce two approaches for analyzing the import of AAC, blue native electrophoresis and folding-induced translocation arrest, that allow a functional staging of AAC transport across the outer membrane. (i) Blue native electrophoresis permits a direct monitoring of the receptor stage of AAC and its chase into mitochondria. Binding to this stage requires the receptor protein Tom70 but not Tom37 or Tom20. (ii) A fusion protein between AAC and dihydrofolate reductase can be selectively arrested in the general import pore complex of the outer membrane by ligand induced folding of the passenger protein. Cross-linking demonstrates that the arrested preprotein is in close contact not only with several receptors and Tim10 but also with the channel protein Tom40, providing the first direct evidence that cleavable preproteins and carrier preproteins interact with the same outer membrane channel. The staging system presented here permits a molecular dissection of AAC transport across the outer mitochondrial membrane, relates it to functional units of the translocases, and indicates a coordinated and successive cooperation of distinct translocase subcomplexes during transfer of the preprotein.

Adenosine Diphosphate↗
PubMed1999

N-acetyltransferase 2 influences cancer prevalence in hMLH1/hMSH2 mutation carriers.

Hereditary nonpolyposis colorectal cancer (HNPCC), an inherited cancer predisposition syndrome, has been associated with germline mutations in DNA mismatch repair (MMR) genes. Because a deficiency in MMR does not predict a specific cancer phenotype, modifying genes may account in part for the variation in disease expression. We determined the N-acetyltransferase 2 (NAT2) genotype in 26 unaffected and 52 cancer-affected hMLH1/hMSH2 mutation carriers coming from 21 Swiss HNPCC families. Slow acetylators were found to be significantly (P < 0.03) more prevalent in the group of affected mutation carriers. Our results suggest a protective effect of the NAT2 rapid acetylator phenotype, an observation that could have implications for genetic counseling and management of MMR gene mutation carriers.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Influence of selection criteria on mutation detection in patients with hereditary nonpolyposis colorectal cancer.

BACKGROUND: Hereditary nonpolyposis colorectal cancer (HNPCC) is linked genetically to mutations in DNA mismatch repair (MMR) genes. Because a deficiency in MMR does not predict a specific phenotype, the original selection criteria may be too restrictive in identifying additional families. The current study was performed to determine whether a relaxation of the Amsterdam criteria (AC) could be applied to identify more families associated with DNA MMR. METHODS: Twenty-eight unrelated Swiss families (15 complying with the AC and 13 fulfilling extended criteria [EC] to include other tumors of the HNPCC spectrum as well) were screened for mutations in the MMR genes hMSH2 and hMLH1, using single-stranded conformation polymorphism and direct DNA sequencing. Microsatellite instability (MSI) was determined in 14 families. A comparison was made between the phenotypic characteristics of the mutation positive and mutation negative families. RESULTS: Ten AC families (67%) harbored germline mutations in hMLH1 (6 kindreds) or hMSH2 (4 kindreds). In none of the EC kindreds could an unambiguous disease-causing mutation be identified. Seven of eight AC families were found to display MSI whereas all colorectal carcinomas (CRC) in eight EC kindreds were MSI stable. CRC patients from mutation positive families had an earlier age at diagnosis (44 years vs. 49 years) and appeared to have a better survival (11.1 years vs. 7.7 years). CONCLUSIONS: Extending the AC to include extracolonic tumors of the HNPCC spectrum results in a very low mutation detection rate for hMSH2 and hMLH1. The EC families appear to represent an alternative genetic entity not necessarily related to DNA MMR gene mutations because they do not display MSI.

Adult↗
PubMed1999

[Early diagnosis of familial adenomatous polyposis based on multiple osteomas of the facial skull].

We describe a 21-year-old patient hospitalised because of a dislocated mandibular fracture and accidentally found to have multiple osteomas of the skull. A subsequent gastroenterological examination revealed the presence of multiple polyps in the large intestine, typical of familial adenomatous polyposis. A disease causing germline mutation in the adenomatous polyposis coli gene was identified by molecular genetic analysis. Although extracolonic features such as multiple osteomas, multiple epidermal cysts and desmoids are frequently found, most cases without a family history of familial adenomatous polyposis or colorectal cancer are only diagnosed because of colonic disease manifestations with colorectal cancer already present. This case report strikingly illustrates that in the absence of a family history the presence of extracolonic features allows presymptomatic diagnosis in familial adenomatous polyposis patients before colorectal cancer has developed.

Adenomatous Polyposis Coli↗
PubMed1999

Differential diagnosis of peri- and postmenopausal ovarian cysts.

OBJECTIVES: To test the value of preoperative and intracystic parameters in the differential diagnosis of ovarian cysts. METHODS: Criteria for admission of 58 patients were age > 47 years, complete history, detection of CA 125 serum level, and ultrasound findings. Tumor markers (CA 125, cancer-associated serum antigen (CASA), CA 72-4), hormones (estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH)), epidermal growth factor (EGF) receptor and c-erb B-2 amplification rate were detected in cyst fluid. RESULTS: Of the 58 subjects, 9 (15.4%) had functional cysts, 37 (63.8%) had benign tumors and 12 (20.8%) had malignant tumors. No functional ovarian cyst presented as echoic or multilocular cyst sonographically. The serum CA 125 values demonstrated significant differences between the non-malignant and malignant patient groups (P < 0.0005). The majority (63.8%, n = 37) of ovarian cysts were obtained at laparotomy, whereas only 36.2% (n = 21) were laparoscopically operated. The cyst fluid levels of FSH (P < 0.005) and LH (P < 0.05) were significantly lower in the functional group than in the benign or malignant group. Malignant cysts were significantly different from non-malignant cysts regarding low E2 (P < 0.01), high FSH (P < 0.05) and CASA (P < 0.02) values. There were no significant correlations between EGF receptor (P = 0.14) and c-erb B-2 (P = 0.06) gene amplification rates and malignant histology. CONCLUSIONS: Simple ovarian cysts combined with normal serum CA 125 levels are candidates for conservative follow-up or laparoscopy. The serum CA 125 is a powerful marker for prediction of histology in postmenopausal ovarian cyst. Laparoscopic surgery may be considered in patients with multilocular sonographic findings and normal CA 125 serum level. Combining serum CA 125 levels with cyst fluid parameters (E2, FSH, CASA) improves the sensitivity and specificity in predicting malignancy.

Age Distribution↗
PubMed1999

Plasma concentrations of carotenoids in healthy volunteers after intervention with carotenoid-rich foods.

AIM OF THE STUDY: The present study was conducted to investigate changes in the plasma concentration of carotenoids and carotenoid oxidation products, vitamin A, alpha- and gamma-tocopherol, and ubiquinone-10 during a dietary intervention trial with 23 male healthy volunteers. METHOD: A two week carotenoid depletion period was followed by a daily consumption of 330 mL tomato juice (40 mg lycopene), then by 330 mL carrot juice (15.7 mg alpha-carotene and 22.3 mg beta-carotene), and then by a 10 g spinach powder preparation (11.3 mg lutein and 3.1 mg beta-carotene) served with main meals for two weeks, respectively. Blood samples were collected in the morning after an overnight fasting and carotenoids, vitamin A, tocopherols, and ubichinone were analyzed by reversed-phase HPLC. RESULTS: During the tomato juice intervention, plasma concentrations of trans- and cis-lycopene increased 3-fold compared to the depletion period. Lycopene oxidation products could be demonstrated in plasma and were significantly elevated compared to control (p < 0.001). After two weeks of carrot juice consumption, alpha-carotene and beta-carotene concentrations increased 8.6- and 3.2-fold, respectively. Finally, during the spinach consumption period the lutein concentration increased 2-fold, while the beta-carotene concentrations were still elevated 2-fold. CONCLUSIONS: The moderate change in dietary habits, e.g., the consumption of 330 mL of carotenoid-rich vegetable juices caused significant changes in the plasma carotenoid concentrations, indicating a high bioavailability of carotenoids from these processed vegetable products. The changes in plasma carotenoid concentrations reflected the carotenoid composition of the consumed foods. However, particularly during the tomato juice intervention period the occurrence of lycopene oxidation products and cis-lycopene isomers in plasma was eminent. The formation may be due to antioxidant reactions of lycopene in the organism.

Adult↗
PubMed1999

Conjugated linoleic acid effects on circulating hormones, metabolites and lipoproteins, and its proportion in fasting serum and erythrocyte membranes of swine.

BACKGROUND: Conjugated linoleic acids (CLA)# refer to a group of linoleic acid (18:2)-derived isomers with conjugated double bonds mostly at carbon atoms 9 and 11 or 10 and 12, and with all possible cis and trans combinations. CLA is a newly recognized nutrient that functions to regulate energy retention and metabolism and that causes a serum lipoprotein profile considered to be less atherogenic. However, rodent models that have been frequently used for these studies are only of limited use because of distinct differences in physiology, compared with man. Additionally, possible differences in food intake between the experimental groups remained often unconsidered in those studies. Thus, it can not be excluded that the beneficial effects of CLA reported in a series of studies may be due, at least partially, to differences in nutrient and energy ingested. AIMS OF THE STUDY: This prompted us to undertake an investigation on the action of CLA by using a pig model and a feeding regimen with controlled amounts of food and antioxidants. The parameters used to assess CLA-specific action were selected hormones and metabolites involved in energy metabolism, individual lipoproteins and the appearance of CLA in fasting serum and erythrocyte membranes. Blood as an easily available biological sample was used for investigation. METHODS: For that purpose 16 adult female pigs were divided into two groups of 8 each, and were isoenergetically fed diets containing 0 (control diet) or 1% level of CLA (by weight) for 6 weeks. Plasma concentrations of total and free thyroxine (T4), total and free triiodothyronine (T3), and insulin were measured by radioimmunoassays. Plasma non-esterified fatty acids (NEFA), beta-hydroxybutyrate, circulating blood ATP and other clinical chemical variables were determined using enzymatic assays. The concentration of alpha-tocopherol was determined by high performance liquid chromatography. The lipoproteins VLDL (density <1.019 kg/L), LDL (density 1.019 - 1.063 kg/L), and HDL (density >1.063 kg/L) were isolated by step-wise ultracentrifugation. Fatty acids of the dietary oils, serum and blood cell membranes were separated and quantified by gas chromatography. RESULTS: At week 6, body weights of the pigs fed the CLA-supplemented diet were not different from that of the controls. CLA-treated pigs exhibited a 37% higher concentration of fasting serum insulin than their controls receiving no CLA (P = 0.11). Circulating free and total T4 and T3 as well as serum levels of beta-hydroxybutyrate, alpha-tocopherol, protein, glucose, urea, creatinine and circulating blood ATP remained unaffected by CLA supplementation. Serum concentrations of non-esterified fatty acids were reduced by 38% in CLA-treated pigs relative to the controls, although this difference was not significant. CLA-treated pigs tended to have lower leukocyte counts in blood than their controls (P <0.1). Erythrocyte and platelet counts, the hematocrit and hemoglobin concentration were similar between the groups. Serum of CLA-treated pigs showed a trend toward increased levels of triacylglycerols, cholesterol and phosphatidylcholine in the very low density and low density lipoproteins (LDL), without distinct changes in the high density lipoprotein fraction (HDL). The LDL cholesterol to HDL cholesterol ratio was significantly increased by CLA. When pigs were fed CLA at a dietary level of 1%, limited proportions of CLA appeared in fasting serum (1.6%) and erythrocyte membranes (1.1%). CONCLUSIONS: Under the present experimental conditions there appeared to be parallels between the effects of CLA and the reported effects of trans fatty acids in the mode of action on lipoproteins and insulin. The failure to demonstrate significant beneficial effects of CLA on the lipoprotein profile which have been observed in other studies requires further research.

3-Hydroxybutyric Acid↗
PubMed1999

SPECT patterns in probable Alzheimer's disease.

The primary objective of this study was to test hypotheses about the relationship between HMPAO-SPECT findings and probable Alzheimer's disease (DAT) in a relatively large sample of patients diagnosed according to DSM-III-R. SPECT patterns of 20 controls and 116 DAT patients were investigated. Left and right frontal, temporal, parietal and occipital regions of the brain were rated as showing a hypoperfusion or not. A wide variety of patterns were found and these are described in detail below. In DAT patients, temporal and/or parietal regions were affected significantly more often (88%, p > 0.001) than frontal and/or occipital regions (70%). A bilateral temporoparietal pattern, which has been repeatedly reported as typical for DAT, was observed in 48% of DAT patients, but also in 25% of controls, and did not differentiate significantly between these two groups (p > 0.05). Conversely, more than three regions with hypoperfusion were observed significantly more often in DAT patients (48%, p < 0.01) than in controls (10%). In DAT patients, the number of regions with hypoperfusion correlated significantly with the score of the Mini Mental State Examination (MMSE, r = 0.33, p < 0.001). The frequency of at least one hypoperfusion was approximately equal in left and right hemispheres (77% vs. 73%, p = 0.2). The hypothesis that cognitive decline in DAT starts in the temporal regions was tested in 14 SPECT patterns showing only one region with hypoperfusion. In 12 of these patterns, a temporal region was in fact affected (p < 0.001). Whereas hypoperfusion in frontal areas was not accompanied by a significantly lower MMSE than when only temporoparietal regions were affected, MMSE scores were significantly lower when occipital regions were affected in addition to temporoparietal regions (p < 0.05). The clinical use of SPECT findings was tested in discriminating analyses with the MMSE and a delayed recall test as additional predictors of DAT. Whereas the MMSE and the delayed recall test differentiated significantly between DAT patients and controls, SPECT findings yielded no further differentiation. In conclusion, the theoretical and clinical implications of SPECT findings and their relationships to other physiological and psychological variables deserve further investigation.

Aged↗