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Biomedical subjects

H Müller

Publications and source records attributed to H Müller.

At least 109 records · Page 6Linked to original sources

Calcium supplementation with calcium-rich mineral waters: a systematic review and meta-analysis of its bioavailability.

The relevance of calcium (Ca2+), an essential bone mineral, to the prevention and treatment of osteoporosis is well established. However, a good deal of evidence casts doubt on the validity of current RDAs (recommended daily allowance), i.e., 800-1000 mg/day. New guidelines consistently advocate higher daily intakes (up to 1500 mg/day), a goal that may be difficult to achieve for many patients. Environmental as well as individual behavioral factors may limit the consumption of dairy products, whereas calcium supplements require a high level of compliance and cause additional costs. Calcium-rich mineral waters may offer a promising alternative. A systematic literature search was performed (Medline, years 1966-1998) to identify experimental studies on the bioavailability of calcium-rich mineral waters. First, all publications on calcium absorption from mineral waters were identified, and, in a second step, studies comparing calcium absorption from mineral waters with that from dairy products. Four studies fulfilled all inclusion criteria. A meta-analysis based on published p values indicated calcium absorption from mineral waters was significantly higher (p = 0.03) than that from dairy products. Although only few studies with a relatively small number of subjects are available to date, the bioavailability of calcium from calcium-rich mineral waters thus seems to be at least comparable to, and possibly better than, that from dairy products. These results are in keeping with the assumption that calcium-rich mineral water is a useful calcium source to achieve new, higher recommended daily allowances of calcium.

Biological Availability↗

The VP2 variable region of African and German isolates of infectious bursal disease virus: comparison with very virulent, "classical" virulent, and attenuated tissue culture-adapted strains.

11 African and two German IBDV strains isolated in the mid '80s from field outbreaks in vaccinated and unvaccinated chicken flocks displayed features of very virulent (vv) IBDV strains. The sequence data of the VP2 variable region and phylogenetic analysis confirm that these strains can be grouped within vv IBDV strains which appeared at the same time on the three continents Africa, Asia, and Europe. Strain Cu-1wt, responsible for severe IBD outbreaks in Germany 13 years earlier, showed some relatedness to these strains, but also significant differences at the genomic level, even though this strain has also features of the vv IBDV strains.

Africa↗

Neuron-glia interactions in the rat retina infected by Borna disease virus.

Neuron-glia interactions in the Borna disease virus (BDV)-infected rat retina were investigated with emphasis on the ultrastructural characterization of degenerative alterations in the ganglion cell and photoreceptor layer. Immuno- and cytochemical techniques were applied to label microglia, macrophages and Müller (macroglial) cells. Four weeks after intracerebral infection of adult rats, the total thickness of the retina was considerably diminished, primarily due to the loss of photoreceptor segments and ganglion cells. A gradual reduction of both plexiform layers was also observed. There was a remarkable increase in the number of microglial cells, predominantly in the ganglion cell and the inner plexiform layers. Ultrastructural analysis confirmed that microglia, but also macrophages, were involved in phagocytosis accompanying severe neuronal degeneration in the ganglion cell and the photoreceptor layer. In contrast, Müller cells showed moderate morphological and cytochemical alterations, indicating that Müller cells play only a minor role in early stages of BDV-induced retinitis. Monitoring neuron-glia interactions in BDV-induced retinopathy, combined with the application of different protocols of immunosuppression effecting the BDV virus and/or the microglia, might help to establish specific strategies to suppress BDV-induced neuronal degeneration.

Animals↗

Endoscopic mucosal resection of early cancer and high-grade dysplasia in Barrett's esophagus.

BACKGROUND & AIMS: In view of the mortality and morbidity rates of esophagectomy and the relatively large group of inoperable patients, local therapeutic techniques are required for high-grade dysplasia and early Barrett's cancer. METHODS: A prospective investigation of endoscopic mucosal resection was conducted in 64 patients (mean age, 65 +/- 10 years) who had early carcinoma (61 patients) or high-grade dysplasia (3 patients) in Barrett's esophagus. Thirty-five patients met the criteria for low risk: macroscopic types I, IIa, IIb, and IIc; lesion diameter up to 20 mm; mucosal lesion; and histological grades G1 and G2 and/or high-grade dysplasia (group A). The remaining 29 patients were included in group B (high risk). RESULTS: A total of 120 resections were performed, with no technical problems encountered. The mean number of treatment sessions per patient was 1. 3 +/- 0.6 in group A and 2.8 +/- 2.0 in group B (P < 0.0005). Only one major complication occurred, a case of spurting bleeding, which was managed endoscopically. Complete local remission was achieved significantly earlier (P = 0.008) in group A than in group B. In May 1999, complete remission had been achieved in 97% of the patients in group A and in 59% of those in group B; however, 1 patient in group A and 9 in group B are still undergoing treatment or awaiting the first check-up. During a mean follow-up of 12 +/- 8 months, recurrent or metachronous carcinomas were found in 14%. CONCLUSIONS: Endoscopic mucosal resection of early carcinoma in Barrett's esophagus is associated with promisingly low morbidity and mortality rates. The procedure may offer a new minimally invasive therapeutic alternative to esophagectomy, especially in low-risk situations. Comparisons with surgical results will need to be done when the long-term results of this procedure become available.

Adult↗

Development of a blocking enzyme-linked immunosorbent assay for the detection of avian polyomavirus-specific antibodies.

Avian polyomavirus, described originally as budgerigar fledgling disease virus, has been associated with devastating contagious disease outbreaks in budgerigar aviaries. At present, this virus affects a wide range of psittacine and non-psittacine birds worldwide, and the serum neutralisation test is used for the serodiagnosis of avian polyomavirus infections. A blocking enzyme-linked immunosorbent assay was developed for the screening of large numbers of sera collected from various avian species. The assay employs a monoclonal antibody directed against the major structural protein VP1 as a blocking antibody in a sandwich blocking procedure. Either purified avian polyomavirus particles or avian polyomavirus VP1 expressed in recombinant baculovirus-infected Sf9 cells were used as antigen. The specificity of the blocking enzyme-linked immunosorbent assay was evaluated by testing sera directed against mammalian polyomaviruses. Using sera obtained from chicken infected experimentally with avian polyomavirus and a collection of psittacine field-origin sera, a good correlation was observed between the results of the blocking enzyme-linked immunosorbent assay and the serum neutralisation test. However, the blocking enzyme-linked immunosorbent assay is more rapid and more economic. Both, avian polyomavirus particles and VP1 produced by recombinant DNA technology proved to be suitable antigens.

Animals↗

Expression of LFA-1 (CD11a/CD18) and ICAM-1 (CD54) in an animal model of renal interstitial fibrosis induced by unilateral ureteral obstruction.

Unilateral ureteral obstruction (UUO) has been used as an experimental model to induce tubulointerstitial damage and interstitial fibrosis. UUO is characterized by cellular proliferation, accumulation of inflammatory cells, and subsequent replacement of renal parenchyma by fibrous tissue. The influx of inflammatory cells into the renal interstitium is mediated by adhesion molecules. In this study, the development of fibrosis in the UUO model of the rat was examined and its relation to the time course of LFA-1 and ICAM-1 expression was assessed by immunohistochemistry. An increase in interstitial connective tissue was detected on day 10 after UUO, with a maximum on day 35. After unilateral ureteral obstruction, LFA-1 was prominently expressed in interstitial infiltrates, and to a lesser degree in glomerular areas. An initial increase in LFA-1-positive cells was noted already on day 10, with a maximum on day 20 and a decline on day 25. During the time course of 35 days after UUO, we observed an increase in ICAM-1 expression in the vascular endothelium, in tubular epithelium and in interstitial areas. This study shows that LFA-1 expression and ICAM-1 expression are concordant and that this process is associated with increasing interstitial fibrosis. ICAM-1 interstitial tissue may facilitate the homing and persistence of an interstitial infiltrate by ICAM-1/LFA-1 interactions, thereby preceding the development of renal interstitial fibrosis.

Animals↗

Evaluation of the cobalt requirement of beef cattle based on vitamin B12, folate, homocysteine and methylmalonic acid.

This investigation was designed to estimate the Co requirement of growing cattle on the basis of plasma and liver levels of vitamin B(12) and folate, plasma levels of homocysteine and methylmalonic acid (MMA) and haematological variables. For this purpose thirty-four male intact cattle of the German Simmental breed (236 kg) were assigned randomly to ten groups and were fed corn silage-based diets which contained 70, 90, 109, 147, 184, 257, 327, 421, 589 or 689 microg Co/kg DM for 40 weeks. One-slope broken-line model analysis and a quadratic model with plateau were used to estimate the Co requirement. The broken-line model estimated the dietary Co requirement of growing cattle to be 257 (se 29) microg/kg dietary DM based on plasma vitamin B(12) as response criterion. The dietary Co levels needed to maximise the liver vitamin B(12) and liver folate were 236 (se 8) and 190 (se 8) microg/kg dietary DM respectively. Plasma folate did not show any response to the different Co levels. The dietary Co was inversely correlated with the plasma concentrations of homocysteine and MMA. Estimates of the dietary Co concentration required to minimise homocysteine were 161 (se 10) microg/kg DM. When MMA was used as response criterion, the linear model yielded a Co requirement of 124 (se 3) microg/kg dietary DM. The quadratic model did not provide a better closeness of regression fit and yielded similar requirements to the linear model. Haemoglobin concentration and haematocrit tended to have a slight response to increasing dietary Co and were only decreased in cattle on diets containing less than 100 microg Co/kg DM. On the basis of the present data, recommended levels of dietary Co for normal folate metabolism and minimum homocysteine and MMA levels can be set to be 150-200 microg/kg DM; for maximum vitamin B12 levels, the desired Co content in the diet seems to be 250 microg/kg DM.

Animals↗

Different functions of fetal and adult AChR subtypes for the formation and maintenance of neuromuscular synapses revealed in epsilon-subunit-deficient mice.

Mice deficient in epsilon-subunits of the acetylcholine receptor (AChR) channel die prematurely due to severe AChR deficiency that leads to the progressive reduction in AChR density at the neuromuscular endplate [Witzemann, V., Schwarz, H., Koenen, M., Berberich, C., Villarroel, A., Wernig, A., Brenner, H.R. & Sakmann, B. (1996) Proc. Natl Acad. Sci. USA, 93, 13286-13291]. The mice may serve as a model for studying AChR-related myasthenic diseases. The postnatal development of the subsynaptic apparatus takes place in the absence of the adult type, epsilon-subunit-containing receptors which normally replace the fetal gamma-subunit-containing receptors. During later development the secondary folds of the postsynaptic membrane disappear concomitant with the decrease in AChR density, so that the flattened-out membrane with its remaining nicotinic receptors is in close proximity to the subsynaptic cytoplasmatic compartment and the subsynaptic myonuclei. The decrease in AChR concentration is correlated with a decrease of postsynaptic rapsyn, but has less effect on agrin, a neuronally released aggregating factor for AChRs. Thus, despite the presence of agrin at the synapse, AChR expression is not maintained at the level required to stabilize normal synaptic structure comprising secondary postsynaptic membrane folds. Collectively the results suggest that the postnatal switch from the global, activity-sensitive gamma-subunit gene transcription to the synapse-specific, activity-independent epsilon-subunit gene transcription is not required for the formation and differentiation of synapses but is essential for the maintenance of the highly organized structure of the neuromuscular endplate.

Age Factors↗

Determination of cytokine mRNA-expression in term human placenta of patients with gestational hypertension, intrauterine growth retardation and gestational diabetes mellitus using polymerase chain reaction.

OBJECTIVE: Our objective was to test the hypothesis, that pregnancy-related diseases are going along with changes in cytokine mRNA-expression at the placental site, either as a part of a pathological process or in connection with regulatory mechanisms induced by disturbances at the feto-maternal interface resulting from previous pathological changes--in the sense of counterregulation. MATERIAL AND METHODS: The cytokines chosen for this investigation are known to 1.) be expressed in the human placental tissue, 2.) to be involved in immunological processes and 3.) the regulation of growth and differentiation processes of different cell types of the placenta or decidua, 4.) to play a role in the angiogenesis at the feto-placental interface and 5.) to be involved in pathological processes in other human diseases. 32 samples derived from term human placentas were examined for messenger RNA levels of interleukin 1 alpha (II-1 alpha), tumor necrosis factor-alpha (TNF-alpha), platelet derived growth factor-A chain (PDGF-A), platelet derived growth factor-B chain (PDGF-B), and platelet derived growth factor receptor (PDGF-R) using a semiquantitative reverse transcriptase (RT) polymerase chain reaction (PCR) protocol. To calibrate samples in our procedure, beta-actin mRNA (messenger ribonucleic acid) known as a "house keeping" gene was proven to be constantly expressed. The sample-groups consisted of normal pregnancies (n = 8), gestational hypertension (GH, n = 7), intrauterine growth retardation (IUGR, n = 6), gestational diabetes mellitus (GDM, n = 5), and gemini (n = 3 x 2). RESULTS: Throughout the 32 samples, a significant correlation between PDGF-A and PDGF-R expression, PDGF-A and TNF-alpha expression was stated (p = 0.007). Compared with the pattern of expression in normal placentas, placentas of growth retarded pregnancies had higher Il-1 alpha mRNA (p = 0.016), PDGF-A (p = 0.029) and PDGF-B (p = 0.001) levels. The samples of the gestational hypertension group and placentas of patients with gestational diabetes displayed a significantly stronger PDGF-R mRNA signal (p = 0.0029 and p = 0.008). CONCLUSIONS: Though these marked differences in cytokine mRNA levels between clinical groups were statistically proven, clear correlation of these differences with clinical data was not found.

Actins↗

[Human amniotic fluid transferrin stimulates progesterone production by human trophoblast cells in vitro].

OBJECTIVE: During pregnancy transferrin plays a key role as an iron transport protein to serve the increased fetal demands of iron. Transferrin is also present in relatively high concentrations in amniotic fluid [6], showing a different glycosylation compared with serum transferrin. The biological function of human amniotic fluid transferrin (hAFT) is still unknown. In addition trophoblast cells also synthesise transferrin. Transferrin synthesised by the trophoblast shows a special glycosylation. We found identical carbohydrate structure of hAFT and trophoblast transferrin. We investigated the influence of hAFT on the progesterone-, cortisol- and hCG-release of trophoblasts in culture compared with the influence of human holo- and apo-serum transferrin on the release of these hormones. MATERIAL AND METHODS: Cytotrophoblast cells were prepared from human term placentae by standard trypsin-DNAse dispersion of villous tissue followed by a percoll gradient centrifugation step. When placed in culture, the trophoblasts were incubated with varying concentrations (50-300 micrograms/ml) of human amniotic fluid- and serum-transferrin. Unstimulated cells of each placenta used as controls. Culture supernatants were assayed for progesterone, hCG and cortisol by enzyme-immunometric methods. RESULTS: Our results show, that the release of progesterone increased in hAFT-treated cell cultures compared to untreated cell cultures. Holo- and apo-serumtransferrin did not show any effect on the progesterone release by trophoblast cells in vitro. Neither hAFT nor holo- and apo-serum transferrin had any effect on the cortisol- and hCG-release in vitro. CONCLUSIONS: Progesterone is a marker for differentiation of trophoblasts in syncytiotrophoblasts. Only hAFT stimulates the progesterone production. We suggest, that hAFT can modulate the endocrine function of trophoblast cells in culture by regulating progesterone production.

Amniotic Fluid↗

[Neuroplasticity and chronic pain].

In the seventies and eighties spinal mechanisms inhibiting pain processing were discovered in animal studies leading to new therapeutic regimens such the use of spinal opioids. During the last decade additional studies revealed an increased sensibility of the spinal cord upon severe, long lasting pain perception, a mechanism called wind-up. Hyperalgesia is accompanied by persisting genetic changes of spinal cord cells, which may contribute to the chronification of pain. The severity and duration of acute pain apparently contributes to the possibility of chronic pain development. Although not all the consequences of these findings are clear, they may influence our way of performing anaesthesia and treating postoperative or acute pain situations, e.g. pain during herpes zoster or pain after trauma and amputation. In general, analgetic measures should be potent enough to prevent spinal sensiblisation, which can be best achieved with spinal blockade by local anesthetics. Another way of counteracting pain-induced spinal plasticity is by blocking or antagonizing its pathways with specific transmitters or their equivalents. All these spinally mediated regimens should be performed prior to later predominating mechanisms of supraspinal plasticity involving psychic changes due to persisting pain, which seem to evolve with delay to spinal processes.

Animals↗

Moderate intervention with carotenoid-rich vegetable products reduces lipid peroxidation in men.

Because of their antioxidant properties, carotenoids may have beneficial effects in preventing cancer and cardiovascular disease. However, in humans consuming carotenoid-rich vegetables, data concerning the antioxidant effects of carotenoids are rather scarce. A human intervention trial was conducted, therefore, to determine whether a moderately increased consumption of carotenoid-rich vegetables would influence the antioxidant status in 23 healthy men. This short-term feeding study lasted 8 wk during which the men consumed a low carotenoid diet. A 2-wk low carotenoid period was followed by daily consumption of 330 mL tomato juice, then by 330 mL carrot juice and then by 10 g of spinach powder, each for 2 wk. Antioxidant status [water-soluble antioxidants in serum, ferric reducing ability of plasma (FRAP) and antioxidant enzyme activities] and lipid peroxidation (plasma malondialdehyde and ex vivo oxidation of LDL) were determined. In a subgroup of 10 men, lipoprotein carotenoids were measured. The consumption of carotenoid-rich vegetables significantly increased selected carotenoids in lipoproteins but had only minor effects on their relative distribution pattern. Tomato juice consumption reduced plasma thiobarbituric acid reactive substances (TBARS) by 12% (P: < 0.05) and lipoprotein oxidizability in terms of an increased lag time (18%, P: < 0.05). Carrot juice and spinach powder had no effect on lipid peroxidation. Water-soluble antioxidants, FRAP, glutathione peroxidase and reductase activities did not change during any study period. In evaluating the low carotenoid diet, we conclude that the additional consumption of carotenoid-rich vegetable products enhanced lipoprotein carotenoid concentrations, but only tomato juice reduced LDL oxidation in healthy men.

Adult↗

Agnoprotein 1a and agnoprotein 1b of avian polyomavirus are apoptotic inducers.

Avian polyomavirus (APV) causes an acute fatal disease in a variety of avian species. DNA laddering indicating apoptosis was demonstrated in APV-infected chicken embryo (CE) cells. DNA laddering, however, was not observed in Vero cells infected with mammalian polyomavirus simian virus 40. Expression of APV agnoprotein 1a and agnoprotein 1b induced apoptosis in insect cells and CE cells. An APV full-length plasmid transfected in CE cells induced apoptosis, and infectious virus was produced. After transfection of CE cells with a plasmid containing a mutated initiation codon for agnoprotein 1a and agnoprotein 1b, however, a considerably lower number of apoptotic cells was observed, and no infectious progeny was produced.

Animals↗

A search asymmetry reversed by figure-ground assignment.

We report evidence demonstrating that a search asymmetry favoring concave over convex targets can be reversed by altering the figure-ground assignment of edges in shapes. Visual search for a concave target among convex distractors is faster than search for a convex target among concave distractors (a search asymmetry). By using shapes with ambiguous local figure-ground relations, we demonstrated that search can be efficient (with search slopes around 10 ms/item) or inefficient (with search slopes around 30-40 ms/item) with the same stimuli, depending on whether edges are assigned to concave or convex "figures." This assignment process can operate in a top-down manner, according to the task set. The results suggest that attention is allocated to spatial regions following the computation of figure-ground relations in parallel across the elements present. This computation can also be modulated by top-down processes.

Attention↗

Nondetected tumor (pT0) after prolonged, neoadjuvant treatment of localized prostatic carcinoma.

OBJECTIVES: 135 patients with stage T1-3N0M0 prostatic carcinoma were submitted to prolonged PSA-monitored neoadjuvant endocrine treatment (PPNET). The rate of pT0 reports was three times higher (15%) than after the standard 3-month therapy (5%). The present work was done to elucidate the initial characteristics of these tumors, to see if additional workup of these prostatectomy specimens is able to detect tumor vestiges and, if so, to describe their morphology. METHODS: The original clinical and histopathological data of 20 pT0 cases were reviewed and an additional histopathological workup of the prostatectomy specimens was done. RESULTS: The majority of patients had initially small (9 patients cT1, 8 patients cT2, 3 patients cT3) and well-differentiated tumors (18 patients Gleason score <7). Microscopic assessment of 4,503 slides revealed very small tumor remnants (mean volume 0.2 ml) in 13 of the 20 prostatectomy specimens. Severe tumor regression was seen in 3 cases, slight to moderate regression in 10 cases. CONCLUSIONS: A pT0 report following detailed routine histopathological workup has to be regarded as a maximal therapeutic effect, but not as tumor elimination. PPNET clearly increases the rate of pT0 reports, implicating that the conventional 3 months of pretreatment does not exploit the possibilities of neoadjuvant therapy.

Androgen Antagonists↗

Human chorionic gonadotrophin-beta transcripts correlate with progesterone receptor values in breast carcinomas.

The pathophysiological role for the expression of human chorionic gonadotrophin (hCG) in malignant neoplasms is currently speculative. We investigated the overall expression of genes hCG-beta 5, 3, 8 and 7 in breast carcinoma (n=214), fibroadenoma (n=37) and macromastia (n=10) by quantitative reverse transcriptase-PCR. Eighty (37.4%) of the breast cancer samples revealed positive hCG-beta mRNA expression and the mean value was 67. 9 copies per 200 ng total RNA (range: 0-1743; 95% confidence interval (CI) for mean: 44-92). Fibroadenomas had more frequently detected (56.8%) and greater hCG-beta copy numbers (mean 86.9; range: 0-845; 95% CI for mean: 35-138). Macromastia probes yielded no positive hCG-beta mRNA. The hCG-beta mRNA expression was significantly different in the three histological subgroups (P=0. 006). Among breast carcinomas, a positive correlation was detected between hCG-beta mRNA copy numbers and progesterone receptor (PgR) values (P<0.001). No significant differences were seen regarding disease-free (P=0.87) and overall survival (P=0.20) depending on hCG-beta mRNA status. Finally, our findings do not support a role for hCG-beta in malignant transformation of human breast cells and indicate a possible involvement of hCG-beta in benign breast disease. The relationship with PgR expression may suggest that progestins regulate the expression of hCG in breast epithelial cells.

Adult↗

Induction of erythroid proliferation and differentiation by a trophoblast-specific cytokine involves activation of the JAK/STAT pathway.

Pregnancy is characterized by increased erythropoiesis within maternal and fetal compartments. The placenta has been shown to produce factors that stimulate erythropoiesis but convincing evidence for placental production of erythropoietin (EPO) is still lacking. Prolactin-like protein E (PLP-E) was recently found to stimulate expression of the adult beta major globin gene in mouse erythroleukemia cells. Here we demonstrate that PLP-E transiently expressed in COS-7 cells stimulates proliferation and erythroid differentiation of murine and human erythroid progenitor cell lines. Electrophoretic mobility shift assays were used to show the activation of STAT5 by PLP-E in the human erythroid cell line TF1. Furthermore, we compared the effects of PLP-E on murine myeloid FDCP1 cells which do not express EPO receptors (EPORs) with effects on cells genetically engineered to express functional EPORs. We provide evidence that PLP-E-dependent proliferation and STAT5 activation is independent of the expression of the EPOR. Taken together, these data suggest that PLP-E acts on specific receptors of erythroid-committed murine and human cells by the activation of intracellular signaling pathways promoting cell growth and differentiation.

Animals↗