Biomedical subjects

A Moser

Publications and source records attributed to A Moser.

At least 37 records · Page 2Linked to original sources

PubMed2001

The peroxin Pex6p gene is impaired in peroxisomal biogenesis disorders of complementation group 6.

Human genetic peroxisomal biogenesis disorders (PBDs), such as Zellweger syndrome, comprise 13 different complementation groups (CGs). Eleven peroxin genes, termed PEXs, responsible for PBDs have been identified, whereas pathogenic genes for PBDs of 2CGs, CG-A (the same CG as CG8 in the United States and Europe) and CG6, remained unidentified. We herein provide several lines of novel evidence indicating that PEX6, the pathogenic gene for CG4, is impaired in PBD of CG6. Expression of PEX6 restored peroxisome assembly in fibroblasts from a CG6 PBD patient. This patient was a compound heterozygote for PEX6 gene alleles. Accordingly, by merging CG6 with CG4, human PBDs are now classified into 12CGs.

ATPases Associated with Diverse Cellular Activitie↗

PubMed2001

Post renal transplantation human herpesvirus 8-associated lymphoproliferative disorder and Kaposi's sarcoma.

Post-transplantation lymphoproliferative disorders (PTLDs) and Kaposi's sarcoma (KS) are immunosuppression-related tumours developing in solid organ transplant patients. Although the Epstein-Barr virus (EBV) is detected in the majority of the PTLDs during the first year after transplantation, the proportion of EBV-negative PTLDs has increased in recent years. We report a case of a 17-year-old man who developed severe immune haemolytic anaemia, KS and human herpesvirus 8 (HHV-8)-associated, polymorphic-type PTLD 9 months after allogeneic renal transplantation from his HHV-8-seropositive father. It is suggested that: (i) HHV-8 may be associated with EBV-negative, polymorphous-type PTLD occurring less than 1 year after transplantation, and (ii) PTLD may be listed among other tumours, including KS, Castleman's disease and primary effusion lymphoma (PEL), that are related to HHV-8 infection.

Adolescent↗

PubMed2001

Upper airway obstruction-related sleep apnea in a child with thalassemia intermedia.

Obstructive sleep apnea can be caused by hypertrophy of tonsils and adenoids or neuromuscular diseases. The authors describe a child with thalassemia intermedia in whom severe obstructive sleep apnea syndrome developed. Computed tomography scanning revealed an obstruction of the nasopharynx resulting from extramedullary hematopoiesis. The child was treated with hydroxyurea and blood transfusions. Relief of symptoms was noted 1.5 months after initial treatment. Extramedullary hematopoiesis causes sleep apnea syndrome in thalassemic patients, and the treatment of hydroxyurea and blood transfusion for extramedullary hematopoiesis should be further studied.

Airway Obstruction↗

PubMed2001

Outcome and long-term side effects after synchronous radiochemotherapy for childhood brain stem gliomas.

Between 1993 and 1999, 11 children with histologically confirmed diffuse and exophytic brain stem glioma (BSG) were treated with intensive induction chemotherapy and simultaneous external beam irradiation. Chemotherapy was performed according to the German/Austrian Pediatric Brain Tumor Study HIT '91 and included two cycles of ifosfamide (days 1-3), etoposide (days 4-6), methotrexate (days 15 and 22), cisplatin (days 29-31) and cytarabine (days 29-31), separated by a 3-week interval. Maintenance chemotherapy with carmustine, carboplatin and vincristine (8 cycles over a 1-year period) was given in those patients who responded clinically or radiographically to induction chemotherapy. Six of 11 patients showed an objective reduction in tumor size on magnetic resonance imaging and 4 of 11 are alive in good general condition >22, >22, >90 and >92 months, respectively, after diagnosis without radiographic evidence of tumor progression (1 complete remission, 2 partial remissions, 1 stable disease), but suffer from moderate to severe long-term side effects. Three patients died due to disease progression after having achieved a partial remission which lasted 5, 6 and 18 months, respectively, whereas only short-term stabilization was observed in 4 patients who died within 1 year after diagnosis. Acute hematologic toxicity was severe but manageable. This intensive combined modality treatment was toxic but yielded objective responses in more than 50% and long-term survivors in one third of childhood BSG patients.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

Cholesterol sulfate stimulates involucrin transcription in keratinocytes by increasing Fra-1, Fra-2, and Jun D.

Lipids that are synthesized de novo in the epidermis, including fatty acids, oxysterols, 1,25-dihydroxyvitamin D(3), and farnesol, can regulate the differentiation of normal human keratinocytes (NHK). Cholesterol sulfate (CS), an epidermal lipid that is produced in the upper nucleated layers of the epidermis coincident with terminal differentiation, has been shown to play a role in the regulation of the late stages of keratinocyte differentiation, including formation of the cornified envelope. In the present study, we determined i) whether CS regulates involucrin (INV), an early keratinocyte differentiation marker, and ii) the mechanism by which CS regulates differentiation. mRNA and protein levels of INV, a precursor protein of the cornified envelope, increased 2- to 3-fold in NHK incubated in the presence of CS. In contrast, cholesterol had no effect on INV protein or mRNA levels. Transcriptional regulation was assessed in NHK transfected with INV promoter-luciferase constructs. CS increased luciferase reporter activity approximately 2- to 3-fold in NHK transfected with a 3.7-kb INV promoter construct. Deletional analysis revealed a CS-responsive region of the INV promoter located between bp --2452 and --1880. A 5-base pair (bp) mutation of the AP-1 site (bp --2117 to --2111) within this responsive region abolished CS responsiveness, suggesting a role for the AP-1 complex in the regulation of INV transcription by CS. Electrophoretic mobility shift analysis demonstrated increased binding of nuclear extracts isolated from CS-treated NHK to AP-1 DNA as compared with vehicle-treated controls. Incubation of the nuclear extract with the appropriate antibodies showed that the AP-1 DNA-binding complex contained Fra-1, Fra-2, and Jun D. Western blots demonstrated that CS treatment increased the levels of Fra-1, Fra-2, and Jun D, and Northern analyses revealed that CS increased mRNA levels for these same AP-1 factors. These data indicate that CS, an endogenous lipid synthesized by keratinocytes, regulates the early stages of keratinocyte differentiation, and may do so through its ability to modulate levels of AP-1 proteins. -- Hanley, K., L. Wood, D. C. Ng, S. S. He, P. Lau, A. Moser, P. M. Elias, D. D. Bikle, M. L. Williams, and K. R. Feingold. Cholesterol sulfate stimulates involucrin transcription in keratinocytes by increasing Fra-1, Fra-2, and Jun D. J. Lipid Res. 2001. 42: 390--398.

Binding Sites↗

PubMed2001

Prenatal diagnosis of malignant osteopetrosis in Bedouin families by linkage analysis.

Autosomal recessive malignant osteopetrosis (MOP) is a lethal disease, unless bone marrow is successfully transplanted. Yet a donor may not always be available, and even when there is one transplantation results are far from optimal. The difficulty in obtaining conclusive results by sonographic and X-ray evaluation of the fetus makes prenatal molecular diagnosis highly desirable. Subsequent to the chromosomal localization of the MOP gene in Arab-Bedouin families from the Negev region in Israel, linkage analysis was used for the prenatal diagnosis of this disease in Bedouin families at risk. Twelve cases were diagnosed, three fetuses were found to be affected, and one of the pregnancies was terminated. The other two pregnancies continued to term and the diagnosis of osteopetrosis was confirmed by X-ray immediately after birth. This is the first report on prenatal diagnosis of autosomal recessive osteopetrosis by linkage analysis.

Adult↗

PubMed2001

[Restoration of blood circulation in reperfusion of ischemic tissues].

In experiment there were studied changes of the tissue blood circulation and microcirculation during postischemic reperfusion of skeletal muscles with various density of capillaries. It was established that reactive hyperemia, caused mainly by enhancement of extracapillary tissue blood flow. While persistence of durable arterial hypertension the capillaries quantity and potential volume of microcirculatory bed are reducing, negatively influencing the blood circulation restoration process during postischemic reperfusion. In chronic ischemia the potential volume of microcirculation is increasing, securing complete restoration of blood circulation in postischemic reperfusion.

Animals↗

PubMed2001

Engineering for problem solving in future: eco-social market economy and eco-social tech.

The paper differentiates approaches in technology (end-of-pipe, cleaner production, industrial ecology, zero emission and eco-social-tech) and compares them in respect to the problem solving capacity on the ecological as well as social dimension by showing the eco-impact reduction and job creation. Eco-social-tech represents the approach with highest problem solution as it is based on "eco-social market economy", which will the replace free market economy. The deep background of these innovations is "ecosophy", the wisdom of nature, which serves as guideline for eco-restructuring the world.

Biotechnology↗

PubMed2000

Oxymyohemerythrin: discriminating between O2 release and autoxidation.

Myohemerythrin (Mhr) is a non-heme iron O2 carrier (with two irons in the active site) that is typically found in the retractor muscle of marine 'peanut' worms. OxyMhr may either release O2, or undergo an autoxidation reaction in which hydrogen peroxide is released and diferric metMhr is produced. The autoxidation reaction can also be promoted by the addition of certain anions to Mhr solutions. This work, using recombinant Themiste zostericola Mhrs, contrasts the results of environmental effects on these reactions. For the O2 release reaction, deltaVdouble dagger(21.5 degrees C) = +28+/-3 cm3 mol(-1), deltaHdouble dagger(1 atm) = +22+/-1 kcal mol(-1), and deltaSdouble dagger(1 atm) = +28+/-4 eu. The autoxidation reaction (pH 8.0, 21.5 degrees C, 1 atm) displays different kinetic parameters: deltaVdouble dagger = -8+/-2 cm3 mol(-1), deltaHdouble dagger = +24.1+/-0.7 kcal mol(-1), and deltaSdouble dagger = +1+/-1 eu. Autoxidation in the presence of sodium azide is orders of magnitude faster than solvolytic autoxidation. The deltaVdouble dagger parameters for azide anation and azide-assisted autoxidation reaction are +15+/-2 and +59+/-2 cm3 mol(-1), respectively, indicating that the rate-limiting steps for the Mhr autoxidation and anation reactions (including O2 uptake) are not associated with ligand binding to the Fe2 center. The L103V and L103N oxyMhr mutants autoxidize approximately 10(3)-10(5) times faster than the wild-type protein, emphasizing the importance of leucine-103, which may function as a protein 'gate' in stabilizing bound dioxygen.

Animals↗

PubMed2000

Monodisperse FePt nanoparticles and ferromagnetic FePt nanocrystal superlattices

Synthesis of monodisperse iron-platinum (FePt) nanoparticles by reduction of platinum acetylacetonate and decomposition of iron pentacarbonyl in the presence of oleic acid and oleyl amine stabilizers is reported. The FePt particle composition is readily controlled, and the size is tunable from 3- to 10-nanometer diameter with a standard deviation of less than 5%. These nanoparticles self-assemble into three-dimensional superlattices. Thermal annealing converts the internal particle structure from a chemically disordered face-centered cubic phase to the chemically ordered face-centered tetragonal phase and transforms the nanoparticle superlattices into ferromagnetic nanocrystal assemblies. These assemblies are chemically and mechanically robust and can support high-density magnetization reversal transitions.

Journal Article↗

PubMed2000

PEX7 gene structure, alternative transcripts, and evidence for a founder haplotype for the frequent RCDP allele, L292ter.

We recently reported cloning a cDNA encoding Pex7p, the peroxisomal PTS2 receptor. PEX7 mutations cause the peroxisome biogenesis disorder (PBD) rhizomelic chondrodysplasia punctata (RCDP). In a survey of 44 RCDP probands, we found that one PEX7 allele, L292ter, accounted for 50% of mutant PEX7 genes. Here we report the characterization of the PEX7 structural gene, which spans 102 kb on chromosome 6q21-q22.2 and contains at least 10 exons. In addition to the predominant full-length transcript, we identified eight smaller PEX7 transcripts generated by alternative exon splicing in several tissues. However, none of these splice forms was able to restore PTS2 protein import into peroxisomes when expressed in RCDP fibroblasts nor did they inhibit PTS2 protein import when expressed in normal fibroblasts. To determine whether the high frequency of the L292ter allele is due to a founder effect, we identified five polymorphic markers (four diallelic markers and one CA repeat) spanning the PEX7 gene. We show that all 12 L292ter homozygotes in our patient sample have an identical haplotype at these five sites, consistent with the hypothesis that the L292ter mutation arose once on an ancestral chromosome in the Caucasian population.

Alleles↗

PubMed2000

Human acid ceramidase gene: novel mutations in Farber disease.

Farber disease is an autosomal recessive disorder caused by lysosomal acid ceramidase (AC) deficiency. It commonly manifests during the first few months after birth with a unique triad of painful and progressive deformed joints, subcutaneous nodules, and progressive hoarseness. In order to understand the molecular mechanism(s) of pathogenesis of Farber disease, we isolated and characterized a full-length human AC gene, mapped its chromosomal location, determined the tissue-specific expression, and analyzed mutations in Farber disease patients. We also studied the AC-mRNA expression in gastrointestinal tumors and adjoining normal tissues. In addition, we determined the pattern of tissue-specific AC-mRNA expression in the adult mouse and during fetal development. Our results show that human AC gene consists of 14 exons and 13 introns spanning approximately 26.5 kb of genomic DNA. It is mapped to human chromosome 8p22-21.2, a region often disrupted in several cancers. The AC-mRNA is expressed in the mouse fetus from the seventh day of gestation. Interestingly, while the AC-mRNA is expressed in all segments of the normal gastrointestinal tract, none of the gastrointestinal tumor tissues had any AC-mRNA expression. We also uncovered four novel mutations in Farber disease patients that were not previously reported. Taken together, our results not only attest to the physiological importance of AC but also uncover several new mutations in Farber disease that may advance our knowledge towards establishing a genotype-phenotype correlation in this disease.

Acid Ceramidase↗

PubMed2000

Effects of ENU dosage on mouse strains.

The germline supermutagen, N-ethyl-N-nitrosourea (ENU), has a variety of effects on mice. ENU is a toxin and carcinogen as well as a mutagen, and strains differ in their susceptibility to its effects. Therefore, it is necessary to determine an appropriate mutagenic, non-toxic dose of ENU for strains that are to be used in experiments. In order to provide some guidance, we have compiled data from a number of laboratories that have exposed male mice from inbred and non-inbred strains or their F(1) hybrids to ENU. The results show that most F(1) hybrid animals tolerate ENU well, but that inbred strains of mice vary in their longevity and in their ability to recover fertility after treatment with ENU.

Animals↗

PubMed2000

The dopamine D2 receptor agonist alpha-dihydroergocryptine modulates voltage-gated sodium channels in the rat caudate-putamen.

Alpha-Dihydroergocryptine (alpha-DHEC), a Dopamine (DA) D2 receptor agonist, is widely used as dopaminergic drug in the treatment of Parkinson's disease. To study the mechanisms involved in the signal transduction process induced by alpha-DHEC on the presynaptic site of the dopaminergic neuron, we incubated slices of the rat caudate-putamen with alpha-DHEC and the indicated substances in static chambers. Following incubation the resulting DA outflow was measured by high-performance-liquid chromatography with electrochemical detection. The addition of alpha-DHEC (10 microM-0.1mM) did not modulate basal DA outflow. Activation of voltage-gated sodium channels by veratridine (VER) from low to relatively high concentrations (1-10 microM) led to a concentration-dependent increase of DA outflow. Using concentrations as high as 10 microM a dramatic increase of DA levels (600% of baseline levels) was observed. The ability of VER to provoke DA release was sensitive to the addition of tetrodotoxin (TTX) and was completely blocked by 1 mM TTX. Coincubation of alpha-DHEC (10microM-0.1mM) and VER (10microM) reduced VER-stimulated DA outflow in a concentration-dependent manner. The time-concentration course of VER-induced DA outflow was not modulated by alpha-DHEC. As described in our earlier studies, the specific D2 receptor antagonist (-)sulpiride (SLP) concentration-dependently enhances extracellular DA levels. Addition of alpha-DHEC almost completely blocked SLP-induced DA-outflow. When slices were incubated with the non-selective DA receptor agonist haloperidol (HLP, 0.1 mM) the effect of alpha-DHEC on VER-induced DA outflow was partially but not completely abolished. These data strongly suggest that the effect of alpha-DHEC on the presynaptic site implies an activation of D2 receptors as well as an inhibitory action on voltage-gated sodium channels. Alpha-DHEC seems to modulate voltage-gated sodium channels in part independently from DA receptors since blockade of D2 receptors with saturating concentrations of haloperidol did not completely abolish its effect. Based on our data we have no evidence that voltage-gated potassium channels, N-type calcium channels or D1, D3-receptors are involved in the action of alpha-DHEC at the presynaptic site of the dopaminergic neuron. The results give one rationale for the proposed neuroprotective effect of alpha-DHEC.

Animals↗

PubMed2000

The wisdom of nature in integrating science, ethics and the arts.

This paper deals with an approach to the integration of science (with technology and economics), ethics (with religion and mysticism), the arts (aesthetics) and Nature, in order to establish a world-view based on holistic, evolutionary ethics that could help with problem solving. The author suggests that this integration is possible with the aid of "Nature's wisdom" which is mirrored in the macroscopic pattern of the ecosphere. The corresponding eco-principles represent the basis for unifying soft and hard sciences resulting in "deep sciences". Deduction and induction will remain the methodology for deep sciences and will include conventional experiments and aesthetic and sentient experiences. Perception becomes the decisive factor with the senses as operators for the building of consciousness through the subconscious. In this paper, an attempt at integrating the concepts of the "true", the "right" and the "beautiful" with the aid of Nature's wisdom is explained in more detail along with consequences.

Art↗

PubMed2000

Reduced leptin levels in starvation increase susceptibility to endotoxic shock.

Malnutrition compromises immune function, reducing resistance to infection. We examine whether the decrease in leptin induced by starvation increases susceptibility to lipopolysaccharide (LPS)- and tumor necrosis factor (TNF)-induced lethality. In mice, fasting for 48 hours enhances sensitivity to LPS. Decreasing the fasting-induced fall in leptin by leptin administration markedly reduced sensitivity to LPS. Although fasting decreases basal leptin levels, LPS treatment increased leptin to the same extent as in fed animals. Fasting increased basal serum corticosterone; leptin treatment blunted this increase. Fasting decreased the ability of LPS to increase corticosterone; leptin restored the corticosterone response to LPS. Serum glucose levels were decreased in fasted mice and LPS induced a further decrease. Leptin treatment affected neither basal glucose nor that after LPS. LPS induced a fivefold greater increase in serum TNF in fasted mice, which was blunted by leptin replacement. In contrast, LPS induced lower levels of interferon-gamma and no differences in interleukin-1beta in fasted compared to fed animals; leptin had no effect on those cytokines. Furthermore, fasting increased sensitivity to the lethal effect of TNF itself, which was also reversed by leptin treatment. Thus, leptin seems to be protective by both inhibiting TNF induction by LPS and by reducing TNF toxicity.

Animals↗

PubMed2000

Congenital dyserythropoietic anemia type I presenting as persistent pulmonary hypertension of the newborn.

Congenital dyserythropoietic anemia (CDA) is a rare group of inherited bone marrow disorders characterized by anemia with ineffective erythropoiesis. We report 3 siblings from a family known to have CDA type I who presented with persistent pulmonary hypertension of the newborn (PPHN). We suggest that the diagnosis of CDA type I should be considered in any neonate with PPHN and anemia.

Anemia, Dyserythropoietic, Congenital↗

PubMed2000

Structured triacylglycerol emulsion, containing both medium- and long-chain fatty acids, in long-term home parenteral nutrition: a double-blind randomized cross-over study.

Structured lipid emulsion, an innovative approach in which both medium-chain and long-chain fatty acids are esterified to the same glycerol backbone, has been recently shown to be a safe and efficient way of providing energy to patients requiring parenteral nutrition. As yet, no assessment has been made of its safety and effect on liver functions during long-term treatment. Twenty-two home parenteral nutrition patients with Crohn's disease or short bowel syndrome were enrolled in a double-blind randomized, cross-over study. Twenty patients who completed the study were treated for 4 wk with a structured lipid emulsion and for 4 wk with long-chain triacylglycerol emulsion. Determined every 1 or 2 wk were blood pressure, body weight, respiratory rate, blood count, liver functions, albumin, transferrin, plasma lipids, free fatty acids (FFAs), and, at the end of each treatment period (weeks 4 and 8), plasma dicarboxylic acids and 3-OH-fatty acids. No differences were observed between the groups or within the groups between the two treatments with respect to either clinical safety and adverse event occurrence or laboratory assessments. Plasma dicarboxylic acids and 3-OH-fatty acids were similar and within normal range. No alteration of liver function occurred in any of the patients treated with the structured lipid emulsion, whereas two of the patients receiving long-chain triaclyglycerol emulsion developed abnormal liver function, which resolved after switching to the structured lipid emulsion. In conclusion, structured triacylyglycerols containing both medium- and long-chain fatty acids appear to be safe and well tolerated on a long-term basis in patients on home parenteral nutrition, and it may be associated with possible reduction in liver dysfunction.

Adolescent↗