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B Spindler

Publications and source records attributed to B Spindler.

At least 19 recordsLinked to original sources
PubMed2006

[Pathological and histopathological findings in the joints of fattening turkeys].

This paper reports on pathological and histopathological findings in the joints of male turkeys (B.U.T. Big 6) reared in two different housing systems. Pathological investigations were conducted on all animals which died between the 6th week of life and the end of fattening (585 birds, 1170 hip, knee and intertarsal joints) from four fattening periods with 3000 birds each. This study included 297 birds kept in a conventional housing system (barn 2) with a stocking density of 2.8 birds/m2, and 288 birds from a barn (1) from which the animals had access to an outdoor scratching area (stocking density 2.5 birds/m2). In all, 157 (26.5%) of the 585 fallen turkeys (barn 1:93; barn 2:70) showed at least one pathological joint alteration. and there were macroscopically detectable changes in 274 (7.8%) of the 3510 investigated joints: 152 (7.8%) of the 1728 joints from barn 1, and 122 (8.8%) of the 1782 from barn 2. In both housing systems the most frequent pathological alterations were in the intertarsal joint affecting 16% (188) of these 1170 joints (barn 1:106; barn 2:82); next most frequent were changes in the knee joint with 4.5% (53) of the 1170 joints affected (barn 1:26; barn 2:27). In both barns, synovial alterations occurred predominantly in the intertarsal and the knee joints. Bacteriological investigation of altered synovial fluids (83) most frequently showed an infection with Staphylococcus spp. (44) and E. coli (15). Macroscopic investigation showed alterations in 31 (2.7%) of the 1170 hip joints (barn 1:19; barn 2:12); 2% (22) of these showed cartilage degenerations of the femoral head (barn 1:15; barn 2:7). Histological investigation of these cartilage lesions showed that they were predominantly (70%) due to osteochondrosis with complete epiphyseolysis affecting 16 femoral heads (barn 1:10; barn 2:6). Partial epiphysiolysis was found in 24% (5) of the femoral heads (barn 1:4; barn 2:1). Furthermore, 43% (9) of the 22 femoral heads with cartilage degeneration also had osteomyelitis and osteochondritis, as well (barn 1:6; barn 2:3). Histological investigation of the 104 femoral heads with no macroscopic findings (barn 1:56; barn 2:48), revealed osteochondrosis in 11 cases (10.6%) (barn 1:6; barn 2:5). Osteomyelitis and osteochondritis were found in 17 (16.3%) of these femoral heads (barn 1:9; barn 2:8). There were no significant (p < 0.05) differences between the two housing systems in the incidence and frequency of joint alterations. It is to be assumed that these joint alterations were the cause of acute, chronic pain.

Animals↗
PubMed2000

Pleiotropic action of aldosterone in epithelia mediated by transcription and post-transcription mechanisms.

The aldosterone-induced increase in sodium reabsorption across tight epithelia can be divided schematically into two functional phases: an early regulatory phase starting after a lag period of 20 to 60 minutes, during which the pre-existing transport machinery is activated, and a late phase (>2.5 h), which can be viewed as an anabolic action leading to a further amplification/differentiation of the Na+ transport machinery. At the transcriptional level, both early and late responses are initiated during the lag period, but the functional impact of newly synthesized regulatory proteins is faster than that of the structural ones. K-Ras2 and SGK were identified as the first early aldosterone-induced regulatory proteins in A6 epithelia. Their mRNAs also were shown to be regulated in vivo by aldosterone, and their expression (constitutively active K-Ras2 and wild-type SGK) was shown to increase the function of ENaC coexpressed in Xenopus oocytes. Recently, aldosterone was also shown to act on transcription factors in A6 epithelia: It down-regulates the mRNAs of the proliferation-promoting c-Myc, c-Jun, and c-Fos by a post-transcriptional mechanism, whereas it up-regulates that of Fra-2 (c-Fos antagonist) at the transcriptional level. Together, these new data illustrate the complexity of the regulatory network controlled by aldosterone and support the view that its early action is mediated by the induction of key regulatory proteins such as K-Ras2 and SGK. These early induced proteins are sites of convergence for different regulatory inputs, and thus, their aldosterone-regulated expression level tunes the impact of other regulatory cascades on sodium transport. This suggests mechanisms for the escape from aldosterone action.

Aldosterone↗
PubMed2000

A novel mutation in KVLQT1, L122P, found in a family with autosomal dominant long QT syndrome.

BACKGROUND: Linkage and mutation analysis in long QT syndrome kindreds has demonstrated locus heterogeneity, with causative mutations reported in at least 5 different genes, including KVLQT1. METHODS AND RESULTS: A 12-year-old male proband with recurrent syncope and a prolonged QT interval underwent clinical assessment and exercise testing along with 3 affected and 3 unaffected family members. The coding regions of 5 putative transmembrane segments (S2-S6) and a putative pore region of the KVLQT1 gene for the proband were amplified with the polymerase chain reaction. DNA sequencing of the KVLQT1 gene of the proband revealed a T-->C transversion at the second position of codon 122, which predicted a substitution of proline for leucine (L122P). By using restriction analysis, the L122P was found to be co-segregated with the electrocardiographic abnormalities in the nuclear family. Although the patient's mother was heterozygous for L122P, neither maternal grandparent was a carrier, suggesting that the mutation arose spontaneously. In comparison, there was a complete absence of the mutation in 1336 alleles from 668 normal individuals of 6 different ethnic backgrounds. CONCLUSION: The KVLQT1 L122P mutation is a rare novel mutation that probably arose spontaneously in this family, leading to long QT syndrome.

Child↗
PubMed2000

Rate-control versus conversion strategy in postoperative atrial fibrillation: a prospective, randomized pilot study.

BACKGROUND: Atrial fibrillation remains a frequent complication after heart surgery. The optimal strategy to treat the condition has not been established. Several retrospective studies have suggested that a primary rate-control strategy may be equivalent to a strategy that restores sinus rhythm. METHODS: Fifty patients with atrial fibrillation after heart surgery were randomly assigned to a strategy of antiarrhythmic therapy with or without electrical cardioversion or ventricular rate control. Both arms received anticoagulation with heparin overlapped with warfarin. The primary end point was time to conversion to sinus rhythm analyzed by the Kaplan-Meier method. Atrial fibrillation relapse after the initial conversion was monitored in the hospital over a 2-month period. RESULTS: There was no significant difference between an antiarrhythmic conversion strategy (n = 27) and a rate-control strategy (n = 23) in time to conversion to sinus rhythm (11.2 +/- 3. 2 vs 11.8 +/- 3.9 hours; P =.8). With the use of Cox multivariate analysis to control for the effects of age, sex, beta-blocker usage, and type of surgery, the antiarrhythmic strategy showed a trend toward reducing the time from treatment to restoration of sinus rhythm (P =.08). The length of hospital stay was reduced in the antiarrhythmic arm compared with the rate-control strategy (9.0 +/- 0.7 vs 13.2 +/- 2.0 days; P =.05). In-hospital relapse rates in the antiarrhythmic arm were 30% compared with 57% in the rate-control strategy (P =.24). There were no significant difference in relapse rates at 1 week (24% vs 28%), 4 weeks (6% vs 12%), and 6 to 8 weeks (4% vs 9%). At the end of the study, 91% of the patients in the rate-control arm were in sinus rhythm compared with 96% in the antiarrhythmic arm (P =.6). CONCLUSIONS: This pilot study shows little difference between a rate-control strategy and a strategy to restore sinus rhythm. Regardless of strategy, most patients will be in sinus rhythm after 2 months. A larger randomized, controlled study is needed to assess the impact of restoration of sinus rhythm on length of stay.

Aged↗
PubMed1999

Amino acid transport of y+L-type by heterodimers of 4F2hc/CD98 and members of the glycoprotein-associated amino acid transporter family.

Amino acid transport across cellular membranes is mediated by multiple transporters with overlapping specificities. We recently have identified the vertebrate proteins which mediate Na+-independent exchange of large neutral amino acids corresponding to transport system L. This transporter consists of a novel amino acid permease-related protein (LAT1 or AmAT-L-lc) which for surface expression and function requires formation of disulfide-linked heterodimers with the glycosylated heavy chain of the h4F2/CD98 surface antigen. We show that h4F2hc also associates with other mammalian light chains, e.g. y+LAT1 from mouse and human which are approximately 48% identical with LAT1 and thus belong to the same family of glycoprotein-associated amino acid transporters. The novel heterodimers form exchangers which mediate the cellular efflux of cationic amino acids and the Na+-dependent uptake of large neutral amino acids. These transport characteristics and kinetic and pharmacological fingerprints identify them as y+L-type transport systems. The mRNA encoding my+LAT1 is detectable in most adult tissues and expressed at high levels in kidney cortex and intestine. This suggests that the y+LAT1-4F2hc heterodimer, besides participating in amino acid uptake/secretion in many cell types, is the basolateral amino acid exchanger involved in transepithelial reabsorption of cationic amino acids; hence, its defect might be the cause of the human genetic disease lysinuric protein intolerance.

Amino Acid Sequence↗
PubMed1999

Aldosterone action: induction of p21(ras) and fra-2 and transcription-independent decrease in myc, jun, and fos.

Adrenal steroids induce an increase in transcellular Na+ reabsorption across Xenopus laevis A6 cell epithelia that requires the action of transcriptionally regulated gene products. In a previous study we identified K-ras2 as an aldosterone-upregulated mRNA in A6 epithelia. Here, we show that in vivo injection of aldosterone in Xenopus (2.5 h) increases K-ras2 mRNA specifically in the kidney (2.5-fold) and that in A6 epithelia aldosterone (2.5 h) increases Ras protein synthesis ( approximately 6-fold). Xl-ras, another ras mRNA expressed at a low level in A6 cells, was also induced (2-fold). Aldosterone was shown to regulate the mRNA levels of several transcription factors as well. After 2 h of aldosterone treatment, fra-2 mRNA was upregulated by 130%, whereas c-myc, c-jun, c-fos, and glucocorticoid receptor mRNAs were downregulated by 23-43%. After 16 h, c-fos and GR mRNAs were further decreased, whereas levels of fra-2, c-jun, and c-myc began to return to control levels. Interestingly, the downregulation of the protooncogene mRNAs was independent of transcription. These results support the view that aldosterone exerts complex pleiotropic transcriptional and nontranscriptional actions that involve the regulation of signaling cascade elements (i.e., K-Ras2) as well as that of transcription factors.

Aldosterone↗
PubMed1998

Functional heterodimeric amino acid transporters lacking cysteine residues involved in disulfide bond.

The protein mediating system L amino acid transport, AmAT-L, is a disulfide-linked heterodimer of a permease-related light chain (AmAT-L-lc) and the type II glycoprotein 4F2hc/ CD98. The Schistosoma mansoni protein SPRM1 also heterodimerizes with h4F2hc, inducing amino acid transport with different specificity. In this study, we show that the disulfide bond is formed by heavy chain C109 with a Cys residue located in the second putative extracellular loop of the multi-transmembrane domain light chain (C164 and C137 for XAmAT-L-lc and SPRM1, respectively). The non-covalent interaction of Cys-mutant subunits is not sufficient to allow coimmunoprecipitation, but cell surface expression of the light chains is maintained to a large extent. The non-covalently linked transporters display the same transport characteristics as disulfide bound heterodimers, but the maximal transport rates are reduced by 30-80%.

Amino Acid Transport Systems↗
PubMed1998

Amino-acid transport by heterodimers of 4F2hc/CD98 and members of a permease family.

Amino-acid transport across cellular plasma membranes depends on several parallel-functioning (co-)transporters and exchangers. The widespread transport system L accounts for a sodium-independent exchange of large, neutral amino acids, whereas the system y(+)L exchanges positively charged amino acids and/or neutral amino acids together with sodium. The molecular nature of these transporters remains unknown, although expression of the human cell-surface glycoprotein 4F2 heavy chain (h4F2hc; CD98 in the mouse) is known to induce low levels of L- and/or y(+)L-type transport. This glycoprotein is found in activated lymphocytes, together with an uncharacterized, disulphide-linked lipophilic light chain with an apparent relative molecular mass of 40,000 (M(r) 40K). Here we identify the permease-related protein E16 as the first light chain of h4F2hc and show that the resulting heterodimeric complex mediates L-type amino-acid transport. The homologous protein from Schistosoma mansoni, SPRM1, also associates covalently with coexpressed h4F2hc glycoprotein, although it induces amino-acid transport of different substrate specificity. The coexpression of h4F2hc is required for surface expression of these permease-related light chains, which belong to a new family of amino-acid transporters that form heterodimers with cell-surface glycoproteins.

Amino Acid Transport Systems↗
PubMed1998

Ras pathway activates epithelial Na+ channel and decreases its surface expression in Xenopus oocytes.

The small G protein K-Ras2A is rapidly induced by aldosterone in A6 epithelia. In these Xenopus sodium reabsorbing cells, aldosterone rapidly activates preexisting epithelial Na+ channels (XENaC) via a transcriptionally mediated mechanism. In the Xenopus oocytes expression system, we tested whether the K-Ras2A pathway impacts on XENaC activity by expressing XENaC alone or together with XK-Ras2A rendered constitutively active (XK-Ras2AG12V). As a second control, XENaC-expressing oocytes were treated with progesterone, a sex steroid that induces maturation of the oocytes similarly to activated Ras. Progesterone or XK-Ras2AG12V led to oocyte maturation characterized by a decrease in surface area and endogenous Na+ pump function. In both conditions, the surface expression of exogenous XENaC's was also decreased; however, in comparison with progesterone-treated oocytes, XK-ras2AG12V-coinjected oocytes expressed a fivefold higher XENaC-mediated macroscopic Na+ current that was as high as that of control oocytes. Thus, the Na+ current per surface-expressed XENaC was increased by XK-Ras2AG12V. The chemical driving force for Na+ influx was not changed, suggesting that XK-Ras2AG12V increased the mean activity of XENaCs at the oocyte surface. These observations raise the possibility that XK-Ras2A, which is the first regulatory protein known to be transcriptionally induced by aldosterone, could play a role in the control of XENaC function in aldosterone target cells.

Aldosterone↗
PubMed1997

Characterization of early aldosterone-induced RNAs identified in A6 kidney epithelia.

The early aldosterone-induced increase in Na reabsorption across tight epithelia is characterized by a transcription-dependent activation of epithelial Na channels (ENaC) and pumps (Na,K-ATPase). In order to contribute towards the identification of transcriptionally regulated mediators of this process, we first tested mRNAs of proteins previously suggested to be involved. Epithelia were treated for 1 h with 10(-6 )M aldosterone, a concentration which produces a maximal transport response and at which both mineralo- and glucocorticoid receptors are occupied. Northern blot analysis showed no change in mRNAs of trimeric G protein alpha subunits, calmodulin, and mitochondrial energy metabolism proteins, whereas Na,K-ATPase alpha1 and beta1 subunit mRNAs were slightly increased (1.2- to 1.4-fold). In a second approach, we visualized 5000 cDNA bands generated from A6 RNAs by differential display polymerase chain reaction (PCR). After 1 h of aldosterone treatment, approximately 0.5% of these appeared to be regulated. Four cDNA fragments corresponding to early adrenal-steroid-upregulated RNAs (ASURs) were cloned and for two of them cDNAs containing entire coding sequences were isolated by library screening. ASUR4 is the Xenopus laevis homologue of human E16 and rat TA1, a membrane protein structurally related to yeast and prokaryotic permeases, and ASUR5 is the A transcript of Xenopus K-ras2. The rapid inductions of the four ASURs correspond to direct transcriptional effects since they were not inhibited by cycloheximide but were blocked by actinomycin D. The K1/2 values were similar or slightly below those reported for stimulation of Na transport. These characteristics of RNA accumulation and their time courses suggest a possible role of one of these induced RNAs in the mediation of the early effect of aldosterone on Na transport.

Aldosterone↗
PubMed1997

Metabolic support of Na+ pump in apically permeabilized A6 kidney cell epithelia: role of creatine kinase.

The contribution of ATP-generating systems to Na+ pump (Na+-K+-ATPase) function was studied in Xenopus laevis A6 kidney epithelia apically permeabilized with digitonin. The ouabain-inhibitable Na+ pump current (I(P)) was measured in the presence of otherwise impermeant inhibitors and/or substrates at Na+ and K+ concentrations that allowed near-maximal pump function. Confocal fluorescence microscopy after apical addition of sulfosuccinimidobiotin (molecular weight of 443) showed that all cells were permeabilized. Less than 15% of the endogenous lactate dehydrogenase and creatine kinase (CK) were released into the apical medium. The I(P) was approximately 5 microA/cm2 in the presence of D-glucose. Blocking glycolysis with 2-deoxy-D-glucose or oxidative phosphorylation with antimycin A decreased it by > or = 50%. Exogenously added ATP prevented these decreases fully or partially, respectively. Two CK isoforms were detected, one likely being mitochondrial and the other corresponding to mammalian B isoform of CK. Phosphocreatine partially restored Na+ pump activity during inhibition of either ATP synthesis pathway. In conclusion, the ATP used by Na+ pumps of apically digitonin-permeabilized A6 epithelia is generated to a similar extent by glycolysis and oxidative phosphorylation. The CK system can partially support the ATP supply to the Na+ pumps.

Adenosine Triphosphate↗
PubMed1997

Identification of a new gene product (diphor-1) regulated by dietary phosphate.

Chronic restriction of dietary Pi elicits an increased reabsorption of Pi in the kidney proximal tubules, which involves a stimulation of apical Na-Pi cotransport. This adaptation is in part a direct cellular response of which the mechanism(s) are poorly understood. In this study, the impact of dietary Pi restriction on the differential expression of rat kidney cortex mRNAs was visualized to identify gene products regulated by the Pi status. When kidney cortex mRNAs of rats fed a low- or a high-Pi diet were compared by differential display-polymerase chain reaction (DD-PCR), thirty modulated cDNA bands were observed, of which four were confirmed as being regulated. We focused on one of the upregulated bands, dietary Pi-regulated RNA-1 (diphor-1). A cDNA containing an open reading frame encoding a 52-kDa protein was cloned by library screening. Diphor-1 exhibits a high degree of identity to the Na/H exchanger regulatory factor and to a tyrosine kinase activating protein. Highest expression of diphor-1 mRNA was detected in the kidney (proximal tubules) and in small intestine. Expression experiments showed that diphor-1 specifically increases Na-Pi cotransport in oocytes of Xenopus laevis coinjected with renal type II Na-Pi contransporter cRNA. Further characterizations of diphor-1 will show whether diphor-1 is primarily or secondarily involved in the response to dietary Pi.

Amino Acid Sequence↗
PubMed1996

Renal type II Na/Pi-cotransporter is strongly impaired whereas the Na/sulphate-cotransporter and aquaporin 1 are unchanged in cadmium-treated rats.

The cellular mechanisms of cadmium (Cd) nephrotoxicity are poorly understood. In this study we investigated the cellular causes of the Cd-induced phosphaturia in the rat. Compared to controls, Cd-treated rats (2 mg Cd/kg body weight, s.c. for 14 days) showed a marked polyuria, proteinuria and phosphaturia. As studied by the rapid filtration technique in isolated cortical brush-border membrane vesicles (BBMV), Na+-gradient-driven uptake of phosphate ([32Pi]) and of [3H] glucose were markedly decreased in Cd-treated rats, whereas uptake of sulphate ([35S]) remained unchanged. By Western blotting of BBMV proteins and by indirect immunocytochemistry in 4-micron thick frozen fixed kidney sections, using an antibody against the type II Na/Pi-cotransporter (NaPi-2), we found a diminished expression of this protein in the brush-border membrane from Cd-treated rats. How ever, the expression of the water channel aquaporin 1, estimated from the specific antibody staining in brush-border membranes, remained unchanged by Cd. Northern blot analysis showed a strong reduction of 2.7 kb NaPi-2-related mRNA in Cd-affected kidneys. Our data indicate that: (1) Cd may reduce reabsorption of Pi in proximal tubules by affecting the expression of the functional Na/Pi-cotransporters in the luminal membrane, and (2) Cd effects on brush-border transporters are selective.

Animals↗
PubMed1996

Corticosteroid regulation of renal Na,K-ATPase.

The nature and the mechanisms of renal Na,K-ATPase (Na pump) regulation by corticosteroids remain a matter of debate. This is mainly due to the limitations of the experimental approaches, the inhomogeneity of the nephron and the complexity of homeostatic feedback mechanisms. However, 'classical' early and late cellular actions of corticosteroids, which are mineralocorticoid-specific in the collecting duct, can be recognized: The 'early action' is characterized by an increase in the number of active (versus inactive) pumps and/or by a change in their kinetic properties. The 'late action' is characterized by an increase in the number of pumps resulting from, at least in part, an increase in the rate of Na,K-ATPase gene transcription. Sodium delivery into the cells and other elements of the regulatory network play permissive or co-regulatory roles in both early and late actions.

Adrenal Cortex Hormones↗
PubMed1986

The effect of hydrocortisone on the production of gamma-interferon and other lymphokines by human peripheral blood mononuclear cells.

Concentrations of hydrocortisone as low as 0.08 microgram/ml significantly reduced the yields of gamma-interferon (IFN-gamma) when phytohemagglutinin (PHA) or concanavalin A (ConA) were used as inducers; however, when staphylococcal enterotoxin A was utilized, higher concentrations (5.0 micrograms/ml) were required to achieve the same effect. Yields of interleukin-2 (IL-2) and lymphotoxin were also found to be sensitive to the effects of the steroids, but expressions of TAC antigen was not generally affected by these agents. In contrast to the effects of steroids on cell proliferation, lymphokine production remained suppressed after steroid withdrawal. Hydrocortisone appeared to influence the concentrations of cyclic nucleotides following lectin stimulation, but attempts to correct these alterations or to add exogenous IL-2 failed to restore lymphokine production to normal levels. Addition of the calcium ionophore A23187 partially restored IFN-gamma production. We conclude that the effects of corticosteroids on the yields of lymphokines, including IFN-gamma, are profound. The depression of lymphokine production appears to be associated with a number of alterations in the cell, including depression of protein synthesis, alterations in cyclic nucleotides, and diminution of the production of cofactors necessary for IFN-gamma production. Enhancement of the flux of calcium into the cell may restore some of the ability to produce IFN-gamma.

Antigens, Surface↗