Biomedical subjects

S Berger

Publications and source records attributed to S Berger.

At least 91 records · Page 5Linked to original sources

PubMed1999

Effects of mineralocorticoid receptor gene disruption on the components of the renin-angiotensin system in 8-day-old mice.

Targeted disruption of mineralocorticoid receptor (MR) gene results in pseudohypoaldosteronism type I with failure to thrive, severe dehydration, hyperkalemia, hyponatremia, and high plasma levels of renin, angiotensin II, and aldosterone. In this study, mRNA expression of the different components of the renin-angiotensin system (RAS) were evaluated in liver, lung, heart, kidney and adrenal gland to assess their response to a state of extreme sodium depletion. Angiotensinogen, renin, angiotensin-I converting enzyme, and angiotensin II receptor (AT1 and AT2) mRNA expressions were determined by Northern blot and RT-PCR analysis. Furthermore, in situ hybridization and immunohistochemistry allowed us to identify the cell types involved in the variation of the RAS component expression. In the heterozygous mice (MR+/-), compared with wild-type mice (MR+/+), there was no significant variation of any mRNA of the RAS components. In MR knockout mice (MR-/-), compared with wild-type mice, there were significant increases in the expression level of several RAS components. In the liver, angiotensinogen and AT1 receptor mRNA expressions were moderately stimulated. In the kidney, renin mRNA was increased up to 10-fold and in situ hybridization showed a marked recruitment of renin-producing cells; however, the levels of angiotensin-I converting enzyme mRNA and AT1 mRNA were not changed. Interestingly, in adrenal gland, renin expression was also strongly up-regulated in a thickened zona glomerulosa, whereas AT1 mRNA expression remained unchanged. Altogether, these results demonstrate that in the MR knockout mice model, RAS component expressions are differentially altered, renin being the most stimulated component. Angiotensinogen and AT1 in the liver are also increased, but the other elements of the RAS are not affected.

Adrenal Glands↗

PubMed1999

De novo development of a cavernous malformation of the spinal cord following spinal axis radiation. Case report.

Analysis of recent reports has suggested that cavernous malformations (CMs) of the brain may have an acquired pathogenesis and a dynamic pathophysiological composition, with documented appearance of new lesions in familial cases and following radiotherapy. The authors report the first case of demonstrated de novo formation of an intramedullary CM following spinal radiation therapy. A 17 year-old boy presented with diabetes insipidus and delayed puberty. Evaluation of endocrine levels revealed hypopituitarism, and magnetic resonance (MR) imaging demonstrated an infundibular mass. The patient underwent a pterional craniotomy and removal of an infundibular germinoma. The MR image of the spine demonstrated normal results. The patient received craniospinal radiation therapy and did well. He presented 5 years later with acute onset of back pain, lower-extremity weakness and numbness, and difficulty with urination. An MR image obtained of the spine revealed an intramedullary T-7 lesion; its signal characteristics were consistent with a CM. The patient was initially managed conservatively but developed progressive myelopathy and partial Brown-Séquard syndrome. Although he received high-dose steroids and bed rest, his symptoms worsened. He underwent a costotransversectomy and excision of a hemorrhagic vascular lesion via an anterolateral myelotomy. Pathological examination confirmed features of a CM. The patient has done well and was walking without assistance within 4 weeks of surgery. De novo genesis of CMs may be associated with prior radiation therapy to the spinal cord.

Abnormalities, Radiation-Induced↗

PubMed1998

Mineralocorticoid receptor knockout mice: pathophysiology of Na+ metabolism.

Mineralocorticoid receptor (MR)-deficient mice were generated by gene targeting. These animals had a normal prenatal development. During the first week of life, MR-deficient (-/-) mice developed symptoms of pseudohypoaldosteronism. They finally lost weight and eventually died at around day 10 after birth from dehydration by renal sodium and water loss. At day 8, -/- mice showed hyperkalemia, hyponatremia, and a strong increase in renin, angiotensin II, and aldosterone plasma concentrations. Methods were established to measure renal clearance and colonic transepithelial Na+ reabsorption in 8-day-old mice in vivo. The fractional renal Na+ excretion was elevated >8-fold. The glomerular filtration rate in -/- mice was not different from controls. The effect of amiloride on renal Na+ excretion and colonic transepithelial voltage reflects the function of amiloide-sensitive epithelial Na+ channels (ENaC). In -/- mice, it was reduced to 24% in the kidney and to 16% in the colon. There was, however, still significant residual ENaC-mediated Na+ reabsorption in both epithelia. RNase protection analysis of the subunits of ENaC and (Na++ K+)-ATPase did not reveal a decrease in -/- mice. The present data indicate that MR-deficient neonates die because they are not able to compensate renal Na+ loss. Regulation of Na+ reabsorption via MR is not achieved by transcriptional control of ENaC and (Na+ + K+)-ATPase in RNA abundance but by transcriptional control of other as yet unidentified genes. MR knockout mice will be a suitable tool for the search of these genes.

Amiloride↗

PubMed1998

Occurrence of proteinaceous 10-nm filaments throughout the cytoplasm of algae of the order Dasycladales.

Previously, whole-mount electron microscopy of nuclei extruded together with residual cytoplasm from the rhizoids of several algal species of the order Dasycladales has revealed the occurrence of an intra- and perinuclear network of 10-nm filaments morphologically indistinguishable from that of mammalian vimentin intermediate filaments. The present investigation demonstrates the existence of a filament system throughout the cytoplasm of the rhizoid, stalk, and apical tip of these giant cells. However, while the perinuclear 10-nm filaments interconnecting the nuclear surface with a perinuclear layer of large, electron-dense bodies filled with nucleoprotein material are of smooth appearance, those continuing within and beyond the perinuclear bodies are densely covered with differently sized, globular structures and, therefore, are of a very rough appearance. The filaments in the very apical tip of the cells are mainly of the smooth type. The transition from smooth to rough filaments seems to occur in the numerous perinuclear dense bodies surrounding the large nucleus. Digestion of the rough filaments with proteinase K removes the globules from the filament surface, revealing that throughout the nonvacuolar, intracellular space the filaments have the same basic 10-nm structure. On the other hand, gold-conjugated RNase A strongly binds to the filament-attached globules but not to the smooth, perinuclear, and the proteinase K-treated, rough filaments. In addition, an antibody raised against Xp54, a highly conserved protein which in Xenopus oocytes is an integral component of stored mRNP particles, decorates the rough but not the smooth 10-nm filaments. These results support the notion that the 10-nm filament system of Dasycladales cells plays a role in the transient storage of ribonucleoprotein particles in the cytoplasm and possibly fulfils a supportive function in the actomyosin-based transport of such material to various cytological destinations.

Chlorophyta↗

PubMed1998

Congenital malformations and perinatal morbidity associated with intestinal neuronal dysplasia.

A close relation between different forms of dysganglionosis such as intestinal neuronal dysplasia (IND) type B and aganglionosis has been established. No systematic analysis of other malformations and diseases accompanying IND has been made as yet. Congenital malformations and perinatal morbidity were analyzed in 109 patients with IND seen at the Department of Pediatric Surgery in Mainz from 1977 to 1996. IND was associated with Hirschsprung's disease in 47 cases; 22 children with IND had other abdominal malformations, including anal atresia, rectal stenosis, sigmoidal stenosis, ileal atresia, pyloric stenosis, and esophageal atresia. A cystic bowel duplication, a choledochal cyst, and a persisting urachus were also found. Extra-abdominal malformations such as Down's syndrome, congenital diaphragmatic hernia, aortic stenosis, and malformations of vertebral bodies were seen. Twin siblings of children with IND were either healthy (n=3) or died in utero (n=1). Seventeen children with IND developed severe intra-abdominal complications during the perinatal period such as necrotizing enterocolitis (NEC), meconium ileus, or bowel perforations. NEC was frequently associated with preterm birth. Bowel perforations were seen in mature and preterm newborns with IND. Taken together, IND is found in a variety of obstructive bowel diseases. This may support the hypothesis that IND is a secondary phenomenon or that congenital atresias and stenoses of the digestive tract have a pathogenesis similar to that of intestinal innervation disturbances. IND may also be a part of complex malformation patterns since it occurs with a number of extraintestinal and non-obstructive intestinal malformations.

Abnormalities, Multiple↗

PubMed1998

Postoperative intussusception in childhood.

Over a period of 10 years, five children developed postoperative intussusception after intra-abdominal procedures at the Department of Pediatric Surgery of the Johannes Gutenberg University Mainz. Two appendectomies, one ileal resection for a Meckel's diverticulum, one operative procedure for Hirschsprung's disease plus intestinal neuronal dysplasia type B, and one hiatoplasty with jejunostomy preceded the intussusception. Three of the five children were older than 2 years. The clinical symptoms consisted primarily of abdominal distension, diffuse abdominal pain, bilious vomiting, and rectal bleeding in one case. Preoperative diagnosis was achieved in four cases by abdominal ultrasound. Plain abdominal radiographs demonstrated dilated loops of small intestine with air-fluid levels in four of the five cases. In the case without radiographic findings, the jejunojejunal intussusception was missed even by a bowel follow-through. The intussusceptions were ileocolic (3), ileoileal (1), and jejunojejunal (1). A hydrostatic procedure to reduce an ileocolic intussusception was not successful. Operative treatment of the intussusception was performed in three cases within 5 days, once at 32 days, and once 3 months after the primary operation, in all cases by laparatomy and simple manual reduction without intestinal resection. In contrast to idiopathic intussusception, noninvasive hydrostatic procedures are not indicated in postoperative intussusception, since protection of intestinal anastomoses from hydrostatic pressure and exclusion of other causes of postoperative ileus are mandatory.

Abdomen↗

PubMed1998

Wide frequency range 31P relaxation in the ion conducting glass LiPO3.

Spin-lattice relaxation studies on the stationary 31P nucleus have been performed in order to investigate to which extent the dynamics of the mobile lithium ions are reflected in the behavior of the glassy network. The temperature dependence of the 31P relaxation, which is governed by the heteronuclear dipole-dipole interaction between lithium and phosphorus, can be described in terms of a Gaussian distribution of activation energies and that over a wide frequency range from about 34 kHz to 81 MHz. A relaxation rate maximum, which provides useful information about correlation times and activation energies of the lithium-ion diffusion process, could only be observed in the rotating frame relaxation measurements.

Lithium↗

PubMed1998

Reversible protein phosphorylation regulates jasmonic acid-dependent and -independent wound signal transduction pathways in Arabidopsis thaliana.

Plants responses to mechanical injury are complex and include the induced expression of defence-related genes. The phytohormone JA has been reported to mediate some of these responses. To elucidate further the signal transduction processes involved, the action of specific agonists and antagonists of known signalling effectors on the response of Arabidopsis thaliana plantlets to JA and wounding was investigated. The identification and characterization of a reversible protein phosphorylation step in a transduction pathway leading to JA-induced gene transcription is reported. This phosphorylation event involved the opposing activities of a staurosporine-sensitive protein kinase, negatively regulating the pathway, and a protein phosphatase, most probably of type 2 A, which activated JA-responsive gene expression. JA activation via this pathway was blocked in the A. thaliana JA-insensitive mutants jin1, jin4 and coi1, and by exogenous application of cycloheximide or auxins. Wound-induced activation of JA-responsive genes was also regulated by this protein phosphorylation step. An alternative wound signalling pathway, independent of JA, was also identified, leading to the transcriptional activation of a different set of genes. This JA-independent pathway was also regulated by a protein phosphorylation switch, in which the protein kinase positively regulated the pathway while the protein phosphatase negatively regulated it. Moreover, a labile protein apparently repressed the expression of these genes. One of the genes analysed, JR3, had a complex pattern of expression, possibly because it was regulated via both of the wound signalling pathways identified. According to the function of an homologous gene, JR3 may be involved in feedback inhibition of the JA response.

Arabidopsis↗

PubMed1998

Study of the influence of salt concentration on Newcastle disease virus matrix protein aggregation.

The aggregation process of Newcastle disease virus matrix protein (M protein) has been studied using light scattering. We observed that the aggregation of M protein is inversely correlated with ionic strength and that this process can be reversed by high salt concentrations. It was found that the oligomeric structure of NDV matrix protein is different from those described earlier for other matrix proteins of enveloped viruses.

Light↗

PubMed1998

A hypersensitive response-like mechanism is involved in resistance of potato plants bearing the Ry(sto) gene to the potyviruses potato virus Y and tobacco etch virus.

Potato plants carrying the Ry(sto) gene from Solanum stoloniferum are extremely resistant to a number of potyviruses, but it is not known at what stage of infection the resistance is expressed. The resistance may be due to Ry(sto) or to a closely linked gene. In this investigation, we used potato virus Y (PVY) and a tobacco etch virus construct that encodes beta-glucuronidase (TEV-GUS) to monitor virus infections of potato plants. Systemic spread of either virus in resistant potato plants was not detectable by serology, RT-PCR, GUS assay or bioassay although each replicated in the initially infected cells of leaves from resistant potato cultivars and was transported into neighbouring cells. However, 3 days post-inoculation (p.i.) a necrotic reaction set in that stopped movement and accumulation of both viruses by 7 days p.i. The resistance reaction (probably a hypersensitive reaction) became visible as necrotic streaks on veins on the lower leaflet surfaces of some potato cultivars carrying the Ry(sto) gene and may be elicited by a common potyviral gene product.

Genes, Plant↗

PubMed1998

The WAIS-R factors: usefulness and construct validity in neuropsychological assessments.

One-hundred and twelve patients were administered the Wechsler Adult Intelligence Scale-Revised (WAIS-R), an abbreviated Wechsler Memory Scale-Revised, and the Halstead-Reitan Neuropsychological Test Battery. In order to replicate an earlier study (Sherman, Strauss, Spellacy, & Hunter, 1995), correlations were generated between the WAIS-R factor scores and neuropsychological and memory tests. The Verbal Comprehension factor (Factor 1) correlated with Speech Sounds Perception Test (SSPT), the Seashore Rhythm Test (SSRT), the Category Test, and memory indices. The Perceptual Organizational factor (Factor 2) correlated with the time, memory, and location scores of the Tactual Performance Test, the SSPT, SSRT, the Category Test, Trails A, Trails B, memory indices, and finger tapping. The Freedom From Distractibility factor (Factor 3) was correlated with the Category Test, the SSPT, the SSRT, Trails A, Trails B, immediate Logical Memory, and Visual Reproduction. Modest correlations suggest that the WAIS-R factors may be useful for understanding underlying cognitive performance and can be functional for generating hypotheses, but should not be utilized exclusively to make clinical inferences.

Journal Article↗

PubMed1998

Transforming growth factor-beta stimulates urokinase expression in tumor-associated macrophages of the breast.

Recent studies have shown that urokinase (uPA) is an independent prognostic marker in breast cancer. uPA plays a key role in the degradation of tumor matrix and promotes tumor progression. Macrophage expression of uPA appears to be important in this context. Our objective in the present study was to provide evidence that tumor growth factor-beta (TGF-beta) released from breast cancer cells markedly up-regulates uPA expression in tumor-associated macrophages (TAMs). TAMs from 32 breast carcinomas were cultured. Blood monocytes from healthy donors and breast cancer patients as well as tissue macrophages from patients with fibrocystic changes of the breast were also examined. After TGF-beta incubation, uPA levels were tested by ELISA, and uPA mRNA levels were determined by Northern blot analysis. TGF-beta receptor and uPA cell surface fluorescence intensities were determined by flow cytometry; TGF-beta receptors were determined by Western blot analysis. Protein kinase-C dependence was also examined, and immunohistochemical stainings for uPA and TGF-beta were performed. We have demonstrated that TGF-beta markedly up-regulates basal uPA expression (mRNA and protein) in TAMs but only modestly increases uPA production in blood monocytes and tissue macrophages. Exposure of macrophages to TGF-beta1 led to a rapid and sustained increase in uPA mRNA levels, which was independent of de novo protein synthesis and completely inhibited by actinomycin D. H7 markedly reduced the ability of TGF-beta to stimulate uPA expression. Likewise, okadaic acid potentiated the ability of TGF-beta to up-regulate macrophage uPA expression. We suggest that TAMs are more responsive to TGF-beta stimulation than are blood monocytes and tissue macrophages because of different TGF-beta receptor densities. TGF-beta stimulates transcription of the uPA gene, increases uPA-mRNA stability, and activates uPA expression via protein kinase-C-dependent mechanisms. The ability of TGF-beta to induce macrophage uPA expression may provide an indirect mechanism by which this growth factor stimulates angiogenesis. It may be, therefore, that TAMs promote tumor progression and tumor angiogenesis.

Breast Neoplasms↗

PubMed1998

General pharmacology of S 15261, a new concept for treatment of diabetes.

The new compound S 15261 (CAS 159978-02-6) is the I-isomer of 3-[2-[2-[4-[2-(alpha-Fluorenylacetylamino)ethyl]benzoyloxy]ethylam ino]-1- methoxyethyl]trifluoromethylbenzene. The general synthetic pathway used for the preparation of S 15261 and related esters is given in this paper. This compound was selected for its promising therapeutical action on blood glucose, insulin resistance and associated risk factors present in patients with non-insulin-dependent Diabetes mellitus (NIDDM). The general pharmacological profile of S 15261 was investigated. The data given in this paper show that S 15261 has presented a very low acute toxicity (lethal dose in mice greater than 1600 mg/kg orally) and did not induce significant behavioural changes in rats. A poor anorectic effects was observed after acute administration in rats. In guinea pigs S 15261 acutely induced a significant and dose-dependent hypoglycaemic effect (ED25 = 40 mg/kg orally). Biogenic amines and their metabolites in different structures of the brain were only slightly affected after acute administration of S 15261. Chronic administration of this compound (2.5 mg/kg bid for 14 days p.o.) did not cause significant alterations in the brain amines content, with the exception of an increase of serotonin (19%) in the striatum, a result not confirmed by the dose-effect study (from 1 mg/kg to 12.5 mg/kg bid for 14 days p.o.). In vitro binding assays with 31 different receptors did not show significant affinity of S 15261 for any of them. The rat arterial blood pressure was decreased (12 mmHg) after acute (25 mg/kg i.v.) or repeated administration (2.5 mg/kg bid for 14 days p.o.) without any dose-dependent effect. We therefore conclude that S 15261 may not have significant adverse effect even at doses higher than the pharmacological effective range of doses. Although the mechanism of action of this new class of compounds was not fully understood, other pharmacological data suggest that S 15261 acts at both the liver (intraportal infusion) and skeletal muscle (microdialysis studies) at least in part to enhance insulin sensitivity. For all these activities S 15261 may be useful to treat patients with NIDDM or insulin resistance known to be the major risk for onset of NIDDM.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1998

Advances in the care of children with heart disease.

As we enter the next millennium, we are encouraged by the progress that has been made in the care of neonates, infants, and children with heart disease. Surgical repair can be offered at an earlier age with excellent results. Diseases that were uniformly fatal in the past have improved outcomes. Research continues in the area of interventional devices such that surgical repair might be eliminated or delayed. We continue to look forward to advances in the next several years that will allow for future improvement in outcome, better quality-of-life and better long-term results.

Child↗

PubMed1997

Immune complexes are potent inhibitors of interleukin-12 secretion by human monocytes.

We have studied the effect of immune complexes (IC) on interleukin (IL)-12 secretion by human monocytes in vitro. Two experimental models of IC were used. IC formed of tetanus toxoid and polyclonal anti-tetanus toxoid antiserum as well as heat-aggregated human serum IgG almost completely inhibited IL-12 (p70 and p40) secretion induced by interferon-gamma and lipopolysaccharide in human blood-derived monocytes. Neutralizing anti-IL-10 antibodies plus indomethacin restored IL-12 secretion in the presence of IC to a high extent, indicating that IL-10 and prostaglandin (PG) partially mediate the IC-induced inhibition of IL-12 secretion. However, neutralization of tumor necrosis factor (TNF)-alpha by specific antibodies also incompletely restored IL-12 secretion. Indeed, monocytes secrete high levels of TNF-alpha upon stimulation by IC. We found that exogenously added TNF-alpha caused a profound inhibition of monocytic IL-12 secretion in the absence of IC, again mediated via the induction of IL-10 and PG. In summary, IC inhibit IL-12 secretion via TNF-alpha-induced IL-10 and PG synthesis. We conclude that IC, typically appearing in the course of chronic inflammatory processes, may influence the balance between Th1 and Th2 responses and may thus contribute to a deprivation of cell-mediated immune responses.

Antigen-Antibody Complex↗

PubMed1997

Effects of diaspirin-cross-linked hemoglobin (DCLHb) on local tissue oxygen tension in striated skin muscle: an efficacy study in the hamster.

Using the dorsal skin fold chamber model in the hamster, we analyzed local tissue partial oxygen pressure (PO2) in the striated skin muscle under nonischemic and postischemic conditions with a Clark-type multiwire oxygen surface electrode. Hypervolemic infusion (500 mg x kg(-1) I.V.) or isovolemic exchange transfusion (3.3 gm x kg(-1) I.V.; hematocrit 30%) with diaspirin-cross-linked hemoglobin (DCLHb) resulted in a slight decrease of the mean value of the local tissue PO2 (mm Hg) 1 hour after administration. Concomitantly, the frequency distribution curves of local tissue PO2 values were found to be more narrow (fewer values > 25 mm Hg and < 10 mm Hg). Resuscitation from severe hemorrhagic shock (bleeding of 33 ml x kg(-1) at 0.4 ml x min(-1)) with autologous blood (AuB), Dx-60, or DCLHb led to an increase of mean tissue PO2 values by 4.2-fold (p < 0.05 versus Dx-60), 1.9-fold, and 3.7-fold (p < 0.05 versus Dx-60), respectively, 2 hours after resuscitation. The reduction of tissue hypoxia (0-5 mm Hg) was significant only in the AuB- and DCLHb-treated animals. This study indicates that DCLHb effectively reverses tissue hypoxia after resuscitation from severe hemorrhagic shock by inducing a more homogeneous distribution of the local tissue PO2 levels.

Animals↗

PubMed1997

Toxicological comparisons of Tetrahymena species, end points and growth media: supplementary investigations to the pilot ring test.

Parallel to an international Pilot Ring Test to standardize a mutigeneration test protocol with the protozoon Tetrahymena pyriformis supplementary investigations were made. Effects on growth rate and 46 h population density were measured using an extended set of 12 chemicals, a further Tetrahymena-species (T. thermophila) and 4 different media (axenic and bacteria based). Results are compared for sensitivity with effects on additional end points (chemosensory response, respiration and vitality). Both species exhibit similar sensitivity towards the chemicals. In some cases the media composition influenced the toxic potential of chemicals. Both growth parameters proved to be a sensitive integral end point for toxicological studies, confirming the one point, photometric measurement of population density after 46 hours in axenic (preferably proteose peptone-) medium an obvious choice for a standard test procedure.

Animals↗

PubMed1997

Induction of antibodies to plant viral proteins by DNA-based immunization.

DNA-based immunization is a promising new technique for generating antibodies in laboratory animals for diagnostic purposes in biological science. The main advantages are the elimination of time and labor and the technically demanding steps of antigen purification. The DNA sequence of the protein of interest, cloned in a suitable in vivo expression vector that is administered intramuscularly or intradermally, is sufficient to induce an immune response in animals. We report the induction of antibodies to tobacco mosaic virus (TMV) coat protein (CP) as a highly immunogenic structural protein and potato virus Y (PVY) P1 protein (P1) as a nonstructural protein. The appropriate nucleotide sequences were introduced in a mammalian expression vector (pSG5) and injected intramuscularly into New Zealand White rabbits (Oryctolagus cuniculus). By 10 days post-injection (dpi) a specific immune response was detected against TMV-CP, while it took about 5 weeks for a response to PVY P1. In both cases the antibody titers were significantly above the corresponding pre-immune serum, however, they were considerably below the titer of the matching conventionally produced antiserum. To our knowledge, this is the first report of DNA-based immunization in order to generate antibodies to plant viral proteins, but further improvements are necessary to increase antibody titers before this promising new technique can be introduced broadly in plant science for diagnostic purposes.

Animals↗