[Postoperative complications after tunnel incision. Chronic iritis with fibrin reaction in the anterior chamger in a 75-year-old woman after operation].
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Aged↗
Biomedical subjects
M Blum
Publications and source records attributed to M Blum.
Photoreceptor visual fields, ommatidial array, and receptor axon projections in the polarisation-sensitive dorsal rim area of the cricket compound eye.
We made intracellular recordings from the photoreceptors of the polarisation-sensitive dorsal rim area of the cricket compound eye combined with dye marking. By measuring visual field sizes and optical axes in different parts of the dorsal rim area, we assessed the optical properties of the ommatidia. Due to the large angular sensitivities (median about 20 degrees) and the high sampling frequency (about 1 per degree), the visual fields overlap extensively, such that a given portion of the sky is viewed simultaneously by a large number of ommatidia. By comparing the dye markings in the retina and in the optic lobe, the axon projections of the retinula cells were examined. Receptors R1, R2, R5 and R6 project to the lamina, whereas R7 projects to the medulla. The microvilli orientation of the two projection types differ by 90 degrees indicating the two analyser channels that give antagonistic input to polarisation-sensitive interneurons. Using the retinal marking pattern as an indicator for the quality of the intracellular recordings, the polarisation sensitivity of the photoreceptors was re-examined. The polarisation sensitivity of recordings from dye-coupled cells was much lower (median: 4.5) than that of recordings in which only one cell was marked (median: 9.8), indicating that artefactual electrical coupling between photoreceptors can significantly deteriorate polarisation sensitivity. The physiological value of polarisation sensitivity in the cricket dorsal rim area is thus typically about 10.
Animals↗
Relative anterior microphthalmos: morphometric analysis and its implications for cataract surgery.
PURPOSE: To evaluate morphometric data and risk factors for complications of cataract surgery in patients with relative anterior microphthalmos (RAM). DESIGN: Retrospective, comparative study (Part I) and matched pairs analysis with controls (Part II). PARTICIPANTS: Sixty-two patients with RAM who underwent cataract surgery at the Department of Ophthalmology, Ruprecht-Karls-University of Heidelberg, Germany, between 1989 and 1997. RAM is defined as eyes with horizontal corneal diameters </=11 mm, axial length of >20 mm, and no other morphologic malformation. MAIN OUTCOME MEASURES: Part I: Patients were examined preoperatively for anterior chamber (AC) depth, lens thickness, total axial length, and refraction. Associated ocular pathologic conditions (such as glaucoma or previous surgical interventions) were recorded. Part II: A matched pairs analysis concerning the anatomic features was performed with a group of 17 patients with RAM and 17 patients (controls) that matched the RAM group in terms of axial length, age, and gender but showed corneal diameters >11 mm. RESULTS: Part I: Anatomic parameters in RAM showed an average corneal diameter of 10.7 +/- 0.34 mm, AC depth of 2.20 +/- 0.49 mm, and average lens thickness of 5. 05 +/- 0.45 mm. Fifty-five percent of the patients had myopic refraction. There was a high incidence of glaucoma (77.4%), cornea guttata (45.2%), and pseudoexfoliation syndrome (16.1%) in the RAM group. Sixty percent of patients had undergone previous glaucoma surgery. After cataract surgery, 51.2% of patients achieved a visual acuity of >20/40 and 69.8% of >20/50. Temporary corneal edema (54. 8%) and ciliolenticular block (11.6%) were the most important complications after cataract surgery. Part II: Matched pairs analysis showed significant differences between RAM and controls in terms of AC depth (P =0.029) but no difference in lens thickness (P = 0.12). CONCLUSIONS: Relative anterior microphthalmos can be characterized in terms of morphometric data as eyes with corneal diameters </=11 mm and AC depths of 2 mm. The small anterior segment, especially the shallow anterior chamber, is responsible for the high incidence of glaucoma and postoperative complications after cataract surgery. Identifying these patients before surgery helps the cataract surgeon to be prepared for potential problems.
Aged↗
Central nicotinic receptors, neurotrophic factors and neuroprotection.
The multiple combinations of nAChR subunits identified in central nervous structures possess distinct pharmacological and physiological properties. A growing number of data have shown that compounds interacting with neuronal nAChRs have, both in vivo and in vitro, the potential to be neuroprotective and that treatment with nAChR agonists elicit long-lasting improving of cognitive performance in a variety of behavioural tests in rats, monkeys and humans. Epidemiological and clinical studies suggested also a potential neuroprotective/trophic role of (-)-nicotine in neurodegenerative disease, such as Alzheimer's and Parkinson's disease. Taken together experimental and clinical data largely indicate a neuroprotective/trophic role of nAChR activation involving mainly alpha7 and alpha4beta2 nAChR subtypes, as evidenced using selective nAChR antagonists, and by potent nAChR agonists recently found displaying efficacy and/or larger selective affinities than (-)-nicotine for neuronal nAChR subtypes. A neurotrophic factor gene regulation by nAChR signalling has been taken into consideration as possible mechanism involved in neuroprotective/trophic effects by nAChR activation and has evidenced an involvement of the fibroblast growth factor (FGF-2) gene as a target of nAChR signalling. These findings suggested that FGF-2 could be involved, according to the FGF-2 neurotrophic functions, in nAChR mechanisms mediating the neuronal survival, trophism and plasticity.
Animals↗
The use of subcutaneous erythropoietin and intravenous iron for the treatment of the anemia of severe, resistant congestive heart failure improves cardiac and renal function and functional cardiac class, and markedly reduces hospitalizations.
OBJECTIVES: This study evaluated the prevalence and severity of anemia in patients with congestive heart failure (CHF) and the effect of its correction on cardiac and renal function and hospitalization. BACKGROUND: The prevalence and significance of mild anemia in patients with CHF is uncertain, and the role of erythropoietin with intravenous iron supplementation in treating this anemia is unknown. METHODS: In a retrospective study, the records of the 142 patients in our CHF clinic were reviewed to find the prevalence and severity of anemia (hemoglobin [Hb] <12 g). In an intervention study, 26 of these patients, despite maximally tolerated therapy of CHF for at least six months, still had had severe CHF and were also anemic. They were treated with subcutaneous erythropoietin and intravenous iron sufficient to increase the Hb to 12 g%. The doses of the CHF medications, except for diuretics, were not changed during the intervention period. RESULTS: The prevalence of anemia in the 142 patients increased with the severity of CHF, reaching 79.1% in those with New York Heart Association class IV. In the intervention study, the anemia of the 26 patients was treated for a mean of 7.2 +/- 5.5 months. The mean Hb level and mean left ventricular ejection fraction increased significantly. The mean number of hospitalizations fell by 91.9% compared with a similar period before the study. The New York Heart Association class fell significantly, as did the doses of oral and intravenous furosemide. The rate of fall of the glomerular filtration rate slowed with the treatment. CONCLUSIONS: Anemia is very common in CHF and its successful treatment is associated with a significant improvement in cardiac function, functional class, renal function and in a marked fall in the need for diuretics and hospitalization.
Aged↗
Pitx2 isoforms: involvement of Pitx2c but not Pitx2a or Pitx2b in vertebrate left-right asymmetry.
During vertebrate left-right development the homeobox gene Pitx2 serves as a mediator between transient nodal signaling in the left lateral plate mesoderm (l-LPM) and asymmetric organ morphogenesis. Misexpression of Pitx2 in chick and frog led to alteration of organ situs. Here we report the presence of different Pitx2 isoforms in mouse and frog. Pitx2c but not Pitx2a or Pitx2b was asymmetrically expressed in the l-LPM, heart and gut, and was specifically induced by nodal in Xenopus animal cap explant cultures and whole embryos. Pitx2c induced its own transcription, suggesting a maintenance mechanism following the down-regulation of nodal in the l-LPM. Pitx2c thus represents the left-specific isoform involved in vertebrate left-right asymmetry.
Amino Acid Sequence↗
[Age-correlation of blood pressure induced myogenic autoregulation of human retinal arterioles in 40 volunteers].
PURPOSE: For the first time noninvasive measurement of the myogenic response of retinal arterioles is possible by the use of the Retinal-Vessel-Analyzer (RVA). This study investigates the influence of age on retinal autoregulation. PATIENTS AND METHODS: In 40 healthy volunteers continuous measurement of a retinal arteriole over a 9-min period was performed. After a 3-min baseline measurement isometric exercise caused a rise in blood pressure of 15-30 mm Hg. During the last 3 minutes recovery was documented. Volunteers were split into a group of 20 younger (18-34 yrs.) and 20 older subjects (35-57 yrs.). For statistical analysis the Mann-Whitney test was used. RESULTS: All volunteers showed a rise in blood pressure. Significant differences in the blood-pressure rise were followed by a myogenic response of 1% up to 10% vasoconstriction. An individual autoregulation-curve was defined with negative gradient. Significant differences between the younger and the older volunteers can be identified by this methodology. CONCLUSION: Age has a significant influence on the myogenic response in human retinal arterioles. Age should be considered as a factor in clinical studies on retinal autoregulation.
Adolescent↗
[Autoregulation of retinal arterioles in patients with diabetes mellitus and normal probands].
BACKGROUND: Measurement of myogenic autoregulation of retinal arterioles was demonstrated by the use of the Retinal-Vessel-Analyzer (Carl Zeiss, Jena). The purpose of the presented study was to find a significant difference of this myogenic response in a group of healthy individuals vs. a group of patients with pathologic conditions. PATIENTS AND METHODS: As a group of patients with known pathology in microcirculation patients with type 1 diabetes were chosen. By isometric exercise an identical rise in mean arterial blood-pressure was provoked in 20 patients with type-1 diabetes and 20 matched healthy volunteers. The myogenic response of retinal arterioles was measured in both groups by the use of the Retinal-Vessel-Analyzer. The Wilcoxon test was used for statistical analysis within the two groups whereas both groups were compared with each other by the use of the Mann-Whitney test. RESULTS: Having the same age and same blood-pressure rise (p = 0.624) a significant better myogenic response was found in the healthy subjects vs. the diabetic group (p = 0.008). In the diabetic group no correlation was found between myogenic response and duration of diabetes (p = 0.982) or HbA1c values (p = 0.83). CONCLUSIONS: In this study significant loss of autoregulation in patients with type 1 diabetes is demonstrated. By the use of the Retinal-Vessel-Analyzer noninvasive testing of the function of autoregulation of retinal arterioles is possible. This method might prove to be of great value in early detection of diabetic vessel pathology.
Adolescent↗
Thyrotoxicosis after interferon-alpha therapy.
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Carcinoid Tumor↗
No obvious abnormality in mice deficient in receptor protein tyrosine phosphatase beta.
The development of neurons and glia is governed by a multitude of extracellular signals that control protein tyrosine phosphorylation, a process regulated by the action of protein tyrosine kinases and protein tyrosine phosphatases (PTPs). Receptor PTPbeta (RPTPbeta; also known as PTPzeta) is expressed predominantly in the nervous system and exhibits structural features common to cell adhesion proteins, suggesting that this phosphatase participates in cell-cell communication. It has been proposed that the three isoforms of RPTPbeta play a role in regulation of neuronal migration, neurite outgrowth, and gliogenesis. To investigate the biological functions of this PTP, we have generated mice deficient in RPTPbeta. RPTPbeta-deficient mice are viable, are fertile, and showed no gross anatomical alterations in the nervous system or other organs. In contrast to results of in vitro experiments, our study demonstrates that RPTPbeta is not essential for neurite outgrowth and node formation in mice. The ultrastructure of nerves of the central nervous system in RPTPbeta-deficient mice suggests a fragility of myelin. However, conduction velocity was not altered in RPTPbeta-deficient mice. The normal development of neurons and glia in RPTPbeta-deficient mice demonstrates that RPTPbeta function is not necessary for these processes in vivo or that loss of RPTPbeta can be compensated for by other PTPs expressed in the nervous system.
Animals↗
Differential response of ventral midbrain and striatal progenitor cells to lesions of the nigrostriatal dopaminergic projection.
In response to injury, progenitor cells in the adult brain can proliferate and generate new neurons and/or glia, which may then participate in injury-induced compensatory processes. In this study, we explore the ability of young adult mice to generate new cells in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesions, which selectively kill nigrostriatal dopaminergic neurons. Using the thymidine analogue 5-bromo-2'-deoxyuridine (BrdU), we labeled dividing cells 3, 10, and 15 days after MPTP lesion. A robust proliferative response was seen specifically in the substantia nigra (SN) and the dorsal striatum 3 days postlesion; the response persisted 10-14 days. To explore the fate of proliferative cells, we administered BrdU 3 days postlesion and examined the phenotype of BrdU(+) cells at various times thereafter, using double immunolabeling. In the striatum, nearly all newly-generated cells rapidly differentiated into GFAP(+) astrocytes that participated in the injury-induced glial reaction. In the SN, however, reactive astroglia were not BrdU(+). Some midbrain cells co-immunostained for BrdU and Mac-1, a microglial marker. However, most BrdU(+) cells in the SN failed to express markers for microglia, astroglia, oligodendroglia, or neurons, suggesting that they may remain as uncommitted progenitors. Thus, progenitors in the vicinity of the degenerating dopaminergic cell bodies respond differently to lesion than progenitors in the vicinity of the degenerating axon terminal. Although the putative midbrain progenitors appear uncommitted 22 days after their birth, it is possible that they may adopt neural or glial fates if allowed to survive longer, or if exposed to exogenous factors.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
Glomerular basement membrane anionic sites in adriamycin nephropathy: effect of saline loading and nitric oxide modulation.
BACKGROUND: In previous studies we found that experimental Adriamycin (ADR) nephropathy is associated with the loss of glomerular basement membrane (GBM) anionic sites provided by heparan sulfate proteoglycans. Chronic saline loading in normal rats resulted in a similar effect on the GBM anionic sites. The L-arginine-nitric oxide synthase-nitric oxide system is involved in the pathogenesis of experimental chronic renal failure. The present study was performed to determine the combined effect of nitric oxide (NO) modulation and chronic saline loading in ADR nephropathy. The modulation of NO was done by chronic administration of L-arginine (NO donor) or N(w)-nitro-L-arginine, a known nitric oxide synthase inhibitor. METHODS: Systolic blood pressure was measured in awake rats by a tail-cuff method. Renal function was assessed by creatinine clearance, FeNa%, and daily protein excretion. The change of mean GBM widths and anionic sites distribution were assessed by electron microscopy. The localization of anionic sites was carried out by cationic colloidal gold. Plasma and urinary nitrates (NO(x)) were measured by nitrite (NO(2)) + nitrate (NO(3)), stable metabolites of NO. RESULTS: Two weeks after the ADR administration (3.5 mg/kg BW iv) the rats had severe renal failure (creatinine clearance 134 +/- 31 microl/min/100 g BW vs. initial values 670 +/- 29 microl/min/ 100 g BW, p < 0.001), high FeNa%, severe proteinuria, increased GBM width, significant reduction of GBM anionic sites and low urinary NO(x) excretion. The saline loading resulted in further reduction of GBM anionic sites count and blood pressure elevation. The inhibition of NO did not change the course of ADR nephropathy. The main finding of the present study is that chronic administration of L-arginine significantly alleviates the renal failure in the ADR (+/- saline loading) nephropathy. The L-arginine-treated rat had higher creatinine clearance, lower FeNa% and protein excretion and complete normalization of GBM anionic sites distribution. CONCLUSIONS: Sodium loading has a deleterious effect on GBM permselectivity. L-Arginine prevents the reduction of GBM anionic sites, decreases proteinuria and alleviates the renal insufficiency in ADR nephropathy.
Animals↗
Goosecoid suppresses cell growth and enhances neuronal differentiation of PC12 cells.
In all vertebrate species, the homeobox gene goosecoid serves as a marker of the Spemann organizer tissue. One function of the organizer is the induction of neural tissue. To investigate the role of goosecoid in neuronal differentiation of mammalian cells, we have introduced goosecoid into PC12 cells. Expression of goosecoid resulted in reduced cell proliferation and enhanced neurite outgrowth in response to NGF. Expression of goosecoid led to a decrease in the percentage of S-phase cells and to upregulation of the expression of the neuron-specific markers MAP-1b and neurofilament-L. Analysis of goosecoid mutants revealed that these effects were independent of either DNA binding or homodimerization of Goosecoid. Coexpression of the N-terminal portion of the ets transcription factor PU.1, a protein that can bind to Goosecoid, repressed neurite outgrowth and rescued the proliferation of PC12 cultures. In contrast, expression of the bHLH transcription factor HES-1 repressed goosecoid-mediated neurite outgrowth without changing the proportion of S-phase cells. These results suggest that goosecoid is involved in neuronal differentiation in two ways, by slowing the cell cycle and stimulating neurite outgrowth, and that these two events are separately regulated.
Animals↗
goosecoid expression represses Brachyury in embryonic stem cells and affects craniofacial development in chimeric mice.
The homeobox gene goosecoid, originally identified in Xenopus, is expressed in the organizer or its equivalent during gastrulation in the frog, chick, zebrafish and mouse. To investigate the role of goosecoid in mouse development, we have generated embryonic stem cells that stably overexpress the murine homolog of goosecoid. These cells show a repression of the gastrulation-associated gene Brachyury. Interestingly, repression of Brachyury is conserved between Xenopus and mouse despite the lack of conservation of the Brachyury promoter. Further characterization of the goosecoid-overexpressing ES cells revealed that they maintain the expression of stage-specific embryonic antigen-1, and teratomas derived from goosecoid-overexpressing cells show the presence of cell types derived from all three germ layers. Some highly chimeric mice derived from goosecoid-overexpressing cells displayed skull defects. These observations suggest that goosecoid may play a role in specification of anterior mesendodermal fates and specifically in mouse craniofacial development.
Animals↗
The nicotinic acetylcholine receptor agonist ABT-594 increases FGF-2 expression in various rat brain regions.
The present experiments were designed to extend previous work showing that acute intermittent (-)nicotine treatment upregulates the level of fibroblast growth factor-2 (FGF2) mRNA in several rat brain regions, by the use of the nicotinic acetylcholine receptor (nAChR) agonist ABT-594 with preferential selectivity for the alpha4beta2 nAChR subtype. ABT594 treatment led to a well-defined temporal and regional upregulation of FGF-2 mRNA. A double labelling analysis showed that the up-regulation of FGF-2 mRNA involves both neuronal and non-neuronal cells. The effects of ABT-594 on FGF-2 expression were antagonized by the preferential alpha4beta2 antagonist dihydrobetaerythroidine (DHbetaE), but not by alpha7 antagonist methyllycaconitine (MLA). In conclusion, FGF-2 mRNA levels can be increased in several brain regions upon alpha4beta2 nAChR activation, suggesting a therapeutic significance in neurodegenerative disorders.
Animals↗
The nicotinic acetylcholine receptor agonist (+/-)-epibatidine increases FGF-2 mRNA and protein levels in the rat brain.
In a previous work, we showed that acute intermittent nicotine treatment up-regulates the level of fibroblast growth factor-2 (FGF-2) mRNA in brain regions of tel- and mesencephalon of rats suggesting that neuroprotective effect of (-)nicotine may, at least in part, involve an activation of the neuronal FGF-2 signalling. The present experiments were designed to extend the study on the nicotinic receptor mediated up-regulation of FGF-2 mRNA levels to the use of the potent nicotinic acetylcholine receptor (nAChR) agonist (+/-)-epibatidine. The (+/-)-epibatidine treatment led to a strong and long lasting up-regulation of FGF-2 mRNA expression in the cerebral cortex, in the hippocampal formation, in the striatum and in the substantia nigra. This FGF-2 mRNA induction, already statistically significant at 4 h, peaked at 12 h from treatment and was only partially returned towards normal levels at 48 h, the last time point examined. Using Western blot analysis it was found that the epibatidine-induced upregulation of FGF-mRNA is accompaned by an increase of FGF-2 protein level at the 20-h time-interval. These (+/-)-epibatidine effects on FGF-2 expression were antagonized by the non-competitive nAChR antagonist mecamylamine, indicating an involvement of nicotinic receptors. In the same brain areas examined, no changes were observed in the fibroblast growth factor receptor-1 (FGFR-1) mRNA levels, in brain-derived neurotrophic factor (BDNF) and in glial cell line-derived neurotrophic factor (GDNF) mRNA levels. In view of the neurotrophic function of FGF-2, these results, together with previous ones, could further help to understand the molecular mechanisms mediating the previously observed neuroprotective effects of (-)nicotine.
Animals↗
A role of the cryptic gene in the correct establishment of the left-right axis.
During vertebrate embryogenesis, a left-right axis is established. The heart, associated vessels and inner organs adopt asymmetric spatial arrangements and morphologies. Secreted growth factors of the TGF-beta family, including nodal, lefty-1 and lefty-2, play crucial roles in establishing left-right asymmetries [1] [2] [3]. In zebrafish, nodal signalling requires the presence of one-eyed pinhead (oep), a member of the EGF-CFC family of membrane-associated proteins [4]. We have generated a mutant allele of cryptic, a mouse EGF-CFC gene [5]. Homozygous cryptic mutants developed to birth, but the majority died during the first week of life because of complex cardiac malformations such as malpositioning of the great arteries, and atrial-ventricular septal defects. Moreover, laterality defects, including right isomerism of the lungs, right or left positioning of the stomach and splenic hypoplasia were observed. Nodal gene expression in the node was initiated in cryptic mutant mice, but neither nodal, lefty-2 nor Pitx2 were expressed in the left lateral plate mesoderm. The laterality defects observed in cryptic(-/-) mice resemble those of mice lacking the type IIB activin receptor or the homeobox-containing factor Pitx2 [6] [7] [8] [9], and are reminiscent of the human asplenic syndrome [10]. Our results provide genetic evidence for a role of cryptic in the signalling cascade that determines left-right asymmetry.
Alleles↗
GOOSECOID inhibits erythrocyte differentiation by competing with Rb for PU.1 binding in murine cells.
Misexpression of the dorsal mesodermal patterning factor goosecoid on the ventral side of amphibian embryos results in inhibition of blood formation in early embryogenesis. To investigate the mechanism of this inhibition, we ectopically expressed goosecoid in erythroleukemia cells. While erythroid differentiation of these cells can be induced by activin, goosecoid expressing cells were unresponsive to activin. We demonstrate an in vitro interaction between the oncogene PU.1, an ets family transcription factor thought to play a role in erythropoiesis, and the goosecoid protein (GSC). Interaction with PU.1 was specific as GSC did not bind to the ets family members, Fli-1 or Ets-2. The ability of goosecoid expressing erythroleukemia cells to differentiate in response to activin was rescued by coexpression of the GSC-binding N-terminal portion of PU.1. The N-terminal portion of PU.1 was co-immunoprecipitated with anti-GSC antibodies as well. The N-terminal domain of PU.1 is the region recognized by the retinoblastoma protein (Rb), a tumor suppressor gene presumably involved in erythroid differentiation. We show that GSC competitively inhibits binding of Rb to PU.1. Our data suggest that the suppression of blood formation by GSC could, at least in part, be mediated by binding to PU.1.
Activins↗