Skeletal muscle troponin I release and magnetic resonance imaging signal intensity changes after eccentric exercise-induced skeletal muscle injury.
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Adult↗
Biomedical subjects
E Müller
Publications and source records attributed to E Müller.
Solute composition and heat shock proteins in rat renal medulla.
The high content of heat shock proteins (HSPs) 25 and 72 in the hyperosmotic inner medulla of the concentrating kidney has been ascribed to the high NaCl and urea concentrations in this kidney zone. To assess the effects of variations in the composition of solutes in the renal medulla on the intrarenal distribution of HSPs, rats were fed either a high- or low-Na diet for 3 weeks. These diets result in greatly differing urine and inner medullary solute composition. Sodium dodecyl sulphate polyacrylamide gel electrophoresis and Western blot techniques were used to analyse HSP25 and HSP72 in the cortex, outer medulla and inner medulla. In addition, the amounts of organic osmolytes (sorbitol, myo-inositol, betaine and glycerophosphorylcholine) and urea in the tissue were determined by high-performance liquid chromatography. Intra- and extracellular electrolyte concentrations at the papillary tip were measured by electron microprobe analysis. In the high-Na group, urine osmolality was about 1000 mosmol/kg lower than in rats fed a low-Na diet, due to lower urea concentrations. The sum of urine sodium and potassium concentrations, however, did not differ between the two groups. Neither in the outer nor in the inner medulla was the sum of the concentrations of organic osmolytes affected by the dietary treatment. The sum of sodium, potassium and chloride concentrations did not differ between the two experimental groups, neither in the interstitial nor in the intracellular compartments. However, the urea content and the amounts of HSP25 and HSP72 were significantly lower in the inner medulla of the group of rats fed a high-Na diet. Our results suggest that urea participates in the regulation of the medullary levels of the HSPs and that both HSP25 and HSP72 are components of mechanisms protecting medullary cells against the deleterious effects of high urea concentrations.
Animals↗
The response of heat shock proteins 25 and 72 to ischaemia in different kidney zones.
Induction of heat shock proteins (HSPs) following cell injury contributes to the protection of vital cell functions. It was, therefore, of interest to study the effects of transient renal ischaemia on the abundance and distribution of two HSPs, HSP25 and HSP72, in renal tissue using Western-blot techniques. Analyses were performed on the supernatant (HSP25, HSP72) and pellet (HSP25) of homogenates obtained from cortex (CX) and outer (OM) and inner (IM) medulla of the rat kidney immediately after 60 min of ischaemia followed by varying periods of reperfusion. Ischaemia of the left kidney caused HSP25 contents to decrease in CX, OM and IM by 73, 89 and 54% respectively, compared with the corresponding zones of the contralateral control kidney. This initial decrease in supernatant HSP25 was accompanied by an increased abundance of HSP25 in the pellet. Following reperfusion, HSP25 contents in the supernatant gradually increased in CX and OM, reaching, after 24 h, values that were 5.4- and 2.5-fold higher, respectively, than those in the control kidneys. After 7 or 14 days of reperfusion, HSP25 contents had not completely normalised in CX, but had reached control levels in OM. In IM, the HSP25 content remained below control throughout the entire reperfusion period. HSP72 (supernatant) was below the detection limit in the CX of the control kidney. Similar to the level of HSP25, that of HSP72 was also markedly lower in OM and IM immediately after ischaemia. The intrarenal distribution of HSP72 and the sequence of zonal changes in HSP72 contents were similar to those observed for HSP25. These results are compatible with the view that, during ischaemia and the initial reperfusion period, HSP25 migrates from the cytoplasmic compartment (supernatant) into the nucleus and/or associates with cytoskeletal structures. The observation that both HSP25 and HSP72 are transiently induced in CX and OM, but not in IM, may be explained by the fact that, while all kidney cells are exposed to ischaemic stress, only inner medullary cells experience a major postischaemic attenuation of osmotic stress.
Animals↗
Prostaglandin E2 stimulates expression of matrix metalloproteinase 2 in cultured rat mesangial cells.
Prostaglandins of the E-series have been demonstrated to reduce extracellular accumulation of collagens in some models of glomerulonephritis. This effect is partially due to reduction of collagen formation by mesangial cells. The potential effects of prostaglandins on the expression of collagen degrading enzymes in mesangial cells are largely unknown. Since rat mesangial cells generate a matrix metalloproteinase 2 (MMP-2) that specifically degrades collagen type IV, the effects of prostaglandin E2 (PGE2) on transcription, steady-state mRNA levels, extracellular enzyme activity and protein concentration of this proteinase were evaluated. Mesangial cells (MC) were incubated with PGE2 (2 microM) for different time-periods (1 to 48 hr), and steady-state mRNA levels of MMP-2 were determined by Northern blotting. PGE2 increased MMP-2 mRNA levels beginning at one hour of incubation and remained elevated up to 24 hours. Nuclear run off experiments revealed that the PGE2-induced increase in mRNA expression for MMP-2 is due to stimulated gene transcription. Western blot analysis and zymography revealed that MMP-2 protein production and enzyme activity was also enhanced by PGE2. The cAMP analogue 8-bromo-cAMP increased MMP-2 mRNA levels, suggesting that PGE2-induced generation of intracellular cAMP plays a role in MMP-2 induction in MC. These studies demonstrate that PGE2 stimulates the transcription, protein formation and enzyme activity of MMP-2 in cultured rat MC. This effect may contribute to the prostaglandin mediated reduction of extracellular collagen deposition in glomerulonephritis.
8-Bromo Cyclic Adenosine Monophosphate↗
Mutation (677 C to T) in the methylenetetrahydrofolate reductase gene aggravates hyperhomocysteinemia in hemodialysis patients.
Hyperhomocysteinemia is frequent in hemodialysis patients and represents an independent risk factor for vascular disease in these patients. Elevated total homocysteine (tHcy) plasma levels can results from defective remethylation of Hcy to methionine due to decreased activity of the enzyme methylenetetrahydrofolate reductase (MTHFR). A genetic aberration in the MTHFR gene (677 C to T substitution) has been shown to result in reduced MTHFR activity. We tested the hypothesis that elevation of tHcy plasma levels in hemodialysis patients is influenced by the 677 C to T mutation of the MTHFR gene and examined the relation of the genotype with tHcy, folate and vitamin B12 plasma levels in these patients. The allelic frequency of the MTHFR mutation was evaluated in 203 patients maintained on chronic hemodialysis treatment. Total Hcy, folate, vitamin B12 levels and the MTHFR mutation were analyzed in 69 of the 203 patients and in 69 age- and sex-matched healthy control subjects. The allelic frequency of the 677 C to T transition in the MTHFR gene in hemodialysis patients was 34.7% versus 35.5% in healthy controls. Of 203 patients 26 (12.8%) were homozygous for the mutation (+/+) versus 10.2% in healthy subjects. The heterozygous (+/-) genotype was identified in 43.8% of patients versus 50.7% in controls. The mean tHcy level in hemodialysis patients was 28.7 +/- 11.0 mumol/liter versus 10.0 +/- 3.0 mumol/liter in control subjects. The mean tHcy levels were 36.4 +/- 13.4 mumol/liter in (+/+) patients and 12.2 +/- 4.5 mumol/liter in (+/+) controls, 28.7 +/- 10.8 mumol/liter in (+/-) patients and 9.9 +/- 2.7 mumol/liter in (+/-) controls and 25.4 +/- 8.5 mumol/liter in (-/-) hemodialysis patients versus 9.7 +/- 2.8 mumol/liter in (-/-) controls: There was no significant difference of folate and vitamin B12 concentrations in patients and controls with different MTHFR genotypes. Analysis of covariance including age, gender, folate concentrations, vitamin B12 levels, albumin and creatinine as covariables revealed a significant influence of the (+/+) genotype, albumin and folate status on tHcy levels in hemodialysis patients. Together, our data demonstrate that the extent of hyperhomocysteinemia in hemodialysis patients is not only the result of uremia or folate status, but is also genetically determined by the (+/+) MTHFR genotype. The presence of the 677 C to T mutation in the MTHFR gene does not appear to represent a risk factor for development of end-stage renal disease.
Adult↗
Inhibition of angiotensin-converting enzyme modulates structural and functional adaptation to loop diuretic-induced diuresis.
The roles of elevated cell sodium concentrations and the angiotensin-aldosterone system (AAS) in the structural and functional adaptation of the distal tubule and collecting duct system to a chronic increase of sodium delivery were examined using electron microprobe and quantitative morphologic/stereologic analyses. Studies were performed on rats given the loop diuretic torasemide acutely (20 min) or chronically (12 days), either alone or in combination with the angiotensin-converting enzyme (ACE) inhibitor, enalapril. In the sodium-absorbing cells of the distal tubule and cortical collecting duct-that is, in distal convoluted tubule (DCT), connecting tubule (CNT) and principal cells-an acute increase in sodium delivery caused a significant rise in intracellular sodium concentration and rubidium uptake, the latter an index of in vivo Na,K(Rb)-ATPase activity. The elevated cell sodium concentrations returned to, or close to, control values during chronic torasemide treatment. Intracellular rubidium concentrations, measured after a 30-second rubidium exposure, were not different from controls in DCT and CNT cells but were still higher in principal cells. Since, however, the distribution space for rubidium was significantly increased in chronic torasemide animals, rubidium uptake, and hence Na,K-ATPase activity, must have increased in proportion to cell volume in DCT and CNT cells, but more than proportionately in principal cells. When ACE was inhibited during chronic torasemide, the epithelial volume of DCT and cortical collecting duct (CCD) was increased mainly by lengthening and not, as was the case in rats given torasemide alone, by thickening of the tubule wall. Adaptation of the proximal tubule exclusively by lengthening was not affected by inhibition of the ACE. These data indicate that changes in cell ion composition may participate in initiating cell processes leading to adaptation of distal nephron segments to chronically increased salt delivery. Inhibition of the ACE reverses the torasemide-induced increase in apparent Na pump density in principal cells and seems to shift the relationship between hypertrophy and hyperplasia noted in DCT and CCD after chronic torasemide in favor of hyperplasia.
Aldosterone↗
Alterations in leukocyte adhesion molecule expression after burn injury.
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Burns↗
Associations of GH gene variants with performance traits in F2 generations of European wild boar, Piétrain and Meishan pigs.
The role of the porcine GH gene was investigated in 292 F2 animals of mating Wild Boar x Piétrain and in 310 F2 animals of mating Meishan x Piétrain. Forty-three traits of fattening, carcass composition, meat quality and stress resistance were recorded. For the analysis of associations between GH gene variants and quantitative traits, two restriction fragment length polymorphisms were examined. In the Meishan x Piétrain family eight traits related to fatness were significantly associated with GH genotypes, while in the Wild Boar x Piétrain family no significant associations were found. In the Meishan x Piétrain cross, the GH locus explained 11.7% to 17.7% of the total phenotypic variance in the F2 population. The possibility of multiple alleles at the GH locus is discussed. Based on these results, we conclude that the GH locus should be further investigated in commercial breeds to determine its suitability for use in marker-assisted selection programmes.
Adipose Tissue↗
[Role of endoluminal ultrasonography in the treatment of rectal carcinoma].
Endoluminal sonography is an excellent technique in preoperative staging of rectal carcinoma. This minimally invasive technology makes individual planning of therapy possible and is a very good tool in postoperative follow-up and documentation. In comparison with the techniques of CT and MRI it is less expensive and the mobile unit can easily be moved e.g. into the operating theatre. There are no contraindications for this examination, postoperative tissue scars and metal implants will not disturb the imaging. We think that endoluminal sonography will be able to facilitate individual decision making in the treatment of rectal carcinoma.
Endosonography↗
Worsening of ischemic damage in hearts from rats with selective growth hormone deficiency.
The effects of growth hormone (GH) deficiency on cardiac function were studied in young male rats administered an anti-GH-releasing hormone (GHRH) serum from postnatal day 20 to 40. Dependence of heart abnormalities on GH deficiency was ascertained by giving a group of anti-GHRH serum-treated rats GH replacement therapy. Heart preparations from anti-GHRH serum-treated rats, undergoing low-flow ischemia, showed a progressive increase in left ventricular end-diastolic pressure with poor recovery of mechanical activity and increased coronary perfusion pressure upon reperfusion. Hearts from anti-GHRH serum + GH-treated rats, undergoing global reduction to the flow, showed only a minimal increase of left ventricular end-diastolic pressure and, upon reperfusion, cardiac mechanical activity recovered almost completely. Similar findings were also observed in heart preparations from control (normal rabbit serum-treated) rats. Infusion of acetylcholine (10(-6) M) into heart preparations in the preischemic period increased coronary perfusion pressure values more markedly in hearts from normal rabbit serum- and anti-GHRH serum + GH-treated rats than in those from anti-GHRH serum-treated rats. These results indicate that selective GH deficiency in young male rats renders the heart more sensitive to ischemic damage and leads to an impairment of cardiac muscarinic receptor function.
Acetylcholine↗
Heat shock proteins HSP25, HSP60, HSP72, HSP73 in isoosmotic cortex and hyperosmotic medulla of rat kidney.
The distribution of heat shock proteins (HSP) HSP60, HSP73, HSP72 and HSP25 in the isoosmotic cortex and the hyperosmotic medulla of the rat kidney was investigated using Western blot analysis and immunohistochemistry. HSP73 was homogeneously distributed throughout the whole kidney. The level of HSP60 was high in the renal cortex and low in the medulla. HSP25 and HSP72 were present in large amounts in the medulla. Only low levels of HSP25 and almost undetectable amounts of HSP72 were found in the cortex. HSP25 exists in one nonphosphorylated and several phosphorylated isoforms. Western blot analysis preceded by isoelectric focussing showed that HSP25 predominates in its nonphosphorylated form in the outer medulla but in its phosphorylated form in cortex and inner medulla. Although this intrarenal distribution pattern was not changed during prolonged anaesthesia (thiobutabarbital sodium), a shift from the nonphosphorylated to the phosphorylated isoforms of HSP25 occurred in the medulla. The characteristic intrarenal distribution of the constitutively expressed HSPs (HSP73, HSP60, HSP25) may reflect different states of metabolic activity in the isoosmotic (cortex) and hyperosmotic (medulla) zones of the kidney. The high content of inducible HSP72 in the medulla most likely is a consequence of the osmotic stress imposed upon the cells by the high urea and salt concentrations in the hyperosmotic medullary environment.
Anesthetics↗
Comparison of the protein quality of dietetically treated phenylketonuria patients with the recommendations of the WHO Expert Consultation.
The protein quality of the diets of phenylketonuria (PKU) children of different ages (3 months, 10 months, 3 years, 8 years, 12 years, 16 years) with low or high phenylalanine (Phe) tolerance was assessed according to the recommendations of the FAO/WHO consultation group [13]. The amount of each essential amino acid (AA) per gram dietary protein was calculated and compared to the reference. The resultant amino acid score (AAS) indicated a limited to inadequate biological protein quality of the diets in 3-month-old infants (2.2 g protein/kg body weight/day) and 10-month-old infants (2.0 g protein/kg body weight/day) with a "high" Phe tolerance. In all other age groups the AAS was > 100%. However remarkable imbalances in the AA pattern were apparent. Beginning with the age of 3 years (1.7 g protein/kg body weight/day) the intake of the AA lysine and isoleucine was three or two times higher than recommended. At the age of 8 years (1.4 g protein/kg body weight/day) the intake of three AA (valine, isoleucine, lysine) was-related to the WHO recommendations-217%, 229% and 291%. Similar results could be found in the age groups of 12 years (1.1 g protein/kg body weight/day) and 16 years (0.9 g protein/kg body weight/day), respectively. These calculations might help to reconsider the composition of the AA mixtures used in the dietetic treatment of PKU patients.
Adolescent↗
Local cerebral glucose utilization in fetal guinea pigs at 0.75 gestation.
OBJECTIVE: Using the 2-deoxyglucose method, measurements of local cerebral glucose utilization in large fetal animals are very difficult and expensive. To circumvent these problems we recently modified the 2-deoxyglucose method for use in the fetal guinea pig in utero (Berger et al., J Neurochem 1994; 63: 271-279). The present study was designed to measure the rates of local cerebral glucose utilization in fetal guinea pigs at 0.75 of gestation. STUDY DESIGN: After intravenous injection of 14C 2-deoxyglucose into the dams, local cerebral glucose utilization of the fetuses was measured from the time integral of the tracer in the maternal plasma and the autoradiographically determined concentration of the tracer in various parts of the fetal brain. RESULTS: Fetal cerebral glucose utilization was low as compared to adult animals and varied in different brain structures from 19 +/- 4 to 29 +/- 7 mumol/100 g/min. CONCLUSION: This study demonstrates the feasibility to measure local cerebral glucose utilization in undisturbed fetal guinea pigs in utero. We conclude that the low rate of cerebral glucose utilization and its small overall variability may reflect the neurological immaturity of the fetal brain.
Animals↗
Functional MR imaging of visual and motor cortex stimulation at high temporal resolution using a FLASH technique on a standard 1.5 Tesla scanner.
Functional magnetic resonance imaging (fMRI) was performed on a conventional 1.5 T scanner by means of a modified FLASH-technique at temporal resolutions of 80 and 320 ms. The method's stability was assessed by phantom measurements and by investigation of three volunteers resulting in a low amplitude (3%) periodic (4 s) signal modulation for the in vivo measurements, which was not observable in the phantom experiments. fMRI activation studies of motor and visual cortices of four adjacent slices were carried out on 12 healthy right-handed volunteers. Stimulation was performed by a triggered single white light flash or single finger-to-thumb opposition movement, respectively. Event-related response of visual and motor activation was traced over 10.24 s with a temporal resolution of 320 ms for the four slice measurements. Brain activation maps were calculated by correlation of measured signal time course with a time-shifted boxcar function. Activation was quantified by calculation of percentual signal change in relation to the baseline. Observed signal magnitudes were about 5-7% in visual and about 8-12% in primary motor cortex. While photic response was delayed by about 2 s, motor stimulation showed an instantaneous increase of the MR signal. MR signal responses for both stimuli had decayed completely after about 5 s. Our results show that event-related fMRI enables mapping of brain function at sufficient spatial resolution with a temporal resolution of up to 80 ms on a conventional scanner.
Adult↗
Oriented 1,2-dimyristoyl-sn-glycero-3-phosphorylcholine/ganglioside membranes: a Fourier transform infrared attenuated total reflection spectroscopic study. Band assignments; orientational, hydrational, and phase behavior; and effects of Ca2+ binding.
Fourier transform infrared (FTIR) attenuated total reflection (ATR) spectroscopy was used to elucidate the hydration behavior and molecular order of phospholipid/ganglioside bilayers. We examined dry and hydrated films of the gangliosides GM1, deacetyl-GM1, lyso-GM1, deacetyllyso-GM1, and GM3 and oriented mixed films of these gangliosides with 1,2-dimyristoyl-sn-glycero-3-phosphorylcholine (DMPC) using polarized light. Analysis of the amide I frequencies reveals that the amide groups are involved in intermolecular interactions via hydrogen bonds of varying strengths. The tilt angle of the acyl chains of the lipids in mixed films was determined as a function of ganglioside structure. Deacetylation of the sialic acid in the headgroup has a stronger influence on the tilt angle than the removal of the ganglioside fatty acid. The phase behavior was examined by FTIR ATR spectroscopy and by differential scanning calorimetry (DSC) measurements on lipid suspensions. At the same molar concentration, lyso-gangliosides have less effect on changes of transition temperature compared to the double-chain analogs. Distinct differences in the amide band shapes were observed between mixtures with lyso-gangliosides and normal double-chain gangliosides. Determined from the dicroic ratio RATR, the orientation of the COO- group in all DMPC/ganglioside mixtures was found to be relatively fixed with respect to the membrane normal. In 4:1 mixtures of DMPC with GM1 and deacetyl-GM1, the binding of Ca2+ leads to a slight decrease in chain tilt in the gel phase, probably caused by a dehydration of the membrane-water interface. In mixtures of DMPC with GM3 and deacetyl-lyso-GM1, a slight increase in chain tilt is observed. The chain tilt in DMPC/lyso-GM1 mixtures is unchanged. Analysis of the COO- band reveals that Ca2+ does not bind to the carboxylate group of the sialic acid of GM1 and deacetyl-GM1, the mixtures in which a decrease in chain tilt was observed. Binding to the sialic acid was only observed for mixtures of DMPC with GM3, lyso-GM1, and deacetyl-lyso-GM1. Ca2+ obviously accumulates at the bilayer-water interface and leads to partial dehydration of the headgroup region in the gel as well as in the liquid-crystalline phase. This can be concluded from the changes in the amide I band shapes. With the exception of DMPC/deacetyl-GM1, the effects on the ester C==O bands are small. The addition of Ca2+ has minor effects on the phase behavior, with the exception of the DMPC/GM1 mixture.
Animals↗
Leukotriene receptors in HL-60 cells differentiated into eosinophils, monocytes and neutrophils.
The expression of leukotriene B4 (LTB4) and leukotriene D4 (LTD4) receptors was determined, by binding assay, in HL-60 cells differentiated into the monocyte/macrophage, neutrophil, and eosinophil lineages. Monocyte/ macrophage- and neutrophil-differentiated cells developed specific LTB4 receptors with high affinities (Kd = 1.27 nM and 2.65 nM, respectively) and low affinities (Kd = 26.41 nM and 55.63 nM, respectively). These receptors were functional and specific as indicated by the ability of LTB4 to elicit an increase in intracellular calcium concentration antagonised by specific antagonists. Eosinophil-differentiated cells developed mainly LTD4 receptors (Kd = 41.91 nM), and stimulation with LTD4 induced an increase in intracellular calcium that was antagonised by a specific LTD4 antagonist. These results show, for the first time, that eosinophil-differentiated HL-60 cells express specific functional LTD4 receptors. These cells could be used for the study of the actions of peptidoleukotrienes on eosinophils, and for studies on the molecular mechanisms regulating LTD4 receptor expression.
Binding Sites↗
Clinical course, early diagnosis, treatment, and prevention of disease in glutaryl-CoA dehydrogenase deficiency.
BACKGROUND: Glutaryl-CoA dehydrogenase deficiency (GDD) is a recessively inherited neurometabolic disorder associated with encephalopathic crises and severe extrapyramidal symptoms. Treatment regimens including glucose and electrolyte infusions during acute illnesses, oral carnitine supplementation and/or a low-protein or lysine-restricted diet have been recommended, but their efficacy has been documented only on an anecdotal basis. SUBJECTS AND METHODS: We conducted a retrospective analysis of 57 patients with proven GDD-relating appearance and severity of neurological disease to age and clinical status at diagnosis, glutaric acid levels in body fluids, and different treatment regimens. RESULTS: Thirty-six patients were diagnosed after the onset of neurological disease (symptomatic group), twenty-one before (presymptomatic group). Carnitine levels were found to be reduced in all patients at diagnosis. In the symptomatic group, macrocephaly had been present around birth and was followed by rapid postnatal head growth in 70% of the children. The patients often showed symptoms such as hypotonia, irritability, and jitteriness followed by an acute encephalopathic crisis occurring on average at 12 months of age. Common neuroimaging findings included frontotemporal atrophy, subependymal pseudocysts, delayed myelination, basal ganglia atrophy, chronic subdural effusions and hematomas. In four patients the latter two findings were initially misinterpreted as resulting from child abuse. Other important misdiagnoses in older siblings who were affected and went undiagnosed include postencephalitic cerebral palsy, dystonic cerebral palsy and sudden infant death syndrome. Metabolic treatment did not convincingly improve the neurological disease, although it may have prevented further deterioration. Symptomatic treatment with baclofen or benzodiazepines was effective in reducing muscle spasms. Children in the presymptomatic group were diagnosed because of familiarity for the disease (n = 13), macrocephaly and/or additional minor neurological signs in infancy (n = 6), or acute encephalopathy, which was fully reversible after prompt treatment (n = 2). After diagnosis, all children were treated with oral carnitine, fluid infusion during intercurrent illnesses and, in addition, a diet was started in 13 of the 21 children. All 21 children except one (born prematurely at 31 weeks) have continued to develop normally up to now. Mean age at report is 6.3 years with a range from 6 months to 14.8 years. In older patients, the neuroradiological changes, present in infancy as in the symptomatic patients, became less prominent and in one girl disappeared. CONCLUSIONS: In presymptomatic children with GDD, the onset of neurological disease can be prevented by vigorous treatment of catabolic crises during illnesses together with carnitine supplementation. The importance of dietary therapy remains unclear and needs further evaluation. The potential treatability of GDD calls for increased attention to early presenting signs in order to recognize the disorder and to initiate treatment before the onset of irreversible neurological disease.
Adolescent↗
[Treatment of aspiration of gastric contents].
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Anesthesia, General↗