The open brain (opb) mutation maps to mouse chromosome 1.
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Animals↗
Biomedical subjects
T Günther
Publications and source records attributed to T Günther.
[Studies of the development of refractive effects in intrastromal refractive corneal surgery with the picosecond laser].
BACKGROUND: Picosecond laser intrastromal photorefractive keratectomy (ISPRK) aims at achieving a flattening of the central cornea by plasma-mediated tissue evaporation without affecting the anterior or posterior corneal layers. We investigated the laser-induced tissue effects to establish a functional relationship between laser parameters and tissue removal and to assess their influence on the healing process and long-term refractive changes. MATERIALS AND METHODS: A modified ISL 2001 System with a cone angle of 30 degrees was used for in vitro investigations of the laser effects in water and porcine cornea. Photographic methods were used to determine the plasma volume and the thickness of the laser-generated intrastromal bubble layer as a function of the pulse energy and the number and separation in which the pulses were applied (216 eyes). Histological evaluation was done by polarization microscopy (9 eyes). RESULTS: Polarization microscopy revealed only minor signs of thermal tissue damage. The maximum amount of tissue that can be evaporated without damaging the outer corneal layers corresponds to a layer about 10 microns thick. With a 6-mm optical zone, this tissue removal yields an immediate refractive effect of only 0.85 dpt. Stronger long-term refractive changes observed in animal experiments and clinical studies must thus be due to the healing response of the cornea. The healing response may be induced by mechanical distortion due to intrastromal bubble formation affecting about one third of the corneal thickness. CONCLUSION: Since the refractive effects are apparently strongly influenced by corneal healing, they are poorly predictable and can probably not be used for clinical purposes.
Animals↗
Factors determining the refractive effects of intrastromal photorefractive keratectomy with the picosecond laser.
PURPOSE: To determine the relationship between laser parameters and tissue removal with picosecond laser intrastromal photorefractive keratectomy (ISPRK) and to assess the effect of the parameters on the healing process and the long-term refractive changes. SETTING: Medical Laser Center Lübeck, Germany. METHODS: A modified Intelligent Surgical Lasers (ISL) 2001 system with a cone angle of 30 degrees was used for in vitro investigations of the laser effects in water and on the porcine cornea. Photographic methods were used to determine the plasma volume and to investigate the thickness of the intrastromal bubble layer as a function of the laser pulse energy, the number of layers in which the pulses were applied, and the layer separation. The data were used to calculate the amount of tissue removal. Histologic evaluation was done by polarization microscopy after Sirius-red staining. RESULTS: The laser pulses produced a sponge-like appearance of the stroma in a layer extending through about one third the corneal thickness, accompanied by mechanical distortions of the stromal lamellae. Thermal changes were weak. Tissue removal was impaired by the cavitation bubbles from preceding laser pulses. The amount of evaporated tissue depended only weakly on laser pulse energy and number of layers in which the pulses were applied. The maximum amount of tissue that could be evaporated without damaging the outer corneal layers was a 10.0 microm thick layer. With a 6.0 mm optical zone, the tissue removal produced an immediate refractive effect of only 0.85 diopter. CONCLUSIONS: Intrastromal PRK does not work as originally envisioned because the amount of evaporated tissue is very small. The greater long-term refractive changes observed in animal experiments and clinical studies must therefore be due to the healing response of the cornea. Because the refractive effects are strongly influenced by the healing response of the cornea, they are poorly predictable.
Animals↗
Testis damage induced by zinc deficiency in rats.
Male Wistar rats were fed a Zn-deficient diet (1.2 mg/kg of Zn) for 28 days. Testes were then studied by light and electron microscopy. Zn deficiency induced necroses of precursors of germ cells leading to tubular atrophy and affected differentiation of spermatids. This was expressed by the occurrence of 2-4 axoneme-dense fibre-mitochondria complexes in one spermatid. Moreover, outer dense fibres, which normally contain 90% of sperm Zn, were "uncoiled" and flattened. The multiplication of the axoneme-dense fibre-mitochondria complexes induced by Zn deficiency might have been produced by an increase of Fe in spermatids and an increased formation of oxygen free radicals.
Animals↗
Prevalence and pattern of Helicobacter pylori gastritis in the gastric cardia.
OBJECTIVES: Helicobacter pylori has a predilection for antral colonization. Local acid production is the major determinant of colonization. Because production is low in the antrum and cardia, H. pylori should also colonize the cardia. We therefore investigated the histologic pattern of gastritis and the prevalence of H. pylori in the cardia compared with the antrum and corpus. METHODS: From 135 H. pylori-infected patients with gastritis, ulcer disease, or reflux esophagitis, biopsies were obtained from the antrum, corpus, and cardia. The prevalence, topography, and histologic parameters of gastritis were examined. RESULTS: All 135 patients had active antral H. pylori gastritis: in the cardia, 132 of these patients (97.7%) showed active gastritis, and 124 patients (91.9%) had H. pylori visible on staining. Gastritis of the cardia in most patients resembled antral gastritis, but the density of bacteria and the inflammatory responses were less marked. The most striking finding in the cardia of patients with gastroesophageal reflux was a lower density of bacteria compared with antrum and corpus. Intestinal metaplasia was found in 32 patients in antral mucosa (23.7%) versus 28 patients in the cardia (20.7%), versus 11 patients in the corpus (8.1%), and was multifocal in 17 patients (12.6%). CONCLUSIONS: H. pylori gastritis commonly involves the cardia. The histologic density of the bacteria and inflammatory responses are lower than in the antrum. Intestinal metaplasia in the cardia is a common finding in H. pylori gastritis. The cause of the lower bacterial density in the cardia of patients with reflux esophagitis needs further investigation.
Atrophy↗
Fluid regulation during prolonged physical strain with water and food deprivation in healthy, trained men.
The aim of this study was to investigate fluidregulating mechanisms, with special regard to the role of plasma proteins in the control of plasma volume (PV), and the role of the superficial tissues as a water storage organ of the body during prolonged physical strain. 29 male subjects (mean age 22.2 +/- 2.8 years) were studied during a 5 day period of survival training with multifactorial strain including restricted water intake (11 H2O.day-1) and food intake (628 kJ.day-1) additionally to physical exercise and sleep deprivation (20 h within 5 days). Under field conditions the heart rate was monitored continuously, and body mass, body composition, thickness of the shell tissues, and blood parameters were measured at (T1), after 72 h (T2), after 120 h (T3) and in the recovery period after 48 h (T4) and 72 h (T5). The estimated energy expenditure was approximately 24,000 kJ.day-1. The mean decrease of body mass was 6.77 kg (9.5%) at T3 (p < 0.001), 0.95 kg (1.3%) at T4 (p < 0.05) and 0.68 kg (0.9%) at T5 (n.s.). A reduction of total body water of 3.8 1 was estimated at T3. Serum creatinine ([Cr]) was raised at T3 by 18.5% (p < 0.0001). No relationship was found between [Cr] and other parameters. The PV decreased by 3.7% (p < 0.0001) at T2, increased by 1.6% (p < 0.0001) at T3 and was not different to baseline at T4 (+0.2%; n.s.). Total protein concentration ([TP]) increased at T2 (11.7%; p < 0.0001) and T3 (2.6%; p < 0.01), and decreased (p < 0.0001) at T4 (8.2%) and T5 (5.7%). Plasma proteins shifted into the intravascular space at T2 and T3 and moved out of the intravascular space at T4 and T5. This gives support to the hypothesis that one of the counterregulatory mechanisms maintaining PV during prolonged exercise is provided by protein shifts from the extravascular into the intravascular space. Our data provide evidence that this mechanism assists PV homeostasis efficiently over a period of 120 h with multifactorial strain, even under conditions with a fluid loss of almost 8% of the total body water.
Adult↗
Erythropoietin in 29 men during and after prolonged physical stress combined with food and fluid deprivation.
The study investigated the influence of prolonged physical stress during survival training with food and fluid deprivation on the serum concentrations of erythropoietin (EPO). A group of 29 male subjects [mean age 22.2 (SD 2.8) years, height 1.78 (SD 0.06) m, and body mass (m(b)) 73.5 (SD 8.6) kg] were studied for 5 days of multifactorial stress including restricted water intake (11 H2O. day(-1)) and food intake (628 kJ. day(-1)) combined with physical exercise (estimated energy expenditure approximately 24000 kJ.day(-1)) and sleep deprivation (20 h within 5 days). Blood samples were taken before (T1), after 72 h (T2) and 120 h (T3) of physical stress, and after 48 h, (T4) and 72 h (T5) of recovery. The samples were analysed for EPO, and concentrations of serum iron (Fe), haptoglobin (Hapto), transferrin (Trans), ferritin (Fer), haemoglobin (Hb) and packed cell volume (PCV). The m(b) had decreased by 6.77 kg at T3 (P <0.01) and 0.68 kg at T5. The EPO and Hapto decreased during the survival training (P <0.01) and increased during the recovery period (P <0.01). The Fe increased during the survival training (P <0.01) and remained above the control concentrations during recovery (P <0.01). The Hapto decreased during the survival training (P <0.01) and remained below control concentration at T4 and T5 (P <0.01). The Trans decreased continuously over the week (P <0.01). The Fer increased during the survival training (P <0.01) and returned to control concentration at T5. The Hb increased from T1 to T2 (P <0.01) and had decreased significantly at T5 (P <0.01). The PCV increased from T1 to T2 (P <0.01) and remained below control levels afterwards (P <0.01). From our study it was concluded that, in humans, prolonged physical stress with food and fluid deprivation induces a marked EPO decrease, which is followed by a rapid increase during recovery to restore the reduced O2 transport capacity.
Adult↗
Integrins on joint cartilage chondrocytes and alterations by ofloxacin or magnesium deficiency in immature rats.
Recently, we showed that magnesium deficiency induces lesions in knee joint cartilage from 5-week-old rats that are very similar to ofloxacin-induced cartilage defects. We concluded that quinolone-induced arthropathy is probably due to chelation of magnesium and thus a deficit in functionally available magnesium in joint cartilage (Stahlmann et al. 1995). As magnesium deficiency in joint cartilage could impair chondrocyte-matrix interaction which is mediated by cation-dependent integrin receptors of the beta 1-subfamily, we investigated integrin expression in joint cartilage from untreated, ofloxacin-treated and magnesium-deficient Wistar rats. With immunohistochemical methods using monoclonal and polyclonal antibodies, we showed that the integrin pattern in joint cartilage from rats corresponded largely to integrin expression described for human cartilage tissue: beta 1, alpha 1, alpha 3 and alpha v subunits and the alpha 5 beta 1 and alpha v beta 3 heterodimers were consistently expressed. Joint cartilage lesions were detected in ofloxacin-treated and magnesium-deficient rats. Lesions were more pronounced in the quinolone-treated group. Expression of several integrins was reduced in the vicinity of lesions after oral treatment with 2 x 600 mg ofloxacin/kg for 1 day. Gross-structural lesions (e.g., cleft formation, unmasked collagen fibres) in magnesium-deficient rats were very similar but changes in integrin expression were less pronounced. On the other hand, changes in cartilage matrix composition showed similar alterations in ofloxacin-treated and magnesium-deficient rats: fibronectin deposition in the cartilage matrix increased in both groups while glycosaminoglycan content decreased. In summary, similar defects occur in ofloxacin-treated and magnesium-deficient rats and with immunohistochemical methods subtle differences are demonstrable.
Animals↗
Effects of ryegrass on biodegradation of hydrocarbons in soil.
The effects of growing ryegrass (Lolium perenne L.) on the biodegradation of hydrocarbons was studied in laboratory scale soil columns. Degradation of hydrocarbons as well as bacterial numbers, soil respiration rates and soil dehydrogenase activities were determined. In the rhizosphere soil system, aliphatic hydrocarbons disappeared faster than in unvegetated columns. Abiotic loss by evaporation was of minor significance. Elimination of pollutants was accompanied by an increase in microbial numbers and activities. The microbial plate counts and soil respiration rates were substantially higher in the rhizosphere than in the bulk soil. The results indicate that biodegradation of hydrocarbons in the rhizosphere is stimulated by plant roots.
Biodegradation, Environmental↗
Severe defects in the formation of epaxial musculature in open brain (opb) mutant mouse embryos.
The differentiation of somite derivatives is dependent on signals from neighboring axial structures. While ventral signals have been described extensively, little is known about dorsal influences, especially those from the dorsal half of the neural tube. Here, we describe severe phenotypic alterations in dorsal somite derivatives of homozygous open brain (opb) mutant mouse embryos which suggest crucial interactions between dorsal neural tube and dorsal somite regions. At Theiler stage 17 (day 10.5 post coitum) of development, strongly altered expression patterns of Pax3 and Myf5 were observed in dorsal somite regions indicating that the dorsal myotome and dermomyotome were not differentiating properly. These abnormalities were later followed by the absence of epaxial (dorsal) musculature; whereas, body wall and limb musculature formed normally. Analysis of Mox1 and Pax1 expression in opb embryos revealed additional defects in the differentiation of the dorsal sclerotome. The observed abnormalities coincided with defects in differentiation of dorsal neural tube regions. The implications of our findings for interactions between dorsal neural tube, surface ectoderm and dorsomedial somite regions in specifying epaxial musculature are discussed.
Animals↗
[Reversible cerebral MRI findings in acute microangiopathic hemolytic anemia].
A case of acute microangiopathic hemolytic anemia in a 29-year-old primiparous patient is presented. Following an unsuspicuous pregnancy and uncomplicated delivery, the patient developed upper abdominal symptoms and transient psychopathologic abnormalities 2 days after delivery. Because of a series of generalized tonic-clonic seizures and respiratory distress she was admitted to the Neuro ICU. Focal neurological symptoms were absent, and CSF analysis was normal. Laboratory findings indicated hemolytic anemia with fragmented erythrocytes in smear specimens, thrombocytopenia, reticulocytosis, marked elevation of liver and pancreatic enzymes, and microhematuria. T2-weighted MR scans of the brain discluded multiple ischemic lesions of the cerebral white and gray matter, caudate nucleus and pons, displaying a hemodynamic pattern. Specific treatment included administration of corticosteroids, repeated plasmapheresis with substitution by fresh frozen plasma and antithrombin III. A control MR performed on the 3rd day of treatment demonstrated the absence of nearly all abnormal findings previously obtained. During a 3-week clinical course the patient showed full recovery, including normalization of hematologic and neuroradiologic findings. This case demonstrates ischemic cerebral lesions in acute microangiopathic hemolytic anemia to be potentially reversible if specific treatment is provided.
Adult↗
Effects of magnesium and iron on lipid peroxidation in cultured hepatocytes.
In primary cultures of rat hepatocytes, the effects of extracellular Mg2+ and Fe on lipid peroxidation (LPO) as measured by means of malondialdehyde (MDA) formation were investigated. Incubation of hepatocytes at decreasing extracellular Mg2+ concentration enhanced LPO, depending on extracellular Fe. About 96% of MDA accumulated in the culture medium. Addition of desferrioxamine prevented LPO. Additionally, the formation of oxygen free radicals was determined by fluorescence reduction of cis-parinaric acid. With this method, an immediate decay of fluorescence was found after addition of Fe2+. Fluorescence reduction was completely prevented by desferrioxamine, indicating the function of extracellular Fe. This mechanism may operate additionally to the increase in intracellular Fe and intracellular formation of oxygen free radicals during Mg deficiency in vivo.
Animals↗
Reversibility of Na+/Mg2+ antiport in rat erythrocytes.
Rat erythrocytes loaded with Mg2+ plus Na+ performed Mg2+ uptake under an intracellular/extracellular Na+ gradient. Mg2+ uptake was coupled to Na+ release at a stoichiometric ratio of 1 Mg2+/2 Na+.Mg2+ uptake was inhibited by amiloride, imipramine and quinidine. Mn2+ was taken up by the same transporter as Mg2+. Similar results had been found for net Mg2+ efflux via Na+/Mg2+ antiport in such rat erythrocytes. Hence, it can be concluded that Na+/Mg2+ antiport in Mg(2+)-loaded rat erythrocytes operates reversibly according to the direction of the Na+ gradient which is a contributing driving force. Net Mg2+ influx was dependent on ATP which increased the affinity of intracellular Mg2+ by activating Na+/Mg2+ antiport. Mg2+ uptake was increased by phorbol ester and inhibited by staurosporine, indicating that ATP may function via protein phosphorylation by protein kinase C.
Adenosine Triphosphate↗
Magnesium deficiency induces joint cartilage lesions in juvenile rats which are identical to quinolone-induced arthropathy.
Quinolones accumulate in cartilage, and because they form chelate complexes with divalent cations, they possess the potential to induce a deficiency of functionally available magnesium. To test the hypothesis that quinolone-induced arthropathy is caused (or aggravated) by magnesium deficiency in cartilage, we induced magnesium deficiency by feeding juvenile rats a magnesium-deficient diet for 9 days and treated the rats with single oral doses of ofloxacin (0, 100, 300, 600, or 1,200 mg/kg of body weight) during this period. Additional groups of juvenile rats on a normal diet were treated with ofloxacin correspondingly. Typical cartilage lesions (e.g., swollen matrix, cleft formation) were found in knee joints of all magnesium-deficient rats, including those without ofloxacin treatment. Lesions in these groups were not distinguishable from lesions induced by a single dose of 600 mg of ofloxacin per kg of body weight or higher in rats on a normal diet. Ofloxacin levels in plasma after 600 mg/kg of body weight were approximately 10-fold higher than those in humans during therapy with this quinolone. Lesions in rats treated with ofloxacin plus magnesium deficiency were more pronounced than those in rats with normal magnesium concentrations. After intake of a magnesium-deficient diet for 9 days, the magnesium concentration in serum (mean +/- standard deviation) was 0.18 +/- 0.05 mmol/liter (control on normal diet, 0.82 +/- 0.10 mmol/liter). Magnesium concentrations in bone (femur) and cartilage (processus xiphoideus) samples were 64.7 +/- 10.5 and 14.3 +/- 3.9 mmol/kg of dry weight, respectively, which corresponded to approximately 50% of the concentrations measured in controls on a normal diet. It was concluded that quinolone-induced arthropathy is probably caused by a deficit of available magnesium in joint cartilage due to the formation of quinolone-magnesium chelate complexes. If juvenile patients must be treated with quinolones for serious infections, it seems prudent to ensure that these patients do not have a disturbed magnesium balance.
Animals↗
Measurement of free magnesium in blood, serum and plasma with an ion-sensitive electrode.
The fraction of total magnesium bound to protein and other substances depends upon the pH. pH-dependency of ionized free magnesium (iMg2+) in serum is expressed by the Siggaard-Andersen equation: iMg2+ (pH) = iMg2+ (7.4) x 10x(7.4 - pH). During preparation of serum or plasma, considerable pH changes occur which have to be corrected on the basis of the above mentioned equation. For pH correction of iMg2+, x < 0.1 has so far been used. However, this is correct only for new Mg(2+)-sensitive electrodes. During the lifetime of Mg2+ electrodes used in the "Microlyte Magnesium" (Kone Instruments, Finland) x increases and x = 0.2 was found to be a suitable approximation for most of the lifetime. By instantaneous iMg2+ measurements in whole blood samples pH changes and the uncertainty of x can be avoided. Dilution of blood by intravenous infusions decreases x nearly proportionally to the decrease of protein concentration in blood. Various methodological influences such as temperature and delay time before centrifugation, storage of serum and venous occlusion were studied. The circadian rhythm of iMg2+ was found to be considerably more pronounced than that of total Mg and was negatively correlated to changes of free fatty acids. To avoid variations of iMg2+ due to circadian changes, blood collection should be carried out between 6 and 10 a.m. The normal range of iMg2+ in blood of 179 healthy subjects was found to be between 0.46 and 0.60 mmol/l and the quotient of free and total Mg between 0.59 and 0.71. The accuracy of "Microlyte Magnesium" (Kone Instruments, Finland) is sufficient in a wide range of iMg2+.
Blood Specimen Collection↗
Changes of ionized magnesium and free fatty acids in serum after acute myocardial infarction.
The most feared early complications after an acute myocardial infarction are ventricular arrhythmias. These may be initiated by changed concentrations of catecholamines and electrolytes. The present study shows a reduction of total serum magnesium after acute myocardial infarction which is normalized within a few days. Further, it could be shown that a more significant decrease of ionized Mg2+ (iMg2+) takes place at the day of acute myocardial infarction in the total group of myocardial infarction patients (n = 36). A closer investigation reveals that iMg2+ was considerably decreased in one third of the patients, whereas two thirds showed minor changes of iMg2+ in both directions. The pronounced decrease of iMg2+ in the first sub-group can be explained by the time course of free fatty acids in serum. On the day of the myocardial infarction free fatty acids in serum were increased. This is probably caused by beta-adrenergic-induced lipolysis due to catecholamines released by the stressful situation of an acute myocardial infarction. The increased free fatty acids in serum bind Mg2+, thus reducing iMg2+. As long as a beneficial effect of a general Mg infusion in all acute myocardial infarction patients is controversial, iMg2+ should be measured and Mg infusion therapy should be applied only in patients with low iMg2+.
Adult↗
Interactions of polyamines with Mg(2+)-sensitive macroelectrodes and Mg2+ buffers.
The polyamines spermine, spermidine and putrescine interact with Mg(2+)-sensitive macroelectrodes based on the neutral carrier ETH 7025; the interaction in decreasing order being spermine, spermidine and putrescine. The effect is small and dependent on the ionized magnesium concentration ([Mg2+]free), only resulting in a significant increase in the measured [Mg2+]free with spermine and spermidine at [Mg2+]free less than 0.5 mM. The polyamines compete with Mg2+ for common binding sites on Mg2+ buffers such as ATP, ADP and citrate, releasing bound Mg2+ and increasing the [Mg2+]free. This effect is most prominent with Mg ATP and the action of the polyamines in decreasing order is spermine, spermidine and putrescine. Increases in polyamines which occur in cell proliferation and cancer could thus secondarily increase the [Mg2+]free resulting in an activation of Mg(2+)-dependent metabolic pathways.
Adenosine Diphosphate↗
Synchronous multifocal bone sarcomas--a case report and molecular pathologic investigation.
A case of a 54-year-old woman is described who developed synchronously two malignant bone tumors: a dedifferentiated chondrosarcoma in the olecranon and a malignant fibrous histiocytoma (MFH) in the lower tibia. The anaplastic part of the dedifferentiated chondrosarcoma revealed an MFH-like pattern. Myogenous differentiations were not observed in the anaplastic sarcoma cells. The MFH in the tibia showed a storiform-pleomorphic pattern. Single tumor cells showed positivity for M-actin and desmin pointing to myogenous differentiation. DNA-cytophotometry of the dedifferentiated chondrosarcoma showed an aneuploid stem cell line. The MFH in the tibia did not reveal aneuploid stem cells. Staining for p53 protein was negative in both tumors. SSCP analysis and sequencing of the p53 gene in both tumors revealed in the dedifferentiated chondrosarcoma a mutation in exon-8 with the transversion from G to T in codon 294 resulting in a substitution of a stop codon for GLU. The mutation was not observed in the MFH. From these immunohistologic, DNA-cytometric and molecular biologic investigations, we consider it probable that the tumor in the lower tibia is a second highly malignant bone tumor and not the metastasis of the dedifferentiated portion of the dedifferentiated chondrosarcoma in the olecranon.
Bone Neoplasms↗