Partial trisomy of chromosome 22 resulting from an interstitial duplication of 22q11.2 in a child with typical cat eye syndrome.
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Abnormalities, Multiple↗
Biomedical subjects
S Langer
Publications and source records attributed to S Langer.
Effect of C-peptide on wound healing and microcirculation in diabetic mice.
AIM: Recent studies have demonstrated that C-peptide is biologically active and might have a beneficial effect on late complications in diabetes mellitus. The aim of this study was to investigate the effects of systemically given C-peptide on dermal wound healing in diabetic mice. METHODS: Experiments were carried out in male SKH-1 hr hairless mice. Dermal wounds were created (diameter 2.5mm) in streptozotozin-diabetic and normal control mice. Mice were randomized into three treatment groups (n = 10 each): Normal controls, diabetic mice with PBS or C-peptide injection twice daily. At various time points (prior wounding as well as days 4, 7, 10 and 15) microcirculation was quantitatively analyzed by intravital fluorescent microscopy to determine wound surface area, vessel diameter, red blood cell velocity, plasma leakage, functional capillary density. In addition, leukocyte/endothelium interaction was quantified by in vivo visualization of leukocytes. RESULTS: Systemic administration of C-peptide showed no influence on wound healing or standard microcirculatory parameters. The leukocyte/ endothelium interaction revealed a significant (p<0.05) increase in the number of adherent leukocytes 15 days after wound creation in C-peptide treated diabetic mice. CONCLUSION: Except for the significantly increased number of leukocytes adherent to venular endothelium in the C-peptide group no alteration was observed in wound healing and microcirculation. Neutrophil recruitment after C-peptide injection is of interest because it may reduce the risk of infection in diabetes mellitus.
Animals↗
[Laparoscopic Collis-Nissen operation for shortened esophagus].
Esophageal shortening as a complication of advanced gastroesophageal reflux disease is seen in 2-4 % of patients with GERD. The Collis gastroplasty with Nissen fundoplication creates an intraabdominal neoesophagus with a fundic wrap and is an effective procedure in the difficult intraoperative situation of esophageal shortening. After own experience with the open Collis gastroplasty and after reports on successful laparoscopic Collis-Nissen operation we performed 2 laparoscopic Collis-Nissen operations. The technique we used is a new modification of the laparoscopic technique described by Johnson and Hunter in 1998. The postoperative course was uncomplicated in both patients. The follow up included endoscopy and barium meal. The patients showed relief from reflux symptoms except a mild dysphagia. There was no persisting esophagitis. The laparoscopic Collis-Nissen gastroplasty is an effective minimal-invasive procedure in patients with shortened esophagus diagnosed intraoperatively.
Aged↗
Orthogonal polarization spectral imaging versus intravital fluorescent microscopy for microvascular studies in wounds.
The aim of this study was to validate orthogonal polarization spectral (OPS) imaging against intravital fluorescence microscopy (IFM) for microvascular measurements in normal skin and during wound healing. Experiments were performed on the ears of hairless mice (N = 8). The diameter of arterioles and venules, red blood cell velocity in venules, and the functional capillary density were assessed under normal conditions using OPS imaging and IFM. After creation of a circular wound, these observations were repeated at the identical microvascular regions on days 4, 7, 10, and 15. Images were videotaped, and CapImage was used for off-line computer-assisted analysis. Using OPS imaging, the microcirculation of wounded skin in hairless mice could be observed successfully. The regression analyses against standard IFM revealed a significant (p < 0.001) correlation for measurements of all microcirculatory parameters investigated (venular diameter: r(2) = 0.98, N = 345; red blood cell velocity: r(2) = 0.51, N = 326; functional capillary density: r(2) = 0.44, N = 156). However, for diameter as well as for functional capillary density measurements, OPS imaging yielded lower absolute values compared with IFM. The authors were able to validate OPS imaging against IFM for the measurement of microvascular parameters in an animal model of skin wound healing. Such a device should now help to study the role of microcirculation in physiology and pathophysiology during wound healing in patients. First clinical investigations are promising.
Animals↗
[Secondary reconstruction after burns of the anogenital area].
The incidence of burns of the genitalia and peri-anal region which may cause a reconstructive intervention is very low. In the most cases the use of split thickness skin grafts yields a sufficient permanent wound closure. Upcoming problems such as painful scare formation require a reconstructive intervention (Z-plasty, full thickness skin grafting, pedicled flaps etc.). In case that the anal sphincter is involved with the consequence of incontinence or major damage of the genitalia occurred, sophisticated operative solutions are necessary.
Anal Canal↗
[Joint infection caused by radiogenic defect: prevention and therapeutic options].
Exposed irradiated joints are characterized by bone and cartilage necrosis with a chronically infected joint space. The indication for treatment results from possible infection spreading and more often because of severe pain. The usual concept of sequential debridement, joint replacement and regional flap coverage, is often impossible due to the radiodermitis and bone necrosis in the neighbourhood of the joint. Even free flaps are associated with a higher failure rate, because of the irradiation of the recipient vessels long vein grafts are often needed. If regional flap coverage is desired, distant flaps with long, not irradiated pedicles must be chosen. Prevention due to special considerations during the first surgery is essential.
Amputation, Surgical↗
[Direct visualization of microcirculation in burn wounds with OPS imaging--is determination of depth of burns possible?].
Adjunct diagnostic techniques might help surgeons to accurately analyse the depth of a burn. However, despite all technical innovations an ideal device for such an application has not been established for routine use as yet. OPS imaging implemented into the CYTOSCAN A/R is a new, recently introduced technique which allows to obtain high contrast images of the microcirculation without the necessity for fluorescent dyes. The aim of the study was to validate OPS imaging as a tool to study microcirculation in skin after burn injury. OPS imaging was applied by no-touch technique and capillary blood flow was videotaped. Subsequent measurements of the microcirculation were performed at the identical site of the burn. Quantitative analysis of the microcirculation was performed off-line using CapImage. OPS imaging produces high quality images of the microcirculation in a burn wound. Data is given as the number of perfused capillaries per observation area (functional capillary density; FCD) [n/cm2]. OPS imaging allows for direct in vivo visualization and quantification of the microcirculation in burned skin. Our preliminary results of the use of OPS imaging in assessing the microcirculation in burns appear promising, and we hope that this novel technique will allow to improve the knowledge of the dynamics of the microcirculation in the pathophysiology of thermal injury.
Blood Flow Velocity↗
[Intravital microscopic analysis of perfusion, leukocyte-endothelial cell interaction and neovascularization after burns: an in vivo study of SKH-1/hr hairless mice]].
Breakdown of skin microcirculation is supposed to play a key role in pathophysiology of burn injury. The aim of the study was to develop a burn model, which allows repetitive quantitative in vivo analysis of microcirculation after burn injury with special focus on leukocyte endothelium interaction over a longer period of time. Male hairless mice (SKH-1/hr) were used. Deep partial thickness burns were inflicted in no-touch-technique to the ears. Intravital fluorescent microscopy in combination with FITC-dextran as a plasma-marker was used to assess standard microcirculatory parameters. Leukocytes were stained with rhodamine-6-G to study their interaction with the endothelium.
Animals↗
In vivo assessment of colon microcirculation: comparison of the new OPS imaging technique with intravital microscopy.
BACKGROUND: The Orthogonal Polarization Spectral (OPS) imaging technique has been introduced for in vivo assessment of microcirculation in humans. Unclear remains, whether the new technique would allow for accurate investigations of the colon microcirculation with respect to the unique conditions of the microvasculature in that particular tissue. Therefore, the aim of this study was to validate the new technique against intravital fluorescence microscopy (IFM) for the visualization of colon microcirculation in a murine model of inflammatory bowel disease (IBD). METHOD: IBD was induced in Balb/c mice by dextran sulfate sodium (DSS), controls received normal water. In each animal, both the CYTO-SCAN A/R and IFM were used to image the microcirculation (n = 7 in each group). Postcapillary venular diameter, venular red blood cell velocity (RBC-V) and functional capillary density (FCD) were analyzed on the colon muscularis and mucosa and compared to each other using linear regression analysis and Bland-Altman plots. RESULTS: All parameters correlated significantly between the both methods. The venular diameters and the RBC-V were significantly different between control and colitis group in contrast to FCD; these results were present while using both methods. CONCLUSION: Our study demonstrates that the new technique for visualization of microcirculation without use of fluorescent dyes, the OPS-imaging, allows for quantitative measurement of the key microcirculatory parameters of the mouse colon.
Animals↗
The influence of organ temperature on hepatic ischemia-reperfusion injury: a systematic analysis.
BACKGROUND: Although hepatic ischemia-reperfusion (I/R) injury can be reduced by cooling of the ischemic organ, a systematic in vivo analysis of the influence of organ temperature in I/R injury is missing. The aim of this study was to systematically investigate the impact of defined temperatures of the ischemic liver tissue on microvascular I/R injury. METHODS: Ischemia of the left liver lobe was induced in C57BL/6 mice for 90 min. The ischemic lobe was placed in a polyethylene well and the temperature was adjusted to 37 degrees C, 26 degrees C, 15 degrees C, and 4 degrees C by superfusion with cooled/warmed saline solution. The ischemia groups (n=7 each) were compared with a sham-operated group (n=7). The sinusoidal perfusion index and the number of leukocytes firmly adherent to the endothelium of postsinusoidal venules were assessed using intravital fluorescence microscopy at 30 min, 120 min, and 240 min of reperfusion, respectively. At the end of the experiment, serum activities of the liver enzymes aspartate aminotransferase/alanine aminotransferase were determined, and tissue specimens were examined by electron microscopy. RESULTS: Core body temperature did not differ significantly between the groups. In the 37 degrees C group, the sinusoidal perfusion index was significantly reduced and the number of adherent leukocytes was significantly increased compared with the sham group. In all hypothermia groups, however, the microcirculatory parameters did not differ from the sham group. Serum activities of aspartate aminotransferase/alanine aminotransferase were significantly increased and hepatocellular integrity was severely affected in the 37 degrees C group as compared with all other groups. CONCLUSIONS: These findings demonstrate that in the mouse liver the known protective effect of hypothermia is already encountered at 26 degrees C. Further reduction of temperature did not generate additional protection from I/R injury.
Alanine Transaminase↗
Assessing the microcirculation in a burn wound by use of OPS imaging.
We report on the use of OPS imaging to visualize the microcirculation in a burn wound. This novel technique produces high quality images of the microcirculation and quantitative analysis of functional capillary density (FCD) was possible. FCD measured at day 3 following the injury was 11.2 +/- 4.6 (n/mm superset2; mean +/- SEM). During the initial phase of healing microcirculatory changes were characterized by a moderate but steady increase of FCD, which showed marked increase beginning from day 12 following the burn (16.6 +/- 6.9). Maximal FCD measured at day 23 (48.2 +/- 19.7) decreased from this point in time to finally reach 25.2 +/- 10.3 n/mm superset2 at the end of observation. OPS imaging allows for direct in vivo visualization and quantification of the microcirculation in burned skin. Our results of the use of OPS imaging in assessing the microcirculation in a burn wound appear promising, and we hope that this novel technique will allow to improve the knowledge of the dynamics of the microcirculation in the pathophysiology of thermal injury.
Adult↗
Securin is required for chromosomal stability in human cells.
Abnormalities of chromosome number are the most common genetic aberrations in cancer. The mechanisms regulating the fidelity of mitotic chromosome transmission in mammalian cells are therefore of great interest. Here we show that human cells without an hSecurin gene lose chromosomes at a high frequency. This loss was linked to abnormal anaphases during which cells underwent repetitive unsuccessful attempts to segregate their chromosomes. The abnormal mitoses were associated with biochemical defects in the activation of separin, the sister-separating protease, rendering it unable to cleave the cohesin subunit Scc1 efficiently. These results illuminate the function of mammalian securin and show that it is essential for the maintenance of euploidy.
Amino Acid Sequence↗
Orthogonal polarization spectral imaging as a tool for the assessment of hepatic microcirculation: a validation study.
BACKGROUND: Quantitative analysis of liver microcirculation using intravital fluorescence microscopy in animals has increased our knowledge about ischemia-reperfusion injury. However, because of the size of the instrumentation and the necessity of fluochromes for contrast enhancement, human liver microcirculation cannot be observed. Orthogonal Polarization Spectral (OPS) imaging is a recently introduced technique that can be used to visualize the microcirculation without the need for fluorescent dyes. It is a small, hand-held device and could potentially be used to study the microcirculation of the human liver in a clinical setting. However, before implementation into clinical use its ability to quantitatively measure microcirculatory parameters must be validated. METHODS: The livers of Spraque-Dawley rats (n=9) were exteriorized, and images were obtained using OPS imaging and intravital fluorescence microscopy of the identical microvascular regions before and after the induction of a 20-min warm lobar ischemia. Images were videotaped for later computer-assisted off-line analysis. RESULTS: OPS imaging can be used to accurately quantify the sinusoidal perfusion rate, vessel diameter, and venular red blood cell velocity. Correlation parameters were significant and Bland-Altman analyses showed good agreement for data obtained from the two methods at baseline as well as during reperfusion. CONCLUSION: OPS imaging can be used to quantitatively measure microcirculatory parameters in the rat liver under both physiological and pathophysiological conditions. Thus, OPS imaging has the potential to be used to make quantitative measurements of the microcirculation in the human liver.
Animals↗
In vivo monitoring of microvessels in skin flaps: introduction of a novel technique.
Orthogonal polarization spectral (OPS) imaging was validated against intravital fluorescence microscopy (IFM) for microvascular measurements in skin flaps of hairless mice. Examinations were performed 1, 6, and 24 hours after elevation (n = 8) with both OPS imaging and IFM. A fluorescent dye was a prerequisite for IFM measurements but not for OPS imaging. Our findings show that OPS imaging can visualize the skin flap microcirculation independent from the application of fluorescent tracers. From these images, quantitative analysis of functional capillary density (FCD) was feasible. As expected, FCD was significantly lower in the distal part of the flap compared with its base (171.8 +/- 34.7 versus 62.0 +/- 25.6, mean +/- SD; 1 hour data). Comparison of OPS imaging and IFM revealed a significant correlation of FCD values (P < 0.001) at all time points. Given the success of this validation study on mouse skin flaps, clinical investigations will have to prove that OPS imaging can also successfully be used to monitor flaps in humans.
Animals↗
Ischemia at 4 degrees C: a novel mouse model to investigate the effect of hypothermia on postischemic hepatic microcirculatory injury.
Hypothermia of the ischemic organ at 4 degrees C protects hepatic microcirculation from ischemia-reperfusion (IR) injury. The effect of hypothermia during ischemia was investigated in animal models using liver transplantation and storage of the harvested organ in cold preservation solutions. No investigation of the isolated influence of hypothermia at 4 degrees C of the ischemic organ on hepatic IR injury exists, due to the lack of an appropriate animal model. Therefore, the aim of our present study was to develop such a model using intravital video fluorescence microscopy (IVM). In C57BL/6 mice, a reversible isolated ischemia of the left liver lobe was induced for 90 min, followed by 240 min of reperfusion. The temperature of the ischemic organ was adjusted to either 4 degrees C or 37 degrees C by superfusion with 0.9% NaCl. Sham-operated animals without IR served as controls. The hepatic microcirculation was analyzed using IVM at 30 min and 240 min after reperfusion by quantifying sinusoidal perfusion and leukocyte-endothelial cell interaction in postsinusoidal venules. At the end of the experiment, blood and tissue samples were taken for measurement of liver enzyme activities and light and electron microscopy. Mean arterial pressure and body temperature were kept constant throughout the experiment, while the temperature of the ischemic liver lobe was adjusted to predefined levels. After normothermic ischemia, hepatic microvascular perfusion was significantly impaired compared with sham-operated animals. Perfusion failure was significantly reduced in hypothermic livers and did not differ from livers of the sham-group. Liver enzyme activities in the normotherimic group were significantly higher than in the sham and hypothermic groups. Light and electron microscopy revealed severe histological alterations at 37 degrees C ischemia, whereas at 4 degrees C ischemia only minimal lesions were encountered. Our novel model allows for isolated adjustment of ischemic liver lobe temperature without changing body temperature and systemic macrohemodynamic parameters. Hypothermia at 4 degrees C largely attenuates postischemic microvascular perfusion injury of the liver.
Animals↗
The tetratricopeptide repeat domains of human, tobacco, and nematode PEX5 proteins are functionally interchangeable with the analogous native domain for peroxisomal import of PTS1-terminated proteins in yeast.
In the yeast Saccharomyces cerevisiae, beta-oxidation of fatty acids is compartmentalised in peroxisomes. Most yeast peroxisomal matrix proteins contain a type 1C-terminal peroxisomal targeting signal (PTS1) consisting of the tripeptide SKL or a conservative variant thereof. PTS1-terminated proteins are imported by Pex5p, which interacts with the targeting signal via a tetratricopeptide repeat (TPR) domain. Yeast cells devoid of Pex5p are unable to import PTS1-containing proteins and cannot degrade fatty acids. Here, the PEX5-TPR domains from human, tobacco, and nematode were inserted into a TPR-less yeast Pex5p construct to generate Pex5p chimaeras. These hybrid proteins were examined for functional complementation of the pex5delta mutant phenotype. Expression of the Pex5p chimaeras in pex5delta mutant cells restored peroxisomal import of PTS1-terminated proteins. Chimaera expression also re-established degradation of oleic acid, allowing growth on this fatty acid as a sole carbon source. We conclude that, in the context of Pex5p chimaeras, the human, tobacco, and nematode Pex5p-TPR domains are functionally interchangeable with the native domain for the peroxisomal import of yeast proteins terminating with canonical PTS1s. Non-conserved yeast PTS1s, such as HRL and HKL, did not interact with the tobacco PEX5-TPR domain in the two-hybrid system. HRL occurs at the C-terminus of the peroxisomal protein Eci1p, which is required for growth on unsaturated fatty acids. Although mutant pex5delta cells expressing a yeast/tobacco Pex5p chimaera failed to import a GFP-Eci1p reporter protein, they were able to grow on oleic acid. We reason that this is due to a cryptic PTS in native Eci1p that can function in a redundant system with the C-terminal HRL.
Animals↗
AcroM fluorescent in situ hybridization analyses of marker chromosomes.
The presence of a de novo supernumerary marker chromosome (SMC) poses problems in genetic counseling. The consequences of the additional chromosomal material may range from harmless to detrimental. As the composition of a SMC cannot be deciphered by traditional banding analysis, sophisticated methods are needed for their rapid and detailed analyses. A new strategy is presented, which allows the elucidation of the composition of SMCs in one or two hybridizations. One hybridization, termed AcroM-FISH, involves a newly generated probe mix, which consists of painting probes for all acrocentric chromosomes, centromere probes for chromosomes 13/21, 14/22, 15, and a probe specific for rDNA, each labeled with a specific combination of fluorochromes. This probe mix is sufficient to characterize approximately 80% of all SMCs. For the other 20% of SMCs, chromosomes can be analyzed in a second hybridization by multicolor karyotyping, for example, multiplex FISH (M-FISH), to check for the presence of euchromatin of other chromosomes. The potential of AcroM-FISH was tested in various applications.
Adult↗
Facilitating haplotype analysis by fully automated analysis of all chromosomes in human-mouse hybrid cell lines.
Recent evidence suggests that haplotype analysis is essential in recognizing genetic factors involved in the tendency toward a particular disease or pharmacogenetic phenotype, as well as to identify genes involved in multigenic disorders. Because of the increasing need for efficient haplotype tests, a new hybrid system, called conversion technology, was developed. Conversion technology aims at converting the diploid chromosome content into a haploid state so that hybrids contain a single copy of any desired chromosome. A number of mutations can now be identified easily, as they are no longer obscured by the normal sequence present on the other copy of the chromosome. However, the efficient use of this hybrid system depends on a complete analysis of both human and mouse chromosome complements in order to assess the stability of the hybrid cells and to accurately determine their human chromosome content. We describe a new multicolor FISH-based method capable of analyzing both genomes simultaneously in a single hybridization. This new technique should become an instrumental part of inexpensive, reliable haplotype tests.
Animals↗