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C Kirchhoff

Publications and source records attributed to C Kirchhoff.

At least 19 recordsLinked to original sources

A new paradigm for profiling testicular gene expression during normal and disturbed human spermatogenesis.

The aim of this study was to identify gene expression patterns of the testis that correlate with the appearance of distinct stages of male germ cells. We avoided the pitfalls of mixed pathological phenotypes of the testis and circumvented the inapplicability of using the first spermatogenic wave as done previously on rodents. This was accomplished by using 28 samples showing defined and highly homogeneous pathologies selected from 578 testicular biopsies obtained from 289 men with azoospermia (two biopsies each). The molecular signature of the different developmental stages correlated with the morphological preclassification of the testicular biopsies, as shown by resampling-based hierarchical clustering using different measures of variability. By using analysis of variance (ANOVA) and extensive permutation analysis, we filtered 1181 genes that exhibit exceptional statistical significance in testicular expression and grouped subsets with transcriptional changes within the pre-meiotic (348 genes), post-meiotic (81 genes) and terminal differentiation (38 genes) phase. Several distinct molecular classes, metabolic pathways and transcription factor binding sites are involved, depending on the transcriptional profile of the gene clusters that were built using a novel clustering procedure based on not only similarity but also statistical significance.

Azoospermia↗

Early diagnosis of colorectal cancer: a preventive task in occupational health.

Morbidity of colorectal cancer is still accreting; therefore in 2003 a total of 57000 patients fell ill and about 28000 died due to colorectal carcinoma. According to the etiology, many different factors are currently in discussion. However, as in about 25-30% of the cases familial clustering can be observed one of the most probable might be the genetic predisposition. Nevertheless only in 3% of all cases this predisposition is also scientifically assured. The high average age of manifestation raised the question if there might be also an occupational relationship for colorectal carcinoma in tense of an occupational disease. Therefore there is sight for occupational health to contribute to early diagnosis of colorectal carcinoma within the scope of routine check-up, health management and research of occupational diseases.

Colorectal Neoplasms↗

Aggressive scapular chondroblastoma with secondary metastasis--a case report and review of literature.

Chondroblastoma is a benign bone tumor, accounting for approximately one percent of all benign bone tumors. It mostly occurs in typical locations such as long bones. Malignant transformation including metastasis has been described in only a few cases. Therefore, we report a unique case of chondroblastoma with tumor manifestation in the 7th decade of life, location of the tumor in the scapula and occurrence of metastasis in the soft tissue of the mandible branch. Due to aggravation of the clinical course, a scapula en bloc resection was performed. The differential diagnosis is discussed and the current literature concerning malignant transformation of chondroblastoma is reviewed.

Aged↗

Role of epididymal receptor HE6 in the regulation of sperm microenvironment.

HE6 (GPR64) is a highly conserved, tissue-specific heptahelical receptor of the human epididymis. The seven transmembrane (TM7) domains are a hallmark of G-protein-coupled receptors (GPCRs) which have a proven history of being excellent therapeutic targets. Of all currently marketed drugs, >30% are modulators of specific heptahelical receptors, emphasizing the potential of HE6 as a target for pharmaceutical intervention. Targeted mutation of the mouse HE6 counterpart resulted in male infertility, further emphasizing its role as a candidate target for male contraception. However, the precise function of HE6, together with its potential ligand(s), and signal transduction pathways have remained largely unknown. On the basis of shared sequence motifs within the TM7 region, HE6 has been grouped into the B class of GPCRs. Within this class, HE6 belongs to the 'large N-termini' family-B seven-transmembrane (LNB-TM7) receptors, also termed the adhesion-GPCRs. Members of this subgroup are 'orphan' receptors, and they all seem to be cleaved within a conserved GPCR proteolytic site (GPS) domain. The biological significance of the two-subunit architecture is still unknown. Clues to the function of HE6 within the epithelium of male excurrent ducts may come from its co-localisation with the apical actin cytoskeleton and from the down-regulation in "knockout" male mice of various proteins specific to the initial segment.

Amino Acid Sequence↗

[Tension pneumopericardium--a rare complication in multiply injured patients].

Thoracic injury is a relevant and common complication in multiply injured patients. Typical patterns of injury comprise rib fractures, serious lung trauma as well as diaphragmatic and aortic rupture. In contrast, posttraumatic tension pneumopericardium following blunt thoracic trauma is a very rare complication. However, if unrecognized it might provoke cardiac tamponade and death. For the development of a pneumopericardium, free air follows the vessel bundles up to the pericardium. Hence, if the number of ruptured alveoli is high, or these alveoli are placed close to the heart, and if additional risk factors, such as high inspiratory ventilation pressure, are present, a tension pneumopericardium can induce cardiac tamponade. The aim of this report is to illuminate diagnostic and therapeutic strategies for posttraumatic pneumopericardium by presentation of a case from our trauma centre and a critical discussion of the present literature.

Humans↗

[The presence of family members in the trauma room].

The fate of multiple trauma patients is witnessed by a considerable number of relatives. Although numerous studies report that the patient's course and treatment success are dependent on the family's confidence as well as its clarification over the clinical situation, scientifically based guidelines for contact with relatives in the context of acute care following severe traumatic injuries do not yet exist. The current guidelines of the European Resuscitation Council recommend the concept of "on scene" presence for the integration of the relatives into acute care in situations of circulatory and heart failure, thus recommending the presence of relatives during acute medical care. This article discusses this concept and argues for a possible assignment of management of trauma care for severe and gravely injured patients.

Attitude of Health Personnel↗

[Iatrogenic lesion of the radial nerve--disability in domestic work concerning liability].

In liability cases caused by accidents, the actual compensation for consecutive sustained damage to the patients' health and pain is not sufficient. Moreover, besides payments for a loss of earning capacity, the compensation for loss of efficiency in daily life such as for domestic work might be necessary. Therefore, distinct indications for the expert's appraisal exist.

Accidents, Occupational↗

Cerebral perfusion pressure for prediction of recurrent intracranial hypertension after primary decompressive craniectomy.

BACKGROUND: Decompressive craniectomy (DC) with dural grafting may be performed in patients with moderate (Glasgow-Coma-Scale [GCS] score 9-12 points) or severe traumatic brain injury (TBI; GCS score <or= 8 points) and threatening herniation. However, its effectiveness especially after primary craniectomy is still discussed due to missing evidence of improved outcome. The objectives of this study were to show the incidence of recurrent intracranial hypertension after primary DC, to identify predictive parameters for secondary DC, and to evaluate the long-term neurological performance 12 months after TBI. METHODS: Between 01/1997 and 06/2001 all consecutive patients admitted with moderate or severe isolated TBI were enrolled in this study. They were treated according to the guidelines of the European Brain Injury Consortium, and the American Association of Neurosurgical Surgeons (AANS) for the management of severe TBI. Process and clinical data as well as every intervention were registered prospectively. The long-term neurological status was reassessed using the Glasgow Outcome Score (GOS) 12 months after TBI. Statistical comparison was performed using Mann-Whitney-U test, and multivariate testing by means of logistic regression analysis. RESULTS: Fifty-one (43 males, 8 females; median age 51.4 years) of 119 isolated TBI patients were included. Ten patients (8 males, 2 females; median age 38.4 years) underwent secondary extended or contralateral DC in their clinical course. Three of them (30%) died at a median of 1 day after revision respectively 6 days after TBI. According to univariate analysis, secondary DC significantly correlated with arterial hypotension (p = 0.020) and otorrhagia at admission (p = 0.041), skull base fracture (p = 0.011) and decreased maximum cerebral perfusion pressure (CPP; p = 0.006) after primary surgery. Multivariate analysis identified decreased maximum CPP as the only independent predictive parameter (p = 0.036) for secondary DC and unfavourable GOS after 12-months follow-up. CONCLUSION: Arterial hypotension, otorrhagia at admission and skull base fractures are negatively influencing the mortality and morbidity of patients with isolated moderate or severe TBI. However, only decreased maximum CPP may independently indicate secondary DC after primary craniectomy in case of recurrent intracranial hypertension.

Adult↗

[Visualization and quantification of large bowel motility with functional cine-MRI].

PURPOSE: To develop and evaluate a method to visualize and quantify large bowel motility using functional cine MRI. METHODS: Fifteen healthy individuals (8 males, 7 females, 20 to 45 years old) with no history or present symptoms of bowel disorders were enrolled in a functional cine MRI examination at 6 a. m. after a starving phase for at least eight hours before and after oral administration of Senna tea (mild stimulating purgative). Two consecutive sets of repeated measurements of the entire abdomen were performed using a 1.5 T MRI system with coronal T2-weighted HASTE sequences anatomically adjusted to the course of the large bowel. A navigator technique was used for respiratory gating at the level of the right dorsal diaphragm. The changes in diameter (given in cm) were measured at 5 different locations of the ascending (AC), transverse (TC) and descending colon (DC), and assessed as parameters for the bowel motility. RESULTS: The mean values as a statistical measure for large bowel relaxation were determined. Before ingestion of Senna tea, the mean diameter measured 3.41 cm (ascending colon), 3 cm (transverse colon) and 2.67 cm (descending colon). After the ingestion of Senna tea, the mean diameter increased to 3.69 cm (ascending colon) to 3.4 cm (transverse colon) and to 2.9 cm (descending colon). A statistically significant difference was demonstrated with the Wilcoxon test (level of confidence 0.05). For the determination of dynamic increase, the changes of the statistical scatter amplitude to the mean value were expressed as percentage before and after the ingestion of Senna tea. Thereby, an increase in variation and dynamic range was detected for the AC (112.9 %) and DC (100 %), but a decrease in the dynamics for the TC (69 %). CONCLUSION: A non-invasive method for the assessment of bowel motility was developed for the first time. The use of functional cine MRI utilizing a prokinetic stimulus allowed visualisation and quantification of large bowel motility. Further studies have to determine whether this technique is clinically relevant.

Adult↗

Analysis of atropine, its degradation products and related substances of natural origin by means of reversed-phase high-performance liquid chromatography.

Chromatographic separation and quantification methods of tropa alkaloids were often described. In order to separate atropine from its degradation products ion-pair chromatography (IPC) has been frequently applied. Beside long equilibration times IPC often suffers from poor robustness. The aim of this study was to develop robust and simple HPLC methods for both stability testing of atropine solutions and limitation of related substances in atropine from plant material. Using a hydrophilic embedded RP18 column and a gradient elution gave baseline separation of all components.

Atropine↗

Cloning and characterization of boar epididymal secretory proteins by homology to the human.

Northern blot analysis suggested that the boar epididymis produces closely related counterparts to human epididymal proteins HE1, HE3, HE4, HE5 and HE12. 'Full-length' cloning by nucleic acid and amino acid sequence similarity was achieved by RT-PCR methods in the case of the porcine counterparts of HE3 and HE4, while the homologues of HE5 and HE12, despite their cross-hybridization during Northern blot analysis, have not yet been cloned. The two novel porcine cDNAs were derived from moderately abundant epididymal mRNAs that were 75 and 83% identical to HE3 and HE4 cDNAs, respectively. To emphasize their relationship to the corresponding HEs, they were named Se3 and Se4 cDNAs. Their open reading frames predicted small secretory proteins with 55% (Se3) and 76% (Se4) conserved amino acids. Monospecific antipeptide antibodies to HE secretory proteins identified He3- and HE12-related proteins on Western blots of porcine epididymal fluid and semen. Both Northern and Western analyses indicated that the Se proteins were produced in a regionalized pattern and accumulated in the cauda fluid.

Amino Acid Sequence↗

Novel sperm-binding proteins of epididymal origin contain four fibronectin type II-modules.

Novel fibronectin type II (Fn2)-module proteins were cloned from human and canine epididymal cDNA libraries. cDNA sequences predicted a highly conserved protein family, related but not homologous to ungulate seminal plasma proteins (approximately 50% sequence identity), and the first known examples of proteins with four tandemly arranged Fn2-domains. By Northern blot and in situ hybridization analyses the encoding mRNAs were shown to be abundant products of the epididymal duct epithelium, but not detectable in other tissues. Homologous mRNAs were identified in the epididymides of various mammals, representing members of this novel protein family of epididymal origin. Within the Fn2-module-encoding stretches, species homologues displayed >85% sequence identity, but showed high variability at their predicted N-termini. An antipeptide antiserum in Western blot analyses detected 30-35 kDa immunoreactive protein bands in epididymal tissue, cauda epididymidal fluid, and sperm membrane protein preparations. The tandem arrangement of increasing numbers of Fn2-modules might functionally correspond to the tendency to form oligomers that has been described for lipid-binding proteins.

Amino Acid Sequence↗

Epididymal epithelium immortalized by simian virus 40 large T antigen: a model to study epididymal gene expression.

Primary cultures of the differentiated, adult epididymal duct epithelium were immortalized by retroviral transduction with the simian virus (SV)40 large T antigen. The canine epididymis was chosen here as a model with high human relevance, representing a convenient and acceptable source of differentiated epididymal tissue and, compared to other animal models, expressing a relatively large number of gene products which are also expressed by the human epididymis. To determine whether the immortalized canine epididymal (IMCE) cells retained a phenotype comparable to the original tissue, epithelial cytokeratins, various epididymal transcription factors as well as mRNAs encoding abundant epididymal secretory proteins, were studied as molecular markers. All IMCE populations obtained after transduction were of epithelial origin. The nuclear androgen receptor (AR) and the polyoma enhancer activator (PEA3), as well as the epididymal mRNA encoding the canine counterparts of human HE1, HE4 and HE5/CD52 epididymal mRNA, were retained in all populations tested. The majority of tested clones were oestrogen receptor ERalpha-positive, but ERbeta-negative, while one ERalpha-negative cell population was positive for ERbeta. The IMCE populations described thus represent useful permanent tools for studying gene expression of the epididymal duct epithelium, and for other types of experiments, examples including drug effects and toxicity on the epididymis.

Animals↗

Changes of the major sperm maturation-associated epididymal protein HE5 (CD52) on human ejaculated spermatozoa during incubation.

HE5 (CD52) is a glycoprotein which is secreted by the epididymis and which becomes inserted onto maturing spermatozoa. We have previously shown that, in cynomolgus monkey spermatozoa, changes occur upon maturation rendering cryptic the epitope to the monoclonal antibody CAMPATH-1G; the recognition site is then re-exposed during incubation under capacitation conditions. The present study investigated human ejaculated spermatozoa during incubation under similar conditions, using monoclonal antibodies that recognize different epitopes of the HE5 molecule comprising parts of the N-glycan (2E5) or peptide segments, including (CAMPATH-1G) or excluding (097) the glycosylphosphatidylinositol (GPI) anchor, to reveal modifications of sperm surface HE5. Flow cytometric analysis showed equally high percentages (approximately 90%) of viable spermatozoa cross-reacting with the antibodies before and after 6 h incubation. However, during incubation, the staining intensity increased 57% with CAMPATH-1G, 31% with 097, but remained unchanged with 2E5. The lymphocyte CD52 antibody CF1D12 stained only approximately 10% of spermatozoa either before or after incubation. Western blotting of sperm protein extracts using lectins indicated an increase in the exposure of sialic acid residues of HE5 after incubation. These results suggest that during incubation in capacitating conditions, there is an opening up of the HE5 glycoprotein molecule, increasing accessibility of some sialic acid residues and of the core peptide, particularly the GPI anchor.

Antibodies, Monoclonal↗

New insights into the origin, structure and role of CD52: a major component of the mammalian sperm glycocalyx.

The sperm glycocalyx represents the primary interface between the male gamete and its environment, and gamete interaction inevitably involves interaction with this structure. Thus, it has potential significance as a target for antibodies that inhibit sperm function. Still, little is known about the components and biological role of the sperm glycocalyx. Despite the apparent complexity of the sperm membrane, surface carbohydrate labelling experiments show a high selectivity suggesting that carbohydrate side chains of CD52, an unusually short, bipolar glycopeptide of epididymal origin, form major components of the sperm glycocalyx in all mammalian species investigated. Acquisition of the highly sialylated, lipid-anchored CD52 antigen is one of the few well-defined modifications that occur to the sperm membrane during epididymal passage. It would explain changes in lectin-binding patterns and also the remarkable surface charge differences occurring during epididymal transit, most probably attributable to its terminal sialic acid residues. CD52 seems to be immunodominant on human spermatozoa, and antibodies directed against it can agglutinate and completely immobilize human sperm in the presence of complement. Expression of the same peptide backbone in lymphocytes had largely discounted its consideration as a candidate for contraceptive development. However, the recent proof of male-specific modifications indicates the feasibility of this approach.

Animals↗

Synthesis and glycosylation of CD52, the major 'maturation-associated' antigen of rat spermatozoa, in the cauda epididymidis.

A western and lectin blot analysis was performed of the major 'maturation-associated' antigen of rat spermatozoa, which is the rat counterpart of human CD52. In the absence of a suitable antibody, direct study of this approximately 26 kDa antigen, named previously SMemG, had been difficult. In the present study, these problems were overcome by raising a polyclonal antibody against a chemosynthetic peptide predicted from the cDNA sequence of the antigen. The antibody bound to a glycoprotein of rat cauda epididymidal tissue and spermatozoa, this glycoprotein was cleaved by phosphatidylinositol-specific phospholipase C and, after deglycosylation, was reduced to approximately 6 kDa. Northern blot analysis confirmed that the CD52 mRNA was transcribed only post-testicularly, and antibody binding to testicular and sperm proteins of different molecular masses was shown to be nonspecific. Flow cytometry also indicated that the antigen was inserted into the sperm membrane during epididymal transit. Moreover, despite the presence of CD52 mRNA in all parts of the rat epididymis, only the 'long' mRNA molecules of the cauda region were efficiently translated and the antigen glycosylated, indicating that expression of rat CD52 is regulated on a post-transcriptional level. Lectin binding and deglycosylation studies supported the contention that there is extensive mucin-type O-glycosylation of rat CD52. In rats, there was no indication of complex N-linked carbohydrates similar to those described for human CD52.

Animals↗

CD52 mRNA is modulated by androgens and temperature in epididymal cell cultures.

Cultured rat epididymal tissue explants formed >90% pure, adherent growing epithelial cell monolayers. Despite their flattened and apparently androgen receptor-negative phenotype, these cells for a short period kept characteristics of the epididymal duct epithelium, i.e., expression of the tissue-specific marker CD52 and responsiveness of its mRNA toward temperature elevation and androgen withdrawal. When cells were grown on permeable supports at 33 degrees C, androgen supplementation or withdrawal specifically modulated the levels as well as the length of the CD52 mRNA. Elevation of the culture temperature to a quasi abdominal milieu of 37 degrees C selectively reduced the CD52 mRNA levels under all culture conditions. This reduction was not affected by the presence of androgens and was not accompanied by changes in length, suggesting that the modulation of CD52 mRNA in epididymal cells by androgens and by temperature is synergic, but may involve different molecular mechanisms. CD52 mRNA levels, however, were not stable in the primary cultures but decreased rapidly to undetectable levels after 4-5 days at all culture conditions. GAPDH mRNA levels, on the other hand, were stable throughout the culture period.

Androgens↗