Biomedical subjects

C Kuhn

Publications and source records attributed to C Kuhn.

At least 19 recordsLinked to original sources

PubMed2007

Steroid receptors ERalpha, ERbeta, PR-A and PR-B are differentially expressed in normal and atrophic human endometrium.

OBJECTIVE: The endometrium expresses estrogen (ER) and progesterone receptor (PR), which are related to autocrine and paracrine processes that respond to estrogen and progesterone. Therefore, the aim of this study was to evaluate the distribution pattern of ERalpha, ERbeta, PR-A and PR-B with monoclonal antibodies in normal human endometrial tissue. STUDY DESIGN: Human endometrial tissue was obtained from 84 premenopausal and 11 postmenopausal patients and immunohistochemically analysed with monoclonal antibodies against ERalpha, ERbeta, PR-A and PR-B. RESULTS: ERalpha, PR-A and PR-B declined significantly (p<0.001, p<0.05, p<0.05 respectively) in glandular epithelium from proliferative to late secretory phase. The ERbeta immunohistochemical reaction showed a similar significant declining pattern (p<0.05), although the staining intensity was lower than that of ERalpha. While ERalpha, ERbeta and PR-B decrease significantly in atrophic endometrial tissue compared to proliferative endometrium, a significant up-regulation of PR-A was observed compared to late secretory phase (p<0.05). CONCLUSION: ERalpha, ERbeta, PR-A and PR-B were expressed in normal human endometrium with a cyclical variation during the menstrual cycle. In normal postmenopausal endometrial tissue, a down-regulation of ERalpha, ERbeta and PR-B occurs with a subsequent higher expression of PR-A. These results show the presence of steroid receptors in human epithelium, indicating that these cells respond to estrogen and progesterone, thus playing a significant role in endometrial physiology.

Atrophy↗

PubMed2006

Expression of inhibin/activin subunits alpha (-alpha), beta A (-beta (A)) and beta B (-beta (B)) in placental tissue of normal and intrauterine growth restricted (IUGR) pregnancies.

During human pregnancy the placenta produces a variety of proteins like steroid hormones and their receptors that are responsible for the establishment and ongoing of the feto-placental unit. Inhibins are dimeric glycoproteins, composed of an alpha-subunit and one of two possible beta-subunits (beta (A) or beta (B)). Aims of the present study were the determination of the frequency and tissue distribution patterns of the inhibin/activin subunits in human placental tissue of normal pregnancies and pregnancies complicated with fetal growth restriction (IUGR). Slides of paraffin embedded placental tissue were obtained after delivery from patients diagnosed with IUGR (n = 6) and normal term placentas (n = 8). Tissue samples were fixed and incubated with monoclonal antibodies inhibin/activin-subunits -alpha, -beta (A), -beta (B). Intensity of immunohistochemical reaction on the slides was analysed using a semi-quantitative score and statistical analysis was performed (P<0.05). A significant lower expression of the inhibin-alpha subunit in IUGR extravillous trophoblast compared to normal pregnancies was observed, while the inhibin-alpha immunostaining was significantly upregulated in syncytiotrophoblast. Additionally, a significant down-regulation of inhibin-beta (B) subunit in extravillous trophoblast cells in IUGR syncytiotrophoblast cells was demonstrated. A co-localisation of inhibin-alpha and the beta-subunits was also observed, suggesting a production and secretion of intact inhibin A and inhibin B. Although the precise role of these inhibin/activin subunits in human placenta and IUGR pregnancies is still unclear, they could be involved in autocrine/paracrine signalling, contributing to several aspects like angiogenesis and tissue remodelling.

Activins↗

PubMed2006

[Fracture of the proximal humerus in children and adolescents. The most overtreated fracture].

BACKGROUND: There is great uncertainty among trauma surgeons regarding the correct treatment of rare proximal humerus fractures in children and adolescents, in spite of the great potential of the proximal humeral epiphysis for self-correction, even in cases of gross malalignment. METHODS: Over a span of 6 years, we treated 52 children and adolescents with closed proximal humerus fractures, 45 of whom had no other injuries. In only three cases did we see an indication for operative treatment at our institution. Operations on another three were performed elsewhere. Forty two patients were available for follow-up exams. RESULTS: They all had good or very good results with regard to fracture healing (constant score) independently of age, sex, fracture morphology, and treatment. CONCLUSIONS: We believe it is particularly important to discuss therapy concepts with parents and the involved outpatient physicians in order to avoid unnecessary and stressful operations.

Adolescent↗

PubMed2006

Development and characterization of monoclonal antibodies for the immunohistochemical detection of glycodelin A in decidual, endometrial and gynaecological tumour tissues.

AIMS: Glycodelin is a glycoprotein with a molecular weight of 28 kDa. Unusual LacdiNAc structures have been identified on glycodelin A, isolated from amniotic fluid. Three major functions of this glycoprotein have been identified. Glycodelin is an immunosuppressive molecule, a marker of morphological differentiation, and a contraceptive. Because no monoclonal antibodies for glycodelin A are commercially available, our aim was to develop and characterize three monoclonal antibodies against this glycoprotein. METHODS AND RESULTS: Glycodelin A was purified from amniotic fluid by three chromatographic steps and its purity was checked by SDS-PAGE. Antibodies were generated from immunized BALB/c mice. Three IgG1 monoclonal antibodies detecting glycodelin A were cloned. All three antibodies recognized carbohydrate structures of glycodelin A and did not cross-react with glycodelin S. They are applicable to immunohistochemistry (frozen and paraffin sections), ELISA and Western blots. CONCLUSION: The new antibodies can be used for the detection of glycodelin A in frozen and paraffin-embedded decidual and endometrial tissue. One antibody (A87-B/D2) can be used for the detection of glycodelin in endometrial and ovarian tumour tissues. Because glycodelin A is a major secretory endometrial product during the luteal phase, in early pregnancy and in gynaecological tumours, the new antibodies are, potentially, valuable tools for the study of endometrial development and tumour progression.

Amniotic Fluid↗

PubMed2006

Expression of inhibin/activin subunits alpha (-alpha), betaA (-betaA), and betaB (-betaB) in placental tissue of normal, preeclamptic, and HELLP pregnancies.

During human pregnancy the placenta produces a variety of proteins for the establishment of the fetoplacental unit, including inhibins and activins. Inhibins are dimeric glycoproteins, composed of an alpha-subunit and one of two possible beta-subunits (betaA or betaB). Aims of the present study were (a) the determination of the frequency and tissue distribution patterns of the inhibin/activin subunits in human placental tissue of normal pregnancies and pregnancies complicated with preeclampsia and HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) and (b) the assessment of a combined expression of inhibin-alpha- and both beta-subunits (betaA-and betaB-subunits) using double immunofluorescence technique. A significant lower expression of the inhibin-alpha subunit in preeclamptic and HELLP placental tissue compared to normal pregnancies was observed, while the inhibin-alpha immunostaining was significantly upregulated in syncytotrophoblast. Additionally, we demonstrated a significant down-regulation of inhibin-betaB subunit in extravillous trophoblast cells between normal and preeclamptic compared to HELLP placental tissue, while inhibin-betaA-subunit was significantly higher in preeclamptic syncytotrophoblast cells. A colocalization of inhibin-alpha and the beta-subunits could be demonstrated, suggesting a production and secretion of intact inhibin A and inhibin B. Therefore, inhibin A and activin A might be useful markers in preeclampsia. Valuable parameters in HELLP syndrome could be inhibin A, rather than inhibin B, and activin B. Furthermore, the lower betaB-subunit production in extravillous trophoblast cells demonstrates that this subunit might have an important role in the pathogenesis of HELLP syndrome. Additionally, the higher production of the betaA-subunit in syncytotrophoblast cells suggest a higher production of activin A rather than inhibin A in preeclampsia that might be utilized as a marker of placental function.

Adult↗

PubMed2005

Expression of glycodelin A in decidual tissue of preeclamptic, HELLP and intrauterine growth-restricted pregnancies.

During pregnancy, the placenta produces a variety of proteins that are responsible for the establishment of the foeto-maternal tolerance and circulation. The aim of this study was to investigate the expression of glycodelin A (formerly named PP14) in decidual tissue of placentas with intrauterine growth restriction (IUGR), preeclamptic patients, hemolysis, elevated liver, low-platelet (HELLP) patients and normal decidual tissue. Slides of paraffin-embedded decidual tissue of patients with IUGR, preeclamptic patients, HELLP patients and normal-term placentas were incubated with either polyclonal or monoclonal antibodies against glycodelin A. Staining reaction was performed with the ABC reagent. Intensity of immunohistochemical reaction on the slides was analysed using a semi-quantitative score. In addition, expression of glycodelin mRNA was analysed by in situ hybridisation. Expression of glycodelin A was significantly reduced in decidual cells of placentas with IUGR and HELLP, as investigated with both monoclonal and polyclonal antibodies and in situ hybridisation. However, preeclamptic decidual tissue showed no significantly different expression of intensity of glycodelin mRNA compared with normal placental tissue controls. A reduced expression of glycodelin A by decidual cells seems to be related to IUGR and HELLP. Therefore, glycodelin A might play an important role in the pathogeneses of these diseases.

Adult↗

PubMed2005

[Abscettic pneumonia in a renal transplantation female patient].

A 39-year old female patient who was kidney transplanted three years ago was admitted to hospital with fever of unknown origin for several days. Blood samples revealed decreased renal function and increased inflammation parameters. Chest X-ray and CT scan showed multiple cavernous structures, some with liquid. Staphylococcus aureus was detected in blood culture samples. With the aid of these results Staphylococcus pneumonia with multiple abscesses was diagnosed. The treatment consisted of removal of the infectious focus and a systemic antibiotic therapy corresponding to the microbiologic results. We describe a case of Staphylococcus pneumonia caused by a infected vascular prosthesis under consideration of immunosuppression in a renal transplanted patient.

Adult↗

PubMed2004

Massage therapy effects on depressed pregnant women.

Eighty-four depressed pregnant women were recruited during the second trimester of pregnancy and randomly assigned to a massage therapy group, a progressive muscle relaxation group or a control group that received standard prenatal care alone. These groups were compared to each other and to a non-depressed group at the end of pregnancy. The massage therapy group participants received two 20 min therapy sessions by their significant others each week for 16 weeks of pregnancy, starting during the second trimester. The relaxation group provided themselves with progressive muscle relaxation sessions on the same time schedule. Immediately after the massage therapy sessions on the first and last days of the 16-week period the women reported lower levels of anxiety and depressed mood and less leg and back pain. By the end of the study the massage group had higher dopamine and serotonin levels and lower levels of cortisol and norepinephrine. These changes may have contributed to the reduced fetal activity and the better neonatal outcome for the massage group (i.e. lesser incidence of prematurity and low birthweight), as well as their better performance on the Brazelton Neonatal Behavior Assessment. The data suggest that depressed pregnant women and their offspring can benefit from massage therapy.

Adult↗

PubMed2004

Atraumatic intracutaneous skin closure with self-made fishing line suture compared to commercial thread.

OBJECTIVE: The aim of this study was to prove, whether the intracutaneous skin closure with self made fishing line suture is equivalent to commercial sutures. DESIGN: It was a randomised blinded animal study. SETTING: The study was performed in December 2002 at the Muhimbili University College of Health Sciences in Dar-es-salaam. SUBJECTS: Both German surgeons from Mannheim, and Tanzanian surgeons from Dar es salaam operated on nine one year old Tanzanian domestic sheep. INTERVENTIONS: 108 standardised cutaneous wounds on the backs of the animals were closed by intracutaneous sutures either with self produced fishing line suture or a commercial nylon suture (Ethilon). MAIN OUTCOME MEASURES: The clinical and histological outcomes, as well as the costs of this self-made fishing line suture, with a commercial nylon thread were evaluated and compared. RESULTS: There are no significant differences between the two sutures in histological or clinical findings, or in the reported ease of use by the surgeons. The cost of a self-produced atraumatic thread is US$ 0.12, less than one-twentieth of the cost of the commercial thread. CONCLUSION: Self-made fishing nylon suture has characteristics and properties in sheep skin wounds comparable to commercial nylon suture. The advantage of the commercial thread is the guaranteed quality assurance. It is discussed whether this quality assurance justifies the large price difference, and whether the self-produced thread should be recommended to surgeons in countries where the costs of surgical material often remains an obstacle for life saving operations.

Animals↗

PubMed2003

[Treatment of emergencies in the hospital--problems and management].

Due to the growing number of high-risk patients, the increasing proportion of geriatric patients and the expansion of surgical and invasive-diagnostic procedures, medical stuff in hospitals are confronted with a rising number of emergency situations. Nearly 50% are of cardio-circulatory origin and occur during surgical interventions or immediately afterwards. Another cause of life-threatening complications are side-effects of orally or intravenously administered agents, especially after treatment with antibiotics, anaesthetics, analgetics and sedatives. Due to a lack of emergency training and management in most hospitals, the survival rate after cardiopulmonary resuscitation in general wards lies between just two and 35%. Thus it seems necessary to perform special training in CPR procedures and emergency management at regular intervals for the entire medical stuff. In addition, a special infrastructure for giving sufficient treatment in emergencies has to be established (emergency team, emergency telephone number, intra-hospital emergency car). The second part of this review presents current diagnostic and therapeutic strategies for the most common emergency situations, e.g. anaphylaxis, myocardial infarction, pulmonary embolism, gastrointestinal bleeding, and heparin-induced thrombocytopenia (HIT).

Cardiopulmonary Resuscitation↗

PubMed2002

Early reduction of BCR-ABL mRNA transcript levels predicts cytogenetic response in chronic phase CML patients treated with imatinib after failure of interferon alpha.

The degree of tumor load reduction as measured by cytogenetic response is an important prognostic factor for chronic myelogenous leukemia (CML) patients on therapy. We sought to determine whether BCR-ABL transcript levels can predict chromosomal response. Residual disease was evaluated in 120 CML patients in chronic phase (CP) treated with the selective tyrosine kinase inhibitor imatinib after resistance or intolerance to interferon alpha (IFN). Median time of therapy was 401 days (range 111-704). BCR-ABL and total ABL transcripts were measured in 486 peripheral blood (PB) specimens with a real time RT-PCR approach using fluorescent-labeled hybridization probes (LightCycler technology) and results were expressed as the ratio BCR-ABL/ABL. Cytogenetic response was determined in 3-monthly intervals: From 101 evaluable patients, 42 achieved a complete (CR, 0% Philadelphia chromosome (Ph)- positive metaphases), 18 a partial (PR, 1-34% Ph+), 13 a minor (MR, 35-94% Ph+), and 26 no response (NR, >94% Ph+). All PB samples were RT-PCR positive. The proportion of Ph+ metaphases and simultaneous BCR-ABL/ABL ratios correlated with r = 0.74, P < 0.0001. In order to investigate whether early molecular analysis may predict cytogenetic response, quantitative RT-PCR data obtained after 1 and 2 months of therapy were compared with cytogenetic response at 6 months. BCR-ABL/ABL ratios after 1 month were not predictive, but results after 2 months correlated with the consecutive cytogenetic response (P = 0.0008). The probability for a major cytogenetic response was significantly higher in patients with a BCR-ABL/ABL ratio <20% after 2 months of imatinib therapy. We conclude that: (1) quantitative determination of residual disease with real time RT-PCR is a reliable and sensitive method to monitor CML patients on imatinib therapy; (2) BCR-ABL/ABL ratios correlate well with cytogenetic response; (3) in IFN-pretreated patients all complete responders to imatinib have evidence of residual disease with the limited follow-up available; and (4) cytogenetic response at 6 months of therapy in CP patients is predictable with real time RT-PCR at 2 months.

Adult↗

PubMed2002

Childhood epidermolysis bullosa acquisita: a novel variant with reactivity to all three structural domains of type VII collagen.

Most patients with epidermolysis bullosa acquisita develop an autoimmune response to the non-collagenous (NC) 1 domain of type VII collagen. We report a 4-year-old girl of white European descent presenting with widespread blistering disease involving the face, hands, genital area and oral mucosa. Histopathology revealed subepidermal blisters, and linear deposits of IgG and C3 were seen along the dermal-epidermal junction on direct immunofluorescence (IF) microscopy of a perilesional skin biopsy. On indirect IF microscopy, circulating autoantibodies exclusively stained the dermal side of 1 mol L-1 NaCl-split skin. The patient's IgG autoantibodies labelled a 290-kDa protein on Western blotting of dermal extracts, and reacted with the NC1, NC2 and triple helical domains of type VII collagen on immunoblotting of recombinant and cell-derived fragments obtained by pepsin and collagenase digestion of the full-length protein. Oral methylprednisolone and dapsone led to clearance of lesions, which healed with mild scarring and milia formation. Treatment was discontinued after 1 year and the patient has now been in remission for more than 3 years.

Autoantibodies↗

PubMed2001

Computer-modeling origin of a simple genetic apparatus.

This computer simulation is based on a model of the origin of life proposed by H. Kuhn and J. Waser, where the evolution of short molecular strands is assumed to take place in a distinct spatiotemporal structured environment. In their model, the prebiotic situation is strongly simplified to grasp essential features of the evolution of the genetic apparatus without attempts to trace the historic path. With the tool of computer implementation confining to principle aspects and focused on critical features of the model, a deeper understanding of the model's premises is achieved. Each generation consists of three steps: (i) construction of devices (entities exposed to selection) presently available; (ii) selection; and (iii) multiplication of the isolated strands (R oligomers) by complementary copying with occasional variation by copying mismatch. In the beginning, the devices are single strands with random sequences; later, increasingly complex aggregates of strands form devices such as a hairpin-assembler device which develop in favorable cases. A monomers interlink by binding to the hairpin-assembler device, and a translation machinery, called the hairpin-assembler-enzyme device, emerges, which translates the sequence of R(1) and R(2) monomers in the assembler strand to the sequence of A(1) and A(2) monomers in the A oligomer, working as an enzyme.

Computer Simulation↗

PubMed2001

Drebrin particles: components in the ensemble of proteins regulating actin dynamics of lamellipodia and filopodia.

Drebrin, an actin-binding 70-kDa protein with an unusually slow SDS-PAGE mobility corresponding to approximately 120 kDa, containing a proline-rich, profilin-binding motif, had originally been reported from neuronal cells, but recently has also been found in diverse other kinds of tissues and cell lines. In biochemical analyses of various cells and tissues, employing gel filtration, sucrose gradient centrifugation, immunoprecipitation and -blotting, we have identified distinct states of soluble drebrin: a approximately 4S monomer, an 8S, ca. 217-kDa putative trimer, a 13S and a > 20S oligomer. In the 8S particles only [35S]methionine-labelled drebrin but no other actin-binding protein has been detected in stoichiometric amounts. By immunofluorescence and immunoelectron microscopy, drebrin-positive material often appeared as "granules" up to 400 nm in diameter, in some cell types clustered near the Golgi apparatus or in lamellipodia, particularly at leading edges, or in dense-packed submembranous masses at tips (acropodia) or ruffles of leading edges, in filopodia and at plaques of adhering junctions. We conclude that these drebrin complexes and drebrin-rich structures allow the build-up and maintenance of high local drebrin concentrations in strategic positions for the regulation of actin filament assembly, thereby contributing to cell motility and morphology, in particular local changes of plasticity and the formation of protrusions.

Actins↗

PubMed2001

Anorexia nervosa symptoms are reduced by massage therapy.

Nineteen women (M age = 26) diagnosed with anorexia nervosa were given standard treatment alone or standard treatment plus massage therapy twice per week for five weeks. The massage group reported lower stress and anxiety levels and had lower cortisol (stress) hormone levels following massage. Over the five-week treatment period, they also reported decreases in body dissatisfaction on the Eating Disorder Inventory and showed increased dopamine and norepinephrine levels. These findings support a previous study on the benefits of massage therapy for eating disorders.

Journal Article↗

PubMed2001

alpha-Actin: disposition, quantities, and estimated effects on lung recoil and compliance.

We have investigated the basis and implications of pneumoconstriction by measuring disposition and quantities of alpha-smooth muscle actin in rat and guinea pig lungs and modeling its effects on lung recoil and compliance. A robust marker of contractility, alpha-smooth muscle actin appears in smooth muscle or myofibroblast-like cells in pleura, airways, blood vessels, and alveolar ductal tissues. In each site, we measured its transected area by immunofluorescent staining and frequency-modulated scanning confocal microscopy. We incorporated these data in a model of the parenchyma consisting of an extensive elastic network with embedded contractile structures. We conclude that contraction at any one of these sites alone can decrease parenchymal compliance by 20-30% during tidal breathing. This is due mostly to the stiffness of activated contractile elements undergoing passive cycling; constant muscle tension would have little effect. The magnitude of the effect corresponds with known responses of the lung to hypocapnia, consistent with a homeostatic function in which gas exchange is defended by redistributing ventilation away from overventilated units.

Actins↗

PubMed2001

AraC-based pharmacotherapy of chronic myeloid leukaemia.

In interferon-alpha (IFN) treated chronic phase chronic myeloid leukaemia (CML) patients, survival depends on individual risk profile and achievement of a complete haematological response (CHR) and a major cytogenetic response (MCR) (< 35% Philadelphia-chromosome-positive metaphases). The highest cytogenetic response rates have been achieved with the combination of IFN and low-dose sc. AraC (10 mg daily to 10-20 mg/m2 for 10-14 days/month). Whether the higher cytogenetic response rates are also associated with a significant improvement of survival still remains controversial. The different results obtained from large randomised and observational trials may be due to the numbers of patients enrolled, distribution of risk profiles and the treatment schedule, which is influenced greatly by the haematological and gastrointestinal toxicity of AraC. An oral formulation (YNK01), which is lipophilic and resistant to deamination, is currently under investigation. Clinically, it has similar activity, but toxicity leads to discontinuation of treatment in a considerable proportion of patients. The clinical benefits may therefore be outweighed by the dose-limiting toxicity for both application forms. Combinations with other drugs, e.g., STI571 or homoharringtonine, have shown promising early results in vitro and in vivo.

Aged↗

PubMed2000

E1A12S-mediated activation of the adenovirus type 12 E2 promoter depends on the histone acetyltransferase activity of p300/CBP.

Activation of the transcription unit early region 2 (E2) promoter of the oncogenic adenovirus serotype 12 (Ad12), which regulates the expression of proteins essential for viral replication, requires the assembly of a ternary complex consisting of cAMP response element-binding protein (CREB)-1/activating transcription factor (ATF)-1, the Ad12 12S oncogene product of early region 1A (E1A(12S)), and the co-activator p300/CBP on the E2(Ad12) cAMP response element (E2-CRE). Here we show that the active E2(Ad12) promoter is associated with acetylated histone H4 whereas an E2-CRE point-mutated promoter which is transcriptionally inactive due to its inability to assemble this ternary complex is not bound by acetylated histone H4. The histone deacetylase 1 as well as Roscovitine, which blocks the activation of the histone acetyltransferase (HAT) activity of CBP by cyclin E-Cdk2, prevents E2(Ad12) promoter activation through E1A(12S). p300/CBP counteracts the repressive function of histone deacetylase 1 in a HAT domain-dependent manner whereas the p300/CBP-associated factor PCAF failed to rescue E2(Ad12) promoter activity. E1A(12S) bound p300/CBP displays strong HAT activity. Most interestingly, E1A(12S)-mediated activation of the E2(Ad12) promoter correlates well with the ability of the viral protein to associate with the HAT activity of p300/CBP in vivo. Taken together these data indicate that the recruitment of the HAT activity of p300/CBP by E1A(12S) plays an important role in E2(Ad12) promoter activation.

Acetyltransferases↗