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Biomedical subjects

R Tauber

Publications and source records attributed to R Tauber.

At least 19 recordsLinked to original sources

[Diclofenac during prostate needle biopsy. Significant pain reduction].

BACKGROUND: The aim of this study was to evaluate the efficacy of diclofenac to reduce pain during prostate biopsy. METHODS: After prospective randomization all patients received an intrarectal lidocaine gel instillation. Group 1 (n=80) functioned as control group, group 2 (n=72) received a placebo, and group 3 (n=76) a 50 mg diclofenac suppository in addition. Patients were asked to identify their pain score (VAS 10) after the biopsy. Two weeks later, the patients were called and asked about the post-biopsy course. RESULTS: Patients in the diclofenac group had significantly lower pain scores than control or placebo group patients. Another biopsy without additional anesthesia was refused by 25% of the control group and 34% of the placebo group, but only by 11% of the diclofenac group (p<0.05). CONCLUSIONS: The preinterventional administration of diclofenac suppositories is a simple but efficient procedure for pain reduction in patients who undergo prostate biopsy.

Analgesics↗

A Doppler-based study on the prevalence of varicocele in German children and adolescents.

The prevalence of varicocele was estimated among pupils of forms 4 and 8 in the city of Hamburg and the severity of the associated venous reflux was analysed. In the school year of 1998/99, a genital examination was performed on 2756 children (median age 10.2 years) and 2008 adolescents (14.6 years). The varicocele degree was determined according to the WHO. Venous reflux was proven by CW-Doppler sonography, distinguishing between Valsalva-induced reflux (VR) and continuous reflux (CR). As a result, varicoceles were detected in 18.0% of the children (1.2% bilaterally) and 42.7% of the adolescents (7.2%). High-graded forms (palpable/visible) occurred with increasing rate (from 7% to 22.9%) on the left side. Subtle forms (subclinical/during Valsalva) counted for >90% of all right-sided findings, whilst an age-related shift towards higher degrees was noted left-sided. VR occurred bilaterally, CR was almost only established left-sided. VR was mainly associated with subtle varicoceles, CR was predominantly found in the high-graded forms. These results suggest that even in children varicoceles are not a rare phenomenon. However, adolescence is the main period of manifestation. A major venous malfunction is already evident in maturing boys, which seems to be associated with the formation of high-graded varicoceles.

Adolescent↗

[Bilateral testicular gunshot injuries].

Gunshot injuries to the testicles are rare and usually result in testicular atrophy. In the case of severe bilateral testicular injuries, this could cause not only infertility but also the need for lifetime testosterone-substitution. We report an 18-year-old patient with bilateral testicular gunshot injury. During the surgical exploration an orchiectomy of the complete ruptured left testicle was necessary. Debridement of the damaged tissue and a partial orchiectomy was performed on the right side. After the operation, the patient developed an incretory hypogonadism and oligozoospermia. During follow-up, an improvement in the sperm count and of the hormonal status occurred. These finally reached normal levels. After genital traumata, immediate surgical exploration should be performed. Based on the above results, the patient benefits from conservative debridement and primary repair of the injured testicle, if possible. An improvement in hormonal status and sperm parameters after testicular injury and consecutive testicular malfunction can occur. Regeneration of the testicular tissue seems possible.

Adolescent↗

[Transurethral resection of bladder tumours in sodium chloride solution].

BACKGROUND: Electrical transurethral resection is a well established and developed procedure. It is performed using high frequency current in a nonconductive irrigation medium. Due to these features this procedure is compromised by two possible complications: (1) spontaneous contractions of adductors caused by electrical stimulation of the obturator nerve may lead to bladder perforation, and (2) excessive flushing of the irrigation medium into the circulation can cause TUR syndrome. We present our initial experiences with a new system for transurethral resection which has overcome these potential sources of complications. The system, developed by Olympus, works with a modified guided high frequency current in 0.9% saline as irrigant. It is called TURIS (transurethral resection in saline). METHODS: A total of 35 resections of bladder tumors were performed using the TURIS technique. The operations were carried out under intravenous anaesthesia without relaxation or nerve block. During resection high frequency current passes through and active electrode (resection loop) to the sheath electrode. About 90% of the current flows through the saline to the sheath of the resectoscope, only a small amount circulates through the body of the patient. The experiences of the surgeons were documented. The resected specimens were histologically examined for artificial thermal changes and compared with a control group of conventionally resected patients. RESULTS: The handling of the TURIS resectoscope is very similar to that of well known instruments. Therefore, no special training was required for the surgeon or the theatre nurse. The control of the cutting was very efficient. Coagulation of bleeding was very good. The lack of carbonisation at the resection ground led to an excellent assessment of the resected areas. The resected tissue did not stick to the resection loop. Contraction due to nerve stimulation was not observed. No complications occurred. Histology showed no significant differences in the quantity or quality of thermal artifacts due to current. CONCLUSIONS: TURIS can be performed safety without a learning curve. Especially in TUR-B, it seems to be advantageous due to the excellent control of the extent of cutting and the lack of nerve stimulation. Quantity and quality of thermal changes in histology are not different from a conventionally resected control group.

Aged↗

[Antegrade sclerotherapy for varicocele testis--possible and avoidable complications].

Antegrade sclerotherapy is an established procedure for the treatment of varicocele. To avoid complications during the dissection of the pampiniform plexus, detailed knowledge of the angioarchitecture of the spermatic cord is recommended. One group of plexus veins is situated ventrolaterally and is surrounded by a yellowish fat which serves as a landmark. This vein group should be chosen for preparation. Phlebography of the internal testicular vein is mandatory. If arteries or major pelvic veins become visible while applying contrast media, sclerotherapy should not be performed. Paravasation of sclerosing agent has to be recognized and treated immediately to prevent deleterious effects.

Catheterization↗

[Long term outcome after percutaneous sclerotherapy of renal cysts with polidocanol].

Methodology and long-term results of treatment of uncomplicated kidney cysts by percutaneous sclerotherapy with polidocanol are presented. Between 1991 and 1998, 132 patients with 151 kidney cysts were treated by percutaneous sclerotherapy with polidocanol as the sclerosing agent. The average volume of the cysts was 288 ml. Over a mean period of 25.8 months, 118 patients with 132 cysts were followed up. In 56% of the cysts treated the cystic cavity disappeared completely, and in 30% the remaining volume was less than 10% of the initial volume. The existing symptoms before intervention remained unchanged only in four (3.4%) patients. The morbidity of the method was 9% and surgical reintervention was not necessary. There was no mortality. The mean hospitalization was 1.06 days. Percutaneous sclerotherapy of uncomplicated kidney cysts with polidocanol offers a high rate of success without the costs and invasiveness associated with laparoscopic surgery and also without the need for repeated interventions associated with sclerotherapy performed with ethanol.

Adult↗

Identification of nucleolin as a new L-selectin ligand.

Apart from leucocyte-endothelial interactions, the adhesion molecule L-selectin mediates the homotypic adhesion of leucocytes during recruitment at sites of acute inflammation, as well as intercellular adhesion of haematopoietic progenitor cells during haematopoiesis. There is evidence that, in addition to P-selectin glycoprotein ligand-1, other as-yet-unidentified proteins function as L-selectin ligands on human leucocytes and haematopoietic progenitor cells. In the present study, we show: (i) by affinity chromatography on L-selectin-agarose; (ii) by protein identification using MS; and (iii) by covalent cell-surface labelling with sulphosuccinimidyl-2-(biotinamido)ethyl-1,3-dithiopropionate that the multifunctional nuclear protein nucleolin is partly exposed on the cell surface, and is a ligand of L-selectin in human leucocytes and haematopoietic progenitor cells.

Amino Acid Sequence↗

The adhesive properties of recombinant soluble L-selectin are modulated by its glycosylation.

The leukocyte adhesion molecule L-selectin, which mediates the initial steps of leukocyte attachment to vascular endothelium, is intensely glycosylated. Different glycoforms of L-selectin are expressed on different leukocyte subsets and differences in L-selectin glycosylation appear to be correlated with the leukocyte's ability to attach to different endothelial targets. In the present study we addressed the question whether glycosylation of L-selectin influences L-selectin-ligand interactions. To obtain different glycoforms of L-selectin, recombinant proteins were expressed both in the baby hamster kidney (BHK) cell line and in the human myelogenous cell line K562, resulting in sL-sel[BHK] or sL-sel[K562], respectively. The glycosylation characteristics of the purified proteins were determined. The most striking differences in glycosylation were seen in the terminal sialylation. Each of the two proteins carried sialic acids in the alpha 2-3 position, while alpha 2-6-bound sialic acids were found exclusively on sL-sel[K562]. To investigate their adhesive properties, both recombinant sL-selectins were used in cell adhesion assays and interactions with the ligands present on various hematopoietic cell lines or activated human cardiac microvascular endothelial cells were examined. The binding capacity of sL-sel[K562] was about 1.6 fold higher compared to sL-sel[BHK] under static as well as under flow conditions. These findings indicate that the terminal sialylation pattern of L-selectin modulates its binding characteristics.

Adhesives↗

The fate of desmosomal proteins in apoptotic cells.

Activation of caspases results in the disruption of structural and signaling networks in apoptotic cells. Recent biochemical and cell biological studies have shown that components of the cadherin-catenin adhesion complex in epithelial adherens junctions are targeted by caspases during apoptosis. In epithelial cells, desmosomes represent a second type of anchoring junctions mediating strong cell-cell contacts. Using antibodies directed against a set of desmosomal proteins, we show that desmosomes are proteolytically targeted during apoptosis. Desmogleins and desmocollins, representing desmosome-specific members of the cadherin superfamily of cell adhesion molecules, are specifically cleaved after onset of apoptosis. Similar to E-cadherin, the desmoglein-3 cytoplasmic tail is cleaved by caspases. In addition the extracellular domains of desmoglein-3 and desmocollin-3 are released from the cell surface by a metalloproteinase activity. In the presence of caspase and/or metalloproteinase inhibitors, both cleavage reactions are almost completely inhibited. As reported previously, the desmosomal plaque protein plakoglobin is cleaved by caspase-3 during apoptosis. Our studies now show that plakophilin-1 and two other major plaque proteins, desmoplakin-1 and -2, are also cleaved by caspases. Immunofluorescence analysis confirmed that this cleavage results in the disruption of the desmosome structure and thus contributes to cell rounding and disintegration of the intermediate filament system.

Apoptosis↗

Development of a novel molecular adapter for the optimization of immunotoxins.

Immunotoxins consisting of catalytic domains of natural toxins and tumor-specific ligands were modified by introducing a molecular adapter that is able to transport the toxic domain more efficiently into cells. The adapter is a three-component structure: its core is a membrane transfer sequence (MTS) flanked by two different cleavable sequences. The directed and irreversible cellular uptake of the construct is driven by either enzymatic or chemical cleavage of the two flanking sequences. In our studies, the purified A-chain of diphtheria toxin (DT) was coupled to two different MTSs via disulfide bonds. A cytotoxicity assay revealed that the constructs containing the MTSs were more potent than DT A-chain alone and that the disulfide bond was cleaved.

Diphtheria Toxin↗

Structural and functional stability of the mature transferrin receptor from human placenta.

The transferrin receptor (TfR) is a N- and O-glycosylated transmembrane protein mediating the cellular iron uptake by binding and internalization of diferric transferrin. In this study, rate constants and dissociation constants of 125I-ferri-transferrin binding to the human TfR were examined dependent on receptor glycan composition, pH, bivalent cations, and temperature. To do so, purified human placental TfR was noncovalently immobilized to polystyrene surfaces and subjected to alterations in various parameters. We found that transferrin binding was clearly dependent on a receptor pretreatment with buffers of various pH in that most of the TfR molecules irreversibly lost transferrin binding activity below pH 6.5. However, the dissociation constant of the remaining active binding sites was not affected. Similarly, we were able to define the thermal stability of the receptor as a function of transferrin binding ability. Binding of transferrin was completely lost provided that the receptor was pretreated at temperatures of at least 65 degrees C. Treatment with EDTA also caused an irreversible loss of transferrin binding activity, indicating that the functionally active conformation of the mature TfR depends on bivalent cations. In order to examine the role of the receptor glycans, we enzymatically removed the sialic acid residues, the hybrid and oligomannosidic N-glycans, or all types of N-glycans. In contrast to the parameters described above, all desialylated and N-deglycosylated TfR variants had exactly the same transferrin binding properties as the native TfR. To assess changes in the secondary structure of the receptor, circular dichroic spectra were recorded from TfR at pH 5.0, from heat pretreated receptor and from deglycosylated TfR. Since the receptor did not exhibit detectable changes in the CD spectrum of the deglycosylated receptor, it can be concluded that the N-linked carbohydrates of the mature, fully processed TfR are not essential for transferrin binding and conformational stability.

Binding Sites↗

LI-cadherin gene expression during mouse intestinal development.

LI-cadherin (Liver-Intestine cadherin) is a member of a subclass (7-D cadherins) within the cadherin superfamily. Although its cellular function as a cell-cell adhesion molecule has been demonstrated in cell culture studies, its physiological function still needs to be explored in the intact organism. After isolating the cDNA for mouse LI-cadherin, we generated specific antibodies against the overexpressed protein and studied its expression pattern in adult mouse tissues and mouse embryos. The mouse LI-cadherin sequence is 91% identical to the sequence of rat LI-cadherin and exhibits the same structural features described for rat LI-cadherin. In mouse adult tissue, LI-cadherin is expressed in the intestine and in small amounts in the spleen. In contrast to rat, Mouse LI-cadherin was not expressed in liver. During mouse embryogenesis, LI-cadherin expression begins at embryonic day 12.5. With the exception of transient expression in the urogenital sinus and the common bile duct on day 13.5, LI-cadherin was found exclusively in the intestinal epithelium. Its expression coincides with the formation of intestinal villi, a developmental stage that includes major tissue remodeling, growth, and differentiation. LI-cadherin is expressed along the entire anterior-posterior axis of the developing intestine as well as along the entire villus axis once villi begin to form. LI-cadherin occupies all cell surfaces of the deeper layers of the epithelium, distributing to basolateral surfaces only in the cells of the outer epithelial layer. LI-cadherin was found to be always co-expressed with E-cadherin.

Amino Acid Sequence↗

Shed L-selectin (sCD62L) load in trauma patients.

BACKGROUND: Low circulating plasma concentrations of the leukocyte adhesion molecule L-selectin (sCD62L) were found to be associated with an increased risk for subsequent lung failure and case fatality after severe trauma. The objective of this study was to determine the robustness of soluble L-selectin, correcting for a broad spectrum of physiological variables. METHODS: Patients with suspected multiple and/or trunk injuries were enrolled into this study over a 1-year period. Plasma samples were obtained on hospital presentation, and circulating soluble L-selectin was measured with a commercially available ELISA kit. Study records comprised all relevant clinical and laboratory data. Thirty-day survival rate, subsequent acute lung failure, and nosocomial pneumonia were defined as study endpoints. Statistical analysis was performed using multivariate logistic regression models. RESULTS: Seventy patients with a mean age of 35.51 years (range, 10-87 years) and a mean ISS score of 36.61 (95% CI, 31.08-42.14) entered the study. Eleven patients died, leading to an attributable mortality of 15.70%. L-Selectin levels did not differ between survivors and nonsurvivors. Five patients progressed to acute lung injury, whereas 11 patients developed hospital-acquired pneumonia. Lower L-selectin levels indicated patients at risk for lung injury with a relative odds estimated at 4.43 (P = 0.017). Statistical significance diminished in the multivariate model. In contrast, plasma concentrations of circulating sCD62L were significantly decreased in patients developing nosocomial pneumonia (P = 0.023), with a twofold increased relative odds (OR, 1.96; 95% CI, 0.51-7.50). No effect modification was observed by the included covariables. CONCLUSIONS: The results of this study highlight the independent predictive value of initially decreased soluble L-selectin levels for the identification of patients susceptible to subsequent respiratory complications after severe trauma.

Adolescent↗

[Repetitive transcranial magnetic stimulation (rTMS) in the acute and long-term therapy of refractory depression--a case report].

We report on a patient with therapy-resistant major depression according to DSM-IV criteria who has been hospitalized for 60 months during the last 7 years. Not even five electroconvulsive therapy (ECT) series (61 single applications) brought lasting remission of symptoms. As cognitive deficits developed and prolonged postnarcotic recovery times were observed, further ECT was contraindicated. The left frontal cortex was chosen as the target site for repetitive transcranial magnetic stimulation (rTMS) treatment. For identification, a neuronavigational system was used that allows online monitoring of the position of the magnetic coil in relation to the individual cortex. The therapeutic progress was monitored by standardized psychiatric ratings (HAMD, BDI). In addition, cognitive performance was tested during the course of treatment. Only a few rTMS applications already caused an obvious brightening in mood, remission of depressive delusional symptoms, and an increase in personal interests and activities. After 4 weeks of daily treatment, the patient was discharged from the ward. The rTMS treatments and psychotherapeutic counseling have been continued on an outpatient basis. Thus, pharmaco- and psychotherapeutic interventions combined with rTMS led to persistent symptom remission and social reintegration.

Adult↗

LI-cadherin: a marker of gastric metaplasia and neoplasia.

BACKGROUND: Intestinal metaplasia is considered a risk factor for the development of gastric adenocarcinomas of the intestinal type and is found in approximately 20% of gastric biopsies. Conventional histology only detects advanced stages of intestinal metaplasia. AIMS: To study expression of the enterocyte specific adhesion molecule liver-intestinal (LI)-cadherin in intestinal metaplasia as well as in gastric cancer, and to evaluate its use as a diagnostic marker molecule. PATIENTS: Gastric biopsies (n=77) from 30 consecutive patients (n=30; aged 28-90 years) as well as surgically resected tissue samples (n=24) of all types of gastric carcinomas were analysed. METHODS: Single and double label immunofluorescence detection on cryosections of gastric biopsies; alkaline phosphatase antialkaline phosphatase method on paraffin embedded carcinoma tissue sections. RESULTS: Of 77 biopsies (from 30 patients), 12 (from 10 patients) stained positive for LI-cadherin. LI-cadherin staining correlated with the presence of intestinal metaplasia. Conventional histological diagnosis however failed to detect subtle gastric intestinal metaplasia (three of 10 patients). In contrast, only LI-cadherin and villin were positive in these cases whereas sucrase-isomaltase also failed to detect intestinal metaplasia in four of 10 patients. Well differentiated gastric carcinomas showed intense staining for LI-cadherin while undifferentiated carcinomas showed only weak diffuse cytoplasmic staining. CONCLUSIONS: To detect early metaplastic changes in the gastric mucosa, LI-cadherin has a sensitivity superior to sucrase-isomaltase and conventional histology and comparable with that of villin. Its specificity exceeds that of villin. Thus LI-cadherin represents a new, reliable, and powerful marker molecule for early detection of gastric intestinal metaplasia and well differentiated adenocarcinomas.

Adenocarcinoma↗

Determination of optimal non-denaturing elution conditions from affinity columns by a solid-phase screen.

The purification of biological macromolecules by affinity chromatography is a widespread technique used to separate a protein from other biological components. However, this method may destroy the protein's physiological activity because elution conditions aimed to dissociate the protein of interest from the high-affinity matrix often irreversibly denature it. In the present work, we have developed a solid-phase assay to determine the optimal elution conditions for any buffer (in two steps) by determining (i) the lowest buffer concentration yielding maximum dissociation from the immobilized component and (ii) the highest buffer concentration that can be used without the loss of the protein's binding activity. Any buffer that can be reasonably used between these defined concentrations is suitable for elution within this interval. The screen is easily performed within a few hours and only requires nanograms to a few micrograms of protein. As an example, we demonstrate that more than 95% of the human transferrin receptor bound to a transferrin-sepharose ligand affinity column can be eluted with full binding activity at KSCN concentrations between 232 and 414 nM, whereas elution with urea is not suitable to purify fully functional protein.

Apoproteins↗