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Biomedical subjects

W Vogel

Publications and source records attributed to W Vogel.

At least 91 records · Page 5Linked to original sources
PubMed2000

An interdisciplinary approach to breast and PCA. International Symposium: Breast and PCA: Genes, Hormones and the Environment, Garmisch-Partenkirchen, Germany, 22-24 April 1999.

Breast and prostate cancer (PCA) are among the leading cancer forms in the developed world. The 'International Symposium: Breast and PCA: Genes, Hormones and the Environment', and interdisciplinary meeting organized by K. Badenhoop (University Hospital, Frankfurt, Germany), J. Köhrle (University Hospital, Würzburg, Germany) and W-D. Schleuning (Schering AG, Berlin, Germany), was intended to promote the exchange of new concepts and emerging paradigms between basic science and clinical research, and to establish interactions with researchers in industry in this field.

Breast Neoplasms↗
PubMed2000

Carbohydrate malabsorption syndromes and early signs of mental depression in females.

Fructose and lactose malabsorption are characterized by impaired duodenal fructose transport or by the deficiency of mucosal lactase, respectively. As a consequence, the nonabsorbed saccharides reach the colon, where they are broken down by bacteria to short fatty acids, CO2, and H2. Bloating, cramps, osmotic diarrhea, and other symptoms of irritable bowel syndrome are the consequence and can be seen in about 50% of carbohydrate malabsorbers. We have previously shown that fructose as well as lactose malabsorption were associated with signs of mental depression. It was therefore of interest to investigate possible interactions between fructose and lactose malabsorption and their influence on the development of signs of depression. In all, 111 otherwise healthy volunteers (81 females and 30 males) with gastrointestinal complaints were analyzed by measuring breath H2 concentrations after an oral dose of 50 g lactose and of 50 g fructose one week apart. They were classified as normals, isolated fructose malabsorbers, isolated lactose malabsorbers, and combined fructose/lactose malabsorbers. All patients filled out a Beck's depression inventory-questionnaire. Twenty-five individuals (22.5%) were neither fructose nor lactose malabsorbers (group 1), 69 (62.2%) were only fructose malabsorbers (group 2), 4 (3.6%) were only lactose malabsorbers (group 3), and 13 (11.7%) presented with fructose and lactose malabsorption together (group 4). Isolated fructose malabsorption and combined fructose/lactose malabsorption was significantly associated with a higher Beck's depression score. Further analysis of the data show that this association was strong in females (P < 0.01), but there was no such association between carbohydrate malabsorption and early signs of depression in males. In conclusion, the data confirm that fructose malabsorption may play a role in the development of mental depression in females and additional lactose malabsorption seems to further increase the risk for development of mental depression.

Adult↗
PubMed2000

A novel binding site for the native hepatic acute-phase protein alpha1-antitrypsin expressed on the human hepatoma cell line HepG 2 and intestinal cell line Caco 2.

AIMS/BACKGROUND: alpha1-antitrypsin (alpha1-AT) is a hepatic acute phase protein which predominantly inhibits neutrophil elastase. Besides this major function, we have also previously shown that alpha1-AT markedly increased H-ferritin mRNA expression and ferritin synthesis in the human hepatoma cell line HepG 2. These actions suggest that alpha1-AT might interact with HepG 2 cells via a specific cell surface binding site. METHODS AND RESULTS: Using radio-labelled native alpha1-AT, we observed saturable binding to HepG 2 cells with a dissociation constant (Kd) of 63.3+/-6.9 nM and a maximal density of binding sites (Bmax) of 0.34+/-0.05 pmol/10(6) cells equivalent to 195,800+/-29,200 sites/cell. The binding of [125I]alpha1-AT was time dependent with a calculated association rate constant of 9.22+/-1.84x10(4)xM(-1)xmin(-1). Binding was highly specific since other acute phase proteins or protease inhibitors failed to block binding. Although alpha1-AT-trypsin, alpha1-AT-elastase and the pentapeptide FVYLI, the minimal binding sequence for the SEC receptor, increased [125I]alpha1-AT binding, in long term experiments these complexes failed to influence the number of alpha1-AT binding sites. Specific, saturable binding of [125I]alpha1-AT was also found on the human intestinal epithelial Caco 2 cells, but not on fibroblast or leukaemic cell lines. CONCLUSION: These experiments demonstrate a specific, high affinity binding site for native alpha1-AT on HepG 2 and Caco 2 cells, cell lines derived from tissues involved in the acute phase response.

Binding Sites↗
PubMed2000

Block of neuronal tetrodotoxin-resistant Na+ currents by stereoisomers of piperidine local anesthetics.

Tetrodotoxin (TTX)-sensitive Na(+) channels in the peripheral nervous system are the major targets for local anesthetics. In the peripheral nociceptive system, a Na(+) channel subtype resistant to TTX and with distinct electrophysiological properties seems to be of importance for impulse generation and conduction. A current through TTX-resistant Na(+) channels displays slower activation and inactivation kinetics and has an increased activation threshold compared with TTX-sensitive Na(+) currents and may have different pharmacological properties. We studied the effects of stereoisomers of piperidine local anesthetics on neuronal TTX-resistant Na(+) currents recorded with the whole-cell configuration of the patch clamp method in enzymatically dissociated dorsal root ganglion neurons of adult rats. Stereoisomers of mepivacaine, ropivacaine, and bupivacaine reversibly inhibited TTX-resistant Na(+) currents in a concentration and use-dependent manner. All drugs accelerated time course of inactivation. Half-maximal blocking concentrations were determined from concentration-inhibition relationships. Potencies for tonic and for use-dependent block increased with rising lipid solubilities of the drugs. Stereoselective action was not observed. We conclude that block of TTX-resistant Na(+) currents may lead to blockade of TTX-resistant action potentials in nociceptive fibers and consequently may be responsible for pain suppression during local anesthesia.

Algorithms↗
PubMed2000

Tonic blocking action of meperidine on Na+ and K+ channels in amphibian peripheral nerves.

BACKGROUND: Among opioids, meperidine (pethidine) also shows local anesthetic activity when applied locally to peripheral nerve fibers and has been used for this effect in the clinical setting for regional anesthesia. This study investigated the blocking effects of meperidine on different ion channels in peripheral nerves. METHODS: Experiments were conducted using the outside-out configuration of the patch-clamp method applied to enzymatically prepared peripheral nerve fibers of Xenopus laevis. Half-maximal inhibiting concentrations were determined for Na+ channels and different K+ channels by nonlinear least-squares fitting of concentration-inhibition curves, assuming a one-to-one reaction. RESULTS: Externally applied meperidine reversibly blocked all investigated channels in a concentration-dependent manner, i.e., voltage-activated Na+ channel (half-maximal inhibiting concentration, 164 microM), delayed rectifier K+ channels (half-maximal inhibiting concentration, 194 microM), the calcium-activated K+ channel (half-maximal inhibiting concentration, 161 microM), and the voltage-independent flicker K+ channel (half-maximal inhibiting concentration, 139 microM). Maximal block in high concentrations of meperidine reached 83% for delayed rectifier K+ channels and 100% for all other channels. Meperidine blocks the Na+ channel in the same concentration range as the local anesthetic agent lidocaine (half-maximal inhibiting concentration, 172 microM) but did not compete for the same binding site as evaluated by competition experiments. Low concentrations of meperidine (1 nM to 1 microM) showed no effects on Na+ channels. The blockade of Na+ and delayed rectifier K+ channels could not be antagonized by the addition of naloxone. CONCLUSIONS: It is concluded that meperidine has a nonselective inhibitory action on Na+ and K+ channels of amphibian peripheral nerve. For tonic Na+ channel block, neither an opioid receptor nor the the local anesthetic agent binding site is the target site for meperidine block.

Analgesics, Opioid↗
PubMed2000

Differential block of fast and slow inactivating tetrodotoxin-sensitive sodium channels by droperidol in spinal dorsal horn neurons.

BACKGROUND: Dorsal horn neurons of the spinal cord participate in neuronal pain transmission. During spinal and epidural anesthesia, dorsal horn neurons are exposed to local anesthetics and opioids. Droperidol is usually given with opioids to avoid nausea and vomiting. A recently developed method of "entire soma isolation" has made it possible to study directly the action of droperidol on different components of Na+ current in dorsal horn neurons. METHODS: Using a combination of the whole-cell patch-clamp recording from spinal cord slices and the entire soma isolation method, we studied the direct action of droperidol on two types of Na+ currents in dorsal horn neurons of young rats. RESULTS: The tetrodotoxin-sensitive Na+ current in isolated somata consisted of a fast inactivating (tauF, 0.5-2 ms; 80-90% of the total amplitude) and a slow inactivating (tauS, 6-20 ms; 10-20% of the total amplitude) component. Droperidol, at concentrations relevant for spinal and epidural anesthesia, selectively and reversibly suppressed the fast component with a half-maximum inhibiting concentration (IC50) of 8.3 microm. The slow inactivating component was much less sensitive to droperidol; the estimated IC50 value was 809 microm. CONCLUSIONS: Droperidol selectively blocks fast Na+ channels, the fast and slow components of the Na+ current in dorsal horn neurons are carried through pharmacologically distinct types of Na+ channels, and the effects of droperidol differ from those of local anesthetics and tetrodotoxin, which equipotently suppress both components. Droperidol may be suggested as a pharmacologic tool for separation of different types of inactivating tetrodotoxin-sensitive Na+ channel.

Adjuvants, Anesthesia↗
PubMed2000

Do the constraints of human speciation cause expression of the same set of genes in brain, testis, and placenta?

Evolution appears to be especially rapid during speciation, and the genes involved in speciation should be evident in species such as humans that have recently speciated or are presently in the process of speciation. Haldane's rule is that when one sex is sterile or inviable in interspecific F(1) hybrids, it is usually the heterogametic sex. For mammals, this implicates genes on the X chromosome as those particularly responsible for speciation. A preponderance of sex- and reproduction-related genes on the X chromosome has been shown repeatedly, but also mental retardation genes are more frequent on the X chromosome. We argue that brain, testis, and placenta are those organs most responsible for human speciation. Furthermore, the high degree of complexity of the vertebrate genome demands coordinate evolution of new characters. This coordination is best attained when the same set of genes is redeployed for these new characters in the brain, testis, and placenta.

Biological Evolution↗
PubMed2000

A comparison of the expression pattern of five genes of the family of small leucine-rich proteoglycans during mouse development.

For five members of the family of the small leucine-rich proteoglycans (SLRPs), the expression pattern during fetal development was analyzed. RNA in situ hybridization on whole body sections of mouse embryos was performed for biglycan (Bgn), decorin (Dcn), fibromodulin (Fmod), chondroadherin (Chad), and lumican (Lum). Special attention was given to the question of whether these patterns coincide only with sites of collagen secretion in connective tissue during tissue modeling or if expression can be observed at specific sites of organ differentiation also. In general, Fmod, Lum, and Bgn are expressed at sites of cartilage and bone formation and interstitial tissue deposition; Chad is expressed only at sites of cartilage; and Dcn is expressed only at sites of interstitial tissue deposition. However, there are some distinct developmental stages where no collagen secretion is known to occur. For example, this applies for the expression of Fmod in the forming somites of stage 9.5 postconception (p.c.), for Dcn and Lum in later stage embryos in the pituitary gland and dorsal root ganglia, and for Bgn and Dcn during differentiation in the kidney. These studies provide further evidence for a role of these molecules during connective tissue organization but also for an involvement at specific sites of organ differentiation.

Animals↗
PubMed2000

Clinical applications of CD34(+) peripheral blood progenitor cells (PBPC).

Recently, a number of devices have been developed for the positive selection of CD34(+) peripheral blood progenitor cells (PBPC) for clinical use in autologous or allogeneic transplantation. The rationale for CD34(+) selection is based on clinical studies showing a two- to five-log reduction of contaminating tumor cells in patients with breast cancer, multiple myeloma and low-grade lymphoma. In addition, a three- to five-log reduction of T cells can be obtained by CD34(+) selection in both autologous grafts for patients with autoimmune disease resistant to conventional therapy and allogeneic grafts to reduce the incidence and severity of acute graft-versus-host disease. Transplantation of positively selected autologous CD34(+) PBPC results in a rapid and stable neutrophil and platelet engraftment in patients who received an infused dose of at least 2.0 x 10(6) CD34(+) cells/kg. Results from randomized trials suggest that time to engraftment is not different compared to unmanipulated PBPC autografts. However, close monitoring for infectious complications (e.g., cytomegalovirus disease) is required. Allogeneic CD34(+) PBPC have also been successfully transplanted and, using novel technologies, megadoses of purified CD34(+) PBPC can be obtained and used to overcome histocompatibility differences betweeen allogeneic donor and patient resulting in stable engraftment, even in a haploidentical setting. Additional randomized phase III trials are required to determine whether tumor cell purging or lymphocyte depletion by CD34(+) cell selection will have a significant impact on progression-free and overall survival in both autologous and allogeneic transplantation.

Antigens, CD34↗
PubMed2000

[Quality assurance in geriatric rehabilitation hospital treatment. Long-term medical and functional outcome].

Clinical geriatric therapy has shown to be beneficial and cost-effective. However, little is known about its long-term results. Based on GEMIDAS (Geriatric Minimal Data Set), a multicenter-Database of the German Federal Association of 140 Clinical Geriatric Institutions, we conducted a one-year-follow-up pilot study focusing on medical and functional results, including needs of technical aids and nursing. Mortality was 16% at 1 year. Two thirds of the deceased had died during the first half year, many with severe stroke. Among the 840 survivors, 81.1% lived in their private housing, 14.5% in nursing homes, 4.4% were actually hospitalized. 37.3% suffered from recurrent diseases such as stroke (5.2%), bone fractures (4.5%), heart attacks (2.1%), severe infections (1.1%), needing hospitalization in 31.9%, repeatedly in 6.9% of the survivors. Technical aids were regularly used in about 80%. Personal help was often necessary and was provided by relatives (66.9%), professional nursing (39.8%), neighbors (5.7%), only 6% of the patients needed no help. The initial functional gain (mean Barthel-Index from 53.4 to 72.3 points) diminished to 59.6 points during follow-up, with similar patterns for most of the single Barthel-items. Our results confirm the initial benefit and clearly show a significant long-term effect of clinical geriatric rehabilitation. For stabilization and further functional improvement, specific and continuous rehabilitation efforts seem to be crucial.

Activities of Daily Living↗
PubMed2000

Lamivudine for treating active hepatitis B in renal transplant recipients: a case report.

AIM: Chronic hepatitis B is still a matter of concern among renal transplantation patients and patients waiting for a renal transplant since it influences negatively morbidity and mortality. Morbidity and mortality are associated with HBV replication. Lamivudine is a new antiviral agent whose use has been advocated to treat HBV-infected liver transplanted patients. SUBJECT AND METHODS: Here we present our experience with an HBV-positive kidney-liver transplanted patient treated with lamivudine after transplantation. RESULTS: After lamivudine was started HBV-DNA became negative (chemiluminescence, Digene Hybrid Capture System, USA 1997) and ALT levels returned to normal. After eighteen months and after steroid pulses treatment for acute rejection, HBV-DNA became positive again, probably due to virus mutation. Lamivudine treatment was not withdrawn since it has been suggested that the mutant form might be less pathogenic than the wild one. To this extent, more than 10 months after, our patient is still in a good clinical general condition and still takes lamivudine 75 mg/day. No lamivudine-related side effects were recorded. CONCLUSIONS: Our case confirms that lamivudine is a safe and useful tool in treating renal transplant recipients with chronic hepatitis B.

Hepatitis B↗
PubMed1999

Human axons contain at least five types of voltage-dependent potassium channel.

1. We investigated voltage-gated potassium channels in human peripheral myelinated axons; apart from the I, S and F channels already described in amphibian and rat axons, we identified at least two other channel types. 2. The I channel activated between -70 and -40 mV, and inactivated very slowly (time constant 13.1 s at -40 mV). It had two gating modes: the dominant ('noisy') mode had a conductance of 30 pS (inward current, symmetrical 155 mM K+) and a deactivation time constant (tau) of 25 ms (-80 mV); it accounted for most ( approximately 50-75 %) of the macroscopic K+ current in large patches. The secondary ('flickery') gating mode had a conductance of 22 pS, and showed bi-exponential deactivation (tau = 16 and 102 ms -80 11 mV); it contributed part of the slow macroscopic K+ current. 3. The I channel current was blocked by 1 microM alpha-dendrotoxin (DTX); we also observed two other DTX-sensitive K+ channel types (40 pS and 25 pS). The S and F channels were not blocked by 1 microM DTX. 4. The conductance of the S channel was 7-10 pS, and it activated at slightly more negative potentials than the I channel; its deactivation was slow (tau = 41.7 ms at -100 mV). It contributed a second component of the slow macroscopic K+ current. 5. The F channel had a conductance of 50 pS; it activated at potentials between -40 and +40 V, deactivated very rapidly (tau = 1.4 ms at -100 mV), and inactivated rapidly (tau = 62 ms at +80 mV). It accounted for the fast-deactivating macroscopic K+ current and partly for fast K+ current inactivation. 6. We conclude that human and rat axonal K+ channels are closely similar, but that the correspondence between K+ channel types and the macroscopic currents usually attributed to them is only partial. At least five channel types exist, and their characteristics overlap to a considerable extent.

Adolescent↗