Biomedical subjects

Frank Wehner

Publications and source records attributed to Frank Wehner.

13 recordsLinked to original sources

PubMed2006

Cell volume-regulated cation channels.

Considering the enormous turnover rates of ion channels when compared to carriers it is quite obvious that channel-mediated ion transport may serve as a rapid and efficient mechanism of cell volume regulation. Whenever studied in a quantitative fashion the hypertonic activation of non-selective cation channels is found to be the main mechanism of regulatory volume increase (RVI). Some channels are inhibited by amiloride (and may be related to the ENaC), others are blocked by Gd(3) and flufenamate (and possibly linked to the group of transient receptor potential (TRP) channels). Nevertheless, the actual architecture of hypertonicity-induced cation channels remains to be defined. In some preparations, hypertonic stress decreases K(+) channel activity so reducing the continuous K(+) leak out of the cell; this is equivalent to a net gain of cell osmolytes facilitating RVI. The hypotonic activation of K(+) selective channels appears to be one of the most common principles of regulatory volume decrease (RVD) and, in most instances, the actual channels involved could be identified on the molecular level. These are BKCa (or maxi K(+)) channels, IK(Ca) and SK(Ca) channels (of intermediate and small conductance, respectively), the group of voltage-gated (Kv) channels including their Beta (or Kv ancilliary) subunits, two-pore K(2P) channels, as well as inwardly rectifying K(+) (Kir) channels (also contributing to K(ATP) channels). In some cells, hypotonicity activates non-selective cation channels. This is surprising, at first sight, because of the inside negative membrane voltage and the sum of driving forces for Na(+) and K(+) diffusion across the cell membrane rather favouring net cation uptake. Some of these channels, however, exhibit a P(K)/P(Na) significantly higher than 1, whereas others are Ca(++) permeable linking hypotonic stress to the activation of Ca(++) dependent ion channels. In particular, the latter holds for the group of TRPs which are specialised in the perception of a variety of different stimuli including mechanical and (hypo-) osmotic stress. As a peculiarity, phospholemman (PLM, a 72 AA peptide also employed in ion transport regulation) appears to be activated under, both, hypertonic and hypotonic conditions, preferentially operating as a cation and anion channel, respectively.

Amiloride↗

PubMed2006

Inhibition of hypertonicity-induced cation channels sensitizes HeLa cells to shrinkage-induced apoptosis.

Hypertonicity-induced cation channels (HICCs) are an effective mechanism of regulatory volume increase (RVI), which is a restoration process of cell volume after osmotic cell shrinkage, in HeLa cells. Since a reduction of cell size is a hallmark of programmed cell death, we tested whether a blockage of HICCs sensitizes HeLa cells to shrinkage-induced apoptosis by using proliferation assays, apoptosis assays, and patch-clamp recordings. Under control conditions, increasing osmolality up to 600 mosmol/kg-H2O had no detectable effect on either cell proliferation or apoptosis. With HICCs blocked by flufenamate and Gd3+, however, a significant reduction of proliferation and a stimulation of apoptosis were observed. Both effects exhibited virtually identical sensitivity profiles to osmotic stress as well as to flufenamate and Gd3+. Moreover, the observed concentration dependency of flufenamate and Gd3+ on proliferation and apoptosis was in excellent accordance with that on HICC inhibition. These results suggest that persistent cell shrinkage may function as a specific signal in the induction of apoptosis. In addition, they provide further evidence for the interplay of proliferation vs. apoptosis and the actual role that mechanisms of cell volume regulation do play in these processes.

Apoptosis↗

PubMed2005

A novel hypertonicity-induced cation channel in primary cultures of human hepatocytes.

In whole-cell recordings on primary cultures of human hepatocytes, we observe the hypertonic activation of a novel type of cation channel with a permeability ratio for Na(+):Li(+):K(+):Cs(+):NMDG(+) of 1:1.2:1.3:1.2:0.6. With a P(Ca)/P(Na) of 0.7 the channel is also clearly permeable to Ca(++). Most likely, the channel is Cl(-) impermeable but its activity critically depends on the extracellular Cl(-) concentration (with the half maximal effect at 88 mmol/l). With a 64% inhibition by amiloride and a complete block by flufenamate and Gd(3+) (at 100 micromol/l each), the channel may represent a molecular link between the amiloride-sensitive and insensitive channels reported so far.

Cells, Cultured↗

PubMed2004

Asphyxia due to pacifiers--case report and review of the literature.

Pacifiers and bottle nipples entail the risk of asphyxia when they are swallowed, self-made or have become porous, or when used by older children whose teeth and chewing musculature have developed beyond the suckling stage. A further danger lies in the various devices used to tie the pacifier to the child, as they can cause strangulation. On the basis of this first case of a 2-year-old biting off a piece of her pacifier and fatally aspirating it, we point to the dangers and security requirements related to pacifiers and bottle nipples, and give a review of the related literature.

Age Factors↗

PubMed2003

Hypertonic activation of a non-selective cation conductance in HeLa cells and its contribution to cell volume regulation.

In whole-cell recordings on single HeLa cells, the hypertonic activation of a cation conductance with a selectivity ratio P(Na):P(Li):P(K):P(Cs):P(NMDG):P(Ca):P(Cl) of 1.00:0.86:0.84:0.56:0.10:0.07:0.15 was observed. This (non-selective) cation conductance was reduced to 59 and 30% of maximal stimulation by Gd(3+) and flufenamate, respectively, but it was insensitive to amiloride (with each compound applied at 100 microm/l). As was determined by the Coulter counter technique, the cation conductance was the main mechanism of regulatory volume increase (RVI) in HeLa cells. Whereas a significant contribution of Na(+)/H(+) antiport was also detectable, Na(+)-K(+)-2Cl(-) symport most likely did not contribute to RVI.

Cations↗

PubMed2003

A cell shrinkage-induced non-selective cation conductance with a novel pharmacology in Ehrlich-Lettre-ascites tumour cells.

In whole-cell recordings on Ehrlich-Lettre-ascites tumour (ELA) cells, the shrinkage-induced activation of a cation conductance with a selectivity ratio P(Na):P(Li):P(K):P(choline):P(NMDG) of 1.00:0.97:0.88:0.03:0.01 was observed. In order of potency, this conductance was blocked by Gd(3+)=benzamil>amiloride>ethyl-isopropyl-amiloride (EIPA). In patch-clamp studies using the cell-attached configuration, a 14 pS channel became detectable that was reversibly activated upon hypertonic cell shrinkage. It is concluded that ELA cells express a shrinkage-induced cation channel that may reflect a molecular link between amiloride-sensitive and -insensitive channels. In addition, because of its pharmacological profile, it may possibly be related to epithelial Na+ channels (ENaCs).

Animals↗

PubMed2003

Hypertonic activation of phospholemman in solitary rat hepatocytes in primary culture.

Under hypertonic conditions, solitary rat hepatocytes in primary culture shrink and subsequently exhibit a distinct regulatory volume increase (RVI). Reverse-transcribed polymerase chain reaction and 5' and 3' RACE (rapid amplification of cDNA ends) techniques reveal that these cells express phospholemman (PLM). In whole-cell recordings, the hypertonic activation of a channel is observed that resembles PLM with respect to unitary conductance (600-700 pS), gating pattern, and non-selectivity for Na(+) over K(+). In Xenopus oocytes expressing hepatocyte PLM, hypertonic stress induces a non-selective cation conductance and noise analysis reveals the activation of a channel with a unitary conductance of approximately 700 pS. These results suggest a role of PLM in the RVI of rat hepatocytes.

Animals↗

PubMed2002

Computer aided shot reconstructions by means of individualized animated three-dimensional victim models.

In cases of lethal firearm injuries with indefinite indications concerning self-versus third-party infliction a computer enhanced reconstruction with the aim of an anatomical feasibility study can provide significant clues concerning the course of the traumatic event. To this end an exact three-dimensional geometrical model of the victim including all relevant anatomical data as well as the careful documentation of the injuries and a three-dimensional model of the characteristic outlines of the weapon true to scale is generated with the help of an animation program (POSER Version 4, Meta Creation, Egisys AG). With this animated digital three-dimensional model of the victim and the weapon a series of simulation sequences is created by variation of the body positions and the grasp of the weapon. Anatomically impossible positions in view of the physical characteristics of the victim and the site and direction of the bullet path are automatically excluded from the reconstruction. An exact match of the simulation sequence and the real injuries is a statement for a possible self-infliction of the gunshot wound.

Computer Simulation↗

PubMed2002

Metallothionein in liver-biopsies from patients with different diseases.

Metallothioneins (MT) are ubiquitous found in eukaryotic organism. MT have a potential for metal-storage and protect the cells against stress. On the genomic level, proinflammatory cytokines like interleukin-6 and transition metals like copper cause induction of MT. Therefore, an estimation of MT in liver-biopsies from patients with different diseases probably could help in identifying acute-phase reactions and processes which lead to increased copper. We investigated paraffin embedded liver biopsies from 170 patients and 13 control biopsies from cases of sudden death. Tissue was stained with a primary antibody against MT and a peroxidase technique was used to make results visible. A grading was performed using an immunoreactive score (IRS from 0-24) and by computer-aided measurement of the optical density (OD) of the stained tissue slides. Patients with cholestasis (IRS: 12.1 +/- 2.8, n = 11), autoimmune (10.6 +/- 3.1, n = 7) or inflammatory bowel diseases (IBD) (13.3 +/- 5.1, n = 4) and lymphoma (9.8 +/- 5.8, n = 21) showed marked increases in MT compared to the controls (5.2 +/- 2.8, n = 13). Patients with chronic hepatitis B or C or chronic alcoholic abuse had no elevation of MT. Furthermore, no correlation was found between histological damage and amount of MT except in cases of cholestasis, in which increased MT was observed. Results by OD confirmed the findings. In summary, we were able to demonstrate a clear increase of MT content in liver-biopsies in proinflammatory and cholestatic conditions. Marked elevation in patients with systemic diseases (like autoimmune-, IBD and lymphoma) seems to be best explained by an acute-phase induction of MT by proinflammatory cytokines. This could help in identifying these conditions in liver biopsies.

Adult↗

PubMed2001

Ionic mechanisms of regulatory volume increase (RVI) in the human hepatoma cell-line HepG2.

We studied the effects of hypertonic stress on ion transport and cell volume regulation (regulatory volume increase; RVI) in the human tumor cell-line HepG2. Ion conductances were monitored in intracellular current-clamp measurements with rapid ion-substitutions and in whole-cell patch-clamp recordings; intracellular pH buffering capacity and activation of Na(+)/H(+) antiport were determined fluorometrically; the rates of Na(+)-K(+)-2Cl(-) symport and Na(+)/K(+)-ATPase were quantified on the basis of time-dependent and furosemide- or ouabain-sensitive (86)Rb(+) uptake, respectively; changes in cell volume were recorded by means of confocal laser-scanning microscopy. It was found that hypertonic conditions led to the activation of a cation conductance that was inhibited by Gd(3+), flufenamate as well as amiloride, but not by benzamil or ethyl-isopropyl-amiloride (EIPA). Most likely, this cation conductance was non-selective for Na(+) over K(+). Hypertonic stress did not change K(+) conductance, whereas possible changes in Cl(-) conductance remain ambiguous. The contribution of Na(+)/H(+)antiport to the RVI process appeared to be minor. Under hypertonic conditions an approximately 3.5-fold stimulation of Na(+)-K(+)-2Cl(-)symport was observed but this transporter did not significantly contribute to the overall RVI process. Hypertonic stress did not increase the activity of Na(+)/K(+)-ATPase, which even under isotonic conditions appeared to be working at its limit. It is concluded that the main mechanism in the RVI of HepG2 cells is the activation of a novel non-selective cation conductance. In contrast, there is little if any contribution of K(+) conductance, Na(+)/H(+) antiport, Na(+)-K(+)-2Cl(-) symport, and Na(+)/K(+)-ATPase to this process.

Alkalies↗

PubMedDate not supplied

[Fatal craniocerebral trauma in a young child. I: Forensic documentation, model generation and geometric impact conditions].

The aim of forensic biomechanics is the reconstruction of traumatic events based on the pathological findings in the victim's morphology and on the traces and shapes of the traumatizing tools. The introduction of Streifenlichttopometrie into forensic science enables 3-dimensional and proportionally accurate documentation of the victim's body and injuring agent with submillimeter precision. The advantages of this method of documentation are the possibilities of producing animated models which correspond exactly to the body's shape and injury topography, and of ascertaining the physical parameters (centers of mass, moments of inertia) of the various body parts and the geometrical impact conditions for the reconstruction of the injury dynamics. This way of proceeding thus enables more precise models than hitherto possible for kinetic and dynamic reconstruction. In the case of an infant who was fatally injured by a wooden sculpture the generation and application of computer aided 3-dimensional reconstruction models are shown.

Accidents↗

PubMedDate not supplied

[Fatal inhalation of butane-propane gas].

Fatal intoxications with butane and/or propane are rare although the inhalation of such liquid gases in order to induce hallucinations is not uncommon amongst youngsters, the number of which is difficult to evaluate. Thus the possibility of gas intoxication should be taken into consideration in all cases of unclear death of youngsters, in which case the macroscopic and histological findings will be unspecific whereas the chemical-toxicological analyses, especially of the native brain, lung and liver tissue, lead to definite conclusions.

Adolescent↗

PubMedDate not supplied

[Suicidal yew poisoning--from Caesar to today--or suicide instructions on the internet].

Already the Celts and ancient Germanic peoples knew about the poisonousness of the yew, which played an important part in the mythology of these civilizations. For hunting, the arrows were made poisonous with yew juice, and yew leaves were used for homicide and suicide. In modern times taxine is rarely used with suicidal intent, although this method is actually recommended on the respective Websites. After a 14-year-old boy had intensively studied poisonous plants and methods of suicide on various Websites, he cut leaves from a yew tree (taxus baccata) in his parents' garden, crushed and ingested them and died soon afterwards. At the forensic autopsy pieces of the partially crushed, partially completely preserved yew leaves were found in the stomach. The histological findings were unspecific, e.g. marked general blood congestion of the internal organs and pronounced cerebral and pulmonary edema. When the tree leaves found in the stomach were viewed under the light microscope, a stoma typical of taxus was observed; chemical-toxicological investigations revealed 3,5-dimethoxyphenol in the gastric content, which is considered a marker for the ingestion of taxus.

Adolescent↗