PubMed Health⌕ Search

Biomedical subjects

S Wilhelm

Publications and source records attributed to S Wilhelm.

At least 73 records · Page 4Linked to original sources
PubMed1999

A novel lipolytic enzyme located in the outer membrane of Pseudomonas aeruginosa.

A lipase-negative deletion mutant of Pseudomonas aeruginosa PAO1 still showed extracellular lipolytic activity toward short-chain p-nitrophenylesters. By screening a genomic DNA library of P. aeruginosa PAO1, an esterase gene, estA, was identified, cloned, and sequenced, revealing an open reading frame of 1,941 bp. The product of estA is a 69.5-kDa protein, which is probably processed by removal of an N-terminal signal peptide to yield a 67-kDa mature protein. A molecular mass of 66 kDa was determined for (35)S-labeled EstA by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. The amino acid sequence of EstA indicated that the esterase is a member of a novel GDSL family of lipolytic enzymes. The estA gene showed high similarity to an open reading frame of unknown function located in the trpE-trpG region of P. putida and to a gene encoding an outer membrane esterase of Salmonella typhimurium. Amino acid sequence alignments led us to predict that this esterase is an autotransporter protein which possesses a carboxy-terminal beta-barrel domain, allowing the secretion of the amino-terminal passenger domain harboring the catalytic activity. Expression of estA in P. aeruginosa and Escherichia coli and subsequent cell fractionation revealed that the enzyme was associated with the cellular membranes. Trypsin treatment of whole cells released a significant amount of esterase, indicating that the enzyme was located in the outer membrane with the catalytic domain exposed to the surface. To our knowledge, this esterase is unique in that it exemplifies in P. aeruginosa (i) the first enzyme identified in the outer membrane and (ii) the first example of a type IV secretion mechanism.

Amino Acid Sequence↗
PubMed1999

Uncouplers of oxidative phosphorylation can enhance a Fas death signal.

Recent work suggests a participation of mitochondria in apoptotic cell death. This role includes the release of apoptogenic molecules into the cytosol preceding or after a loss of mitochondrial membrane potential DeltaPsim. The two uncouplers of oxidative phosphorylation carbonyl cyanide m-chlorophenylhydrazone (CCCP) and 2, 4-dinitrophenol (DNP) reduce DeltaPsim by direct attack of the proton gradient across the inner mitochondrial membrane. Here we show that both compounds enhance the apoptosis-inducing capacity of Fas/APO-1/CD95 signaling in Jurkat and CEM cells without causing apoptotic changes on their own account. This amplification occurred upstream or at the level of caspases and was not inhibited by Bcl-2. The effect could be blocked by the cowpox protein CrmA and is thus likely to require caspase 8 activity. Apoptosis induction by staurosporine in Jurkat cells as well as by Fas in SKW6 cells was unaffected by CCCP and DNP. The role of cytochrome c during Fas-DNP signaling was investigated. No early cytochrome c release from mitochondria was detected by Western blotting. Functional assays with cytoplasmic preparations from Fas-DNP-treated cells also indicated that there was no major contribution by cytochrome c or caspase 9 to the activation of effector caspases. Furthermore, an increase of rhodamine-123 uptake into intact cells, which has been explained by mitochondrial swelling, occurred considerably later than the caspase activation and was blocked by Z-VAD-fmk. These data show that uncouplers of oxidative phosphorylation can presensitize some but not all cells for a Fas death signal and provide information about the existence of separate pathways in the induction of apoptosis.

2,4-Dinitrophenol↗
PubMed1999

Expression of AE2 anion exchanger in mouse intestine.

We have characterized expression of anion exchanger 2 (AE2) mRNA and protein in the mouse intestine. AE2 mRNA abundance was higher in colon than in more proximal segments. AE2a mRNA was more abundant than AE2b mRNA throughout the intestine, and AE2c mRNA was expressed at very low levels. This AE2 mRNA pattern contrasted with that in mouse stomach, in which AE2c > AE2b > AE2a. AE2 polypeptide abundance as detected by immunoblot qualitatively paralleled that of mRNA, whereas AE2 immunostaining exhibited a more continuous decrease in intensity from colon to duodenum. AE2 polypeptide was more abundant in colonic surface cells than in crypts, whereas ileal crypts and villi exhibited similar AE2 abundance. AE2 was also observed in mural and vascular smooth muscle. Localization of AE2 epitopes was restricted to the basolateral membranes of epithelial cells throughout the intestine with three exceptions. Under mild fixation conditions, anti-AE2 amino acids (aa) 109-122 detected nonpolarized immunostaining of ileal enterocytes and of Paneth cell granule membranes. An epitope detected by anti-AE2 aa 1224-1237 was also localized to subapical regions of Brunner's gland ducts of duodenum and upper jejunum. These localization studies will aid in the interpretation of anion exchanger function measured in epithelial sheets, isolated cells, and membrane vesicles.

Animals↗
PubMed1999

Self-injurious skin picking: clinical characteristics and comorbidity.

BACKGROUND: Repetitive skin picking, a self-injurious behavior that may cause severe tissue damage, has received scant empirical attention. The authors examined the demographics, phenomenology, and associated psychopathology in a series of 31 subjects with this problem. METHOD: Subjects were administered the Structured Clinical Interview for DSM-IV for Axis I and Axis II disorders. They also completed several mood questionnaires and a new self-report inventory designed to assess phenomenology, triggers, cognitions, emotions, and consequences associated with skin picking. RESULTS: The mean age at onset on self-injurious skin picking was 15 years, and the mean duration of illness was 21 years. All subjects picked at more than one body area, and the most frequent sites of skin picking were pimples and scabs (87%). The most common comorbid Axis I diagnoses were obsessive-compulsive disorder (OCD; 52%), alcohol abuse/dependence (39%), and body dysmorphic disorder (32%). Forty-eight percent (N = 15) of the subjects met criteria for at least one mood disorder, and 65% (N = 20) for at least one anxiety disorder. The most common Axis II disorders were obsessive-compulsive personality disorder (48%) and borderline personality disorder (26%). CONCLUSION: Self-injurious skin picking is a severe and chronic psychiatric and dermatologic problem associated with high rates of psychiatric comorbidity. It may be conceptualized as a variant of OCD or impulse-control disorder with self-injurious features and may, in some cases, represent an attempt to regulate intense emotions.

Adolescent↗
PubMed1998

The emotional counting Stroop paradigm: a functional magnetic resonance imaging probe of the anterior cingulate affective division.

BACKGROUND: The emotional counting Stroop (ecStroop) functional magnetic resonance imaging (fMRI) activation paradigm was designed to recruit the anterior cingulate affective division (ACad). METHODS: Nine normal, healthy male and female subjects (mean age 24.2 years) reported via button press the number of neutral and negative words that appeared on a screen while reaction time and fMRI data were acquired. RESULTS: We observed a) greater ACad activation for negative versus neutral words during initial presentation blocks; b) lower overall ACad signal intensity during task performance (i.e., both negative and neutral words) compared to the baseline fixation condition; and c) no reaction time increase to negative versus neutral words. CONCLUSIONS: In a companion study of a cognitive version of the counting Stroop (Bush et al 1998), these same 9 subjects a) activated the more dorsal anterior cingulate cognitive division; b) also showed the overall decrease in ACad signal intensity; and c) demonstrated a reliable reaction time effect. Taken together, these data offer a within-group spatial dissociation of AC function based upon information content (i.e., cognitive vs. emotional) and/or presence of behavioral interference. We propose that the ecStroop will be a useful fMRI probe of ACad function in anxiety disorders.

Adult↗
PubMed1998

Thrombomodulin modulates growth of tumor cells independent of its anticoagulant activity.

Thrombomodulin (TM), recognized as an essential vessel wall cofactor of the antithrombotic mechanism, is also expressed by a wide range of tumor cells. Tumor cell lines subcloned from four patients with malignant melanoma displayed a negative correlation between TM expression and cell proliferation in vitro and in vivo. Overexpression of wild-type TM decreased cell proliferation in vitro and tumor growth in vivo. TM mutants with altered protein C activation capacity lead to a similar effect. In contrast, transfection of melanoma cells with mutant TM constructs, in which a portion of the cytoplasmic or lectin domain was deleted, abrogated the antiproliferative effect associated with overexpression of wild-type TM. Experiments performed with either peptide agonists/antagonists of the thrombin receptor, with hirudin, or with inhibitors of thrombin-TM interaction did not alter the growth inhibitory effect of TM overexpression. These data suggest that TM exerts an effect on cell proliferation independent of thrombin and the thrombin receptor, possibly related to the binding of novel ligands to determinants in the lectin domain which might trigger signal transduction pathways dependent on the cytoplasmic domain.

Animals↗
PubMed1998

Activation of caspase-3-like enzymes in non-apoptotic T cells.

The activation of the caspase family of cysteine proteases is a key step in the implementation of apoptotic cell death leading to further downstream effects such as DNA fragmentation. In cultured tumor cells, caspase activity appears only when cells are undergoing apoptosis. Here we show that human and murine T lymphocytes acquire high intracellular activities of cell death-specific caspases upon activation by mitogens and IL-2 without evidence that apoptosis is proceeding. The highest activity is seen when cells are mitogen activated for 3 days. On a per cell basis, caspase activity in activated T cells is much higher than in tumor cells induced to undergo apoptosis. In the presence of exogenously added IL-2 cells stay alive and maintain a high level of caspase activity while IL-2 withdrawal results in cell death and decline of caspase activity. Caspase activity can also be measured in extracts from spleen and lymph nodes from mice injected with superantigen. While in tumor cell lines caspase activity correlates with cleavage of poly(ADP)-ribose polymerase (PARP) and DNA fragmentation, in activated T cells cleavage products of cellular PARP can be detected whereas DNA fragmenting activity appears only upon IL-2 withdrawal which coincides with cell death. These data show that caspase activation in intact cells does not necessarily lead to cell death and argue for a checkpoint in the apoptotic pathway downstream of caspases. Furthermore, they provide a molecular correlate for the high susceptibility of activated T cells for apoptosis.

Animals↗
PubMed1998

[Bovine hemoglobin. HBOC-201 causes a reduction of the oxygen partial pressure in poststenotic skeletal muscle].

UNLABELLED: We investigated the effects of ultrapurified polymerized bovine hemoglobin (HBOC-201) on skeletal muscle tissue oxygen tension when applied before establishment of a nearly complete arterial stenosis. METHODS: Twelve foxhounds were anaesthetized IV and mechanically ventilated with 30% oxygen in air. Catheters were inserted into the right femoral artery and vein for measurements of haemodynamic parameters and blood-gas sampling. Arterial blood flow of the left popliteal artery was measured by an electromagnetic flow probe. Skeletal muscle tissue oxygen tension (tpo2) was measured in the left gastrocnemic muscle using a stepwise-driven polarographic needle probe, creating histograms from 200 single tpO2 measurements. Following isovolaemic haemodilution with Ringer's solution to a target haematocrit of 20%, the animals were randomly assigned to receive either 200 ml of predonated fresh blood (group 1) or 200 ml of HBOC-201 (MW 32,000-500,000; Hb 13 +/- 1 g-dl-1, group 2). After a 15-min stabilization period, a 95% artificial stenosis of the left popliteal artery was established. While animals of group 1 received two applications of 200 ml 6% hetastarch (HES, 200,000; 0.5), animals of group 2 received 200 ml Ringer's solution 45 and 75 min after establishment of the arterial stenosis, respectively. Variables were measured at baseline, after haemodilution and application of the respective compound, and 30, 60 and 90 min after establishment of the stenosis. RESULTS: Demographic data, muscle temperature and arterial blood gases did not differ between groups. With the exception of a higher mean pulmonary artery pressure in HBOC-201-treated animals, haemodynamics did not differ between groups. In both groups oxygen delivery and oxygen consumption of the muscle decreased in parallel to the decreasing blood flow during arterial stenosis. In contrast, oxygen extraction ratio increased after infusion of HBOC-201 and remained unchanged during stenosis (P < 0.05). In group 1, the tpO2 decreased during stenosis when compared to baseline (P < 0.001) and remained decreased after administration of HES. In contrast, administration of 200 ml of HBOC-201 before establishment of the arterial stenosis sustained the tpO2 values at nearly baseline levels during stenosis. Skeletal muscle tissue oxygen tension was higher after HBOC-201 infusion during stenosis when compared to HES infusion (P < 0.001). CONCLUSION: These data suggest that haemoglobin solutions can reach poststenotic tissues. The increased oxygen extraction after application of HBOC-201 is associated with improved skeletal muscle oxygen tension during severe arterial stenosis.

Animals↗
PubMed1998

Bovine haemoglobin-based oxygen carrier for patients undergoing haemodilution before liver resection.

We have studied the use of ultrapurified polymerized bovine haemoglobin (HBOC-201) in patients undergoing preoperative haemodilution before liver resection. After autologous blood donation of 1 litre, 12 patients (six males, six females, mean age 59 (35-69) yr) received Ringer's lactate solution 2 litre and, in a random design, 6% hydroxyethyl starch 70,000/0.5 (HES) 3 ml kg-1 or HBOC-201 0.4 g kg-1 within 30 min. Blood samples were obtained for blood chemistry, co-oximetry, haematology, coagulation profiles and immunology examinations before operation, on the day of surgery, on days 2-4 and 7 after operation, on the discharge day and 3 months after operation. There were no differences in patient characteristics, blood loss, amount of solutions infused, transfused allogeneic blood or duration of hospital stay. There were no local or systemic allergic reactions with infusion of HES or HBOC-201. Patients receiving HBOC-201 developed more pronounced leucocytosis and reticulocytosis during the early postoperative days compared with HES-treated patients. The mean maximum plasma haemoglobin concentration was 1.0 (SD 0.2) g dl-1 at the end of infusion of HBOC-201 was 8.5 h. Patients in both groups experienced temporary changes in liver enzymes and coagulation variables which returned to normal before discharge. Urinalysis revealed no difference between groups and no free haemoglobin was detected in urine. Patients receiving HBOC-201 showed no IgE and only a slight increase in IgG titres to HBOC-201 on the day of discharge; these were not detectable at 3 months. Single-dose administration of HBOC-201 was well tolerated by patients undergoing elective liver resection surgery and appears to be safe as a substitute during preoperative haemodilution.

Adult↗
PubMed1998

Transcranial Doppler sonography mean flow velocity during infusion of ultrapurified bovine hemoglobin.

A number of studies have shown that polymerized bovine hemoglobin (HBOC-201) does not cause clinically significant side effects. This has been demonstrated in spite of the fact that a primary increase in oxygen extraction ratio has been associated with an increase in systemic vascular resistance (SVR) and a decrease in cardiac index (CI). The current study investigated the effects of HBOC-201 on cerebral circulation. Middle cerebral artery mean flow velocity (Vm) was measured using Transcranial Doppler sonography. After institutional review board approval and informed consent were obtained, 12 patients (mean age 59+/-10 years), scheduled for hepatic resection, were enrolled. Anesthesia during the induction period consisted of etomidate (0.3 mg/kg), fentanyl (3 mcg/kg), and vecuronium (0.1 mg/kg). Anesthesia during the maintenance period consisted of isoflurane (0.64-0.8 vol%)/O2/N2O (FiO2=0.3), fentanyl, and vecuronium. End-tidal carbon dioxide partial pressure (PetCO2), arterial carbon dioxide partial pressure (PaCO2), mean arterial blood pressure (MAP), CI, SVR, mean flow velocity, and pulsatility index were measured in each patient. Hemodilution was performed in all patients, followed by randomized assignment to two groups: Group 1 (n=6) received 0.4 g/kg HBOC-201, Group 2 (n=6) received a corresponding volume of hydroxyethyl starch (mw 70,000). Measurements were taken at six points (PMs): before hemodilution (PM 1); following hemodilution (PM2); and at 3, 10, 20, and 30 minutes (PM 3-6) after infusion of HBOC-201 or starch. Systemic vascular resistance rose in Group 1 as compared with Group 2, with significant differences at PM 3-6. The greatest difference was at PM 6 (Group 2=1071 dyne x s x cm(-5); Group 1=2154 dyne x s x cm(-5)). Cardiac indices were significantly lower in Group 1 (1.7-1.8 l/minute x m(-2)) than in Group 2 (2.4-2.7 l/minute x m(-2)) after PM 3. After hemodilution, mean flow velocity showed an insignificant increase in both groups, ranging from 39 to 46 cm/second. Although SVR increased significantly following HBOC-201 -infusion, the results of this study did not reveal changes in cerebral blood flow that establish significant group-to-group differences.

Adult↗
PubMed1998

Thrombomodulin, a receptor for the serine protease thrombin, is decreased in primary tumors and metastases but increased in ascitic fluids of patients with advanced ovarian cancer FIGO IIIc.

The human ovarian cancer cell line OV-MZ-19, established from a patient with cystadenocarcinoma of the ovary, expressing thrombomodulin (TM), a cell surface receptor for the serine protease thrombin, interacts with monoclonal and polyclonal antibodies having different specificity for TM. These antibodies detect TM antigen by means of flow cytofluorometry, laser scanning microscopy, immunocytochemistry, and ELISA. Therefore a highly sensitive ELISA for TM antigen was established using two different monoclonal antibodies to quantify TM in tissue extracts and biological fluids, e.g. peritoneal malignant ascites. Primary malignant ovarian tumors and metastases of the omentum and intestine contain TM antigen as determined by ELISA but in significantly lower concentrations than benign ovarian tumors (p=0.0056). In contrast, malignant ascitic fluid of patients with advanced ovarian cancer (FIGO IIIc) contain significantly elevated concentrations of soluble TM than benign peritoneal exudates (p=0.0003). Immunoaffinity purified ascites-derived TM efficiently activates protein C. Protein C activation of ascites-derived TM as well as TM expressed by the tumor cells is inhibited by the monoclonal antibodies. TM abrogates the procoagulant activity of thrombin, reduces pericellular thrombin via internalization, accelerates the thrombin-mediated inactivation of pro-uPA, and the EGF domains of TM exhibit mitogenic activity towards fibroblasts and tumor cells. Both, thrombin and pro-uPA play important roles in tumor invasion and metastasis. Therefore, downregulation and/or release of TM into ascitic fluid may play an important role in the malignant behavior of tumor cells.

Antibodies, Monoclonal↗
PubMed1998

[Urologic complications after kidney transplantation (II)].

Urological complications after renal transplantation are often responsible for postoperative morbidity and mortality in spite of a decrease in incidence and severity of such complications in the last decades. It is of particular interest to detect this complications early and to treat them in an adequate manner especially in regard to the increasing lack of human organs for transplantation. The number of transplanted patients in the population is still increasing and they are treated not only in transplant centers but also by general practitioners, nephrologists and urologists in private consultings. This necessitates a survey about the most important complications including diagnostics and therapeutic options. Measures of prevention and early detection are taken into account. Questions concerning impotence and incontinence are discussed in detail. Attention must be paid to the fact of immunosuppression and its peculiarities in transplanted patients. In this way the outcome of patients and transplants can be prolonged.

Female↗
PubMed1997

[Preoperative hemodilution with bovine hemoglobin. Acute hemodynamic effects in liver surgery patients ].

UNLABELLED: Haemoglobin solutions can be an alternative to allogeneic red-cell transfusions because they combine colloid osmotic with oxygen transport properties. Since severe toxic side effects have been overcome by ultrapurification, clinical interest has been focused on haemodynamics changes during application of haemoglobin preparations. The present clinical study examines changes of haemodynamic and oxygen transport parameters during and after haemodilution with ultrapurified polymerized bovine haemoglobin (HBOC-201) in comparison to hydroxyethyl starch (HES). METHODS: After approval of the Ethics Committee, 12 patients (6 males and 6 females, mean age 59 +/- 10 years, ASA 1-2) undergoing elective liver resection were randomly allocated to receive either 3 ml.kg-1 6% HES 70,000/0.5 (group 1) or 0.4 g.kg-1 HBOC-201 (group 2) within 30 min following autologous blood donation of 1 l and substitution with 2 l Ringer's lactate. Measurements of blood gases, haemodynamics, and oxygen transport parameters were performed after induction of general anaesthesia, prior to and after blood donation, during and after infusion, at the beginning of surgery, and in the intensive care unit. RESULTS: Demographic characteristics did not differ between groups. In contrast to the HES group, mean arterial pressure increased by 18% over baseline measurements in group 2. While pulmonary vascular resistance showed a trend to higher values in group 2, systemic vascular resistance increased to a maximum of 42% over baseline in group 2 and was twice as high as in the HES group. The cardiac index was lower in the HBOC-201 group than in the HES group. During and after HBOC-201 infusion, mixed-venous oxygen saturation and content and calculated oxygen delivery were lower in group 2 in comparison to group 1, while the oxygen extraction ratio was higher in group 2. Free haemoglobin reached a maximal concentration of 1.0 +/- 0.2 g.dl-1 30 min after the HBOC-201 infusion was started, but was not detectable in urine over time. The mean intravascular half-life of HBOC-201 was 8.5 h. CONCLUSIONS: Patients did not show any severe complications during and after infusion of HBOC-201. However, vasoconstrictive side effects resulted in increased systemic but not pulmonary resistance. Ongoing studies with higher doses of HBOC-201 applied in a larger number of patients will probably reveal potential clinical consequences of the demonstrated haemodynamic changes.

Adult↗
PubMed1997

[Continuous spinal anesthesia vs. combined spinal-epidural anesthesia in emergency surgery. The combined spinal-epidural anesthesia technique does not offer an advantage of spinal anesthesia with a microcatheter].

UNLABELLED: In this prospective study we investigated the efficacy of microcatheter spinal anaesthesia in comparison with a combined spinal-epidural technique in trauma patients. METHODS: After institutional approval 60 patients undergoing urgent lower-limb surgery randomly received either CSA (22 G Sprotte needle, 28 G nylon catheter) in group 1 or CSE (18 G Tuohy needle, 22 G epidural catheter and 25 G pencil-point needle) in group 2. An initial subarachnoid bolus of 2 ml of plain bupivacaine 0.5% was injected in both groups. Difficulties with the lumbar puncture or catheter insertion, the time required for performance of either technique and the onset of analgesia at T12 were documented. If analgesia did not reach T12 within 20 min, supplemental bupivacaine was injected either intrathecally or epidurally up to a maximum of 5 ml in the CSA group or 16 ml in the CSE group. RESULTS: The number of lumbar punctures (CSA: n = 1.8 +/- 1.5; CSE: n = 2.6 +/- 1.8; P = 0.05) and the incidence of technical problems (CSA: 13%, CSE: 47%; P = 0.012) was higher in the CSE group. In contrast to CSA, performance of CSE was more time consuming (CSA: 8 +/- 3 min, CSE: 15 +/- 8 min; P = 0.0003), and the total dose of local anaesthetics was higher in the CSE group (CSA: 3.2 +/- 1 ml, CSE: 9.7 +/- 5 ml; P < 0.0001). CONCLUSIONS: Because of the higher incidence of technical problems, more time was required for the performance of CSE. As a consequence, microcatheter CSA might be preferred over CSE in trauma patients.

Aged↗
PubMed1997

A modified confocal laser scanning microscope allows fast ultraviolet ratio imaging of intracellular Ca2+ activity using Fura-2.

A confocal, ultraviolet laser scanning microscope (LSM) for reliable ratio measurements of localized intracellular Ca2+ gradients using the Ca2+-sensitive dye Fura-2 was developed. In a commercial LSM, the filter wheels for the excitation band-pass filters and the grey filters were replaced by acousto-optic tunable filters (AOTF) for rapid switching (</=1.5 micros) of the ultraviolet (351 and 364 nm) and the visible (457, 476, 488, 514 nm) excitation light. This enabled dual wavelength excitation of Fura-2, or 2'7'-biscarboxyethyl-5(6)-carboxyfluorescein (BCECF) for pH measurements. Changing to a transmitted-light detector of high sensitivity allowed for simultaneous recording of differential interference contrast images of the preparation with the excitation light. The AOTF fine control of the intensity of the excitation light and improvements in the emission detector sensitivity enabled the acquisition of up to 120 ratio pairs of high-quality images from a single cell. The optical capabilities and limitations of the instrument were evaluated with fluorescent beads and dye-loaded cultured cells. Agonist-induced intracellular Ca2+ transients in HT29 cells were recorded to test for the instrument's ability to measure changes in [Ca2+]i. Ratio z-sections from Fura-2-loaded cells showed an inhomogeneity of the Fura-2 loading with an accumulation of the dye mostly in the mitochondria. We show, as an example of the microscope's achievable resolution, the spatial and temporal heterogeneity of [Ca2+]i signals in mitochondria and the cytosol in response to agonist-evoked stimulation of HT29 cells. In addition, we show that the lipophilic, membrane-bound Fura-2 derivative Fura-C18, for measurements of near-membrane Ca2+ changes, can be used with this confocal microscope. This new LSM is expected to deepen our understanding of localized [Ca2+]i signals; for example, the nuclear Ca2+ signalling or the [Ca2+]i changes that occur during stimulation of ion secretion in polarized epithelial cells.

Calcium↗
PubMed1997

Bovine hemoglobin increases skeletal muscle oxygenation during 95% artificial arterial stenosis.

BACKGROUND: This study investigates the effect of a stroma-free ultrapurified bovine hemoglobin solution (HBOC) on skeletal muscle tissue oxygenation in comparison with hetastarch during nearly complete arterial stenosis. METHODS: Fourteen foxhounds were intravenously anesthetized and mechanically ventilated with 30% oxygen in air. Catheters were inserted into the right femoral artery and vein for measurements of hemodynamic parameters and blood gas sampling. Arterial blood flow of the left popliteal artery was measured by means of an electromagnetic flow probe. Skeletal muscle tissue oxygen tension (tpO2) was measured in the left gastrocnemius muscle by using a stepwise driven polarographic needle probe creating histograms from 200 single tpO2 measurements. After isovolemic hemodilution with Ringer's lactate solution to a hematocrit of 25%, a 95% artificial stenosis of the popliteal artery was established. The animals then randomly received two applications of either 50 ml HBOC (molecular weight, 32,000 to 500,000; hemoglobin, 13 +/- 1 gm/dl-1) or 200 ml 6% hetastarch 200,000/0.5. Variables were measured at baseline, after hemodilution, 30 minutes after stenosis, and 15 minutes after two applications of the respective compound. RESULTS: Demographic data, muscle temperature, and arterial blood gases did not differ between groups. With the exception of higher mean arterial and mean pulmonary artery pressures in HBOC-treated animals, hemodynamics did not differ between groups. In both groups oxygen delivery and oxygen consumption of the muscle decreased in parallel to the decreasing blood flow during arterial stenosis. In contrast, oxygen extraction ratio increased after infusion of HBOC and was higher after the second application when compared with hetastarch-treated animals (p < 0.05). During stenosis tpO2 was decreased in both groups when compared with baseline (p < 0.001). Mean tpO2 remained at decreased levels after administration of hetastarch but increased to nearly baseline values after HBOC treatment (p < 0.001). CONCLUSIONS: The data suggest that increased oxygen extraction in the HBOC group is associated with improved skeletal muscle tissue oxygenation during severe arterial stenosis.

Animals↗
PubMed1997

Inhibition of etoposide-induced apoptotic events by azide.

Azide is reported to be an inducer of necrotic rather than apoptotic cell death. Using various parameters of cell death, we demonstrate here that azide is capable of completely inhibiting apoptosis induced by VP-16/etoposide. Azide was found systematically to protect Jurkat cells against VP-16-induced effects as determined by an array of biochemical and morphological parameters. The cells were able partially to recover proliferative activity following removal of the drugs. We conclude that azide inhibits apoptosis induced by VP-16 at an early point in the apoptotic pathway and that inhibition of apoptosis might be the mechanism of necrosis-induction by azide.

Antineoplastic Agents, Phytogenic↗