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Biomedical subjects

C Werner

Publications and source records attributed to C Werner.

At least 235 records · Page 13Linked to original sources

Auxotrophic mutants of the yeast Trichosporon adeninovorans.

We have isolated and characterized auxotrophic mutants of Trichosporon adeninovorans, strain PAR-4 to get genetic markers that cover the entire nuclear genome of this thermotolerant yeast of technological interest. The nitrosoguanidine mutagenesis yielded mutants at a high frequency. We detected a broad spectrum of auxotrophic phenotypes in the random mutant samples. Obviously, strain PAR-4 is a haploid or hyperhaploid yeast. In correspondence we determined a low DNA content per cell. In contrast to NG1), UV light was an inefficient mutagen. UV survival curves were without the typical shoulder indicating suppression of repair of UV-induced lethal lesions. Thus, the response of PAR-4 to UV was different from those of Saccharomyces cerevisiae and other yeasts.

Dose-Response Relationship, Radiation↗

Differential recognition of two cloned Brugia malayi antigens by antibody class.

The humoral and cellular immune response to filarial parasites is complex. Numerous studies have shown that antibodies to a large number of protein and non-protein antigens may be produced over the course of infection and that immune recognition of any given antigen may vary by disease manifestation and by immunoglobulin class. We have used the techniques of molecular cloning to attempt to dissect this complex interaction, and describe here two clones, isolated from an expression library constructed from Brugia malayi genomic DNA, whose products are recognized by distinct immunoglobulin classes. A lambda gt11 fusion protein containing part of the B. malayi myosin tail region is recognized by antibodies of the IgG class from a high percentage of bancroftian filariasis patients. A fusion protein containing a collagen-like sequence is less frequently and weakly recognized under the same experimental conditions, but is almost universally recognized when the developing reagent is specific for IgE. We thus identify specific filarial proteins against which the infected human host responds preferentially with antibodies of a specific immunoglobulin class.

Adolescent↗

[Increase in blood flow velocity in the middle cerebral artery following low-dose ketamine].

Low-dose ketamine is recommended in patients requiring sufficient analgetic support in emergency situations. There is still controversy in the discussion on ketamine-induced effects on cerebral blood flow and intracranial pressure. We investigated the effect of 0.25 mg x kg-1 ketamine i.v. on the blood flow velocity in the basal cerebral arteries in 10 healthy volunteers by transcranial Doppler sonography (TCD). Peak and mean blood flow velocities, pulsatility index, arterial blood pressure, heart rate, oxygen saturation and end tidal carbon dioxide tension were measured during the study. There was a significant increase in the hemodynamic parameters and in blood flow velocities, paralleled by a decrease in pulsatility index and constant values for oxygen saturation and CO2-tensions following injection of ketamine. The results indicate a transient stimulation of the cardiocirculatory system with a concomitant reduction of the cerebral vascular resistance. The question of informative detection of intracranial hemodynamics following application of intravenous anesthetics will be discussed.

Adult↗

[Pulse oximetry in surgery of the bronchial system].

Oxygen saturation was determined by pulse oximetry in 35 children and adults during general anaesthesia using jet- or manually assisted ventilation for minor elective laryngeal and tracheo-bronchial surgery. The method is non-invasive and provides continuous information about the arterial oxygen saturation (saO2) and heart rate. Compromised arterial oxygenation during anaesthesia and the effects and brief ventilatory arrest are accurately detectable. Data such as pO2, pCO2 or pH cannot be assessed by pulse oximetry; carbon monoxide and methemoglobinaemia may lead to less accurate results. Pulse oximetry provides on-line information about sudden hypoxic events and allows early therapeutic intervention because arterial desaturation precedes the clinical signs and symptoms of hypoxia.

Anesthesia, General↗

Contribution of the trabecular component to mechanical strength and bone mineral content of the femoral neck. An experimental study on cadaver bones.

Both proximal femora from 10 females were acquired at autopsy. The trabecular component of the femoral neck of one specimen from each pair was evacuated, while the contralateral specimen was left intact as a reference. Bone mineral content (BMC) of the femoral neck, demonstrated only a slight (mean 4.8%) individual side to side variation. After evacuation of the trabecular component, BMC was reduced with mean 23.5%. Mechanical strength of the specimens, determined by applying a force to the femoral head perpendicularly to the axis of the femoral shaft, was reduced by mean 39.5%. Correlation between BMC and fracture strength was poor. There was no correlation between reduction in BMC and reduction in mechanical strength after evacuation, indicating that bone fracture strength is influenced by factors other than the mineral content.

Aged↗

Congenital anaplastic astrocytoma with favorable prognosis. Case report.

A large intracranial tumor that caused macrocrania leading to dystocia was demonstrated by prenatal ultrasound examination. After birth, computerized tomography (CT) confirmed the presence of a giant supratentorial tumor with a large cyst. When the infant was 20 days old, the tumor was radically extirpated. Neuropathological examination revealed an astrocytoma with focal signs of anaplasia showing a macrocyst as well as multiple microcysts resulting from hemorrhages into the tumor. Although no adjuvant radio- or chemotherapy was administered, the child had nearly normal psychomotor development without clinical or CT evidence of tumor recurrence, and is now 3 years old.

Astrocytoma↗

[The electroencephalogram and somatosensory evoked potentials following intravenous administration of 0.5 mg/Kg ketamine].

UNLABELLED: Because of its analgesic potency without affecting consciousness, low-dose ketamine (0.5 mg/kg) has been advocated for traumatized patients in order to ensure the possibility of neurological assessment. This study describes the effects of 0.5 mg/kg ketamine on spontaneous and evoked brain electrical activity. METHODS: Nine unpremedicated, healthy volunteers aged 22-35 years and free of CNS-active drugs took part in the study. The EEG was recorded from C3P3, C4P4, and vertex versus linked earlobes (Cz/A1-A2) (bandpass: 1-45 Hz). For artefact control the electro-oculogram (EOG) was recorded from supra- and infraorbital electrodes with the same filter settings. EEG and EOG were stored on magnetic tape and were digitized off-line (sampling rate: 100/s) followed by Fourier transformation (epoch-length: 5.2 s). Somatosensory evoked potentials (SEP) were elicited by constant current pulses at the median nerve near the wrist. Recording sites were at the cervical spine (Cv6), the ipsi- and contralateral somatosensory projection area, and the vertex (Cz) vs a frontal reference (Fz). Bandpass: 10-2000 Hz, stimulation frequency: 4 Hz, twofold motor threshold, analysis time: 100 ms. Electrocardiogram, blood pressure, and arterial oxygen saturation (pulse oximeter) were monitored continuously. After an adaptation session of 30-45 min, 0.5 mg ketamine was administered intravenously. EEG and SEP were recorded for the following 45-60 min. Data were subjected to analysis of variance (ANOVA) and Scheffé-test if appropriate (P less than or equal to 0.05). RESULTS: All subjects lost consciousness within 45-110 s (mean: 70 s) after administration of ketamine. Mean blood pressure levels increased by about 20% and heart rate by about 10% after 5-10 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Evidence for the involvement of a reperfusion injury in galactosamine/endotoxin-induced hepatitis in mice.

Simultaneous intraperitoneal administration of 700 mg/kg galactosamine and 33 micrograms/kg Salmonella abortus equi endotoxin to male NMRI albino mice resulted in fulminant hepatitis as assessed after nine hours by measurement of serum transaminases as well as sorbitol dehydrogenase activities. Intraperitoneal pretreatment of animals with 2 X 100 mg/kg allopurinol, or intravenous pretreatment with 33 kU superoxide dismutase or 1 MU catalase fully prevented hepatitis. Administration of 10 micrograms/kg of the prostacyclin analogue iloprost antagonized liver injury when given simultaneously with galactosamine/endotoxin but did not protect when given 90 min later. Tocopherol or desferal pretreatment of the animals had no significant protective effect. Together with our recent finding that hepatic leukotriene D4 production is likely to be responsible for galactosamine/endotoxin-induced hepatitis we interpret these results as evidence for a leukotriene-induced hepatic ischemia followed by a reperfusion syndrome.

Allopurinol↗

Disposition and hepatoprotection by phosphatidyl choline liposomes in mouse liver.

Small unilamellar liposomes with an average diameter of 80 nm were prepared from phosphatidyl choline of various sources using the dialysis method with cholate as a detergent. When 14C-labeled soybean liposomes were intravenously injected into male NMRI mice, up to 10% of the total label was found in the liver lipid. The uptake was dose-dependent and reached an apparent saturation 4 h after injection. The liver maintained a constant radioactivity corresponding to 1.9 +/- 0.13 mg phospholipid/g liver until ten hours after injection of 850 mg labeled phosphatidyl choline/kg body wt. Little radioactivity was taken up by the spleen. Analogous doses of liposomes prepared from egg yolk phosphatidyl choline led to a radioactivity corresponding to 1.3 +/- 0.4 mg lipid/g liver 4 h after injection. Liposomes with a similar size were prepared from hydrated, i.e., saturated phosphatidyl choline. After intravenous administration of these liposomes, an amount of 5.3 +/- 0.5 mg labeled lipid was found per g liver after 4 h. In contrast to unsaturated liposomes, 5.8 +/- 0.8 mg lipid per gram spleen was trapped by the spleen. The pharmacodynamic effect of these different liposomes was studied in benzo[a]pyrene-pretreated mice intoxicated with 400 mg/kg paracetamol. Animals which received paracetamol exhibited serum alanine aminotransferase activities of 4220 +/- 1140 units/l after 4 h and exhaled 120 +/- 19 nmol ethane kg-1 h-1. When pretreated with 850 mg soybean phosphatidyl choline/kg body wt. (i.v.) 2 h prior to paracetamol, the increase in serum transaminase activity was reduced to 117 +/- 104 units/l and ethane exhalation amounted to 18 +/- 8 nmol kg-1 h-1. In contrast, similar pretreatment with egg yolk phosphatidyl choline or hydrated phosphatidyl choline failed to protect against paracetamol-induced hepatotoxicity. The different pharmacodynamic effects of the two phosphatidyl cholines of plant or animal origin cannot be explained on the basis of their different pharmacokinetics. In the case of soybean phosphatidyl choline liposomes, the amount of radioactive lipid found in the liver correlated with the hepatoprotective potency.

Acetaminophen↗

Acute and long-term alterations in the granulocyte/macrophage progenitor cell (GM-CFC) compartment of dogs after partial-body irradiation: irradiation of the upper body with a single myeloablative dose.

The acute and long-term effects of a single dose of partial-body irradiation on the granulocyte/macrophage progenitor cell compartment were studied in dogs. A myeloablative dose of 11.7 Gy (dose rate 6.5 cGy/min) was given to the upper body which contains approximately 70% of the total bone marrow mass. The lower part of the body (pelvis, lower extremities and tail) was shielded by a lead box. In the non-irradiated bone marrow, the concentration of the GM-CFC/10(5) mononuclear cells was slightly decreased within the first 7 days and showed some fluctuations around the normal value for several weeks thereafter. In the irradiated bone marrow, virtually no GM-CFC could be detected on day 1 after exposure. Beginning on day 7, a continuous increase took place up to day 21 when the GM-CFC concentration reached between 25% (sternum) and 43% (humerus) of the initial value. No further increase took place up to day 80. Between day 120 and 380 a secondary increase was observed which reached near-normal bone marrow GM-CFC concentrations. The blood GM-CFC concentration first showed a strong depression followed by a transient increase between day 10 and 30. This coincided with GM-CFC normalization in the protected bone marrow as well as with the initial phase of regeneration in the irradiated sites. A prolonged secondary long-lasting depression between day 33 and 120 amounted to 20 to 50% of normal values. This depression was closely related to the stagnation in the GM-CFC recovery in the irradiated bone marrow sites. The GM-CFC concentration in the blood was found to be supranormal at day 380 when the bone marrow GM-CFC had recovered. The colony stimulating activity in the serum showed an increase within the first 20 days after exposure, that is, within the same interval the bone marrow GM-CFC concentration experienced the strongest alterations, and was inversely related to the changes in the blood granulocyte values.

Animals↗

Bacteremia following transurethral instrumentation. The predictive value of a serum bactericidal activity test.

The bacteremic rate following transurethral instrumentation and the possibility of a serum bactericidal activity test to predict which patients that were at an increased risk of developing bacteremia was evaluated. Of 33 investigated patients, all elderly men, 14 underwent transurethral prostatic resection, 14 cystoscopy and 5 urethrotomy. None of the patients received prophylactic antibiotic treatment. The majority (97%) of the patients had bacteria isolated from the urinary tract before the instrumentation. Gram-positive cocci accounted for about two thirds (64%) and Gram-negative rods for about one third (31%) of all isolates. The most frequent species isolated were coagulase negative staphylococci (29%), Streptococcus faecalis (19%) and Klebsiella pneumoniae (12%). The bacteremic rate was 21%. None of the patients developed septicemia. Forty-four per cent of the patients with greater than or equal to 10(5) colony forming units/ml (cfu/ml) in urine developed bacteremia compared with 8% in patients with a sterile urine or less than 10(5) cfu/ml in urine (p less than 0.05). The urethral/prostatic flora was the source of bacteremia in at least one patient. Eighty-one per cent of the isolated strains were serum resistant. About half (54%) of the Gram-negative rods were more or less sensitive against actual, fresh patient serum. All Gram-positive cocci were resistant. There was no difference in the serum sensitivity between bacteria isolated from bacteremic patients and non-bacteremic patients. In conclusion, this study confirmed the relative high risk of developing bacteremia following transurethral instrumentation, especially if the urine is infected.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Fetal liver transplantation in the dog. II. Repopulation of the granulocyte-macrophage progenitor cell compartment by fetal liver cells from DLA-identical siblings.

The restoration of the granulocyte-macrophage progenitor cell (CFU-GM) compartments in blood and bone marrow, and the recovery of blood monocytes were followed for up to one year in ten beagles that had been exposed to fractionated (3 X 6 Gy) total-body irradiation before being transfused with cryopreserved fetal liver cells (FLC) from sibling donors that were genotypically matched for dog leukocyte antigens. Grafts contained 0.2-1.6 X 10(8) mononuclear cells and 0.9-19.8 X 10(4) CFU-GM/kg body weight. Numbers of circulating monocytes rose parallel to granulocyte numbers after day 6 and became normal by day 18 posttransplant. In bone marrow aspirates, low numbers of CFU-GM were detected on day 3 and their incidence per 10(5) mononuclear cells was normal after day 14. Circulating CFU-GM were present in significant numbers by day 7 and their elevated concentration per milliliter of blood after day 14 continued for one year. Dextran sulfate injection mobilized normal numbers of CFU-GM into the blood early after transplantation, and spontaneously circulating CFU-GM in a later phase did not differ from blood progenitors of normal animals with respect to radiation sensitivity and sedimentation velocity. Thus, FLC transplantation effected a rapid restoration of granulopoiesis and monocytopoiesis, which was reflected at both the level of mature blood cells and the compartments of CFU-GM in blood and bone marrow, underlining the high repopulating capacity of fetal liver stem cells.

Animals↗

Fetal liver transplantation in the dog. I. Restoration of hemopoiesis with cryopreserved fetal liver cells from DLA-identical siblings.

Fetal liver cells (FLC) were obtained from beagle fetuses 52 days postconception, and were cryopreserved prior to transplantation into ten sibling recipients that had previously been exposed to total-body irradiation delivered in 3 fractions of 6 Gy each at 4 days, 2 days, and 2 hr before grafting. Donors and hosts were genotypically identical for dog leukocyte antigens (DLA)-A, B, and D. A rapid and lasting engraftment was achieved in all animals following the transfer of 0.2 X 10(8) to 1.6 X 10(8) mononuclear FLC/kg body weight, which were equivalent to 0.9 X 10(4) to 19.8 X 10(4) granulocyte/macrophage progenitor cells (CFU-GM)/kg. Between days 14 and 20 posttransplant pretreatment levels were detected for blood granulocytes, between days 23 and 28 for circulating platelets, and between days 35 and 40 for the erythrocyte count and hemoglobin concentration. Increasing the number of CFU-GM transfused resulted in an accelerated granulocyte and platelet recovery. Bone marrow cells were of donor origin throughout the observation interval, but declining proportions of host lymphocytes circulated in the peripheral blood during the initial recovery phase. In two dogs, skin alterations that might indicate slight graft-versus-host disease (GVHD) were noted following days 20 and 70, respectively. Six recipients had to be sacrificed due to inanition, probably secondary to radiation-induced pancreatic insufficiency two to three months after grafting. The results of this study indicate that cryopreserved FLC are highly effective in restoring hemopoiesis in DLA-compatible sibling dogs. Transplantation of canine FLC may prove valuable in analyzing mechanisms pathogenetically related to graft rejection or to the development of GVHD following the transfer of T-cell-depleted hemopoietic grafts at a preclinical stage.

Animals↗

Hemopoiesis and immune functions in dogs following fetal liver transplantation.

Ten beagles were exposed to total body X-irradiation (3 X 6 Gy) and rescued with cryopreserved fetal liver cells from DLA-identical siblings obtained around the 52nd day of gestation. Grafts contained 0.2-1.6 X 10(8) mononuclear cells/kg and 0.9-19.8 X 10(4) granulocyte-macrophage progenitor cells/kg. Hemopoiesis and immune functions were followed for up to one year after fetal liver transplantation (FLT). There was a prompt engraftment in all recipients. Bone marrow metaphases were always of donor origin, whereas some host lymphocytes circulated for 2-3 months. Blood granulocytes and monocytes rose to pre-treatment levels within 2-3 weeks of FLT and platelets and erythrocytes were normal within 3-4 and 5-6 weeks, respectively. The relative incidence of bone marrow CFU-GM was normal by day 14 and the absolute numbers of circulating CFU-GM remained elevated for one year after day 14. Blood lymphocytes reached control numbers between days 35 and 101 with a faster B cell than T cell recovery. Their response to mitogen stimulation was normal by day 75, while the mixed lymphocyte reaction tended to be reduced for one year. Serum levels of IgM (day 35) and IgG (day 49) recovered earlier than IgA levels (day 270). Thus, cryopreserved canine fetal liver cells can restore hemopoiesis and immunocompetence with considerable rapidity in histocompatible, adult siblings pre-treated with total body irradiation, and, since they lack mature T cells, may be used to analyze effector mechanisms that mediate rejection of T cell-depleted allografts under less favourable conditions.

Animals↗