Machine learning predictive performance evaluation of conventional and fuzzy radiomics in clinical cancer imaging cohorts.

BACKGROUND: Hybrid imaging became an instrumental part of medical imaging, particularly cancer imaging processes in clinical routine. To date, several radiomic and machine learning studies investigated the feasibility of in vivo tumor characterization with variable outcomes. This study aims to investigate the effect of recently proposed fuzzy radiomics and compare its predictive performance to conventional radiomics in cancer imaging cohorts. In addition, lesion vs. lesion+surrounding fuzzy and conventional radiomic analysis was conducted. METHODS: Previously published 11C Methionine (MET) positron emission tomography (PET) glioma, 18F-FDG PET/computed tomography (CT) lung, and 68GA-PSMA-11 PET/magneto-resonance imaging (MRI) prostate cancer retrospective cohorts were included in the analysis to predict their respective clinical endpoints. Four delineation methods including manually defined reference binary (Ref-B), its smoothed, fuzzified version (Ref-F), as well as extended binary (Ext-B) and its fuzzified version (Ext-F) were incorporated to extract imaging biomarker standardization initiative (IBSI)-conform radiomic features from each cohort. Machine learning for the four delineation approaches was performed utilizing a Monte Carlo cross-validation scheme to estimate the predictive performance of the four delineation methods. RESULTS: Reference fuzzy (Ref-F) delineation outperformed its binary delineation (Ref-B) counterpart in all cohorts within a volume range of 938-354987 mm3 with relative cross-validation area under the receiver operator characteristics curve (AUC) of +4.7-10.4. Compared to Ref-B, the highest AUC performance difference was observed by the Ref-F delineation in the glioma cohort (Ref-F: 0.74 vs. Ref-B: 0.70) and in the prostate cohort by Ref-F and Ext-F (Ref-F: 0.84, Ext-F: 0.86 vs. Ref-B: 0.80). In addition, fuzzy radiomics decreased feature redundancy by approx. 20%. CONCLUSIONS: Fuzzy radiomics has the potential to increase predictive performance particularly in small lesion sizes compared to conventional binary radiomics in PET. We hypothesize that this effect is due to the ability of fuzzy radiomics to model partial volume effects and delineation uncertainties at small lesion boundaries. In addition, we consider that the lower redundancy of fuzzy radiomic features supports the identification of imaging biomarkers in future studies. Future studies shall consider systematically analyzing lesions and their surroundings with fuzzy and binary radiomics.

Effect of early administration of tranexamic acid on ongoing haemorrhage in dogs with non-surgically treated haemoabdomen.

INTRODUCTION: Tranexamic acid (TXA) is an antifibrinolytic drug used for the prophylaxis and treatment of haemorrhage of various origin. This retrospective study investigated the effect of TXA on ongoing bleeding in dogs with nonsurgically treated haemoabdomen. The study population consisted of 48 dogs treated in the period 2009-2020 at the Small Animal Clinic of the Vetsuisse Faculty of Zurich. Twenty-eight of 48 dogs were treated with 20 mg/kg TXA IV within 3h of diagnosis of haemoabdomen. Dogs treated with and without TXA were monitored over 48 hours for signs of ongoing haemorrhage. Ongoing haemorrhage was defined as an increase in abdominal fluid accumulation, a decrease in haematocrit of >5% over time or need for surgical exploration after at least 12 hours of medical treatment. Transfusion requirements, cumulative amount of fluid therapy, heart rate, respiratory rate, temperature, systolic and mean arterial pressure, estimate of abdominal fluid identified by FAST analysis, venous haematocrit, abdominal haematocrit, serum albumin, serum lactate and thrombocyte count were extracted from patient records at 6, 12, 24 and 48 hours after diagnosis of haemoabdomen. Groups were comparable at presentation, however dogs of the TXA group showed a significantly lower abdominal haematocrit at presentation (37 vs 45%, P=0,034) and a higher fluid accumulation (P=0,019), both persisting over time. None of the outcome parameters for ongoing haemorrhage was significantly different between groups. Transfusion requirement was low and similar in both groups. Of interest, none of the 16 dogs undergoing thromboelastometry showed hyperfibrinolysis at presentation. We conclude that other mechanisms than antifibrinolytic therapy was responsible for cessation of bleeding in the majority of patients.

INTRODUCTION: L'acide tranexamique (TXA) est un médicament anti fibrinolytique utilisé pour la prophylaxie et le traitement des hémorragies d'origines diverses. Cette étude rétrospective a examiné l'effet du TXA sur les saignements en cours chez les chiens présentant un hémoabdomen traité sans chirurgie. La population étudiée était composée de 48 chiens traités entre 2009 et 2020 à la clinique pour petits animaux de la faculté Vetsuisse de Zurich. Vingt-huit des 48 chiens ont été traités avec 20 mg/kg de TXA IV dans les 3 heures suivant le diagnostic de l'hémoabdomen. Les chiens traités avec et sans TXA ont été surveillés pendant 48 heures pour détecter les signes d'hémorragie en cours. L'hémorragie en cours a été définie comme une augmentation de l'accumulation de liquide abdominal, une diminution de l'hématocrite de >5% dans le temps ou la nécessité d'une exploration chirurgicale après au moins 12 heures de traitement médical. Les besoins transfusionnels, la quantité cumulative de traitement liquidien, la fréquence cardiaque, la fréquence respiratoire, la température, la pression artérielle systolique et moyenne, l'estimation du liquide abdominal identifié par l'analyse FAST, l'hématocrite veineux, l'hématocrite abdominal, l'albumine sérique, le lactate sérique et la numération des thrombocytes ont été extraits des dossiers des patients à 6, 12, 24 et 48 heures après le diagnostic d'hémoabdomen. Les groupes étaient comparables à la présentation, mais les chiens du groupe TXA présentaient un hématocrite abdominal significativement plus faible à la présentation (37 vs 45 %, P=0,034) et une accumulation de liquide plus importante (P=0,019), ces deux phénomènes persistant dans le temps. Aucun des paramètres de résultat pour l'hémorragie en cours n'était significativement différent entre les groupes. Les besoins en transfusion étaient faibles et similaires dans les deux groupes. Il est intéressant de noter qu'aucun des 16 chiens soumis à la thromboélastométrie ne montrait d'hyperfibrinolyse à la présentation. Nous concluons que d'autres mécanismes que le traitement anti fibrinolytique étaient responsables de l'arrêt des saignements chez la majorité des patients.

Influence of fracture stability on Staphylococcus epidermidis and Staphylococcus aureus infection in a murine femoral fracture model.

Fracture-related infection (FRI) is a major complication in surgically fixed fractures. Instability of the fracture after fixation is considered a risk factor for infection; however, few experimental data are available confirming this belief. To study whether stable fractures led to higher infection clearance, mouse femoral osteotomies were fixed with either stable or unstable fixation and the surgical site was contaminated with either Staphylococcus epidermidis (S. epidermidis)or Staphylococcus aureus (S. aureus)clinical isolates. Infection progression was assessed at different time points by quantitative bacteriology, total cell counts in spleen and lymph node and histological analysis. Operated, non-inoculated mice were used as controls. Two inbred mouse strains (C57BL/6 and BALB/c) were included in the study to determine the influence of different host background in the outcome. Stable fixation allowed a higher proportion of C57BL/6 mice to clear S. epidermidis inoculation in comparison to unstable fixation. No difference associated with fixation type was observed for BALB/c mice. Inoculation with S. aureus resulted in a more severe infection for both stable and unstable fractures in both mouse strains; however, significant osteolysis around the screws rendered the stable group functionally unstable. Our results suggested that fracture stability could have an influence on S. epidermidis infection, although host factors also played a role. No differences were observed when using S. aureus, due to a more severe infection, leading to osteolysis and loss of stability in both groups. Further studies are required in order to address the biological features underlying the differences observed.

Femoral and sciatic nerve blockades and incision site infiltration in rabbits undergoing stifle joint arthrotomy.

This study was designed to determine whether perineural injections of local anaesthetics decreases intraoperative nociception and improves postoperative analgesia in New Zealand White rabbits undergoing experimental stifle arthrotomy. All animals were anaesthetized using isoflurane and received morphine intramuscularly. The sciatic and femoral nerves of the leg to be operated on were located using a nerve stimulator (1 Hz, 0.5 mA). Rabbits were assigned to a treatment group (LB; n = 12) or a placebo group (P; n = 12) in a randomized blinded fashion. Group LB received lidocaine 2% (1 mg/kg) combined with bupivacaine 0.5% (0.25 mg/kg) injections around the sciatic and femoral nerves (0.1 mL/kg total volume per site) and subcutaneous infiltration of the incision site with lidocaine 1% (1.25 mg/kg). Group P received the same volume of 0.9% NaCl. Rabbits in group P required higher doses of intraoperative fentanyl and propofol to reduce heart rate and suppress increase in systolic blood pressure, and maintain an adequate anaesthetic plane. Interventional analgesia (buprenorphine and carprofen) was required significantly earlier in rabbits in group P (2 and 6 h after the first nerve blockade, respectively) based on assessment of their pain-related behaviour and range of motion. Using a visual analogue scale (0 mm= no pain to 100 mm= maximal possible pain), rabbits in group LB were judged to show significantly less pain compared with rabbits in group P (14 ± 10 mm and 37 ± 25 mm, respectively) 2 h after nerve blockade. In conclusion, this technique of perineural analgesia combined with incision site infiltration reduced intraoperative fentanyl requirements and improved postoperative analgesia in rabbits.

Coherent Backscattering of Light Off One-Dimensional Atomic Strings.

We present the first experimental realization of coherent Bragg scattering off a one-dimensional system-two strings of atoms strongly coupled to a single photonic mode-realized by trapping atoms in the evanescent field of a tapered optical fiber, which also guides the probe light. We report nearly 12% power reflection from strings containing only about 1000 cesium atoms, an enhancement of 2 orders of magnitude compared to reflection from randomly positioned atoms. This result paves the road towards collective strong coupling in 1D atom-photon systems. Our approach also allows for a straightforward fiber connection between several distant 1D atomic crystals.

Short- and long-term effects of intensive training and motivational programme for continued physical activity in patients with inflammatory rheumatic diseases.

BACKGROUND: Despite the positive health effects of (intensive) exercise in patients with inflammatory rheumatic diseases, they are very often inactive. Motivational exercise interventions in other patient samples have shown good effects in promoting exercise behaviours. AIM: To evaluate the short- and long-term effects of an intensive exercise training programme in rheumatic patients with additional motivation for continued physical activity. DESIGN: Controlled prospective intervention study with repeated measures over 12 months. SETTING: Rheumatologic inpatient rehabilitation in two centres in Germany. POPULATION: Three-hundred-and-seven patients with chronic polyarthritis or spondyloarthritis. METHOD: The patients were assigned to a control group (CG, standard therapy, N.=156) or an intervention group (IG, motivation and intensive training, N.=151). Socio-demographic (age, gender, social background, employment) and health parameters (SF-36, HFAQ, HADS, pain, disease activity), exercise motivation, physical activity and costs of illness were assessed by questionnaires at baseline (t1), discharge (t2), and 12-months-follow-up (t5). Participants evaluated the rehabilitation programme at t2. RESULTS: At t2, IG-patients rated their rehabilitation better than CG-patients and reported higher exercise motivation. All patients had a better health status at t2 compared to t1. At t5, IG-patients reported more physical activity in everyday life. An unexpected lower physical component score (SF-36) of the IG compared to the CG lacked clinical relevance. No other variable showed significant group differences. Both CG- and IG-patients showed improvements in their health-related quality of life, pain, psychological well-being, sports activities, and exercise self-efficacy. CONCLUSION: The rehabilitation programme that included intensive training was perceived to be better than the conventional programme and the patients benefited more from the motivation intervention. Long-term improvements in all participants may be indicators of the positive effects of conventional rheumatic rehabilitation in Germany. Intensive training with motivation also improves physical activity and may have positive socio-economic effects. Future research needs to identify the most effective factors of the intervention and the patient groups that benefit most. CLINICAL REHABILITATION IMPACT: Intensive training with motivation is appropriate for patients with inflammatory rheumatic diseases aged up to at least 60 years and without severe health impairments. It enhances patients' exercise motivation and increases physical activity over at least 1 year.

The atopy patch test -- reproducibility and comparison of different evaluation methods.

BACKGROUND: There is still a lack of standardization of the atopy patch test (APT) in test procedures and evaluation methods. Our aim was to examine the reproducibility of APT results and to compare visual evaluation to chromametry and laser Doppler imaging. METHODS: Fifty-two volunteers with atopic eczema/dermatitis syndrome (AEDS) were included. The APT was performed on tape-stripped and unstripped test fields on their backs using cat dander, house dust mite and grass pollen allergens from two different suppliers. Responders were re-tested 4-12 weeks later with the same allergens on their forearms. RESULTS: Using Allergopharma allergens, 14 (26.9%) volunteers showed one or more positive reactions. The reproducibility rate was 56.3%. The Erlangen atopy score in APT-positive and negative volunteers was 19 +/- 6 vs 15 +/- 6. The test agreement in volunteers tested with both allergens, from Allergopharma and Stallergènes, was poor. Correlation of the results between the three evaluation methods was significant (P < or = 0.001). CONCLUSIONS: The low reproducibility rate of APT results and the poor inter-test-agreement using allergens from different suppliers show that much work remains to make the APT a reliable tool in identifying relevant aeroallergens that lead to flare ups of AEDS. Compared to chromametry and laser Doppler imaging, visual scoring was superior in differentiation between irritative and allergic reactions.

Inhibition of the renin-angiotensin system ameliorates genetically determined hyperinsulinemia.

This study was performed in order to assess the potentially different effects of the angiotensin-converting enzyme inhibitor captopril and of the angiotensin II receptor antagonist irbesartan on the metabolic syndrome in an animal model. Male NZO/BL6 F1 mice were treated with captopril, irbesartan, or placebo for 10 months: Control animals treated with placebo developed a metabolic syndrome with obesity (55.5+/-6.3 g), hypertension (146+/-10 mm Hg), hyperinsulinemia (7.2+/-5.7 ng/ml), hypercholesterolemia (5.1+/-0.7 mmol/l), cardiac hypertrophy (269+/-44 mg) and atherosclerotic plaques in the ascending aorta (3.6+/-1.5 microm(2)). Treatment with angiotensin-converting enzyme inhibitor or angiotensin II receptor antagonist significantly (p<0.001) reduces hypertension (73+/-5 and 78+/-11 mm Hg), cardiac hypertrophy (203+/-26 and 202+/-18 mg) and atherosclerosis (2.2+/-0.9 and 1.8+/-0.8 microm(2)). In addition, they prevented the development of obesity (42.2+/-3.5 and 38.3+/-2.8 g) and hyperinsulinemia (3.6+/-1.5 and 1.8+/-0.4 ng/ml). In conclusion, long-term treatment with an angiotensin-converting enzyme inhibitor or an angiotensin II receptor antagonist can ameliorate obesity and hyperinsulinemia in a genetically determined mouse model.

[Clinical effectiveness and tolerance of climbazole containing dandruff shampoo in patients with seborrheic scalp eczema]. / Klinische Wirksamkeit und Verträglichkeit eines Climbazol-haltigen Antischuppen-Shampoos bei Patienten mit seborrhoischem Kopfhautekzem.

Pityrosporum ovale appears to play an important role in the pathogenesis of dandruff as a symptom of seborrheic dermatitis. Climbazole is an antimycotic agent with a high in vitro and in vivo efficacy against P. ovale. In the presented work we investigated the efficacy and safety of a climbazole 0.65% shampoo on seborrheic dermatitis of 30 volunteers. Subjects were diagnosed as having moderate to severe seborrheic dermatitis of the scalp. After a 1-week washout and a 4-week treatment the clinical evaluation showed a successful reduction of dandruff, skin redness and itching in 80% of the volunteers and a mild improvement in 20% of the volunteers. The cosmetic acceptability was very good by the majority. It is concluded that the formulation tested is effective in the treatment of moderate to severe dandruff.

Effects of preventative footwear on foot pressure as determined by pedobarography in diabetic patients: a prospective study.

AIMS: This study analysed the effects of specially manufactured insoles on foot pressures in diabetic patients during a 1-year prospective observation period. METHODS: We studied 81 type 2 diabetic patients without foot lesions. Using pedobarography three different regions of interest were examined: maximum peak pressure (MPP) of the total foot area, heel region and head of metatarsal bone I-III. Eighteen patients with high risk pressure (MPP of total foot 474 +/- 183 kPa; heel region 278 +/- 147 kPa, metatarsal 389 +/- 222 kPa) received optimal insole support. Sixty-three patients as a control group (MMP of total foot 367.7 +/- 157 kPa; heel 263.1 +/- 127 kPa, metatarsal 339.9 +/- 171 kPa) received conventional footwear. RESULTS: After insole support a 30% pressure reduction of total foot MMP (474 +/- 183 kPa vs. 290 +/- 106 kPa) was achieved in the treatment group. After 6 months (324 +/- 127 kPa) and 1 year (380 +/- 190 kPa) a pressure reduction was found. Between the 6- and 12-month controls plantar pressures again increased. In the control group a significant increase of all peak pressures occurred. CONCLUSIONS: Early insole support is successful in reducing plantar pressure. A repeated adjustment should be performed every 6 months to prevent foot pressure increases. The comparison of foot pressure development between the two groups showed constant levels in the treatment group. In the control group a marked increase of the pressure values was found. Identification and subsequent support of patients with high ulceration risk may help to reduce the high amputation rate.

[Juxta-articular fibroid nodules and acrodermatitis chronica atrophicans in late stage Lyme borreliosis]. / Juxta-artikuläre fibroide Knoten und Acrodermatitis chronica atrophicans bei Lyme-Borreliose im Spätstadium.

A 60-years old female patient developed juxta-articular fibroid nodules and erythrocyanotic lesions of acrodermatitis chronica atrophicans after several tick bites. The woman was treated with ceftriaxon (Rocephin) 2 g daily parenterally without adverse reactions.

In vitro differentiation of endothelial cells from AC133-positive progenitor cells.

Recent findings support the hypothesis that the CD34(+)-cell population in bone marrow and peripheral blood contains hematopoietic and endothelial progenitor and stem cells. In this study, we report that human AC133(+) cells from granulocyte colony-stimulating factor-mobilized peripheral blood have the capacity to differentiate into endothelial cells (ECs). When cultured in the presence of vascular endothelial growth factor (VEGF) and the novel cytokine stem cell growth factor (SCGF), AC133(+) progenitors generate both adherent and proliferating nonadherent cells. Phenotypic analysis of the cells within the adherent population reveals that the majority display endothelial features, including the expression of KDR, Tie-2, Ulex europaeus agglutinin-1, and von Willebrand factor. Electron microscopic studies of these cells show structures compatible with Weibel-Palade bodies that are found exclusively in vascular endothelium. AC133-derived nonadherent cells give rise to both hematopoietic and endothelial colonies in semisolid medium. On transfer to fresh liquid culture with VEGF and SCGF, nonadherent cells again produce an adherent and a nonadherent population. In mice with severe combined immunodeficiency, AC133-derived cells form new blood vessels in vivo when injected subcutaneously together with A549 lung cancer cells. These data indicate that the AC133(+)-cell population consists of progenitor and stem cells not only with hematopoietic potential but also with the capacity to differentiate into ECs. Whether these hematopoietic and endothelial progenitors develop from a common precursor, the hemangioblast will be studied at the single-cell level.

[Determination of reference ranges and effect of maternal and fetal factors on insulin and C-peptide level in umbilical cord blood]. / Die Ermittlung von Referenzbereichen und der Einfluss von mütterlichen und kindlichen Faktoren auf Insulin- und C-Peptidspiegel im Nabelschnurblut.

OBJECTIVE: The risks of pregnancy caused by maternal diabetes are well known. Patients with unrecognized gestational diabetes mellitus (GDM) represent a special problem. The aim of our study was to find out, whether the determination of insulin and C-peptide in cord blood serum offers a valuable tool for retrospective analysis. MATERIAL AND METHODS: In 600 paired serum samples from maternal venous blood and neonatal cord blood insulin and C-peptide were determined radioimmunologically. A reference group consisting of 338 mothers and their newborns was established by exclusion of all patients with known pregnancy complications. RESULTS: Positive correlations could be identified between fetal insulin and fetal C-peptide, as well as correlations of these parameters with birth weight and body length, with maternal values of insulin, C-peptide, body-mass index, weight, and weight gain during pregnancy respectively. Increased levels of cord serum insulin were found in complicated pregnancies as well as in patients with previous pregnancy losses, preterm deliveries or stillbirths. CONCLUSIONS: Cord serum insulin and C-peptide were found to be useful parameters for immediate postnatal identification of impaired glucose tolerance during the course of pregnancy.

A contribution to safety assessment of veterinary drug residues: in vitro/ex vivo studies on the intestinal toxicity and transport of covalently bound residues.

1. The gastrointestinal fate of protein-bound residues of the model compound furazolidone (FZD) was investigated in vitro and ex vivo. Protein-bound residues were generated in rat liver microsomes, isolated by solvent extraction and digested with 0.5% hydrochloric acid and Pronase E. 2. During digestion, 3-amino-2-oxazolidinone (AOZ), the side chain of furazolidone, was partly released from bound residues. 3. The absorption of free AOZ and digested protein-bound residues was tested in isolated perfused rat gut segments (IPGS) and in the intestinal cell line Caco-2. Free AOZ was transfered both in the IPGS model and in Caco-2 monolayer cultures, while no indications for passage of bound residues were obtained. 4. No acute toxicity of AOZ or digested food residues respectively was observed in gut segments and Caco-2 cells at concentrations that were substantially above maximum residue levels to be expected in food of animal origin after administration of therapeutic doses. 5. The results demonstrate that digestive processes can alter the chemical nature of drug residues and yield degradation products that may be bioavailable for the consumer. Thus, the covalent binding of xenobiotics to macromolecular tissue constituents cannot necessarily be regarded as an irreversible endpoint of residue bioavailability and toxicity.

Transplantation of transduced nonhuman primate CD34+ cells using a gibbon ape leukemia virus vector: restricted expression of the gibbon ape leukemia virus receptor to a subset of CD34+ cells.

The transduction efficiencies of immunoselected rhesus macaque (Macaca mulatta) CD34+ cells and colony-forming progenitor cells based on polymerase chain reaction (PCR) analysis were comparable for an amphotropic Moloney murine leukemia virus (MLV) retroviral vector and a retroviral vector derived from the gibbon ape leukemia virus (GaLV) packaging cell line, PG13. On performing autologous transplantation studies using immunoselected CD34+ cells transduced with the GaLV envelope (env) retroviral vector, less than 1% of peripheral blood (PB) contained provirus. This was true whether bone marrow (BM) or cytokine-mobilized PB immunoselected CD34+ cells were reinfused. This level of marking was evident in two animals whose platelet counts never fell below 50,000/microliter and whose leukocyte counts had recovered by days 8 and 10 after having received 1.7 x 10(7) or greater of cytokine-mobilized CD34+ PB cells/kg. Reverse transcriptase(RT)-PCR analysis of CD34+ subsets for both the GaLV and amphotropic receptor were performed. The expression of the GaLV receptor was determined to be restricted to CD34+ Thy-1+ cells, and both CD34+ CD38+ and CD34+ CD38dim cells, while the amphotropic receptor was present on all CD34+ cell subsets examined. Our findings suggest that, in rhesus macaques, PG13-derived retroviral vectors may only be able to transduce a subset of CD34+ cells as only CD34+ Thy-1+ cells express the GaLV receptor.

[Legal determinations concerning narcotics which are important for the veterinarian]. / Für den Tierarzt wichtige betäubungsmittelrechtliche Bestimmungen.

In January 1998 the German legislation of narcotic drugs was subject of important changes also concerning the use of narcotic drugs in veterinary practice. The annexes I-III of the law of narcotic drugs (BtMG) containing all substances classified as narcotics were reorganized. Furthermore, the directive on the prescription of narcotic drugs (BtMVV) was changed with the aim to facilitate the prescription as well as the supply of narcotic drugs by veterinarians in their home dispensary. The directive on inland trade of narcotics (BtMBinHV) regulating the distribution of narcotic drugs from wholesalers to veterinarians remained unchanged. The following regulations of prescription or distribution of narcotic drugs by veterinarians for treated animals are described in detail: notification of participation on supply of narcotic drugs, general principles of the use of narcotic drugs, safety measurements, inactivation of narcotics, prescription for patients or for use in veterinary practice/clinics, details of prescription, supply to animal owners by the veterinarian home-dispensary, book-keeping, purchase of narcotic drugs.

Inward rectifier K+ channel from human heart and brain: cloning and stable expression in a human cell line.

We have cloned the human homologue of the inward rectifier K+ channel from both heart and brain tissue (HHBIRK1). The human clones were identical to each other in their coding regions and were highly homologous to the mouse macrophage (IRK1) channel. The inward rectifier currents from human and mouse clones were characterized using a novel strategy for stable ion channel expression in a human cell line. The permeability of the expressed inwardly rectifying channels was greater for K+ than for Rb+, whereas no current was observed when K+ was replaced by Na+. A prominent time- and voltage-dependent block was observed in the presence of Ba2+, whereas a small decay in the steady-state current was observed with millimolar concentrations of Na+. Single-channel conductances of 49.1 +/- 3.3 pS (n = 6) and 40.2 +/- 2.5 pS (n = 3) (P = 0.005) were obtained for the HHBIRK1 and IRK1 clones, respectively. These results indicate that sequence dissimilarities between human and mouse inward rectifier K+ channels may have significant functional consequences.

Lipoproteins and hydrolysis of organophosphorus compounds.

Paraoxonase of human and animal sera was shown to be a structural part of high density lipoproteins (HDL) by immunoprecipitation, heparin- or polyethyleneglycol fractionation, ultracentrifugation and gel chromatography. Frequency distribution of paraoxonase activity in human sera is trimodal. Human individuals, with respect to paraoxon detoxication, can be distinguished into low and high detoxicators using ratios of phenylacetate and paraoxon hydrolysis as well as activation with ethanolamine and sodium chloride. With conversion of alpha-lipoprotein subtype HDL3 to HDL2, specific activities of paraoxonase and arylesterase are increasing about 3.5-fold in low detoxicator individuals and 1.9-fold in high detoxicators, indicating that more than 90% of HDL2 particle-bound paraoxonase and arylesterase activity are incorporated during the HDL conversion process. HDL cholesterol concentrations in individual sera were shown to be positively correlated to both serum paraoxonase and arylesterase activities.