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Biomedical subjects

W Luck

Publications and source records attributed to W Luck.

At least 37 records · Page 2Linked to original sources
PubMed1995

Determinants of cord-blood IgE concentrations in 6401 German neonates.

For screening atopy risk in 6401 (84%) of all infants born during the year 1990 in six obstetric departments of five German cities, cord-blood IgE values were determined with CAP-RAST-FEIA. After cases with elevated IgA values had been excluded, 25% of the values were above the detection limit of 0.35 kU/l, and 8.5% were above 0.9 kU/l. Boys had significantly higher values than girls (P < 0.001). The distribution of values was significantly different for different nationalities of mothers (P < 0.001). The percentage of elevated values (> 0.9 kU/l) increased significantly with the number of close family members with atopic history (P < 0.001). Regarding the atopic history of the father, siblings, and mother separately, only the mother's history had a significant association with the cord-blood IgE class (P < 0.001). The IgE values of 81 twin pairs correlated significantly with a coefficient of r = 0.4909 (P < 0.001). The smoking history of the parents during pregnancy showed an association with cord-blood IgE values (P < 0.02). No significant association could be shown between cord-blood IgE distribution and other variables, i.e., gestational age, birth size, birth modus, Apgar score, cord-blood pH value, neonatal problems, parity, age of the mother, medication during pregnancy, educational level of mother or father, time of year, or obstetric department. It is hypothesized that, in addition to some postpartum contamination or placental transfer of maternal IgE, cord-blood IgE values are also determined by the fetal immunologic reaction to intrauterine exposure to allergens and trigger factors, and by genetic influences.

Adrenal Cortex Hormones↗
PubMed1994

Serum vitamin B12 and transcobalamin levels in early HIV disease.

A cohort of asymptomatic human immunodeficiency virus (HIV) seropositive patients was followed over a 2 1/2-year period, to establish changes in serum vitamin B12 (B12) concentrations. Serum B12, CD4 count, and clinical progression to acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) were measured. The unsaturated B12 binding capacities of the transcobalamins were also determined at the start of the study and compared to those from a homosexual HIV seronegative control group. The geometric mean of serum B12 in 218 asymptomatic HIV seropositive patients was significantly lower than of a homosexual HIV seronegative control group (P = 0.02) and the unsaturated B12 binding capacities of transcobalamins I and II were significantly higher in the asymptomatic patients compared with the same control group (P < 0.03, P < 0.0001, respectively). Fifty-nine of the asymptomatic HIV seropositive patients were followed over a 2 1/2-year period during which most had falling serum B12 levels (64%). Twelve patients progressed clinically to ARC or AIDS, of which nine had repeat serum B12 estimation prior to progression. All nine patients had or developed falling serum B12 levels without any evidence of an HIV-related bowel disorder. All patients progressing had falling CD4 counts. Subnormal serum B12 levels are common in HIV disease and occur at an early stage. B12 levels fall in most patients with time and may help predict those patients whose disease will progress the most rapidly.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Influence of glycosphingolipids on the release of histamine and sulfidopeptide leukotrienes from human basophils.

Glycosphingolipids (GSLs) are physiological membrane components known to modulate various cellular functions. In order to study their influence on basophil mediator release washed leukocytes obtained from allergic asthmatics and nonatopics were preincubated with varying concentrations of different GSLs. Cells were washed and stimulated with anti-IgE, allergen, and calcium ionophore A23187. None of the GSLs induced mediator release by itself. Preincubation with the acidic gangliosides GM2, GM3, and GD1a significantly enhanced the release of both mediators when stimulated with anti-IgE or allergen but not with calcium ionophore A23187. Highest enhancement was seen with ganglioside GM2. Mediator release was higher in asthmatics than in nonatopics. The acidic galactosylceramide-sulfate (sulfatide) showed a significantly enhanced mediator release as well, whereas the neutral GSLs lactosyl ceramide and asialo GM2 did not influence mediator release. It is concluded that IgE receptor-dependent mediator release could be modulated by acidic GSLs.

Adult↗
PubMed1993

Increased cerebral blood flow velocities in newborn infants of smoking mothers.

Cerebral blood flow velocities (CBFV) were measured by the pulsed Doppler method in 41 infants of smoking mothers and in 59 apparently healthy control infants. Although gestational age, birth weight, and systolic blood pressure were lower in infants exposed to tobacco smoke prenatally, systolic (65 +/- 11 vs. 47 +/- 12 cm/s, mean +/- SD; P < 0.001), mean (36 +/- 6 vs. 25 +/- 6 cm/s; P < 0.001), and diastolic (17 +/- 4 vs 13 +/- 4 cm/s; P < 0.001) CBFVs in the anterior cerebral artery were significantly higher when compared to control infants. Similar differences were seen in the internal carotid and in the basilar arteries. Multiple regression analysis did not reveal differences other than maternal smoking to explain these observations. We conclude that prenatal tobacco smoke exposure is related to increased CBFVs in newborn infants. Further studies should determine whether this relation is not only statistical but causal and whether increased CBFVs are an indicator of prolonged effects of prenatal tobacco smoke exposure.

Birth Weight↗
PubMed1990

Identification and characterization of cysteinyl-leukotriene formation in tissue slices from human intracranial tumors: evidence for their biosynthesis under in vivo conditions.

In previous studies, it had been shown that human gray and white matter tissue slices have the capacity to synthesize large amounts of cysteinyl-leukotrienes (cysteinyl-LT) in vitro. This study was initiated to investigate cysteinyl-LT formation by tissue slices from intracranial tumors in comparison with cyclooxygenase products such as prostaglandin (PG) F2 alpha and thromboxane (TX) B2. Tissue slices from meningiomas and astrocytomas were found to release large amounts of cysteinyl-LT spontaneously and even higher amounts after ionophore A 23187 stimulation, which could not be accounted for by blood possibly remaining in the tissue slices. Cysteinyl-LT were identified by their immunoreactive characteristics, their biological activity in the guinea pig ileum bioassay, and their retention time on reversed-phase HPLC. With increasing malignancy, astrocytomas were shown to have an increasing biosynthetic capacity for cysteinyl-LT and TXB2 in vitro. In comparison with meningioma patients, malignant astrocytoma patients had an enhanced urinary excretion of LTE4, the major urinary metabolite of cysteinyl-LT in humans, which dropped in level within 7 days after operation by 79%. A correlation exists between the in vivo cysteinyl-LT production in patients with malignant astrocytomas and that observed under basal conditions in the tissue slices in vitro. The results provide evidence that in malignant astrocytoma patients, the tumor tissue produces large amounts of cysteinyl-LT, which may be detected in the patients' urine.

Astrocytoma↗
PubMed1989

Clotting of whole human blood induces cysteinyl-leukotriene formation.

Using radioimmunoassay techniques we studied the formation of the 5-lipoxygenase-derived cysteinyl-leukotrienes (LT) in comparison to the cyclooxygenase product thromboxane (TX) B2 in whole human blood allowed to clot at 37 degrees C in vitro. Spontaneous clotting resulted in a time-dependent release of smaller amounts of cysteinyl-LT as well as release of large amounts of TXB2 into the serum. Cysteinyl-LT were characterized by their immunoreactive behaviour and their biological activity in the guinea pig ileum bioassay, an effect which could be antagonized by the SRS-A antagonist FPL 55712 (0.38 microM). By reversed phase HPLC cysteinyl-LT in the serum were identified as a mixture of LTC4, LTD4 and LTE4. At 90 and 120 min part of the immunoreactive material consisted of the omega-oxidized metabolite 20-OH-LTE4. Almost complete inhibition of cyclooxygenase activity by indomethacin (2.8 microM) did not affect cysteinyl-LT formation by clotting whole human blood in vitro nor did activation of platelets by compounds such as the TX mimetic U 46619 (10 microM), platelet-activating factor (PAF, 1 microM) or thrombin (3 IU/ml). In contrast, the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA, 10 microM), the Ca2+-chelating anticoagulants trisodium citrate (10 microM) and edetate disodium (EDTA, 5.4 mM) as well as the functionally unrelated heparin (20 IU/ml) significantly inhibited the formation of cysteinyl-LT as well as of TXB2. Thus, an event related to the process of clotting of whole human blood appears to be able to induce cysteinyl-LT formation in amounts which might be functionally relevant during thromboembolic events.

Adult↗
PubMed1989

H1-antihistamines and calmodulin antagonists inhibit the ionophore A23187-induced eicosanoid formation by human leukocytes.

The effects of the H1-antihistamines astemizole, oxatomide and pyrilamine, of the calmodulin antagonists trifluoperazine and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), on the ionophore A23187 (5 mumol/l)-induced release of cysteinyl-leukotrienes (LT) and thromboxane (TX) B2 from mixed human leukocytes were investigated in comparison to those of the cyclooxygenase inhibitor indomethacin and the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA). In contrast to pyrilamine both astemizole and oxatomide inhibited the release of cysteinyl-LT and TXB2 with IC50 values between 4 and 23 mumol/l. Both astemizole and oxatomide were about twice as effective in inhibiting cysteinyl-LT release as compared to TXB2 release. Similar to astemizole and oxatomide the calmodulin antagonists trifluoperazine and W-7 inhibited the eicosanoid release. W-7 was, however, clearly less effective and in contrast to trifluoperazine no difference was observed in its potency to inhibit cysteinyl-LT or TXB2 release. The H1-antihistamines, astemizole and oxatomide as well as the calmodulin antagonists did not cause intracellular retention of the eicosanoids tested. The reference compounds indomethacin and NDGA proved to be the most potent inhibitors. The results demonstrate that the therapeutic antihistamines astemizole and oxatomide as well as the classical calmodulin antagonists trifluoperazine and W-7 are able to inhibit eicosanoid formation.

Astemizole↗
PubMed1989

Embryo-maternal distribution of basic compounds in the CD-1 mouse: doxylamine and nicotine.

The intracellular pH of the early postimplantation rodent embryo (pHi) is alkaline with respect to the corresponding plasma of the pregnant dam. This transplacental pH gradient is of considerable importance in the accumulation of teratogenic weak acids by the embryo. The importance of pH in the partitioning of basic drugs across the early mammalian placenta has not been investigated. Theoretically, the maternal plasma should retain a higher concentration of basic drugs than the embryo due to a greater degree of drug ionization in the more acidic plasma. To explore the significance of pH partitioning upon the transplacental distribution of basic compounds, two bases, doxylamine and nicotine, were administered to pregnant CD-1 mice during early organogenesis. The maternal plasma and embryonic concentrations of the bases were measured and the resulting embryo/maternal plasma (E/P) ratio was calculated and compared to the ratio predicted by the Henderson-Hasselbalch equation. Following ip injection of nicotine on Day 9 of gestation, the E/P ratio was significantly greater than the predicted ratio 10 min after injection and continued to rise for 3 hr. For doxylamine succinate administered by oral gavage on Day 9 or 10, the E/P ratio was also significantly greater than the ratio predicted from the pH gradient. Our results indicate that the partitioning of these basic compounds between the maternal plasma and the early postimplantation rodent embryo is not a consequence of the pH gradient between the two compartments alone.

Animals↗
PubMed1988

Formation of cysteinyl-leukotrienes by human brain tissue.

Using sensitive radioimmunoassay techniques, the formation of cysteinyl-leukotrienes (LT) and prostaglandin (PG) F2 alpha was investigated in human brain tissue slices in vitro. Under basal conditions spontaneous release of considerable amounts of LTC4-like material and PGF2 alpha could be detected from slices of both human grey and white matter. Ionophore A23187 stimulated the release of large amounts of LTC4-like material while leaving unaffected the formation of the cyclo-oxygenase product PGF2 alpha. Incubation of grey or white matter in the presence of the cyclo-oxygenase inhibitor indomethacin inhibited the release of PGF2 alpha but did not affect that of LTC4-like material. Preincubation of brain tissue in the presence of the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) abolished the ionophore A23187-induced release of LTC4-like material from both grey and white matter and also significantly reduced the spontaneous release of LTC4-like material from white matter slices. Formation of PGF2 alpha was not affected by NDGA. Using the isolated guinea pig ileum the LTC4-like material was shown to possess biological activity which could be antagonized with the slow-reacting substance of anaphylaxis (SRS-A) antagonist FPL 55712. By reversed phase HPLC the immunoreactive LTC4-like material from human grey matter was shown to coelute with authentic LTC4, LTD4 and LTE4, while material from human white matter coeluted with authentic LTD4 and LTE4. The capacity of human brain tissue to synthesize cysteinyl-LT may be important for cellular functions in the central nervous system.

Brain↗
PubMed1988

Inhibition of cysteinyl-leukotriene production by azelastine and its biological significance.

Azelastine is a phthalazinone derivative with a wide spectrum of pharmacological activities. Actively sensitized guinea pigs were used to examine the broncholytic effect of azelastine in vivo. Furthermore, the influence of azelastine on the production of arachidonic acid (AA) metabolites was investigated in vitro and compared to the effects of nordihydroguaiaretic acid (NDGA), indomethacin and ketotifen. In vivo, azelastine protected actively sensitized guinea-pigs against ovalbumin-induced bronchospasm with an ID50 of 0.08 mg/kg orally. Ketotifen was similarly active (ID50 = 0.05 mg/kg). Antigen-induced contraction of isolated tracheal rings of sensitized guinea-pigs was concentration-dependently inhibited by azelastine and NDGA with IC50-values of 94.1 and 34.2 mumol/l, respectively. Ketotifen exerted only weak inhibitory activity (18% at 100 mumol/l). The arachidonic acid-induced contraction of isolated guinea-pig tracheal rings was also inhibited both by azelastine (IC50 = 92.6 mumol/l) and NDGA (IC50 = 20.4 mumol/l). Ketotifen was inactive on this model. Antigen challenge of chopped lung tissue from sensitized guinea-pigs resulted in the release of cysteinyl-leukotrienes (LT) which were identified by reversed phase high pressure liquid chromatography (HPLC) as LTD4 and LTE4. The release of cysteinyl-LT from sensitized guinea-pig lung tissue induced by antigen challenge was concentration-dependently inhibited by azelastine (IC50 = 35.2 mumol/l) and NDGA (IC50 = 8.4 mumol/l) but not by ketotifen and indomethacin. By contrast, indomethacin caused a pronounced augmentation of cysteinyl-LT release. The concentration of indomethacin, which augmented cysteinyl-LT release by 50% was 0.19 mumol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Transcobalamin II deficiency: long-term follow-up of two cases.

Two Spanish siblings, a boy and girl, with transcobalamin II (TCII) deficiency are described. Both have grown and developed mentally normally after 10 years of vitamin B12 therapy. Two other siblings died soon after birth and it is almost certain that they also suffered from TCII deficiency.

Anemia, Megaloblastic↗
PubMed1988

Radioreceptor assay for leukotriene B4. Use for determination of leukotriene B4 formation by whole human blood.

A crude membrane fraction from guinea-pig splenic tissue containing leukotriene (LT) B4-binding sites was prepared and used in a radioreceptor assay for the quantitative determination of LTB4 in clotting whole human blood as well as in eluates from reversed-phase HPLC. Binding of [3H]LTB4 to the binding sites was inhibited by 50% with 0.31 ng LTB4. The relative cross-reaction of 20-OH-LTB4, 20-COOH-LTB4 and 12-hydroxyeicosatetraenoic acid (HETE) was 9.51%, 0.41% and 0.03%, respectively. The relative cross-reaction of various other prostanoids, cysteinyl-LT, mono-HETE's and arachidonic acid was below 0.01%. The spleen binding sites are useful for a rapid, simple and specific quantification of LTB4 in biological material.

Animals↗