Identification of 5-oxo-15-hydroxy-6,8,11,13-eicosatetraenoic acid as a novel and potent human eosinophil chemotactic eicosanoid.

Incubation of human eosinophils with arachidonic acid led to the formation of a novel and potent eosinophil chemotactic lipid (ECL) (Morita, E., Schröder, J.-M.

A study on coronary hemodynamics during acetylcholine-induced coronary spasm in patients with variant angina: endothelium-dependent dilation in the resistance vessels.

The epicardial coronary artery of patients with variant angina is hyperreactive to the constrictive effect of acetylcholine, but it is not known whether the coronary microvasculature also constricts in response to acetylcholine. Incremental doses of acetylcholine were injected into the left coronary artery of 57 patients with variant angina and with spasm in this artery. By measuring coronary sinus blood flow, coronary hemodynamic status just before angiographic documentation of spasm was examined.

Effect of gastrointestinal maturation on absorption of beta-lactam antibiotics.

Gastrointestinal absorption of cefazolin, which is poorly absorbed in adults, and of cephradine, which is well absorbed in adults, was studied in rats during their development. Significantly higher concentrations of cefazolin in plasma after oral administration were observed in 1- and 2-week-old rats compared with 3-week-old and adult rats. A marked difference in the absorption of cefazolin by 2- and 3-week-old rats (at weaning period) was observed.

Augmented secretion of brain natriuretic peptide in acute myocardial infarction.

In order to elucidate biosynthesis and secretion of natriuretic peptides in the early phase of acute myocardial infarction (AMI), we measured the plasma level of brain natriuretic peptide (BNP), a novel cardiac hormone secreted from the ventricle, in patients with AMI and compared with that of atrial natriuretic peptide (ANP). The plasma level of BNP increased rapidly (within hours from the onset of AMI) and markedly (greater than 100 times the normal level) as compared to that of ANP. The plasma ANP level correlated with pulmonary capillary wedge pressure (PCWP), whereas the plasma BNP level did not correlate with PCWP but highly correlated inversely with cardiac index.

Hemodynamic, renal, and hormonal responses to brain natriuretic peptide infusion in patients with congestive heart failure.

Background: This study was designed to examine the hemodynamic, renal, and hormonal effects of brain natriuretic peptide (BNP) infusion in patients with congestive heart failure (CHF) and in control subjects.

Methods And Results: We infused synthetic human BNP at a rate of 0.1 micrograms/kg/min.

Transcoronary chemical ablation of atrioventricular node for the treatment of paroxysmal supraventricular tachycardia--a case report.

We applied transcoronary chemical ablation of the atrioventricular (AV) node to a patient with uncontrollable paroxysmal supraventricular tachycardia (PSVT). Through an angioplasty dilatation catheter. 99% ethanol at a dose of 1.

Effect of age on the gastrointestinal absorption of acyclovir in rats.

Drug elimination from the body after intravenous administration of acyclovir (20 mg kg-1) was delayed in 1-week-old rats but the pharmacokinetic data for 2.5-week-old rats were the same as those for 8-week-old rats. The areas under the plasma concentration-time curves at 0-infinity h (AUC) after oral administration of acyclovir (20 mg kg-1) decreased with increasing age.

Gradient fields and homeobox genes.

We review here old experiments that defined the existence of morphogenetic gradient fields in vertebrate embryos. The rather abstract idea of cell fields of organ-forming potential has become less popular among modern developmental and molecular biologists. Results obtained with antibodies directed against homeodomain proteins suggest that gradient fields may indeed be visualized at the level of individual regulatory molecules in vertebrate embryos.

Overexpression of a homeodomain protein confers axis-forming activity to uncommitted Xenopus embryonic cells.

The anteroposterior character of mesoderm induced by a peptide growth factor (XTC-MIF) was tested by transplantation into host Xenopus gastrulae. Both retinoic acid and a homeodomain protein were able to override the anteriorizing effect of the growth factor. Microinjection of a posteriorly expressed homeobox mRNA can respecify anteroposterior identity, transforming head mesoderm into tail-inducing mesoderm.

Clinical significance of urinary enzymes in diabetic nephropathy.

Urinary enzyme activities (N-acetyl-beta-D-glucosaminidase [NAG], alkaline phosphatase [ALP], leucine aminopeptidase [LAP], gamma-glutamyl transpeptidase [gamma-GTP]) were investigated to determine their clinical significance in diabetic nephropathy. There were correlations among ALP, LAP, and gamma-GTP, though no correlation existed between NAG and the other three enzymes. Activities of NAG isozymes (both A and B) were higher than in normal controls.

Production of 15-hydroxyeicosatetraenoic acid by purified human eosinophils and neutrophils.

In the presence of high concentrations of exogenous arachidonic acid (greater than or equal to 10 microM), eosinophils produced 15-hydroxyeicosatetraenoic acid (15-HETE) in the absence of stimuli. The calcium ionophore A23187, as well as the chemotaxins used in this study--complement split product C5a, platelet-activating factor (PAF), and N-formyl-methionyl-leucyl-phenylalanine (FMLP)--failed to increase 15-HETE production, indicating that eosinophil 15-lipoxygenase is already active. Production of 15-HETE from eosinophils increased with increasing concentrations of arachidonic acid, exogenously added.

[Clinical significance of urinary enzymes in diabetes mellitus].

The aim of this study was to clarify the clinical significance of urinary enzyme activity in patients with diabetes mellitus. Patients were divided into two groups: group A - 102 outpatients, group B-23 inpatients. Spot urine samples before breakfast from group A and aliquots of 24-hours urine collections at 4 degrees C from group B were used.

The Xenopus XIHbox 6 homeo protein, a marker of posterior neural induction, is expressed in proliferating neurons.

XIHbox 6 is an early spatially restricted marker for molecular studies of neural induction. The sequence of the full-length XIHbox 6 protein is reported. An antibody raised against a beta-galactosidase/XIHbox 6 fusion protein was used to analyze the expression of XIHbox 6 proteins during frog embryogenesis.

Identification of a novel and highly potent eosinophil chemotactic lipid in human eosinophils treated with arachidonic acid.

Purified human eosinophils generate eosinophil chemotactic lipids (ECL), when incubated with arachidonic acid without any stimulus. Reversed phase HPLC of incubation supernatants revealed major lipid-like eosinophil chemotactic activity eluting in a peak containing 5(S), 15(S)dihydroxy-6,13-trans-8,11-cis-eicosatetraenoic acid (5,15-DiHETE) as well as a 8,15-dihydroxyeicosatetraenoic acid. For further characterization of the ECL, some authentic dihydroxyeicosatetraenoic acids were tested for eosinophil chemotactic activity.

Comparison of the pharmacokinetics of five beta-lactam antibiotics between neonatal and adult rats.

The pharmacokinetics of beta-lactam antibiotics in adult and neonatal rats were compared after their intravenous or oral administration. The distribution volumes of cefazolin, cefamandole and cefmetazole were larger for the neonatal than the adult rats, whereas the distribution volumes of cephradine and cephalexin were smaller for the neonates. Neonatal rats showed lower clearances than adults for all antibiotics tested.

Effects of a novel cholecystokinin (CCK) receptor antagonist, MK-329, on gallbladder contraction and gastric emptying in humans. Implications for the physiology of CCK.

To explore the physiology of cholecystokinin (CCK) in humans, we investigated the effect on gallbladder contraction and gastric emptying of a recently developed CCK receptor antagonist, MK-329. In a double-blind, four-period crossover study eight subjects received single doses of 0.5, 2, or 10 mg MK-329, or placebo, followed by an intravenous infusion of CCK-8 (30 pmol/kg.

Chemotactic responsiveness of eosinophils isolated from patients with inflammatory skin diseases.

We determined the chemotactic responsiveness of peripheral eosinophilic granulocytes (eosinophils) isolated from patients with inflammatory dermatoses and healthy volunteers. Ten patients with atopic dermatitis, five patients with drug reactions, ten patients with psoriasis, and fourteen healthy volunteers were studied. Well characterized chemotaxins, the complement split product C5a, leukotriene B4 (LTB4), platelet activating factor (PAF), and N-formyl-methionyl-leucyl-phenylalanine (FMLP), were used as chemoattractants.

[Establishment of a human skin squamous cell carcinoma cell line (SCC-1CB) in vitro and its characteristics].

A human skin tumor cell line SCC-1CB has been established in vitro. A specimen from a surgically excised tumor with moderately differentiated squamous cell carcinoma of skin from a Japanese male, aged 62, was transplanted subcutaneously into nude mice. After growth, a part of the tumor was passaged with a transplantation needle.

Differential sensitivities of purified human eosinophils and neutrophils to defined chemotaxins.

Functions of eosinophils and neutrophils isolated from normal human blood were determined by measuring chemotactic migration and release of beta-glucuronidase. Four well-characterized chemotaxins, the complement fragment C5a, formyl-methionyl-leucyl-phenylalanine (FMLP), platelet-activating factor (PAF), and leukotriene B4 (LTB4) were used as stimuli. Neutrophils showed remarkable chemotactic responses to all four chemotaxins.

Intestinal absorption of pyridoxal 5'-phosphate at physiological levels in rats.

The intestinal absorption of pyridoxal 5'-phosphate (PLP) at physiological levels (10(-7) -10(-6) M) was studied in comparison with that of pyridoxal (PL) in rat, using in vitro everted sac and an intestinal preparation that permitted continuous in situ collection of mesenteric venous blood. After PLP administration (10(-6) -10(-3) M) in situ, larger amounts of PLP were found in the mesenteric venous plasma than after PL administration at the same dose. The amount of PLP found in the mesenteric venous plasma was dependent on its dose at lower concentrations up to 10(-4) M but became independent at higher concentrations.

Physiological role for cholecystokinin in reducing postprandial hyperglycemia in humans.

It is known that the ingestion of glucose alone causes a greater increase in plasma glucose levels than ingestion of the same amount of glucose given with other nutrients. Since physiological plasma concentrations of cholecystokinin (CCK) prolong gastric emptying, it is proposed that after a meal, CCK may modify plasma glucose levels by delaying glucose delivery to the duodenum. To evaluate the effect of CCK on oral glucose tolerance, plasma CCK, insulin, and glucose levels and gastric emptying rates were measured in eight normal males before and after the ingestion of 60 g glucose with the simultaneous infusion of either saline or one of two doses of CCK-8 (12 or 24 pmol/kg per h).

Characterization of the human granulocyte-macrophage colony-stimulating factor promoter region by genetic analysis: correlation with DNase I footprinting.

T-cell activation induces expression of the hematopoietic growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF). To define the molecular events involved in the induction of GM-CSF gene expression more clearly, we prepared and analyzed deletion mutants of GM-CSF promoter recombinant constructs. The results localized inducible expression to a 90-base-pair region (-53 to +37) which is active in uninfected and human T-cell leukemia virus-infected T-cell lines but not in resting or mitogen-stimulated B cells.

Purification and partial biochemical characterization of a human monocyte-derived, neutrophil-activating peptide that lacks interleukin 1 activity.

A novel monocyte-derived neutrophil-activating peptide (MONAP) produced by lipopolysaccharide- and phorbol myristate acetate-stimulated human peripheral blood monocytes was purified by sequential ion exchange-high performance liquid chromatography (HPLC), size exclusion HPLC, and reversed phase HPLC. Biologic activities of the purified cytokine were monitored by either an enzyme release assay or a chemotaxis assay, using peripheral human neutrophils. Purified MONAP was found to be homogeneous, giving a single peak on size-exclusion HPLC, reversed-phase HPLC, as well as a single 10-kDa band on silver-stained polyacrylamide gels.

Gastrointestinal absorption of sulfaguanidine in neonatal and adult rats.

The pharmacokinetics of sulfaguanidine in rats was studied after its intravenous or oral administration. In adult rats, its elimination from plasma, after intravenous administration of 2.5 or 25 mg/kg doses, could be described by a two-compartment open model, while its plasma concentration after oral administration of 25 mg/kg doses, agreed with the one- or two-compartment open model.