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Biomedical subjects

F Rose

Publications and source records attributed to F Rose.

At least 37 records · Page 2Linked to original sources
PubMed1999

Role of actin depolymerization in the surfactant secretory response of alveolar epithelial type II cells.

Alveolar epithelial type II cells (AET2) respond with exocytosis of surfactant containing lamellar bodies to stimulation with mechanical stretch and secretagogues, a process that is fundamental for maintaining alveolar stability and lung gas exchange. In the present study in cultured rat AET2, we employed botulinum C2 toxin, a binary toxin which ADP ribosylates nonmuscle G-actin, as a specific tool to probe the role of the actin microfilament system in the surfactant secretory process. Incubation of AET2 with C2 toxin caused a dose-dependent decay of the cellular F-actin content to a minimum of 20% of baseline, concomitant with an increase in monomeric actin. In parallel, a significant augmentation of baseline surfactant secretion up to twofold elevated levels above control was noted, as assessed by the release of prelabeled phosphatidylcholine. Pretreatment with phalloidin, which stabilized F-actin and reduced the level of G-actin, prevented the C2 toxin-elicited enhancement of baseline surfactant secretion. Even low C2 toxin concentrations, resulting in a reduction of total cellular F-actin content of approximately 10%, sufficed to augment secretagogue (ATP) and, more impressively, mechanical stress elicited an increase in surfactant secretion; the response to the biophysical challenge more than doubled. When investigated in the absence of toxin, different secretagogues (ATP, phorbol ester, betamimetics) caused a rapid-onset, transient reduction of F-actin in the range between 15 and 25% as a consistent part of their secretory response pattern. These data suggest that the state of actin polymerization is intimately linked to the exocytosis process underlying surfactant secretion in AET2. Microfilament system-related compartmentalization effects and/or or the impact of the state of actin assembly on signaling events may be considered as underlying events.

Actins↗
PubMed1999

Prostacyclin enhances stretch-induced surfactant secretion in alveolar epithelial type II cells.

Inhalative vasodilator therapy, employing gaseous nitric oxide (NO) or aerosolized prostaglandin PGI(2), is of interest for regional pulmonary vasodilation in ARDS and pulmonary hypertension. We investigated the impact of the NO donor spermine NONOate as well as PGI(2) and its stable chemical analog iloprost on cultured rat alveolar epithelial type II cell (ATII) surfactant secretion. The NO donor provoked a significant increase in the ATII cGMP content, further enhanced by type V phosphodiesterase (PDE) inhibition, but affected neither baseline nor mechanical stretch-induced surfactant secretion. The prostanoids caused a marked increase in the epithelial cAMP content, further amplified by coadministration of type III/IV PDE inhibitors. Baseline surfactant secretion was not altered by this approach, but mechanical stretch-induced liberation of surfactant was significantly increased, most prominently in the ATII with the highest cAMP levels due to the presence of both iloprost and PDE III/IV inhibitors. In contrast, epithelial phosphoinositide metabolism, well responsive to purinergic stimulation as positive control, was unchanged in prostanoid-exposed cells. We conclude that the PGI(2)-cAMP axis, but not the NO-cGMP axis, forwards a markedly enhanced secretory response to the physiological stimulus of cell surface stretching, which may be relevant for therapeutic use of these agents.

Analysis of Variance↗
PubMed1997

Human endothelial cell activation and mediator release in response to the bacterial exotoxins Escherichia coli hemolysin and staphylococcal alpha-toxin.

Escherichia coli hemolysin (HlyA) and Staphylococcus aureus alpha-toxin are membrane-perturbating bacterial exotoxins that have been implicated as significant virulence factors in human diseases. We investigated the capacity of these toxins to cause cell activation and mediator release in human endothelial cells, compared with the efficacies of thrombin and the Ca2+ ionophore A23187. Concentration ranges tested were 1 to 1000 ng/ml (HlyA), 0.01 to 10 micro/ml (alpha-toxin), 0.01 to 10 U/ml (thrombin), and 0.01 to 10 microM (A23187). All stimuli caused dose-dependent generation of platelet-activating factor, nitric oxide, and prostaglandin I2. HlyA and thrombin effected time- and dose-dependent accumulation of large quantities of inositol phosphates, with maximum effects at 100 ng/ml and 1 U/ml, respectively. Corresponding time course and dose dependency were noted for HlyA-elicited diacylglycerol formation. In contrast, only the highest concentrations of alpha-toxin (10 microg/ml) and A23187 (10 microM) effected some moderate inositol phosphate accumulation, and this was suppressed in the presence of the platelet-activating factor antagonist WEB 2086. Metabolic and secretory responses elicited by alpha-toxin were dependent on the presence of extracellular Ca2+. We conclude that both HlyA and alpha-toxin are potent inductors of inflammatory and vasodilatory mediators in human endothelial cells. HlyA-elicited effects may proceed predominantly via activation of the phosphatidylinositol hydrolysis-related signal transduction pathway, whereas transmembrane Ca2+ flux appears to be the major event underlying the release of mediators in response to alpha-toxin. These toxin properties may contribute to vasoregulatory and inflammatory disturbances encountered in states of severe infection and sepsis.

Animals↗
PubMed1997

The intellectual functioning of adolescents with anorexia nervosa and bulimia nervosa.

The aim of this study was to investigate the intellectual functioning of a large group of eating disordered adolescents in order to test two hypotheses, viz, that the intellectual functioning of eating disordered adolescents conforms to the normal distribution, and that eating disordered adolescents do not perform better in verbal abilities than in nonverbal abilities. Standard intelligence tests were applied to 190 consecutive out- and inpatients with eating disorder diagnoses. The results were compared with those of a group of patients with other disorders, similar in age, sex, SES, and year of admission. The IQ of the eating disordered patients was significantly higher than that of patients in the comparison group. Patients in the comparison group and bulimic patients, but not anorexic patients, showed better nonverbal than verbal intellectual performance.

Adolescent↗
PubMed1997

Ro 32-3555, an orally active collagenase inhibitor, prevents cartilage breakdown in vitro and in vivo.

1. Ro 32-3555 (3(R)-(cyclopentylmethyl)-2(R)-[(3,4,4-trimethyl-2,5-dioxo-1- imidazolidinyl)methyl]-4-oxo-4-piperidinobutyrohydroxamic acid) is a potent, competitive inhibitor of human collagenases 1, 2 and 3 (Ki values of 3.0, 4.4 and 3.4 nM, respectively). The compound is a selective inhibitor of collagenases over the related human matrix metalloproteinases stromelysin 1, and gelatinases A and B (Ki values of 527, 154 and 59 nM, respectively). 2. Ro 32-3555 inhibited interleukin-1 alpha (IL-1 alpha)-induced cartilage collagen degradation in vitro in bovine nasal cartilage explants (IC50 = 60 nM). 3. Ro 32-3555 was well absorbed in rats when administered orally. Systemic exposure was dose related, with an oral bioavailability of 26% at a dose of 25 mg kg-1. 4. Ro 32-3555 prevented granuloma-induced degradation of bovine nasal cartilage cylinders implanted subcutaneously into rats (ED50 = 10 mg kg-1, twice daily, p.o.). 5. Ro 32-3555 dosed once daily for 14 days at 50 mg kg-1, p.o., inhibited degradation of articular cartilage in a rat monoarthritis model induced by an intra-articular injection of Propionibacterium acnes. 6. Ro 32-3555 is a potential therapy for the treatment of the chronic destruction of articulating cartilage in both rheumatoid and osteoarthritis.

Administration, Oral↗
PubMed1996

The listerial exotoxins listeriolysin and phosphatidylinositol-specific phospholipase C synergize to elicit endothelial cell phosphoinositide metabolism.

Exotoxins such as listeriolysin (LLO) and phosphatidylinositol-specific phospholipase C (PIcA) have been implicated in listerial infection and sepsis. Employing different Listeria strains, mutated in individually known virulence genes, we examined exotoxin-related induction of endothelial cell signaling. Listeria monocytogenes was a potent inductor of phosphatidylinositol (PtdIns) metabolism in HUVEC. This effect was completely absent in a LLO-negative strain. Using a recombinant Listeria innocua strain, engineered to produce high levels of LLO, PtdIns metabolism was restored to approximately 30% of that produced by the parental L. monocytogenes strain. A recombinant L. innocua strain expressing only PIcA did not induce any PtdIns metabolism. Even higher than wild-type levels of PtdIns hydrolysis products were, however, evoked when engineered bacteria secreted both LLO and PIcA. These effects occurred in the absence of bacterial uptake by the endothelial cells. Corresponding results were observed with regard to endothelial diacylglycerol (DAG) generation. The amplification of endothelial cell signaling could be reproduced by engaging purified LLO and PIcA in the absence of bacteria. In these experiments, the unrelated pore-forming agent staphylococcal alpha-toxin, a very weak stimulus for endothelial phosphoinositide metabolism by itself, substituted for LLO to allow marked PtdIns hydrolysis when co-applied with PIcA. We conclude that the listerial exotoxins LLO and PIcA cooperate to provoke potent second messenger synthesis in endothelial cells, in the absence of cell invasion by the bacteria. This is an impressive example of synergism between a pore-forming and an enzymatic bacterial exotoxin in provoking cell signaling and inflammatory events.

Bacterial Proteins↗
PubMed1996

Chronic intestinal giardiasis with isolated levothyroxine malabsorption as reason for severe hypothyroidism--implications for localization of thyroid hormone absorption in the gut.

We report a case of isolated levothyroxine malabsorption in the course of chronic intestinal giardiasis, leading to severe hypothyroidism. Infection with Giardia lamblia was proved histologically by jejunal biopsy. Treatment with metronidazole resulted in complete elimination of parasites and recovery of regular intestinal thyroid hormone absorption. Stable euthyroidism was accomplished with common replacement doses of orally administered levothyroxine.

Antiprotozoal Agents↗
PubMed1996

Listeriolysin is a potent inducer of the phosphatidylinositol response and lipid mediator generation in human endothelial cells.

The impact of Listeria monocytogenes listeriolysin O (LLO) secretion on phosphoinositide metabolism and mediator (platelet-activating factor and prostaglandin I2) generation was investigated in human umbilical vein endothelial cells. Wild-type L. monocytogenes, purified LLO, and an L. innocua strain engineered to secrete LLO all elicited a strong response, whereas mutant strains defective in LLO production were ineffective. Thus, human umbilical vein endothelial cell stimulation by listeriae is linked to production of LLO.

Bacterial Toxins↗
PubMed1995

[School refusal--a catamnestic study on the diagnostic concept ov "school phobia" and "school anxiety"].

Twenty-six patients diagnosed with school refusal were examined 2.4 years after inpatient treatment. The long-term course of patients with "school phobia" (school refusal unrelated to school) and that of patients with "school anxiety" (school refusal related to school) were compared. In addition, an attempt was made to identify variables predictive of a good outcome. The mean age of the 12 patients with "school phobia" and the 14 patients with "school anxiety" was 12.7 years at the start of inpatient treatment. The assessment of psychiatric disturbances was based on structured interviews for parents and adolescents (MEI and MADEL, 1989) and the dimensional assessment scales of functioning for children and adolescents (MSBF). The variables assessed for predictive value were taken from the patients' records during inpatient treatment and from the hospital documentation system. There was no difference in outcome between the two syndrome groups. There was a tendency to less autonomy in the patients with "school phobia". Girls had a better outcome than boys, as did patients with less absence from school prior to inpatient treatment. Overall there was no difference in the outcome of "school phobia" and "school anxiety". Therefore a new classification should be considered.

Adolescent↗
PubMed1994

Sepsis modifies the contribution of different organs to whole-body protein synthesis in rats.

1. Protein synthesis rate was measured in the liver, muscle, intestine and whole body of septic rats and pair-fed controls by administration of a large dose of L-[U14C]valine. Sepsis was induced by intravenous injection of live bacteria, and protein synthesis measurements were carried out 48 h later. 2. Septic rats exhibited a reduction in food intake to between 10 and 50% of the normal level on the 2 days after infection. Animals lost body weight and the relative organ weight was increased in liver, unchanged in intestine and decreased in skeletal muscle. 3. The fractional protein synthesis rate of the whole body excluding liver was increased by 19% in septic rats in comparison with pair-fed controls, but the absolute protein synthesis rate was similar in the two groups because of the low protein content of the infected group. 4. The fractional protein synthesis was increased in whole intestine and liver but was decreased in skeletal muscle. In muscle and liver, the difference between infected and pair-fed animals was more pronounced for the absolute than for the fractional protein synthesis rate. In intestine, the fractional protein synthesis rate was similarly increased in whole intestine and the muscular layer of ileum. This suggests different regulation of protein synthesis in skeletal and smooth muscles. 5. The present investigation shows a complete redistribution of protein synthesis in sepsis. Liver represents about a third of the whole-body protein synthesis instead of 15% and becomes predominant over synthesis of muscle.

Animals↗
PubMed1994

[Category system for microanalysis of early mother-child interaction].

As part of a prospective longitudinal study on the pathogenesis of neuropsychiatric disorders in children at biological and psychosocial risk, a system of categories was developed for the assessment of early mother-child interaction. A computer program for recording observational data in synchrony with video images by online coding was developed for this purpose. It permits second-by-second recording of basic categories and complex interactional behavior of mother and child. An evaluation of instrumental validity, interrater reliability and the validity of the system with 48 mother-child dyads yielded positive results. Measures of interaction (synchrony, reciprocity, elicit) and of disturbed interactions were defined.

Child↗
PubMed1993

[Importance and determinants of early mother-child relations].

In a prospective longitudinal study on child development from birth to age eight 362 first-born infants and their families were investigated. The subjects were distributed across the nine cells of a two-factorial design, factor 1 representing the degree of organic, factor 2 the degree of psychosocial risk. At age 3 months mother-child interaction was videotaped and evaluated with microanalytic technique. The quality of MCI could be demonstrated to be as predictive for later cognitive development as early developmental tests. Social-emotional problems of the toddler and preschool child was predicted better by parameters of early MCI than by temperament. Disturbed interactions were associated with later cognitive retardation and enhanced behavior problems. MCI is significantly determined by neglect and rejection, which showed typical behavioral patterns. The early separation of mother and high risk newborn itself did not lead to alterations in maternal attachment. Compared with mother daughter dyads early interaction of mother and son was characterized by more reactivity and positive emotion.

Affect↗
PubMed1992

Protein synthesis in skeletal muscle of uremic patients: effect of low-protein diet and supplementation with ketoacids.

The purpose of this study was to investigate the modifications of muscle protein synthesis activity in uremic patients fed a low-protein diet and a low-protein diet supplemented with a keto acid-amino acid mixture. The protein synthesis activity was evaluated in vitro on isolated muscle ribosomes incubated in a cell-free medium with tritiated leucine. Simultaneously, nitrogen kinetics and amino acid patterns were examined. Protein synthesis activity is correlated with the protein content of the diet in uremic patients. The keto acid-amino acid supplementation enhances protein synthesis. Variations of protein synthesis can be correlated with the variations of nitrogen balance which implies a major role of protein synthesis activity in muscle protein metabolism. Variations in plasma levels of the essential amino acids, mainly leucine and valine, can be correlated with the variations of protein synthesis activity, and these amino acids seem therefore to be mediators of the dietary effects on protein synthesis in uremia.

Aged↗
PubMed1991

Now quality means service too.

In the latest phase of the quality campaign, managers are discovering that the point is not only to satisfy but also to delight the customer. Just ask IBM or Federal Express.

Consumer Behavior↗
PubMed1990

[Nutrition, metabolic and endocrine complications during extrarenal dialysis].

Patients with chronic renal failure treated by maintenance dialysis often have nutritional disorders, metabolic disorders concerning lipids, proteins and carbohydrates, and disorders of endocrine systems involved in the regulation of these metabolisms. These disorders are difficult to diagnose, as their clinical symptoms are few and of little pathognomonic value. Hence the need for anthropometric measurements as well as biochemical and physiological exploration of metabolic pathways for intermittent overall evaluation and longitudinal follow-up. These patients have reduced subcutaneous fat reserves, intolerance to carbohydrates by resistance to insulin (partially corrected by haemodialysis), low levels of plasma aminoacids, notably valine, type IV hyperlipidaemia with low levels of essential fatty acids, fragile immune system and increased requirements for vitamins B, especially B6. Dietary recommendations include: food energy 35 kiloCal/kg bodyweight/day; proteins 1 to 1.2 g/kg bodyweight/day (50 p. 100 of which must be complete proteins) and supplements of vitamins. Dialysis must be optimal for clearance of nitrogen compounds and body homeostasis.

Endocrine Glands↗
PubMed1989

Rehabilitation of microsomal enzymes in malnourished rats: comparison of parenteral versus oral refeeding.

Protein malnutrition decreases the activity of drug-metabolizing liver microsomal enzymes. In the first part of our study, we evaluated those enzymes during malnutrition and refeeding. Then we compared the effects of different nutritional patterns on these parameters. During malnutrition (M), rats were fed a 5% casein diet. During refeeding, they were randomized in 3 groups: oral refeeding (20% casein diet: A), continuous total parenteral nutrition (TPN: B) and oral energy refeeding (glucose + lipids) + continuous amino-acid infusion (C). Rats were sacrificed before and at various times during malnutrition and refeeding (2 to 28 days). There was no difference in caloric intake between the 3 groups. Nitrogen balance was not different in A and B. It was lower in C, though nitrogen intake was not different. Body and liver weights were not different between the 3 groups. Microsomal proteins and cytochrome P-450 were improved in A and B but not in C compared to M. Our results suggest that TPN (but not continuous amino-acids infusion + oral energy intake) is as effective as oral nutrition on rehabilitation of microsomal enzymes in malnourished rats.

Journal Article↗