Search PubMed⌕ Search

Biomedical subjects

S Suter

Publications and source records attributed to S Suter.

At least 55 records · Page 3Linked to original sources

Spatial-frequency-tuned channels in early infancy: VEP evidence.

Spatial frequency (SF) adaptation of 3-, 6-, and 12-week-old infants produced changes in steady-state VEP amplitude to SF sweeps that closely resemble post-adaptation changes reported previously in adults. Following SF adaptation, VEP amplitude was attenuated to SFs near the adapting SF, and enhanced at SFs removed from the adapting SF in all age groups. This is interpreted as evidence for bandpass SF-tuned channels with coinhibitory interactions. The data presented here, in combination with VEP estimates of infant acuity, imply the existence of multiple bandpass SF-tuned channels with inhibitory relationships by 3 weeks of age. We hypothesize that neonatal spatial frequency filters are qualitatively adultlike.

Adaptation, Ocular↗

The role of bacterial proteases in the pathogenesis of cystic fibrosis.

Among the roles of mediators damaging the respiratory epithelium in patients with cystic fibrosis (CF) during the course of chronic, purulent bronchitis, that of neutrophil proteases is well established. The role of bacterial proteases is less well known. Among all pathogens colonizing the airways in CF, Pseudomonas aeruginosa is quantitatively the dominant pathogen; Staphylococcus aureus and Haemophilus influenzae are present in lower numbers. Anaerobic bacteria may be detected in numbers exceeding those of Staphylococcus aureus and Haemophilus influenzae. Among all enzymes secreted by these bacterial strains, Pseudomonas elastase and alkaline protease were shown to be secreted in vivo over prolonged periods in the airways. These enzymes, mainly elastase, have proteolytic activity on many proteins involved in host defense mechanisms, often the same as those hydrolyzed by neutrophil proteases. Pseudomonas elastase has damaging effects on the respiratory epithelium; it has recently also been shown to augment the permeability of the respiratory epithelium cultured in vitro by proteolytic attack of tight junctions. The potential role of proteases and other enzymes secreted by anaerobic bacteria has not been studied in this disease. In conclusion, bacterial proteases secreted in vivo may play a role in the pathogenesis of the airway disease in CF; their relative importance to the role of host proteases is, however, often difficult to determine.

Cystic Fibrosis↗

Delayed onset of insulin activation of the insulin receptor kinase in vivo in human skeletal muscle.

During the infusion of insulin in vivo, the rate of activation of glucose disposal lags significantly behind the rate of increase in serum insulin levels. To determine whether this delay was related to transcapillary transport of insulin, we determined increments in serum insulin levels, glucose disposal rates (GDR), and insulin receptor (IR) kinase activity measured during continuous infusions of insulin (40 and 120 mU.m-2.min-1) administered to 8 nondiabetic males; similar studies were done at 1,200.m-2.min-1 in 2 of the subjects. Half-maximal insulin levels were achieved at a mean of 4.9 and 7.2 min during the 40 and 120 mU.m-2.min-1 clamps, respectively, with corresponding half-maximal GDR stimulation at a mean of 59 and 47 min. Unlike the rise in insulin levels, IR kinase activation was much slower with half-maximal activity occurring at approximately 40-60 min in the 2 clamps. Thus, the rise in serum insulin levels in each clamp was much faster than the increment in either kinase activity or glucose disposal. Insulin infusion increased both IR kinase and GDR maximally approximately 10-fold, with half-maximal stimulation at approximately 3,600 and approximately 700 pM, indicating spare kinase for glucose disposal. These results demonstrate that the delay in stimulation of glucose disposal by insulin is related to a rate-limiting step between the intravascular space and the cell-surface of skeletal muscle. This may involve delayed transendothelial transport of insulin.

Adult↗

Thrombocytopenia in a case of neonatal mumps infection: evidence for further clinical presentations.

We report a rare case of congenital mumps infection in a newborn girl. Her mother developed bilateral parotitis beginning the day of the delivery. The child was subsequently severely ill and suffered from fever, splenomegaly and thrombocytopenia, however, without parotitis nor pancreatic involvement. Both mother and child recovered well with symptomatic treatment. A review of the literature shows that clinical mumps is rare and usually benign in neonates. However, severe respiratory distress may occur. The recent appearance of mumps outbreaks in adolescents and young adults calls for a reinforcement of mumps vaccination and should prompt an immunological assessment of pregnant women after exposure.

Adult↗

Guillain-Barré syndrome following immunisation with Haemophilus influenzae type b conjugate vaccine.

The Guillain-Barré syndrome (GBS) is an immune-mediated disease often associated with viral or bacterial infections and with immunisation. IgM antibodies have been implicated as the main trigger event in GBS. So far, only four cases of GBS have been observed following immunisation with a conjugate vaccine against Haemophilus influenzae type b. We report another patient with GBS after this vaccination. We measured immunoglobulins against the H. influenzae type b polysaccharide (PRP) component of the vaccine. Surprisingly the anti-PRP IgM antibody level was markedly elevated (100 micrograms/ml) in the plasma of this patient. We speculate that an excessive anti-PRP IgM antibody response to the vaccine might be the cause of GBS.

Bacterial Vaccines↗

Childhood tuberculosis at a Swiss university hospital: a 2-year study.

The incidence of tuberculosis (TB) presenting to the University Hospital, Geneva, Switzerland, was studied over 2 years. Clinical data on all children receiving antituberculous drug therapy was collected. Of the 43 identified cases, 42% had active disease (i.e. clinical evidence of organ involvement), the remaining 58% being asymptomatic. All 43 children originated from countries other than Switzerland. Symptomatic, drug induced hepatitis necessitated temporary interruption of therapy in 2 children (5%). Contact screening yielded three new cases of pulmonary TB, three previously diagnosed cases and seven instances of a positive medical history in relatives living in other countries. Of the 34 families in this study, contact screening could not be completed in 8. The results of this study indicate that children with TB are primarily associated with families originating from countries other than Switzerland, particularly those in which TB remains endemic. Tuberculin skin testing should therefore be targeted at this group. Contact tracing has also been shown to be beneficial.

Adolescent↗

Need for prevention of invasive Haemophilus influenzae type b infections in Geneva, Switzerland.

Based on a retrospective study of invasive Haemophilus influenzae type b (Hib) diseases in Geneva from 1976 to 1989, we analysed the need for prevention of invasive Hib infections by vaccination in Geneva, Switzerland. The overall incidence rate among children younger than 5 years of age was 60.2/100,000 population but it was 121.5/100,000 and 92.1/100,000 in 1988 and 1989 respectively, indicating a statistically significant increase of invasive Hib infections during the study period. Of patients, 41.5% had meningitis, 36.6% epiglottitis and 21.9% had other forms of Hib infections. The occurrence was 2.1% in children under 3 months of age and 92.3% in children younger than 5 years of age. From 1984, > 21% of all new isolates were beta-lactamase-producing Hib strains. From 1976 to 1989, two children (1.1%) died from epiglottitis and 12 children with meningitis (15.8%) developed serious neurological deficits. These data emphasize the need for prevention of invasive Hib infections by vaccination in all infants in Geneva.

Adolescent↗

Early and late VEPs for reading stimuli are altered by common binocular misalignments.

Effects of mild binocular anomalies on early and late evoked response complexes to word stimuli were examined in visual evoked potentials (VEPs) recorded over occipital cortex, Wernicke's area, and its right side homolog in university students with (fixation disparity group) and without (normal group) fixation disparity. Stimuli were monocularly or binocularly viewed words of a paragraph presented individually for 100 ms, one per second, and a binocular control condition without linguistic content. An early complex (P125-N170) recorded at Oz and a late complex (N170-late P) recorded from the temporoparietal placements were analyzed. The early complex was not influenced by linguistic content. Binocular stimuli generally resulted in larger early and late VEP amplitudes than did monocular stimuli except that the fixation disparity group had no binocular amplitude enhancement at Oz. Left hemisphere amplitude was greater than right for all conditions, more so for words than for nonlinguistic stimuli. For words, the left hemisphere advantage was significant only for the normal group. Relationships between basic visual processing and language processing in relation to early and late complexes are considered from several perspectives.

Cognition↗

Regulation of cytokine secretion by cystic fibrosis airway epithelial cells.

Chronic airway inflammation is an important feature of cystic fibrosis (CF), markedly influencing morbidity and mortality. We wanted to assess the contribution of the respiratory epithelium in the mediation of local inflammatory events, and, more particularly, its regulating role through cytokine secretion. We have studied the regulation of interleukin-6 and 8 (IL-6 and IL-8) production by the SV40 transformed airway epithelial cell line JME/CF15 (homozygous for the deletion of Phe 508). We show that unstimulated JME/CF15 cells secrete IL-6 and IL-8. Neutrophil chemotactic activity (NCA) is detected in supernatants. The secretion of IL-6 and IL-8 is increased following stimulation of the JME/CF15 cells by IL-1 beta and neutrophil elastase. Lipopolysaccharide and granulocyte macrophage colony stimulating factor (GM-CSF) have no effect on secretion of IL-6 or IL-8. Neutrophil elastase inactivates recombinant human IL-6 at 37 degrees C in vitro, but has no effect at 4 degrees C, suggesting a proteolytic effect of elastase on IL-6. IL-8 activity remains preserved, even after prolonged exposure to elastase. Our data suggest that the airway epithelium may play an active role in the mediation of neutrophil chemotaxis. Local production of IL-8 in response to elastase and IL-1 beta, together with the inactivation of the anti-inflammatory protein IL-6, may result in a significant upregulation of airway inflammation in cystic fibrosis.

Cells, Cultured↗

High bronchoalveolar levels of tumor necrosis factor and its inhibitors, interleukin-1, interferon, and elastase, in patients with adult respiratory distress syndrome after trauma, shock, or sepsis.

Intrapulmonary activation of leukocytes and release of cellular mediators and enzymes are involved in the pathophysiology of the adult respiratory distress syndrome (ARDS). To investigate a possible role of local cytokines, we measured bronchoalveolar fluid (BALF) and plasma levels of tumor necrosis factor alpha (TNF-alpha) and its soluble inhibitors (sTNF-RI + RII), interleukin-1 beta (IL-1 beta), interferon-alpha (IFN-alpha), and granulocyte elastase in 14 patients at risk for ARDS and in 35 patients developing ARDS after trauma, sepsis, or shock. During clinical development of severe ARDS, BALF cytokines increased markedly: TNF-alpha from 116 +/- 36 to 10,731 +/- 5,048 pg/ml (mean +/- SEM), p = 0.001; sTNF-RI + RII from 3.7 +/- 1.4 to 24.6 +/- 2.6 ng/ml, p less than 0.05; and IL-1 beta from 7,746 +/- 5,551 to 42,255 +/- 19,176 pg/ml, p = 0.01. Plasma cytokines were not increased in most patients, nor were they correlated with the development or severity of ARDS. BALF elastase was higher in patients developing ARDS than in those at risk but not going into pulmonary failure (0.97 +/- 0.26 versus 0.28 +/- 0.13 U/ml, p = 0.026), and the highest values were observed in the early stages of severe ARDS (1.85 +/- 0.39 U/ml). BALF elastase levels correlated with IFN-alpha (r = 0.72, p less than 0.001). In conclusion, local release of TNF-alpha and IL-1 beta, possibly by pulmonary macrophages or other cells, and/or accumulation in the lung is associated with the development of ARDS.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchoalveolar Lavage Fluid↗

Secretory leucocyte proteinase inhibitor: inhibition of fibronectin degradation by neutrophil elastase.

Degradation of surface-bound fibronectin of the upper respiratory tract by human leucocyte elastase (HLE) was shown to favour colonization of these mucosal surfaces by Gram-negative bacteria. We investigated the degradation of fibronectin by purified HLE and by enzymes released from stimulated human polymorphonuclear leucocytes (PMNs), in the presence of recombinant secretory leucocyte proteinase inhibitor (rSLPI) and alpha 1-proteinase inhibitor (alpha 1-PI), the two main inhibitors of HLE within the airways. Our results show that HLE degraded fibronectin at concentrations as low as 0.2 nM. To inhibit the degradation of fibronectin by pure HLE in an experimental system in which the enzyme was premixed with inhibitor, a twofold molar excess of rSLPI and an equimolar concentration of alpha 1-PI were required. On the other hand, a fivefold molar excess of rSLPI was necessary to inhibit degradation of fibronectin by enzymes released from stimulated neutrophils. In order to estimate the role of oxidants generated by stimulated PMNs in the activation of the inhibitory capacity of rSLPI by stimulated PMNs, we preincubated PMNs with antioxidants such as superoxide dismutase, methionine, catalase or Na-azide prior to stimulation of the cells. Under these conditions, a threefold molar excess of rSLPI over released HLE was required to inhibit the degradation of fibronectin, raising the possibility that either exogenous or endogenous antioxidants in the lung could be important in improving the efficacy of this therapeutic antiprotease. We conclude that a molar excess of rSLPI to HLE is always necessary to inhibit fibronectin degradation by HLE, and that addition of antioxidants partly prevents the inactivation of rSLPI by oxidants released from stimulated PMNs.

Antioxidants↗

The chymotrypsin inhibitor carbobenzyloxy-leucine-tyrosine-chloromethylketone interferes with the neutrophil respiratory burst mediated by a signaling pathway independent of PtdInsP2 breakdown and cytosolic free calcium.

The effects of carbobenzyloxy-leucine-tyrosine-chloromethylketone (zLYCK), an inhibitor of chymotrypsin, were investigated on the activation pathways of the human neutrophil respiratory burst. At 10 microM zLYCK, a parallel inhibition was observed of superoxide production stimulated with the chemo-attractant FMLP and of chymotrypsin-like activity of human neutrophils. By contrast, superoxide production induced by PMA was minimally affected by zLYCK. The known transduction pathways triggered by FMLP were analyzed. zLYCK did not affect either the FMLP-induced cytosolic free calcium transient, inositol 1,4,5 trisphosphate formation, nor the PMA-induced phosphorylation of the 47-kDa substrate of protein kinase C. zLYCK did not affect the activity of protein kinase C extracted from neutrophils. In Ca(2+)-depleted cells, in which phosphatidylinositol 4,5-biphosphate breakdown does not occur, zLYCK inhibited the FMLP-induced respiratory burst in cells primed by low doses of PMA. The activity of the NADPH oxidase tested with active membranes from stimulated neutrophils or in a cell-free system was not inhibited by zLYCK. We conclude that: 1) zLYCK inhibits superoxide production through the inhibition of a chymotrypsin-like protease of the neutrophil, 2) zLYCK inhibits FMLP-induced activation of NADPH oxidase through a pathway independent of PtdInsP2 breakdown and cytosolic free calcium, and 3) zLYCK may prove a useful probe for the characterization of its target protease in neutrophil activation.

Amino Acid Chloromethyl Ketones↗

Osteoarticular infections due to Kingella kingae in children.

By the description of two cases of osteoarticular infections due to Kingella kingae in two young children we wish to draw the attention of clinicians to invasive infections due to this micro-organism. Since its biological characterization in 1976, K. kingae has been increasingly reported as a human pathogen. Most common presentations are endocarditis, bacteraemia, septic arthritis, osteomyelitis and spondylodiscitis. Interestingly, osteorticular involvement is largely predominant in previously healthy children. From the literature, we reviewed 51 cases of K. kingae bone and joint infections, representing 23 cases of septic arthritis, 17 of osteomyelitis and 11 spondylodiscitis. Of the cases 88% occurred in children below 5 years of age and in all cases only one bone or joint was involved. An underlying disorder could be found in only 4 patients. Since these infections have a favourable outcome with intravenous antibiotic treatment, proper isolation and identification of K. kingae is essential.

Arthritis, Infectious↗

Spatial-frequency-tuned attenuation and enhancement of the steady-state VEP by grating adaptation.

Steady-state visual evoked potentials (VEPs) were recorded from adults using 10% C fast spatial frequency (SF) sweeps of horizontal gratings under two conditions: (a) after exposure to a 40% C grating of 6 or 4 c/deg, and (b) after exposure to a blank screen equalling the adapting gratings in space-averaged luminance. SF adaptation attenuated VEP amplitude near the adapting SF, but maximum attenuation was displaced from the adapting SF for 6 c/deg adaptation. Small displacements in maximum attenuation would be expected if underlying neural subunits are tuned to a small number of different center SFs. In addition, SF adaptation caused amplitude enhancement 1.0-2.0 octaves below the adapting SF, providing electrophysiological evidence in humans for coinhibitory relationships among neural mechanisms that have been postulated on the basis of analogous psychophysical findings. The results are consistent with coinhibition between SF-tuned subunits and between transient and sustained mechanisms.

Adaptation, Ocular↗