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Biomedical subjects

G Koch

Publications and source records attributed to G Koch.

At least 235 records · Page 13Linked to original sources

[Effect of methylxanthines on periodic respiration and acid gastroesophageal reflux in newborn infants].

The treatment of neonatal apnea and bradycardia with methylated xanthines--theophylline and caffeine--is generally accepted. Besides the desired effects of these drugs they induce a wide range of side effects including relaxation of smooth muscles and increased gastric secretion. The aims of this study were, at first to investigate the coincidence of periodic breathing (PA) and acid gastro-esophageal reflux (GER) in neonates (n = 15) without therapy; at second to examine the influence of the consecutive medication with theophylline and caffeine on these parameters in patients (n = 10) with recurrent episodes of bradycardia and apnea. A 24 h esophageal pH-monitoring and 24 h cardiorespirography were performed simultaneously under standarized conditions. In the 15 neonates studied a weak correlation was found between the time spent breathing periodically and the duration of GER; the overlap of PB and GER was minimal. Theophylline and caffeine medication resulted in a marked reduction of PB which was more pronounced than it could be expected from maturation. The total time of a 24 h esophageal pH-monitoring was subdivided in an early postprandial time (FPP: first two hours after the beginning of a meal) and a late postprandial time (SPP: remaining time until the following meal). An increased duration of acid GER was observed during the SPP under therapy with theophylline and even more distinct with caffeine treatment.

Bradycardia↗

Analysis of an immunodominant region of infectious bronchitis virus.

We analyzed the antigenic fine-structure of an immunodominant region in the peplomer protein of infectious bronchitis virus. This region near the N-terminus of the S2 subunit is recognized by polyclonal antisera and by the majority of mAb that cross-react with denatured protein. Despite their involvement in neutralization, epitopes in this region were conserved in different serotypes. Epitopes of four mAb and two chicken antisera were localized by using prokaryotic expression of cDNA fragments, and overlapping peptides with lengths increasing from 3 to 12 residues (PEPSCAN). We found overlapping epitopes with lengths of 6, 9, 11, and more than 17 residues. The results indicate that the expression products are antigenically equivalent to denatured protein fragments. This suggests a general strategy for the localization of sequential epitopes in large proteins. We propose that the immunodominance of the N-terminal region of S2 is explained by features of the protein structure. Presumably, this region is a protruding protein segment of about 20 residues with a high local mobility, as indicated by the antigenicity of the peptides. The conservation of the sequence points to an involvement in a molecular recognition process during infection.

Amino Acid Sequence↗

The Na+,K+,2Cl- -cotransport system in HeLa cells and HeLa cell mutants exhibiting an altered efflux pathway.

We have investigated the characteristics of a transport system in HeLa cells, which turned out to be very similar to a previously described Na+, K+, 2Cl- -cotransport system. For further understanding about the physiological role of the cotransporter, we have mutagenized HeLa cells and selected progeny cells for growth in low potassium (0.2 mM) medium. The selected HeLa cells (LK1) exhibited alterations in the Na+,K+,2Cl- -cotransport system. LK1 cells showed a remarkable reduction of 86Rb+ efflux via the cotransporter when compared to the parental HeLa cells. In contrast, bumetanide-sensitive potassium influx, measured by 86Rb+ uptake, was increased in the LK1 cells (increase in Vmax). Km values of the cotransporter in HeLa cells and LK1 mutants revealed similar properties for 86Rb+ and 22Na+ uptake. In addition, (3H)-bumetanide binding studies were carried out on intact HeLa cells; 1.7 pmol/mg protein (3H)-bumetanide was specifically bound to HeLa parental cells, which could be calculated to a number of 103,000 binding sites/cell. LK1 cells present, 1.44 pmol/mg protein, specifically bound (3H)-bumetanide and, respectively, 137,000 binding sites/cell. The LK1 cells also exhibited an increase in the number of (3H)-ouabain binding sites as well as an increase in the activity of the Na+,K+-ATPase, expressed as a function of ouabain-sensitive 86Rb+ uptake. Furthermore, LK1 cells were different in the concentrations of intracellular Na+ (increases) and K+ (decreases) when compared to the HeLa parental cells. When grown in low K+ medium (0.2 mM K+), protein content and cell volume were increased in the LK1 cells, while the DNA content was not significantly different between both cell lines.

Biological Transport↗

Inhibition of the contraction of the isolated longitudinal muscle of the guinea-pig ileum by botulinum C2 toxin: evidence for a role of G/F-actin transition in smooth muscle contraction.

The effect of botulinum C2 toxin was studied on the contractions of the guinea pig ileum myenteric plexus longitudinal muscle preparation. Botulinum C2 toxin inhibited the muscle contraction induced by electrical stimulation (60 V; 0.5 ms; 0.33 Hz) in a time and concentration dependent manner. The inhibitory effect occurred with a time lag of about 1 h, and depended on the presence of both toxin components. After 4 h of incubation with 1.7 micrograms/ml of component I and 6.7 micrograms/ml of component II of botulinum C2 toxin, the smooth muscle contraction was inhibited by about 60%. At these toxin concentrations, about 55% of the modifiable smooth muscle actin was ADP-ribosylated. Smooth muscle contraction induced by bradykinin and bethanechol were similarly inhibited. Moreover, the C2 toxin inhibited muscle contraction induced by Ba2+, and by direct muscle membrane depolarization (60 V; 10 ms; 0.33 Hz) after suppression of acetylcholine release by normorphine. Also cytochalasin D inhibited the electrically evoked contraction of the ileum longitudinal muscle. In contrast to botulinum C2 toxin, inhibition of contractility by cytochalasin D occurred without a lag phase, and was reversed by washing off the toxin. In contrast of guinea pig ileum longitudinal muscle, botulinum C2 toxin did not reduce the contraction of the rabbit aortic smooth muscle stimulated by K+-depolarization or noradrenaline.

Actins↗

Postnatal development of mucosa-associated lymphoid tissues in chickens.

The postnatal development of chicken mucosa-associated lymphoid tissues of the eyes, lungs, and intestines were investigated with monoclonal antibodies specific for either all leucocytes, B lymphocytes, mononuclear phagocytes, IgM, IgG, or IgA. Attention has been paid to the relation of lymphoid infiltrates with their surrounding mucosae, the segregation into B-cell and T-cell areas, development of germinal centers, and secretory immunoglobulins. Abundant secretory IgM and IgA was detected in the epithelium of the Harderian glands in the orbits, even though they lacked large leucocyte infiltrates with germinal centers. Lymphoid tissues in the mucosae of lungs and intestines developed separate B-cell and T-cell areas. The proventriculus, Meckel's diverticulum, and Peyer's patches generally contained germinal centers from 12 weeks of age on. Because chickens as young as 2 weeks old had germinal centers in bronchus-associated lymphoid tissue and cecal tonsils, these areas were probably highly stimulated by antigens. Isotype-specific monoclonal antibodies were used to detect IgM-, IgG-, and IgA-bearing follicular cells in the same germinal center.

Animals↗

Responses of glomerular filtration, renal blood flow and salt-water handling to acute cardioselective and non-selective beta-adrenoceptor blockade in essential hypertension.

The effects on renal hemodynamics and salt-water handling of equipotent doses of the cardioselective beta-blocker metoprolol (M, 100 mg) and of the non-selective (intrinsic sympathetic activity) beta-antagonist pindolol (P, 10 mg) were compared in 30 WHO Grade 1-2 hypertensive men. M lowered pulse rate more than P. Systolic pressure was equally reduced by both agents, and diastolic and mean pressures were decreased only after P. Glomerular filtration rate was not significantly altered by either antagonist, and renal blood flow decreased by approximately 11% both after M and P. Renal vascular resistance was unchanged after P, and was increased by 10% after M. It is concluded that, like the effects on central haemodynamics, ISA is more important in the renal response to beta-adrenoceptor blockade than is beta-receptor selectivity.

Adrenergic beta-Antagonists↗

Antigenicity of the peplomer protein of infectious bronchitis virus.

To study the antigenic structure of the peplomer protein of the avian coronavirus infectious bronchitis virus, fragments from the peplomer gene were generated by restriction-enzyme cleavage or by limited DNase digestion and inserted in the Escherichia coli expression plasmid pEX (Stanley and Luzio, 1984). The antigenicity of the expression products was tested using a number of polyclonal antisera and monoclonal antibodies. The polyclonal antisera recognized different sets of epitopes in the 1162-residue sequence. The N-terminal region of one of the two subunits, S2, was recognized by all polyclonal sera and by two monoclonal antibodies. This clearly immunodominant region contains at least two adjacent or overlapping epitopes, one of which has been localized within 18 residues. The epitopes found as antigenic pEX expression products do not coincide with the regions in the S1 subunit that have been found to contain hypervariable sequences. We suggest that these regions constitute conformation dependent neutralization epitopes that cannot be detected in the pEX system. The relevance of our findings for vaccine development is discussed.

Amino Acid Sequence↗

Hemodynamic and adrenergic effects of combined alpha/beta-receptor blockade versus combined beta-receptor and slow channel calcium blockade in patients with ischemic heart disease.

The effects of combined alpha/beta-adrenoceptor blockade and of beta-receptor/slow channel calcium blockade on systemic and pulmonary hemodynamics and on adrenergic activity were compared in 2 matched groups of men suffering from ischemic heart disease. They were studied at rest supine and during ischemia-inducing exercise in the seated posture using invasive percutaneous techniques. Fourteen patients received 200 mg labetalol as a single oral dosis, 15 metoprolol (100 mg) plus nifedipine (10 mg). Both regimens reduced pressures in the systemic and pulmonary circulation under all conditions. At rest, stroke volume and cardiac output slightly decreased after labetalol and increased after metoprolol/nifedipine. During exercise the changes induced by the two regimens were virtually identical: heart rates and vascular resistances were reduced, stroke volume increased, cardiac output was not significantly changed. Plasma renin activity was lowered by labetalol, unchanged by metoprolol/nifedipine. Plasma adrenaline increased after metoprolol/nifedipine only, noradrenaline with both regimens. Both combinations significantly lowered stroke work and the rate pressure product and had similar beneficial effects on the onset and the duration of angina. It is concluded that both combinations attenuate or offset the potential adverse hemodynamic effects of beta-receptor blockade alone without loss but rather enhancement of symptomatic efficacy.

Adult↗

Poliovirus-associated protein kinase: destabilization of the virus capsid and stimulation of the phosphorylation reaction by Zn2+.

The previously described poliovirus-associated protein kinase activity phosphorylates viral proteins VP0 and VP2 as well as exogenous proteins in the presence of Mg2+. In this paper, the effect of Zn2+ on the phosphorylation reaction and the stability of the poliovirus capsid has been studied in detail and compared to that of Mg2+. Phosphorylation patterns of viral and other proteins depend on the divalent cation present. In the presence of Zn2+, phosphorylation of capsid proteins VP2 and VP4 is significantly higher while phosphorylation of VP0 and exogenous phosphate acceptor proteins is not detected. Our results indicate the activation of more than one virus-associated protein kinase by Zn2+. The ion-dependent behavior of the enzyme activities is observed independently of whether the virus was obtained from HeLa or green monkey kidney cells. The poliovirus capsid is destabilized by Zn2+. The destabilization leads to a substantially increased permeability of virus particles to ethidium bromide and RNase, concomitant with decreased infectivity of the sample. This alteration of the poliovirus capsid structure is a prerequisite for effective phosphorylation of viral capsid proteins. The increased level of phosphorylation of viral capsid proteins results in further destabilization of the viral capsid. As a result of the conformational changes, poliovirus-associated protein kinase activities dissociate from the virus particle. High-performance liquid chromatography-purified viral protein VP2 is phosphorylated by the released enzymes on serine, threonine, and tyrosine in the presence of Zn2+. We suggest that the destabilizing effect of phosphorylation on the viral capsid plays a role in uncoating of poliovirus.

Amino Acids↗

Enamel fluoride and caries in Icelandic children and a comparison of enamel fluoride in Swedish and Icelandic children.

The fluoride content in surface enamel and its relationship to caries experience was studied in a group of Icelandic schoolchildren living in a low-fluoride area. Fluoride content was assessed by means of in vivo enamel biopsies sampled from 248 subjects aged 11 and 12 years. Dental examinations were performed in conjunction with the biopsy sampling and by the same examiner 1 year later. The prevalence and incidence of initial (DSI) and manifest (DFS) caries lesions were recorded separately. A median fluoride concentration of 610 ppm at a median biopsy depth of 4.2 microns was observed. A significant positive correlation was found between DSI and enamel fluoride content in girls and all older children. Additionally, surface enamel fluoride was measured in 72 Swedish children from a low-fluoride area but exposed to regular topical fluoride treatments. The difference in mean fluoride concentrations between the Icelandic and Swedish study populations was highly significant. From the measured fluoride concentrations the enamel fluoride profiles for both study populations were constructed. The differences in fluoride content were most pronounced in the outermost layer, apparently reflecting the higher exposure to and acquisition of topical fluoride in the Swedish children.

Age Factors↗

Immunoreactive beta-casomorphin-8 in cerebrospinal fluid from pregnant and lactating women: correlation with plasma levels.

We measured plasma and cerebrospinal fluid (CSF) beta-casomorphin-8, a product of beta-casein hydrolysis which has opioid activity, by RIA in women during late pregnancy and lactation and in nonpregnant nonpuerperal women. Before RIA, the samples were acidified and extracted by reverse phase silica gel chromatography, which removed most of the beta-casein. Lactating women had a significantly higher mean plasma beta-casomorphin-8 concentration (2.66 nmol/L; n = 8) than women in late pregnancy (0.82 nmol/L; n = 8) and nonpregnant women (0.32 nmol/L; n = 5). The CSF beta-casomorphin-8 concentration also was significantly higher in lactating women (mean, 0.35 nmol/L; n = 8) than during late pregnancy (0.22 nmol/L; n = 8) or in nonpregnant women (0.15 nmol/L; n = 5). A positive correlation was found between plasma and CSF beta-casomorphin-8 levels in the entire study group. The milk beta-casomorphin-8 concentration, measured in five puerperal women, averaged 19.8 nmol/L. Thus, there is a decreasing concentration gradient between milk and plasma and between plasma and CSF. Chromatographic analysis revealed mol wt heterogeneity of the RIA-active material. In CSF at least three different components were detected, two of mol wt around 900-2,000 and one of approximately 12,000. One of the low mol wt components coeluted in several chromatographic systems with synthetic beta-casomorphin-8 (mol wt, 900). Such a component was not found in milk or plasma, in which the major activity was due to larger sized peptides. The major peaks in milk were around 1,500-2,000 and 12,000 mol wt, corresponding to the larger peaks in CSF. The results suggest that fragments of the milk protein beta-casein may cross the breast parenchyma-blood barrier into plasma and subsequently penetrate the blood-brain barrier to reach the central nervous system. Thus, mammary tissue may assume endocrine function during galactopoiesis, and beta-casein could be considered a prohormone.

Adult↗

Class I and II composite resin restorations: 4-year clinical follow up.

The clinical properties and longevity of two posterior composite materials were studied during a 4-year period. 137 Class I and II restorations in 65 patients were evaluated directly using USPHS criteria. Araldite casts were used to categorize quantitatively the amount of occlusal wear according to the Leinfelder method. No differences could be found between the two materials regarding clinical properties and failure rate. The overall success rate was high (84%). The average occlusal deterioration after 4 years was about 140 microns.

Acid Etching, Dental↗

Fluorine profiles in human enamel after in vitro treatment with dentifrices of different compositions and acidities.

Fluorine uptake has been measured in human enamel after in vitro treatment with slurries of dentifrices of different compositions and acidities. Secondary ion mass spectrometry (SIMS) was used to determine the quantitative in-depth distribution profiles of fluorine. Five dentifrices were examined: ACTA (pH 5.5) with 250, 1000 and 1500 ppm F as NaF; Colgate (pH 7) with 1000 ppm F as MFP and 400 ppm F as NaF; and Pepsodent (pH 7) with 1000 ppm F as MFP. The results establish that acidulated dentifrice with low F concentration gives about the same fluorine uptake in near-surface enamel as do pH 7 dentifrices with higher F contents. In addition, at depths greater than ca 3 microns, the low F acid dentifrice in fact introduces considerably higher levels of fluorine, and yields at least three times deeper penetration, than do the non-acidulated toothpastes. The study illustrates the advantages of enhanced fluorine uptake, and thereby improved cariostatic effect, by using acidulated dentifrices even at relatively low fluoride concentration.

Cariostatic Agents↗