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Biomedical subjects

K Holmberg

Publications and source records attributed to K Holmberg.

At least 91 records · Page 5Linked to original sources

Disposition of salicylic acid in malnourished Ethiopian children after single oral dose.

The disposition of salicylic acid and salicyluric acid was studied in 57 Ethiopian children of varying nutritional status after oral administration of sodium salicylate in single doses of either 12.5 or 25 mg/kg. There was no apparent influence of nutritional status on oral salicylate disposition when related to total plasma concentrations. Unbound concentrations were predicted from total plasma concentrations on the basis of a single time point determination of protein binding in each individual, according to a Scatchard model. Areas under the unbound plasma concentration-time curve were larger and the fractional excretion of salicyluric acid was lower in children with kwashiorkor compared with control individuals. This was interpreted as lower hepatocellular metabolic activity in patients with kwashiorkor. Children with marasmus retained an unimpaired capacity for salicylate metabolism. The influence of saturable distribution and elimination are discussed.

Administration, Oral↗

Reduction of fibrinogen adsorption on PEG-coated polystyrene surfaces.

Reduction of protein adsorption by coating surfaces with polyethylene glycol (PEG) is well documented. The present work has four goals related to these previous studies: first, to develop chemistry providing densely packed, covalently bound PEG on polystyrene (PS); second, to determine the ability of these modified surfaces to reject fibrinogen; third, to compare the protein-rejecting ability of branched and linear PEGs; and fourth, to examine the utility of an ELISA-type procedure for measuring protein adsorption. It was found that PEG-epoxide could be readily coupled to amine groups of poly(ethylene imine) (PEI), which had been preadsorbed onto an oxidized PS surface. The PEG groups on branched PEGs appear to act as an excluded volume to repel proteins, similar to arguments previously raised for linear PEGs. The results of protein adsorption studies showed that fibrinogen adsorption is significantly reduced by coating polystyrene with either linear or branched PEGs of 1500 to 20,000 in molecular weight. The ELISA technique was found to be equivalent in sensitivity to radiolabeled fibrinogen for estimating adsorption levels. It is expected that PEG-coated PS will have much utility in a variety of biomedical applications.

Adsorption↗

Impaired expression of chimaeric major histocompatibility complex transgenes associated with plasmid sequences.

Plasmid vector sequences were retained (vector+), or removed (vector-) from hybrid major histocompatibility complex gene constructs prior to microinjection of fertilized ova for the production of transgenic mice. In transgenic mice containing integrated vector+ gene constructs, low levels of class II cell surface determinants were detected on splenocytes from only two out of six independent lines. Class II membrane determinants were not detectable on splenocytes from the remaining four vector+ transgenic lines. Expression of transgene products did not correlate with transgene copy number which ranged from 1-10 copies. Low levels of mRNA transcripts were detected in thymic mRNA from vector+ lines. In contrast, high levels of thymic and splenic mRNA transcripts were detected in offspring from all four vector- transgenic lines. Spleen cells from the vector- transgenic animals also expressed high levels of the hybrid major histocompatibility complex transgene products. These results implicate plasmid vector sequences in the inhibition of expression of the hybrid class II-class I major histocompatibility complex genes in transgenic mice. This putative inhibition of transgene expression presumably occurs at the level of gene transcription.

Animals↗

Plaque formation in vivo and bacterial attachment in vitro on permanently hydrophobic and hydrophilic surfaces.

Highly hydrated polyethylene oxide (PEO) films represent one type of surface modification which may interfere with biofilm formation. Protein adsorption and saliva-mediated bacterial adherence were investigated in vitro on normal and hydrophobized glass surfaces and on glass surfaces with immobilized PEO films. More protein and bacteria bound to untreated compared to hydrophobized and PEO-treated glass. Pellicle and plaque formation was also studied in vivo on ceramic crown surfaces either untreated, hydrophobized or with immobilized PEO films. Pellicle and plaque formation was similar on the untreated ceramic and PEO surfaces. Less plaque seemed to collect on these surfaces compared to adjacent normal tooth surfaces. Almost no plaque accumulated on the hydrophobic crown surface and it was virtually devoid of stainable pellicle. Even after 7 days in the mouth without oral hygiene this surface was very hydrophobic and the disclosing solution could not spread.

Actinomyces↗

The use of a bone lid to close the anterior wall defect after surgery in the maxillary sinus.

Surgery was performed in the maxillary sinus with restoration of the surgical defect in the anterior wall with a resutured bone-lid, in 12 patients with an average age of 45 years, the technique is described and evaluated clinically and radiographically (computed tomography). During the followup time of 1-4 years, the condition of the maxillary sinus was normalized. It is our opinion that the bone-lid technique for maxillary sinus surgery is useful, especially when good overview and access is necessary.

Adult↗

Overexpression of beta 2-microglobulin in transgenic mouse islet beta cells results in defective insulin secretion.

Overexpression of heavy chains of the class I major histocompatibility complex in islet beta cells of transgenic mice is known to induce nonimmune diabetes. We have now overexpressed the secretory protein beta 2-microglobulin in beta cells. Transgenic mice of one lineage had normal islets. Mice of another lineage did not become overtly diabetic but showed significant depletion of beta-cell insulin. When mice were made homozygous for the transgene locus, they developed diabetes. Introduction of the beta 2-microglobulin chain into class I heavy chain transgenic mice resulted in a significant improvement in their islet morphology and insulin content, and the female mice remained normoglycemic. These results suggest that different transgene molecules overexpressed in beta cells can cause islet dysfunction, though not necessarily overt diabetes, and that this effect is mediated by the level of transgene expression. Evidence is provided to show that beta-cell disruption by transgene overexpression occurs at the level of protein and involves a defect in insulin secretion.

Animals↗

Tryptase in nasal lavage fluid after local allergen challenge. Relationship to histamine levels and TAME-esterase activity.

The activation of mast cells is generally considered to be an important trigger mechanism in the immediate allergic response. This study focused on the determination of three markers of mast cell activation after an allergen challenge. Nasal allergen challenges were performed in 25 subjects with seasonal allergic rhinitis using three allergen doses increasing in 10-fold steps in a standardised nasal lavage model for the subsequent recovery of the markers of mast cell activation. The levels of histamine and tryptase in the nasal lavage fluid were determined using radioimmunoassays, while the TAME-esterase activity was determined using a radiochemical technique. The nasal symptoms obtained on challenge were assessed using a scoring technique. The allergen challenge resulted in significant increases in the levels of all three markers, tryptase, histamine and TAME-esterase. In the individual measurements after the challenges there was a highly significant correlation between the TAME-esterase levels and the tryptase levels (r = 0.71; P less than 0.001), while the generation of histamine and tryptase was not significantly correlated. When comparing the cumulative generation of the three markers, significant correlations were found between all three. Allergen challenges in six non-allergic controls using the same technique did not result in any increase in tryptase levels. The findings suggest that the determination of tryptase in nasal lavage fluid may be a valuable indicator of mast cell activation in the upper airways.

Adult↗

Inhibition of Streptococcus mutans adherence to hydroxyapatite with combinations of alkyl phosphates and nonionic surfactants.

Seven alkyl phosphate derivatives and three nonionic surfactants were examined for their ability to inhibit the adherence of 3H-labelled cells of Streptococcus mutans to hydroxyapatite (HA) treated with buffer (BHA) or parotid saliva (SHA). None of the compounds alone hindered binding of bacteria to BHA or SHA effectively. A combination of certain of the alkyl phosphates, notably a disodium phosphate of 1-octadecanol, and nonionic surfactant at a 1:1 molar ratio gave a strong inhibition of S. mutans adherence. Treatment of SHA with this combination resulted in 98% reduction of adherence. Adsorption of the two types of surface-active agents alone and in combinations was studied using 14C-labelled agents. Electrophoretic measurements revealed that surfaces treated with only alkyl phosphate became highly negatively charged, while surfaces treated with the combination had a zeta-potential of around zero. The results suggest that treatment with surfactants might be used to interfere with bacterial adherence on the tooth surface.

Bacterial Adhesion↗

Vascular effects of topically applied bradykinin on the human nasal mucosa.

To evaluate the vascular effects of topically applied bradykinin on the human nasal mucosa, 13 asymptomatic hay fever patients and 11 non-allergic subjects were challenged with diluent or bradykinin in three increasing doses. Mucosal blood flow was determined with the 133Xenon wash-out method and expiratory peak flow measurements used to assess nasal airway resistance before and after challenge. Nasal symptoms were recorded. Nasal secretion quantity was measured from preweighed paper handkerchiefs. Bradykinin induced a slight increase in nasal airway resistance which was similar in both allergic and non-allergic subjects. Nasal secretion was clearly increased after challenge with bradykinin compared with challenge with diluent in both allergic and non-allergic subjects. Bradykinin did not, however, induce any change in mucosal blood flow in either group. The present findings could be explained by direct effects of bradykinin on the vascular bed without reflex activity. Bradykinin would then induce an increase in vascular permeability with subsequent oedema formation and increased amounts of fluid on the mucosal surface. In contrast to allergen challenge, bradykinin challenge had no effect on the resistance vessels, changes of which had previously been shown to be largely reflex-mediated.

Administration, Topical↗

Modulation of bacterial binding to salivary pellicle by treatment with hydrophilizing compounds.

Two hydrophilizing agents, a branched polyethylene glycol derivative and a non-ionic cellulose ether (EHEC) bind to buffer-treated hydroxyapatite and prevent attachment of Streptococcus mutans. EHEC gives a more efficient surface modification, presumably due to a more complete surface coverage. Neither of the 2 hydrophilizing agents were effective on hydroxyapatite which had been pre-treated with saliva. In a small clinical trial, EHEC was found to be moderately effective in preventing plaque formation.

Adhesiveness↗

Inhibition of Streptococcus mutans adherence by means of surface hydrophilization.

Derivatives of polyalkylene oxide (PAO) were examined for their ability to inhibit adherence of 3H-labeled cells of Streptococcus mutans to hydroxyapatite (HA) and to plastic surfaces treated with buffer or parotid saliva from two individuals. Pellicles formed on HA with saliva from the two subjects were distinct in their binding capacity. One saliva promoted and the other saliva reduced adherence, as compared with the buffer control (BHA). Three of the PAO compounds effectively hindered binding of bacteria to BHA. However, on saliva-treated HA (SHA) the inhibition was not as effective. One compound, a phosphated polypropylene glycol, was potent in inhibiting adherence both to BHA and to the plastic surfaces treated with either buffer or saliva. However, treatment of HA with this compound followed by saliva incubation only gave a limited reduction in the number of bacteria binding. Evidently, salivary constituents are capable of interacting also with the PAO-treated surface. When 14C-labeled hydrophilizing agent was used, it was shown that the PAO was not replaced by salivary molecules. Instead, the components of the saliva that mediate the binding of bacteria seemed capable of adhering directly to the PAO layer.

Bacterial Adhesion↗

Hormonal correlates of male attractiveness during mate selection in the mallard duck (Anas platyrhynchos).

The aims of the present study were (1) to examine if feeding condition prior to mating influences male hormone levels and behavior, (2) to evaluate the effect of age on male hormone levels, (3) to examine a possible association between male social display activity and four steroid hormones (testosterone, dihydrotestosterone, estrogen, and corticosterone), and (4) to examine if female behavior influences male hormone levels. Thirty male and fifteen female mallards were used in this study. Observations were made on a mixed flock of mallards for 10 consecutive days in autumn. Five weeks before the observations, males were randomly assigned to a feeding regime with either an unlimited food supply (UL group) or a limited food supply (L group). Males in the UL group showed significantly greater social display activity compared to the L group males. Females never incited (courted) males from the L group. Dihydrotestosterone levels were significantly higher in males showing social display activity as compared to males not showing these behavior patterns. Testosterone levels were significantly higher in males incited by females compared to males not incited by females.

Age Factors↗

Hprt mutations and karyotype abnormalities in T-cell clones from healthy subjects and melphalan-treated ovarian carcinoma patients.

In vivo mutations at the locus for hypoxanthine phosphoribosyl transferase (hprt) were studied in 6-thioguanine (TG)-resistant T-lymphocyte clones from healthy male and female subjects and ovarian carcinoma patients treated with melphalan. Southern blot analysis of 108 clones showed alterations in 14% (4/29) of the clones from healthy males, 4.3% (2/47) of the clones from healthy females and 3.1% (1/32) of the clones from melphalan-treated patients. 2 of the 7 abnormal clones had a total deletion of the hprt gene; the others had partial deletions. Karyotype analysis of 82 clones revealed 1 clonal abnormality in 29 mutant clones from healthy males (3.6%). Loss or structural aberration of 1 X-chromosome occurred in 6% of the clones from healthy females. The frequency of karyotypic abnormalities (excluding those affecting one of the X-chromosomes) was significantly higher in clones from patients (37%) as compared to healthy females (5.9%). No aberration was found to affect the hprt locus at Xq27 in any of the 82 clones studied.

Blotting, Southern↗

The effect of topical nasal anaesthesia on allergen-induced symptoms, obstruction and blood flow.

The effect of topical anaesthesia on the nasal mucosa before and after allergen challenge was evaluated in 12 subjects with strictly seasonal allergic rhinitis. A single-blind randomized placebo-controlled design was used. The nasal challenge was carried out after pre-treatment of the nasal cavity with 52 mg of lidocaine/nasal cavity, or placebo applied topically in spray form. The number of sneezes was counted. The amount of nasal secretion was estimated by weighing used paper handkerchiefs. The capacitance and resistance vessel reactions were monitored by determining nasal peak flow and 133Xe wash-out respectively. After placebo pre-treatment the two doses of allergen induced moderate symptoms and vascular changes. Pre-treatment with local anaesthesia did not affect any of the symptoms nor did it affect the decrease in the tone of the capacitance vessels. It was found that topically applied lidocaine per se did not have any effect on nasal mucosal blood flow as measured using the 133Xe wash-out technique. However, the local anaesthesia did block the allergen-induced increase in the tone of the resistance vessels. In conclusion, a redundancy of systems appears to be involved in nasal allergic reactions. Although a reflex-induced mechanism may well play a significant role in the induction of the signs and symptoms of nasal allergic reactions, the redundancy of systems involved may well override any reduction in one single system, as appears to be the case in the present study. Lidocaine per se did not influence the nasal mucosal blood flow.

Administration, Topical↗