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Biomedical subjects

M Lindberg

Publications and source records attributed to M Lindberg.

At least 19 recordsLinked to original sources
PubMed1992

Molecular characterization and expression of a gene encoding a Staphylococcus aureus collagen adhesin.

Some strains of Staphylococcus aureus bind collagen with a high degree of specificity and affinity. This interaction can represent a mechanism of substrate adhesion and may be an important step in the pathogenesis of osteomyelitis and infectious arthritis. We now report on the cloning, sequencing, and expression of a gene name cna, encoding a S. aureus collagen adhesin. The cna gene was isolated from a lambda GT11 S. aureus genomic library and encodes an 1185 amino acid polypeptide. The deduced amino acid sequence reveals several structural characteristics similar to previously described Gram-positive bacterial cell surface proteins. Antibodies raised against the native collagen adhesin from S. aureus recognize the recombinant collagen adhesin. Collagen binding activity can be detected in a lysate obtained from Escherichia coli cells, which harbor the cloned cna gene on an expression plasmid. Collagen-binding proteins can be detected in the lysate when analyzed by a Western blot type assay in which the membrane-transferred proteins are probed with radioactively labeled collagen. Finally, the bacterial lysate containing the recombinant adhesin can effectively inhibit the binding of soluble collagen to cells of S. aureus.

Adhesins, Bacterial↗
PubMed1992

Cloning and expression of two different genes from Streptococcus dysgalactiae encoding fibronectin receptors.

Binding of bacteria to fibronectin has been implicated as a mechanism of bacterial adhesion to the host tissue. In this report we have analyzed the binding of a strain of Streptococcus dysgalactiae to fibronectin. The cells bind to a site in the NH2-terminal domain of the protein via trypsin-sensitive cell surface components. Furthermore, a lysate prepared by sonication of streptococcal cells contained fibronectin-binding proteins that inhibit the binding of the ligand to intact bacteria. When the proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, blotted to an Immobilon-P filter, and probed with 125I-labeled fibronectin, a 140-kDa fibronectin-binding protein was identified along with a number of smaller binding proteins. A genomic DNA library was constructed and screened for the expression of fibronectin-binding proteins. Two clones were isolated and shown to contain unrelated inserts by restriction mapping and cross-hybridization experiments. The two encoded proteins were also immunologically distinct although both bound to the same region of the fibronectin molecule, and both effectively inhibited the binding of 125I-fibronectin to bacterial cells. Immunological analyses showed that only one of the two proteins tentatively identified as fibronectin receptors was expressed in detectable quantities in the Streptococcus dysgalactiae strain under the culture conditions employed.

Bacterial Adhesion↗
PubMed1992

Toremifene and its metabolites enhance doxorubicin accumulation in estrogen receptor negative multidrug resistant human breast cancer cells.

The enhanced accumulation of doxorubicin by agents known to reverse multidrug resistance provides a good functional test for evaluating modulating activity. In the present study, the non-steroidal triphenylethylene toremifene selectively increased doxorubicin accumulation in multidrug resistant estrogen receptor negative MDA A-1 human breast cells compared to the MDA 231 wild type cells. MDA A-1 cells were noted to be 1,000 fold resistant to doxorubicin (IC 50 = less than 0.1 microgram/ml MDA 231; IC 50 = 100 micrograms/ml MDA A-1). Total accumulation of doxorubicin, expressed as area under the time concentration curve (AUC), was increased significantly in doxorubicin resistant cells (156% increase) versus wild type MDA 231 cells (6% increase). Correction of the accumulation defect to doxorubicin in drug resistant cells required a 18-20 hour pre-incubation with toremifene. The effects of toremifene on cell cycle in MDA A-1 cells was analyzed by flow cytometric techniques. Toremifene had a dose response relationship in blocking cells in G0-G1 reducing the number of cells entering S phase of the cell cycle. This effect was maximal at concentrations which increased the accumulation of doxorubicin in MDA A-1 cells. Several metabolites of toremifene were also noted to increase doxorubicin accumulation in MDA A-1 doxorubicin resistant cells. Tore XVIII (deaminocarboxytoremifene), Tore IV (4-hydroxy-N-desmethyltoremifene) and N-desmethyltoremifene all increased the accumulation of doxorubicin significantly (114%, 128% and 42% respectively). Finally, we show evidence that toremifene and its active metabolites are present in high concentrations in human plasma following a single 200 mg oral dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗
PubMed1992

Pharmacologic properties of (-)-3PPP (preclamol) in man.

The dopamine (DA) autoreceptor agonist (-)-3PPP (preclamol) was tested in male schizophrenic volunteers for safety. The drug was administered intramuscularly in a single rising dose design, crossed with a similar "rising dose" placebo period; all evaluations and raters were blind to drug or placebo administration. Pharmacokinetic, endocrine, safety, and mental status outcome measures were completed before and after each single dose of drug or placebo. Pharmacokinetic analysis showed blood levels between 200-500 pmoles/ml after the intramuscular drug doses of 30-40 mg. Drug half life is 2-2.5 hrs. Growth hormone (GH) levels were elevated in a linear fashion to the 30 mg dose; whereafter, the drug failed to affect GH at all. All safety evaluations were negative, including any untoward effects on the major organ systems. After single dose drug administration, evidence of antipsychotic action occurred in two of the four subjects. This study suggests that (-)-3PPP/preclamol is a safe drug for study in the treatment of schizophrenia and may have antipsychotic efficacy.

Administration, Oral↗
PubMed1992

Density and morphology of Langerhans cells in basal cell carcinomas of the face and trunk.

We investigated the density and morphology of Langerhans cells in epidermal sheets of basal cell carcinomas in chronically sun-exposed skin (face) and less exposed skin (trunk) of 65 patients. Langerhans cells in perilesional and control skin at the same anatomical sites as the tumours were also examined. Two markers (ATPase and OKT6) were used in a parallel fashion to identify Langerhans cells. The density of the cells was reduced, and their morphology was changed in epidermis overlying tumours of both the face and trunk. These alterations were confined to tumour areas, as Langerhans cells in perilesional skin were normal when compared with control skin at both anatomical sites. Results with both markers were the same.

Adult↗
PubMed1992

Permeation and destructive effects of disinfectants on protective gloves.

In working situations where there is a possibility of acquiring blood-borne infections, the use of disinfectants is important. It is also important to use protective gloves, both to protect the skin against disinfectants and to protect against infections. Changes in the structure of the glove material may, however, interfere with the protective capability of the gloves. The influence of 4 disinfectants on the material structure and protective effect of 6 different brands of protective gloves was studied. The proposed International Organization for Standardization (ISO) standard method for determining the liquid chemical resistance of air-impermeable materials was used for permeation testing. Pieces of latex and vinyl glove were also exposed to isopropanol and ethanol for 10, 30 and 60 min and then viewed in a scanning electron microscope. Isopropanol permeated through latex and vinyl gloves in less than 10 min. The polyethylene (PE) gloves were of quite variable quality, and the breakthrough time ranged from 4 to greater than 240 min. The latex and vinyl gloves were also permeated by ethanol, but at a much lower rate. The disinfectants Blifacid, based on p-chloro-m-cresol, and Cidex, based on glutaraldehyde, did not permeate any of the gloves tested within 60 min. Isopropanol had a destructive effect on the material, which became opaque, stiff and brittle. This change in structure was verified with the scanning electron microscope. The tested gloves of latex, vinyl and PE, gave acceptable protection from contact with Blifacid and Cidex for at least 60 min. The same gloves do not give any total protection from contact with isopropanol and ethanol.

Disinfectants↗
PubMed1992

The acetic acid test in evaluation of subclinical genital papillomavirus infection: a comparative study on penoscopy, histopathology, virology and scanning electron microscopy findings.

OBJECTIVES: To evaluate colposcopic criteria in acetowhite lesions of the penis ("penoscopy") for the diagnosis of subclinical genitoanal papillomavirus infection (GPVI) compared with histopathological criteria of HPV involvement and to various hybridisation assays for HPV DNA detection, and to depict typical lesions by scanning electron microscopy. DESIGN: The study included 101 randomly selected male partners of females with known GPVI, or with penile symptoms such as itching, burning and dyspareunia who did not exhibit overt genital warts but appeared to be afflicted with acetowhite penile lesions after topical application of 5% acqueous acetic acid. Lesions were judged by penoscopy as either typical, conspicuous or nontypical for underlying HPV infection. Biopsy specimens from 91 men were examined by light microscopy and by either Southern blot (SB), polymerase chain reaction (PCR) and/or in situ hybridisation (ISH) assays for the presence of HPV DNA of the HPV types 6, 11, 16, 18, 31, 33 and 42 (Group A). From another ten men lesions clinically typical for GPVI were also examined topographically by scanning electronic microscopy (Group B). SETTING: The STD out-patient clinic of the Department of Dermatovenereology of Karolinska Hospital, Stockholm, Sweden. RESULTS: Group A Seventy eight (86%) of the biopsied lesions met the penoscopy criteria of being either typical of or conspicuous for GVPI. The agreement between penoscopy and histopathology was fairly good, as HPV diagnosis was made by both methods in 56 (62%) of the cases. The reliability of applying strict colposcopic hallmarks was further substantiated by the finding that 55 (60%) of the biopsy specimens taken from penoscopically typical/conspicuous lesions contained HPV DNA. However, there are diagnostic pitfalls for the acetic acid test. Coexistence of an eczematoid reaction with changes indicative of HPV influence was detected in six (7%) of the cases, while an inflammatory response only occurred in 17 (19%) of the specimens. Additional histopathological diagnoses (normal epithelium, lichen sclerosus et atrophicus, balanitis circinata parakeratotica, verruca plana) were established in another eight (9%) of the cases. Among the HPV DNA positive cases, all of the HPV types tested for were detected with the exception of HPV 18. A severe penile intraepithelial neoplasia (PIN III) was revealed in five (5%) of biopsies; HPV 16 was present in two and HPV 42 in one of these biopsy specimens. GROUP B: Scanning electron microscopy depiction harmonised with the penoscopy findings showing that subclinical GPVI characteristically exhibits a well demarcated, slightly elevated border and that the central area of lesions often displays a "groove" in which the epithelium appears to be thin with protrusions from beneath that probably represent capillaries. CONCLUSION: Use of the acetic acid test for evaluation of GPVI should be combined with a colposcopic evaluation based on strict topographic hallmarks, followed by a directed biopsy for light microscopic evaluation. We found that the positive predictive value of colposcopy was as high when correlated with histopathological findings (72%) as when virological methods were used, whether HPV DNA hybridisation testing was performed with the well established SB and ISH assays (45%), or by applying the newly introduced and highly sensitive PCR assay as well (71%). False positivity from the acetic acid test occurs and is mainly due to inflammatory conditions but also to the presence of other conditions. Epithelial fissures are evidently associated with some subclinical GPVI lesions and may potentially represent loci minores for infectious stimuli and perhaps facilitate the transmission of some blood-borne STDs. We prose that the term "papillomavirus balanoposthitis" should be used for penile HPV infection associated with inflammatory responses. Our study indicates that PIN III frequently occurs in a subclinical form and may be associated with not only previously identified "high-risk" HPV types such as type 16, but also with the HPV type 42 that has not previously been considered as oncogenic.

Acetates↗
PubMed1992

Self-reported prevalence of disability after subarachnoid haemorrhage, with special emphasis on return to leisure and work.

The prevalences of motor and language impairments and of disabilities in activities of daily living (ADL), leisure and work were investigated in a consecutive series (n = 296) of long-term survivors of subarachnoid haemorrhage (SAH). Motor and language impairments were present in 17 and 20%, respectively. The majority reported independence in self-care (91%) and instrumental (80%) ADL, but among the self-care independent, 23% reported need of personal assistance. Leisure disability occurred in 48% and vocational disability in 40%. Hence, disabilities are more common after SAH than is indicated by occurrences of motor and language impairments. It is concluded that the discrepancy between the prevalences of impairments and of disabilities may be to a great extent caused by coping difficulties in relation to socio-demographic and geographic circumstances. The findings indicate a need for rehabilitative follow-up for virtually all SAH-patients.

Activities of Daily Living↗
PubMed1992

Quantitative analysis of Langerhans' cells in epidermis at irritant contact reactions using confocal laser scanning microscopy.

Confocal laser scanning microscopy (CLSM) was used for quantitative analysis of CD1a+ cells in epidermis at irritant reactions. Sodium lauryl sulphate (2% and 4%) or non-anoic acid (20% and 80%) were applied to the skin of healthy volunteers under occlusion for 24 h. Skin biopsy specimens were taken after additional 24 h and were snap frozen. Freeze-sections, 25 microns thick, were stained with anti-CD1a antibodies (Leu-6) followed by FITC-labelled rabbit anti-mouse IgG. The sections were viewed and optically sectioned in the CLSM at four depth levels. The data was analysed using a threshold value for the fluorescence. The obtained result is presented as the proportion of specimen area having a fluorescence intensity above the threshold. The result demonstrates that the CLSM is a useful tool for obtaining not only structural information but also quantitative information from a defined tissue volume. In the present investigation it was possible to demonstrate variations in CD1a+ reactivity in epidermis at detergent-induced irritant reactions with a marked decrease in CD1a+ after 80% non-anoic acid exposure and only minor differences in the CD1a+ after 2% and 4% sodium lauryl sulphate exposure.

Cell Count↗
PubMed1992

Elemental changes in guinea pig epidermis at repeated exposure to sodium lauryl sulfate.

Epidermal hyperplasia is the response of the epidermis to external harmful stimuli. The control and regulation of this hyperplasia is not completely understood. It has been proposed that changes in the cellular sodium/potassium ratio are of importance in the regulation of cell proliferation. To evaluate if such a change in the elemental content of epidermal cells can be one factor to consider at irritant contact dermatitis, we performed a quantitative assessment of sodium lauryl sulfate (SLS)-induced contact reactions in the guinea pig. SLS was applied 1, 2 or 3 times and biopsies were obtained at 24 and 84 h after the last application. It was found that repeated exposures to SLS induced a hyperplasia of epidermis at 24 h persisting at 84 h. At 24 h there were significant changes in the sodium and potassium content of the keratinocytes. At 84 h there was still an increased potassium level in the cells and the sodium/potassium ratio was significantly decreased in epidermis exposed three times to SLS. This implies that changes in cellular sodium/potassium ratios occur in epidermal hyperplasia following irritant stimuli.

Animals↗
PubMed1991

Two different genes encode fibronectin binding proteins in Staphylococcus aureus. The complete nucleotide sequence and characterization of the second gene.

A gene encoding a fibronectin binding protein (FnBP) has recently been isolated and sequenced from Staphylococcus aureus strain 8325-4. In the same bacterial strain, 682 bp downstream to the stop codon of this gene (fnbA), a second gene termed fnbB has not been discovered, encoding another FnBP (FnBPB). The two genes show in large parts striking sequence homologies. The complete amino acid sequence encoded by fnbB has been deduced and compared to that deduced from fnbA. In FnBPB a stretch of 66 amino acids downstream to the signal peptide has 75% identity with the corresponding region in FnBPA. At the C-terminal site another 394 amino acid stretch is almost identical in both gene products. This stretch contains the 38 amino acid long D repeats, the wall spanning Wr repeats and the hydrophobic membrane spanning domain. In FnBPA each of the three D repeats has been identified as a fibronectin binding structure. These structures are highly conserved in FnBPB and most likely represent the major Fn-binding domain of this protein. However, a subclone of gene fnbB lacking the coding region for the D repeats also clearly expresses fibronectin binding activity. This additional binding site is so far unique for FnBPB and interacts like the D domains with the N-terminal 24-31-kDa fragment of fibronectin. The purified recombinant FnBP fragment (not containing the D repeats) completely inhibits the binding of fibronectin to whole cells of S. aureus.

Amino Acid Sequence↗
PubMed1991

Molecular dynamics simulation of the renin inhibitor H142 in water.

H142 is a synthetic decapeptide designed to inhibit renin, an enzyme acting in the regulation of blood pressure. The inhibiting effect of H142 is caused by a reduction of a -Leu-Val-peptide bond (i. e. C(= O)-NH----CH2-NH). The conformational and dynamical properties of H142 and its unreduced counterpart (H142n) was modelled by means of molecular dynamics simulations. Water was either included explicitly in the simulations or as a dielectric continuum. When water molecules surround the peptides, they remain in a more or less extended conformation through the simulation. If water is replaced by a dielectric continuum, the peptides undergo a conformational change from an extended to a folded state. It is not clear whether this difference is a consequence of a too short simulation time for the water simulations, a force-field artifact promoting extended conformations, or if the extended conformation represents the true conformational state of the peptide. A number of dynamic properties were evaluated as well, such as overall rotation, translational diffusion, side-chain dynamics and hydrogen bonding.

Amino Acid Sequence↗
PubMed1991

The influence of a single application of different moisturizers on the skin capacitance.

Moisturizers are believed to improve the skin condition by increasing the water content of the stratum corneum. A variety of techniques for assessing skin hydration has been developed. In the present study the capacitance following a single application of different moisturizers to normal skin on 12 volunteers was measured with the commercial available Corneometer 420. The moisturizers were pure petrolatum and three oil-in-water creams. The latter contained either glycerine, glycerine and pyrollidone carboxylic acid, or urea as humectant agents. The first measurement of the change in the capacitance was done 2 h after application of the products. All tested products increased the capacitance in the same order of magnitude. For the creams the values were significantly enhanced during the experimental period (6 h). Excess product were removed from some skin areas after the 2 h measurement. This caused immediately a significant decrease in the capacitance of the cream treated sites, whereas a tendency towards higher values were noted on the petrolatum-treated sites. These findings indicate that the non-absorbed components influences the capacitance values. Hence, the interpretation of electrical measurements with respect to skin moisture should be made with caution.

Adult↗
PubMed1991

Differential effects of sodium lauryl sulphate and non-anoic acid on the expression of CD1a and ICAM-1 in human epidermis.

Normal human skin was exposed to two different detergents, sodium lauryl sulphate in distilled water and non-anoic acid in isopropanol at different concentrations. The detergents were applied under occlusion in epicutaneous tests for 24 h and biopsies were taken at 24 or 48 h. Frozen sections were labelled with monoclonal antibodies against CD1a, CD3 and ICAM-1. The evaluation of the labelled sections showed that there were differential effects on the expression of ICAM-1 and CD1a+ cells in epidermis. After non-anoic acid application ICAM-reactivity could not be detected and there was a decrease of staining for CD1a after exposure to 80% non-anoic acid. Sodium lauryl sulphate treatment, however, induced ICAM-1 expression on keratinocytes and had minor effects on the number of CD1a+ cells. ICAM-1 expression was also detected in normal epidermis in 3 of 9 unexposed control biopsies and after occlusion with the vehicles distilled water and isopropanol. An increased amount of CD3+ cells was found in the skin exposed to both detergents. The results show that there are dose and time dependent variations in the epidermal response to irritants which might influence the immunological events taken place in the epidermis.

Adult↗
PubMed1991

Studies of irritant reactions on epidermis: the application of energy dispersive x-ray microanalysis.

Modern man is exposed to an increasing amount of chemicals in the environment. The skin is a complex tissue with regards to both structure and function. Contact with external stimuli can lead to various responses in the skin depending on the type of stimuli, the dose and time of exposure and the status of the exposed individual. The electron probe microanalytic technique can be used to obtain information on physiological alterations within the skin and especially the epidermis when the normal homeostasis is disturbed by contact with external stimuli. The present paper presents a review of some aspects of contact dermatitis and the possibility of using the electron probe microanalytic technique for analysis of epidermal events of this condition.

Animals↗