Biomedical subjects
Publications and source records attributed to M Jonsson.
The coagulum proteins of human semen, semenogelins I and II, are secreted in abundance by the seminal vesicles. Their function in reproduction is poorly understood as they are rapidly degraded in ejaculated semen. However, more recent results indicate that it is time to put the semenogelins in a broader physiological perspective that goes beyond reproduction and fertility.
The objective of this study was to evaluate a new C. trachomatis screening method based on a home sampling strategy and using the internet as a facility for the participants to obtain their test results. A population based screening study was designed in primary care setting in Umeå, Sweden. It included all males aged 22 years (n=1074), living in Umeå, a city with 100 000 inhabitants. The participation rate was 38.5%. In the study group, 1.1% were infected with C. trachomatis. Participants obtained their results on the internet and three quarters of males infected with C. trachomatis sought medical treatment independently. The number of times the internet was visited exceeded the number of urine samples tested. The internet C. trachomatis screening strategy achieved the highest male participation rate yet published, and also reached young males outside the high risk groups.
BACKGROUND: Vecuronium depresses carotid body chemosensitivity during hypoxia. We hypothesized that this is caused by inhibition of cholinergic transmission of the carotid body. METHODS: The carotid body with its sinus nerve was removed en bloc from thiopentone-anaesthetized adult male New Zealand rabbits and perfused in vitro with modified Tyrodes buffer solution at constant perfusion pressure, temperature, a buffer pH of 7.4 and normocapnia. Chemoreceptor discharge and spike frequencies (fx) were recorded from the whole sinus nerve after administration of 500 microg nicotine, given as duplicated controls and thereafter following 30 min perfusion of equipotent concentrations of atracurium (28.1 microM) or vecuronium(10 microM), after 30 min of neostigmine perfusion (9.2 microM) and finally after 30 min wash-out with buffer solution only. A short-lasting hypoxic test was performed before and at the end of the experimental period to confirm the responsiveness and validity of the preparation. RESULTS: Atracurium (n = 7) and vecuronium (n = 6) reduced chemoreceptor responses to nicotine by 70 +/- 30% and 66 +/- 19% (SEM) (P<0.05). Chemoreceptor discharges showed full recovery after neostigmine in the atracurium group and partial recovery in the vecuronium group (P<0.05). Finally, after wash-out the chemoreceptor responses to nicotine had fully recovered in both groups. CONCLUSION: Atracurium and vecuronium in equipotent concentrations block nicotine-induced chemoreceptor responses of the carotid body.
Oxidation potentials, E1/2(ox) of alpha-hydroxyalkyl radicals of the type R(1)R(2)C(*)OH (denoted K(1)H(*)) have been obtained in acetonitrile by photomodulated voltammetry. The values of E1/2(ox) increase as the R(1) and R(2) groups are changed from alkyl to aryl and, in particular, strong electron-withdrawing functionalities such as CN and CF3. Using rate data available in the literature for the pinacol photoexchange reaction K + K(1)H(*) --> KH(*) + K(1), it is found that as the difference in the standard potential of the ketone K, EK degrees and the oxidation potential of K(1)H(*), E1/2(ox), increases there is a modest increase in the exchange rate constant, k(ex). This indicates that even if some charge transfer may occur between the hydroxyalkyl radical and the ketone in the transition state, it is certainly not to the extent of a complete electron transfer. If the exchange reaction is treated as a simple hydrogen atom transfer process within the Marcus model, the intrinsic barrier is found to be 8-13 kcal mol(-1) due to the changes occurring in bonds, hybridizations, and bond angles. Finally, acid dissociation constants for K(1)H(*) are provided by means of a thermochemical cycle.
The objective of this study was to compare cerebrospinal fluid (CSF) levels of the light subtype of the neurofilament proteins (NFL), tau, and beta-amyloid42 (Abeta42) in individuals with moderate or severe white matter changes (WMC) and in those with mild or no WMC. Twenty-two patients with Alzheimer's disease (AD), nine patients with subcortical vascular dementia (SVD), and 20 normal controls were included in the study. The occurrence of WMC was evaluated by a neuroradiologist using the Blennow-Wallin scale. Thirty-seven subjects had no or only punctate WMC; 14 had moderate to severe WMC. Both diagnostic group and WMC, but not gender or apolipoproteinE E4 inheritance, contributed to the variance in the CSF levels of tau, NFL, and Abeta42. In patients with moderate to severe WMC, CSF NFL (P < 0.01), but not CSF tau or CSF Abeta42, was increased also after correction for age, gender, and degree of cognitive impairment. A comparison between patients and controls with any signs of WMC and those without such signs yielded a similar result: CSF NFL (P < 0.001) was increased in the group with signs of WMC. As in numerous previous studies, we found that CSF tau was increased in AD (P < 0.001) compared with controls. Furthermore, CSF NFL was increased in both AD and SVD compared with controls (P < 0.001 for both). Although diagnostic group seems to be a stronger predictor of the variance found in CSF NFL, a clear association between the presence of WMC and increased CSF NFL was found. Because NFL is located mainly in large myelinated axons, increased CSF NFL in individuals with WMC probably reflects axonal degeneration.
A novel synthesis of 2,3-dihydrobenzo[b]thiophene-5-ol based on intramolecular homolytic substitution on sulfur was reported. The "antioxidant profile" of the series of 2,3-dihydrobenzo[b]furan-5-ol (2a) its 1-thio (2b), 1-seleno (2c) and 1-telluro (2d) analogues was determined by studies of redox properties, the capacity to inhibit stimulated lipid peroxidation, the reactivity toward tert-butoxyl radicals, the ability to catalyze decomposition of hydrogen peroxide in the presence of glutathione, and the inhibiting effect on stimulated peroxidation in liver microsomes. The one-electron reduction potentials of the aroxyl radicals corresponding to compounds 2a-2d, E degrees (ArO(*)/ArO(-)) were 0.49, 0.49, 0.49, and 0.52 V vs NHE, respectively, as determined by pulse radiolysis. With increasing chalcogen substitution the compounds become slightly more acidic (pK(a) = 10.6, 10.0, 9.9, and 9.5, respectively, for compounds 2a-2d). By using Hess' law, the homolytic O-H bond dissociation enthalpies of compounds 2a-2d (340, 337, 336, and 337 kJ mol(-)(1), respectively) were calculated. The reduction potentials for the proton coupled oxidation of compounds 2a-2d (ArOH --> ArO(*) + H(+)) as determined by cyclic voltammetry in acetonitrile were 1.35 (irreversible), 1.35 (quasireversible) 1.13 (reversible), and 0.74 (reversible) V vs NHE, respectively. As judged by the inhibited rates of peroxidation, R(inh), in a water/chlorobenzene two-phase lipid peroxidation system containing N-acetylcysteine as a thiol-reducing agent in the aqueous phase, the antioxidant capacity increases (2d > 2c = 2b > 2a) as one traverses the group of chalcogens. Whereas the times of inhibition, T(inh), were slightly reduced for the oxygen (2a) and sulfur (2b) derivatives in the absence of the thiol-reducing agent, they were drastically reduced for the selenium (2c) and tellurium (2d) derivatives. This seems to indicate that the organochalcogen compounds are continuously regenerated at the lipid aqueous interphase and that regeneration is much more efficient for the selenium and tellurium compounds. The absolute rate constants for the oxidation of compounds 2a-2b by the tert-butoxyl radical in acetonitrile/di-tert-butyl peroxide (10/1) were the same-2 x 10(8) M(-)(1) s(-)(1). Whereas the oxygen, sulfur, and selenium derivatives 2a-2c were essentially void of any glutathione peroxidase-like activity, the organotellurium compound 2d accelerated the initial reduction of hydrogen peroxide, tert-butyl hydroperoxide, and cumene hydroperoxide in the presence of glutathione 100, 333, and 213 times, respectively, as compared to the spontaneous reaction. Compounds 2a-2d were assessed for their capacity to inhibit lipid peroxidation in liver microsomes stimulated by Fe(II)/ADP/ascorbate. Whereas the oxygen, sulfur, and selenium compounds showed weak inhibiting activity (IC(50) values of approximately 250, 25, and 13 microM, respectively), the organotellurium compound 2d was a potent inhibitor with an IC(50) value of 0.13 microM.
The prevalence of exfoliation syndrome was studied in 39 patients suffering from dementia and cognitive impairment; a positive finding of exfoliation was detected in 11/39 of these patients. A comparison with an age-matched population survey showed that the prevalence of ocular exfoliation and the relative risk were significantly elevated. These results suggested that lesions related to the exfoliative process might be located also in the brain of patients suffering from dementia and cognitive impairment.
BACKGROUND: Electrophoresis of serum samples allows detection of monoclonal gammopathies indicative of multiple myeloma, Waldenström macroglobulinemia, monoclonal gammopathy of undetermined significance, and amyloidosis. Present methods of high-resolution agarose gel electrophoresis (HRAGE) and immunofixation electrophoresis (IFE) are manual and labor-intensive. Capillary zone electrophoresis (CZE) allows rapid automated protein separation and produces digital absorbance data, appropriate as input for a computerized decision support system. METHODS: Using the Beckman Paragon CZE 2000 instrument, we analyzed 711 routine clinical samples, including 95 monoclonal components (MCs) and 9 cases of Bence Jones myeloma, in both the CZE and HRAGE systems. Mathematical algorithms developed for the detection of monoclonal immunoglobulins (MCs) in the gamma- and ss-regions of the electropherogram were tested on the entire material. Additional algorithms evaluating oligoclonality and polyclonal concentrations of immunoglobulins were also tested. RESULTS: CZE electropherograms corresponded well with HRAGE. Only one IgG MC of 1 g/L, visible on HRAGE, was not visible after CZE. Algorithms detected 94 of 95 MCs (98.9%) and 100% of those visible after CZE. Of 607 samples lacking an MC on HRAGE, only 3 were identified by the algorithms (specificity, 99%). Algorithms evaluating total gammaglobulinemia and oligoclonality also identified several cases of Bence Jones myeloma. CONCLUSIONS: The use of capillary electrophoresis provides a modern, rapid, and cost-effective method of analyzing serum proteins. The additional option of computerized decision support, which provides rapid and standardized interpretations, should increase the clinical availability and usefulness of protein analyses in the future.
We have analyzed the content of N-unsubstituted glucosamine in heparan sulfate from glypican-1 synthesized by endothelial cells during inhibition of (a) intracellular progression by brefeldin A, (b) heparan sulfate degradation by suramin, and/or (c) endogenous nitrite formation. Glypican-1 from brefeldin A-treated cells carried heparan sulfate chains that were extensively degraded by nitrous acid at pH 3.9, indicating the presence of glucosamines with free amino groups. Chains with such residues were rare in glypican-1 isolated from unperturbed cells and from cells treated with suramin and, surprisingly, when nitrite-deprived. However, when nitrite-deprived cells were simultaneously treated with suramin, such glucosamine residues were more prevalent. To locate these residues, chains were first cleaved at linkages to sulfated l-iduronic acid by heparin lyase and released fragments were separated from core protein carrying heparan sulfate stubs. These stubs were then cleaved off at sites linking N-substituted glucosamines to d-glucuronic acid. These fragments were extensively degraded by nitrous acid at pH 3.9. When purified proteoglycan isolated from brefeldin A-treated cells was incubated with intact cells, endoheparanase-catalyzed degradation generated a core protein with heparan sulfate stubs that were similarly sensitive to nitrous acid. We conclude that there is a concentration of N-unsubstituted glucosamines to the reducing side of the endoheparanase cleavage site in the transition region between unmodified and modified chain segments near the linkage region to the protein. Both sites as well as the heparin lyase-sensitive sites seem to be in close proximity to one another.
In this work we have quantitatively analyzed substituent effects on the homolytic bond dissociation enthalpy of 79 different compounds using a method based on discrete distance dependent atomic contributions to a molecular property. The resulting empirical relationship can be used to predict C-H bond dissociation enthalpies (within +/-10 kJ mol(-1)) for molecules where resonance contributions and captodative stabilization are insignificant. For species where captodative stabilization of the corresponding C-centered radical is possible, the method clearly overestimates the C-H bond dissociation enthalpy.
AIMS: To determine the inter-rater reliability in scoring sensory and motor function and in defining sensory and motor levels in incomplete spinal cord injury, using the revised 1992 International Standards for Neurological and Functional Classification of Spinal Cord Injury (ISCSCI-92) and to determine the effect on raters agreement of one standardising assessment. METHODS: Two physicians and two physiotherapists at the Spinal Cord Injury Unit, Karolinska Hospital, classified 23 patients according to the ISCSCI-92. Kappa values were calculated. RESULTS: Kappa values varied from 0 to 0.83 (poor to very good) for the pin-prick scores, from 0 to 1 for the light touch scores and from 0 to 0.89 for motor function after the standardising assessment. Kappa values for sensory and motor levels were fair to poor after the standardising assessment. The results showed improvement in degree of agreement in 35/46 dermatomes for scoring pin-prick, in 15/42 for light touch, in 14/19 segments for motor function and for three out of four sensory and motor levels. CONCLUSION: This study indicates a weak inter-rater reliability for scoring incomplete SCI lesions using the ISCSCI-92.
Adenoviral vectors effectively transfer genes to rat salivary glands. However, potent immune responses limit their use in vivo. Mice offer more opportunities than rats for the study of these immune processes. We first established conditions for infection of mouse salivary glands, with an adenoviral vector. The effects of time, viral dose, viral diluent buffer volume, and dexamethasone on expression of a transgene, luciferase, were determined by means of the recombinant vector AdCMVluc. Optimal luciferase expression was observed when the vector was suspended in 50 microL of buffer. This volume completely filled the gland parenchyma and slightly distended the capsule. Dexamethasone increased immediate transgene expression and reduced the acute inflammation one day following viral administration, but did not alter subsequent mononuclear inflammation or transgene expression 14 or 28 days later. An adenoviral vector encoding either anti-inflammatory cytokine IL-4 or IL-10 was co-administered with AdCMVluc to increase transgene expression at 14 and 28 days. While this strategy did not extend the duration of luciferase expression, co-administration of AdCMVIL-10 with AdCMVluc almost completely eliminated the chronic inflammatory infiltrate in the glands after 28 days. This study demonstrates that adenoviral-mediated gene transfer to mouse submandibular glands is possible by intraductal cannulation and that reduction of either the acute or chronic inflammatory infiltrates was insufficient to increase long-term transgene expression in this tissue.
In this work, a new topological approach based on simple matrix algebra is introduced to explore substituent effects at the level of atomic additivity in the absence of significant resonance contributions. In the framework of the suggested method, all atoms are classified according to element and valence state. The sums of the inverse squared distances between the substituent atoms and the reaction centre of the molecule are used as operational parameters in the present method. The approach implies atomic level of consideration of inductive and steric effects and allows for quantification of substituent effects without the use of pre-established group substituent constants. The practical application of the model is illustrated by the quantitative interpretation of ionization energies and gas basicity of a broad range of amines. Further development of the elaborated approach is also discussed.
The efficacy of calcium propionate for the prevention of parturient paresis (milk fever) was compared with that of calcium chloride using 194 cows that had experienced milk fever during the previous calving. The cows were mainly of the Swedish Red and White and Swedish Friesian breeds and were divided randomly into an experimental group (n = 99) and a control group (n = 95). The cows in the experimental group received up to six boluses of 20 g of calcium as calcium propionate between 36 h before and 24 h after calving; the cows in the control group received up to four doses of 54 g of calcium as a commercially available oily solution of calcium chloride during the same period. Incidence of milk fever was recorded as the percentage of cows that were treated by a veterinarian because they showed clinical signs of the disease and had a blood calcium concentration less than 8.0 mg/dl. Twenty-five (25.3%) cows in the experimental group and 22 cows (23.2%) in the control group developed milk fever. The incidence of milk fever for cows in both groups was significantly lower than the 36.0% found in 713 cows that had experienced milk fever during their previous calving but received no prophylactic treatment. Therefore, calcium propionate was considered to have had a significant preventive effect, comparable with that of calcium chloride.
We present a study of how kinks, flexible bends, and flexible joints in the DNA helix, induced by binding cis-diamminedichloroplatinum(II) (cis-DDP), transdiamminedichloroplatinum(II) (trans-DDP), and chlorodiethylenetriammineplatinum(II) (dien-Pt) to the DNA, affect the electrophoretic migration of DNA in agarose gels. For long DNA the conformation oscillates between extended and compact states during the migration, as for native DNA. The presence of flexible joints decreases both the length of time and the step length of the cycles, but in a compensatory manner so that there is no net effect on the mobility. This demonstrates that in some cases mobility alone cannot detect pertubations in the DNA helix. Kinks and flexible bends reduce the mobility because they both lead to longer time periods of the cycles. With kinks the reduction is strongest at low fields because at high fields the kinks are straightened out; the steps thus become even longer than for native DNA. The results suggest that a combination of mobility and orientation measurements on reptating DNA can be used for distinguishing different kinds of structural alterations in the DNA.
OBJECTIVE: To evaluate acetowhite changes of the cervix and vulva as a predictor of human papillomavirus (HPV) infection. METHODS: In this population-based study all women aged 19, 21, 23, and 25 years and registered as living in a primary health care area within the city of Umeå, Sweden were eligible for inclusion. Each participant underwent a gynecologic examination with sampling of epithelial cells for HPV-DNA detection and Papanicolaou smear. Colposcopy was performed 5 minutes after application of 5% acetic acid. A two-step polymerase chain reaction (PCR) technique was employed for HPV-DNA detection. RESULTS: Colposcopy and sampling of epithelial cells could be performed in 535 women. The sensitivity of detection of HPV infection by the acetowhitening of the cervix was 22% (95% confidence interval [CI] 18%, 26%). The specificity of detection of HPV infection by the acetowhitening of the cervix was 90% (95% CI 87%, 93%). The sensitivity of detection of HPV infection by cytology was 13% (95% CI 10%, 16%), and the specificity was 99% (95% CI 98%, 100%). The combination of acetowhitening and cytology did not improve the diagnostic value. CONCLUSION: Acetowhitening of the cervix and vulva has low sensitivity as a predictor of HPV infections as determined by PCR.
The aim of this study was to determine the associations between risk behaviour and women's reported sexually transmitted diseases (STDs). All the women aged 19, 21, 23 and 25, residing in a specified housing area, were invited to answer a questionnaire regarding their sexual behaviour, smoking and alcohol consumption and previous history of STD. Of the 611 women participating, one out of 4 women had a history of at least one STD. In an univariate analysis, self-reported STD was found to be related to age, having more than 4 lifetime sexual partners, having practised intercourse at first date, inconsistent use of condoms, alcohol consumption of more than 3 bottles of wine per month and smoking. These factors were, however, not independent of each other and when subjected to a multivariate logistic regression analysis 2 factors, i.e. the lifetime number of sexual partners (more than 4 partners vs one; OR 7.94, (3.41-18.50)) and coitus on first date (practised more than once vs never, OR 2.99 (1.55-5.78)) emerged as independently associated with a previous STD.
Epidermal Langerhans cells (LC) may occur in subsets with different phenotypic and functional characteristics. In this work give further evidence that the CD1a-positive LC population in the normal human epidermis may be heterogeneous. We found that one of our monoclonal antibodies (TE4B) to stratum corneum chymotryptic enzyme (SCCE) stained a population of dendritic cells in the normal epidermis in addition to high suprabasal keratinocytes. The staining of the dendritic cells was seen only when the biopsies had been fixed with formaldehyde and when the sections had been pretreated, either with proteolytic enzymes or with Triton X-100. The binding of the antibody was mediated through its antigen binding site, as it could be inhibited by adsorption with recombinant pro-SCCE. Experiments with double labelling showed that the TE4B-positive dendritic cells were also CD1a-positive. On the other hand, not all CD1a-positive cells were TE4B-positive. By means of confocal microscopy of double-labelled cells, the TE4B binding site could be localized intracellularly. SCCE-mRNA could be detected by in situ hybridization in high suprabasal keratinocytes only. A possible explanation may be that there is a subset of LC which have taken up SCCE secreted by high suprabasal keratinocytes. Alternatively, TE4B may bind to an epitope present in a subgroup of epidermal LC which cross-reacts immunologically with SCCE. It is suggested that the demonstrated heterogeneity of the population of LC in the normal epidermis should be taken into account in studies on the possible role of epidermal autoantigens in the development of immune-mediated skin diseases.