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Biomedical subjects

M Lundqvist

Publications and source records attributed to M Lundqvist.

At least 19 recordsLinked to original sources

Direct and indirect exposure to pets - risk of sensitization and asthma at 4 years in a birth cohort.

INTRODUCTION: There are conflicting data on the association between early exposure to pets and allergic diseases. Bias related to retrospective information on pet ownership has been addressed as a reason for distorted study results. OBJECTIVE: To elucidate how early exposure to cat and dog relates to IgE-sensitization and asthma in children at 2 and 4 years of age, in a prospective birth-cohort study. METHODS: Four thousand and eighty-nine families with children born 1994-1996 in predefined areas of Stockholm answered questionnaires on environmental factors and symptoms of allergic disease at birth, one, two and four years of age. Dust samples collected from the mothers' beds at birth were analysed for Fel d 1 and Can f 1 in a subgroup of the cohort. Blood samples taken at four years from 2614 children were analysed for allergen-specific IgE to common airborne allergens. Risk associations were calculated with a multiple logistic regression model, with adjustment for potential confounders. RESULTS: A correlation was seen between allergen levels and reported exposure to cat and dog. Exposure to cat seemed to increase the risk of cat sensitization, OR (odds ratio) 1.44 (95% confidence interval 1.03-2.01), whereas dog exposure did not have any effect on dog sensitization, OR 1.16 (0.79-1.72). Dog ownership was related to a reduced risk of sensitization to other airborne allergens, OR 0.36 (0.15-0.83), and a similar tendency was seen for cat ownership OR 0.63 (0.37-1.07). Early dog ownership seemed to be associated with a lower risk of asthma, OR 0.50 (0.24-1.03), with no corresponding effect after cat ownership, OR 0.88 (0.56-1.38). CONCLUSION: Early exposure to cat seems to increase the risk of sensitization to cat but not of asthma at 4 years of age. Dog ownership, on the other hand, appears to be associated with lowered risk of sensitization to airborne allergens and asthma. Both aetiological relationships and selection effects have to be considered in the interpretation of these findings.

Adult↗

Prostasome-like granules from the PC-3 prostate cancer cell line increase the motility of washed human spermatozoa and adhere to the sperm.

OBJECTIVE: Prostasome-like granules are present in the PC-3 prostate cancer cells. Since the seminal prostasomes are able to promote the forward motility of human spermatozoa, we conducted a study to determine whether PC-3 prostasomes exerted effects similar to those of seminal prostasomes on buffer-washed spermatozoa from normospermic semen samples. STUDY DESIGN: We used computer-assisted sperm analysis (CASA) and immunostaining of prostasomes to find out where these granules are located on the spermatozoa. RESULTS: Addition of PC-3 prostasomes increased the proportion of motile spermatozoa from 12-15% to 50-70% (p<0.001). The optimal protein concentration of these prostasomes was 0.1mg/ml. Heat treatment of PC-3 prostasomes did not decrease their motility-promoting effect. Immunostaining with anti-prostasome monoclonal antibody (mAb78) revealed that the PC-3 prostasomes and seminal prostasomes adhered to the sperm cells. The staining, which occurred all over the spermatozoa, was intense on the mid-pieces and weaker on the sperm heads. Herewith, some prostasome component may activate the spermatic mitochondrial function, thus increasing sperm motility. CONCLUSION: It is concluded that PC-3 prostasomes bear a functional resemblance to seminal prostasomes as regards sperm motility promotion.

Cell Adhesion↗

Reducing the time of co-incubation of gametes in human in-vitro fertilization has no beneficial effects.

Reports concerning the benefit of reducing the co-incubation time of gametes in connection with IVF have been conflicting. The present randomized study was undertaken to determine whether a reduced co-incubation time would improve the embryo development and consequently the pregnancy and implantation rates. Oocytes from 87 patients were collected and half the oocytes from each patient (n = 488, group A) were randomized to 2 h incubation and the other half (n = 504, group B) to overnight incubation. The oocytes were then cultured according to our standard procedure. Significant difference (P = 0.02) was observed between the two groups regarding fertilization rate and polyspermy (group A 72.5%, 3% and group B 80.5%, 6% respectively). However, no difference was observed in further development and morphology of the embryos. The two embryos with the best morphological score were selected for transfer. No significant difference was found between the different transfer groups regarding positive serum HCG and implantation rate. CONCLUSION: The present results and results from previously published studies indicate that the most important factor in connection with the culture method currently used is the amount of sperm added for co-incubation. This should be optimized to reduce the concentration of harmful sperm waste products and create optimal culture conditions.

Journal Article↗

Does pronuclear morphology and/or early cleavage rate predict embryo implantation potential?

A total of 340 patients referred for in-vitro fertilization was included in a retrospective, comparative study in which zygotes were studied regarding alignment and polarization of nucleolar precursor bodies (NPB) and also early cleavage in relation to implantation and pregnancy rates for the 680 transferred embryos. At assessment of the pronucleus 18-19 h after sperm injection, NPB were checked for alignment/polarization. Twenty-six hours after sperm insemination the zygotes were assessed for early cleavage. At embryo transfer the two embryos with the best morphological score, irrespective of polarization and early cleavage, were selected for transfer. The overall rate of positive HCG tests 17 days after embryo transfer was 42% and the implantation rate 23%. Fourteen percent of the patients received two embryos with polarized NPB, with a positive HCG test of 51%. Embryo transfer with early-cleaved embryos was carried out in 21% of the cycles, with a pregnancy rate of 45%. Embryos with polarized NPB and/or early cleavage were transferred in 34% of the cycles, with a pregnancy rate of 51%, compared with a pregnancy rate of 38% when none of the embryos fulfilled these criteria (P-value 0.02). In this study the pregnancy rate was significantly higher when one or two embryos were polarized and/or early cleaved. It is concluded that in a cohort of morphologically good embryos, assessment for alignment/polarization of NPB and/or early cleavage can, together with conventional morphological criteria, serve as a simple non-invasive method for selection of embryos with high implantation potential.

Journal Article↗

Circulating human antisperm antibodies recognize prostasomes.

PROBLEM: The presence of naturally occurring antisperm antibodies (ASA) is a well-known cause of infertility in men and women, but the antigens for these antibodies are usually poorly characterized. Prostasomes, organelles secreted by human prostatic acinar cells and expelled into the seminal plasma at ejaculation, can adhere to sperm cells. Thus, we have examined whether prostasomes could be an antigen for ASA. METHOD OF STUDY: We have studied the reactivity of chicken antiprostasome antibodies with sperm cells in an agglutination test and conversely the reactivity of serum positive for ASA from 20 infertile patients, with spermatozoa using flow cytometry and with purified prostasomes using enzyme-linked immunosorbent assay. RESULTS: The chicken antiprostasome antibody caused agglutination of sperm cells similarly to the agglutination observed with patients' sera. All of these patients' sera contained IgG antibodies against prostasomes. CONCLUSIONS: The high percentage of patients with antiprostasome antibodies in this study shows that prostasomes could be one of the major targets for ASA.

Animals↗

The solution structure of the homeodomain of the rat insulin-gene enhancer protein isl-1. Comparison with other homeodomains.

Homeodomains are one of the key families of eukaryotic DNA-binding motifs and provide an important model system for DNA recognition. We have determined a high-quality nuclear magnetic resonance (NMR) structure of the DNA-binding homeodomain of the insulin gene enhancer protein Isl-1 (Isl-1-HD). It forms the first solution structure of a homeodomain from the LIM family. It contains a well-defined inner core (residues 12-55) consisting of the classical three-helix structure observed in other homeodomains. The N terminus is unstructured up to residue 8, while the C terminus gradually becomes unstructured from residue 55 onwards. Some flexibility is evident in the loop parts of the inner core. Isl-1-HD has, despite its low sequence identity (23-34 %), a structure that is strikingly similar to that of the other homeodomains with known three-dimensional structures. Detailed analysis of Isl-1-HD and the other homeodomains rationalizes the differences in their temperature stability and explains the low stability of the Isl-1-HD in the free state (tm 22-30 degrees C). Upon DNA binding, a significant stabilization occurs (tm>55 degrees C). The low stability of Isl-1-HD (and other mammalian homeodomains) suggests that in vivo Isl-1-HD recognizes its cognate DNA from its unfolded state.

Amino Acid Sequence↗

A high degree of aneuploidy in frozen-thawed human preimplantation embryos.

We have studied the chromosomal content in 68 normally fertilised freeze-thawed human embryos of good morphology from 34 patients with an average maternal age of 32,6 years. Forty embryos showed post-thaw cellular division and twenty-eight post-thaw cleavage arrest. After spreading of the embryos on microscope slides, analysis of chromosomes X, Y, 15, 16, 17 and 18 was performed using two rounds of fluorescent in situ hybridisation (FISH). According to the results, the embryos were divided into four groups: (I) normal, all nuclei uniformly diploid, (II) diploid mosaics, normal diploid blastomeres in combination with abnormal blastomeres, (III) abnormal, all nuclei abnormal, (IV) chaotic, the chromosome constitution varies randomly from cell to cell. Approximately 25% of the embryos had normal number of the chromosomes tested, while the majority of the embryos were abnormal. Most of the abnormal embryos were diploid mosaics (57%). This was true for the embryos showing cleavage division as well as the embryos showing cleavage arrest. Our data show a slightly higher incidence of abnormal embryos compared to those obtained with FISH in non-cryopreserved embryos and confirm that the majority of preimplantation embryos fertilised in vitro contain abnormal blastomeres. The results, mechanisms, significance and implications are discussed.

Aneuploidy↗

Influence of the mu-chain C-terminal sequence on polymerization of immunoglobulin M.

Immunoglobulin (IgM) is found in various states of covalent polymerization (microL)n, where n is typically 8, 10, or 12. The usual form of IgM of bony fish is tetrameric (8 microL units) as compared to the pentameric form (10 microL units) observed in cartilaginous fish and mammals. Two hypotheses were tested in this study. First, that the length of the mu-chain C terminus following Cys575 determines whether an IgM polymerizes as a tetramer or as a pentamer. This was tested by examining the covalent polymerization state of mouse IgM mutated to contain a series of mu-chain C-termini from bony and cartilaginous fish. The results proved this hypothesis wrong: mouse IgM bearing the C-terminal sequence of shark, salmon and cod mu-chain behaved identically to native mouse IgM, forming predominantly (microL)10 and (microL)12 forms. The second hypothesis was that an additional Cys residue near the C terminus of the mu-chain is responsible for the multiple covalent structures seen in IgM of the channel catfish. The addition of a catfish C terminus to the mouse mu-chain resulted, as predicted, in the production of a series of covalently bonded forms, with the major species being (microL)4. When a Ser-Cys unit was removed from the catfish C terminus added to the mouse mu-chain, this resulted in production of IgM indistinguishable in structure from that of wild-type mouse IgM.

Animals↗

Detective quantum efficiency dependence on x-ray energy weighting in mammography.

An evaluation of the dependence of detective quantum efficiency (DQE) on the incident energy spectrum has been made for mammography. The DQE dependence on the energy spectrum has been evaluated for energy-integrating detectors, photon-counting detectors, and detectors that measure the energy of each photon. To isolate the effect of the x-ray energy spectrum the detector has been assumed to be ideal, i.e., all noise sources are assumed to be zero except for quantum fluctuations. The result shows that the improvement in DQE, if the energy-integrating detector is compared to a single-photon counting detector, is of the order of 10%. Comparing the energy-integrating detector and the detector measuring the energy for each photon the improvement is around 30% using a molybdenum anode spectrum typical in mammography. It is shown that the optimal weight factors to combine the data in the case the energy is measured are very well approximated if the weight factors are proportional to E(-3). Another conclusion is that in calculating the DQE, a detector should be compared to one that uses ideal energy weighting for each photon since this provides the best signal-to-noise ratio. This has generally been neglected in the literature.

Humans↗

Shared tumor antigens in colorectal carcinoma and neuroendocrine tumors.

ND4 monoclonal antibody recognizes a tumor marker found on poorly differentiated colorectal cancer. We demonstrate its expression in 25% of gastrointestinal neuroendocrine tumors, which also express CEA in 37% of cases. As in colorectal cancer the ND4 marker is predominantly membrane bound in a colonic neuroendocrine tumor cell line, LCC-18 (p < 0.05). The ND4 marker is absent in a poorly differentiated colorectal cancer cell line that does not express CEA or other tumor antigens. Shed antigen in the serum of patients with neuroendocrine tumors is detected in only five of seven patients with the carcinoid syndrome and two of four of those without evidence of the syndrome. However, the reactivity was less in the patients with localized disease, and this test is unlikely to be of diagnostic utility in this group of patients. The sharing of this antigen in colorectal cancer and neuroendocrine tumors is not universal, but does support the common-cell progenitor theory for the origin of these tumors.

Animals↗

Ig light chain gene in the Siberian sturgeon (Acipenser baeri).

Elasmobranch and teleost fish have their Ig light (L) chain loci organized in multiple clusters (VL-JL-CL). The VL segments of teleosts are in opposite transcriptional orientation to the CL genes, suggesting that in teleosts and elasmobranchs there may have been separate evolutionary events leading to this organization. To address this problem, the IgL locus from the Siberian sturgeon (Acipenser baeri) (representative of a branch between elasmobranchs and teleosts) was investigated. Sequence analysis of cDNA clones shows that sturgeon VL genes are most similar to those of teleosts, but that sturgeon CL genes are more similar to those of the sharks. Southern blot analyses of sturgeon erythrocyte DNA with VL- and CL-specific probes showed that there are more than 20 VL segments in both the tetraploid Siberian sturgeon and the diploid sterlet (Acipenser ruthenus), but only a few CL segments in the genome of the Siberian sturgeon and up to four CL segments in that of the sterlet. Screening of an unamplified genomic library gave more than 300 VL-positive and four CL-positive clones. None of these contained inserts positive for both probes. PCR analysis of a genomic CL clone using IC and CL-specific primers suggested that upstream of the CL segment there are at least seven JL segments. it is concluded that sturgeons have a kappa-like organization of their IgL locus and that the clustered organization of IgL loci in bony fish and sharks arose from two distinct evolutionary events.

Amino Acid Sequence↗

EGF-receptors in human normal and pathological thyroid tissue.

Expression of the epidermal growth factor receptor (EGFR) was studied in cryosections from human thyroid tissues. Normal tissue (4 cases), nodular goitre (12), toxic goitre (9), adenoma (9), follicular carcinoma (1), papillary carcinoma (7) and poorly differentiated carcinoma (1) were used for immunohistochemistry. Northern blot analysis was performed in two nodular goitres, three adenomas, two papillary carcinomas, one follicular carcinoma and the adjacent normal tissue in five cases as well as in two cell lines from anaplastic carcinomas. Epidermal growth factor receptor immunoreactivity was detected in all tissues examined. The amount of EGFR mRNA did not differ between normal and abnormal tissues. However, the EGFR staining was weaker in normal thyroid tissue compared to the adjacent neoplastic areas suggesting an upregulation at the posttranslational level in the latter. A strong staining was also seen in hyperfunctioning thyroid glands. The EGFR location was mainly basal or basolateral in all thyroid tissues with normal histology and in toxic diffuse goitre. Pericellular and sometimes cytoplasmatic staining was seen in neoplastic tissues. In nodular goitre the staining was both basal, lateral and apical and varied in intensity. Our data suggest that a non-polarized location of EGFR probably indicates a loss of the normal epithelial cell polarity and could be interpreted as an early sign of dedifferentiation. Furthermore, a role for the EGFR is proposed, not only in the development of thyroid neoplasias but also in goitre formation.

Adenocarcinoma, Follicular↗

Omeprazole inhibits growth of cancer cell line of colonic origin.

The direct effects of omeprazole on colonic cells has not been evaluated. Controversy exists regarding the potential adverse effects of omeprazole on cell proliferation. In order to mimic the in vivo situation in the patient treated with omeprazole, proliferation cell culture experiments were performed, monitoring directly the effects of gastrin and omeprazole both alone and in combination. Three colonic cancer cell lines were used, two with neuroendocrine features (NCI-H716, LCC-18) and one (DLD-1) not known to have these features. In these in vitro proliferation experiments, only the NCI-H716 colorectal cancer cell line responded to omeprazole by decreased proliferation (P < 0.05). The effect was concentration dependent shown for all doses of omeprazole used. Gastrin had a statistically significant effect on increasing proliferation in the NCS-H716 cell line alone but only at the highest concentration (10(-6) M). Omeprazole has a cytostatic effect on one of three colorectal cancer cell lines but the mechanism for this effect of omeprazole and its potential role in treatment awaits elucidation.

Cell Division↗