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K Petersen

Publications and source records attributed to K Petersen.

At least 37 records · Page 2Linked to original sources
PubMed2001

Pim-1: a serine/threonine kinase with a role in cell survival, proliferation, differentiation and tumorigenesis.

Pim-1 belongs to a family of serine/threonine protein kinases that are highly conserved through evolution in multicellular organisms. Originally identified from moloney murine leukemia virus (MuLV)-induced T-cell lymphomas in mice, Pim-1 kinase is involved in the control of cell growth, differentiation and apoptosis. Expression of Pim-1 kinase can be stimulated by a variety of growth factors and regulated at four different levels: transcriptional, post-transcriptional, translational and post-translational. Several signal transduction pathways may be associated with the regulation of Pim-1's expression; accumulating data support that the expression of Pim-1 protein is mediated through activation of JAK/STATs. Recent studies of Pim family kinases indicate that Pim-1 kinase plays important roles outside of the hematopoietic system as well.

Animals↗
PubMed2000

Increased disease burden and antibiotic resistance of bacteria causing severe community-acquired lower respiratory tract infections in human immunodeficiency virus type 1-infected children.

To improve the management of lower respiratory tract infections (LRTI) in human immunodeficiency virus type 1 (HIV-1)-infected children, we assessed the burden of disease, clinical outcome and antibiotic susceptibility of bacteria causing severe community-acquired LRTI in children. A prospective, descriptive study was performed in the pediatric wards at a secondary and tertiary care hospital in South Africa. Urban black children aged 2-60 months admitted with severe acute LRTI from March 1997 through February 1998 were enrolled. HIV-1 infection was present in 45.1% of 1215 cases of severe LRTI. Bacteremia occurred in 14.9% of HIV-1-infected and in 6.5% of HIV-1-uninfected children (P<.00001). The estimated relative incidence of bacteremic severe LRTI in children aged from 2 to 24 months were greater in HIV-1-infected than in -uninfected children for Streptococcus pneumoniae (risk ratio [RR], 42.9; 95% confidence interval [CI], 20.7-90.2), Haemophilus influenzae type b (RR, 21.4; 95% CI, 9.4-48.4), Staphylococcus aureus (RR, 97.9; 95% CI, 11.4-838.2) and Escherichia coli (RR, 49.0; 95% CI, 15.4-156). Isolation of Mycobacterium tuberculosis was also more common in HIV-1-infected than in -uninfected children (RR, 22.5; 95% CI, 13.4-37.6). In HIV-1-infected children, 60% of S. aureus and 85.7% of E. coli isolates were resistant to methicillin and trimethoprim-sulfamethoxazole, respectively. The case-fatality rates among HIV-1-infected children was 13.1%, and among HIV-1-uninfected children, 2.1% (adjusted odds ratio [AOR]; 6.52, 95% CI, 3.53-12.05; P<.00001). The changing spectrum of bacteria and antibiotic susceptibility patterns in HIV-1-infected children requires a reevaluation of the empirical treatment of community-acquired severe LRTI in children from developing countries with a high prevalence of childhood HIV-1 infection.

AIDS-Related Opportunistic Infections↗
PubMed2000

Influence of zona pellucida thickness of human embryos on clinical pregnancy outcome following in vitro fertilization treatment.

PURPOSE: To evaluate the correlation between the degree of zona pellucida thickness variation (ZPTV) of transferred embryos with identical morphologies and subsequent clinical pregnancy rates during 141 intracytoplasmic sperm injection (ICSI) treatment cycles. METHODS: A total of 141 women participating in the study group comprising mostly male factor infertilities and some repeat in vitro fertilization (IVF) failures were transferred, 2 days after ovum pickup, with two to three embryos with identical grades created by fertilization with ICSI. All selected embryos were subjected to zona pellucida thickness measurements immediately prior to transfer using a computerized embryo measurement program from videocinematography recordings. RESULTS: A total of 326 identical-grade transferred pre-embryos resulted in 70 clinical pregnancies with live-born implantation rate of 27.6%. A highly significant correlation was observed between ZPTV of transferred embryos and the IVF outcome with 77.1% and 83.64% of the clinical pregnancies resulting from transferred embryos with ZPTV values greater than 20 and 25, respectively. The mean ZPTV values for 70 conceptual cycles and 62 nonconceptual cycles were 28 +/- 6.43 and 17.85 +/- 8.11, respectively. No significant correlation between ZP thickness and number of blastomeres in the transferred embryos was evident, though embryos with better scores had significantly thinner zonae and higher ZPTV values. Though average zona thickness of embryos declined with age, the mean ZPTV value for women less than 30 years old was significantly higher (25.84 +/- 8.57) as compared with those from women older than 35 years (20.72 +/- 8.45). CONCLUSIONS: The degree of ZPTV of the transferred embryos exhibits a strong correlation with clinical pregnancy outcome following IVF treatment. This potentially reliable indicator of IVF success rate could be used as a criteria for embryo selection during clinical transfers.

Adult↗
PubMed2000

Impact of human immunodeficiency virus type 1 on the disease spectrum of Streptococcus pneumoniae in South African children.

BACKGROUND: HIV-infected children are at increased risk of developing invasive Streptococcus pneumoniae disease. OBJECTIVE: To determine the impact of the HIV epidemic on the epidemiology of invasive pneumococcal disease in hospitalized African children. METHODS: Children <12 years of age with invasive pneumococcal disease were enrolled between March, 1997, and February, 1999. RESULTS: The seroprevalence of HIV was 64.9% (146 of 225). In children with pneumococcal isolates from serogroups 6, 9, 14, 19 or 23 (pediatric serogroups), pneumonia and pneumonia with concurrent meningitis was more common in HIV-infected children (P = 0.03 and P = 0.003, respectively), whereas septic shock occurred more often in HIV-uninfected children (P = 0.0003). The overall burden of severe invasive pneumococcal disease was 41.7 (95% confidence interval, 26.5 to 65.6) fold increased in HIV-infected compared with HIV-uninfected children. Reduced susceptibility to penicillin (45.91% vs. 27.9%, P = 0.009), trimethoprim-sulfamethoxazole (44.5% vs. 19.0%, P = 0.0002) and multiple drug resistance was more common in HIV-infected than in HIV-uninfected children (24.0% vs. 6.4%, P = 0.01), respectively. The increased burden of disease and reduced antibiotic susceptibility of pneumococcal isolates in HIV-infected children was because of a heightened susceptibility to disease caused by pediatric serogroups in these children than in HIV-uninfected children (P = 0.01). Although the case fatality rates did not differ between HIV-infected and -uninfected children, mortality in HIV-infected children with advanced AIDS (Stage C, 22 of 61; 36.1%) was greater than that in children with moderate AIDS (Stage B, 12 of 85; 14.1%, P = 0.002). CONCLUSIONS: In children with invasive pneumococcal disease caused by the pediatric serogroups, HIV-infected children have more antibiotic-resistant isolates and have a different clinical presentation than do HIV-uninfected children.

Age Distribution↗
PubMed2000

Effects of leptin on basal and FSH stimulated steroidogenesis in human granulosa luteal cells.

BACKGROUND: Body weight influences fertility and studies in mice have indicated that leptin is one of the mediators of this effect. Leptin is believed to centrally stimulate the hypothalamic-pituitary axis resulting in increased gonadotropin release. Moreover, leptin is present in follicular fluid and the receptor is expressed in the human ovary. The aim of this study was to evaluate the direct effect of leptin on cultured human granulosa cell steroidogenesis. METHODS: Granulosa cells were obtained in connection with IVF procedures, and then cultured in a serum-free medium containing androstenedione (1 microM) for a total of 4 days. After 2 days of culture the medium was changed and the hormones under study were added. We tested the effect of leptin (1, 20, 100 ng/ml) on basal, FSH (10-100 ng/ml), and FSH (10-100 ng/ml)+IGF-I (30 ng/ml) stimulated steroidogenesis. RESULTS: Leptin (20 ng/ml and 100 ng/ml) significantly reduced basal and FSH-stimulated estradiol secretion (p<0.05). Basal and FSH (10 and 30 ng/ml) stimulated progesterone production was significantly inhibited by leptin 20 ng/ml, whereas leptin 100 ng/ml significantly reduced basal but not FSH stimulated progesterone production. Finally, steroidogenesis stimulated by IGF-I alone and in combination with FSH was not influenced by leptin. CONCLUSION: These results suggest that leptin acts directly to inhibit basal and FSH stimulated estradiol and progesterone production in cultured human granulosa cells. This raises the possibility that high circulating leptin levels as seen in obese women may compromise fertility through peripheral mechanisms.

Body Weight↗
PubMed1999

Genomic structure, chromosomal location, and mutation analysis of the human CDC14A gene.

Human CDC14A is a dual-specificity phosphatase that shares sequence similarity with the recently identified tumor suppressor, MMAC1/PTEN/TEP1. By radiation hybrid mapping, we localized CDC14A to chromosome band 1p21, a region that has been shown to exhibit loss of heterozygosity in highly differentiated breast carcinoma and malignant mesothelioma. We have mapped the exon-intron structure of CDC14A gene and found an in-frame ATG at 14 codons upstream of the previously reported start site (GenBank Accession No. AF000367). In screening a panel of 136 cDNAs from tumor cell lines for coding mutations, we have identified a 48-bp in-frame deletion in the cDNA of the breast carcinoma cell line, MDA-MB-436. This deletion is the result of an acceptor splice site mutation (AG to AT) in intron 12 that causes the skipping of exon 13 in the gene. Loss of expression of the wildtype allele in the same breast cell line supports the possibility that CDC14A may be a tumor suppressor gene that is targeted for inactivation during tumorigenesis.

Alternative Splicing↗
PubMed1999

Developmental expression of alpha-synuclein in rat hippocampus and cerebral cortex.

Alpha-synuclein is an evolutionary highly conserved neuronal protein localized in presynaptic nerve terminals. The protein has been suggested to be involved in the pathogenesis of neurodegenerative diseases, but little is known about the physiological function of the protein. In the present study we used newborn, three, 14, 93 and 710-day-old rats to examine the expression of alpha-synuclein messenger RNA and protein during development of the hippocampus and cerebral cortex. Using in situ hybridization and an S1 nuclease protection assay, we found a high expression of alpha-synuclein messenger RNA during early postnatal development, followed by a marked decrease between postnatal days 14 and 93. In contrast, the amount of alpha-synuclein protein, as determined by immunoblotting, continued to increase throughout development and remained at a high level for at least two years. The persistent high expression of alpha-synuclein protein throughout development suggests that the protein is involved in maintaining synaptic function. Furthermore, the discrepancy between the levels of alpha-synuclein messenger RNA and protein after postnatal day 14 indicates that the amount of alpha-synuclein is determined by post-transcriptional regulation, and not by messenger RNA expression alone. To estimate the changes of alpha-synuclein expression per synapse, we compared the developmental expression of alpha-synuclein with synaptophysin, a well-established synaptic marker. The alpha-synuclein/synaptophysin messenger RNA and protein ratio was high during early development, but low in adult (postnatal day 93) and old (postnatal day 710) rats. This could indicate a higher expression of alpha-synuclein per synapse during early development.

Aging↗
PubMed1999

Detection of micrometastasis by cytokeratin 20 RT-PCR is limited due to stable background transcription in granulocytes.

The reverse transcription polymerase chain reaction (RT-PCR) amplification of cytokeratin 20 (CK20) mRNA is considered a promising candidate method for the detection of circulating tumour cells in bone marrow and peripheral blood of cancer patients. In this study we have investigated the diagnostic specificity of the CK20 mRNA detection in samples from healthy donors (HD; n = 33), intensive care units patients (ICU; n = 20) and bone marrow obtained from patients suffering from chronic inflammatory diseases (CID; n = 14). RNAs purified from stabilized lysates showed positive results in 24% of the HD group (8/33), 35% of the ICU group (8/20) and in 40% of the CID group (5/14). The use of Ficoll gradients to separate nucleated cells completely restored the specificity of this CK20 RT-PCR assay. The CK20-expressing cells are positively identified to belong to the granulocyte fraction of leucocytes, which appear to express the gene on a background level. Our results demonstrate for the first time that CK20 mRNA expression is not limited to epithelium. Its occurrence in normal granulocytes has to be considered in tests designed to detect circulating cancer cells or micrometastases.

Biomarkers, Tumor↗
PubMed1999

A Danish national cohort of 730 infants born after intracytoplasmic sperm injection (ICSI) 1994-1997.

This national cohort study included all clinical pregnancies obtained after intracytoplasmic sperm injection (ICSI) registered in Denmark between January 1994 and July 1997 at five public and eight private fertility clinics. Laboratory and clinical data were obtained from the fertility clinics. The couples answered a questionnaire regarding the pregnancy and the health of the child (response rate 94%). Data validation was carried out through discharge charts. The mean age of the women was 32.1 years. In 84.2% of couples, male factor was the main reason for performing ICSI, and in 4.8% epididymal spermatozoa were used. The mean number of embryos replaced was 2.3 (range 1-3) and in 95% of cases fresh embryos were transferred. Only 183 women (28.5%) underwent prenatal diagnosis, resulting in 209 karyotypes with seven (3.3%) chromosome aberrations. Six major chromosomal abnormalities (2.9%) and one inherited structural chromosome aberration (0.5%) were found, but no sex chromosome aberrations. The frequency of multiple birth, Caesarean section rate, gestational age, preterm birth, and birth weight were comparable with previous studies. The perinatal mortality rate was 13.7 per 1000 children born with a gestational age of 24 weeks or more. In 2.2% (n = 16) of the liveborn infants, and in 2.7% (n = 20) of all infants, major birth defects were reported by the parents. Minor birth defects were found in nine liveborn infants (1.2%). In conclusion, the results of this study on outcome of ICSI pregnancies are in line with earlier reports, except that no sex chromosome abnormalities were found.

Adult↗
PubMed1999

Rapid, automated nucleic acid probe assays using silicon microstructures for nucleic acid concentration.

A system for rapid point-of-use nucleic acid (NA) analysis based on PCR techniques is described. The extraction and concentration of DNA from test samples has been accomplished utilizing silicon fluidic microchips with high surface-area-to-volume ratios. Short (500 bp) and medium size (48,000 bp) DNA have been captured, washed, and eluted using the silicon dioxide surfaces of these chips. Chaotropic (GuHCl) salt solutions were used as binding agents. Wash and elution agents consisted of ethanol-based solutions and water, respectively. DNA quantities approaching 40 ng/cm2 of binding area were captured from input solutions in the 100-1000 ng/mL concentration range. For dilute samples of interest for pathogen detection, PCR and gel electrophoresis were used to demonstrate extraction efficiencies of about 50 percent, and concentration factors of about 10x using bacteriophage lambda DNA as the target. Rapid, multichannel PCR thermal cycling modules with integrated solid-state detection components have also been demonstrated. These results confirm the viability of utilizing these components as elements of a compact, disposable cartridge system for the detection of NA in applications such as clinical diagnostics, biowarfare agent detection, food quality control, and environmental monitoring.

Automation↗
PubMed1998

Effects of amygdaloid lesions, hippocampal lesions, and buspirone on black-white exploration and food carrying in rats.

Unlesioned rats exploring a black-white two compartment box spent most of the time in the covered, black half of the box and only little time in the uncovered, white half (67 s/5 min). Large radio-frequency lesions of the amygdala or hippocampus did not alter this pattern of exploration, but rats with hippocampus lesions were more active than the other two groups of rats. Treatment with the 5-HT1A receptor agonist buspirone (0.1 mg/kg, s.c.) increased the time that unlesioned rats spent in the uncovered compartment (103 s), an effect that was less pronounced in hippocampus-lesioned rats and completely abolished by amygdala lesions. In a food transport test, unlesioned rats that traveled from a home cage to an exposed food source consumed small and medium-sized pellets immediately at the food source. Larger pellets, however, were carried back to the home cage for consumption. Rats with amygdala lesions ate fewer pellets at the food source and tended to carry more pellets back to the home cage for consumption than unlesioned rats. Rats with hippocampus lesions carried fewer pellets back to the home cage and ate more pellets at the food source. Buspirone (0.5-1.5 mg/kg, s.c.) reduced the carrying of large food items to the home cage and increased consumption of these pellets at the food source in all groups of rats. These results suggest that neither the amygdala nor the hippocampus play an important role in controlling exploratory behavior in a black-white compartment box, but that the amygdala may have some role in mediating the effect of buspirone to increase exploration of the white/open compartment. Further, the amygdala and hippocampus have opposing influences on the transport of food items to a shelter, the amygdala suppressing food carrying, and the hippocampus enhancing it. Neither structure is essential for the effect of buspirone to reduce food carrying. The hypothesis that limbic structures mediate 'fear/anxiety' responses is discussed critically.

Acoustic Stimulation↗
PubMed1998

Resumption of mitosis during post-thaw culture: a key parameter in selecting the right embryos for transfer.

This retrospective study of 701 thaw cycles analysed the clinical importance of whether or not embryos resumed mitosis during 24 h of post-thaw culture. A total of 3360 frozen embryos were thawed; 1922 embryos survived the freeze-thaw procedure with at least one intact blastomere and were then cultured for 24 h before transfer. All transfers were registered into either the 'cleaved embryo group' (n = 459), which was defined as transfers where at least one of the transferred embryos cleaved during the post-thaw culture period, or the 'non-cleaved embryo group' (n = 153), where none of the transferred embryos cleaved during the post-thaw culture period. A total of 1408 thawed embryos were transferred in 612 cycles; 459 embryo transfers were in the cleaved embryo group, resulting in an implantation rate of 10%, significantly higher than the 4% in the non-cleaved embryo group (P = 0.0003). A total of 130 pregnancies (28% per transfer) were obtained in the cleaved embryo group which was significantly higher than the 17 pregnancies (11% per transfer) obtained in the non-cleaved embryo group (P = 0.0001). However, the average number of transferred embryos was significantly higher in the cleaved embryo group (2.46 +/- 0.03) compared to the non-cleaved embryo group (1.82 +/- 0.07). No difference was found in the age of the women between the two groups. When analysing transfers where all transferred embryos had cleaved during the post-thaw culture period the clinical pregnancy rate increased significantly from 13% transferring two embryos to 36% transferring three embryos (P = 0.0136). In this latter subgroup an implantation rate as high as 17% was obtained. The overall multiple pregnancy rate was 16%. The multiple pregnancy rate was 19% in the cleaved embryo group. In conclusion, 24 h post-thaw culture may allow a better selection of the embryos and thereby we may be able to increase the implantation and pregnancy rates. This may enable us further to reduce the number of embryos transferred.

Adult↗
PubMed1998

Immunogenicity of a combined hepatitis B and Haemophilus influenzae type b conjugate vaccine in Alaska Native infants.

UNLABELLED: Hepatitis B and Haemophilus influenzae b (Hib), prevalent diseases in Alaska Native infants, have been reduced 95% following universal vaccination. Therefore, we were interested in studying a new combined Hib and hepatitis B vaccine in this population. METHOD: Healthy Alaska Native infants free from Hib and hepatitis B exposure were randomized into four groups, three with different lots of bivalent Hib and hepatitis B vaccine, and one with Hib and hepatitis B monovalent controls. The Hib component had 7.5 micrograms of polyribosylribitol phosphate polysaccharide (PRP) bound to 125 micrograms of Neisseria meningitidis outer membrane protein complex (OMP); the hepatitis B component was 5 micrograms of recombinant hepatitis B surface antigen. The vaccines were given at 2 months, 4 months, and 12-15 months of age. RESULTS: There were no differences in the responses to the bivalent compared to the monovalent controls except for a lower Hib anti-PRP level at 12-15 months in the bivalent recipients; this did not persist after the booster. CONCLUSION: A combined Hib and hepatitis B vaccine appears immunogenic. The recommended schedule for the Hib component (PRP-OMP) of 2 months, 4 months, and 12-15 months appears to promote an optimal response to the hepatitis B component as well.

Alaska↗
PubMed1997

The complete amino acid sequence of human placental oxytocinase.

The complete amino acid sequence of human placental oxytocinase (placental leucine aminopeptidase) has been determined by cDNA cloning and sequencing. Oxytocinase is a type II integral membrane protein of 1025 amino acid residues, consisting of an acidic intracellular region of 110 amino acids followed by a hydrophobic transmembrane segment of 22 residues and 893 extracellular residues containing the characteristic Zn2+ coordination sequence element His-Glu-Xaa-Xaa-His-(18 residues)-Glu found in gluzincins. Two sets of cDNA clones with different 5'-ends were isolated and suggested to represent different spliced products of 3.6 kb (mature mRNA) and 12 kb, respectively. Oxytocinase mRNA is present in large amounts in placenta, heart and skeletal muscle and in small amounts in brain, kidney, liver and pancreas. A conserved sequence element, the GAMEN motif, which distinguishes the aminopeptidase family among gluzincins from other gluzincins, has been identified.

Amino Acid Sequence↗
PubMed1997

The effect of erythromycin on resolution of symptoms among adults with pharyngitis not caused by group A streptococcus.

OBJECTIVE: To determine the effect of treatment with erythromycin on the resolution of symptoms among adults with pharyngitis not caused by group A streptococcus (GAS). DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Ambulatory setting (hospital-based general internal medicine practices, walk-in clinic, employee health service, and university health service). PATIENTS: One hundred and eighty-six adults who met eligibility criteria and whose chief complaint included sore throat. Patients with positive cultures for GAS were excluded. INTERVENTION: Ninety-three patients received erythromycin (333 mg three times daily for 10 days) and 93 control patients received placebo. MEASUREMENTS AND MAIN RESULTS: Major outcome measurements included time to improvement in sore throat, time to improvement in cough, time to improvement in activity level, and subjective sense of well-being. The average age of the patients studied was 26.6 years; 35% were men. Patients given erythromycin had more rapid resolution of sore throat symptoms (hazard ratio 1.43: 95% confidence interval [CI] 1.00, 2.03: p = .049). Cough also resolved more rapidly in patients receiving erythromycin (hazard ratio 2.22: 95% CI 1.01, 4.88: p = .05). There were no differences between the two treatment groups in improvement of activity level or how sick patients felt in general. Most of the benefit in resolution of sore throat was conferred on patients who sought medical care within 2 days of onset. CONCLUSIONS: Our results suggest that the benefit of erythromycin treatment for patients with non-GAS pharyngitis is small and of borderline statistical significance. Because of the small size of the effect and because widespread use of erythromycin could promote drug resistance, we do not recommend routine use of erythromycin in adult patients with this type of pharyngitis.

Adult↗
PubMed1997

Embryo morphology or cleavage stage: how to select the best embryos for transfer after in-vitro fertilization.

This retrospective study of 1001 in-vitro fertilization (IVF) cycles included a consecutive series of single transfers (n = 341), dual transfers (n = 410) and triple transfers (n = 250) where all the transferred embryos in each cycle were of identical quality score and identical cleavage stage. In our 2 day culture system, transfer of 4-cell embryos resulted in a significantly higher implantation rate and pregnancy rate (23 and 49%) compared with 2-cell embryos (12 and 22%) and 3-cell embryos (7 and 15%). Furthermore, the transfer of 4-cell embryos resulted in a significantly higher pregnancy rate compared with embryos that had cleaved beyond the 4-cell stage (28%). The implantation rate (21%) and pregnancy rate (43%) after transfer of embryos of score 1.0 were significantly higher than after transfer of embryos of score 2.0 (14 and 32% respectively). Transferring embryos of score 2.1 resulted in significantly higher implantation rates (26%) and similar pregnancy rates compared with score 1.0. Transferring embryos of score 2.2-3.0 resulted in a significantly lower implantation rate (5%) and pregnancy rate (15%). A striking finding was that embryos of quality score 2.0 had a significantly lower implantation rate compared with embryos of quality score 1.0 and 2.1 and a significantly lower pregnancy rate compared to embryos of quality score 1.0. We also found a lower implantation rate and pregnancy rate when transferring 3-cell embryos. These findings may indicate periods of increased sensitivity to damage during the cell cycle. In conclusion, these results substantiate the idea of the superiority of 4-cell embryos and demonstrate that minor amounts of fragments in the embryo may not be of any importance. These findings may call for a shift when weighing the two main morphological components (quality score and cleavage stage) in the sense that reaching a 4-cell cleavage stage even with the presence of a minor amount of fragments should be preferred to a 2-cell embryo with no fragments.

Adult↗