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Biomedical subjects

J B Pedersen

Publications and source records attributed to J B Pedersen.

At least 19 recordsLinked to original sources

Singlet and triplet products of the geminate recombination of a radical pair with a single magnetic nucleus (I = 1/2).

The double-channel recombination and separation of the photochemically created singlet radical pair is investigated, taking into account the spin conversion in a zero magnetic field and the arbitrary initial distance between the radicals. The quantum yields of the singlet and triplet products and the free radicals production are found analytically, assuming that the recombination of the diffusing radicals occurs at contact. All the yields are related to the singlet and triplet populations of the recombining radical pair, subjected to spin conversion and contact exchange interaction. The general analytical expressions for the quantum yields are specified for the particular limits of the weak and strong exchange. They are greatly simplified in the case of polar solvents, especially at the contact start. A close similarity is obtained with the results of a previously developed incoherent model of spin conversion, provided that the conversion rate is appropriately related to the hyperfine coupling constant.

Journal Article↗

Gastro-esophageal reflux demonstrated by radiography in infants less than 1 year of age. Comparison with pH monitoring.

PURPOSE: To correlate gastro-esophageal reflux (GER) demonstrated on radiography, with reflux determined on 24-h pH monitoring among infants of less than 1 year of age. MATERIAL AND METHODS: Twenty-one infants with suspected GER were examined. In the supine position the infants drank 20-60 ml of barium contrast, and the presence or absence of hiatal hernia, gastric outlet obstruction, or intestinal malrotation was evaluated. The infant was placed in the 25 degrees right oblique supine position and fed 2-3 swallows of milk by a feeding bottle. GER was scored as positive on radiography when the contrast column reached a level of at least 3 vertebral segments above the gastro-esophageal junction (GEJ). An antimony intraluminal esophageal pH probe was positioned 2 vertebral segments above the GEJ as identified by the barium swallow, confirmed on radiography after positioning and prior to probe removal. A total time of esophageal pH <4 exceeding 5% was assigned as pathological. RESULTS: The radiological method of GER evaluation showed a specificity of 50% and a sensitivity of 29%, as compared to 24-h pH monitoring. CONCLUSION: The radiological method was of no value among infants of less than 1 year when demonstrating GER.

Female↗

Intensive exposure as a risk factor for severe polio: a study of multiple family cases.

To examine the importance of intensity of exposure for the outcome of the poliomyelitis infection 429 polio cases were identified belonging to families with 2, 3 or 4 polio cases, all hospitalized in Copenhagen from 1919 to 1953. Furthermore, 87 pairs of polio cases living on the same stairway, but not in the same household, were identified. Severity among multiple cases in families analysed according to time of appearance showed a U-shaped curve. Initial cases had a higher risk of developing paralysis [relative risk (RR) = 1.5, 95% confidence interval (CI) 1.2-1.91 and of dying (RR = 2.5, 95% CI 0.9-6.9). Decreased severity was observed among subsequent cases appearing within 11 d after the initial case (RR = 1.0); however, severity increased again, with higher mortality for cases likely to have been infected by the initial case (cases appearing more than 11 d later) (RR = 5.7, 95% CI 1.8-17.8). The pattern described among multiple family cases was not found among cases from the same stairway. Since family cases appearing within 11 d were probably infected simultaneously, a short incubation period is associated with severe disease and a prolonged incubation period with milder infections. Furthermore, intensive exposure from being infected in the household increased severity. These observations therefore suggest that intensity of exposure and dose of infection are important factors in the severity of poliomyelitis.

Denmark↗

Non-melanoma skin cancer may be a marker of poor prognosis in patients with non-Hodgkin's lymphoma.

According to recent results, patients with non-melanoma skin cancers are at increased risk of developing non-Hodgkin's lymphoma (NHL). The prognostic significance of this association is unknown. Two cohorts of patients with a first diagnosis of non-melanoma skin cancer and a subsequent diagnosis of either NHL (n = 170) or colon cancer (n = 435) were established using national cancer registry data in Denmark. Two other cohorts of patients in whom NHL (n = 600) or colon cancer (n = 1,541) was the patients' first known malignancy served as comparison groups. Mortality rates were compared using Cox's regression analysis. Among patients younger than 80 years at NHL diagnosis, a history of non-melanoma skin cancer was associated with significantly increased mortality [relative risk (RR) = 1.54; 95% confidence interval: 1.19-1.99]. This association was present in both men (RR = 1.38; 1.02-1.86) and women (RR = 2.15; 1.31-3.54) and was similar after both major subtypes of non-melanoma skin cancer. Overall, antedating non-melanoma skin cancer had no prognostic significance for colon cancer patients (RR = 1.00; 0.84-1.18). Whatever the underlying mechanism, our observation has potential clinical implications. If substantiated in other settings, NHL patients with prior non-melanoma skin cancer may constitute a subgroup of lymphoma patients in need of particular therapeutic attention.

Adult↗

HTLV-1 infection in a population-based cohort of older persons in Guinea-Bissau, West Africa: risk factors and impact on survival.

In 1989, a population-based cohort of persons aged > or = 50 years was established in an urban area of Guinea-Bissau, West Africa. Overall, 346 persons were interviewed in detail about risk behaviors and had capillary blood drawn. Among women, 12.4% were HTLV-1 seropositive, compared with 4.6% in men. No HTLV-2 was found. Seropositivity varied considerably according to place of birth and ethnic group. In women, but not in men, HTLV-1 seropositivity was strongly associated with early sexual debut (10-14 yrs, 33.3%; 15-17 yrs, 26.0%; 18-20 yrs, 6.5%; 21+ yrs, 0%; ptrend = 0.001), lifetime number of male partners (ptrend = 0.006), and the male partner's number of co-wives (ptrend = 0.006). There was also a 3.1-fold increased risk of being HTLV-1 seropositive if the woman was also HIV-2 seropositive. In a multivariate-risk-factor analysis, the strongest association with HTLV-1 was a history of having been bitten by a monkey (n = 11; combined OR adjusted = 10.1; 95% CI 2.3-44.4). Ornamental scarification was associated with a 3.3-fold increased risk. Ethnic affiliation also significantly influenced the risk of being HTLV-1 seropositive. Follow-up performed in January 1996 revealed no difference in survival between HTLV-1-seropositive and -seronegative individuals over 6 years (rate ratio = 1.4, 95% CI 0.7-2.8). In conclusion, this population, which has very high HIV-2 seroprevalence, is also highly endemic for HTLV-1. Whereas sexual behaviors are clearly important for HTLV-1 spread in women, non-sexual risk factors were the only ones of potential importance in men. HTLV-1 had no impact on survival in this older population.

Aged↗

Testicular cancer risk and maternal parity: a population-based cohort study.

The aim was to study, in a population-based cohort design, whether first-born sons run a higher risk of testicular cancer than later born sons; to investigate whether this difference in risk was affected by birth cohort, age of the son, maternal age, interval to previous delivery and other reproductive factors; and, finally, to evaluate to what extent changes in women's parity over time might explain the increasing incidence of testicular cancer. By using data from the Civil Registration System, a database was established of all women born in Denmark since 1935 and all their children alive in 1968 or born later. Sons with testicular cancer were identified in the Danish Cancer Registry. Among 1015994 sons followed for 15981 967 person-years, 626 developed testicular cancer (443 non-seminomas, 183 seminomas). Later born sons had a decreased risk of testicular cancer (RR = 0.80, 95% CI = 0.67-0.95) compared with first-born sons. The RR was 0.79 (95% CI = 0.64-0.98) for non-seminomas and 0.81 (95% CI = 0.58-1.13) for seminomas. There was no association between testicular cancer risk and overall parity of the mother, maternal or paternal age at the birth of the son, or maternal age at first birth. The decreased risk of testicular cancer among later born sons was not modified by age, birth cohort, interval to the previous birth, sex of the first-born child, or maternal age at birth of the son or at first birth. The increased proportion of first-borns from birth cohort 1946 to birth cohort 1969 only explained around 3% of an approximated two-fold increase in incidence between the cohorts. Our data document a distinctly higher risk of testicular cancer in first-born compared with later born sons and suggest that the most likely explanation should be sought among exposures in utero. The increase in the proportion of first-borns in the population has only contributed marginally to the increase in testicular cancer incidence.

Adolescent↗

Birth order, sibship size and risk of Hodgkin's disease in children and young adults: a population-based study of 31 million person-years.

It has been proposed that Hodgkin's disease (HD) may have an infectious origin and that delayed exposure to infection may increase the risk of HD in young adults. This hypothesis is addressed by studying the family structure among children and young adults. The Civil Registration System was used to establish a population-based cohort consisting of all persons whose mothers were born in Denmark since 1935. Persons who developed HD were identified by linkage with the Danish Cancer Registry. HD incidence rate ratios were estimated based on a log-linear Poisson regression model. The cohort of 2.1 million persons (aged 0-42 years) was followed for 31.1 million person years, during which period 378 cases of HD occurred. Among children (< 15 years, n = 72), the relative risk (RR) of HD tended to increase with increasing sibship size, the relative increase in risk per increase in sibship size (the trend) being 1.28 [95% confidence interval (CI) 1.00-1.63]. The trend for birth order was 1.26 (95% CI 0.92-1.73). Among young adults (> or = 15 years, n = 306) the risk of HD, on the contrary, tended to decrease with increasing sibship size [trend = 0.91 (95% CI, 0.81-1.03)] and birth order (trend = 0.85 (95% CI, 0.71-1.01). These trends among young adults were significantly different from the corresponding trends among children (p < 0.05). Siblings of cases were at increased risk of HD (RR = 18; 95% CI, 2.2-65, n = 2). Our findings are compatible with the hypothesis that delayed exposure to infection may be a risk factor for HD in young adults, and that early exposure perhaps to another infectious agent may increase the risk of HD in children.

Adolescent↗

Birth characteristics, sibling patterns, and acute leukemia risk in childhood: a population-based cohort study.

BACKGROUND: The occurrence of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) during childhood may be influenced by factors operating in fetal life. Furthermore, childhood ALL has been suggested to be linked to patterns of infection during infancy. PURPOSE: To explore these hypotheses and other associations, we studied the impact of sibling patterns (e.g., birth order) and birth characteristics (e.g., birth weight) on the risk of childhood ALL and AML. METHODS: By linkage of records of population-based registries, a cohort of all children whose mothers were born in Denmark from April 1935 through March 1978 was established. Children who developed ALL or AML during the period from April 1968 through December 1992 were identified by linkage with the Danish Cancer Registry. Birth weights were obtained for children born during the period from January 1973 through December 1992 by linkage with the Medical Birth Registry. RESULTS: The cohort of approximately 2.0 million children was followed for the diagnosis of ALL or AML for 20.9 million person-years. A total of 704 cases of childhood ALL were identified. Among 0-4 year olds, the relative risks (RRs) of ALL for birth order positions 1, 2, 3, and 4+ were 1.00 (reference), 0.85 (95% confidence interval [CI] = 0.68-1.07), 0.91 (95% CI = 0.66-1.25), and 0.57 (95% CI = 0.30-1.06), respectively (P for trend = .09). A decreasing trend was not observed among 5-14 year olds. A significant log-linear association between birth weight and the risk of ALL was observed for both age groups. Overall, the RR of ALL increased by a factor of 1.46 (95% CI = 1.18-1.81) (P = .0005) for each kilogram of increase in birth weight. A total of 114 cases of childhood AML were identified. Children born second or later in the birth order had an increased risk of AML (RR = 1.53; 95% CI = 1.01-2.32) compared with firstborns. A particularly high risk of AML at ages 2 (RR = 2.53; 95% CI = 1.46-4.40) and 3 years was associated with having siblings compared with being an only child at those ages. Similar to the findings for ALL risk, there was a significant association between birth weight and AML risk. The relative increase in AML risk per 1-kg increase in birth weight was 2.14 (95% CI = 1.19-3.85; P = .009). CONCLUSION AND IMPLICATIONS: The association between birth weight and childhood leukemia suggests the importance of intrauterine factors. A plausible explanation may be that increasing birth weight is associated with a higher rate of cell proliferation and/or a larger number of precursor cells being at risk of malignant transformation. The inverse association between birth order and ALL risk among 0-4 year olds was weak, but it was compatible with the hypothesis that delayed exposure to infection may increase the risk of ALL in this age group. The association of childhood AML with birth order and sibship size at young ages deserves further attention in the search for environmental factors that affect childhood AML risk.

Acute Disease↗

Use of neural networks to diagnose acute myocardial infarction. I. Methodology.

We investigated several aspects of using neural networks as a diagnostic tool: the design of an optimal network, the amount of patients' data needed to train the network, the question of training the network optimally while avoiding overfitting, and the influence of redundant variables. The specific clinical problem chosen for illustration was the diagnosis of acute myocardial infarction, given only the electrocardiogram and the concentration of potassium in serum at the time of admission. We found that, in contrast to usual practice, the termination of the training process should be based on the generalization performance and not on the training performance. We also found that a principal component analysis can be used to eliminate redundant variables, thereby reducing the data space. The diagnostic performance of the neural network we used was 78%--superior to that of linear discriminant function analysis but similar to that of quadratic discriminant function analysis.

Diagnosis, Computer-Assisted↗

Use of neural networks to diagnose acute myocardial infarction. II. A clinical application.

We investigated the ability of neural networks to diagnose acute myocardial infarction (AMI) from laboratory data only. Several networks were trained with different combinations of data obtained at admission and within the first 12 h and 24 h after admission. The data used included the electrocardiogram (ECG) and the concentrations in serum of potassium, creatine kinase B-subunit (CKB), and lactate dehydrogenase isoenzyme 1 for 250 patients with suspected AMI. Based on admission data, the correct diagnosis was predicted for 76% of the patients in the test group from the ECG data only, and the best combination of ECG results with other variables yielded correct diagnoses for 85% of the test group. Using all of the data available within 24 h, the network predicted the correct diagnosis for 99% of the test data. Almost the same high predictability was obtained by using only two CKB values-recorded at admission and within 12 h after admission-or by using just the latter one. Neural networks and quadratic discriminant analysis performed similarly, but the neural networks were more robust for combinations with many laboratory data.

Creatine Kinase↗

A comparison of the hairpin stability of the palindromic d(CGCG(A/T)4CGCG) oligonucleotides.

The palindromic deoxyribonucleotides 5'-CGCGA-TATCGCG-3' and 5'-CGCGTTAACGCG-3' have been characterized by 1H NMR spectroscopy. The NMR data identified both B-DNA duplex conformations and hairpin conformations, the latter with loop regions consisting of the four central nucleotides. The resonances of the various conformations were assigned by use of two-dimensional NMR methods. The relative stability of the various conformations was investigated as a function of temperature, ionic strength and nucleotide concentration. The duplexes were found to be stabilized at high ionic strength and at low temperature, while the hairpins were stabilized at low ionic strength and at medium temperature. The thermodynamics of the duplex-hairpin and the hairpin-random coil transitions were examined, and compared to the other two oligonucleotide in the palindromic d(CGCG(A/T)4CGCG) oligonucleotide family. The relative stabilities of the duplex conformations with respect to the random coil conformations are similar for the d(CGCGAATTCGCG), d(CGCGATATCGCG) and d(CGCGTATACGCG) oligonucleotides. The duplex conformation of d(CGCGTTAACGCG) is less stable. The hairpin of d(CGCGTTAACGCG) seems also to be less stable relative to the random coil conformation than in the case of the other oligonucleotides at an equal oligonucleotide concentration. A cruciform intermediate between the duplex and hairpin conformations is suggested to explain some discrepancies observed in this work in case of the d(CGCGTTAACGCG) oligonucleotide. This is similar to what has been reported for the d(CGCGTATACGCG) oligonucleotide.

DNA↗

Site selective bis-intercalation of a homodimeric thiazole orange dye in DNA oligonucleotides.

We have used one and two dimensional 1H NMR spectroscopy to characterize the binding of a homodimeric thiazole orange dye, 1,1'-(4,4,8,8-tetramethyl-4,8-diaza-undecamethylene)-bis-4- (3-methyl-2,3-dihydro-(benzo-1,3-thiazole)-2-methylidene)-quinolin ium tetraiodide (TOTO), to various double stranded DNA oligonucleotides. TOTO binds strongly to all the oligonucleotides used, but usually more than one complex is observed and exchange between different binding sites broadens the lines in the NMR spectra. Complete precipitation occurs when TOTO is bound to small oligonucleotides. Binding to larger oligonucleotides occurs by bis-intercalation. The 1:1 complex of TOTO with the oligonucleotide d(CCGACTGATGC):d (GCATCAGTCGG) gave only one complex that was shown to be a bis-intercalation in the CTGA:TCAG binding site. The binding to this site was also characterized by studying the TOTO complex with the d(CCGCTGAGC):d(GCTCAGCGG) oligonucleotide. NOE connectivities and molecular modelling were used to characterize the complex. The 1:1 complex of TOTO with the oligonucleotide d(CCGCTAGCG):d(CGCTAGCGG) containing a CTAG:CTAG binding site was similarly characterized by NMR. It was concluded that the binding of TOTO to larger oligonucleotides is site selective with CTAG:CTAG as the preferred binding site.

Base Sequence↗

Interpretation and analysis of receptor binding experiments which yield non-linear Scatchard plots and binding constants dependent upon receptor concentration.

Receptor-binding assays with radiolabelled ligands are widely used to evaluate the biological activity of drugs and hormones. The affinity, usually expressed as the dissociation constant (Kd), and the capacity (Bmax) of the receptor preparation for various ligands are determined in order to compare quantitatively various agonists and antagonists. Experiments with the same ligand and receptor, however, often yield rather disparate values for these binding parameters. One obvious reason for variability in Kd is that straight lines are fitted to data that are clearly curved. Another and more serious reason is that a ligand's apparent dissociation constant decreases when the receptor preparation is diluted and so experiments done at different receptor concentrations do not give identical results. We demonstrate that both of these observations, i.e. the effect of receptor concentration and the curvature of Scatchard plots, can be explained by the presence of a competitive inhibitor in the receptor preparation, a possibility which is not normally considered in the analysis and interpretation of receptor binding assays. We show that the apparent Kd obtained by the conventional one- or two-site analysis may be several orders of magnitude larger than the true dissociation constant and the affinity is therefore seriously underestimated. Application of a model, which assumes that an inhibitor is present in the receptor preparation, will improve the quantitative determination of Kd and Bmax significantly. As a simple alternative method we explain how the apparent binding parameters obtained by the conventional method should be interpreted and how they can be used to estimate the true affinity, provided sufficiently low concentration data are available.

Animals↗

Attitudes to aging and old age.

In the 1980s a marked shift in the attitude to aging and the elderly made itself felt. In the beginning of the decade the commission for the elderly proposed a policy based on continuity and self-determination and with a starting point in the resources of the elderly. This attitude has come through in the political activities on different levels and is also reflected in the DaneAge Future study, where three cohorts--40-44 years, 50-54 years, 60-64 years--show an optimistic and self-confident attitude to their own old age.

Adult↗

Contamination by a competitive ligand as an explanation for the inverse dependence of HABA binding parameters upon the protein concentration.

There is evidence that the apparent association constant (K) and/or the number of binding sites (n) are inversely dependent upon protein concentration for a number and variety of ligands with no obvious structure-activity relationships. A model recently shown to explain this effect with an inorganic ligand has now been applied to 2-(4'-hydroxybenzeneazo) benzoic acid (HABA) and also explains the inverse protein dependence of the binding of this compound to human albumin. The model explains this inverse dependence on the basis of a highly bound contaminant which competes with the ligand for the high affinity site. HABA was found to interact with human albumin at three or more sites, the high affinity site which was about 95% contaminated had an association constant of 2 x 10(5)/M, an order of magnitude higher than that found previously when the effect of a contaminant was not considered. The association constant of the competitive contaminant was estimated to be about 5 x 10(6)/M. Since the model accounts for the phenomenon in terms of a property of the protein, rather than of the ligand, it could provide a general explanation for this effect with other ligand-acceptor combinations including a wide variety of drug and hormone receptor preparations.

Albumins↗

Effect of a contaminating competitive ligand on ligand-binding curves. Inverse protein concentration dependence.

A theoretical binding model is considered which provides an explanation for the inverse protein concentration dependence observed for a variety of ligands. The model describes the inhibition of binding caused by a highly bound contaminant. The complete binding equation is derived and examined in terms of form, limits, and protein dependence. Furthermore, several approximate relations are derived which are useful for obtaining initial estimates of the model parameters and for a qualitative test of the applicability of the model. It is found that the binding curve may show a characteristic plateau at a saturation equal to the uncontaminated fraction of the protein and that the free ligand concentration at half saturation depends linearly on protein concentration. The practical implications of the present findings are discussed based on an analysis of simulated as well as experimental data.

Binding, Competitive↗