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Biomedical subjects

P Kristensen

Publications and source records attributed to P Kristensen.

At least 55 records · Page 3Linked to original sources
PubMed1998

Central administration of Y5 receptor antisense decreases spontaneous food intake and attenuates feeding in response to exogenous neuropeptide Y.

A number of neuropeptide Y (NPY) receptor subtypes, including the recently cloned Y5 receptor, have been implicated in the stimulation of food intake. In the present study, Y5 receptor antisense oligodeoxynucleotides (ODNs) were used to assess the potential involvement of the Y5 receptor in the regulation of spontaneous as well as NPY-induced food intake. Repeated central administration of Y5 antisense ODN significantly decreased spontaneous food intake and subsequently resulted in a significant weight loss. Furthermore, Y5 antisense ODN pre-treatment significantly inhibited the robust feeding response elicited by central administration of NPY (5.3+/-0. 8 vs 1.08+/-0.28 g, vehicle+/-s.e.m. vs Y5 ODN+/-s.e.m.). The present results provide evidence that central Y5 receptors are involved in both spontaneous as well as NPY-induced food intake, which may prove to be a new therapeutic route in the treatment of obesity and other disorders of appetite.

Analysis of Variance↗
PubMed1997

Gestational age, birth weight, and perinatal death among births to Norwegian farmers, 1967-1991.

Perinatal health was investigated by linkage with the Medical Birth Registry of Norway for 192,417 births that took place between 1967 and 1991 among parents identified as farm holders in Norwegian agricultural censuses in 1969-1989. In a comparison with 61,351 births to nonfarmers in agricultural municipalities, farmers' births had an advantageous distribution of gestational ages and birth weights. Perinatal mortality was similar in the two groups, but the proportion of late-term abortions (gestational weeks 16-27) was higher among farmers' birth (odds ratio (OR) = 1.9, 95% confidence interval (CI) 1.6-2.3). Exposure indicators were classified on the basis of information given in the agricultural censuses and climate data for the grain harvest seasons of 1966-1991. The main hypotheses were that perinatal death is associated with parental exposure to pesticides. Toxoplasma contracted from infected sheep or pigs, or mycotoxins found in grain farming. There was no convincing evidence that perinatal death is associated with use of pesticides, sheep farming, or pig farming. The increase in late-term abortion among the farmers could to some extent be attributed to an excess of midpregnancy (weeks 21-24) deliveries among grain farmers; grain farmers had 132 deliveries at this time in pregnancy (2.8 per 1,000 pregnancies), while the nongrain farmers had 236 deliveries in midpregnancy (1.8 per 1,000). The authors found odds ratios (95% CI) that indicated that grain farming risk was higher after the harvest (1.8, 1.1-2.8), in seasons with a poor quality harvest (2.4, 1.5-3.8), and in pregnancies with multiple births (3.8, 1.7-8.2). These results support the hypothesis that occupational exposure to mycotoxins in grain induces labor at an early stage of pregnancy.

Abortion, Spontaneous↗
PubMed1997

Environmental factors, reproductive history, and selective fertility in farmers' sibships.

In a national study of births to farmers in Norway, grain farming was associated with short gestational age (21-24 weeks). An impact of selective fertility and maternal heterogeneity on the association was suspected but could not be assessed further in a traditional birth-based design. Thus, analyses based on the mother as the observational unit were performed. A total of 45,969 farmers with a first birth in 1967-1981 were followed for subsequent births and perinatal mortality. A perinatal loss increased farmers' likelihood to continue to another pregnancy, but this selective fertility was less dominant than in the general population due to a higher baseline fertility. The effect of the mother's reproductive history on the grain farming-midpregnancy delivery association was analyzed in 59,338 farmers with more than one single birth in 1967-1991. A history of preterm birth (< 37 weeks) in previous or subsequent pregnancies both was an independent determinant of midpregnancy delivery and also increased the effect of grain exposure. Nongrain farmers with a history of only term births had 1.3 midpregnancy deliveries per 1,000 births; grain farmers with a history of only term births had 1.8 cases per 1,000 (odds ratio (OR) 1.4, 95% confidence interval (CI) 1.0-1.9); nongrain farmers with a history of preterm birth had 6.8 cases per 1,000 (OR 5.5, 95% CI 4.0-7.6), whereas grain farmers with a history of preterm birth had 13.7 cases per 1,000 (OR 11.0, 95% CI 7.7-15.9). Selective fertility had only a marginal impact on the association. The study demonstrates that a maternally based design can contribute in the assessment of joint effects of environmental and maternal factors.

Agriculture↗
PubMed1997

Subunit arrangement in the human 20S proteasome.

In human 20S proteasomes two copies of each of seven different alpha-type and seven different beta-type subunits are assembled to form a stack of four seven-membered rings, giving the general structure alpha(1-7), beta(1-7), beta(1-7), alpha(1-7). By means of immunoelectron microscopy and chemical crosslinking of neighboring subunits, we have determined the positions of the individual subunits in the proteasome. The topography shows that for the trypsin-like, the chymotrypsin-like, and the postglutamyl cleaving activities, the pairs of beta type subunits, which are thought to form active sites, are nearest neighbors.

Amino Acid Sequence↗
PubMed1997

The neuropeptide Y (Y4) receptor is highly expressed in neurones of the rat dorsal vagal complex.

Recently, the cDNA encoding the Y4 neuropeptide Y (NPY) receptor cDNA was cloned from a rat genomic library. The Y4 receptor is characterized by having a high affinity for pancreatic polypeptide (PP) and peptide YY (PYY). By using in situ hybridization histochemistry with 35S-labelled riboprobes, we have visualized the cellular expression of mRNA encoding the Y4 receptor protein in the rat dorsal vagal complex at the light microscopical level. High densities of silver grains were observed over neurones of the dorsal vagal motor nucleus, and over neurones of a subregion of the nucleus of the solitary tract known as the subnucleus gelatinosus. Furthermore, cells within the ventral margin of the area postrema expressed high levels of Y4 mRNA. These observations indicate that circulating PP and/or NPY/PYY via the blood-brain barrier-free area postrema and subpostremal area could influence neurones of the dorsal vagal complex with profound influence on numerous homeostatic mechanisms governed by this nuclear complex.

Animals↗
PubMed1997

Birth defects among offspring of Norwegian farmers, 1967-1991.

We investigated birth defects (N = 4,565) reported to the Medical Birth Registry of Norway among 192,417 births between 1967 and 1991 to parents identified as farmers in five agricultural and horticultural censuses between 1969 and 1989. The prevalences at birth of all and specific birth defects deviated little from those among 61,351 births to non-farmers in agricultural municipalities. We classified exposure indicators on the basis of information provided at the agricultural censuses. The main hypotheses were that parental exposure to pesticides was associated with defects of the central nervous system, orofacial clefts, some male genital defects, and limb reduction defects. We found moderate increases in risk for spina bifida and hydrocephaly, the associations being strongest for exposure to pesticides in orchards or greenhouses [spina bifida: 5 exposed cases, odds ratio (OR) = 2.76, 95% confidence interval (CI) = 1.07-7.13; hydrocephaly: 5 exposed cases, OR = 3.49, 95% CI = 1.34-9.09]. Exposure to pesticides, in particular in grain farming, was also associated with limb reduction defects (OR = 2.50; 95% CI = 1.06-5.90). We also saw an association with pesticides for cryptorchism and hypospadias. We found less striking associations for other specific defects and pesticide indicators, animal farming, and fertilizer regimens.

Abnormalities, Drug-Induced↗
PubMed1997

Proteoglycan expression in the normal rat kidney.

Proteoglycans constitute a heterogenous group of complex macromolecules, consisting of a backbone core protein and a variable number of sulfated polysaccharide side chains covalently linked to the core. A dual function for these polyanionic glycosaminoglycans in kidney physiology has been proposed: to maintain a fixed negative charge in the glomerular filtration barrier, and to bind and sequester cytokines essential for renal development and function. With the aim of identifying proteoglycan genes expressed in kidney glomeruli, we have performed in situ hybridization for selected proteoglycan core proteins in the normal rat kidney. Syndecan-4, glypican-1 and biglycan were all expressed in normal glomeruli, whereas syndecan-1, perlecan and versican mRNAs were confined to the papillary area. Decorin mRNA was detected in interstitial cells found between tubuli and surrounding larger vessels. No signal for betaglycan mRNA could be detected. By hybridizing adjacent sections with a probe for the podocyte-specific PTPase GLEPP-1, the glomerular cells containing mRNA for syndecan-4 and glypican-1 could be identified as podocytes, whereas the cells expressing biglycan were identified as mesangial cells. These results demonstrate that seven out of the eight proteoglycans investigated are expressed in the normal kidney in detectable amounts and, importantly, that each proteoglycan gene shows a unique pattern of expression. The constitutive expression of syndecan-4, glypican-1 and biglycan in glomerular cells points to a role for these polyanionic molecules in maintaining the integrity of the glomerular filtration barrier.

Amino Acid Sequence↗
PubMed1996

A model phage display subtraction method with potential for analysis of differential gene expression.

In order to establish a subtractive procedure that makes it possible to enrich selectively phage displayed antibodies directed against proteins constituting a difference between two populations of cells, a competitive selection strategy utilising two solid phases was developed and tested. Antibodies recognising a defined difference between two otherwise identical protein mixtures were isolated and their specificity confirmed. To test further the efficacy of selection inhibition during the competitive selections, selections towards a total cell extract were performed with and without competition from the same extract. An analysis of the resulting phage antibodies confirmed the subtractive nature of the system described.

Animals↗
PubMed1996

Newly identified pair of proteasomal subunits regulated reciprocally by interferon gamma.

Interferon (IFN) gamma induces replacements of the proteasomal subunits X and Y by LMP7 and LMP2, respectively, resulting in an alteration of the proteolytic specificity. We found a third pair of proteasome subunits expressed reciprocally in response to IFN-gamma. Molecular cloning of a cDNA encoding one subunit designated as Z, downregulated by IFN-gamma, showed that it is a novel proteasomal subunit with high homology to MECL1, which is markedly induced by IFN-gamma. Thus, IFN-gamma induces subunit replacements of not only X and Y by LMP7 and LMP2, respectively, but also of Z by MECL1, producing proteasomes responsible for immunological processing of endogenous antigens. When processed from their precursors, three pairs of the 10 homologous, but distinct, beta-type subunits of eukaryotic proteasomes, that is, X/LMP7, Y/LMP2, and Z/MECL1, have an NH2-terminal threonine residue, assumed to be part of a catalytic center. These findings suggest that the altered molecular organization of the proteasome induced by IFN-gamma may be responsible for acquisition of its functional change.

Amino Acid Sequence↗
PubMed1996

Cancer in offspring of parents engaged in agricultural activities in Norway: incidence and risk factors in the farm environment.

In this study of cancer in offspring we demonstrate that factors linked to horticulture and use of pesticides are associated with cancer at an early age, whereas factors in animal husbandry, in particular poultry farming, are associated with cancers in later childhood and young adulthood. Incident cancer was investigated in offspring born in 1952-1991 to parents identified as farm holders in agricultural censuses in Norway in 1969-1989. In the follow-up of 323,292 offspring for 5.7 million person-years, 1,275 incident cancers were identified in the Cancer Registry for 1965-1991. The standardized incidence for all cancers was equal to the total rural population of Norway, but cohort subjects had an excess incidence of nervous-system tumours and testicular cancers in certain regions and strata of time that could imply that specific risk factors were of importance. Classification of exposure indicators was based on information given at the agricultural censuses. Risk factors were found for brain tumours, in particular non-astrocytic neuroepithelial tumours: for all ages, pig farming tripled the risk [rate ratio (RR), 3.11; 95% confidence interval (CI), 1.89-5.13]; indicators of pesticide use had an independent effect of the same magnitude in a dose-response fashion, strongest in children aged 0 to 14 years (RR, 3.37; 95% CI, 1.63-6.94). Horticulture and pesticide indicators were associated with all cancers at ages 0 to 4 years, Wilms' tumour, non-Hodgkin's lymphoma, eye cancer and neuroblastoma. Chicken farming was associated with some common cancers of adolescence, and was strongest for osteosarcoma and mixed cellular type of Hodgkin's disease. The main problem in this large cohort study is the crude exposure indicators available; the resulting misclassification is likely to bias any true association towards unity.

Acute Disease↗
PubMed1996

Communication Concerning the Risks of Occupational Exposures in Pregnancy.

The health professional who is involved in communicating information about reproductive risks from occupational hazards needs to consider several important aspects. Uncertainties in risk assessment, timing of exposure in relation to pregnancy, and the consequences of different preventive measures for the woman (family), as well as for the employer and other persons at the workplace are examples of such aspects. The basis for the pregnant woman's perception of risk must be recognized. The risk-communication goal is that the persons concerned fully understand the risk and its possible consequences, so that they will be able to make informed decisions about how to act. More attention should be given to risk communication in the training of health professionals.

Journal Article↗
PubMed1996

Incidence and risk factors of cancer among men and women in Norwegian agriculture.

OBJECTIVES: The objective of the study was to examine cancer incidence and identify risk factors among subjects born in 1925-1971 and engaged in agricultural activities in Norway. METHODS: A cohort was established through linkage between agricultural censuses in 1969-1989 and the Central Population Register, which identifies farm holders and their spouses. Available census information on the activity of the farm provided the exposure indicators. Incident cancer in 1969-1991 was identified in the Cancer Register. In an analysis for standardized incidence ratios (SIR), the cohort was compared with the total rural population of Norway. Associations with exposure indicators were investigated in a Poisson regression analysis. RESULTS: In the follow-up of 136,463 men for 1.5 million person-years and 109,641 women for 0.6 million person-years, 3333 and 2145 cancer cases were identified, respectively. The subset defined as farmers had an SIR of 77 [95% confidence interval (95% CI) 73-81] for the men and 92 (95% CI 85-99) for the women, with particularly low SIR values for lung cancer and other sites linked to life-style. The several positive associations found confirmed the a priori hypothesis of an association between dairy farming and acute leukemia among men [rate ratio 1.76, 95% CI 1.02-3.05]. Multiple myeloma was associated with pesticide indicators for both genders, mainly for subjects cultivating potatoes. CONCLUSIONS: The results support the hypothesis of a relationship between acute leukemia and animal contact and between multiple myeloma and pesticides in potato cultivation. Other exposure associations, especially for cancer among women, warrant further investigation.

Adult↗
PubMed1996

Testicular cancer and parental use of fertilizers in agriculture.

Testicular cancer incidence is increasing rapidly in several countries. Environmental causes acting early in life are suspected but have not yet been identified. We conducted a cohort study to identify parental risk factors for testicular cancer among farmers' sons. Children born in 1952-1991 to parents who were farm holders at the time of the agricultural censuses in 1969-1989 were identified in the Central Population Register (Oslo, Norway). The resulting cohort of male offspring (n = 166,291) were followed up in the Cancer Registry of Norway (Oslo, Norway) for 1965-1991. Exposure indicators were derived from census information on activities on the farm. The cancer incidence was compared with that of the total rural population, and potential risk factors were analyzed by Poisson regression. In a follow-up of 2,924,663 person-years, 158 incident cases of testicular cancer were identified. The study population had a higher incidence of testicular cancer than did the total rural population, particularly at ages 15-19 years and in western Norway. Specific fertilizer regimens on the farm were associated with testicular cancer (rate ratio = 2.44; 95% confidence interval = 1.66-3.56), in particular nonseminoma (rate ratio = 4.21; 95% confidence interval = 2.13-8.32). The rate ratio estimates were highest for boys ages 15-19 years and for a subset of study subjects who were considered more likely to have grown up on a farm. Nondifferential misclassification and bias toward unity are likely because exposure information was available only at the farm level and only for census years. The fertilizer indicators were not available early in life for most subjects, and precise interpretations are difficult. A hypothesis worth considering is that excess nutrient run-off from agriculture constitutes a risk. However, inferences concerning the biological basis of our observations can scarcely be made.

Adolescent↗
PubMed1996

Normal levels of the vitamin D receptor and its message in psoriatic skin.

Treatment with vitamin D3 analogs improves psoriasis. The vitamin D receptor (VDR) mediates most, if not all, the effects of vitamin D3. The purpose of this study was to determine the levels of the VDR mRNA and VDR protein in normal and in involved and uninvolved psoriatic skin. Although VDR mRNA was not detected by Northern analysis of human skin samples, it was readily detectable by use of the more sensitive ribonuclease protection assay. The VDR mRNA levels were normal in acute guttate as well as in chronic plaque lesions. There was also no difference in VDR mRNA levels between normal and uninvolved psoriatic skin. The VDR protein was detected by Western analysis using the monoclonal 9A7 gamma anti-VDR antibody and a polyclonal rabbit anti-VDR antibody. For comparison, VDR levels were analyzed in cultures of normal human keratinocytes and the epithelial cell line MCF-7. Studies of the extraction procedures for VDR showed that at least 60% of Escherichia coli-expressed VDR added to the skin biopsy specimens was recovered. The VDR concentration in normal human adult skin was approximately 50 pg/microgram protein, and the concentrations of VDR in involved and uninvolved psoriatic skin were of the same order of magnitude. Using the 9A7 gamma anti-VDR antibody, the VDR (M(r) 53,000) was constantly present in lower amounts than a band of M(r) 80,000 in both skin specimens and keratinocyte cultures. This high-molecular-weight band is most likely a cross-reacting protein not related to VDR, because it was absent when using the polyclonal anti-VDR antibody.

Adult↗
PubMed1995

The human proteasome subunit HsN3 is located in the inner rings of the complex dimer.

Subunit HsN3 of the human proteasome is a beta-type subunit homologous to PRE4 from yeast, X1 beta from Xenopus and RN3 from the rat. Using electron microscopy, the binding sites of a monoclonal antibody with specificity for subunit HsN3 have been located in the two juxtaposed inner rings of the human proteasome. Subunit HsN3 was present in two copies, one in each ring, in accordance with our concept of two identical halves making up the complete human proteasome. The subunit is involved in the trypsin-like as well as the peptidylglutamyl-peptide cleavage activities.

Amino Acid Sequence↗