PubMed Health⌕ Search

Biomedical subjects

P K Lund

Publications and source records attributed to P K Lund.

At least 19 recordsLinked to original sources
PubMed1992

Ontogeny of glucagon messenger RNA in the rat pancreas.

The synthesis of proglucagon mRNA was studied in rat pancreas from day 11 of fetal gestation (E11) to maturity. Proglucagon mRNA was first detected on E11, the time that the pancreatic bud forms in developing rats. The synthesis of proglucagon mRNA and its translation product at this early time point in pancreatic development suggests an early differentiation of A cell function. Between E17 prenatally and day 10-14 postnatally, pancreatic proglucagon mRNA abundance was higher than in adult pancreas. Regulation of the abundance of pancreatic proglucagon mRNA therefore appears to underlie the previously documented increases in serum and pancreatic glucagon immunoreactivity in the late fetal and perinatal periods. By day 20 postnatally, pancreatic proglucagon mRNA declined to levels found in adult pancreas. Prenatally between E17 and E21, changes in proglucagon mRNA abundance did not parallel previously reported developmental changes in relative mass of proglucagon-producing pancreatic A cells. This suggests that changes in proglucagon mRNA abundance during these times may be attributed to changes in proglucagon gene transcription or proglucagon mRNA stability per cell. In contrast between E21 and maturity, changes in proglucagon mRNA abundance paralleled previously reported changes in relative A cell mass, suggesting no major changes in proglucagon gene transcription or mRNA stability per cell during these times.

Animals↗
PubMed1992

Nutrient-independent increases in proglucagon and ornithine decarboxylase messenger RNAs after jejunoileal resection.

To assess potential mediators of adaptive bowel growth, ileal proglucagon messenger RNA (mRNA) ornithine decarboxylase (ODC) mRNA, plasma enteroglucagons, and plasma glucagonlike peptide I (GLP-I) were analyzed in rats soon after jejunoileal resection or control transection. Analyses were performed before and after refeeding to establish whether responses are nutrient dependent. The elevation of ileal proglucagon and ODC mRNAs within 12 hours after resection and before refeeding shows a nutrient-independent component of the adaptive response. The onset of adaptive growth of the ileum required luminal nutrient but occurred very rapidly, within 4 hours of refeeding. The onset of adaptive growth was accompanied by transient elevation of ileal ODC mRNAs. Ileal proglucagon mRNA and plasma GLP-I levels were also elevated, and these increases were sustained up to 8 days after resection. These early and sustained increases in proglucagon mRNA and plasma GLP-I indicate that in addition to the enteroglucagons, other intestinal proglucagon-derived peptides must be considered as potential mediators of adaptive growth after jejunoileal resection.

Adaptation, Physiological↗
PubMed1991

Colchicine enhances mRNAs encoding the precursor of calcitonin gene-related peptide in brainstem motoneurons.

Hybridization signals indicating mRNAs encoding the precursor of calcitonin gene-related peptide (CGRP) and CGRP immunoreactivity were detected on parallel sections containing brainstem motor nuclei using in situ hybridization histochemistry and immunohistochemistry. In untreated and saline-injected rats the motoneurons in the hypoglossal, facial motor nuclei and in the ambiguus nucleus showed weak to moderate hybridization signals. In these motoneurons CGRP immunoreactivity was restricted to the Nissl bodies of the perikarya. Twenty-four and 42 hours after intracerebroventricular colchicine injection the intensity of both the hybridization signal and the immunoreaction product increased. The distribution of CGRP immunoreactivity changed from discrete perikaryal localization to diffuse reaction in the perikarya and along the proximal dendritic tree. Motoneurons in the rest of the brainstem motor nuclei (VIth, Vth, IVth and IIIrd) of untreated and saline-injected rats showed neither hybridization signal nor CGRP immunoreactivity. After intracerebroventricular injection of colchicine these motoneurons showed both hybridization signal and CGRP immunoreactivity. In all nuclei the size of motoneurons decreased and their Nissl structure changed to an amorphous basophilic mass following colchicine treatment.

Animals↗
PubMed1991

Performance of cell counters in primary health care.

The results are presented from two external quality control surveys of cell counters in primary health care. The precision of haemoglobin measurements in the normal range was better than that obtained by conventional haemometers. The analytical quality of leucocyte analyses was about the same as that performed by hospital instruments. The precision of cell counters with respect to thrombocytes was poorer than that obtained on hospital instruments, especially in the lower level. Celldyn and Sysmex instruments performed best among the instruments examined. Reliable cell counter results were associated with medical laboratory technicians as operators of the instruments. To improve the analytical quality of the laboratory in primary health care, it appears necessary to establish an external quality assurance programme, including a laboratory consultancy service.

Blood Cell Count↗
PubMed1990

Ontogeny of glucagon messenger RNA and encoded precursor in the rat intestine.

The ontogeny of proglucagon mRNA and encoded precursor was studied in rat intestine from day 11 of fetal gestation (E11) to maturity. The earliest time point for detection of proglucagon antigenic determinants by immunocytochemistry, and of proglucagon mRNA by in situ hybridization histochemistry, was day 14 of fetal gestation (E14), suggesting this time as the point of onset of intestinal proglucagon gene expression and mRNA translation. Between day 17 and 18 of gestation (E17 and E18) there was a significant 10 fold increase in intestinal L cell density, indicating that this time in gestation is one of increased L cell differentiation and/or proliferation. Proglucagon mRNA abundance in developing rat intestine showed a major 8 fold increase between E17 and E18. Similar magnitude of increases in L cell density and proglucagon mRNA abundance suggests that the increase in proglucagon mRNA abundance reflects an increase in L cell numbers rather than increases in proglucagon gene transcription or mRNA stability per cell.

Aging↗
PubMed1990

Species-specific expression of cholecystokinin messenger RNA in rodent dorsal root ganglia.

The expression of cholecystokinin (CCK) messenger RNA (mRNA) was examined in dorsal root ganglia of rat and guinea pig using in situ hybridization histochemistry and RNA (Northern) blot hybridization with synthetic oligodeoxyribonucleotide (oligomer) probes. In guinea pig, CCK mRNA was detected in small and medium-sized neuronal perikarya comprising approximately 10-15% of the total dorsal root ganglia cell population. In contrast, in neurons of rat dorsal root ganglia, CCK mRNA was not detectable. Northern blot analyses revealed a single CCK mRNA species of expected size (0.8 kb) in guinea pig, but not rat, dorsal root ganglia. A 0.8 kb CCK mRNA was, however, detected in cortex of both rat and guinea pig. These data suggest that CCK is normally not synthesized in neurons of rat dorsal root ganglia and that there are species differences in CCK gene expression in mammalian sensory ganglia.

Animals↗
PubMed1990

Practical experience with a quality control procedure using retained patient specimens on Technicon H1 and COULTER S 880.

External quality assessment and internal quality control in hematology is complicated by the lack of good control materials. Commercial materials do not always behave as patient blood and they are expensive. Patient specimens are unstable, but may be used either within certain time limits or as in Bull's moving average for red cell indices. We have used retained patient specimens for internal quality control supplemented by a commercial control material. Three patient-specimens were run alternatively on a Technicon H1 and a Coulter 880 at regular intervals. The variations for each instrument and between instrument were computed. We used the 2 of 3 (2s) control rule. Our conclusion is that the Coulter 880 had an overall better performance than the Technicon H1 when using retained patient specimens. But both instruments practically met suggested analytical goals.

Goals↗
PubMed1990

Molecular biology of gastrointestinal peptides and growth factors: relevance to intestinal adaptation.

New approaches towards understanding regulation of growth and adaptation of the small intestine are made possible by the isolation and characterization of genes and complementary DNAs (cDNAs) encoding gastrointestinal peptides, growth factors and their receptors. Nucleotide sequencing provides prerequisite structural information. Analyses of gene expression by quantitation and localization of mRNAs provide information about correlations between local alterations in peptide or receptor synthesis and intestinal growth. Analyses of intestinal growth in transgenic animals that overexpress or underexpress growth factor or receptor genes provides direct information about peptide effects on growth. Our recent studies with genes and cDNAs encoding proglucagon and the growth hormone dependent insulin-like growth factor 1 (IGF-I) represent examples of these approaches. Sequences of proglucagon and IGF-I cDNAs provide the primary structures of the peptide precursors. Analyses of proglucagon mRNA during adaptive growth after small bowel resection indicate that increases in proglucagon gene transcription or mRNA stability underly previously observed increases in serum enteroglucagons during adaptive growth. Analyses of IGF-I mRNAs in intestine indicate that small intestine expresses only a subset of the IGF-I mRNAs expressed in liver due to utilization of specific promotors and/or exon splicing mechanisms. Oligomers derived from the 3' end of the rat IGF-I gene detect a novel intestinal specific IGF-I related mRNA that shows an aboral decline in abundance from duodenum to colon and is upregulated in a number of situations of adaptive growth. Transgenic mice that overexpress growth hormone or IGF-I are under analysis to establish the effects of growth hormone and IGF-I on intestinal growth.

Adaptation, Physiological↗
PubMed1990

Effect of massive small bowel resection on components of the peptidergic innervation of the rat small intestine.

The effect of massive small bowel resection on the immunostaining of neuropeptides in the submucous plexus of the retained small intestine was examined. The neuropeptides chosen were somatostatin and vasoactive intestinal polypeptide because these are markers for two of the major populations of neurons in the plexus. Three different methods were used to assess the effect of resection on the enteric nervous system. Firstly immunocytochemical staining of neuropeptide containing neurons and nerve fibers was compared between test and control animals. The results demonstrated a significant increase in the number and size of the vasoactive intestinal polypeptide containing neurons with no change in the number of somatostatin neurons although these were also increased in size. Secondly the possibility that the increase in neuron number might be the result of neuronal division was examined by 3H-thymidine incorporation experiments. The results demonstrated that no neuronal elements were labelled. Finally the possibility that the increase in vasoactive intestinal peptide was the result of an increase in transcription was assessed by Northern blot analysis. The results demonstrated a small but significant increase in mRNA levels. It was concluded that massive small bowel resection directly affects neuropeptide levels in the submucous plexus, resulting in an increase in vasoactive intestinal polypeptide-immunoreactive neurons.

Animals↗
PubMed1990

Different half-lives of insulin-like growth factor I mRNAs that differ in length of 3' untranslated sequence.

Rat liver insulin-like growth factor 1 (IGF-I) mRNAs encoding the same IGF-I and precursor exist as two predominant size classes of 7.5-7.0 and 1.2-0.9 kilobases (kb). The different sized mRNAs, differ only in length of 3' untranslated sequence (3'UT) and appear to derive from the use of alternate polyadenylation sites. Since the long 3'UT of the 7.5-7.0 kb IGF-I mRNAs contain sequences implicated in mRNA destabilization, we compared decay of the 7.5-7.0 and 1.2-0.9 kb mRNAs, during in vitro incubation in a reticulocyte lysate cell-free translation system. The 7.5-7.0 kb mRNAs decayed to 30% of the initial abundance after 10 min in reticulocyte lysate and were undetectable after 60 min. In contrast, 80% of the 1.2-0.9 kb mRNAs remained after 60 min in reticulocyte lysate. The rapid decay of the large IGF-I mRNAs during incubation in reticulocyte lysate demonstrates that analysis of mRNA translation in cell-free systems must take into account the rate of mRNA decay. Induction and decay of the two rat liver IGF-I mRNAs was also analyzed in vivo in hypophysectomized rats given a single i.p. injection of human growth hormone (GH). While GH induced parallel increases in abundance of the two mRNAs, their decay rates differed. The time taken for decay to 50% maximum abundance was 4 h for the 7.5-7.0 kb mRNAs and 14 h for the 1.2-0.9 kb mRNAs. Differential in vitro and in vivo half-lives of liver IGF-I mRNAs that encode the same protein, derive from the same gene, and differ only in length of 3'UT indicates novel post-transcriptional mechanisms for control of liver IGF-I synthesis. Such mechanisms may have major significance in non-hepatic tissues such as brain where the 7.5-7.0 kb IGF-I mRNAs predominate. These findings with IGF-I mRNAs have general implications for products of other genes with multiple polyadenylation sites.

Animals↗
PubMed1989

[Correct handling of serum separating gel tubes is of significance].

We review the construction, handling, advantages and drawbacks of serum separator tubes. A study is reported, which demonstrates that serum potassium measurements are less reliable when gel-barrier sampling tubes are used incorrectly. We give guidelines for correct use of such equipment.

Blood Chemical Analysis↗
PubMed1989

[Hypercholesterolemia. Use of laboratory analysis].

The article summarizes the use of laboratory analysis as described in the recently published Norwegian program for diagnosis and treatment of hypercholesterolemia in adults. Serum cholesterol is used both to diagnose hypercholesterolemia and to monitor the effect of treatment. Serum triglycerides should be measured when hypercholesterolemia has been found and dietetic treatment is considered. High density lipoprotein (HDL) cholesterol should be measured when dietetic treatment has not reduced hypercholesterolemia sufficiently and drug treatment is considered. We do not at present recommend measurement of apolipoproteins and factors within coagulation/fibrinolysis, but such measurements might be of importance in the near future. Blood cholesterol exhibits large biological variations, which makes retesting necessary before hypercholesterolemia is diagnosed. Analytical variation is usually less than biological variation, but requires use of quality control materials. This control is equally important for small dry chemistry analyzers as for wet chemistry analyzers.

Blood Chemical Analysis↗
PubMed1989

Distribution of neurons expressing calcitonin gene-related peptide mRNAs in the brain stem, spinal cord and dorsal root ganglia of rat and guinea-pig.

In situ hybridization histochemistry was used to localize calcitonin gene-related peptide mRNAs in spinal cord, brain stem and dorsal root ganglion neurons of the rat and guinea-pig. A 32P-labeled 23-base-long (23mer) oligodeoxyribonucleotide (oligomer) complementary to calcitonin gene-related peptide mRNA sequences encoding residues 23-30 of calcitonin gene-related peptide was used primarily as a probe (CGRP I probe). A 32mer complementary to mRNA sequences for residues 10-20 of calcitonin gene-related peptide (CGRP II probe) was also used as a positive control for specificity of the 23mer for calcitonin gene-related peptide mRNA. In both the guinea-pig and rat calcitonin gene-related peptide mRNA was localized specifically to neurons of the dorsal root ganglion, to spinal motoneurons and to motoneurons of the hypoglossal, facial and accessory facial motor nuclei. Differences in the distribution of calcitonin gene-related peptide mRNA between the rat and guinea-pig included a higher proportion of rat dorsal root ganglion neurons containing calcitonin gene-related peptide mRNA and the localization of calcitonin gene-related peptide mRNA to motoneurons of the ambiguus motor nucleus, parabrachial and peripeduncular nucleus of the rat but not the guinea-pig. In the guinea-pig, in contrast, calcitonin gene-related peptide mRNA was localized also to motoneurons of the abducens, trigeminal, trochlear and oculomotor nerves. The neuronal groups in the intact rat found here to contain calcitonin gene-related mRNA have also been shown previously to contain calcitonin gene-related peptide immunoreactivity in colchicine-treated rats. Colchicine-treated rats, however, have been found to contain additional groups of calcitonin gene-related peptide immunoreactive neurons which, in the intact rats used in the present study, showed no detectable hybridization with the calcitonin gene-related peptide probe.

Animals↗
PubMed1989

Performance of dry-chemistry instruments in primary health care.

The results from an external quality control of dry-chemistry instruments are presented. The performance with regard to imprecision was good. With regard to accuracy, the performance was poor for aspartate aminotransferase, creatine kinase, lactate dehydrogenase, triglycerides and uric acid. The inaccuracy of alanine aminotransferase, bilirubin, cholesterol, creatinine, glucose and potassium was comparable to that obtained by hospital instruments using wet chemistry. There were no large differences with respect to quality between Seralyzer and Reflotron. However, Seralyzer users performed more analyses per week, analysed a higher number of constituents and had more experienced operators than the Reflotron users. Reflotron users more often analysed the sample in connection with the consultation. The importance of an established quality control programme for these instruments is underlined.

Blood Chemical Analysis↗
PubMed1989

The size heterogeneity of rat insulin-like growth factor-I mRNAs is due primarily to differences in the length of 3'-untranslated sequence.

Previous studies have revealed multiple size classes of rat insulin-like growth factor-I (IGF-I) of estimated size 7.5-7.0, 1.9-1.5, and 1.2-0.9 kilobases (kb). Available sequence information accounts for only 2.1 kb of the 7.5-7.0 kb IGF-I mRNAs. We used oligomer directed ribonuclease H (RNase H) mapping to define the extent to which the unknown sequence in the large molecular weight mRNAs lies 5' or 3' to known sequence. Rat liver polyadenylated RNAs were incubated with oligomer probes complementary to internal rat IGF-I precursor (E domain) coding sequences. RNase H was used to hydrolyze IGF-I mRNAs at the point of annealment with the oligomers. Resultant 5' and 3'-IGF-I mRNA fragments were analyzed on Northern blots. A probe specific for type 1 (class C) 5'-sequences (the most predominant of multiple 5'-sequence types found on rat IGF-I mRNAs) identifies intact IGF-I mRNAs of 7.5-7.0, 1.9-1.5 and 1.2-0.9 kb but, after oligomer directed RNase cleavage of these mRNAs, identified only a single IGF-I mRNA 5'-fragment. Major differences in the length of sequence 5' to the IGF-I coding sequence therefore, do not account for the multiple size classes of type 1 (class C) IGF-I mRNAs. The size of the 5'-fragment suggests that the extent of sequence 5' to the IGF-I coding sequence is 0.4-0.7 kb in type 1 (class C) IGF-I mRNAs. Identification of multiple 3'-fragments of IGF-I mRNAs demonstrated heterogeneity in the 3'-ends of rat IGF-I mRNAs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

In situ hybridization of peptide mRNAs on vibratome sections.

In situ hybridization procedures that have been used successfully for the localization of somatostatin and cholecystokinin mRNAs in neurons on cryostat sections of rat brain, were tested for applicability to vibratome sections of rat and guinea pig brain. Somatostatin and cholecystokinin mRNAs were localized to neurons in 30 microns thick vibratome sections of brain from both species by use of 32P labelled oligodeoxyribonucleotide (oligomer) probes. Somatostatin mRNAs was localized to neurons in the periventricular region of the preoptic area of rat, and guinea pig brain. Cholecystokinin mRNAs were localized to neurons of rat hippocampus. Hybridization signal, background and resolution achieved with vibratome sections were comparable to those obtained with the more commonly used cryostate sections.

Animals↗
PubMed1988

Distribution of glucagonlike peptide I (GLP-I), glucagon, and glicentin in the rat brain: an immunocytochemical study.

Although glucagonlike immunoreactants (GLIs) are present in the central nervous system of several mammalian species, their structural relationship with pancreatic proglucagon is not defined, and their precise anatomical distribution has not been studied extensively. To obtain further information about the structure and biological significance of brain GLIs, the anatomical distribution of three different antigenic determinants of pancreatic proglucagon--glucagonlike peptide I (GLP-I), glucagon, and glicentin--was mapped in the brain of colchicine-treated rats by immunocytochemistry using the avidin-biotin-peroxidase method. Neuronal cell bodies immunoreactive with antisera specific for GLP-I, glucagon, and glicentin were found only in the caudal medulla oblongata. Within the caudal medulla immunostained cell bodies were found at levels from approximately 0.55 mm rostral to the obex to 0.45 mm caudal to the obex, and were located within the nucleus of the solitary tract (NTS) and the dorsal (MdD) and ventral (MdV) parts of the medullary reticular nucleus. The NTS contained three times more immunoreactive cell bodies than the MdD and MdV, and these cell bodies were located in the midline, medial, and lateral subnuclei of the caudal third of the NTS. Immunostaining of the same cell bodies in paired adjacent sections incubated with GLP-I and glucagon antisera or glucagon and glicentin antisera provided evidence for coexistence of the three antigens within the same neurons of the NTS. Nerve fibers and terminals immunoreactive with GLP-I, glucagon, and glicentin antisera were widely distributed throughout the rat brain and there was no discernible difference in the distribution of fibers and terminals immunoreactive with each of the three antisera. The highest densities of immunostained fibers and terminals were observed in the hypothalamus, thalamus, and septal regions, and the lowest in the cortex and hindbrain. The localization of neuronal cell bodies containing GLP-I, glucagon, and glicentin within the NTS and the MdD and MdV, and the extensive distribution of immunoreactive fibers and terminals throughout the rat brain suggest a role for these peptides in the integration of autonomic as well as central nervous system functions.

Animals↗