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Biomedical subjects

J L Thomsen

Publications and source records attributed to J L Thomsen.

At least 19 recordsLinked to original sources
PubMed2004

Markers of fetal growth and serum levels of insulin-like growth factor (IGF) I, -II and IGF binding protein 3 in adults.

Fetal growth has been linked with increased risk of cancer and cardiovascular disease later in life. The insulin-like growth factor (IGF) axis has recently been proposed as a predictor of risk of subsequent cancer and cardiovascular disease. However, only few data are available on the possible association between fetal growth and levels of IGFs later in life. We examined the association between markers of fetal growth, i.e. birth weight, birth length and Ponderal Index, from birth records and serum IGF-I, IGF-II, and IGF binding protein 3 (IGFBP-3) levels in 545 middle-aged Danish men and women. We fitted separate multivariate models including birth weight, birth length, Ponderal Index and serum IGF-I, IGF-II, and IGFBP-3, respectively. After adjustment for age, alcohol intake, smoking, diabetes mellitus, systolic and diastolic blood pressure, serum total cholesterol and current height and weight, we found negative associations between birth weight and Ponderal Index, respectively, and serum IGF-II in men, i.e. the mean regression coefficients were -49.41 (95% CI: -87.06-11.77) (microg/l)/kg and -3.49 (95% CI: -6.73-0.25) (microg/l)/(kg/m3), respectively. Furthermore, in men birth weight was negatively associated with the (IGF-I + IGF-II)/IGFBP-3 and IGF-II/IGFBP-3 ratios, which are believed to be indicators of bioavailable IGF and IGF-II, respectively. However, no other associations were found in any of the models. Between 1 and 16% of the variance in serum IGF-I, IGF-II, and IGFBP-3, respectively, could be explained by the statistical models used in the analyses. We found very little support to the hypothesis of an association between fetal growth and the IGF axis throughout life.

Aged↗
PubMed2000

Significance of various analytical methods with reference to the causes and manners of death in alcoholics.

It was the aim of the present investigation to apply a broad spectrum of analyses to forensic autopsies of alcoholics in order to estimate the significance of the various analytical methods with reference to the cause and manner of death. The analyses were performed on a consecutive series of 73 medico-legal autopsies in alcoholics. Both extensive histology as well as toxicology and microbiology were used. The microbiology did not contribute substantially to the determination of the cause of death, while histology was decisive in six cases. Toxicology analyses were necessary for determining the cause of death in 37 cases. The results of the investigation may help in the selection of analytical priorities.

Adult↗
PubMed2000

Endothelin-1 (ET-1)-potentiated insulin secretion: involvement of protein kinase C and the ET(A) receptor subtype.

Endothelin-1 (ET-1), a potent vasoconstrictor peptide of endothelial origin, is capable of influencing hormone secretion from endocrine tissues, eg, pancreatic islet cells. We have shown a direct stimulatory effect of ET-1 on insulin secretion from isolated mouse islets of Langerhans. However, it is unknown as to whether the peptide acts through specific receptors on the islet cells and which mechanisms are involved in this insulinotropic action. We have therefore used the specific ET(A) receptor antagonist BQ123, the ET(B) receptor agonist BQ3020, and classic alpha- and beta-adrenergic and cholinergic antagonists. ET-1 (100 nmol/L) stimulated insulin secretion from islets incubated at 8.3, 11.1, 16.7, and 25 mmol/L glucose (P < .05). At 3.3 mmol/L glucose, no alteration in insulin secretion was found. The cholinergic receptor antagonist atropine (5 micromol/L) or the adrenergic receptor antagonists propranolol (5 micromol/L) or phentolamine (5 micromol/L) did not affect ET-1 (100 nmol/L)-stimulated insulin secretion. BQ123 (10 pmol/L to 10 nmol/L) and BQ3020 (1 nmol/L to 1 micromol/L) had no effect on glucose (16.7 mmol/L)-stimulated insulin secretion, but BQ123 counteracted the stimulatory effect of ET-1 (100 nmol/L) at concentrations of 1 nmol/L to 10 micromol/L (P < .01). We also studied the relative role of protein kinase C (PKC) and a Wortmannin-sensitive pathway for ET-1-induced insulin secretion using 12-O-tetradecanoyl phorbol-13-acetate (TPA), Calphostin C, and Wortmannin, respectively. At 5.6 mmol/L glucose, ET-1 (100 nmol/L) had no effect per se, whereas in the presence of 1 micromol/L TPA, which acutely stimulates PKC, the peptide did potentiate insulin secretion (P < .05). Furthermore, the insulinotropic effect of ET-1 at 16.7 mmol/L glucose was counteracted by the PKC inhibitor Calphostin C (P < .05) and by downregulation of PKC by 24 hours of exposure of islets to TPA (0.5 micromol/L, P < .05). Wortmannin (1 micromol/L) did not alter ET-1-potentiated insulin secretion. In conclusion, our results suggest that ET-1 acts through specific ET-1 receptors, most likely the ETA subtype. Furthermore, PKC plays an essential role in the insulinotropic action of ET-1 in mouse islets.

Adrenergic Antagonists↗
PubMed2000

Lipids in the proximal tubules of the kidney in diabetic coma.

Vacuolization of the renal tubular epithelial cells (the Armanni-Ebstein lesion) associated with diabetic hyperglycemia is usually regarded as an accumulation of glycogen. In a case of death of diabetic coma, the vacuoles were stained strongly for lipids. This observation may have both clinical and therapeutic consequences, and may increase our knowledge of the metabolism in diabetes.

Diabetic Coma↗
PubMed2000

The role of the pathologist in human rights abuses.

The objective and unbiased statement is much valued in international work against human rights abuses. Pathologists play an increasingly important role. In this article, this role is illustrated by examples and the international set of rules is described. It is emphasised that under no circumstances should physicians assist in procedures, such as torture, which can weaken a human being. There is ongoing research into the sequelae of torture, both by gross and microscopic examination and in the living and dead victims.

Autopsy↗
PubMed1999

Bacteria in lung tissue from an autopsy population of alcoholics.

The retrieval of bacteria from the lungs postmortem was examined in a population of alcoholics who had a medico-legal autopsy performed. The results were compared with non-alcoholic controls. Pneumococci were found more frequently in alcoholics, but in general there were no major differences. Proteus mirabilis was detected in three out of five alcoholics with unascertainable cause of death. It is speculated whether this species may cause septicaemia in some alcoholics due to abnormal splanchnicus circulation.

Adult↗
PubMed1999

The insulinotropic effect of endothelin-1 is mediated by glucagon release from the islet alpha cells.

AIMS/HYPOTHESIS: The circulating concentrations of endothelin-1 (ET-1), a peptide derived from endothelium, are increased in hypertension and diabetes. Endothelin-1 has recently been shown to be an insulinotropic agent. The mechanism of action of endothelin-1 on the endocrine pancreas has not yet been clarified. METHODS: We investigated the action of endothelin-1 on the insulin secretion, the binding of (125)I-ET-1 to beta cells as well as its effects on purified beta and non-beta cells from normal rats. The expression of endothelin receptors in alpha- and beta-cell lines and in normal rat islets was also studied. RESULTS: First, we studied the effects of endothelin-1 on insulin secretion from beta-cell lines (INS-1, betaTC3 and MIN6). At all endothelin-1 concentrations applied (1 pmol/l to 1 micromol/l) no change in insulin secretion was found. Ligand-binding experiments on betaTC3 cells showed no specific binding of (125)I-ET-1. A prominent expression of ET(A)-receptor mRNA in an alpha-cell line (alphaTC1.9) and in normal rat islets was found whereas no expression was found in INS-1 cells. No influence of endothelin-1(1 micromol/l) on insulin secretion stimulated by glucose was detected from purified beta cells. Endothelin-1-(100 nmol/l) increased, however, both insulin and glucagon secretion from a mixture of purified beta and non-beta cells indicating that alpha cells seem to have a key role for the action of ET-1 on insulin secretion. CONCLUSION/INTERPRETATION: The insulinotropic impact of endothelin-1 is not caused by a direct action on the beta cells but seems to be mediated by a paracrine action, probably secondary to enhanced release of glucagon from the endothelin receptor positive alpha cells. [Diabetologia (1999) 42: 1302-1307]

Animals↗
PubMed1999

Differential effects of cis and trans fatty acids on insulin release from isolated mouse islets.

In vitro and in vivo studies in animals have shown that elevated levels of free fatty acids (FFAs) induce impaired beta-cell function corresponding to the abnormalities observed in non-insulin-dependent diabetes mellitus (NIDDM). Previously, it was demonstrated that the chain length and degree of unsaturation are of importance for the insulinotropic effect of fatty acids. However, it is not known if the spatial configuration of the fatty acid influences beta-cell function. The present study examines whether cis and trans fatty acids acutely influence insulin release and glucose oxidation in isolated mouse islets in the same way and to the same extent. Thus, we studied the impact of both cis and trans forms of C 18:1 fatty acids. We found that cis and trans vaccenic acid (cis and trans C 18:1 delta11), as well as oleic acid (cis C 18:1 delta9) and elaidic acid (trans 18:1 delta9), caused a dose-dependent increase in glucose (16.7 mmol/L)-stimulated insulin secretion during static islet incubations. The maximal stimulatory effect for cis and trans vaccenic acid and for oleic and elaidic acid was observed at concentrations of 2.0 and 3.0 mmol/L, respectively. The trans isomers, trans vaccenic and elaidic acid, elicited a higher maximal insulin output than the respective cis isomers, cis vaccenic and oleic acid. In the presence of another insulin secretagogue, L-leucine, trans vaccenic but not elaidic acid caused a higher response than their cis isomeric fatty acids. The higher potency of trans fatty acids compared with the cis forms was confirmed in perifusion experiments. Both cis and trans C 18:1 fatty acids stimulated insulin secretion in a glucose-dependent manner. Also, glucose oxidation was influenced differentially by the isomers of fatty acids. Glucose oxidation at 16.7 mmol/L glucose was significantly inhibited by oleic and cis vaccenic acid compared with elaidic and trans vaccenic acid, respectively. In summary, our results demonstrate that the fatty acid spatial configuration modulates glucose oxidation and insulin secretion in mouse beta cells.

Animals↗
PubMed1998

Intra- and inter-observer variation in histological criteria used in age at death determination based on femoral cortical bone.

The microscopic method of age at death determination was introduced by Kerley in 1965. The method, which relies on the quantification of selected elements in cortical bone tissue, has been widely used, and several other researchers have modified or added to the method. Yet, very few studies have been carried out dealing with the intra- and inter-observer error. Furthermore, when such studies have been completed, the statistical tools for assessing variability have not been adequate. This study presents the results of applying simple quantitative statistics on several counts of microscopic elements as observed on photographic images of cortical bone, in order to assess intra- and inter-observer error. Overall, substantial error was present at the level of identifying and counting secondary osteons, osteon fragments and Haversian canals. Only secondary osteons can be reliably identified, precluding the use of osteon fragments and Haversian canals. The observers in this study included experienced and inexperienced users of the microscopic method, yet the variability was uniformly large for all observers, suggesting fundamental problems in definition and identification of the structural elements. Until more rigorous definitions of such elements have been agreed upon, the use of microscopical methods must be discouraged as a sole or uncontrolled method of evaluating age at death.

Age Determination by Skeleton↗
PubMed1997

Post-mortem radiological examination in infants: evidence of child abuse?

We examined the value of post-mortem radiological examination of infants who were brought in for medico-legal autopsy. Twenty children between the age of 1 month and 15 months died under the picture of SIDS. No radiological or other signs of previous child abuse were seen in our autopsy material. A fatal case of child abuse with several metaphyseal fractures is reported. Some fractures were not visible on gross examination, but could be demonstrated by radiography and histology. In our material no association between SIDS and child abuse was found. In suspected cases of child abuse, particularly rib fractures and metaphyseal fractures should be sought. We recommend that post-mortem radiography is performed in such cases. If fractures are demonstrated, they should be verified by histologic examination.

Autopsy↗
PubMed1997

A prospective toxicology analysis in alcoholics.

A prospective and comprehensive investigation was done on 73 medico-legal autopsies in alcoholics. The results of the toxicology analyses are described. Alcohol intoxication was the cause of death in 8%, combined alcohol/drug intoxication in 15% and drugs alone in 19%. Alcoholic ketoacidosis was found to be the cause of death in 7%. Altogether toxicology analyses were necessary for determining the cause of death in 51% of the cases. In four cases the cause of death would not have been found, had this investigation not been made. It is concluded that toxicology analyses should be the rule rather than the exception in deaths in alcoholics.

Adult↗
PubMed1997

[Atherosclerosis in alcoholics].

A cohort of alcoholics who underwent a medico-legal autopsy during a five-year period was compared with non-alcoholic controls who did not differ from the alcoholics in selection criteria. The degree of atherosclerosis in the coronary arteries and the aorta was examined. Alcoholic men and old women had a significantly lower degree of atherosclerosis in the coronary arteries, while the opposite was found in young women. In the aorta there was no significant difference in the degree of atherosclerosis between alcoholics and controls in men. Alcoholic women generally had a lower degree of atherosclerosis in the aorta. The so-called U-shaped curve for the relationship between the daily alcohol intake and atherosclerosis is described together with some of the investigations on which it is based. There is much positive evidence for the U-shaped curve, although a causal association has not been proven as yet. The present results indicate a complex relationship, in which different confounding factors are likely to play a role.

Adult↗