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Biomedical subjects

A Jensen

Publications and source records attributed to A Jensen.

At least 19 recordsLinked to original sources

Environmental cadmium in Europe.

The present article reviews information from the latest 10 years concerning fate and exposure of cadmium in the environment, on ecotoxicological effects, and on critical pathways leading to human and environmental exposure. It emphasizes the situation within the Community of European Countries by referring to limit values used in the EEC and some of its member states for emissions to water, air and soil. Estimates have been made on total emission balances for the Netherlands, Denmark, and for the EEC as a whole. The balances show that 70-90% of all cadmium circulating in the Community is disposed of as waste in solid waste deposits. Production and use patterns are presently changing, as indicated by reduced consumption in recent years of cadmium for plating, stabilizers and pigments in several countries as a result of regulations. However, significant increases in consumption for cadmium-containing batteries have occurred, resulting globally in increasing trends for the total consumption and production. Cadmium in sediments is more mobile than described earlier. Aquatic organisms can be classified in order of decreasing accumulation: algae greater than molluscs greater than crustaceans greater than fish. There is no evidence of biomagnification of cadmium within marine or fresh water food webs. Cadmium may enter into plants via roots or by foliar adsorption following atmospheric deposition. Biomagnification in terrestrial food chains is not observed. The uptake into plants is plant specific. Within plants significant variations are seen with concentrations generally decreasing in the order: roots greater than leaves greater than fruiting parts greater than seeds. A compilation of cadmium in air, in the aquatic environment and in soil is given. A downward trend during the 1970s to mid-1980s seems to be evidenced from various Northern European studies on cadmium air concentrations as well as for deposition rates of cadmium. In rivers, the dissolved cadmium concentrations are generally found to be relatively low (10-500 ng/L). In seawater, cadmium concentrations are found at 0.5-10 ng/L in oceanic or open marine areas, while elevated concentrations are reported in more closed marine areas and especially in coastal zones close to polluted estuaries. In fresh water, lake sediments concentrations 3-30 times higher than the background concentrations are reported in the surface layers of sediments. A significant decrease in such pollution has been observed within the recent 10 years. For marine sediments, enrichment factors of two are found in sediments from open areas and locally even 5-10 times.(ABSTRACT TRUNCATED AT 400 WORDS)

Cadmium

[Risk of cerebral hemorrhage in premature and mature newborn infants].

We launched a prospective cranial ultrasound screening study at the Maternity Hospital of the University of Giessen to examine the incidence and severity of brain damage in newborns. More than 90% of all neonates born during 1984-86 were included in the study (n = 2781) and were screened for cerebral abnormalities on 5.9 +/- 3.3 (SD) day post partum. There were in 7.8% sonographic abnormalities, the most frequent being peri/intraventricular haemorrhages (5.2% PIVH of various degrees (grade I-III). Periventricular leucomalacia, porencephalia, subarachnoidal haemorrhages, and hydrocephali were rare (less than or equal to 0.2%). The incidence of PIVH increased progressively with decreasing gestational age, e.g. from 1.5% at 41 weeks up to 61% at 24-30 weeks of gestation. A large percentage of babies with cerebral haemorrhages were clinically normal. There was a close inverse relationship between the Apgar score at 1,5 and 10 min and both incidence and severity of PIVH. However, the relation between PIVH and both cardiotocography (matched-pairs analysis) and arterial cord blood-pH was poor. The incidence of PIVH was increased in growth retarded newborns (pH less than or equal to 7.29), preterm multiples and amnionitis, but not after preeclampsia and premature rupture of membranes. It is interesting to note that, in mature newborns (greater than or equal to 38 weeks), there was no difference in the incidence of PIVH between spontaneous deliveries, vacuum extractions, and Caesarean sections, and that there was no difference between vaginally delivered (1.5%) and sectioned breech presentations (3.5%) in this group. In preterms at 35-37 weeks with protracted labour and secondary Caesarean section, the incidence of PIVH was high (19%). We conclude, that neonatal cranial ultrasound screening is an important tool for risk assessment and quality control in obstetrics. It clearly improves both the quality of the advice given to the patients and the clinical management of high-risk pregnancies.

Acid-Base Equilibrium

Cerebral energy metabolism in immature and mature guinea pig fetuses during acute asphyxia.

In immature fetuses circulatory centralization caused by acute asphyxia is less effective than that in mature fetuses (Jensen & Berger, 1991). This suggests that cerebral oxygenation may be poor in immature fetuses during asphyxia. On the other hand cerebral oxygen consumption is lower in immature than that in mature fetuses. To determine, whether or not there is an imbalance between oxygen supply and demand in one or the other group, we compared the time course of the changes of cerebral concentrations of both high-energy phosphates and glycolytic intermediates between immature and mature guinea pig fetuses during acute asphyxia caused by arrest of uterine blood flow. The fall in the cerebral concentrations of adenosine triphosphate and glucose, and the rise in those of adenosine monophosphate and lactate were slower in immature than in mature fetuses. There were no differences between the levels of cerebral adenosine diphosphate and creatine phosphate of the two groups. From these results we conclude that during acute asphyxia the imbalance between cerebral oxygen supply and demand is less marked in immature than in mature fetuses.

Acute Disease

Foetal circulatory responses to arrest of uterine blood flow in sheep: effects of chemical sympathectomy.

Acute foetal asphyxia, caused by arrest of uterine blood flow, increases both sympathetic activity and peripheral vascular resistance and decreases blood flow to peripheral organs (Jensen et al., J. Dev. Physiol., 9, 543-559). The rapidity and uniformity of this peripheral vasoconstriction suggest that the sympatho-neuronal system may reflexly cause these initial blood flow changes during acute asphyxia. To test this hypothesis, we studied 5 intact and 6 chemically sympathectomized (6-hydroxy-dopamine, 46.1 +/- 6 mg/kg foetal weight) chronically prepared normoxaemic foetal sheep in utero at 0.9 of gestation. Organ blood flows (microsphere method), plasma concentrations of catecholamines, vasopressin, and angiotensin II, acid-base balance and blood gases were measured before, during and after arrest of uterine blood flow for 2 min, i.e., at 0, 1, 2, 3, 4 & 30 min. In intact foetuses there was a progressive increase in arterial blood pressure and a rapid circulatory centralization in favour of the brain stem and heart and at the expense of most of the peripheral organs. The changes in peripheral blood flow during and after asphyxia were well reflected by those in the skin and scalp. In chemically sympathectomized foetuses, arterial blood pressure fell transiently at 1 min of asphyxia and cardiac output was redistributed towards the carcass and intestinal organs at the expense of the heart, spinal medulla, and placenta. We conclude that in foetal sheep at 0.9 of gestation, the short-term adaptation to arrest of uterine blood flow is a rapid and profound peripheral vasoconstriction to effect an increase in arterial blood pressure. This initial response during circulatory centralization, which is necessary to increase or maintain blood flow to the heart, brain stem, and placenta, is blunted by sympathectomy. Thus, the foetal sympatho-neuronal system is important for short-term adaptation to and intact survival of asphyxia.

Adaptation, Physiological

Localization of human immunodeficiency virus core antigen in term human placentas.

Evidence of human immunodeficiency virus (HIV) replication was sought in human placentas obtained at term from pregnancies complicated by maternal HIV infection. Placentas were obtained from the pregnancies of 19 HIV-seropositive women, 4 women who were seronegative, and 4 untested women with no risk factors for HIV infection. These placentas were each examined by immunoperoxidase immunocytochemistry using monoclonal anti-p24/55 antibodies. In addition, minced placental tissue from 11 of the seropositive pregnancies and the 3 seronegative pregnancies were co-cultivated with stimulated human peripheral blood mononuclear cells. The clinical status of the infants born to the HIV-seropositive women was assessed when the infants were 8 to 28 months of age. P24/55 antigen was detected in 5 of the 19 placentas of the HIV-seropositive pregnancies and in none of the 8 placentas of seronegative or low-risk pregnancies. This HIV core viral antigen was located exclusively in the cytoplasm of villous cells with morphological characteristics of macrophages. The HIV antigen-containing cells were very sparsely distributed. Staining of the trophoblast was not observed in any placental specimen. Human immunodeficiency virus was isolated in culture from 3 of the 11 placentas from seropositive pregnancies. Clinical follow-up has not revealed a relationship between infection of the infant and either p24/55 antigen identification or isolation of virus from the placenta. Virological and histological evidence of HIV replication is found in approximately one fourth of placentas obtained at term from pregnancies complicated by maternal HIV infection. Replicating virus appears localized to sparse macrophages located within the chorionic villi, but specifically not within the trophoblastic layer.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome

Regional brain blood flow and oxygen supply in guinea pig fetuses near term.

To examine brain blood flow and oxygen supply to 14 brain regions in fetal guinea pigs near term, 6 fetuses were catheterized under general anaesthesia of the dam between days 61 and 63 of pregnancy. Fetal arterial blood pressure was measured and a blood sample was taken from the right axillary artery to determine fetal blood gases and acid-base balance. Isotope-labelled microspheres were then injected in a lateral saphenous vein and a reference blood sample was taken from the right axillary artery according to Carter and Gu. Preductal arterial haemoglobin oxygen saturation ranged from 16-33% (26.7 +/- 6.3 mean +/- SD) and pH from 7.08-7.30 (7.20 +/- 0.09); oxygen content varied between 3.0-6.7 ml/dl. Blood flow to the whole brain was 105-258 ml/min per 100 g (167 +/- 58), oxygen supply to the brain was 6.6-10.7 ml O2/min per 100 g (8.0 +/- 1.6). Both regional brain blood flow and oxygen supply were significantly different in the various brain parts. They were highest in the spinal medulla and in other parts of the brain stem and lowest in the cerebrum. Brain blood flow increased significantly with increasing pCO2 and systolic blood pressure and with decreasing haemoglobin oxygen saturation, pH, base excess, and arterial oxygen content. On the other hand, except for the mid portion of the spinal medulla, there were no correlations between blood gas and acid-base balance variables and the oxygen supply to the whole brain or to various regions of the brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

The lentivirus regulatory proteins REV and REX are site specific RNA binding proteins.

These studies demonstrate that HIV-1 REV and HTLV-1 REX are site specific RNA binding proteins. In addition, the REV protein studies indicate a protein domain essential for biological function that is not involved in RRE binding. Lentiviruses are unique among retroviruses in providing gene products to switch expression from early to late genes. Rather than transcriptional control, this is accomplished by regulating RNA transport. A further understanding of these lentiviral genes may identify means of inhibiting viruses responsible for insidious human disease.

Amino Acid Sequence

Prevalence of amblyopia in old people without previous screening and treatment. An evaluation of the present prophylactic procedures among children in Denmark.

An epidemiological study of amblyopia was performed among old people without previous screening and treatment. The study revealed a prevalence of 2.9% (strabismic in 2.3%, anisometropic in 0.6%). Present residual amblyopia among Danish school children is about 1% according to literature. The rate of cure of amblyopia by the present Danish system of prophylaxis and treatment is estimated to be 60-70%.

Aged

Effects of reducing uterine blood flow on fetal blood flow distribution and oxygen delivery.

We examined the effect of graded reduction in uterine blood flow on distribution of cardiac output and oxygen delivery to fetal organs and venous blood flow patterns in 9 fetal sheep using the radionuclide-labeled microsphere technique. We reduced uterine blood flow in two steps, decreasing fetal oxygen delivery to 70% and 50% of normal, and compared the results with those from a similar study from our laboratory on graded umbilical cord compression. With 50% reduction in fetal oxygen delivery, blood flow and the fraction of the cardiac output distributed to the brain, heart, and adrenal gland increased and that to the lungs, carcass, skin, and scalp decreased. Oxygen delivery to the brain and myocardium was maintained, while that to the adrenal doubled, and that to the brain stem increased transiently. The decrease in oxygen delivery to both carcass and lower body segment correlated linearly with oxygen consumption (P less than 0.001). The proportion of umbilical venous blood passing through the ductus venosus increased from 44.6% to 53% (P less than 0.05). The preferential distribution of ductus venosus blood flow through the foramen ovale to the heart and brain increased, but that to the upper carcass decreased so that ductus venosus-derived blood flow to the upper body did not change. Hence, the oxygen delivered to the brain from the ductus venosus was maintained, and that to the heart increased 54% even though ductus venosus-derived oxygen delivery to the upper body fell 34%. Abdominal inferior vena caval blood flow and its contribution to cardiac output decreased, but the proportion of the abdominal inferior vena caval blood distributed through the foramen ovale also increased from 23.0 to 30.9%. However, the actual amount of inferior vena caval blood passing through the foramen ovale did not change. There was a 70% fall in oxygen delivery to the upper body segment from the inferior vena cava. A greater portion of superior vena caval blood was also shunted through the foramen ovale to the upper body, but the actual amounts of blood and oxygen delivered to the upper body from this source were small. Thus, graded reduction of uterine blood flow causes a redistribution of fetal oxygen delivery and of venous flow patterns, which is clearly different from that observed previously during graded umbilical cord occlusion.

Animals

Effects of acute asphyxia on brain energy metabolism in fetal guinea pigs near term.

In a previous study we suggested that--unlike other forms of asphyxia--acute asphyxia caused by arrest of uterine blood flow is accompanied by a fall in oxygen delivery to the fetal brain (Jensen et al., 1987). This may change cerebral energy metabolism by causing an increase in the glycolytic rate. To test this hypothesis we studied the time course of the changes in the levels of high-energy phosphates and glycolytic intermediates in the cerebral cortex of unanaesthetized fetal guinea pigs near term before and after 2 and 4 min of acute asphyxia. During asphyxia there was a progressive fall of adenosine triphosphate, creatine-phosphate, glucose and fructose-1,6-diphosphate concentrations, whereas adenosine diphosphate, adenosine monophosphate and lactate concentrations increased. Pyruvate concentrations did not change. We conclude that fetal cerebral energy metabolism becomes increasingly anaerobic during acute asphyxia caused by arrest of uterine blood flow, because oxygen delivery to the fetal brain falls.

Animals

Fetal circulatory responses to oxygen lack.

The knowledge on fetal and neonatal circulatory physiology accumulated by basic scientists and clinicians over the years has contributed considerably to the recent decline of perinatal morbidity and mortality. This review will summarize the peculiarities of the fetal circulation, the distribution of organ blood flow during normoxemia, and that during oxygen lack caused by various experimental perturbations. Furthermore, the relation between oxygen delivery and tissue metabolism during oxygen lack as well as evidence to support a new concept will be presented along with the principal cardiovascular mechanisms involved. Finally, blood flow and oxygen delivery to the principal fetal organs will be examined and discussed in relation to organ function. The fetal circulatory response to hypoxemia and asphyxia is a centralization of blood flow in favour of the brain, heart, and adrenals and at the expense of almost all peripheral organs, particularly of the lungs, carcass, skin and scalp. This response is qualitatively similar but quantitatively different under various experimental conditions. However, at the nadir of severe acute asphyxia the circulatory centralization cannot be maintained. Then there is circulatory decentralization, and the fetus will experience severe brain damage if not expire unless immediate resuscitation occurs. Future work in this field will have to concentrate on the important questions, what factors determine this collapse of circulatory compensating mechanisms in the fetus, how does it relate to neuronal damage, and how can the fetal brain be pharmacologically protected against the adverse effects of asphyxia.

Animals

Hypoxia reduces oxygen consumption of fetal skeletal muscle cells in monolayer culture.

In a previous study on acute asphyxia in unanesthetized fetal sheep near term we showed that reduced oxygen delivery to peripheral organs reduces total oxygen consumption, suggesting that oxygen itself may be a determinant of oxygen consumption (Jensen, Hohmann & Künzel, 1987). To test this hypothesis we developed an in vitro perfusion model, which enabled us to measure the oxygen consumption of fetal skeletal muscle cells in monolayer culture in a control period (at approximately 145 mmHg) and during various degrees of hypoxia (6-140 mmHg). In 57 experiments on 57 cultures the mean oxygen consumption at a mean 'entry PO2' of 145.3 +/- 10.4 mmHg was 10.3 +/- 9.3 (SD).10(-6) microliters O2 per h per skeletal muscle cell. These measurements were made after an average of 4.2 +/- 2.3 transfers of the cells and at a cell density of 2.0 +/- 1.2.10(5) cells per cm2. In 54 of these experiments hypoxia was induced. There was a close positive correlation between the PO2 of the perfusate entering the Petridish ('entry PO2') and the change of the oxygen consumption of the cells (y = 5.17 - 0.54x + 0.03x2 - 0.00016x3, r = 0.97, p less than 0.0001). When oxygen tension fell, there was a concomitant fall in cellular oxygen consumption. We conclude that oxygen is a determinant of cellular oxygen consumption. Thus, hypoxia may reduce oxygen consumption of skeletal muscle cells, and oxygen may be preserved to maintain oxidative metabolism in central fetal organs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Cerebral energy metabolism in guinea pig fetuses during development.

During development fetal arterial oxygen tension falls, whereas cerebral oxygen consumption rises due to an increase in cerebral metabolism. To compensate for this increase in oxygen consumption, blood flow and therefore oxygen delivery to the cerebrum rises. To determine whether during development oxygen delivery to the cerebrum meets cerebral oxygen consumption, we measured the concentrations of high-energy phosphates and glycolytic intermediates in the cerebral cortex of fetal guinea pigs at different gestational ages. During development there was no change in the concentrations of adenosine triphosphate, creatine phosphate, adenosine monophosphate, and lactate. However, cerebral concentrations of adenosine diphosphate increased and those of glucose decreased. Our results suggest that the increase in fetal cerebral oxygen delivery during development meets cerebral oxygen consumption with increasing gestational age. We speculate that the measured rise in the concentrations of adenosine diphosphate may accelerate glycolysis during development and therefore may cause a rise in both cerebral blood flow to maintain oxygen delivery.

Adenosine Diphosphate

Alpha 3, alpha 5, and beta 4: three members of the rat neuronal nicotinic acetylcholine receptor-related gene family form a gene cluster.

We have identified two additional members of the neuronal nicotinic acetylcholine receptor (nAChR)-related gene family. cDNA clones for one new gene, designated alpha 5, were isolated from rat hippocampus and rat PC12 cell line cDNA libraries. The alpha 5 gene encodes a protein of 48,800 daltons (424 amino acids) which exhibits significant overall amino acid sequence identity with the previously cloned rat nAChR subunits alpha 1 (49%), alpha 2 (55%), alpha 3 (52%), and alpha 4 (49%). Features characteristic of other nAChR alpha-subunits are present such as conserved cysteine residues at positions 127, 141, 191, and 192, and four strongly hydrophobic domains. A second addition to the nAChR-related gene family, designated beta 4, is encoded in overlapping rat genomic clones lambda DD15 and lambda RG518A. The beta 4 gene, encoding a mature protein of 53,300 daltons (475 amino acids), consists of 6 exons and has a transcription unit length of approximately 18 kilobase pairs. The beta 4 gene encoded protein shows considerable amino acid sequence identity with nAChR beta 1 (43%), beta 2 (64%), and beta 3 (44%) subunits. Northern blots showed that, along with alpha 3 and beta 2, transcripts for both the alpha 5 and beta 4 genes are present in the PC12 cell line, while in situ hybridization experiments demonstrated expression of the alpha 5 and beta 4 genes in a small number of nuclei in the central nervous system. Finally, the genes that encode the beta 4, alpha 3, and alpha 5 proteins are transcribed with convergent polarities and form a tightly linked gene cluster spanning approximately 60 kilobase pairs.

Amino Acid Sequence

Metoclopramide (Primperan) in the treatment of ureterolithiasis. A prospective double-blind study of metoclopramide compared with morphatropin on ureteral colic.

A prospective double-blind study was performed to compare metoclopramide (Primperan) with morphatropin in the treatment of ureteral colic. Twenty-one patients (10 in the morphatropin group and 11 in the metoclopramide group) entered the study and diagnosis was confirmed radiologically. Using the Mann-Whitney rank sum test, no significant difference was found in the pain-relieving effect 10, 20, or 30 min after treatment with either 1 ml morphatropin s.c. or 20 mg metoclopramide i.v. Two patients in the morphatropin group developed nausea and giddiness, respectively, and 1 patient from this group was omitted due to the development of urticaria. No side effects occurred in the metoclopramide group. Thus metoclopramide seems to be an alternative to the traditional treatment of ureteral colic with morphia.

Acute Disease