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Biomedical subjects

S Hansen

Publications and source records attributed to S Hansen.

At least 19 recordsLinked to original sources
PubMed1992

Partial protective effect of MK-801 on MPTP-induced reduction of striatal dopamine in mice.

The protective effect of MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced reduction of striatal dopamine (DA) was examined in C57 BL/6 mice. Striatal DA levels were significantly higher in animals receiving parenteral MK-801 before and for 48 h following MPTP administration after 28 days than in animals receiving MPTP alone. The effect was not due to inhibition of monoamine oxidase-B (MAO-B) by MK-801. These data suggest that NMDA receptors may be involved in some of the neurotoxicity produced by MPTP.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1992

Crystal structures of phosphate, iodide and iodate-inhibited phospholipase C from Bacillus cereus and structural investigations of the binding of reaction products and a substrate analogue.

The crystal structure of the complex formed between phospholipase C (PLC) from Bacillus cereus and inorganic phosphate (Pi), which is an inhibitor, has been determined and refined to 2.1 A resolution. The final R-factor is 19.7%. We have also studied the binding of two other inhibitors, iodide and iodate, to PLC. X-ray data for these two complexes were collected to 2.8 A resolution during the search for heavy-atom derivatives. A series of screening experiments where PLC crystals have been treated with several reaction products and a substrate analogue were carried out to clarify the question of substrate binding. The results have so far been ambiguous but are discussed briefly. Phosphate and iodate are both found to bind to the three metal ions in the protein molecule, suggesting that these ions are involved directly in the catalytic process and thereby identifying the active site. PLC also binds nine iodide ions, eight of which are on the surface of the molecule and of lower occupancy. The ninth blocks the entrance to the active site cleft and is of higher occupancy. Altogether, these results suggest that the substrate, a phospholipid, is associated directly with the metal ions during catalysis.

Bacillus cereus↗
PubMed1992

Prenatal diagnosis of monosomy 18 and ring chromosome 18 mosaicism.

The case of monosomy 18/ring chromosome 18 mosaicism which was detected prenatally by amniocentesis is presented. The pregnancy was terminated in week 18. Autopsy showed complex malformation of the fetus consisting of cebocephaly, hypotelorism, microphthalmia, severe defects of brain development, and arrest of placental maturation.

Adult↗
PubMed1992

Substrate-enzyme interactions and catalytic mechanism in phospholipase C: a molecular modeling study using the GRID program.

Based on the high-resolution X-ray crystallographic structure of phospholipase C from Bacillus cereus, the orientation of the phosphatidylcholine substrate in the active site of the enzyme is proposed. The proposal is based on extensive calculations using the GRID program and molecular mechanics geometry relaxations. The substrate model has been constructed by successively placing phosphate, choline and diacylglycerol moieties in the positions indicated from GRID calculations. On the basis of the resulting orientation of a complete phosphatidylcholine molecule, we propose a mechanism for the hydrolysis of the substrate.

Binding Sites↗
PubMed1992

Contrast variation studies of clathrin coated vesicles by small-angle neutron scattering.

Structural information on clathrin coated vesicles has been obtained by small angle neutron scattering using contrast variation. A characteristic peak in the neutron scattering profile, which is apparent in 75% D2O, as well as in H2O, disappears when contrast matching the protein component of the coated vesicles in 42% D2O. Neutron, as well as dynamic, light scattering give a coated vesicle size of about 900 A in H2O and D2O, but for neutron scattering the diameter decreases when matching out the protein coat of the clathrin coated vesicles. From the match point for the clathrin coated vesicles it is demonstrated that the clathrin cages do contain internal membrane. The mass of 34 MD and composition of 75% protein and 25% lipid found from the analysis of the small-angle scattering data are both in good agreement with the values reported in the literature. Electron microscopy gives an average outer diameter of 880 A for the coated vesicles and an average diameter of 460 A for the vesicle itself.

Biophysical Phenomena↗
PubMed1992

Osteoblast-specific expression of growth hormone stimulates bone growth in transgenic mice.

Growth hormone (GH) is an important regulator of postnatal growth, acting on a wide variety of target tissues. Here, we show that local production of GH in osteoblasts is able to stimulate bone growth directly without significant systemic effects. Mice were made transgenic by microinjection of an osteocalcin-human GH (osteocalcin-hGH) gene construct in which approximately 1,800 bp of the rat osteocalcin promoter was fused to the hGH gene. Five lines of transgenic mice, each with measurable amounts of serum hGH (ranging from 1 to 1,000 ng/ml), were analyzed. Northern (RNA) blot hybridization showed that the hGH transcript was detectable only in the bone. Further characterization of hGH mRNA distribution by in situ hybridization revealed that in neonates the most intense signal was found in periosteal osteoblasts, while in adults, trabecular and endosteal osteoblasts were favored. In one transgenic line (992-1), hGH was expressed at a much lower level and had minimal systemic effects; however, the local concentrations of hGH in bone were sufficient to stimulate bone growth in these animals.

Animals↗
PubMed1992

Excitatory amino acid receptor antagonist in murine motoneuron disease (the wobbler mouse).

Recent evidence has suggested a potential role for involvement of excitatory amino acids (EAA) in the pathogenesis of the neuron loss in motoneuron diseases. We have examined the ability of an antagonist of N-methyl-D-aspartate (NMDA) receptors to halt or retard the progression of neurological symptoms in a murine form of motoneuron disease. The wobbler mouse is an autosomal recessive mutant which develops progressive neurological symptoms secondary to motoneuron loss. Treatment of wobbler mice with the NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5, 10-imine maleate (MK-801) did not retard neurological deterioration as assessed by a semiquantitative clinical scale. We conclude that NMDA receptor activation is probably not involved in the pathogenesis of motoneuron loss in the wobbler mouse.

Amyotrophic Lateral Sclerosis↗
PubMed1991

The wobbler mouse: amino acid contents in brain and spinal cord.

Reductions in glutamate and aspartate contents, together with increased contents of taurine, have been observed in the autopsied brains and spinal cords of patients who have died with amyotrophic lateral sclerosis (ALS). The wobbler mouse develops an inherited degeneration of motoneurons within the brainstem and spinal cord, and has been proposed as an animal model of ALS. In symptomatic wobbler mice we found brain contents of glutamate, aspartate, and taurine similar to those in unaffected littermates, while brain contents of glutamine were increased, and those of serine and alanine were decreased. Spinal cords of wobbler mice had slightly decreased contents of glutamate, aspartate and glycine compared to normal littermates. Abnormalities of amino acid contents in the nervous system of wobbler mice are dissimilar to those in ALS patients suggesting a different pathogenesis of motoneuron loss.

Amino Acids↗
PubMed1991

Peripheral anosmia attenuates female-enhanced aggression in male rats.

It is well established that male rats with prior access to sexually active females show enhanced offensive aggression toward unfamiliar male intruders. The present study assessed the importance of the sense of smell for this facilitatory effect. It was found in 2 independent experiments that anosmia, induced peripherally by surgically removing the olfactory epithelium and cutting the olfactory nerves, reduced baseline levels of offensive aggression and significantly attenuated the female-enhanced aggression effect. It was also found that sexual performance of anosmic rats was context-dependent, in that it was more impaired in the homecage environment than in standard observation cages. In contrast to sham-operated males, the experimental animals showed no preference for estrous over anestrous females in a mate choice test. Anosmic males did not appear more fearful than controls, as assessed in a hyponeophagia test, but they showed less exploratory behavior (rearing and head-dipping) in the hole-board test, and less rearing activity in automated activity boxes.

Aggression↗
PubMed1991

The effects of 6-OHDA-induced dopamine depletions in the ventral or dorsal striatum on maternal and sexual behavior in the female rat.

The effects of dopamine-depleting 6-OHDA infusions in the ventral or dorsal striatum on maternal and sexual behaviors were examined in female rats. Like sham-operated controls, lactating rats receiving 6-OHDA in the ventral striatum built good nests, nursed the infants and showed maternal aggression toward strange intruders. By contrast, the lesioned females performed poorly in tests for pup retrieval, as reflected in greatly protracted retrieval latencies. There was no effect of ventral striatal DA depletions on proceptive and receptive elements of female sexual behavior, which was studied after lactation following ovariectomy and exogenous administration of ovarian hormones, but these animals did show an attenuated hyperactivity response to a low dose of amphetamine. Females with dopamine lesions in the dorsal striatum did not differ from controls with respect to maternal and sexual behavior, but they did show an enhanced hyperactivity response to amphetamine treatment.

Amphetamine↗
PubMed1991

Mesotelencephalic dopamine system and reproductive behavior in the female rat: effects of ventral tegmental 6-hydroxydopamine lesions on maternal and sexual responsiveness.

The effects of lesions to the mesolimbic dopamine system on maternal and sexual behaviors in the female rat was assessed. Rat dams that were given ventral tegmental area microinfusions of 6-hydroxydopamine (6-OHDA) during lactation showed a persistent deficit in pup retrieval but were not impaired with respect to nursing, nest building, or maternal aggression. In addition, 6-OHDA-lesioned females failed to respond to amphetamine by showing locomotor hyperactivity. Administration of the dopamine blocker raclopride to neurologically intact dams also inhibited pup retrieval but had no effect on nursing. Females given 6-OHDA during pregnancy appeared completely unresponsive to pups, whereas no maternal deficits were seen in females that received 6-OHDA 8 weeks before parturition. Proceptive (hopping and darting) and receptive (lordosis) components of sexual behavior, assessed after ovariectomy and exogenous steroid hormone treatment, were not affected by mesolimbic 6-OHDA lesions.

Animals↗
PubMed1991

Amyotrophic lateral sclerosis: fasting plasma levels of cysteine and inorganic sulfate are normal, as are brain contents of cysteine.

Recent reports suggest that amyotrophic lateral sclerosis (ALS) is caused by one or more unidentified neurotoxins that are poorly metabolized in patients to less toxic and more readily excreted compounds, and that a genetically determined defect in cysteine degradation and in inorganic sulfate production is the mechanism underlying a failure to metabolize xenobiotics normally in ALS. We measured concentrations of total cysteine and of inorganic sulfate in the plasma of age-matched groups of ALS patients and healthy control subjects and found no differences. L-Cysteine, a putative endogenous neurotoxin in ALS, was present in equal concentrations in autopsied brain from ALS patients and controls.

Adult↗
PubMed1990

What excitotoxin kills striatal neurons in Huntington's disease? Clues from neurochemical studies.

Amino acid analyses of both caudate nucleus and putamen obtained at autopsy from patients dying with Huntington's disease (HD), and from control subjects, showed significantly decreased mean glutamate contents in the HD patients. In addition, the mean glutamate concentration was significantly increased in the CSF of living HD patients as compared with controls. Neurochemical studies also showed that neither aspartic acid, proline, 5-oxoproline, nor homocysteic acid is likely to act as a causative excitotoxin in HD. Excessive striatal glycine content, or deficient glutathione content, is unlikely to contribute to the effects of a causative excitotoxin in HD. We suggest that glutamic acid may be the proximate causative neurotoxin in the striatum in HD, as a result of an unexplained failure in the reuptake mechanism for glutamate released there as an excitatory neurotransmitter.

Adult↗
PubMed1979

Gamma-aminobutyric-acid deficiency in brain of schizophrenic patients.

Gamma-aminobutyric acid (G.A.B.A.) was measured in the nucleus accumbens and thalamus of brains from patients who had died with schizophrenia or Huntington's chorea (H.C.) and from control subjects. Mean G.A.B.A. content was significantly reduced in both brain areas in schizophrenia and in H.C. Extraneous factors, such as age, interval from death to necropsy, cause of death, and drug use, did not readily explain the observed reduction in brain G.A.B.A. G.A.B.A. deficiency may be a biochemical characteristic of some forms of schizophrenia.

Brain Chemistry↗