Population and the environment.
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Africa↗
Biomedical subjects
S Hansen
Publications and source records attributed to S Hansen.
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↗
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↗
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↗
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↗
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↗
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↗
Comparison of two methods for measuring thermal thresholds.
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Diabetic Neuropathies↗
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↗
Amyotrophic lateral sclerosis: amino acid levels in plasma and cerebrospinal fluid.
Concentrations of glutamic acid have been reported to be elevated in fasting plasma and cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS); glycine concentrations have also been reported to be increased in the CSF of such patients. Autopsy studies have shown glutamate contents to be significantly decreased in brain and spinal cord in ALS. These observations suggested that a systemic abnormality of glutamate metabolism might underlie the pathogenesis of ALS. We report here the findings of our studies of amino acid concentrations in patients with the sporadic form of ALS. Glutamate concentrations were normal in the fasting plasma of a great majority of the patients with ALS. Concentrations of glutamate, aspartate, and glycine were normal in the CSF of all 17 patients examined. beta-N-Methylamino-L-alanine, a plant neurotoxin possibly responsible for causing the Guamanian form of ALS, was not detectable in the plasma or CSF of any of our patients. Our findings do not lend support to the hypothesis that the sporadic form of ALS results from overexcitation of motor neurons by excitatory amino acids.
Adult↗
Mechanisms involved in the control of punished responding in mother rats.
In a previous study we found that mother rats show more drinking responses than virgins in the punished drinking paradigm, an animal model for anxiety. The present investigation was carried out to determine the possible mechanisms underlying this naturally occurring anticonflict effect. In Experiment 1, we investigated whether the induction of maternal behavior in virgin females (by long-term estrogen and progestin treatment in combination with pup exposure) enhances punished drinking. However, no release from shock-induced (0.25 mA) suppression of drinking was observed in maternally responsive virgins deprived of water for 24 hr. Unlike natural mothers, then, no anticonflict effect is seen in maternal virgins. A considerable body of evidence suggests that facilitation of gamma-aminobutyric acid (GABA) activity in the brain increases punished responding in rats. In the second experiment, therefore, lactating females were injected with pentylenetetrazol, a GABA antagonist, before being monitored for punished drinking. The drug attenuated the enhanced acceptance of shock in mothers, the effect being observed at a dose level that did not reliably affect unpunished responding. Experiment 3 addressed the possible influence of ovarian and adrenal hormones on punished drinking in lactating females. No significant behavioral effects were observed in mothers subjected to adrenalectomy or ovariectomy 4 days before testing.
Animals↗
Brain amino acid contents are dissimilar in sporadic and Guamanian amyotrophic lateral sclerosis.
Amino acid contents were measured in autopsied brains of five Guamanian patients with amyotrophic lateral sclerosis (ALS) or parkinsonism-dementia. Absence of the glutamate deficiency and taurine excess characteristic of sporadic ALS suggest that, despite clinical similarities, Guamanian ALS is a different disorder from sporadic ALS.
Aged↗
Female-enhanced aggression in male rats: effects of genital anesthesia, castration, or preoptic lesions.
Male rats that had cohabited with ovariectomized females for 2 weeks became more aggressive toward male intruders after a novel estrous female had been placed in their home cages for a period of 4 hr on the previous day. No increase in aggression was seen in males exposed to anestrous females. Genital anesthesia did not attenuate the female-enhanced aggression effect. By contrast, no enhancement of aggression was observed in long-term castrated males after 24 hr of exposure to estrous females. Rats with bilateral electrolytic lesions in the medial preoptic area showed a normal female-enhanced aggression effect. The observations that exposure to females facilitates aggression in males subjected to genital anesthesia and in males with preoptic lesions raise the possibility that copulatory cues are not always required for the effect.
Aggression↗
Repeatability of the acetylene rebreathing method in measuring cardiac output: influence of acetylene concentration.
The acetylene rebreathing method is a reliable noninvasive method for estimation of cardiac output. However, the method is not commonly used for clinical purposes. This is due mainly to the fact that acetylene is explosive at concentrations above 2% and that acetylene at concentrations above 0.5% has an unpleasant taste. In the present study we have investigated whether it is possible to reduce the concentration of acetylene to 0.3% in the rebreathing bag without degrading the repeatability of the estimated cardiac output. The problem was elucidated theoretically and experimentally. A theoretical investigation was carried out by producing an acetylene rebreathing curve from a single alveolus lung model. The theoretical study showed that the random noise arising from the gas analyzer gives rise to less than 10% of the total variation of the estimated cardiac output. The results of the experimental study showed that it is possible to reduce the acetylene concentration to 0.3% without decreasing the reproducibility of the acetylene rebreathing method.
Acetylene↗
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↗
Dominantly inherited apathy, central hypoventilation, and Parkinson's syndrome: clinical, biochemical, and neuropathologic studies of 2 new cases.
We describe 2 new patients from a family in which 10 persons in 3 successive generations had a dominant neuropsychiatric disorder characterized by apathy, central hypoventilation, and parkinsonism. Neuropathologically, both patients showed severe neuronal loss and reactive gliosis in the substantia nigra. Neurochemical studies showed a marked depletion of dopamine in substantia nigra, putamen, and caudate nucleus, as well as reduction in serotonin content in the substantia nigra. Glutamate contents were low in frontal cortex and thalamus, and gamma-aminobutyric acid (GABA) contents were low in thalamus and substantia nigra of both patients. In addition, phosphoethanolamine contents were reduced in all brain regions of both patients, especially in the substantia nigra. One patient with severe symptoms had low levels of homovanillic acid, 5-hydroxyindoleacetic acid, and GABA in his CSF repeatedly for 3 years before death (aged 58), while the 2nd patient died (aged 51) of an unrelated cause before developing any symptoms of the familial disorder. Because brain deficiencies of multiple neurotransmitters appear to be involved, this disorder is unlikely to respond to treatment; however, neurochemical studies of CSF may make presymptomatic diagnosis feasible.
Adult↗
Suckling-induced release of cholecystokinin into plasma in the lactating rat: effects of abdominal vagotomy and lesions of central pathways concerned with milk ejection.
Plasma levels of cholecystokinin were increased in response to suckling in lactating rats. Efferent electrical stimulation of the vagal nerve increased the concentration of cholecystokinin in plasma. Abdominal vagotomy was found to block the suckling-induced release of cholecystokinin. Furthermore, lesions to the lateral midbrain, which disrupt the oxytocin-mediated milk-ejection reflex, were shown to inhibit the increase in plasma cholecystokinin. These results show that the suckling-induced release of cholecystokinin into plasma in lactating rats is dependent upon the vagal nerves and the central neural structures concerned with milk let-down.
Animals↗
The role of pediatric nurses in a federal program for infants and young children with handicaps.
The Education of the Handicapped Act Amendments of 1986 (PL 99-457) represent the most far-reaching public legislation ever enacted for handicapped and developmentally vulnerable children. This article presents a basic overview of the law and discusses potential roles for pediatric nurses.
Child↗