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Biomedical subjects

A Heller

Publications and source records attributed to A Heller.

At least 163 records · Page 9Linked to original sources
PubMed1984

Release of dopamine from mesencephalic neurons in aggregate cultures: influence of target and non-target cells.

Spontaneous release of [3H]dopamine (DA) was observed from reaggregates of dissociated cells from fetal rostral mesencephalic tegmentum (RMT) containing DA neurons cocultured with their axonal target cells from striatum (CS) or frontal cortex (FCx), or with non-target cells from occipital cortex (OCx), or tectum. Such release increased in response to 50 mM K+. Tetrodotoxin (TTX) suppressed the spontaneous release from RMT-CS and RMT-FCx reaggregates by 42%; from RMT-tectum reaggregates by 24%, and did not significantly inhibit the release from RMT-OCx cocultures. Since TTX blocks spontaneous neuronal activity, these results suggest that the presence of axonal target cells enhances the activity of the dopamine neurons. DA neurons within RMT-FCx reaggregates released significantly more [3H]DA in response to 50 mM K+ than in RMT-CS cocultures. This result is in accord with the findings in vivo that inhibitory feedback mechanisms on DA release, present in the striatum, are lacking in the frontal cortex.

Animals↗
PubMed1984

Management of forensic psychiatry patients who refuse medication--two scenarios.

An Ohio federal court set Wyatt-type standards for treatment rights of forensic psychiatry patients and ordered legal due process-type hospital hearings to protect patients from what the court considers harmful clinical practices. Experience with this legal method for management of patients who refuse medication is examined for its impact on staff and patient care. Under legal pressure Ohio has built new regional forensic psychiatry hospitals. In one, spurred by legal activism, the prevalence of patients refusing medication has become pandemic. In its typical 16-bed ward, when 2 or more patients refuse medication, danger escalates rapidly for patients and staff. The method adopted to manage these situations is to assess the emergency of danger to patient or others, and if warranted to administer medication despite objections. This emergency management is dramatic in improving patient behavior and defusing milieu tensions. The psychiatrist ordering emergency management, however, faces challenges from several quarters--patient advocates, outside patients' rights legal advocates, and the commissioner of mental health. The clinically managed process contrasts markedly also with the legally imposed one in its impact on the personal and professional integrity of the responsible psychiatrist. Both scenarios illustrate the task yet remaining--integration of the clinical and legal concerns into a multisystem resolution of diverse interests, values, ethics, and rights.

Behavior Control↗
PubMed1983

Enhanced dopamine cell survival in reaggregates containing telencephalic target cells.

Dissociated, 14-day-old embryonic cells of the rostral mesencephalic tegmentum (RMT), including the dopamine neurons of this region, were allowed to reaggregate and develop in rotatory culture for 7 days in the presence of dissociated embryonic cells from the target areas of the dopaminergic neurons, corpus striatum (CS) or frontal cortex (FCx). Alternatively, RMT cells were allowed to reaggregate by themselves or in the presence of dissociated cells from a telencephalic area, occipital cortex (OCx), or mesencephalic area, tectum (T), which are not target areas for the dopamine neurons. Histofluorescence analysis revealed the number of dopamine neurons contained within reaggregates of any given type. Approximately 4 times as many dopamine neurons were found in RMT-CS coaggregates and 1.5 times as many in RMT-FCx coaggregates than in aggregates constituted from cells of the RMT either alone, or in coaggregates from RMT-OCx or RMT-T. Since axonal process formation and maintenance can only be observed in RMT-CS and RMT-FCx coaggregates, the enhanced dopamine neuron survival is probably due to an interaction of dopaminergic axonal processes with target cells within the reaggregates.

Animals↗
PubMed1983

Carcinoembryonic antigen and interferon as tumor markers in breast cancer.

A total of 239 determinations of CEA plasma levels were performed for 83 breast cancer patients during chemotherapy or follow-up. In addition, 137 plasma samples were assayed for interferon levels. Patient clinical status was carefully scored according to objective criteria and recorded at each evaluation. Liver function tests (LFT) were performed to establish a full clinical picture at each visit. The results obtained proved a 73 to 83% positivity rate when the results of the 4 tests were compared. The importance of routine CEA assays and careful clinical evaluation and LFT are stressed. An analysis of interferon levels defined 4 distinct groups that differed by the amount of interferon present and also by clinical status and CEA levels. The results are discussed in terms of tumor volume-dependent interferon production.

Breast Neoplasms↗
PubMed1983

Effects of neonatal destruction of the medial forebrain bundle in the cat: long-term neurochemical, locomotor, and regulatory deficits.

Neonatal kittens (N = 27) 11 to 22 days of age received bilateral electrolytic lesions of the medial forebrain bundle (MFB). These lesions transected the rostral course of the nigrostriatal tract, disrupted other fiber tracts that constitute the MFB, damaged the indigenous neurons of the lateral hypothalamic region, and interrupted striatal output pathways. The behavioral development of these animals was assessed and compared with that of intact littermates (N = 37) and a group of littermates that received lesions that did not encroach upon the MFB (control lesions, N = 16). The MFB lesions produced transient periods of decreased body weight gains. Animals with large MFB lesions had to be tube fed for various periods. Decreased ponderal weight in animals with large MFB lesions occurred throughout the duration of their survival (1 to 2 years of age). Development of locomotor activity was assessed in an open field. At about 6 weeks of age animals with MFB lesions became hyperactive compared with their intact littermates and this hyperactivity was still apparent at 6 months of age when testing was discontinued. Caudate dopamine and tyrosine hydroxylase were measured after the animals were killed. Large MFB lesions produced a marked decrease in concentrations of caudate dopamine (75%) and the activity of tyrosine hydroxylase (62%). These results indicate that early postnatal damage to the MFB in cats produces a constellation of behavioral deficits that differ both quantitatively and qualitatively from the effects of similar lesions produced in the adult animal.

Animals↗
PubMed1983

Locomotor hyperactivity in neonatal rats following electrolytic lesions of mesocortical dopamine neurons.

These experiments examined the effects on locomotor activity of brain lesions that destroyed either mesocortical or nigrostriatal dopamine (DA) neuronal projections in neonatal rats. Electrolytic lesions of the medial ventral tegmental area in 4-day-old rats reduced the content of DA within the frontal cortex and septum by 42-57% and resulted in a 2-fold increase in locomotor activity during days 22-24 of life. In contrast, bilateral electrolytic lesions of the substantia nigra in 4-day-old rats reduced the content of DA within the caudate putamen by 68%, but failed to alter locomotor activity during days 22-24 of life. These results suggest that loss of mesocortical DA neurons may underlie the locomotor hyperactivity seen following brain DA-depleting 6-hydroxydopamine injections in neonatal rats and that these mesocortical DA neurons may normally influence the ontogeny of locomotion in the rat.

Animals↗
PubMed1983

Release of dopamine from coaggregate cultures of mesencephalic tegmentum and corpus striatum.

Dissociated dopamine (DA) neurons from 14-day fetal mice were dissected from the rostral mesencephalic tegmentum (RMT) and were allowed to reaggregate in vitro with cells from the corpus striatum (CS). As previously demonstrated under these conditions, DA neurons develop punctate fluorescent varicosities and the capacity to synthesize, accumulate, and retain DA (Kotake, C., P. C. Hoffmann, and A. Heller (1982) J. Neurosci. 2: 1307-1315). After 17 to 22 days in culture, the RMT-CS coaggregates were assessed for their ability to release DA. Coaggregates were incubated in 5.6 x 10(-6) M [3H]DA, washed, and then superfused at 100 microliters/min for 2 hr. Fractions were collected every 2 min. Basal efflux of [3H]DA/2 min was 1% of tissue stores of 3H. K+, 70 mM infused for 8 min induced a peak release of 5.87% of tissue stores of 3H, and 50 mM K+ induced a peak release of 2.13%. The potassium-induced release of [3H]DA was calcium dependent. When d-amphetamine was infused for 12 min, 100 microM solutions induced a peak release of 8.91%, 10 microM induced a peak release of 4.36%, and 1 microM induced a peak release of 1.85% of tissue stores of 3H. Substance P at 100 microM induced a peak release of 2.19% of tissue stores of 3H. Tetrodotoxin (0.5 and 2.5 microM) decreased basal efflux by 40%, blocked substance P-induced release, but did not affect either potassium- or d-amphetamine-induced release of [3H]dopamine.

Animals↗
PubMed1982

The effect of development of thermoregulatory function on the biochemical assessment of the ontogeny of neonatal dopaminergic neuronal activity.

Previous studies from this laboratory on the functional ontogeny of impulse flow in the nigrostriatal pathway of the neonatal rat were interpreted as indicating that there was an abrupt onset of impulse flow between 6 and 8 days of age. The functional development was assessed by determining the age at which the biochemical responses of these neurons to physical or pharmacological manipulation were similar to those of adult neurons. Further studies of these phenomena demonstrate that the age-dependency of these biochemical markers of impulse traffic are directly related to the development of thermoregulatory function in the neonatal rat. Accordingly, provided that 4-day-old or even younger rats are maintained at or near litter temperature, they exhibit qualitatively all of the biochemical responses characteristic of the 10-day-old or adult animal in which impulse flow is known to be present.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1981

Target neuron-specific process formation by embryonic mesencephalic dopamine neurons in vitro.

Mesencephalic dopamine neurons from the embryonic mouse brain were dissociated, aggregated in vitro in the presence of dissociated cells from appropriate or inappropriate target neuron areas, and visualized by the Falck-Hillarp histofluorescence technique after exposure to 1 microM exogenous dopamine. When aggregated with the surrounding rostral mesencephalic tegmentum cells only or with the addition of rostral tectum cells, the dopamine neurons formed a dense dendritic arborization, but no axons were observed. In the presence of dopamine-neuron target cells from the corpus striatum, a dense axonal plexus characteristic of that formed in this area in vivo was observed. In contrast, in aggregates formed with target cells from the frontal cortex, branching fluorescent axons bearing irregularly spaced and shaped varicosities were found coursing through the neuropil, as is characteristic of the dopaminergic innervation to the frontal cortex in vivo. Only proximal dendrites were observed in the presence of these axonal target cells. Dopamine neurons cultured with inappropriate target cells from the occipital cortex did not form either extensive axonal or dendritic processes. Thus, the presence, type, and distribution of dopamine neuronal processes are dependent on the presence of appropriate target cells. The formation of unique patterns of neuronal processes by dissociated neurons in vitro suggests that the information necessary for this differentiation is intrinsic to the dopamine neurons and their target cells. This system provides a useful model with which to study basic mechanisms underlying neuronal recognition.

Animals↗
PubMed1981

Interactions of Pseudomonas aeruginosa lectins with Escherichia coli strains bearing blood group determinants.

Pseudomonas aeruginosa lectins interact with Escherichia coli strains O86B7 and O128B12, which possess B and H (O) blood group determinants, respectively. The interaction could be demonstrated by specific agglutination of the bacteria, by haemagglutination inhibition tests and by lectin-mediated peroxidase binding to the bacteria. The agglutination of E. coli O86B7 by the Pseudomonas galactose-binding lectin was inhibited by D-galactose and by the lipopolysaccharide extracted from E. coli O86B7. Similarly, the specific agglutination of E. coli O128B12 by the Pseudomonas mannose-binding lectin (which also binds L-fucose, L-galactose and D-fructose) was inhibited by D-mannose, L-fucose, L-galactose and D-fructose, as well as by athe lipopolysaccharide extracted from E. coli O128B12. The interaction between E. coli O128B12 and the Pseudomonas mannose-binding lectin was also demonstrated by lectin-mediated peroxidase binding to the bacterial surface. Peroxidase binding was also inhibited by the above-mentioned sugars and E. coli O128B12 lipopolysaccharide. Treatment of cells of the two E. coli strains with protein-denaturing agents did not reduce their agglutination by the Pseudomonas lectins. On the other hand, oxidation of the cell surface sugars by sodium metaperiodate or boiling the cells in the presence of 1% acetic acid for 1 h abolished their agglutination by the two lectins. It is, therefore, suggested that the Pseudomonas lectins interact with the B and H (O) blood group determinant sugars (D-galactose in E. coli O86B7 and L-fucose in E. coli O128B12) residing in the lipopolysaccharides of these E. coli strains.

ABO Blood-Group System↗
PubMed1981

The psychosocial functioning of young adults born with cleft lip or palate. A follow-up study.

A follow-up study of 96 young adults born with a cleft lip and/or cleft palate was conducted to determine their present psychosocial adjustment and to evaluate the services offered to them. Medical histories were obtained from hospital charts. Telephone interviews focusing on educational achievement, work performance, and social integration showed that 10 to 33%, depending on the criteria used, experienced psychosocial maladjustment, There was a high rate of persistent dissatisfaction with appearance, hearing, speech, teeth, and social life. An analysis of the services offered to these young adults, in the light that counseling or other social support might be offered routinely during childhood and, of equal importance, during adolescence when further medical, surgical, and dental treatment may also be required.

Adolescent↗
PubMed1980

Cost of forensic psychiatric hospitalization.

In recent years the daily expenditure per patient treated in Ohio's forensic hospital has increased tenfold and now exceeds $100. The figure reflects both a declining patient population and increased fiscal support, in part as the result of a 1974 federal court order mandating major improvements in conditions at the state's only forensic hospital. The author compares population and costs trends in the forensic division with trends in Ohio's mental health and mental retardation divisions and presents cost data obtained in a survey of forensic facilities in other states. He concludes that forensic facilities will tend to become smaller and to serve fewer patients, but services will be costly. Because of legal pressure to provide proper treatment and the possibility of personal damage suits, clinicians may be forced to refuse to practice in such facilities unless they are adequately funded.

Commitment of Persons with Psychiatric Disorders↗
PubMed1979

Pharmacological analysis of the functional ontogeny of the nigrostriatal dopaminergic neurons.

Functional development of the dopaminergic nigrostriatal projection was studied by determining the age at which the biochemical responses of these neurons to physical or pharmacological manipulation are similar to those of adult neurons. Transection of the pathway acutely elevates striatal dopamine in adult and 8- and 10-day-old rats, but not in the 4- or 6-day-old animal. This axotomy-induced increase in striatal dopamine is believed to be a response of the dopaminergic terminals to cessation of impulse traffic and is secondary to a decrease in dopamine release and a concomitant increase in dopamine synthesis resulting from tyrosine hydroxylase activation. Therefore, this response to axotomy acts as an indicator of (1) the presence of impulse traffic in the pathway, and (2) the ability of tyrosine hydroxylase to be activated in response to a reduction in such impulse traffic. In vivo estimation of tyrosine hydroxylase activity showed that axotomy activates the enzyme at 10 days, but not at 4 days, whereas gamma-hydroxybutyrate is effective at both ages. The fact that the enzyme can be activated by gamma-hydroxybutyrate at 4 days indicates that the lack of effect of axotomy at this age is due to the absence of impulse traffic in the system. This conclusion is supported by the finding that the AMT-induced depletion of striatal dopamine is not related to impulse conduction at 4 days since transection of the pathway has no effect on the rate of dopamine loss whereas such transection blocks the AMT-induced depletion at 10 days of age. Nevertheless, despite the absence of neuronal activity at 4 days of age, these neurons are capable of generating and conducting impulse traffic since both 4- and 10-day-old rats showed increased striatal dihydroxyphenylacetic acid (DOPAC) levels when treated with haloperidol indicating increased dopamine release; such increase in DOPAC being dependent on an intact pathway. Given this data, the most parsimonious explanation of the abrupt development of the response to axotomy after the 6th day of age is that an event occurs which physiologically initiates impulse traffic. This event may be activation of afferent neuronal inputs to the cell bodies of the nigrostriatal projection.

Aging↗
PubMed1979

Age-dependent effects of 6-hydroxydopamine on locomotor activity in the rat.

This experiment examined the effects on locomotor activity of intraventricular 6-hydroxydopamine (6-OHDA) administered to developing and adult rats. 6-OHDA was administered subsequent to pargyline treatment at 3 and 6 days of age; or 6-OHDA was administered subsequent to desmethylimipramine (DMI) treatment (6-OHDA/DMI) at 3 and 6 days of age, 11 and 14 days of age, 20 and 23 days of age, or 46 and 48 days of age. Locomotor activity of vehicle-treated rats assessed in stabilimeter cages peaked between 14 and 16 days of age and subsequently declined to levels characteristic of the adult. Treatment with pargyline and 6-OHDA at 3 days of age, or 6-OHDA/DMI at 3 and 6 or 11 and 14 days of age, did not alter the early rise in locomotor activity but prevented the decline in activity normally seen during the third and fourth weeks of life. When tested as adults, locomotor activity was greater in rats that had been treated with 6-OHDA/DMI at 3 and 6 and at 11 and 14 days of age than in those that had been treated at 20 and 23 days of age. Treatment with 6-OHDA/DMI at 46 and 48 days of age was without significant effect on locomotor activity. 6-OHDA (with pargyline pretreatment) produced large decreases in NE content in telencephalon and diencephalon and in dopamine (DA) content in striatum. 6-OHDA-DMI also produced large decreases in DA content in striatum and, in some of the treatment groups, only small decreases in norepinephrine (NE) content in telencephalon, diencephalon, and brain stem. These data suggest that the maturation of neuronal systems utilizing dopamine as a neurotransmitter is essential for the suppression of locomotor activity normally seen during development. The data further suggest that dopamine depletion per se does not lead to increased locomotor activity, but rather it is the destruction of dopamine-containing fibers prior to the normal period of locomotor suppression that increases locomotor activity.

Age Factors↗