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Biomedical subjects

M Hauptmann

Publications and source records attributed to M Hauptmann.

At least 19 recordsLinked to original sources
PubMed2005

Incidence of haematopoietic malignancies in US radiologic technologists.

BACKGROUND: There are limited data on risks of haematopoietic malignancies associated with protracted low-to-moderate dose radiation. AIMS: To contribute the first incidence risk estimates for haematopoietic malignancies in relation to work history, procedures, practices, and protective measures in a large population of mostly female medical radiation workers. METHODS: The investigators followed up 71,894 (77.9% female) US radiologic technologists, first certified during 1926-80, from completion of a baseline questionnaire (1983-89) to return of a second questionnaire (1994-98), diagnosis of a first cancer, death, or 31 August 1998 (731,306 person-years), whichever occurred first. Cox proportional hazards regression was used to compute risks. RESULTS: Relative risks (RR) for leukaemias other than chronic lymphocytic leukaemia (non-CLL, 41 cases) were increased among technologists working five or more years before 1950 (RR = 6.6, 95% CI 1.0 to 41.9, based on seven cases) or holding patients 50 or more times for x ray examination (RR = 2.6, 95% CI 1.3 to 5.4). Risks of non-CLL leukaemias were not significantly related to the number of years subjects worked in more recent periods, the year or age first worked, the total years worked, specific procedures or equipment used, or personal radiotherapy. Working as a radiologic technologist was not significantly linked with risk of multiple myeloma (28 cases), non-Hodgkin's lymphoma (118 cases), Hodgkin's lymphoma (31 cases), or chronic lymphocytic leukaemia (23 cases). CONCLUSION: Similar to results for single acute dose and fractionated high dose radiation exposures, there was increased risk for non-CLL leukaemias decades after initial protracted radiation exposure that likely cumulated to low-to-moderate doses.

Adult↗
PubMed2001

Using splines to analyse latency in the Colorado Plateau uranium miners cohort.

BACKGROUND: Different approaches have been proposed to investigate latency in epidemiologic studies where detailed exposure histories are available. METHODS: We demonstrate the application of a flexible, yet parsimonious, spline function model to investigate latency patterns for radon progeny exposure and lung cancer in the Colorado Plateau uranium miners cohort. The model extends a previously proposed bilinear model. RESULTS: The excess relative risk (ERR) reached a maximum of 0.6 per 100 working level months, for exposures received 14 years previously. The ERR then declined, and was estimated to approach zero for exposures received 35 years and more in the past. The point-wise 95% confidence intervals supported ERRs > 0 for the period 9-32 years before the event. The estimated latency curve was homogeneous across categories of attained age, duration of exposure, rate of exposure, and smoking. CONCLUSIONS: The proposed spline model is a flexible tool for latency analyses, and extends previously used methods.

Adult↗
PubMed2000

Mortality among radiologic technologists in the united states (1926-1997). 2(nd) Follow up.

PURPOSE: To evaluate risk for all-cause and cause-specific mortality in a large, primarily female (73%) cohort of radiologic technologists.METHODS: The study consists of 145,915 radiation technologists, certified in the American Registry of Radiologic Technologists (1926-1982) and followed through 1997. Causes of death were obtained from death certificates or, more recently, through NDI Plus. Standardized Mortality Ratios (SMR) were computed and tests of homogeneity were performed to detect differences in mortality among causes. Poisson models were used to estimate risks using an internal comparison group.RESULTS: Significantly low SMRs were observed for all causes (0.76), all cancers (0.82), and diseases of circulatory system (0.69). Compared to U.S. women, the risk for breast cancer mortality bordered around unity (SMR 1.01, 95% CI 0.94-1.09). However, relative to all other cancers, breast cancer mortality was significantly increased (RSMR 1.24, p < 0.01). Elevated risk for breast cancer was associated with certification before 1940 (SMR 1.55, 95% CI 1.24-1.91), and duration of certification of 20-29 (SMR 1.21, 95% CI 1.06-1.37) and 30+ years (SMR 1.77, 95% CI 1.54-2.02). A 35% increase in leukemia risk was evident for women certified for a duration of 20-29 years and a 36% increase among women certified for 30+ years. Poisson analysis revealed a significant increase in breast cancer risk with increasing number of years certified among women first certified before 1940 (p < 0.001) and during 1940-49 (p = 0.05) compared to women first certified in 1950 or later.CONCLUSIONS: Preliminary findings of this study suggest increased breast cancer risk associated with occupational radiation exposures prior to 1950 and with long-term cumulative exposures. However, potential confounding by reproductive and other risk factors needs to be evaluated.

Journal Article↗
PubMed2000

The use of sliding time windows for the exploratory analysis of temporal effects of smoking histories on lung cancer risk.

To examine the time-dependent effects of exposure histories on disease we use sliding time windows as an exploratory alternative to the analysis of variables like time since last exposure and duration of exposure. The method fits a series of risk models which contain total cumulative exposure and an additional covariate for exposures received during fixed time intervals. Characteristics of the fitted models provide insight into the influence of exposure increments at different times on disease risk. A simulation study is performed to check the validity of the approach. We apply the method to data from a recent German case-control study on smoking and lung cancer risk with about 4300 lung cancer cases and a similiar number of controls. The sliding time window approach indicates that the amount of cigarettes smoked from two to 11 years before disease incidence is most predicitive of lung cancer incidence. Among different smoking profiles that result in the same lifelong cumulative number of cigarettes smoked, those with a concentration of smoked cigarettes within 20 years before interview bear substantially larger risk than others.

Aged↗
PubMed2000

Analysis of exposure-time-response relationships using a spline weight function.

To examine the time-dependent effects of exposure histories on disease, we estimate a weight function within a generalized linear model. The shape of the weight function, which is modeled as a cubic B-spline, gives information about the impact of exposure increments at different times on disease risk. The method is evaluated in a simulation study and is applied to data on smoking histories and lung cancer from a recent case-control study in Germany.

Biometry↗
PubMed1992

Effects of high-dose methamphetamine on monoamine uptake sites in rat brain measured by quantitative autoradiography.

The neurotoxicity of methamphetamine to monoaminergic neurons was examined. Neurotoxicity was assessed by quantitative autoradiography using radioligands specific for binding to norepinephrine, dopamine, and serotonin uptake sites. High-dose administration of methamphetamine led to decreases in binding to uptake sites for the three monoamines. Norepinephrine binding sites were decreased in certain amygdaloid nuclei and in the dorsomedial hypothalamic nucleus. Serotonin binding sites were reduced in widespread brain areas, while dopamine binding sites were reduced in the caudate putamen, olfactory tubercle, and nucleus accumbens. The decreases in binding site density for the three monoamines are limited to terminal field areas; cell body areas are not affected. Our results indicate that methamphetamine is neurotoxic to serotonin, dopamine, and norepinephrine neurons. The neurotoxicity to norepinephrine neurons is in selected brain areas.

Animals↗
PubMed1992

Lack of effect of high-dose cocaine on monoamine uptake sites in rat brain measured by quantitative autoradiography.

There have been a number of claims that high-dose administration of cocaine to rats leads to neurotoxic effects on dopamine neurons. In this study possible neurotoxic effects on monoamine neurons were examined by measuring the effects of cocaine (35 mg/kg daily for 10 days) on the binding of radioligands to uptake sites for dopamine, serotonin and norepinephrine using qualitative autoradiography. No effects of cocaine on any of the binding sites were observed and therefore, it is concluded that cocaine, unlike amphetamine derivatives which have similar pharmacologic properties, does not produce neurotoxic effects on monoamine neurons.

Animals↗
PubMed1991

Central administration of 1-isoproterenol in vivo induces a preferential regulation of beta 2-adrenoceptors in the central nervous system of the rat.

1-Isoproterenol has equal affinity for beta 1- and beta 2-adrenoceptors and is a full agonist at both subtypes. However, when infused in vivo into the rat brain, it has been shown to induce a preferential reduction of central beta 2-adrenoceptors. To investigate this phenomenon further, in the present study rats were infused centrally with higher doses of 1-isoproterenol (15 or 45 micrograms/h). Furthermore, isoproterenol was infused into rats lesioned neonatally with 6-hydroxydopamine (6-OHDA). Subtypes of beta-adrenoceptors were measured by quantitative autoradiography of the binding of [125I]iodopindolol ([125I]IPIN). In sham lesioned rats, infusions of isoproterenol at both doses caused comparable reductions in the density of [125I]IPIN binding sites in many brain regions. The binding to beta 2-adrenoceptors was decreased in a larger number of brain areas than the binding to beta 1-adrenoceptors and the magnitude of the reduction was greater for beta 2- than for beta 1-adrenoceptors. However, isoproterenol at these doses did produce greater effects on the beta 1-subtype than those found previously with a lower dose. Treatment with 6-OHDA induced significant increases in the binding of [125I]IPIN to both beta 1- and beta 2-adrenoceptors in cerebral cortical and hippocampal areas, indicating that endogenous norepinephrine may regulate both subtypes in these regions. Even in the 6-OHDA-lesioned rats, the binding of [125I]IPIN to beta 2-adrenoceptors was reduced to a greater extent that the binding to beta 1-adrenoceptors. Thus, these studies demonstrate that the non-selective beta-adrenergic agonist isoproterenol induces a preferential regulation of beta 2-adrenoceptors, even at relatively high doses and in norepinephrine-depleted animals.

Animals↗
PubMed1991

Preferential reduction of binding of 125I-iodopindolol to beta-1 adrenoceptors in the amygdala of rat after antidepressant treatments.

This study utilized quantitative receptor autoradiography to examine the effects of repeated administration of antidepressants to rats on the binding of the beta adrenoceptor antagonist, 125I-iodopindolol (125I-IPIN) to either beta-1 or beta-2 adrenoceptors in various regions of brain. Antidepressants were selected to represent various chemical and pharmacological classes including tricyclic compounds (desipramine and protriptyline), monoamine oxidase inhibitors (clorgyline, phenelzine and tranylcypromine), atypical antidepressants (mianserin and trazodone) and selective inhibitors of the uptake of serotonin (citalopram and sertraline). Additionally, rats were treated with various psychotropic drugs that lack antidepressant efficacy (cocaine, deprenyl, diazepam and haloperidol). Repeated treatment of rats with desipramine, protriptyline, clorgyline, phenelzine, tranylcypromine or mianserin reduced the binding of 125I-IPIN to beta-1 adrenoceptors in many brain areas. Only in the basolateral and lateral nuclei of the amygdala did all six of these antidepressants significantly reduce 125I-IPIN binding to beta-1 adrenoceptors. In these amygdaloid nuclei, the magnitude of the reduction in the binding of 125I-IPIN caused by each of these drugs was comparable to or greater than the reduction in binding produced in any other region of brain. Reductions of binding of 125I-IPIN after antidepressant treatments were not consistently observed in the cortex, the area of brain examined most often in homogenate binding studies. Only the monoamine oxidase inhibitors caused reductions in the binding of 125I-IPIN to beta-2 adrenoceptors, and this effect was generally localized to the amygdala and hypothalamus. Repeated treatment of rats with citalopram, sertraline, or trazodone or with drugs lacking clinical antidepressant efficacy caused no significant effects on the binding of 125I-IPIN to either subtype of beta adrenoceptor in any region of brain. These results demonstrate that amygdaloid beta-1 adrenoceptors are particularly susceptible to regulation by certain antidepressant treatments and implicate the amygdala as an important site of action for antidepressants with pharmacological activity on noradrenergic neurons.

Adrenergic beta-Antagonists↗
PubMed1989

The role of brain serotonin in the electroconvulsive shock-induced changes in behavioural effects of intra-hippocampally injected clonidine.

The influence of central serotonin depletion upon behavioural effects of intra-hippocampally injected clonidine in the electroconvulsive shock-treated rats (ECS), was studied. Repeated ECS significantly attenuated the depressive influence of clonidine upon the locomotor activity of the rats in the open field test. Chemical lesions to the median raphe nucleus (MR) did not significantly affect ECS-induced changes in clonidine activity in this test. In the forced swimming the MR lesions revealed the stimulatory potency of clonidine microinjections upon rat active behaviour. In animals pretreated with repeated ECS, clonidine also significantly potentiated swimming activity, but no evident synergism of ECS and MR lesion could be observed. Taking into account these and other data it is concluded that central serotonin depletion might differentially affect the adaptive processes occurring in the alpha 2-adrenoceptors in the course of treatment with tricyclic antidepressants and ECS, but it does not seem to be a strong phenomenon. Moreover, it is suggested that clonidine effects in the open field and forced swimming tests may be mediated by different neuronal substrates within the rat hippocampus.

Animals↗
PubMed1988

Brain neurotransmitter systems mediating behavioral deficits produced by inescapable shock treatment in rats.

The effect of inescapable footshock (IS) upon rats' motor activity (the open field and forced swim tests) was studied in rats subjected to drugs, and neurotoxin treatments, affecting their central neurotransmitter systems. The agonists of GABA-receptor complex, dopamine, noradrenaline and serotonin neuronal systems, as well as the cholinergic antagonist, partially reversed motor suppression induced by IS, while the dopamine agonist, chlorpromazine, and the cholinergic antagonist, physostigmine, potentiated it. The effects of chemical lesions of the brain monoaminergic neurons with p-chlorophenylalanine (pCPA), N-chloro-ethyl-2,2-bromo-benzylamine (DSP-4), 6-hydroxydopamine (6-OHDA) and 5,7-dihydroxytryptamine (5,7-DHT) were more complex, depending upon the extent of monoamine depletion, and the kind of test applied. It is concluded that a decrease in the brain noradrenergic, serotonergic, dopaminergic and GABAergic neuronal activity, as well as the central cholinergic hyperactivity, might contribute to the behavioral suppression after IS. Thus the central mechanisms of behavioral deficits produced by IS involve multiple neurotransmitter systems, and the analysis of their role in more complicated behavioral patterns must also take into account changes in animals' baseline and stimulated motor activity.

Alanine↗
PubMed1988

Evaluation of mono- and dibenzoyl esters of dopamine as potential pro-drugs for dopamine in the central nervous system.

In this study, two ester pro-drugs of dopamine (DA) were synthesized and evaluated. These derivatives were the monobenzoyl (MBDA) and dibenzoyl (DBDA) esters of DA. MBDA was 300-fold and DBDA was 20,000-fold more lipophilic than DA itself. The half-lives of hydrolysis for MBDA and DBDA at physiologic pH and temperature were 15 and 420 min respectively. These compounds were radiolabelled and their uptake into brain measured. 14C-DBDA penetrated the brain rapidly; 0.28% of the dose injected was taken up per gram of brain tissue at 5 min. However DBDA did not produce measurable increases in DA levels in the brain. 14C-MBDA was found not to penetrate the brain. However, when MBDA was administered intracerebroventricularly (i.c.v.) to rats, it caused DOPAC levels to increase significantly both in the striatum and in the rest of the brain. The increase in the amount of DOPAC measured in the striatum was 3 to 10-fold greater than that seen in the rest of the brain. In rats that were pretreated with the MAO inhibitor, pargyline, MBDA given i.c.v. caused increases in DA levels in both the striatum and in the rest of the brain. The increased DA levels in striatum were considerably greater than those seen in the rest of the brain. From these results, it is inferred that MBDA is being hydrolyzed in vivo in the brain to form DA which is then taken up into dopaminergic neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Suppression of ethanol tolerance and dependence in rats treated with DSP-4, a noradrenergic neurotoxin.

The formation of tolerance to the hypothermic effect of ethanol was inhibited in rats after intraperitoneal injection of the neurotoxin DSP-4 50 mg/kg. The neurotoxin also significantly suppressed the ethanol withdrawal syndrome; hyperlocomotion, audiogenic seizures and spasticity. These behavioural changes were accompanied by a 52% decrease of the brain norepinephrine (NE) content, with no alterations in the dopamine or serotonin levels. The results indicate that intact NE neurons are necessary for the development of tolerance to ethanol-induced hypothermia and are involved in the expression of the ethanol withdrawal syndrome.

Alcoholism↗
PubMed1985

Effects of ATP gamma S in isolated rat brain synaptosomes.

The effects of ATP gamma S, a slowly hydrolyzable analogue of ATP, were investigated in the preparation of synaptosomes isolated from rat cerebral cortex. It was found that addition of [35S]ATP gamma S resulted in substantial magnesium-dependent incorporation of 35S into synaptosomal proteins which was prevented completely by ATP. The most prominently labeled polypeptides were those with apparent molecular weights of 100,000; 84,000; 74,000; 62,000; 55,000; 48,000; and 41,000. The rate and extent of thiophosphorylation were unaffected by addition of cAMP, veratridine or sodium fluoride. ATP gamma S at 50-100 microM had no effect on either uptake or release of gamma-aminobutyric acid (GABA) and dopamine; at a concentration of 1 mM it inhibited incorporation of dopamine by about 20%. This inhibition was also seen with 1 mM GTP, beta, gamma-methylene-adenosine 5'-triphosphate and adenylylimidodiphosphate, which suggests that the nucleotide triphosphates themselves, and not membrane protein phosphorylation, were responsible for the effect observed. It is concluded that ATP gamma S is an effective tool for studying the possible role of ATP released in synaptic transmission. The results obtained thus far suggest that neither extrasynaptosomal ATP nor phosphorylation of external proteins of the presynaptic membrane is sufficient for modulation of neurotransmitter uptake or release. They may, however, play a role in combination with other conditions.

Adenosine Diphosphate↗
PubMed1983

High affinity proline uptake in rat brain synaptosomes.

The uptake of L-proline by synaptosomes isolated from different regions of the brain was investigated. The highest rates of transport and the largest accumulation ratios were found in synaptosomes from the midbrain, striatum, hippocampus and hypothalamus, with lower activity in the cortex and medulla (+ pons) and lowest in the cerebellum. The high affinity, Na+-dependent proline uptake had a Km of 12 microM, a Vmax of 0.6 nmol . min-1 . mg protein-1 and the maximum accumulation ratio ( [proline]i/[proline]o) at 2 microM added radioactive amino acid was 40-50. Our results suggest that: (1) only 5-10% of the synaptosomal population accumulates proline through the high-affinity uptake; (2) the characteristics of the proline uptake system into the prolinergic nerve endings are remarkably similar to those of other amino acid neurotransmitters (GABA, aspartate and glutamate); (3) the behavior of proline is consistent with this amino acid being a neurotransmitter in the central nervous system.

Animals↗
PubMed1983

Interaction between noradrenergic and serotonergic brain systems as evidenced by behavioral and biochemical effects of microinjections of adrenergic agonists and antagonists into the median raphe nucleus.

The effects of microinjections of adrenergic receptors agonists and antagonists into the median raphe nucleus (MR) on behavior and serotonin (5HT) metabolism was examined in rats. Administration of adrenergic alpha 1 and alpha 2 receptor agonists (noradrenaline, phenylephrine, clonidine) produced behavioral excitation in the open field test and a tendency to decrease the forebrain 5-hydroxyindolo-acetic acid (5HIAA) concentration. Opposite effects were seen after microinjection of adrenergic alpha receptor antagonists (phenoxybenzamine, phentolamine but not yohimbine). A significant negative correlation was found between the effects on locomotor activity and 5HIAA levels in these rats. No effect was present after injection of beta receptor agonist salbutamol or antagonist propranolol. It is suggested that noradrenaline released from noradrenergic terminals in the MR tonically inhibits the activity of 5HT neurons thus producing symptoms of 5HT deficiency and that this action of noradrenaline is probably limited to the effects on alpha 1 but not alpha 2 nor beta adrenoceptors in this brain region.

Adrenergic Agonists↗
PubMed1983

Studies on biogenic amine metabolizing enzymes (DBH, COMT, MAO) and pathogenesis of affective illness. III. Platelet monoamine oxidase activity in endogenous depression.

Platelet MAO activity was determined in blood from 31 healthy persons and 43 persons with endogenous depressive syndrome. It was found that the enzyme activity is significantly higher in women than in men, both in healthy controls and in affective illness groups. Statistically significant lowering of the enzyme activity was found in the group of women with affective illness as compared with healthy women controls (P less than 0.05). Although the latter phenomenon is true of all three diagnostic subgroups of affective disorder (bipolar, unipolar, undifferentiated), it is most pronounced, and statistically significant only in the group of women with an undifferentiated course of disease. A small rise in the enzyme activity was noticed in some patients during remission, as compared with a period of depression, but this was not statistically significant. Analysis of the possible links between MAO activity and the clinical picture, or the severity of depression, revealed no significant correlations. No correlation was found between the level of MAO activity and a family history of psychiatric disturbances in general, and affective disorders in particular--in either women or in men.

Adult↗