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Biomedical subjects

M Mintz

Publications and source records attributed to M Mintz.

At least 19 recordsLinked to original sources
PubMed2003

Effect of TNF and LTA polymorphisms on biological markers of response to oxidative stimuli in coal miners: a model of gene-environment interaction. Tumour necrosis factor and lymphotoxin alpha.

INTRODUCTION: Interaction between genetic background and oxidative environmental stimuli in the pathogenesis of human lung disease has been largely unexplored. METHODS: A prospective epidemiological study was undertaken in 253 coal miners. Intermediate quantitative phenotypes of response to oxidant exposure, including erythrocyte glutathione peroxidase (GSH-Px) and catalase activities, were studied. Oxidant exposures studied were smoking habits and cumulative dust exposure assessed by job history and ambient measures. Disease phenotypes included subclinical computed tomography score at the first survey and x ray profusion grades twice, five years apart, to assess established coal workers' pneumoconiosis (CWP). Miners were genotyped for common functional polymorphisms in the gene for tumour necrosis factor alpha (TNF) and lymphotoxin alpha (LTA), two proinflammatory cytokines that have been implicated in the pathogenesis of chronic lung diseases. RESULTS: Regarding gene-environment interaction on intermediate phenotypes, results showed interaction of a promoter polymorphism at the -308 position in TNF with occupational exposure on erythrocyte GSH-Px activity with a significant association in those with high exposure (p=0.003), whereas no association was observed among those with low exposure (interaction p=0.06). Regarding gene intermediate phenotype interaction on clinical outcome, results showed an association of CWP prevalence with an NcoI polymorphism in LTA in those with low catalase activity (p=0.05), whereas no association was observed in those with high activity (interaction p=0.03). No other significant association was observed. CONCLUSION: The results suggest that interactions of genetic background with environmental exposure and intermediate response phenotypes are important components in the pathogenesis of CWP.

Catalase↗
PubMed2001

Social attraction between rats in open field: long-term consequences of kindled seizures.

Kindling of the amygdaloid complex in rats results in an enhanced emotionality frequently expressed by an elevated anxiety and defensive attitude toward other animals. Defensive attitude may have important consequences in social context and if tested in a large space it may eventually lead to social withdrawal. To test this hypothesis, rats were subjected to daily kindling sessions and their behavior was compared to implanted-sham and intact rats. Blood was collected after selected kindling trials for assessment of corticosterone response. Behavioral tests started 1 month after the last kindling trial and consisted of two open field sessions. A solitary rat was tested in the 1st session and pair of rats was tested simultaneously in the second session. Results showed that kindling changed the balance between exploration and occupation of a home base (HB) in the open field, in favor of higher preference of the home base occupancy. These results were apparent only during the social session leading to the conclusion that rats preferred to stay in the home base to maximize the proximity to a partner rat. This was supported by the observation that by increasing the occupancy of the HB, the kindled rats accomplished the longest concurrent presence with the partner rat in the common HB. We discuss the level of inter-rats aggression as a factor defining whether the anxious kindled rats will respond with increased or decreased social attraction in the open field test.

Amygdala↗
PubMed2001

Two-stage theory of conditioning: involvement of the cerebellum and the amygdala.

Classical conditioning is thought to proceed through two successive stages: fast rate emotional conditioning followed by slower motor conditioning. To verify the involvement of the amygdala and the cerebellum in these two stages of learning, rats were subjected to paired tone-airpuff (CS-US) trials. Lick suppression to CS was used as an index of conditioned emotional response (emotional CRs) and head movement was used as an index of motor CRs. The results showed that the fast acquisition of emotional CRs was dependent on the integrity of the amygdala and the slow acquisition of motor CRs was dependent on the integrity of the cerebellar interpositus nucleus. Cerebellar lesions had no effect on the acquisition of the emotional CRs but prevented the extinction of the emotional CRs seen in intact rats after massive conditioning. These findings suggest that the amygdala and the cerebellum provide the neuronal substrates of the fast and slow conditioning systems, respectively, and that conditioning-related cerebellar output interacts with the amygdala-based emotional conditioning.

Acoustic Stimulation↗
PubMed2001

Involvement of the amygdala in classical conditioning of eyeblink response in the rat.

The two-factor theory postulates that classical conditioning proceeds through two stages, which support successive acquisition of emotional and motor responses. Emotional conditioning is thought to facilitate the subsequent acquisition of the motor response. This form of interaction between the two stages of learning can be investigated while considering the central role of the amygdala and the cerebellum in emotional and motor conditioning, respectively. Rats with bilateral lesions of the amygdala or the cerebellar interpositus or intact rats were subjected to a fear conditioning session followed by four eyeblink conditioning sessions. Another group of intact rats was subjected to eyeblink conditioning only. The CS in the fear conditioning session was a 73 dB tone, paired with a 100 dB noise-US. The same CS was paired with a periorbital electroshock-US during eyeblink conditioning. Results showed that fear preconditioning facilitated the subsequent eyeblink conditioning among the intact groups. Amygdaloid lesions abolished this facilitatory effect of fear conditioning. These findings demonstrate that amygdala-mediated emotional conditioning facilitates the subsequent acquisition of cerebellum-mediated motor responses.

Amygdala↗
PubMed2000

The expression of the calcium binding protein calretinin in the rat striatum: effects of dopamine depletion and L-DOPA treatment.

The activity of the striatum is regulated by glutamate and dopamine neurotransmission. Consequent to striatal dopamine depletion the corticostriatal excitatory input is increased, which in turn can raise intracellular calcium levels. We investigated changes in the neuronal expression of the calcium binding protein calretinin related to dopamine depletion and l-DOPA administration. Immunohistochemical methods were used to assess calretinin in the striatum of rats with unilateral lesions of the nigrostriatal system. In these animals we observed a loss of the patchy distribution of calretinin fibers. Moreover, after dopaminergic depletion we detected two new, not previously described, calretinin cell types, the presence of which could be related to morphological changes induced by loss of a dopaminergic input. We also found an increase in the number of calretinin-labeled cells in the striatum ipsilateral to the lesion compared to the contralateral striatum or to the striatum of normal rats. This increase was mostly evident at 3 weeks postlesion and tended to decrease toward normal levels at 6, 10, and 18 weeks postlesion. In unlesioned animals, l-DOPA administration did not induce changes in the expression of calretinin. In unilaterally lesioned animals, l-DOPA reversed the increase in the number of calretinin-positive cells induced by the lesion. However, chronic l-DOPA administration was less effective than acute l-DOPA in reversing the effect of the lesion. The present data suggests that striatal calretinin neurons are sensitive to dopamine depletion. Increased expression of calretinin in striatal cells may be consequent to enhanced striatal excitatory input.

Animals↗
PubMed2000

Phytonadione therapy in a multiple-drug overdose involving warfarin.

We cared for a patient who ingested an unknown amount of acetaminophen with zopiclone and warfarin. The only liver function test that was abnormal was an increased international normalized ratio (INR), which remained elevated despite treatment with subcutaneous phytonadione and a prolonged infusion of N-acetylcysteine. An interaction between acetaminophen and warfarin may have decreased the hepatic metabolism of warfarin. The patient received numerous antibiotics that may have contributed to the increased INR. The prolonged elevation of INR also may have been due to infrequent administration of phytonadione.

Acetaminophen↗
PubMed1999

Effects of prenatal exposure to gamma rays on circling and activity behavior in prepubertal and postpubertal rats.

The study departs from the finding that postural asymmetries in low-weight female neonates are greatly increased following prenatal lesions inflicted by gamma irradiation at day 15. Given that amphetamine-induced rotation in adult rats could be predicted by their infantile axial asymmetry we expected a greater tendency for circling in rats exposed at day 15. To examine this prediction, Sprague-Dawley rats were exposed to a single dose of gamma radiation at 1.5 Gy with a dose-rate of 0.15 Gy/min. The dose was delivered on one of the embryonic days (E15, 17 or 19) throughout the whole body of pregnant dams. Sham prenatal exposure of controls consisted of placing pregnant rats in the same environment for 10 min. All rats were tested during the active part of the circadian cycle. At postnatal day 27 (P27) exposed pups did not differ in rates of either spontaneous or d-amphetamine-induced circling from the shams. At P57, in keeping with our prediction, E15 rats manifested enhanced rotation and higher net asymmetry. However, E17 also showed higher gyration tendency compared to their shams while exposed E19 rats did not differ from their shams. The role of intrinsic DAergic imbalance presumably sharpened by irradiation at E15 and of neocortical deficit inflicted at E15 and E17 are discussed.

Animals↗
PubMed1999

Clinical features and treatment interventions for human immunodeficiency virus-associated neurologic disease in children.

HIV-1 infection in children and adolescents can cause progressive neurologic disease, affective brain growth, motor function, and neurodevelopment. In addition, myelopathies, neuropathies, myopathies, strokes, and psychiatric or behavioral manifestations can be a result of HIV-1 infection, OI, or toxicities of treatment interventions. CNS OI are important causes of morbidity and mortality, often mimicking the HIV-1 associated neurologic syndromes. Psychometric, clinical, neuroradiologic, and laboratory testing are valuable for diagnostic and treatment decisions. The cornerstone of treating HIV-1-associated neurologic disease is providing an effective regimen of antiretroviral drugs to reduce the viral burden. It is also necessary to provide rehabilitation, optimize nutrition, supply appropriate antimicrobial prophylaxis against OI, minimize pain, and treat neurobehavioral or psychiatric complications. Efforts at preventing HIV-1 infection are important for diminishing and allaying the growth of this international pandemic.

Central Nervous System Diseases↗
PubMed1999

Neurologic, neurocognitive, and brain growth outcomes in human immunodeficiency virus-infected children receiving different nucleoside antiretroviral regimens. Pediatric AIDS Clinical Trials Group 152 Study Team.

OBJECTIVES: To compare the impact of three different nucleoside reverse transcriptase inhibitor regimens, zidovudine (ZDV) monotherapy, didanosine (ddI) monotherapy, and ZDV plus ddI combination therapy, on central nervous system (CNS) outcomes in symptomatic human immunodeficiency virus (HIV)-infected children. METHODS: Serial neurologic examinations, neurocognitive tests, and brain growth assessments (head circumference measurements and head computed tomography or magnetic resonance imaging studies) were performed in 831 infants and children who participated in a randomized double-blind clinical trial of nucleoside reverse transcriptase inhibitors. The Pediatric AIDS Clinical Trials Group study 152 conducted between 1991 and 1995 enrolled antiretroviral therapy-naive children. Subjects were stratified by age (3 to <30 months of age or 30 months to 18 years of age) and randomized in equal proportions to the three treatment groups. RESULTS: Combination ZDV and ddI therapy was superior to either ZDV or ddI monotherapy for most of the CNS outcomes evaluated. Treatment differences were observed within both age strata. ZDV monotherapy showed a modest statistically significant improvement in cognitive performance compared with ddI monotherapy during the initial 24 weeks, but for subsequent protection against CNS deterioration no clear difference was observed between the two monotherapy arms. CONCLUSIONS: Combination therapy with ZDV and ddI was more effective than either of the two monotherapies against CNS manifestations of human immunodeficiency virus disease. The results of this study did not indicate a long-term beneficial effect for ZDV monotherapy compared with ddI monotherapy.

Adolescent↗
PubMed1998

Reevaluation of the striatal role in the expression of turning behavior in the rat model of Parkinson's disease.

A traditional view holds the belief that the behavioral effects of l-dihydroxyphenilalanine (l-DOPA) in Parkinsonian patients are achieved through the action of the newly produced dopamine (DA) on striatal DA receptors. In contrast to this view, recent studies in the rat model of Parkinson's disease point to the substantia nigra pars reticulata as an important target for the behavioral effects of l-DOPA. In the present study, we tested the contribution of the substantia nigra vs. that of the striatum, in the expression of contralateral turning induced by l-DOPA in rats with unilateral dopaminergic depletion. Rats turned contralaterally to the lesion in response to either intrastriatal or systemic l-DOPA administration. Injections of lidocaine into the denervated striatum substantially decreased, and occasionally completely abolished, the contralateral turning after systemic l-DOPA. These findings indicate that activation of the DA depleted striatum is both sufficient and essential for the expression of behavioral response after systemic administration of l-DOPA. The contribution of the substantia nigra to this behavioral response seems to depend to a great extent on an active striatal outflow.

Animals↗
PubMed1998

Dissociation between startle and prepulse inhibition in rats exposed to gamma radiation at day 15 of embryogeny.

The role of prenatal trauma in disordered sensory gating was explored in albino rats of the Sprague-Dawley strain. Pregnant rats were exposed to 1.5 Gy (0.15 Gy/min) of the whole-body gamma radiation on days 15, 17, or 19 of gestation. Controls were sham-exposed during 10 min in the same conditions. Exposed and control offsprings were evaluated for the auditory startle response (ASR) and its gating by either the habituation process or by the preceding weak sensory stimulus in the prepulse inhibition of startle (PPI) procedure. The tests were conducted when the animals reached 27 and 57 days of age. A noticeable hyperresponding and delayed habituation of startle were found in rats exposed at E15, with meager effects in rats exposed at E17 and E19. Maximal deficit was obtained on tests conducted on P57 but not on P27. However, in rats pretreated with amphetamine, dysfunctional startle was unmasked already on the P27 test. By contrast, PPI was insensitive to the damaging effect of prenatal irradiation at either period. This dissociation is reminiscent of one observed in patients with posttraumatic stress disorder (PTSD).

Acoustic Stimulation↗
PubMed1997

A neuronal and neuroanatomical correlate of HIV-1 encephalopathy relative to HIV-1 encephalitis in HIV-1-infected children.

Progressive central nervous system dysfunction analogous to the AIDS dementia complex (ADC) seen in adults (HIV-1-associated progressive encephalopathy or HIV-1 encephalopathy) commonly occurs in HIV-1-infected children. The cause appears to be directly or indirectly related to HIV-1, rather than to other opportunistic pathogens. The exact mechanism(s) by which the virus affects brain function is not known. To determine whether the virus might modify brain function via an alteration in cortical neurons, we examined peptide neurotransmitter expression in the frontal cortex of HIV-1-infected cases with clinical HIV-1 encephalopathy relative to pathologic HIV-1 encephalitis. In situ hybridization was used to determine the level of peptide neurotransmitter expression of somatostatin in the frontal cortex of cases with and without HIV-1 encephalopathy and/or HIV-1 encephalitis. A 2-fold higher number of preprosomatostatin mRNA-positive interneurons was present in layer IV of cases with HIV-1 encephalitis compared with cases without HIV-1 encephalitis. In cases with PE, this neuronal alteration was 4- to 5-fold higher than in cases without PE, and was present in subcortical white matter in addition to layer IV. In cases having both PE and HIV-1 encephalitis, and in cases with HIV-1 encephalitis alone, these neuronal alterations in layer IV and/or subcortical white matter related to disseminated microglial nodules, even when these potentially viral-infected cells were negative for HIV-1 p24 antigen, a marker of productive viral infection. An alteration in preprosomatostatin mRNA-expressing cells occurring with HIV-1 encephalitis may be at least one mechanism that contributes to HIV-1 encephalopathy. When compared with other cortical laminae, layer IV receives most of its synaptic input from the mediodorsal nucleus of the thalamus. Neurons in the subcortical white matter project to the thalamus. The thalamus has been shown to have high amounts of viral antigen and increased metabolic activity in patients with AIDS. An alteration in preprosomatostatin mRNA-expressing cells may play a role in HIV-1 encephalopathy.

AIDS Dementia Complex↗
PubMed1996

Delayed habituation of the skin-conductance orienting response correlates with impaired performance on the Wisconsin Card Sorting Task in schizophrenia.

The skin-conductance orienting response (SCOR) in schizophrenia is often characterized by either nonresponding or delayed habituation to repeated nonsignal tones. These abnormalities are poorly related to other dimensions of schizophrenia. In the present study, we confirmed that about 50% of patients with chronic schizophrenia are SCOR nonresponders. Nonresponders, however, did not differ from responders on postmorbid psychiatric or pharmacological course, and we therefore could not confirm the hypothesis that course of illness follows a more marked pattern of increasing severity in nonresponders. Performance on the Wisconsin Card Sorting Test (WCST) was particularly poor in a subgroup of responders who exhibited either delayed habituation and/or dishabituation of SCORs to tones applied after a short rest period. It is possible that pathology of the prefrontal cortex mediates the SCOR abnormalities that characterize schizophrenic patients who perform poorly on the WCST.

Adult↗
PubMed1996

Kindled seizures do not affect adenosinergic inhibition of DA or ACh release in rat accumbens or PFC.

Epileptic seizures are thought to terminate largely as a result of the extracellular accumulation of the purinergic neuromodulator, adenosine, released by discharging neurons. However, the postictal surge in extracellular adenosine and its widespread inhibitory effects are limited in time to only a few minutes and cannot directly account for increased resistance to seizures and the complex behavioural and motivational effects that may persist for hours or days after a seizure. The present study examined whether kindled seizures might alter the sensitivity or efficacy of inhibitory presynaptic adenosine receptors, and thereby induce more enduring changes in downstream transmitter systems. Rats were kindled in the amygdala of the dominant cerebral hemisphere, contralateral to the preferred direction of rotation, and their brains were removed either 2 h or 28 days after completion of kindling. Inhibition of electrically stimulated release of dopamine (DA) and acetylcholine (ACh) by the A1 adenosine-receptor agonist, R-phenylisopropyladenosine (R-PIA) was then measured in the prefrontal cortex (PFC) and nucleus accumbens. R-PIA (1.0 microM) inhibited [1H]DA release from PFC and nucleus accumbens tissue, and [14C]ACh release from nucleus accumbens tissue, but release was unaffected by prior kindling, regardless of the intervening interval. These results do not support suggestions that DA or ACh might mediate the effects of seizure-induced changes in purinergic inhibitory tone so as to cause long-term shifts in seizure threshold and postictal behavior.

Acetylcholine↗
PubMed1996

Neurological and developmental problems in pediatric HIV infection.

Human immunodeficiency virus type-1 (HIV-1)-associated neurologic disease, known as "HIV-1-associated progressive encephalopathy" (PE), is a common concomitant in the progression towards AIDS. PE, characterized by a triad of symptoms including impaired brain growth, progressive motor dysfunction, and loss or plateau of developmental milestones, is believed to result from both direct and indirect effects of HIV-1 infection on the central nervous system (CNS). Consequent to the hallmark systemic immune deficiency of HIV infection, the CNS becomes susceptible to opportunistic infections which add further morbidity and mortality, and may contribute either directly or indirectly to neurologic symptoms which can often mimic PE. Static encephalopathies (SE) represent fixed, nonprogressive neurologic or neurodevelopmental deficits in HIV-infected children. SE may or may not be caused by HIV infection but are often associated with such identifiable insults as prematurity, in utero exposure to toxins or infectious agents, or head trauma. Additional neurological manifestations of HIV infection are seizures, cerebrovascular complications (i.e., stroke), myelopathies, neuromuscular syndromes, and CNS complications of opportunistic infections. Neurobehavioral aberrations have also been observed in pediatric HIV infection. In addition to the neuropathogenesis, theories regarding the timing and detection of the neurological problems associated with pediatric HIV infection are discussed along with a presentation of current treatment paradigms and their rationales. The importance of identifying the numerous environmental factors, including nutritional status, that may confound the ability to discriminate between a primary or secondary role of HIV infection in the various neurological problems of HIV infection is discussed.

AIDS Dementia Complex↗
PubMed1996

Epidural hematoma of a cauda equina in a child with hemophilia A.

PURPOSE: The presenting signs, treatment, and outcome of an epidural hematoma of the cauda equina in a child with severe hemophilia are reported for the first time. PATIENTS AND METHODS: A 20-month-old boy with severe hemophilia A (factor VIII <0.01 U/ml) presented with a 12-day history of refusal to stand and constipation of 5-7 days duration. He had normal deep tendon reflexes with normal sensation and withdrawal to pinprick of his lower extremities bilaterally. He stood on his right leg, but had inversion of his left foot and refused to bear weight on his left leg. MRI revealed an epidural hematoma of the cauda equina and a distended bladder. Factor VIII replacement therapy and lumbosacral laminectomy with evacuation of the hematoma resulted in recovery of a normal gait, but bladder dysfunction persisted for 11 months. Clean intermittent catheterization (CIC) was required until bladder function returned. RESULTS: Complete neurologic recovery occurred 11 months after presentation CONCLUSION: This case demonstrates the following points: (a) an epidural hematoma of the cauda equina in a child with severe hemophilia can present with neurologic findings that are as subtle as those seen in normal children; (b) CIC can be performed safely over an extended period without factor VIII replacement; and (c) complete recovery is possible, despite prolonged bladder dysfunction and a 12-day interval between the onset of symptoms and treatment.

Cauda Equina↗