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Biomedical subjects

J Szabo

Publications and source records attributed to J Szabo.

At least 91 records · Page 5Linked to original sources
PubMed1985

Dose-response toxicity studies on tributoxyethyl phosphate orally administered to Sprague-Dawley rats.

The response of the peripheral nervous system to various dose levels of tributoxyethyl phosphate (TBOP) was investigated in Sprague-Dawley rats. Groups of randomized female and male rats (10 rats/gender/dose level) were administered a single oral dose of TBOP (1.0 to 3.2 g/kg for females; 1.0 to 9.0 g/kg for males). Physiological parameters were measured in surviving rats three weeks following TBOP administration. A significant reduction (p less than 0.05) in caudal nerve conduction velocity (NCV) was observed in both female and male rats. Light and electron microscopic examination of sciatic nerve sections showed degenerative changes in both myelinated and unmyelinated fibers of female (2.0 g/kg) and male (6.8 g/kg) groups. Advanced degeneration was observed only in the highest dose level of both genders (3.2 g/kg for females; 8.0 and 9.0 g/kg for males). Although similar morphological changes were observed in both genders, females were more susceptible than males to the toxic effects of this compound.

Administration, Oral↗
PubMed1984

A stereotaxic atlas of the brain of the cynomolgus monkey (Macaca fascicularis).

Outline drawings of representative frontal sections of the Macaca fascicularis brain are presented in stereotaxic coordinates. The levels extend from the rostral tip of the neostriatum to the posterior end of the deep cerebellar nuclei. The illustrations are based on the photographs of unstained frozen sections of three formalin-fixed brains in which stainless steel needles were inserted to mark the horizontal zero and several anteroposterior positions. The sections were not stained in order to prevent shrinkage. Stereotaxic measurements were taken in situ of the highest points on the cortical surface, the position of the central and lunate sulcus, and of certain landmarks at the base of the cranium in a large number of monkeys. These data along with brain dimensions and the weight of animals are displayed in tables to indicate individual variations and to aid investigators in determining the best stereotaxic coordinates for a given structure. It is recommended that the cortical point of entry for an electrode or needle be routinely noted and be compared to the parameters in the atlas to compensate for deviations in the horizontal plane.

Animals↗
PubMed1984

Induction of electrophysiological and morphological changes in Sprague-Dawley rats fed tributoxyethyl phosphate.

The effects of a widely used trialkyl phosphate (TP), tributoxyethyl phosphate (TBOP), on the peripheral nervous system of Sprague-dawley (SD) rats were investigated. Male and female SD rats were administered this chemical by gavage over a period of 18 weeks (low dose: 0.25 ml kg-1; high dose: 0.50 ml kg-1). Electrophysiological changes observed at 18 weeks in all test animals included a significant reduction (P less than 0.001) in nerve conduction velocity and an important increase (P less than 0.001) of both relative (RRP) and absolute refractory period (ARP). Light and electron microscopic examination of sciatic nerve from all test animals showed the presence of degenerating myelin sheaths accompanied by axonal swelling. An advanced stage of degeneration was indicated by the presence of lamellated electron dense inclusions in unmyelinated nerve fibres.

Animals↗
PubMed1984

Covalent binding of isomeric 7-(2,3-epoxypropoxy)actinomycin D to DNA.

We have examined the ability of 7-(2,3-epoxypropoxy)actinomycin D (EPA) to bind covalently to DNA and to 2'-deoxyribonucleoside 5'-monophosphates in a simple system in vitro. We have observed initially that EPA binds to DNA and deoxymono- and deoxydinucleotides with intercalative or stacking interactions that are characteristic of actinomycin D (AMD). When EPA is incubated (37 degrees C) for a prolonged period (pH 7.4, 6 h) in contact with either DNA or deoxyribonucleotides, it forms covalent adducts. Deoxyguanosine is always the preferred site of reaction by EPA. After enzymatic digestion of EPA-DNA adduct, three deoxyguanosine (EPA-dG) adducts, one major and two minor, were isolated. These adducts are separable from one another and from other deoxyribonucleoside adducts, e.g., EPA-dA and EPA-dC by reverse-phase HPLC. The authentic EPA-dG, EPA-dA, and EPA-dC adducts were synthesized by a chemical reaction of the epoxide in EPA with the deoxyribonucleotides followed by enzymatic dephosphorylation of the products. From the EPA-DNA adduct the EPA-dG adducts accounted for congruent to 2.2% of EPA employed; the remainder of EPA was completely hydrolyzed to an epoxide ring opened diol derivative, DHPA. DHPA binds to DNA by intercalation only and it does not form covalent adducts. Another model analogue of EPA (EPAMDEA) has the same epoxide-substituted chromophore but lacks the peptide lactone functions; it fails to associate with DNA and consequently it shows no covalent binding of its epoxide with DNA. Formation of a noncovalent intercalation complex between EPA and DNA appears to be a prerequisite for the covalent reaction. Presumably because of these dual interactions, EPA demonstrates superior antitumor activities both in human leukemic cells (CCRF-CEM) in vitro and P388 and L1210 cells in mice. The DNA base specific alkylating activity of EPA, which is derived from a combination of the actinomycin D (AMD) structure and the new epoxide function in the molecule of EPA, attributes to EPA a potentially novel pharmacological behavior that is not inherent of AMD.

Animals↗
PubMed1983

Effects of tri-n-butyl phosphate on the peripheral nervous system of the Sprague-Dawley rat.

Tri-n-butyl phosphate, a widely used plasticizer and solvent, was orally administered to male and female Sprague-Dawley rats for 14 consecutive days (low dose: 0.28 mL/kg; high dose: 0.42 mL/kg). Effects of this industrial chemical were investigated on the peripheral nervous system of these animals. A significant (P less than 0.05) reduction in conduction velocity of caudal nerve was observed in high dose male rats. Electron microscopic examination of sciatic nerve showed morphological changes such as retraction of Schwann cell processes surrounding unmyelinated fibres in both sexes of high dose groups.

Animals↗
PubMed1980

Distribution of striatal afferents from the mesencephalon in the cat.

In a series of cats, various quantities of horseradish peroxidase were injected in different parts of the striatum to map out the extent and the topography of the afferent projections from the mesencephalon. Following large injections in the head of the caudate nucleus and putamen, the majority of cells were retrogradely labeled in the substantia nigra pars compacta (SNc) and in its dorsal extension the retrorubral nucleus or pars dorsalis (SNd), confirming previous reports. Numerous HRP positive neurons were also present in the ventral tegmental area (VTA) and the rostral raphe nuclei, including the rostral linear (LR) and intrafascicular (IF) nuclei, forming a mediolateral continuum with SNc. More caudally, labeled cells were found in central linear (LC), superior central (CS) and dorsal raphe nuclei (DR), in the ventrolateral tegmentum and between the decussating fibers of the brachium conjunctivum. Small injections in different mediolateral, dorsoventral and anteroposterior sites of the neostriatum resulted in retrograde transport of HRP to a variety of cell groups in this striatal projecting system indicating a topographical organization. Efferents from SNc and SNd distribute in the striatum in a mediolateral, anteroposterior and to some extent in an inverse dorsoventral topographical pattern. The terminal fields in the striatum overlap considerably. The topographical relations are more evident mediolaterally than in the other principal planes. The projections of the raphe nuclei and VTA terminate in the nucleus accumbens and the ventral half of the striatum. Within this territory, they display a mediolateral topography. In accord with earlier reports, fibers from the dorsal raphe nuclei have a wider distribution. An inverse topographical relationship is also established between the VTA cells and the ventral parts of the striatum.

Afferent Pathways↗
PubMed1980

Organization of the ascending striatal afferents in monkeys.

Horseradish peroxidase was injected in various parts of the caudate nucleus and the putamen of monkeys to ascertain the relative locations of striatal projecting cells in the mesencephalon. The nigrostriatal component, as expected, is the greatest but numerous cells of the mesencephalic raphe system also project to the striatum. The projections from the pars compacta are organized in a topographical manner in all principal planes. The rostral two thirds of the substantia nigra are related to the head of the caudate nucleus. Nigral neurons projecting to the putamen are more posteriorly located and display an anteroposterior topography. The medial two thirds of the pars compacta send efferents to the head of the caudate nucleus from ventromedial to laterodorsal regions, reflecting a mediolateral topographical relationship. An inverse relationship exists dorsoventrally between nigra and caudate so that ventral compacta cells project to dorsal caudate and the dorsally situated neurons project to ventral-ventro-medial caudate regions. The dorsal and lateral parts of the putamen are more intimately related to the lateral and posterior nigra; by contrast, the ventral and ventromedial putamen receives more afferents from medial and central regions of the substantia nigra. A large group of cells in the tegmentum dorsal and medial to the medial lemniscus shows continuity with the pars compacta, and has similar connections with the striatum. This cell group should be included with the pars compacta. Significant overlap exists between the projection fields in all planes, making the nigrostriatal topographical organization seem less than precise. This apparent lack of point-to-point reciprocity may be due to the considerable size difference between the striatum and the substantia nigra. The raphe nuclei project to the greater part of the striatum but more significantly to its ventral and medial regions. The paranigral cell group sends its efferents mainly to the ventral striatum.

Afferent Pathways↗
PubMed1977

Thalamic projections of the superior colliculus in the rhesus monkey, Macaca mulatta. A light and electron microscopic study.

The projections of the superior colliculus to the thalamus have been studied in the monkey, Macaca mulatta, with anterograde degeneration techniques. The superior colliculus has been shown to project to the inferior nucleus of the pulvinar in a topographical manner with the lower visual field represented dorsomedially and the upper field ventrolaterally. The peripheral zone is located along the medial border and the fovea at the dorsolateral angle adjacent to the lateral geniculate nucleus. The superior colliculus also sends a dense projection to the ipsilateral intralaminar complex, i.e., to the parafascicular, central lateral and paracentral nuclei, and a lesser projection to the same contralateral nuclei. Degenerating tectal fibers were also found in the lateral geniculate nuclei. Four types of vesicle containing profiles were observed in the inferior pulvinar and paracentral nucleus. The large RL and small RS terminals contain round vesicles of uniform size and form asymmetric contacts mainly with large and small dendrites respectively. The F terminal contains a mixture of small round and flat vesicles. It forms symmetric contacts with dendrites and cell somata. The P profile is very pale and contains a relatively sparse population of vesicles showing a great variation in size. It forms symmetric contacts with medium to large dendrites. It is frequently found postsynaptic to the other types, especially the RL terminal, and is regularly seen as the intermediate element of serial and triadic synaptic arrangements. The experimental electron microscopic study has shown that many fibers from the superior colliculus terminate as RL profiles, undergoing direct dense degeneration, in both the inferior pulvinar and the paracentral nucleus. Others probably end as smaller RS terminals.

Afferent Pathways↗
PubMed1977

Electron microscopic investigation on the zona glomerulosa of rats after treatment with heparin and potassium.

Adrenal zona glomerulosa of rats was investigated by means of electron microscopy after stimulation with potassium and suppression with heparin. Both intreated and control animals two types of mitochondria -- one with tubular and the other with tubulosaccular cristae -- were found. Stimulation with potassium increased the amount of mitochondria with tubular cristae, heparin treatment caused a simplification of the structure of tubulosaccular cristae. It was assumed that these two mitochondrium-poulations contain different enzyme systems, which catalyze the different step-series of aldosterone biosynthesis. On the basis of cytoplasmic density, dark and light cells could be distinguished only in the zona glomerulosa of control rats, they were absent in both groups of treated animals. The density of these cells probably did not depend on their metabolic activity, but rather on their hormone storage.

Adrenal Cortex↗
PubMed1976

Events related to microembolism during extracorporeal perfusion in man: effectiveness of in-line filtration recorded by ultrasound.

Microparticle generation during cardiopulmonary bypass was monitored continuously in 60 adult patients who underwent open-heart operations. Echo-ultrasound transducers of 5 mHz frequency were interposed in a bubble oxygenator arterial line proximal and distal to a commercially available micropore filter. Ordinary perfusion events correlated with an increase in embolic counts and were recorded graphically. Calculation of filter efficiency revealed that all filters decreased measurable embolic counts. Platelet and leukocyte determinations and plasma hemoglobin values were not altered beyond limits ordinarily encountered during perfusion without filters. No patient in any filter group experienced postoperative respiratory distress, diffuse pulmonary infiltrate, or low PaO2. The 20 mu woven nylon mesh filter and the Dacron-wool filter showed greater than 90% effectiveness in removing recorded particles. Insertion of a cardiotomy filter did not appreciably alter recorded embolic counts distal to the arterial line filter.

Blood Cell Count↗
PubMed1976

Amino acid assignment to one of three blood-brain barrier amino acid carriers.

The percentages of 22 14C-labeled amino acids remaining in rat brain 15 s after carotid injection were measured relative to a simultaneously injected diffusible internal standard, 3HOH. The injected solution also contained a nondiffusible internal standard, [113mIn]EDTA to correct for incomplete brain blood compartment washout. Self-inhibition and cross-inhibition was demonstrated by inclusion of unlabeled amino acids and carboxylic acids. All amino acids tested, excluding proline, alanine, and glycine, could be assigned to one, and only one, blood-brain barrier carrier system. The neutral carrier system transported phenylalanine, leucine, tyrosine, isoleucine, methionine, tryptophane, valine, DOPA, cysteine, histidine, threonine, glutamine, asparagine, and serine. Affinity for a basic amino acid carrier system was demonstrated for arginine, ornithine, and lysine. A third, low-capacity independent carrier system transporting aspartic and glutamic acids was demonstrated.

Amides↗