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Biomedical subjects

M R Krigman

Publications and source records attributed to M R Krigman.

70 records · Page 4Linked to original sources

Brain function and macromolecules. VI. Autoradiographic analysis of the effect of a brief training experience on the incorporation of uridine into mouse brain.

In agreement with the data of Beach et al. (these Proceedings, 62, 692 (1969)) on the effects of avoidance training on protein synthesis, we report autoradiographic evidence for the increased incorporation of radioactive uridine into limbic system structures of the brains of trained mice. There is also a decreased incorporation into the outer layers of the neocortex. The observed responses in labeling are restricted to the nuclei of neurons. The significance of these changes in brain function is not known but they may be related to those processes of the memory consolidation phenomenon affected by inhibitors of protein and RNA synthesis.

Amygdala↗

Effect of lead on the developing peripheral nervous system.

The effect of lead on the developing nervous system was studied in the Long-Evans rat. Pups were intoxicated with lead from day 2 through the 20th day of life with a dosage of 1 gm Pb/kg body weight. Doses were administered via gastric gavage on the second and third days of life, and bidaily thereafter. Lead-treated and age-matched controls were then studied at selected intervals up to and including 20 days of age. Central and peripheral nervous systems were examined by light and electron microscopy. Morphometric analysis focused on defined segments of proximal and distal sciatic nerves and the 6th dorsal and ventral lumbar roots. For teased fiber studies, a segment of the contralateral proximal sciatic nerve was used. The investigation revealed that during the period studied, the myelin formed is stable. Multiple lead effects, however, were found: the Schwann cell is initially swollen but this effect gradually wanes during the 20 day period; myelin compaction is initially delayed, particularly in the ventral roots; axonal segregation proceeds, but appears to be accelerated in the ventral roots of the lead-treated pups where the larger bundles of naked axons disappear by five days of life. All of the changes noted, except axonal segregation, are reversed in the face of continued lead intoxication. While the hallmarks of "classical" lead neuropathy--segmental demyelination and the selective involvement of large fibers were not observed--the sensitivity of the somatic efferent fibers to lead was apparent in the accentuation of the lead effects in the ventral roots.

Animals↗

Pathology of disulfiram neuropathy.

The pathological changes in a sural nerve biopsy from a 42-year-old woman with disulfiram-induced peripheral neuropathy were assessed by quantitative light microscopy, electron microscopy, and the study of teased nerve fibres. The nerve had a marked loss of myelinated fibres; of the remaining myelinated fibres some were undergoing Wallerian-type axonal degeneration. Large myelinated fibres were preferentially involved. Primary demyelination, remyelination, and evidence of regeneration were not present. Because of the marked differences between the pathological findings in disulfiram neuropathy and carbon disulfide neuropathy, it is concluded that carbon disulfide is not responsible for the neurotoxic effect of disulfiram.

Adult↗

Temporal changes in dopaminergic and serotonergic function caused by administration of trimethyltin to adult rats.

Previous studies have demonstrated that at day 7 following treatment, administration of 3 or 7 mg/kg trimethyltin (TMT) to male Long-Evans rats caused decreases in the concentrations of DA in nucleus accumbens, and perturbed serotonergic function in regions of brain that receive serotonergic innervation from the raphe nuclei. The present series of experiments extended these observations by examining the time course of these events from 14 to 28 days after treatment. Following a dose of 7 mg/kg, changes in serotonergic function, as evidenced by increased turnover and decreased concentrations of 5-HT, were present in striatum, olfactory tubercle, septum and frontal cortex. In nucleus accumbens, concentrations of DA were decreased up to 21 days, while in frontal cortex concentrations of DOPAC and HVA were elevated only at 14 days. In concert with our previous studies, these data indicate that administration of TMT continues to affect serotonergic systems up to 28 days, and dopaminergic systems up to 21 days after exposure, with striatum, nucleus accumbens, olfactory tubercle and septum exhibiting persistent effects due to administration of this neurotoxicant. These prolonged alterations in serotonergic function suggest that this system may play an important role in the response to intoxication with TMT.

3,4-Dihydroxyphenylacetic Acid↗

CT recognition of subcortical hematomas.

Subcortical hematomas develop in brain trauma and less commonly in hypertensive intracerebral hemorrhage. Six cases are reported that exhibit a spectrum of computed tomographic (CT) findings in this entity. Pathologic correlates in four cases are presented. It is theorized that subcortical hematomas form in trauma secondary to shearing stresses in the brain. Differential movement of gray and white matter may disrupt cortical medullary vessels. Rupture of degenerative vessels at this junction may account for hypertensive hematomas.

Adolescent↗

Chronic neonatal organotin exposure alters radial-arm maze performance in adult rats.

Long-Evans rats were intubated with 0.3 or 1.0 mg/kg of triethyltin sulfate (TET) or 0.3 mg/kg of trimethyltin hydroxide (TMT) from postnatal day 3-29. 1.0 mg/kg of TMT was given on alternate days beginning on postnatal day 3. Learning and memory were assessed in an automated radial-arm maze when the rats were 180-200 days old. With this maze accuracy and activity data can be collected simultaneously. TET or TMT treatment resulted in an increase in the number of days required to adequately perform and radial-arm maze task, and a transient deficit in accuracy. However, the most pronounced effect in both TET and TMT-treated animals was hyperactivity which became manifest on the second day of testing and persisted throughout the remainder of testing.

Analysis of Variance↗

Comparative organotin toxicity in the developing rat: somatic and morphological changes and relationship to accumulation of total tin.

The effect of the structure of organotin compounds on their toxicity and neurotoxicity to the developing rat has been studied. Oral administration was used after selection of a vehicle that gave uniform organotin solubilization as evidenced by toxicity and chemical solubility data. This vehicle was milk plus Tween-80. Eight different organotin compounds were systematically surveyed for effects in the neonatal rat. Trimethyl- and triethyltin were most toxic, and were somewhat more toxic than tri-n-propyltin. Tri-n-butyltin was somewhat less toxic, while tricyclohexyl-, triphenyl-, diethyl- and dimethyltin were least toxic. Some higher doses of trimethyl- or triethyltin caused neuropathological changes that were characteristic for each compound, these changes being absent for the other agents. Regardless of their toxicity, significant amounts of tin, as the element, were found in brain, kidney, and liver after treatment with all agents. However, detectable blood values were only obtained for trimethyl- and triethyltin.

Administration, Oral↗