Methyl isobutyl ketone (MIBK) induction of alpha2u-globulin nephropathy in male, but not female rats.

Male F-344 rats were administered corn oil (vehicle control), d-limonene (positive control, 300mg/kg), or MIBK (1000mg/kg) and female F-344 rats corn oil (vehicle control) or MIBK for 10 consecutive days by oral gavage. Approximately 24h after the final dose the kidneys were excised and the left kidney prepared and evaluated for histological changes including protein (hyaline) droplet accumulation, immunohistochemical staining for alpha2u-globulin (alpha2u), and proliferating cell nuclear antigen (PCNA) to quantitate renal cell proliferation. The right kidney was prepared for quantitation of total protein and alpha2u using an ELISA. MIBK elicited an increase in protein droplets, accumulation of alpha2u, and renal cell proliferation in male, but not female rats, responses characteristic of alpha2u-mediated nephropathy. MIBK produced identical histopathological changes in the male rat kidney when compared to d-limonene, an acknowledged inducer of alpha2u-nephropathy except that the grade of severity tended to be slightly lower with MIBK. MIBK did not induce any effects in female rats. Therefore, renal histopathology, along with the other measures of alpha2u accumulation, provides additional weight of evidence to support the inclusion of MIBK in the category of chemicals exerting renal effects through a alpha2u-nephropathy-mediated mode-of-action.

Hereditary adult-onset Alexander's disease with palatal myoclonus, spastic paraparesis, and cerebellar ataxia.

We describe a progressive neurologic disorder in three sisters characterized clinically by palatal myoclonus, spastic weakness, hyperreflexia, mild cerebellar dysfunction, and ocular motor abnormalities. Postmortem examination of one patient demonstrated widespread Rosenthal fiber deposition associated with demyelination. The father previously was reported to have similar pathologic findings and carried a clinical diagnosis of multiple sclerosis. These clinical and pathologic findings describe a rare familial leukodystrophy that corresponds most closely to cases reported as adult Alexander's disease. Although similar pathologically to the well-characterized infantile variant of Alexander's disease, it is not known whether this adult variant represents the same disease process.

Physiological and behavioral effects of tilt-induced body fluid shifts.

This paper addresses the "fluid shift theory" of space motion sickness. The primary purpose of our research was the development of procedures to assess individual differences in response to rostral body fluid shifts on earth. Experiment I examined inner ear fluid pressure changes during head-down tilt in intact human beings. Tilt produced reliable changes. Differences among subjects and between ears within the same subject were observed. Experiment II examined auditory threshold changes during tilt. Tilt elicited increased auditory thresholds, suggesting that sensory depression may result from increased inner ear fluid pressure. Additional observations on rotation magnitude estimation during head-down tilt, which indicate that rostral fluid shifts may depress semicircular canal activity, are briefly described. The results of this research suggest that the inner ear pressure and auditory threshold shift procedures could be used to assess individual differences among astronauts prior to space flight. Results from the terrestrial observations could be related to reported incidence/severity of motion sickness in space and used to evaluate the fluid shift theory of space motion sickness.

Self-motion magnitude estimation during linear oscillation: changes with head orientation and following fatigue.

Two types of experiments concerning estimated magnitude of self-motion during exposure to linear oscillation on a parallel swing are described in this paper. Experiment I examined changes in magnitude estimation as a function of variation of the subject's head orientation, and Experiments II a, II b, and II c assessed changes in magnitude estimation performance following exposure to sustained, "intense" linear oscillation (fatigue-inducing stimulation). The subjects' performance was summarized employing Stevens' power law (R = k . Sn, where R is perceived self-motion magnitude, k is a constant, S is amplitude of linear oscillation, and n is an exponent). The results of Experiment I indicated that the exponents, n, for the magnitude estimation functions varied with head orientation and were greatest when the head was oriented 135 degrees off the vertical. In Experiments II a-c, the magnitude estimation function exponents were increased following fatigue. Both types of experiments suggest ways in which the vestibular system's contribution to a spatial orientation perceptual system may vary. This variability may be a contributing factor to the development of pilot/astronaut disorientation and may also be implicated in the occurrence of motion sickness.