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Biomedical subjects

Y Kishimoto

Publications and source records attributed to Y Kishimoto.

At least 343 records · Page 19Linked to original sources
PubMed1977

alpha-Hydroxylation of fatty acids in brain. Substrate specificity and deuterium isotope effect.

The alpha-hydroxylation of fatty acids with various chain length by a rat brain postnuclear preparation was investigated. The maximum velocity of the alpha-hydroxylation were higher for lignoceric (tetracosanoic), tricosanoic, docosanoic, and heneicosanoic acids and lower for hexacosanoic, pentacosanoic, eicosanoic, and nonadecanoic acids. Stearic palmitic, and phytanic (3,7,11,15-tetramethylpalmitic) acids were not hydroxylated by this preparation. Apparent Km values were lower for fatty acids with the higher Vmax and higher for those with the lower Vmax values. The relative order of alpha-hydroxylation strongly resembles the relative distribution of these fatty acids in brain cerebrosides, and we suggest that alpha-hydroxylation plays an important role in determining this distribution. An improved synthesis of [U-14C]phytanic acid is described. The rate of alpha-hydroxylation with [2-2H2]lignoceric acid was one-fifth of nondeuterated lignoceric acid and one-third of [3-2H2]lignoceric acid, while apparent Km values for these acids were similar. The reduced rate with [2-2H2]lignoceric acid indicates that the cleavage of the C-H bond is the rate-limiting step of the alpha-hydroxylation.

Animals↗
PubMed1977

[Studies on the resistance of a congenic resistant strain of mice (DKIR) against infection with Salmonella enteritidis (author's transl)].

A congenic strain of mice (DKIR) having a relatively resistant gene for mouse typhoid was established by the beckcross mating between C3H/He and DKI strains. DKI strain is highly and uniformly susceptible to the infection with Salmonella enteritidis and C3H/He is relatively resistant to that infection. The present paper reported the consistency of resistance to Salmonella infection of DKIR strain throughout generations after 10 backcross matings. Difference of the number of infected organisms in the peritoneal fluid and organs between DKIR and DKI or C3H/He strains was also described. The newly established DKIR strain seems to be a suitable experimental animal for the study of genetical resistance for mouse typhoid when compared with its original DKI strain.

Animals↗
PubMed1976

Alpha-Hydroxylation of lignoceric and nervonic acids in the brain. Effects of altered thyroid function on postnatal development of the hydroxylase activity.

Rat brain postnuclear preparations catalyzed the alpha-hydroxylation of nervonic acid with an apparent Km of 3 muM. Evidence has been presented which suggests that nervonic acid in the brain is hydroxylated by the same enzyme system which hydroxylates lignoceric acid. The hydroxylase activity in brains of normal (euthyroid) rats increased rapidly from a low in the period immediately following birth to a maximum at the 23rd day and then declined to a low level characteristic of the mature brain. Neonatal hypothyroidism retarded the development of the activity and shifted its peak to the 39th day after birth. Conversely, neonatal hyperthyroidism accelerated the entire developmental pattern and shifted the peak to the 16th day after birth. The hydroxylase activity in mouse brain was also increased by thyroid hormone administration from the 13th through the 18th day after birth. Unlike normal mice, the low activity in jimpy mice was not affected by this treatment. It is concluded that thyroid hormones play an important role in the control of brain fatty acid alpha-hydroxylation. The stimulation of alpha-hydroxy fatty acid synthesis in response to hyperthyroidism during the early postnatal period may be one of the major effects of thyroid hormones in accelerating myelination of the central nervous system.

Aging↗
PubMed1976

Cholesterol sulfate in rat tissues. Tissue distribution, developmental change and brain subcellular localization.

1. A reliable micromethod for the determination of the tissue level of cholesterol sulfate has been developed. Cholesterol sulfate was separated from the bulk of the free cholesterol by silica gel column chromatography, and the cholesterol sulfate fraction subjected to benzoylation. A small amount of contaminating free cholesterol and other lipids remaining in this fraction were converted to benzoyl esters while the cholesterol sulfate remained unreacted. The cholesterol sulfate was then separated from the benzoylated contaminants by a second silica gel chromatography column and subjected to solvolysis. The liberated cholesterol was determined by gas-liquid chromatography. 2. The cholesterol sulfate contents of the visceral organs of 43-day-old rats were determined. Every tissue examined contained small amounts of this sulfate. Kidney contained the highest concentration of cholesterol sulfate (250-300 mug/g dry tissue weight) followed by spleen (77 mug/g), adrenal gland (50-70 mug/g) and lung (50-57 mug/g). 3. In brain, cholesterol sulfate level rises sharply from 17 mug/g dry weight in 7-day-old rats to more than 50 mug/g in 15-day-olds, then it declines rapidly to 15 mug/g in the 40-day-olds and this level is maintained to adulthood. The developmental pattern in the liver resembles that in the brain, except that the peak is somewhat flatter with the highest value (60 mug/g dry weight) occurring in the 21-day-old animal. In contrast to the above two tissues, the level of kidney cholesterol sulfate increases steadily from 15 mug/g in 7-day-olds and reaches the adult level of approx. 200 mug/g in 50-day-olds. 4. The highest level of cholesterol sulfate in subcellular fractions of rat brain occurred in a fraction rich in nerve endings. The level here was 10 times higher than that in the mitochondrial fraction, which contained the lowest levels of this steroid sulfate.

Adrenal Glands↗
PubMed1975

Alpha hydroxylation of lignoceric acid to cerebronic acid during brain development. Diminished hydroxylase activity in myelin-deficient mouse mutants.

Alpha Hydroxylation of lignoceric acid (n-tetracosanoic acid) to cerebronic acid (2-hydroxylignoceric acid) by postnuclear preparations of brains from developing rat, mouse, and several neurological mouse mutants was studied. The preparations of brains from jimpy and myelin synthesis deficiency (msd) mice were found to synthesize cerebronic acid at less than 10 percent of their control rates, and those from quaking and dilute-lethal approximately 30 and 50 percent, respectively. The apparent low rate of in vitro hydroxylation by brains of the mutant mice appeared to be due to decreased synthesis rather than increased oxidation of cerebronic acid. Mixing experiments eliminated the possibility of an inhibitor in the mutant or an activator in normal animals. The preparations of brains from wabbler-lethal, ducky, and weaver mice showed normal activity. The developmental pattern of the hydroxylase activity was examined in quaking, jimpy, and their control mice. In normal brains the hydroxylase activity was low in the immediate postnatal period, increased sharply between 10 and 20 days after birth, and fell to a low level following maturation of the brain. The hydroxylase activity in quaking mice changed similarly during brain development but at a much reduced level. The brains of jimpy mice had barely detectable hydroxylase activity which changed little with age and reached a peak at about 15 days postpartum. The subnormal hydroxylase activity in brains of quaking mice and the near absence in brains of jimpy and msd mice correlate with the observations that myelin deficiency is more severe in jimpy and msd than in quaking. These results suggest a close association of the synthesis of cerebronic acid with the synthesis of the characteristic myelin lipid that is cerebroside (N-acyl sphingosine beta-D-galactoside).

Aging↗
PubMed1975

3-Ketosphingolipids: application to the determination of sphingolipids which contain 4-sphingenine.

1. Ceramides and cerebrosides, both with 2-hydroxy or non-hydroxy fatty acids, and sphingomyelins were converted quantitatively to the corresponding 3-keto derivatives with the oxidative reagent 2,3-dichloro-5,6-dicyanobenzoquinone. Sulfatides were converted to 3-ketocerebrosides. 2. The conversion of these sphingolipids to the alpha,beta-unsaturated ketone permits three methods of quantitation: in Method I, the absorption of the reaction product is measured at 230 nm; Method II utilizes high performance liquid chromatography and an ultraviolet light detector; in Method III, the product is reduced with NaB3H4 and the radioactivity of the reduced products is determined. All three methods can be used to measure sphingolipids in nanomole quantities. 3. Methods I and II have been applied to the determination of cerebroside and sulfatide content of normal and metachromatic leukodystrophy brains. In the white matter of the pathological brains, there was a greater accumulation of sulfatides containing non-hydroxy fatty acids than of those containing 2-hydroxy fatty acids. The ceramide levels of the cerebellum in a Farber's disease patient and a control were determined by Method II. Method III was used to determine the content of free ceramides in human sera.

Brain↗
PubMed1975

Specific tritium labeling of cerebrosides at the 3-positions of erythro-sphingosine and threo-sphingosine.

Cerebrosides containing either threo- or erythro-[3-3-H]sphingosine were synthesized by a new procedure. Glucopyranosyl or galactopyranosyl ceramides were converted to their 3-keto derivatives with 2,3-dichloro-5,6-dicyanobenzoquinone and reduced with 3-H-labeled sodium borohydride. The resulting tritiated cerebrosides, which contained erythro- and threo-sphingosines in the ratio of 84:16, were deacylated with butanol-KOH, and the erythro- and threo-psychosines were separated by silica gel column chromatography and reacylated with lignoceroyl chloride.

Animals↗