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Biomedical subjects

Y Sakakihara

Publications and source records attributed to Y Sakakihara.

15 recordsLinked to original sources
PubMed1992

Partition of free dolichol in human urine.

We have demonstrated that dolichol is present in the urinary supernatant. Most of the dolichol present in the supernatant seems to be associated with cellular debris or membrane fragments. The amount of sediment in healthy subjects correlate well with the volume of urine. Although it is illogical to express urinary dolichol relative to urine volume, a good correlation between the amount of sediment and urine volume has made its use justifiable. Because of the presence of a substantial amount of dolichol in the supernatant, it seems better to use uncentrifuged whole urine as the sample for measurement of dolichol.

Adult↗
PubMed1992

[Autonomic dysfunction in metabolic diseases].

Among many metabolic disorders, porphyrias and Fabry disease are known to affect autonomic nervous system. In patients with acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria, autonomic symptoms such as abdominal pain, vomiting, hypertension and tachycardia are among the most prominent clinical manifestations. Fabry disease is clinically characterized by severe limb pain, hypohidrosis, angiokeratomas and various autonomic symptoms. In both porphyrias and Fabry disease, pathological changes in the central and peripheral autonomic nervous system have been documented. In porphyrias, a loss of myelinated fibers, axonal degeneration, and segmental demyelination in peripheral autonomic nerves as well as chromatolysis of several brain stem nuclei have been found. In Fabry disease, abnormal amount of the substrates of alpha-galactosidase, i.e. ceramide di- and trihexoside, are found to be accumulated in the central and peripheral autonomic nerves.

Autonomic Nervous System Diseases↗
PubMed1991

Age-associated changes in the symptomatology of Guillain-Barré syndrome in children.

The medical records were reviewed of 83 children with Guillain-Barré syndrome, with reference to the age-associated changes found in the initial symptoms, the intervals between the preceding illness and the onset of disease, and the patterns of affected cranial nerves. A close correlation was observed between cranial nerve involvement and respiratory complications. The findings suggest the involvement of nervous system maturation in the clinical manifestations of Guillain-Barré syndrome in children.

Adolescent↗
PubMed1991

[A case of right femoral anastomotic aneurysm accompanied by obstruction of left iliac and femoral artery].

The case was a 66-year-old man. Three years ago under a diagnosis of Arteriosclerosis obliterans he received: right aorto-femoral bypass grafting. This time left intermittent clandication was observed and we performed resection of aneurysm and femorofemoral cross over bypass grafting following a diagnosis of right aorto-femoral anastomotic aneurysm accompanied by obstruction of left iliac and femoral artery. Anastomotic aneurysm is one of the complications after prosthetic bypass grafting. In this paper we discussed the causes, precautions and treatment of anastomotic aneurysms.

Aged↗
PubMed1989

Changing spectrum of pediatric neurologic disorders during 18 selected years, 1900-1980, at the Hospital of University of Tokyo.

In order to assess the changing pattern of pediatric neurologic disorders during this century, we retrieved and analyzed the medical records of hospitalized patients with neurologic disorders in our hospital from 1900 to 1980. It was demonstrated that bacterial meningitis had been by far the most common cause of death until 1950. After 1950, both the incidence and the mortality rate of bacterial meningitis declined rapidly probably because of the improved medical care and introduction of various antibiotics. We noticed several interesting features in the changing spectrum of bacterial meningitis as described below. First it was demonstrated that the incidence of tuberculous meningitis declined almost a decade later than those of other kinds of purulent meningitis. Second, the incidence of bacterial meningitis declined even before the introduction of antibiotics. Although the development of antibiotics was the main contributing factor in improving the prognosis for bacterial meningitis, it is suggested from our data that other factors such as improved general supportive care and carrying out of public health programs also played an important role in improving the overall prognosis for bacterial meningitis.

Bacterial Infections↗
PubMed1988

Dolichyl phosphate: rapid increase and predominant form of brain dolichol compounds during early brain development.

Of brain dolichol compounds, dolichyl phosphate is most critical since it serves as the carrier of saccharide moieties to be utilized for N-linked protein glycosylation. The objectives of the current study were to determine (1) whether the proportion of dolichyl phosphate to dolichol in brain is relatively large and/or changes with development, and (2) whether the subcellular distribution of these isoprenoid compounds differs and/or changes with development. A recently described, improved technique for isolation and quantitation of dolichyl phosphate was employed. The data show that in the first 4 weeks of postnatal life in the rat dolichyl phosphate is, in fact, the predominant form of total dolichol compounds in brain. Subsequently, concentrations of dolichol exceeded those of dolichyl phosphate in adult brain, particularly with aging. Dolichyl phosphate was found to be localized primarily in microsomes; dolichol was found in only small amounts in microsomes but was enriched in the fraction that contained lysosomes. The observations indicate that during early brain development, an active time period for differentiating events, many of which are mediated by glycoproteins, dolichyl phosphate is present in high concentration at the subcellular site of N-linked glycoprotein synthesis, i.e., endoplasmic reticulum.

Aging↗
PubMed1987

Dolichol kinase and the regulation of dolichyl phosphate levels in developing brain.

The developmental changes of dolichol kinase activity and dolichyl phosphate levels have been studied in rat brain. Because both dolichol kinase activity and dolichyl phosphate were enriched in microsomes, detailed study of this subcellular fraction was carried out. Dolichol kinase specific activity in brain microsomes increased postnatally 3-fold to a maximum at ca. 30 days of age. This increase was observed whether exogenous dolichol was present or not and whether Zn2+ or Ca2+ was utilized as the cation for the enzyme. Zn2+ was the most effective cation in developing brain, as we have shown previously for adult brain (Sakakihara, Y. and Volpe, J.J., J. Biol. Chem., 260 (1985) 15413-15419). Although the Vmax for the enzyme increased by three-fold with development, the Km for dolichol and for CTP did not change, indicating that the developmental increase was not related to an alteration in catalytic efficiency of the enzyme. A striking and parallel increase in dolichyl phosphate levels in brain microsomes was defined with development. Levels were lowest in one-day-old animals and then increased ca. 13-fold to a maximum at 30 days of postnatal age. The parallel increase in dolichol kinase activity and dolichyl phosphate levels in microsomes of developing brain suggests that dolichol kinase is the principal determinant of cellular levels of dolichyl phosphate, the critical intermediate in the dolichol-linked pathway to glycoproteins.

Animals↗
PubMed1987

Dolichol-linked glycoprotein synthesis in developing mammalian brain: maturational changes of the N-acetylglucosaminylphosphotransferase.

The enzyme UDP-N-acetylglucosamine:dolichyl phosphate, N-acetylglucosamine-1-phosphate transferase (GlcNAc-1-P transferase), the first committed step in the dolichol-linked oligosaccharide pathway for glycoprotein biosynthesis, has been studied in developing rat brain. The enzyme was shown to be localized in microsomes, particularly heavy microsomes, and to be activated by Mg2+ and inhibited by tunicamycin. Study of the enzyme with brain development demonstrated two prominent findings. First, the accentuation of enzymatic activity caused by addition of a saturating concentration of dolichyl phosphate was greater in brain of older (3-4 weeks of age and subsequently) animals (25-fold) than in brain of younger (less than two weeks of age) animals (10-fold). This difference suggests that dolichyl phosphate may be limiting for GlcNAc-1-P transferase activity in endoplasmic reticulum of the older animals. Second, a marked (3.5-fold) increase in activity occurred over a discrete time period (3-4 weeks of postnatal life) during brain development. That this increase reflected an increase in enzyme amount rather than in catalytic efficiency was suggested by kinetic studies. Coupled with our previous demonstrations of increases in brain dolichol, dolichol kinase activity, and dolichyl phosphate levels during approximately the same developmental period (Sakakihara, Y. and Volpe, J.J., Dev. Brain Res., 14 (1984) 225-262; Volpe, J.J. et al., Dev. Brain Res., in press), the data suggest a temporally discrete period of activation of the dolichol-linked pathway to glycoproteins. Whether the pathway is regulated coordinately or sequentially is a fertile topic for future study.

Aging↗
PubMed1985

Zn2+, not Ca2+, is the most effective cation for activation of dolichol kinase of mammalian brain.

The cation specificity of dolichol kinase of mammalian brain and the potential involvement of a Ca2+-calmodulin system in regulation of this enzyme have been studied. Among 10 divalent cations examined, Zn2+ was found to be most effective for the activation of dolichol kinase of rat and calf brain and cultured C-6 glial cells. The activations with Ca2+, Co2+, and Mg2+ were 53%, 32%, and 18% of the full activation with Zn2+, respectively. No combinations of the cations could activate the enzyme as much as Zn2+ alone. A role for a Ca2+-calmodulin system in the regulation of brain dolichol kinase was not supported by our data. First, the concentration of free Ca2+ required for the maximum activation of dolichol kinase was two to three orders of magnitude greater than the concentration required by typical calmodulin-dependent enzymes. Second, neither the depletion of calmodulin from the microsomal fraction nor the addition of exogenous calmodulin caused an alteration in the activation of dolichol kinase by Ca2+ (or Zn2+). Third, antagonists of calmodulin failed to suppress the activation of the enzyme by Ca2+ (or Zn2+). The data raise the possibility that Zn2+ is involved in the regulation of dolichol kinase in brain.

Animals↗
PubMed1985

Dolichol in human brain: regional and developmental aspects.

Distinct regional differences in dolichol content were defined in human brain from 15 to 76 years of age. Concerning the regional distribution of dolichol, levels were: higher in cortical gray matter than in subcortical white matter, highest among cortical regions in temporal gray matter, highest among all brain regions in thalamus, and lowest among all brain regions in lower brain stem and spinal cord. The developmental changes in the contents of dolichol were found to be different among brain regions. For example, among regions with the highest levels of dolichol, in thalamus there was a six to sevenfold increase, but in parietal gray matter, only a 2.5-fold increase. Regional and developmental changes in the proportions of the individual molecular species (isoprenologues) of dolichol were also observed. The findings indicate that the metabolism of dolichol is not uniform among regions of developing and aging human brain and may have implications for the role of dolichol in normal and diseased human brain.

Adolescent↗