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Biomedical subjects

K Sudo

Publications and source records attributed to K Sudo.

At least 307 records · Page 17Linked to original sources
PubMed1983

Congenital hydrocephalus revealed in the inbred rat, LEW/Jms.

We studied the development of congenital hydrocephalus found in a colony of an inbred strain of Wistar-Lewis rats (LEW/Jms) at various intervals after birth. The disorder was transmitted as a simple recessive mendelian character. Hydrocephalic neonates were recognized 2 days after birth by stretching of the skin over the head. Death usually occurred between 10 and 20 days of age. The findings suggested the possibility of a disturbance of cerebrospinal fluid circulation resulting from primary occlusion of the 3rd or lateral ventricles during embryological development. In later phases, the hydrocephalus was aggravated by obliteration of the subarachnoid space and by stenosis of the aqueduct occurring secondary to compression of these structures from increased pressure within the brain. In some animals, external hydrocephalus occurred as a result of rupture of the occipital pole and the establishment of a direct communication between the lateral ventricles and the subdural space. We looked for antibodies against viruses that have been known to produce hydrocephalus in experimental animals and obtained entirely negative results.

Animals↗
PubMed1983

Lactate dehydrogenase A-subunit and B-subunit deficiencies: comparison of the physiological roles of LDH isozymes.

Different clinical features exist for lactate dehydrogenase A-subunit and B-subunit deficiencies. The metabolic basis for these clinical differences was elucidated by investigating carbohydrate metabolism in the affected tissues. Glycolysis was markedly retarded at the position of glyceraldehyde 3-phosphate dehydrogenase, and significant increases of glyceraldehyde 3-phosphate, dihydroxyacetone phosphate, and fructose 1,6-diphosphate were observed. The physical and kinetic properties of glyceraldehyde 3-phosphate dehydrogenase prepared from human erythrocytes and skeletal muscle were almost identical, but the mode of inhibition of the enzyme was slightly different in erythrocytes and in skeletal muscle. In erythrocytes, impaired reoxidation of NADH followed by the deficiency of substrate NAD+ causes a reduction of glyceraldehyde 3-phosphate dehydrogenase activity. However, in skeletal muscle, the increased level of NADH markedly inhibits the enzyme under anaerobic conditions. A flux of triose phosphates from glycolysis occurred in skeletal muscle of a patient with A-subunit deficiency. This flux is attributable to the high cytosol alpha-glycerophosphate dehydrogenase activity in skeletal muscle. for these reasons the ATP production was significantly impaired in the patient and the damage to muscle cells brings about the release of cytosolic enzymes and muscle rigidity after hard exercise. In contrast in the erythrocytes, the level of alpha-glycerophosphate dehydrogenase is very low and another red cell-specific NADH reoxidizing system such as NADH-cytochrome b5 reductase (NADH-methemoglobin reductase) is operating. In this manner, the NAD+ level in erythrocytes is compensated for without the flux of triose phosphates derived from glucose. Therefore, the ATP production in erythrocytes is sufficiently maintained by glycolysis even in a patient with complete lactate dehydrogenase B-subunit deficiency. Thus, impaired ATP production in anaerobic stage is a condition which is specific for lactate dehydrogenase A-subunit deficiency but does not occur for B-subunit deficiency. The different clinical features of the A- and B-subunit deficiencies have been clearly elucidated.

Erythrocytes↗
PubMed1983

Antiestrogen pharmacology and mechanism of action.

Antiestrogens are nonsteroidal compounds that are capable of antagonizing many of the actions of estrogens. They have long half-lives in serum, and during their action in vivo, the antiestrogens C1628, U23,469 and tamoxifen undergo bioactivation to more polar forms that have a higher affinity for the estrogen receptor. Utilizing the high affinity antiestrogens C1628M and trans-hydroxytamoxifen in radiolabeled form, we find differences in the interaction of the estradiol receptor complex and antiestrogen receptor complex with DNA cellulose and differences in their association in the nucleus. In MCF-7 human breast cancer cells, there are marked differences in the sedimentation rate and chromatographic properties of the nuclear estrogen receptor when complexed with antiestrogen (5.5 +/- 0.06 s, 5.93 +/- 0.20 nm Stokes radius, 137,000 mol. wt) as opposed to estrogen (4.1 +/- 0.03 s, 4.84 +/- 0.20 nm Stokes radius, 83,000 mol. wt). Our data are consistent with the association of the antiestrogen receptor with an additional nuclear protein of approx. 55,000 mol. wt. This antiestrogen promoted change in receptor association with another cellular component, which may function as a possible nuclear "blocking protein" and the alterations in antiestrogen-receptor association with DNA and nuclei, may be important aspects of the estrogen antagonist and growth inhibiting properties of these compounds. In addition to binding directly to the estrogen receptor, antiestrogens can be found associated with binding sites that are distinct from the estrogen receptor. These sites are present in a wide variety of estrogen target and non-target tissues in the rat, and in estrogen receptor positive and negative human breast cancer cell lines (MCF-7, T47D, MDA-MD-231) that differ markedly in their sensitivity to antiestrogens. These sites have a subcellular distribution and ligand binding specificity very different from those of the estrogen receptor. While their wide distribution and order of binding affinities for different antiestrogens raise questions about their role in mediating directly the classically recognized estrogen antagonism of antiestrogens, these sites might alter the apparent distribution volume of antiestrogens and hence their biological potency and pharmacokinetics.

Animals↗
PubMed1982

Specific interaction of radioactive anti-androgen TSAA-291 with androgen receptor in rat prostates.

A steroidal anti-androgen ISSA-291 (16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one) bound to a macromolecular component in the cytosol of rat ventral prostates with high affinity (kd = 5.0 X 10-9 M) and in a saturable manner. The number of binding sites was comparable to that for 5 alpha-dihydrotestosterone (5 alpha-DHT). [3H]TSAA-291 binding was effectively displaced by unlabelled 5-alpha-DHT, 19-nortestosterone and cyproterone acetate but to a lesser degree by corticosterone. Glycerol density-gradient centrifugation analysis revealed that the sedimentation coefficient of the [3H]-TSAA-291-macromolecule complex was 3-4.5 S. However, when the unlabelled cytosol was fractionated by glycerol density-gradient centrifugation before the binding of [3H]TSAA-291 was examined, specific binding of [3H]TSAA-291 was observed in fractions corresponding to 8-10 S. Binding of the [3H]TSAA-291-macromolecules complex to prostatic nuclei and DNA-cellulose was considerably less than binding by the [3H]5 alpha-DHT-macromolecule complex. Instability of the TSAA-291 binding component on heat treatment before and after complex formation was also revealed and the results are discussed in terms of the anti-androgenic activity of TSAA-291.

Animals↗