Noboru Taniguchi

Prediction of the Distribution Volumes of Cefazolin and Tobramycin in Obese Children Based on Physiological Pharmacokinetic Concepts

So as to estimate the appropriate dose of antibacterial drugs in obese children, prediction of the volume of distribution in these children was attempted based on physiological pharmacokinetic concepts which had been constructed from results in normal-weight children. Serum concentration–time data after intravenous drip infusions of tobramycin and cefazolin were analyzed using noncompartmental analysis of obese children in whom the degree of obesity ranged from 30 to 80%. Volume of distribution at steady state (Vss) per total body weight of tobramycin was significantly less than that for normal-weight children (P < 0.05), whereas the value of cefazolin was almost equal to that for normal-weight children. The equation to express the difference of Vss between cefazolin and tobramycin obtained in normal-weight children failed in obese children, suggesting that there is a large decrease in the extracellular space in obese children exceeding the interindividual variations in normal-weight children. The Vss value (liter) for tobramycin was predicted by using the equation 0.261 · {ideal body weight (kg) + 0.4 · [total body weight (kg) – ideal body weight (kg)]}. The Vss value of cefazolin was predicted to be 0.3 · (predicted Vss of tobramycin) + 0.052 · total body weight (kg). A good correlation between the predicted and the observed Vss values was obtained.

Age differences in the pattern of urinary glycosaminoglycan excretion in normal individuals

Abstract 1. (1) Age-dependent changes of the pattern of sulfated glycosaminoglycan excretion in urine were investigated by electrophoresis on cellulose acetate membrane in 0.05 M barium acetate buffer. Clear separation between sulfated glycosaminoglycans could be achieved by this method. 2. (2) The relative proportion of urinary glycosaminoglycans resistant to testicular hyaluronidase or to chondroitinase ABC increased with advancing age. More precisely, the increase in the excretion of the materials resistant to chondroitinase ABC was characteristic of aged individuals. 3. (3) Urinary glycosaminoglycans resistant to testicular hyaluronidase were separable into two fractions by electrophoresis or ion-exchange column chromatography. Chemical analysis and enzymatic susceptibility of these materials suggest that these two fractions might be composed of heparan sulfate and dermatan sulfate, respectively. 4. (4) The electrophoretic patterns of glycosamonoglycans in Hurler-Hunters urine were quite different from that of normal urine. The relative proportions of dermatan sulfate, heparan sulfate and chondroitin sulfate A/C were important for the differentiation between Hurler and Hunter syndrome.

Characterization of glycosaminoglycans in rabbit plasma and leukocytes at disaccharide subunit level

Abstract The glycosaminoglycans in rabbit plasma were found exclusively in the protein fraction precipitated with trichloroacetic acid. The concentration, estimated as glucuronic acid, was approximately 100 μg per 100 ml of plasma. Electrophoretic characteristics and disaccharide subunit assay with chondroitinase indicated that the major glycosaminoglycans in rabbit plasma were chondroitin 4-sulfate and undersulfated chondroitin 4-sulfate. Although electrophoretic mobility and enzymatic susceptibility suggested the presence of a small amount of hyaluronic acid in rabbit plasma, the disaccharide subunit assay failed to demonstrate the existence of this material. The glycosaminoglycan content of rabbit marrow cells was about 150 μg of glucuronic acid per 100 mg dry weight. The disaccharide subunit assay indicated the major glycosaminoglycan in rabbit marrow cells to be chondroitin 6-sulfate. Chondroitin 4-sulfate, dermatan sulfate and hyaluronic acid were also identified as minor constituents. The chondroitinase AC-II digests of the glycosaminoglycans in marrow cells contained another ultraviolet-absorbing spot which was slower in migration rate on chromatography than the reference disaccharides and was completely degraded by chondroitinase ABC. These results suggest that a hybrid structure might be present in dermatan sulfate obtained from rabbit marrow cells but the exact nature of this material is still to be elucidated.

Diagnosis of genetic mucopolysaccharidoses: Electrophoretic and enzymatic characterization of urinary glycosaminoglycans

Abstract Urinary glycosaminoglycans from healthy children and the patients with genetic mucopolysaccharidoses (Type I, II, and III) were characterized by means of electrophoresis on cellulose acetate membrane in barium acetate buffer and of enzymatic method with chondroitinase. The amounts of chondroitin sulfate A C , dermatan sulfate, and heparan sulfate calculated on the basis of electrophoretic pattern agreed well with those estimated by enzymatic method. The electrophoretic pattern seemed to be specific for a certain genotype; at least, for Hurler, Hunter, and Sanfilippo syndromes. Therefore, electrophoretic separation of urinary glycosaminoglycans was suitable for the tentative classification of these mucopolysaccharidoses. There were no significant qualitative differences in disaccharide subunits of urinary chondroitin sulfate isomers between normal individuals and the patients with mucopolysaccharidoses. But, the urinary excretion of chondroitin sulfate A C in almost all the patients with these genotypes was approximately twice the amounts in normal individuals.

Characterization of glycosaminoglycans in human leukocytes: Enzymatic subunit assay of isomeric chondroitin sulfates

Abstract The leukocytes of human peripheral blood contained glycosamino-glycans at the level of 100 μg of glucuronic acid per 100 mg of the dry weight of defatted material. The major portion was chondroitin 4-sulfate. However, the disaccharide subunit assay with chondroitinase indicated that, in addition to unsaturate 4-sulfated disaccharide, the glycosamino-glycans in human leukocytes contained considerable amounts of unsaturated nonsulfated disaccharide as a constituent. The electrophoretic pattern in 0.1 m HCl also suggested that the isomers of chondroitin 4-sulfate type were heterogeneous with regard to the degree of sulfation. The presence of chondroitin 6-sulfate, dermantan sulfate, and hyaluronic acid could not be demonstrated by means of electrophoretic analysis and of disaccharide subunit assay. A small fraction of these polysaccharides was resistant to chondroitinase ABC digestion. This material corresponded in electrophoretic mobility closely with authentic heparan sulfate. These electrophoretic characteristics and the results of chemical analyses of this material suggested that heparan sulfate might be a minor constituent of glycosamino-glycans in human leukocytes.

Separation and Identification of Glycosaminoglycans

Abstract The term “mucopolysaccharides” was originally introduced by Meyer to describe “hexosamine-containing heteropolysaccharides of animal origin occurring in a pure state or as protein salts”. Many of the names originally assigned to the mucopolysaccharides have since been revised in an effort to systematize the nomenclature (Table 1). Jeanloz2 in 1960 proposed the term “glycosaminoglycuronoglycans” in place of mucopolysaccharides as in most cases they are composed of amino sugars (glycosamino-) and uronic acids (glycurono-) joined in long chains(-glycans). For the sake of simplicity, the term “glycosaminoglycans” is getting acceptance in place of the rather lengthy term “glycosaminoglycuronoglycans” as well as the old and perhaps more familiar term “mucopolysaccharides”. As a matter of convenience, the term “polysaccharides” will be frequently used here, instead of glycosaminoglycans.

Subunit structure of isomeric chondroitin sulfates from normal human urine.

Abstract In addition to the well-known 4-sulfated, 6-sulfated, and non-sulfated disaccharide subunits, chondroitinase AC-digests of urinary glycosaminoglycans from normal individuals contained two kinds of oversulfated disaccharides as minor structural subunits. The results of the digestion with chondrosulfatases indicated that one of these oversulfated disaccharides might be Δ 4 -glucuronido - acetylgalactosamine - 4,6-disulfate, while the other seemed to be Δ 4 -sulfoglucuronido - acetylgalactosamine-6-sulfate. Chondroitinase ABC-digests of urinary dermatan sulfate also contained an oversulfated disaccharide as a minor structural subunit which appeared to be a derivative of 4-sulfated disaccharide bearing an extrasulfate residue on the uronic acid moiety, Δ 4 -sulfoglucuronido-acetylgalactosamine-4-sulfate. One hybrid oligosaccharide was identified in the chondroitinase AC-digests of urinary glycosaminoglycans. It was degraded by chondroitinase ABC to yield 4-sulfated and 6-sulfated disaccharides at a molar ratio of 3 to 1. These results suggested that hybrid structure might be present in urinary dermatan sulfate chains.

An autopsy case of lymphopenic hypogammaglobulinemia

A case of an infant with severe developmental failure of the thymus and the lymphoid tissues, and with IgG globulin level of 120 mg per 100 ml and peripheral lymphocyte count of 500 per mm3 at the terminal stage of the illness is reported. A criterion of congenital lymphopenic hypogammaglobulinemia was briefly discussed. ACTA PATH. JAP. 17: 465–473, 1967