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Biomedical subjects

T Kasama

Publications and source records attributed to T Kasama.

At least 109 records · Page 6Linked to original sources

Cerebrotendinous xanthomatosis: clinical and biochemical evaluation of eight patients and review of the literature.

We present the clinical and laboratory findings of 8 patients with cerebrotendinous xanthomatosis. The clinical features consisted of a combination of bilateral Achilles tendon xanthomas, cataracts, low intelligence, pyramidal signs, cerebellar signs, convulsions, peripheral neuropathy, foot deformity, cardiovascular disease or atherosclerosis, EEG abnormality, and increased CSF protein. Increased cholesterol was present in the serum, CSF and red cell membrane of all 8 patients. The bile of one patient with late age onset of the disease showed an attenuated production of bile acids and bile alcohols. Three of the 7 had obstruction and/or marked narrowing of the coronary arteries. Data on 136 patients reported throughout the world are reviewed.

Achilles Tendon↗

Effects of dietary glucose or fructose on the secretion rate and particle size of triglyceride-rich lipoproteins in Zucker fatty rats.

Effects of dietary carbohydrate on the secretion rate and particle size of triglyceride-rich lipoproteins were examined in Zucker fatty rats fed fructose and glucose and were compared with those of Zucker lean rats. Carbohydrates were supplied as 10% drinking solutions for 14 days. As compared with lean rats, Zucker fatty rats had hyperinsulinemia and hypertriglyceridemia associated with an increased rate of triglyceride secretion into the circulation. Feeding fructose and glucose to fatty rats produced an increase in plasma glucose levels, whereas plasma insulin concentrations did not show significant changes. Neither fructose nor glucose supplementation produced significant changes in the rate of triglyceride secretion. Despite this, plasma triglyceride concentrations in fructose-fed fatty rats were twice as high as those in glucose-fed rats or those receiving no supplementary carbohydrate. Particle diameters of lipoproteins of density between 0.96 and 1.006 were larger in fructose-fed fatty rats than in those receiving no sugar. The results suggest that feeding fructose, but not glucose, into fatty rats is associated with an impairment of triglyceride removal and a resultant increase in plasma triglyceride concentration, the latter of which is accompanied by an increase in triglyceride contents in each particle.

Animals↗

Composition of long chain bases in ceramide of the guinea pig Harderian gland.

Ceramide of the guinea pig Harderian gland was isolated and characterized. The purified ceramide gave two spots on thin-layer chromatography. Ceramide with the higher Rf value (NHCer) contained non-hydroxy fatty acids and that with the lower Rf value (HCer) contained 2-hydroxy fatty acids. The ratio of NHCer to HCer was 6:1. The non-hydroxy fatty acids of NHCer were composed of straight-chain acids (94.9%) and branched-chain acids (5.1%). The 2-hydroxy fatty acids were also composed of straight-chain acids (94.2%) and branched-chain acids (5.8%). The ratio of straight-chain acids to branched-chain acids was similar in NHCer and HCer. The long chain bases of NHCer and HCer consisted of straight chain sphinganines and sphingenines, and methyl-branched long chain bases. In NHCer, 59.9% of the total bases were methyl branched, and in HCer, 48.3%. The characteristics of ceramide, that is, the large amount of methyl-branched long chain bases and relatively small amount of methyl-branched fatty acids, are similar to those of cerebroside and sphingomyelin isolated from the same organ, although the ratios of constituents are different among these sphingolipids.

Animals↗

Isolation and characterization of a monosialosylgangliopentaosyl ceramide from Xenopus laevis oocyte.

A monosialosylgangliopentaosyl ceramide was isolated from Xenopus laevis oocytes. It represented 5.8% of the total acidic glycosphingolipids. From the results of sugar-composition analysis, enzymatic hydrolysis, permethylation analysis, and negative ion fast atom bombardment mass spectrometry, the structure of the ganglioside was determined to be as follows: [sequence: see text] The predominant species of fatty acids were alpha-hydroxy fatty acids, h22:0, h24:0, and h24:1. The long chain bases of this ganglioside consisted mainly of d18:1 sphingosine and phytosphingosine. Other acidic glycolipids were also characterized. The most abundant component of acidic glycolipids was sulfatide, which represented 85.7% of the total acidic glycolipid mixture. GM3, GM2, GM1a, and GD1a were also detected.

Animals↗

Lysosomal enzyme activities in experimental granulomatous inflammation.

Foreign-body (dextran beads) and hypersensitivity (antigen-coupled agarose beads) lung granulomas were induced in BALB/c mice by the intratracheal injection of beads. Large granulomas developed, which reached peak intensity within 3 days and declined in size thereafter. Aqueous extracts of both granulomas contained high levels of lysosomal enzymes N-acetyl-beta-D-glucosaminidase (NAG) and lysozyme. Lysosomal enzyme activities in the extracts correlated with granuloma sizes. Dispersed granuloma cells were able to produce these enzymes. These results suggest that lysosomal enzymes may reflect the activity/size of granulomatous inflammation.

Acetylglucosaminidase↗

Pharmacological activities of the prenylcoumarins, developed from folk usage as a medicine of Peucedanum japonicum THUNB.

In connection with the chemical structure of coumarin 1 (a mixture of acetylangeloylkhellactone and acetyltigloylkhellactone), a compound isolated from Peucedanum japonicum THUNB., we synthesized eight coumarin compounds (3-10) and performed pharmacological studies on these nine compounds, as well as on another coumarin, praeruptorin A (= Pd-Ia) (2), a compound isolated from Peucedanum praeruptorum DUNN. We studied the effects of compounds 1-5 on isolated smooth muscle and of compounds 1-10 on the cardiovascular system. These compounds showed dose-related antagonistic effects on histamine- and Ca(2+)-induced contractions in smooth muscle and the potencies were in the order 2 greater than 1 greater than seselin (3) greater than xanthyletin (4) = 2.2.10-trimethyl-2H,8H-benzo[1,2-b: 3,4-b']dipyran-8-one (5). All the compounds except 7-geranyloxy-4-methylcoumarin (10) produced a dose-related increase in vertebral, carotid and femoral blood flow. Compounds 1, 5, and 4-methyl-7-(3-methyl-2-butenyloxy)coumarin (8) caused an increase in blood pressure, but 3 and 4 caused a slight decrease. Compounds 2, 3, 4, 5, and 8 increased heart rate. Jatamansinone (6) and jatamansinol (7) caused only slight changes in blood pressure. All the compounds except 10 increased heart rate. Compound 1 also increased blood flow in the cerebral cortex. Thus, compound 1 was confirmed to have an inhibitory effect on contraction in isolated smooth muscle and an action increasing arterial blood flow. Among the compounds tested in this study, 3, as well as 6 and 7 synthesized on the basis of 3, showed actions similar to those of Ca2+ blockers and some compounds had papaverine-like activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

High levels of plant sterols and cholesterol precursors in cerebrotendinous xanthomatosis.

We measured the cholestanol, cholesterol precursor (lathosterol), and plant sterol (campesterol and sitosterol) concentrations of serum and bile in 11 patients with cerebrotendinous xanthomatosis. The mean values of serum cholestanol, lathosterol, campesterol, and sitosterol were, respectively, 8.4-, 2.5-, 2.7-, and 1.4-times higher in the patients than in normal control subjects (n = 26). Cholestanol (6.7-fold) and campesterol (3.7-fold) levels in bile (n = 4) were also elevated in the patients. There was no significant difference of serum sterol levels between patients with coronary artery disease and those without it. Chenodeoxycholic acid treatment for periods ranging from 6 months to 3 years and 4 months lowered serum lathosterol (57.7% reduction) and campesterol (57.8%) levels in parallel with cholestanol (70.8%) level, but the sitosterol level (19.7%) decreased less. Thus, increased levels of cholesterol precursor (lathosterol), plant sterols (campesterol and sitosterol), and cholestanol were found in the serum and bile in cerebrotendinous xanthomatosis. Chenodeoxycholic acid treatment effectively reduced the levels of these sterols, except for sitosterol.

Adult↗

Involvement of interleukin-1-like factor(s) in type II collagen-induced arthritis in mice.

To explore the role of interleukins in development of arthritis, we induced collagen-induced arthritis in mice and examined interleukin activities in the inflamed joints. Arthritis developed in 90% of mice 4-5 weeks after primary immunization with type II collagen. Joint extracts from mice with collagen-induced arthritis contained high levels of interleukin 1 (IL-1)-like activity but not interleukin 2 (IL-2) or interleukin 4 (IL-4) activity. IL-1-like activities in the lesions were correlated with development of arthritis assessed by joint swelling and erythema. These results suggest that IL-1-like factor(s) may participate in the etiopathogenesis of collagen-induced arthritis in mice.

Animals↗

Abnormal movements in brindled mutant mouse heterozygotes: as related to the development of their offspring--biochemical and morphological studies.

As a possible preventive measure for brain dysfunction in Menkes disease, prenatal treatment by maternal administration of zinc, vitamin E and copper was examined in brindled mutant mice. During pregnancy and lactation, female heterozygous mice received 20 ppm zinc or 0.004% alpha-tocopherol acetate (vitamin E) throughout and 6 ppm copper from gestational day 13 in the drinking fluid, ad libitum. The maternal administration of zinc and vitamin E, as antioxidants, or copper resulted in decreased fetal and neonatal death of offspring, especially those of hemizygous males, as compared with the administration of water only. When offspring did not grow, maternal abnormal movements, which comprised rotatory movements of high speed with tremor and ataxia, were frequently observed. In the heterozygotes with abnormal movements, the level of lipid peroxidation in cerebrum and the concentration of copper in kidney were much higher than those in the heterozygotes with normal movement. Morphologically, in cerebellum of the heterozygotes with abnormal movements, the loss of Purkinje cells, abundance of lipofuscin granules and abnormal mitochondria or degenerative bodies of high electron density were frequently observed, as compared with heterozygotes with normal movement. These findings suggest that the development of hemizygous male mice may be influenced by both copper and oxygen radical metabolism.

Animals↗

Regulation of Mycobacterium bovis BCG and foreign body granulomas in mice by the Bcg gene.

Natural bactericidal resistance to Mycobacterium bovis BCG is under the control of a single gene, designated Bcg. Lung granuloma formation in susceptible (Bcgs) and resistant (Bcgr) mice was studied in two sets of Bcg-congenic systems, namely, the BALB/c (Bcgs)-C.D2 (BALB/c.Bcgr) pair and the B10.A (Bcgs)-B10.Ar (Bcgr) pair, by using BCG as well as foreign body granuloma-inducing agents (dextran beads). Large granulomas of the lung induced by the intratracheal instillation of either BCG or dextran beads developed in Bcgs mice. In contrast, minimal inflammation was produced in Bcgr mice given BCG or dextran beads. Aqueous extracts prepared from pulmonary granuloma lesions induced by Bcgs mice by either BCG or dextran beads contained high levels of interleukin-1 (IL-1) activity but not interleukin-2 (IL-2) or interleukin-4 (IL-4) activity. Very low IL-1 activity was detected in extracts from Bcgr mice injected with BCG and dextran beads. The activity of IL-1 was correlated closely with the activity and size of the granulomatous inflammation in mice. These results suggest that pleiotropic effects of the Bcg gene are involved in the development of granulomas induced by either BCG or nonspecific foreign body agents (dextran beads) and that monokines participate in granuloma formation.

Animals↗

Composition of long-chain bases in sphingomyelin of the guinea pig Harderian gland.

Sphingomyelin from the guinea pig Harderian gland was isolated and characterized. The purified sphingomyelin gave a broad spot on thin-layer chromatography. The fatty acid composition of the whole sphingomyelin was 71% nonhydroxy acids and 29% 2-hydroxy acids. Methyl-branched fatty acids were only 2% of the total acids. The long-chain bases were composed of straight-chain sphingenines (50%) and sphinganines (6%). Methyl-branched long-chain bases were 44% of the bases. The sphingomyelin was further separated into four fractions (I, II, III, IV) by high-performance liquid chromatography. The ratio of fractions I, II, III, and IV was approximately 2:5:2:1, respectively. The fatty acids of fractions I and II consisted of nonhydroxy acids and those of fractions III and IV were 2-hydroxy acids. The long-chain bases of fractions I and III were sphinganines including 10-, 9-, and 8-methylsphinganines and anteiso-sphinganines. These methyl-branched bases occupied about 70% of the total sphinganines. The long-chain bases of fractions II and IV consisted of sphingenines. The methyl-branched unsaturated bases were only 30% of the total sphingenines, all in the anteiso-form. Thus, the sphingomyelin obtained from guinea pig Harderian gland had complex compositions of fatty acids and long-chain bases, and half the number of long-chain bases had methyl branches. The methyl-branched fatty acids were only a minor component. These characteristics are similar to those of cerebrosides isolated from the same source.

Animals↗

Antibodies to interleukin 2 in sera of autoimmune-prone mice.

Autoimmune-prone mice spontaneously develop the disease characterized by autoantibodies to a wide variety of antigens. In the present study, we have demonstrated that IgG antibodies to interleukin 2 (IL-2) are to be found in serum of autoimmune mice in association with ageing. These antibodies can neutralize the biological activity of IL-2 and thus play an important role in the etiopathogenesis of autoimmune disease.

Aging↗

Effects of dietary sucrose on age-related changes in VLDL-triglyceride kinetics in the rat.

The effects of sucrose feeding on in vivo kinetics of triglyceride metabolism were compared in rats aged 2 and 12 months. Sucrose was supplied as a 10% solution in their drinking water for 2 weeks. Although plasma triglyceride concentrations doubled with age, total triglyceride secretion rates for the whole rat (mg/min/rat) increased by 40%, suggesting a decrease in the efficiency of triglyceride removal from plasma with aging. The rate of triglyceride secretion per unit body mass (mg/min/kg body weight), however, decreased by 40% as the rats grew to 12 months of age. These age-related differences were statistically significant only in rats receiving supplementary sucrose. Feeding sucrose to rats of both ages doubled the secretion rates of triglyceride not only for the whole rat but also per unit body mass. However, it tripled triglyceride concentrations, implying that the sugar decreases the removal efficiency of plasma triglyceride equally in rats at either age. Fasting hypertriglyceridemia induced by sucrose supplement was much greater in old rats than in young rats (162 +/- 30 vs. 80 +/- 8 mg/dl). The present studies demonstrate that dietary sucrose enhances age-related changes in triglyceride kinetics in the rat.

Aging↗

Combined effect of exogenous insulin and sucrose on alterations in plasma lipoproteins induced by cholesterol feeding in the rat.

We have recently reported increased cholesterol concentrations in high-density and very-low-density lipoproteins (HDL and VLDL) in sucrose-fed rats with exogenous hyperinsulinemia. In order to see if exogenous hyperinsulinemia has any effect on the alterations in plasma lipoproteins induced by cholesterol feeding, we fed a cholesterol-rich diet supplemented with lard, cholic acid and propylthiouracil to hyperinsulinemic, sucrose-supplemented rats and examined plasma lipoprotein profiles. Three control groups were investigated: one receiving chow only, the other receiving a cholesterol-rich diet, the third receiving exogenous insulin, sucrose, and no cholesterol-rich diet but chow. Hyperinsulinemia was induced by a constant s.c. infusion of porcine insulin (6 U/day) from an osmotic minipump. Insulin infusion plus sucrose produced an increase in HDL cholesterol concentrations similar to that seen in the previously reported injection model in the face of no change in total and low-density lipoprotein (LDL) cholesterol. Rats receiving a cholesterol-rich diet but no insulin developed marked hypercholesterolemia characterized by an elevation of cholesterol not only in LDL but also in intermediate-density lipoprotein (IDL) and VLDL. Infusing insulin into cholesterol-fed rats produced a further increase in IDL and VLDL cholesterol but was not accompanied by any further increase in LDL cholesterol. HDL cholesterol was decreased below normal.

Animals↗

Neutrophil chemotaxis, phagocytosis and parameters of reactive oxygen species in human aging: cross-sectional and longitudinal studies.

To assess the effect of aging on neutrophil (PMN) functions and the parameters related to reactive oxygen species (ROS), we measured the following in blood samples from 166 asymptomatic aged individuals: PMN activities including chemotaxis, phagocytosis and generation of ROS; the activity of superoxide dismutase (SOD) of blood cell; and serum lipid peroxide levels. Compared with non-aged adults, the older individuals showed markedly attenuated PMN chemotaxis, and slightly elevated serum lipid peroxide levels. Other parameters were not significantly different between the two aged groups. In contrast both to the elderly group as a whole and to the subgroup 65 to 79 years old, the subjects over greater than or equal to 80 years old showed normal PMN chemotaxis and serum lipid peroxide levels, as defined by the young adult control group. Thirty-two subjects who entered the study at ages 69 to 72 years were followed with serial assays for seven years; twenty-one of these subjects died during this observation period. There was a striking and significant difference between the survivors and nonsurvivors with regard to PMN chemotaxis and serum lipid peroxide levels; even when asymptomatic upon initial examination, the nonsurvivors showed diminished PMN chemotaxis and elevated lipid peroxide levels. It seems from both the cross-sectional and longitudinal parts of our study that PMN chemotaxis and serum lipid peroxide levels correlate with survival to advanced age.

Adolescent↗

Production of interleukin 1-like factor from human peripheral blood monocytes and polymorphonuclear leukocytes by superoxide anion: the role of interleukin 1 and reactive oxygen species in inflamed sites.

In the present study, we investigated the possibility that oxidative stress to human peripheral blood monocytes and polymorphonuclear leukocytes (PMNs) can induce interleukin 1 (IL-1)-like activity. Oxidative stress that we used was superoxide anion (O2-) and hydrogen peroxide (H2O2). O2-, but not H2O2, could induce an IL-1-like factor(s) from monocytes and PMNs. IL-1-like activity from monocytes and PMNs induced by O2- was due to de novo synthesis because no IL-1-like activity was found in culture supernatants and in the lysate of unstimulated cells. We next examined the effects of radical scavengers on production of an IL-1-like factor(s). Generation of IL-1-like activity from monocytes was amplified by preincubation with catalase (H2O2 scavenger), although it was suppressed by preincubation with either superoxide dismutase (O2- scavenger) or vitamin E (antioxidant analogs). These results suggest that production of an IL-1-like factor(s) from monocytes and PMNs was due to O2- stimulation. Our data that production of an IL-1-like factor(s) from inflammatory cells by stimulation with O2- imply a model of the up-regulation mechanism of inflammation mediated by enhanced IL-1-like factor production stimulated with reactive oxygen species.

Glucose Oxidase↗

Hair copper and zinc concentrations in the Rett syndrome.

The hair copper and zinc concentrations in patients with the Rett syndrome in 9 hospitals or institutions, and female age-matched controls were investigated. The copper and zinc concentrations in the 23 patients were 15.1 +/- 3.6 and 177 +/- 20 micrograms/g dry weight (mean +/- SD), respectively, and those in the 22 controls were 14.7 +/- 3.4 and 181 +/- 22, respectively. No significant differences were detected between the copper or zinc concentrations in the patients and controls. The copper and zinc concentrations did not change with age, or the hospital or institution. The ratio of the copper and zinc concentrations was also constant. We conclude that the hair copper and zinc concentrations in patients with the Rett syndrome are the same as those in controls.

Adolescent↗