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Biomedical subjects

T Kasama

Publications and source records attributed to T Kasama.

At least 145 records · Page 8Linked to original sources
PubMed1987

Branched long chain bases in cerebrosides of the guinea pig Harderian gland.

Cerebrosides obtained from the guinea pig Harderian gland were analyzed. The purified cerebrosides gave a single spot on thin-layer chromatography, the Rf value being similar to that of phrenosine obtained from whale brain. The cerebrosides consisted of 74.7% of glucosylceramide and 25.3% of galactosylceramide. The fatty acid composition of these cerebrosides was 0.7% of non-hydroxy fatty acids and 99.3% of alpha-hydroxy fatty acids. Among these alpha-hydroxy fatty acids, a small amount of methyl branched acids was detected. The substituted position of methyl branching of alpha-hydroxy fatty acids was the 16th carbon atom from the carboxyl end irrespective of the carbon chain length. The long chain bases were composed of sphinganine (78%) and sphingenine (22%). 4-D-Hydroxysphinganine was not found. The most remarkable feature of the long chain bases of cerebrosides in the Harderian gland was the presence of a large amount of methyl branched sphinganine. The cerebrosides obtained from the cerebrum and cerebellum of the same animal were also analyzed. The sugar, fatty acid, and long chain base compositions of these cerebrosides were similar to those of whale brain cerebrosides. Methyl branched sphinganine was not found in guinea pig brain.

Animals↗
PubMed1987

Inhibition of interleukin 2 by serum in healthy individuals and in patients with autoimmune disease.

To study the mechanisms that regulate the activity of interleukin 2 (IL 2) and possibly limit its activity, we have examined normal human serum for its ability to inhibit IL 2-mediated proliferation of a cloned IL 2-dependent cytotoxic T lymphocyte line (CTLL). Normal human serum contains a factor capable of inhibiting IL 2 dependent proliferation of CTLL cells. This factor is absorbed with the cells but not IL 2 molecules. The inhibitor is heat-labile and inactivated by trypsin treatment. The molecular weight of the inhibitor is 70,000-220,000. The imbalance of the inhibitor is observed in serum from patients with autoimmune disease including systemic lupus erythematosus and rheumatoid arthritis. These results suggest that the serum IL 2 inhibitor may play an important role in the in vivo regulatory mechanism of IL 2 activity and in aberrant immune functions in humans.

Arthritis, Rheumatoid↗
PubMed1987

Deficiency of interleukin 2 inhibitor activity in serum from autoimmune-prone mice.

To study the mechanisms that regulate the activity of interleukin 2 (IL 2) and possibly limit its activity, we have examined normal mouse serum for their ability to inhibit IL 2-mediated proliferation of a cloned IL 2-dependent cytotoxic T lymphocyte line (CTLL). Normal mouse serum contains a factor capable of inhibiting IL 2 dependent proliferation of CTLL cells. This factor is absorbed with IL 2-dependent cells, but not with IL 2 molecules. Decreased activity of the inhibitor is observed in serum from autoimmune-prone mice such as NZB and NZBWF 1 hybrid mice. The results suggest that the serum IL 2 inhibitor may play an important role in the in vivo regulatory mechanism of IL 2 activity and that lack of the inhibitor may be associated with aberrant immune functions.

Animals↗
PubMed1986

A simultaneous quantitation of leukotriene B4 and its omega-oxidized products by gas chromatography-mass spectrometry.

We developed a highly sensitive and specific method for the simultaneous quantitation of leukotriene B4 (LTB4) and its omega-oxidized metabolites (20-hydroxy-LTB4 and 20-carboxy-LTB4) by mass fragmentography using deuterated compounds as internal standards. The ions produced by the cleavage of the C12-13 bond of the methyl ester dimethylisopropylsilyl ether derivatives of LTB4 and its metabolites were measured by selective ion monitorings. The detection limit of LTB4 was less than 10 pg and about 100-fold lower than that by high performance liquid chromatography. By using this method, the synthesis and further metabolism of LTB4 in human polymorphonuclear leukocytes were investigated.

Gas Chromatography-Mass Spectrometry↗
PubMed1986

Effect of CS-514, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on lipoprotein and apolipoprotein in plasma of hypercholesterolemic diabetics.

CS-514, one of the derivatives of ML-236B which is an inhibitor of endogenous cholesterol synthesis, has been previously shown to effectively reduce low density lipoprotein (LDL) cholesterol in dogs, rabbits and humans. We determined the effect of CS-514 on glucose, lipid, lipoprotein and apolipoprotein (apo) levels in plasma of 8 hypercholesterolemic diabetics (2 males). Total and LDL cholesterol and apo B levels were significantly decreased (P less than 0.005) 3 months after CS-514 treatment. High density lipoprotein (HDL) cholesterol was increased (P less than 0.05). Fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) did not change throughout the observation period. No clinically serious adverse effects were experienced by the patients. We conclude that CS-514 can be a useful drug in the treatment of hypercholesterolemic diabetics and is remarkably free of any evidence of toxicity or unwanted side effects even in diabetics.

Apolipoproteins↗
PubMed1986

Biochemical diagnosis of cerebrotendinous xanthomatosis using reversed phase thin layer chromatography.

We developed a simple quantitative procedure for cholestanol in serum involving reversed phase thin layer chromatography. This procedure was satisfactory with regard to the linearity of the calibration curve in the range of 100 ng to 1,000 ng, recovery and reproducibility. Only 100 microliter of serum was needed for determination of the cholestanol concentration. Prior to thin layer chromatography, cholesterol was converted to alpha- and beta-epoxides with m-chloroperbenzoic acid, which were clearly distinguishable from cholestanol on TLC. Detection of sterols was performed by spraying with phosphomolybdic acid solution. Quantification of cholestanol was carried out with a TLC scanning densitometer. When serum cholestanol in cerebrotendinous xanthomatosis (CTX) patients was quantified by TLC, GC-MS, and GC, the correlation among the three methods was found to be approximately 1:1:1. It was found that the present method was useful for the primary diagnostic screening of CTX because of its simplicity and because many samples could be analyzed at one time.

Achilles Tendon↗
PubMed1986

Stereochemistry of 2,3-alkanediols obtained from the Harderian gland of Mongolian gerbil (Meriones unguiculatus).

The stereochemistry of the alcohol moieties of 2,3-alkanediol diacyl esters obtained from the Harderian gland of the Mongolian gerbil was investigated. There were five major 2,3-alkanediols, C14-C22 (even carbon numbers), all having the erythro configuration as determined by GC-MS analysis of their isopropylidene derivatives in comparison with synthetic erythro- and threo-2,3-hexadecanediols. 13C-NMR spectroscopy of the synthetic materials showed distinct differences of chemical shift at the C-1, C-3, and C-4 carbons, from which the native 2,3-alkanediols were definitely determined to be in the erythro series. The absolute configurations of the C-2 and C-3 asymmetric centers were assigned as 2S and 3R, respectively, based on known 2S,3R-octanediol.

Animals↗
PubMed1986

An in situ experimental model in rabbits for the study of rectal absorption.

An in situ experimental model of rectal absorption was studied in rabbits compared with in vivo determination of drug concentration in the plasma of postcaval vein using indomethacin as drug. Pharmacokinetic parameters were similar between in vivo and in situ. When results from both studies were compared, 60% of the drug administered to the rectum was absorbed from the superior hemorrhoidal vein and the remaining 40% was absorbed from the inferior hemorrhoidal vein. When an aspirin suppository was used in this model, the amount of unaltered aspirin absorbed in the rectal mucosa or space was greater than the absorbed salicylic acid which was metabolized or degradated from aspirin. In the case of insulin, these differences were not seen in the insulin concentration of venous plasma between insulin physiological saline and surfactant suspension. However, using the in situ model, the surfactant effect on rectal absorption of insulin was observed. From the above results, it was concluded that this in situ experimental model of rectal absorption has advantages in that it can be used directly to measure the rectal absorption rate and to determine ratios of easily metabolized and poorly absorbed drugs. Therefore, this model appears to be useful in evaluation of rectal absorption.

Animals↗
PubMed1986

[Effects of oxybutynin hydrochloride on the urinary bladder and urethra in in situ preparations].

Effects of oxybutynin on the urinary bladder and urethra were studied in comparison with atropine and flavoxate in cats and rabbits. Oxybutynin at 10 mg/kg, i.v., significantly inhibited the bladder contractions induced by electrical stimulation of the peripheral end in pelvic nerve. Oxybutynin was about one half the potency of atropine. On the contrary, 10 mg/kg of flavoxate, i.v., showed both effects of potentiation and inhibition. The bladder contractions induced by acetylcholine (ACh) and AHR-602 were markedly inhibited by oxybutynin and atropine. Oxybutynin was about one-fifteenth the potency of atropine. DMPP-induced contractions were inhibited by oxybutynin and atropine in a high dose, but oxybutynin was about two-fifths the potency of atropine. In addition, 3 mg/kg of oxybutynin, i.v., inhibited the contraction induced by hypogastric nerve stimulation, but 10 mg/kg of oxybutynin, i.v., significantly inhibited this contraction following initial potentiation. Oxybutynin showed an inhibitory effect on spontaneous rhythmical contraction, bladder tone and pelvic nerve discharge, similar to the effects of atropine. On the contrary, flavoxate potentiated this contraction and increased the bladder tone and pelvic and hypogastric nerve discharge. Urethra contractions induced by norepinephrine, ACh and hypogastric nerve stimulation were inhibited by oxybutynin, but not markedly. Oxybutynin and atropine dose-dependently increased the infusion volume, bladder volume capacity and micturition threshold pressure in the cystometrogram in rabbits. Flavoxate also increased them. From these results, it si suggested that oxybutynin is therapeutically a useful agent for pollakisurea nervosa.

Animals↗
PubMed1986

[Effect of oxybutynin hydrochloride on isolated smooth muscles (ileum, urinary bladder and urethra)].

Effects of oxybutynin hydrochloride on isolated smooth muscle were investigated in preparations of isolated rabbit bladder body, bladder base, collum vesicae and urethra. ACh produced a marked contraction of the preparation from the bladder body and produced no response in the collum vesicae and the urethra; however, NE caused a marked contraction of the preparations from the collum vesicae and the urethra and relaxation in the bladder body. Oxybutynin and papaverine hardly had any effect on these preparations. Effects of oxybutynin on the contractile response of the isolated ileum or urinary bladder of rabbit, guinea pig and rat in comparison with atropine, papaverine, flavoxate and other drugs were investigated. The responsibility of these preparations to ACh were approximately 100 times higher in the ileum than in the urinary bladder. Oxybutynin showed a competitive inhibition to contractile response induced by ACh in the ileum and urinary bladder, whose potency was about 1/7-1/10 that of atropine. In the ileum of rats which were treated with oxybutynin orally at a dose of 1, 10 or 100 mg/kg for 60 days, the response to ACh in the preparations of the animals treated by 100 mg/kg were decreased, but the anticholinergic action in the groups treated with oxybutynin were not significantly different compared with the nontreated or saline treated group. On the other hand, oxybutynin showed a non-competitive inhibition to contractile response induced by Ba2+, Ca2+ and histamine in the guinea pig ileum and Ba2+, high-K+, Ca2+ and ATP in the rabbit urinary bladder. These potencies of oxybutynin were equal or slightly stronger than that of papaverine or flavoxate. However, oxybutynin had no effect on the contraction induced by NE in the rabbit urethra. The above results suggest that oxybutynin has atropine-like anticholinergic action and direct muscle relaxant action evidenced by non-competitive inhibition to contractile response induced by several agonists.

Acetylcholine↗
PubMed1986

Abnormalities of cerebral lipids in GM1-gangliosidoses, infantile, juvenile, and chronic type.

Cerebral lipids of patients with GM1-gangliosidoses, infantile, juvenile, and chronic type which are caused by deficiency of beta-galactosidase, were examined and compared to each other. The infantile type demonstrated abnormal accumulation of GM1 and asialo-GM1 in contrast with marked decrease in such major cerebral lipids as cholesterol, phospholipids, cerebroside, and sulfatide. It was also noted that significant amounts of such unusual lipids as free fatty acids, GlcCer, LacCer, GbOse3Cer, and GbOse-4Cer plus nLcOse4Cer were found in the brain. These findings pointed out that this infantile type might accompany a severe cerebral dysgenesis with poor myelination. The juvenile type also showed marked increase in GM1 and asialo-GM1, but the decrease in cholesterol, phospholipids, cerebroside, and sulfatide was not so much as the infantile type. These findings along with the occurrence of cholesterol ester suggested that the brain caused progressive demyelination after the immature myelin appeared. An autopsized brain tissue of a male patient who was eventually diagnosed as a case of GM1-gangliosidosis chronic type after his death, showed some accumulation of GM1 and asialo-GM1 particularly in the caudate nucleus and putamen, whereas it showed moderate amounts of GM1 in apparently normal gray and white matters. It seemed that there are no abnormal cerebral lipids except for gangliosides and some neutral glycosphingolipids in the chronic type.

Adult↗
PubMed1985

Evidence that arachidonic acid is deficient in phosphatidylinositol of Drosophila heads.

We have found that arachidonic (20 : 4) acid is indetectable in phosphatidylinositol and diacyglycerol extracted from Drosophila heads. After careful examinations of the lipid extraction processes and fatty acid detection system (gas-liquid chromatography), we excluded the possibility of the oxidation of polyunsaturated fatty acids or of having overlooked a trace amount of the fatty acid. The precursors of arachidonic, dihomo gamma-linolenic (20 : 3), and gamma-linolenic (18 : 3) acid, were also indetectable in these lipids. On the basis of these results, it appears that the arachidonic acid cascade is essentially absent in Drosophila head, including the brain and compound eyes. Since arachidonic acid is considered to be a key molecule in phosphatidylinositol turnover in the brain, it is of interest that Drosophila brain and eyes do not require arachidonic acid for their functions.

Animals↗
PubMed1984

Cerebral and visceral organ gangliosides and related glycolipids in gm1-gangliosidosis type 1, type 2 and chronic type.

Biochemical analyses of the samples of GM1-gangliosidosis Type 1, Type 2, and Chronic type at autopsy showed that GM1 and asialo-GM1 are markedly increased in the whole cerebral tissues of patients with Type 1 and Type 2, but mainly in the basal ganglia including caudate nucleus and putamen in the Chronic Type as already reported by Kobayashi and Suzuki in 1981. On the other hand, the finding that the Type 1 visceral organs contained unusual glycolipids rather than gangliosides was contrasted to those of Type 2 which seemed less abnormal. The unusual glycolipids included particularly fucolipid I and II consisting of glucose:galactose:N-acetylglucosamine:fucose (1:2:1:1) and (1:3:2:2), respectively. The chemical structure of oligosaccharide moiety of fucolipid I may be identical with Lacto-N-fucopentaose II or Lacto-N-fucopentaose III. The fucolipid II may be proposed to be Lacto-N-difucooctanose.

Brain Chemistry↗
PubMed1984

Effects of drug-induced reduction in oxyhemoglobin affinity on survival time of mice in severe hypoxic conditions.

We studied the effect of ortho-iodo sodium benzoate (OISB) given intraperitoneally to mice. 300 and 600 mg/kg of OISB increased P50 from the control value of 41.2 mmHg to 42.7 mmHg and 45.7 mmHg, respectively. The mice were then exposed to two experimental hypoxias, namely, hypobaric hypoxia and carbon monoxide hypoxia. Mean survival time was prolonged from 67.8 (control saline) to 94.8 sec (OISB 300 mg/kg) and 112.2 sec (OISB 600 mg/kg) in the hypobaric hypoxia, and from 201.3 sec (control saline) to 329.7 sec (OISB 300 mg/kg) and 407.7 sec (OISB 600 mg/kg) in the carbon monoxide hypoxia. We concluded that OISB had prolonged survival time by reducing oxyhemoglobin affinity, thus facilitating oxygen release in severe hypoxic conditions.

Animals↗