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Biomedical subjects

R K Yu

Publications and source records attributed to R K Yu.

269 records · Page 15Linked to original sources
PubMed1976

Gamma hydroxybutyrate. Correlation of serum and cerebrospinal fluid levels with electroencephalographic and behavioral effects.

Gamma hydroxybutyrate was administered to adult cats by intravenous infusion at varying dosages while an electroencephalogram (EEG) was recorded from electrodes placed stereotactically in the right and left hippocampus and thalamic intralaminar nucleus and from cortical electrodes. Blood cerebrospinal fluid samples were assayed for gamma hydroxybutyrate. The first EEG change, slowing was occasional spikes, was seen at serum levels of 75 mug per milliliter. Changes in the recordings progressed through a number of stages, culminating in bursts of poly spiking interspersed among periods of electrical silence first seen at 350 mug per milliliter. Behavior was characterized by a progressively deepening trancelike state punctuated at higher serum levels by spontaneous and stimulus-induced myoclonic jerks. These changes were correlated with serum levels and are more similar to petit mal stupor than any kind of natural sleep-like state previously used to describe them.

Animals↗
PubMed1972

Gangliosides of human, bovine, and rabbit plasma.

Gangliosides were isolated from human, bovine, and rabbit plasma and were quantified by gas-liquid chromatography. Purification was achieved by sequential use of partitioning in solvents, DEAE-Sephadex chromatography, base treatment, and silicic acid chromatography. Human and bovine plasma yielded slightly more than 1 micro mole of lipid-bound sialic acid/100 ml; for rabbit plasma the value was 0.28 micro mole/100 ml. The total bovine plasma ganglioside fraction contained equal amounts of N-acetylneuraminic and N-glycolylneuraminic acids, rabbit plasma gangliosides had about 1% of the latter, and the human plasma sample contained only the former. Thin-layer chromatography revealed important differences among the plasmas from the three species, but all possessed hematosides and hexosamine-containing gangliosides. The approximate ratios of these two categories, based on sialic acid content, were (hematosides: hexosamine-type): human, 2:1; rabbit, 3:2; and bovine, 2:3. The fatty acid compositions of both categories were characteristic of extraneural gangliosides and included six major acids: palmitic, stearic, behenic, tricosanoic, lignoceric, and nervonic. The major long-chain base in each sample was sphingosine, while only a trace of the C(20) isomer was detected.

Animals↗
PubMed1970

Gas--liquid chromatographic assay of lipid-bound sialic acids: measurement of gangliosides in brain of several species.

A method is described for analysis of gangliosides by GLC assay of the sialic acid component. Mild acid treatment in methanol converted the latter to methyl ketoside methyl ester, which was then chromatographed as the TMS derivative. The major methanolysis product was shown to be the beta-anomer, and its chromatographic peak was used for quantification. NANA and NGNA could be analyzed simultaneously, while an O-acetylated derivative of NGNA was detected qualitatively. Standard curves were obtained for the three following representative samples: (a) a mixture of beef brain gangliosides, (b) Tay-Sachs ganglioside, and (c) hematoside-NANA. These had different slopes which reflected the variation in yield of beta-NANA obtained from methanolysis. The smallest sample analyzed in the present study contained 0.3 micro g of NANA. The advantage of GLC in solving the problem of false chromogens is illustrated in a comparative study with two colorimetric procedures. Two columns are described whose combined use is highly effective in establishing identity and in eliminating false peaks when they arise. The GLC method has been applied to analysis of the total brain ganglioside content of several species, and a general trend was observed toward decreasing levels in the lower vertebrates. In addition, NGNA was detected and quantified in several of these samples.

Adrenal Medulla↗
PubMedDate not supplied

Heterogeneity of antibody specificity in Taiwanese patients with polyneuropathy and IgM paraproteinemia.

About half of the Caucasian patients with chronic polyneuropathy and IgM paraproteinemia show serum anti-myelin-associated glycoprotein (MAG) and anti-sulfoglucuronosyl glycosphingolipid (SGGLs) activities. These antibody activities have been demonstrated to react with a carbohydrate epitope known as the HNK-1 or sulfoglucuronic acid (SGA) epitope. However, in Asian populations the occurrence of serum anti-SGA activities has been reported to be relatively rare. We investigated 5 cases of chronic polyneuropathy with IgM paraproteinemia from Taiwan and found that 3 of them had high-titer serum anti-SGA (SGGL/MAG) antibody activities. The clinical symptoms of these 3 patients were consistent with sensory dominant polyneuropathy with a severer involvement of the lower limbs than of the upper limbs. Electromyography and nerve conduction studies revealed severe sensory nerve involvement (no response in 3 cases) and moderate slowing of motor conduction velocity (MCV) without conduction block. The decrease in MCV correlated well with anti-SGA antibody titer (less than 30 m/s with the titration of 1:12, 800, normal 55-60 m/s). Pathological findings showed active demyelinating polyneuropathy with myelin ovoid and myelinated fiber loss. Our data suggest that anti-SGGL antibody activities may not be very rare among Asian populations. Additionally, there seems an intriguing possibility that the titer of this antibody correlates with the severity of peripheral nerve involvement in patients of demyelinating polyneuropathy with IgM paraproteinemia.

Aged↗
PubMedDate not supplied

Role of tumor-associated gangliosides in cancer progression.

Neuroectodermic tumors can mostly be characterized by the presence of tumor-associated glycosphingolipid antigens, such as gangliosides, defined by monoclonal antibodies. Recently, cumulative evidence indicates that gangliosides modify the biological effects of several trophic factors, in vitro and in vivo, as well as the mitogenic signaling cascade that these factors generate. The functional roles of gangliosides in tumor progression can be revisited: (i) ganglioside antigens on the cell surface, or shed from the cells, act as immunosuppressors, as typically observed for the suppression of cytotoxic T cells and dendritic cells, (ii) certain gangliosides, such as GD3 or GM2, promote tumor-associated angiogenesis, (iii) gangliosides strongly regulate cell adhesion/motility and thus initiate tumor metastasis, (iv) ganglioside antigens are directly connected with transducer molecules in microdomains to initiate adhesion coupled with signaling, and (v) ganglioside antigens and their catabolites are modulators of signal transduction through interaction with tyrosine kinases associated with growth factor receptors or other protein kinases. Given the potential importance of these sialylated gangliosides and their modulating biological behavior in vivo, further studies on the role of gangliosides are warranted.

Adjuvants, Immunologic↗
PubMedDate not supplied

The effect of storage on the ganglioside content of human platelets.

Gangliosides are glycolipids which contain sialic acid and are found in the membranes of mammalian cells. By analogy with recent studies of other cells, it is possible that gangliosides play a role in the membrane functions and in vivo survival of platelets. In order to determine if ganglioside destruction plays a role in the storage-induced loss of platelet viability and function (storage lesion), the ganglioside content of platelets was measured after 24 and 96 hours of storage. Samples were taken from platelet concentrates that were stored either on a flat-bed shaker (n = 6) or on a circular rotator (n = 6). Total ganglioside content was determined colorimetrically from the total lipid extracts of purified platelet pellets using the Svennerholm resorcinol method. Ganglioside GM3 content was determined by Folch partitioning, high performance thin-layer chromatography, and densitometric scanning. Ganglioside content, measured as microgram of lipid-bound sialic acid per 10(10) platelets, was significantly decreased (p less than 0.005) between 24 and 96 hours of storage, whether measured as total or GM3 ganglioside. The mean values +/- SEM at 24 and 96 hours of storage were 9.4 +/- 0.6 and 6.7 +/- 0.6, respectively (n = 12 for each). These data indicate that storage causes irreversible loss of membrane ganglioside, which may be detrimental to the function and in vivo survival of platelets.

Blood Platelets↗
PubMedDate not supplied

Modulation of phospholipases A2 and C activities against dilauroylphosphorylcholine in mixed monolayers with semisynthetic derivatives of ganglioside and sphingosine.

Most of the semisynthetic ganglioside and sphingosine derivatives studied here decreased the rate as well as the extent of hydrolysis of monomolecular layers of dilauroylphosphorylcholine (dlPC) by both phospholipase A2 (PLA2) and C (PLC). For PLA2, the rate of enzymatic activity was inversely correlated (p < 0.001) with the duration of the latency period of the enzymatic reaction. The correlation between the rate of activity and the latency period was not statistically significant for PLC. The potency to inhibit PLA2 and PLC was not significantly correlated with the presence of specific chemical groups. Also, the inhibitory effect is not correlated to changes of the substrate intermolecular spacing or surface potential caused by the sphingolipids (SLs). Conversely, for PLA2 the variation of the kinetic parameters of the reaction with the molecular polarization vector of the SLs are statistically significant (p < 0.01). The rate of phospholipid degradation by PLA2 decreased, and the lag times tended to become longer, with increasing values of the SLs' polarization vector. The kinetic parameters of the reaction with PLC did not show statistically significant correlation with the polarization vector of the SLs. Our results suggest that the configuration of the electrostatic field across the interface is more important than are formal charges or specific chemical moieties in modulating the activity of PLA2. Inhibition of phospholipase activities of these types by specific SLs or their metabolites may be important as supramolecular regulatory steps at the membrane level of the amplification of lipid-mediated signaling pathways.

Carbohydrate Sequence↗
PubMedDate not supplied

Ganglioside changes associated with temporal lobe epilepsy in the human hippocampus.

To understand better the molecular and cellular events associated with status epilepticus, a multifaceted analysis has begun on hippocampal tissues therapeutically removed from patients with temporal lobe epilepsy. In this first study, quantitative changes in major ganglioside species are reported, as well as the immunocytochemical localization on the ganglioside GD3 in epileptic human hippocampus. Although significant variations were found between patients, the pattern of change was consistent when compared to normal values obtained from an autopsied specimen and the literature. Total ganglioside content was reduced in epileptic hippocampi, which was attributable, in part, to pyramidal cell loss found in CA1 and CA3. In each case, the percentage of ganglioside GD3 was increased significantly, while ganglioside GD1a decreased. The former change is probably associated with reactive astrocytosis and the latter with loss of neuronal dendrites. Immunocytochemical localization revealed GD3 in the stratum radiatum and the subgranular layer of the dentate gyrus. In these areas, GD3 was present in punctate structures and astrocytes. These findings indicate that GD3 increases in selected areas of the sclerotic hippocampus and is presumably related to localized accumulation of reactive glial cells. Since gangliosides have a high affinity for calcium and localized increase in extracellular calcium could disrupt normal neuronal function, the localized increase in GD3 may not only denote reactive glial cells but may contribute directly to the altered, hyperexcitable condition of epilepsy.

Chromatography, Thin Layer↗
PubMedDate not supplied

Heritability and biochemistry of gangliosidosis in emus (Dromaius novaehollandiae).

The progeny of two emu breeder pairs, which had a history of producing offspring with gangliosidosis, were monitored for 15 mo. DNA fingerprinting revealed that individuals in each breeder pair were not related to each other. One breeder pair had 13 progeny that reached or exceeded the age of 1 mo, and six of these progeny developed gangliosidosis. The mean age at which these affected emus were euthanatized, with distinct neurologic disease, or died was 5.7 mo. The second emu pair had 13 progeny, seven of which developed gangliosidosis, with a mean age of euthanasia/death of 4.6 mo. Affected emus died or were euthanatized from 2 to 8 mo of age. The primary clinical sign in the affected emus was mild to severe ataxia. Severe hemorrhage into the body cavity or the muscles of the thigh was noted in 8 of 13 of the affected emus. Brain ganglioside levels were evaluated in six of the affected emus and six controls. Significant increases (P < 0.05) in gangliosides GM1 and GM3 were noted, with 2.3- and 4.9-fold increases in these two gangliosides, respectively, in affected emus. Furthermore, the diseased emu brains contained ganglioside GM2, whereas this monosialoganglioside was undetectable in the brains of normal controls. Total mean brain ganglioside sialic acid in affected emus was increased 3.3-fold in comparison with controls. Serum chemistries revealed elevated cholesterol and decreased uric acid levels in affected emus. Gangliosidosis in emus is an inherited disease process that, in the current study, caused 50% mortality in the progeny of two emu breeder pairs. The elimination of this lethal gene from emu breeder stock is essential for the long-term economic viability of the United States emu industry.

Animals↗