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Biomedical subjects

Y Ikeda

Publications and source records attributed to Y Ikeda.

At least 19 recordsLinked to original sources
PubMed1992

1H-NMR study on the chitotrisaccharide binding to hen egg white lysozyme.

Interaction between hen egg white lysozyme and chitotrisaccharide was investigated by 1H-NMR spectroscopy using partially acetylated chitotrisaccharides and chemically modified lysozyme. Monoacetyl (GlcN-GlcN-GlcNAc), diacetyl (GlcN-GlcNAc-GlcNAc), or triacetyl chitotrisaccharide [(GlcNAc)3] was added to the lysozyme solution, and the changes in the 1H-NMR signals of the lysozyme were analyzed. Although many of the resonances were affected by addition of the saccharide, the most remarkable effect was seen on the signal of Trp28 C5H which is in a hydrophobic box adjacent to the saccharide-binding site. The signal shifted upfield by 0.2 ppm upon (GlcNAc)3 binding, whereas the chemical shift change of the signal resulting from binding of GlcN-GlcNAc-GlcNAc or GlcN-GlcN-GlcNAc was smaller than that resulting from (GlcNAc)3 binding. When the Asp101-modified lysozyme was used instead of the native lysozyme, the chemical shift change of the Trp28 C5H signal resulting from (GlcNAc)3 binding was also smaller than that for the native lysozyme. The chemical shift change of the signal reflects the conformational change of the hydrophobic box region which should synchronize with the movement of the binding site resulting from the saccharide binding. Therefore, the conformational change resulting from the saccharide binding might be reduced when the sugar residues located at binding subsites A and B of the lysozyme are deacetylated, as well as when Asp101 interacting with the sugar residues at the same subsites is modified.

Animals↗
PubMed1992

Differential effect of subspecies of lipoprotein containing apolipoprotein A-I on cholesterol efflux from cholesterol-loaded macrophages: functional correlation with lecithin: cholesterol acyltransferase.

Two species of lipoprotein containing apoA-I, one containing only apoA-I (LpA-I), and the other containing apoA-I and apoA-II (LpA-I/A-II), were tested for their effects on macrophage foam cells. Rat macrophages were converted to foam cells by incubation with radiolabeled acetylated LDL. Incubation with LpA-I or LpA-I/A-II decreased the cellular cholesteryl esters (CE) mass. However, the free cholesterol (FC) mass was only reduced by LpA-I. All the radioactivity excreted into the medium was associated with LpA-I or LpA-I/A-II; 39% of the excreted radioactivity was esterified in LpA-I and 10% in LpA-I/A-II. Upon complete inactivation of lecithin: cholesterol acyltransferase (LCAT) activity with dithiobisnitrobenzoic acid, the cholesterol reducing capacity of LpA-I was weakened significantly. However, the CE mass reducing capacity of LpA-I/A-II was not affected. When LpA-I and LpA-I/A-II were combined, the cholesterol reducing capacity of the mixture was similar to that of LpA-I alone. However, LpA-I re-isolated from the medium showed a lower esterification rate than did the re-isolated LpA-I/A-II, thereby indicating that the cholesterol esterified in LpA-I was transferred to LpA-I/A-II. These results suggest that (i) the function of LpA-I is closely linked to the LCAT activity while that of LpA-I/A-II is not, and (ii) LpA-I in concert with LpA-I/A-II induces a series of extracellular events; LCAT-mediated esterification of excreted FC by LpA-I and a subsequent CE transfer to LpA-I/A-II. These mechanisms might be important for net cholesterol efflux from macrophage foam cells in physiological states.

Adolescent↗
PubMed1992

A monoclonal antibody-based enzyme immunoassay for human GMP-140/P-selectin.

Two hybridoma cell lines producing monoclonal antibodies WGA-1 and PL7-6, reactive only with thrombin-stimulated human platelet have been established. Both these antibodies were investigated for their specific reactivity against GMP-140, based on the amino acid composition analysis of immunopurified antigen and N terminal amino acid sequencing of its protease fragments. A two-site enzyme immunoassay for quantification of human GMP-140 was developed using WGA-1 monoclonal antibody immobilized on 96-well microplates and horseradish peroxidase-labeled PL7-6 monoclonal antibody as detector. The assay was able to measure GMP-140 in serum and plasma with a sensitivity of about 5 ng/ml and a precision better than 10%. This assay will be useful for the detection of GMP-140 derived from platelets or endothelium in biological fluids and tissue extracts.

Amino Acid Sequence↗
PubMed1992

[Role of growth hormone in the pathogenesis of dawn phenomenon in IDDM].

The early morning hyperglycemia of diabetic patients has been commonly referred to as the "dawn phenomenon". Recently the nocturnal surges of growth hormone (GH) have been suggested as an important factor in the pathogenesis of the dawn phenomenon. In order to reassess the role of the nocturnal GH secretion in the dawn phenomenon, seven C-peptide negative diabetic patients were studied during 48hr-feedback control using a closed-loop insulin infusion device (Biostator). They received oral sleeping medication only on the first night (control) and sleeping medication with anticholinergic agent (pirenzepine 75mg) on the second night, and blood glucose, insulin requirements, GH and cortisol concentrations during 0000hr and 0700hr were measured. The peak of sleep-induced GH secretions was markedly suppressed by pirenzepine in comparison with the control night (19.8 +/- 3.7 vs. 3.0 +/- 1.2ng/ml; p less than 0.05). Insulin requirements during 0500hr and 0700hr were suppressed significantly by pirenzepine (3.0 +/- 0.2 vs. 2.0 +/- 0.2U/2hr; p less than 0.05). Insulin infusion ratio, i.e. insulin requirements during 0500hr and 0700hr divided by those during 0000hr and 0200hr, was decreased by pirenzepine (2.2 +/- 0.3 vs. 1.5 +/- 0.2; p less than 0.05). There were no significant differences in blood glucose and cortisol concentrations whether or not the anticholinergic agent was given. In conclusion, these results have shown that an anticholinergic agent may be useful in the management of insulin-treated patients with marked dawn phenomenon.

Adult↗
PubMed1992

Phase II study: treatment of non-Hodgkin's lymphoma with an oral antitumor derivative of bis(2,6-dioxopiperazine).

BACKGROUND: Although razoxane (ICRF-159), a derivative of bis(2,6-dioxopiperazine), has shown significant antitumor activity in several murine tumors, inadequate bioavailability has limited its clinical efficacy. Sobuzoxane (MST-16), another derivative of bis(2,6-dioxopiperazine), has shown activity against a broad spectrum of murine tumors and human tumor xenografts in nude mice and a lack of cross-resistance to vincristine, doxorubicin, cyclophosphamide, fluorouracil, etoposide, and mitomycin C. These findings suggest that MST-16 has a mode of cytocidal activity different from that of other antitumor agents. PURPOSE: The present late phase II study was conducted to evaluate the clinical efficacy and toxicity of MST-16 in non-Hodgkin's lymphoma (NHL). METHODS: As part of a multi-institutional cooperative study, we conducted a study of MST-16 in 27 patients with NHL who were assessable for drug efficacy and toxicity. MST-16, a bis(2,6-dioxopiperazine) analogue and an inhibitor of topoisomerase II, was administered orally at a dose of 1600 mg/m2 a day for 5-7 days at intervals of 2-3 weeks. RESULTS: Response consisted of one complete remission and seven partial remissions in 27 assessable patients. Response was achieved at a median of 13 days (range, 9-62 days) after initiation of therapy and lasted a median of 46 days (range, 29-155 days). Major toxic effects were leukopenia in 70% of the patients, thrombocytopenia in 44%, and gastrointestinal disorders in 37%. CONCLUSIONS: MST-16 was shown to be effective in NHL and deserves further clinical trial, since the drug shows little cross-resistance to available antitumor drugs. IMPLICATIONS: Phase II clinical studies of MST-16 in treatment of breast cancer, gastric cancer, and adult T-cell leukemia and lymphoma are also being conducted in Japan. Future trials of combination chemotherapy using MST-16 with other antitumor drugs are warranted in view of the additive effects observed in studies of MOLT-3 cells and studies of L1210 leukemia in mice.

Administration, Oral↗
PubMed1992

A new type of hepatitis C virus in patients in Thailand.

Partial nucleotide sequences in the tentative NS5 region of the hepatitis C viral genome obtained from patients with chronic hepatitis in Thailand were analyzed by reverse transcription followed by the polymerase chain reaction. Of ten samples studied, four showed low homologies to any known type of HCV: the homologies of the nucleotide sequences of these clones with HCV-J, -US, -K2a and -K2b were 66.5-69.1%, 66.5-68.2%, 61.2-64.1% and 64.4-66.2%, respectively, and the homologies of their deduced amino acids sequences were 71.7-75.2%, 71.7-75.2%, 69.0-72.6% and 69.9-73.5%, respectively. These four clones were classified a new distinct type of HCV, named HCV-T. Moreover, the nucleotide and amino acid sequence homologies of the four HCV-T clones showed that the HCV-T type could be classified into two genotypes, HCV-Ta and HCV-Tb.

Amino Acid Sequence↗
PubMed1992

Glycoprotein Ia/IIa-mediated activation-dependent platelet adhesion to collagen.

In the presence of anti-glycoprotein (GP) IIb/IIIa antibody at the concentration which completely inhibit platelet aggregation, ADP (0.5-3 microM) increased platelet adhesion to collagen in a concentration-dependent manner under static conditions when platelet-rich plasma (PRP) was used for the assay instead of washed platelets. This was also supported by the results of scanning electron microscopic analyses. The ADP-induced platelet adhesion to collagen was inhibited by PGI2 or beraprost, a stable analogue of PGI2, in a concentration-dependent manner (1-10 ng/ml). These findings suggested the presence of activation-dependent platelet adhesion to collagen. ADP-induced platelet adhesion to collagen was almost completely inhibited by anti-GPIa/IIa and anti-GPIIa antibodies. In the present study, we provide the first direct evidence that the activation-dependent platelet adhesion to collagen is induced by ADP and that GPIa/IIa also plays an important role in the mechanisms of this adhesion.

Adenosine Diphosphate↗
PubMed1992

Long-term callosal lesions and learning of a black-white discrimination by one-eyed rats.

We know from our previous studies that mature rats with monocular enucleation at birth (OEBs), as well as animals enucleated at maturity (OETs), were unable to learn a black-white discrimination when they were trained after lesions of the visual cortex contralateral to the remaining eye. Since it is well known that synaptic reorganization takes place in the adult rat brain through reactive synaptogenesis following deafferentation, we wondered if long-term callosal lesions in OEBs and OETs would bring out such synaptic reorganization in the visual cortex and, consequently, affect the outcome of the discrimination mentioned above. In the present study, two experiments were carried out: in Experiment 1 the previous experiment was replicated in that OEBs and OETs of 3 months of age were trained on the discrimination 10 days following unilateral visual cortex lesions; in Experiment 2, effects of callosal lesions made 10 weeks earlier either at 3 weeks of age or 13 weeks of age were investigated. The results were: 1) the findings of the previous experiment were confirmed; 2) the long-term callosal lesions facilitated the acquisition of discrimination in OEBs but not in OETs; 3) the facilitative effects were more prominent in OEBs with callosal lesions at 3 weeks of age than in those at 13 weeks of age. The findings were discussed in relation to possible synaptic reorganization produced in the visual cortex ipsilateral to the remaining eye following callosal lesions made 10 weeks earlier and also in relation to reorganization of the uncrossed visual pathways resulting from monocular enucleation at birth.

Aging↗
PubMed1992

Amplification of plasmid (L factor) DNA and increased production of a plasmid gene product (gamma-interferon) in mouse L cells.

It has previously been reported that composite DNAs derived from L factor, a polyoma-related mammalian plasmid, can be established in several mouse cell lines after transfection. Here, we report that the copy number of a plasmid composite DNA consisting of L factor, pBR DNA, dihydrofolate reductase (dhfr) gene, and gamma-interferon (gamma-IFN) gene was increased more than 10-fold after two successive adaptations of the plasmid-bearing mouse L cells to increasing concentrations of methotrexate (MTX), an inhibitor of dhfr. The structure of the amplified L factor plasmid remained intact during prolonged cell culture, but the copy number remained to be amplified only when the selective pressure (presence of MTX in the medium) has been exerted during the culture. Cells bearing the amplified plasmid produced a higher level of gamma-IFN compared with the original clone, which was likely to be derived from the plasmid gamma-IFN gene amplified along with L factor and the dhfr gene.

Animals↗
PubMed1992

Fastigiofugal fibers encoding horizontal and vertical components of saccades as determined by microstimulation in monkeys.

To identify the routes by which oculomotor vermis signals control eye movements (saccadic signals), saccades evoked by microstimulation were studied in the region of the uncinate fasciculus (UF) and juxtarestiform body (JB) in the macaque monkey. Anatomical pathways of axons from the fastigial oculomotor region (FOR) were studied by anterograde transport of wheatgerm agglutinin conjugated horseradish peroxidase (WGA-HRP). The routes were identified by comparing maps of low threshold for evoking saccades with the anatomical map of anterogradely labeled axons arising from the FOR. Microstimulation of a region of the UF and JB demonstrated that saccadic signals are carried exclusively by decussated FOR axons which leave the cerebellum via the contralateral UF. The fibers in the JB do not carry saccadic signals. The horizontal component of saccadic signals is conveyed by fibers in the descending limb of the UF, while the vertical component is conveyed by a smaller group of fibers which separate from the UF and enter the midbrain with the contralateral superior cerebellar peduncle.

Animals↗
PubMed1992

Comparison of clinical usefulness of very-low-calorie diet and supplemental low-calorie diet.

Forty-five overweight patients (12 male, 33 female) were prescribed a very-low-calorie diet (VLCD) or a supplemental low-calorie diet (LCD), randomly, at an outpatient clinic. Twenty obese patients [31.6 +/- 13.1 y; body mass index (BMI) 32.9 +/- 6.1] were treated with a VLCD of 1757 kJ/d for 1-2 mo (five packages of Optifast 70/d; Sandoz Nutrition, Minneapolis). Another 25 patients (35.3 +/- 11.7 y; BMI 31.9 +/- 4.4) were treated by a supplemental LCD of 3515-5021 kJ/d for 1-2 months, which consisted of two to three packages of Optifast 70 and 2678-3682 kJ of conventional balanced meals. By the fourth week, the weight reduction obtained by the VLCD was significantly greater than that achieved by the supplemental LCD (P less than 0.01). At the eighth week, however, effect of the VLCD and the supplemental LCD in terms of weight reduction did not differ significantly. No serious side effects were observed in either treatment group. However, remarkable elevation of serum uric acid concentration was detected in seven patients on the VLCD. The treatment period of the VLCD is limited to less than or equal to 3 mo. On the other hand, obese patients can be treated with the supplemental LCD for greater than 3 mo. Therefore, the supplemental LCD is considered to be useful in the treatment of moderately obese Japanese patients on an outpatient basis.

Adult↗
PubMed1992

Lipoprotein-containing apolipoprotein A-I: sex-related quantitative and qualitative changes in this lipoprotein subspecies after ingestion of fat.

We investigated the postprandial changes of two species of lipoproteins containing apolipoprotein (apo)A-I: lipoprotein containing apo A-I but no apo A-II (LpA-I), and lipoprotein containing apo A-I and apo A-II (LpA-I/A-II). These lipoproteins were isolated from 10 men and 11 women at 0, 4, and 6 h after they had eaten butter. In LpA-I, the concentrations of all lipids except triglyceride were increased at 4 and 6 h in the women. In the men all lipids were increased only at 4 h. The increase of apo A-I concentration was found at 6 h only in the women. In LpA-I/A-II, the concentrations of all lipids were increased at 4 h and only phospholipid (PL) was increased at 6 h in the women. In the men, free cholesterol and PL were increased at 4 and 6 h. The increases of apo A-I and apo A-II concentrations were found at 4 and 6 h only in the men. These results suggest that the postprandial changes are sex-related and may relate to the different incidence of atherosclerotic cardiovascular disorders.

Adult↗
PubMed1992

Soybean protein isolate and soybean lectin inhibit iron absorption in rats.

Inhibitory effects of soybean protein isolate (SPI) and soybean lectin on the intestinal absorption of nonheme iron were investigated by in vivo studies in rats. Rats fed the SPI-based diet absorbed significantly less iron than did control rats fed the casein-based diet. Supplementing the SPI diets with 8% D-galactose significantly increased the incorporation of iron into liver ferritin, although D-galactose did not significantly increase iron absorption. Heat treatment of SPI significantly increased iron absorption. Ascorbate did not enhance iron absorption in rats fed the SPI-based diet. The presence of lectin in an aqueous extract of SPI was suggested by hemagglutination activity as well as by immunoreactivity with soybean lectin antibody. Soybean lectin introduced into ligated segments of the upper small intestine of rats inhibited ferrous iron absorption. This inhibitory effect, especially in the mucosal uptake, was significantly improved by addition of N-acetyl-D-galactosamine to soybean lectin. Soybean lectin had no effect on ferric iron absorption. Our results suggest that a portion of the reduction in iron absorption in rats fed SPI may be due to lectins.

Animals↗
PubMed1992

Histopathological development of gastric tumors induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats.

The development of carcinoma was examined in male Wistar rats (n = 120) exposed to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in the drinking water (83 micrograms/ml) for 16 weeks. After MNNG administration, rats were investigated by endoscopic observation, visualization of microvascular structure, and estimation of lectin binding sites. Changes of bile reflux to the stomach was observed endoscopically at 24 weeks as well as the development of gastric mucosal erosions. Protruding and expansive ulcerating carcinomas developed at 36 weeks and had a microvascular pattern similar to that of human adenocarcinoma. Estimation of lectin binding site and pattern was useful to evaluate the malignant potential of cell proliferation. We postulate that endoscopic observation is valuable in investigating the development of gastric carcinoma, and microvascular structure and lectin binding pattern may be useful to demonstrate the mechanism of growth of gastric carcinoma.

Animals↗
PubMed1992

Demonstration of bicarbonate secretion in rat duodenal brush border membrane vesicles.

This study was designed to characterize the mechanisms available for bicarbonate transport across the apical membrane using rat duodenal brush border membrane vesicles (BBMVs), including the morphological findings. BBMVs were purified using a double Mg2+ precipitation technique. Electron microscopy of the final pellet showed only membrane material without contaminating organelles of cytoskeletal aggregates. BBMVs were enriched 15.1 +/- 3.2-fold in A-lp and 12.5 +/- 2.4-fold in LAP. The time course of 36Cl uptake into BBMVs demonstrated a good response curve and equilibrated to the intravesicular space over 120 min. In this present study, these BBMVs were purified and showed a stabilized structure. Therefore, these results suggest that this model was useful for studying HCO3- secretion and ulcer etiology.

Animals↗
PubMed1992

Development of diabetic complications in a new diabetic strain of rat (WBN/Kob).

The development of ocular, renal, and neural lesions was examined in male diabetic WBN/Kob rats with endoexocrine pancreatic insufficiency. As for the ocular lesions, around 15 months of age, opacity of the lens began to appear. Opacity was first observed in the periphery of the lens, and then increased rapidly in severity, extending concentrically and centripetally, until total cataracts developed. The incidence of cataracts in male rats was gradually increased and reached almost 100% at 24 months of age. As for renal lesions, the 24-h urinary total protein began to increase at about 13 months of age and reached 50-300 mg/24 h at 13-28 month of age, which was significantly higher than in age-matched male Wistar rats (15-25 mg/24 h). Electrophoretic analysis revealed that the urinary protein was almost all albumin. Morphologically, an increased GBM thickness and glomeruli with segmental or global enlargement of mesangial areas were observed. As for neural lesions, a reduction in motor nerve conduction velocity was demonstrated electrophysiologically, and a marked decrease in density and diameter of myelinated fibers in the sciatic nerves were observed morphometrically. In conclusion, the WBN/Kob rat strain with slowly developing but severe lesions associated with pancreatopathy presents a suitable model for human diabetic complications.

Albuminuria↗
PubMed1992

Antibodies against sulphatide in sera from patients with autoimmune rheumatic diseases.

We tested sera of patients with various autoimmune rheumatic diseases for the presence of antibodies against sulphatide (an acidic glycosphingolipid), identified as a target antigen for antibodies against the liver cell membrane. Thirty-five percent (7/20) of patients with lupus in the active stage possessed anti-sulphatide antibodies, whereas 10% (2/20) of those in the inactive stage and 20% (4/20) of those in the stationary stage possessed such antibodies. Moreover, 10% (3/29) of patients with other autoimmune rheumatic diseases also possessed anti-sulphatide antibodies. The level of anti-sulphatide antibodies was significantly correlated with the levels of anti-double-stranded (ds) DNA antibodies (r = 0.634, P less than 0.001) and dextran sulphate-binding IgG (r = 0.407, P less than 0.001). The serum levels of antibodies against sulphatide were correlated with a history of seizures or psychosis in patients with autoimmune rheumatic diseases. Gels coupled with polyanionic dextran sulphate, monoanionic sulphanilic acid and DNA were shown effectively to adsorb anti-sulphatide antibodies in the sera of patients with active systemic lupus erythematosus (SLE) and autoimmune chronic active hepatitis (AI-CAH). These results suggest that the observed reactivity with sulphatide is due to the presence of antibodies capable of reacting with various anionic molecules in the sera of patients with autoimmune rheumatic diseases as well as those with AI-CAH.

Adsorption↗