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Biomedical subjects

M Kikuchi

Publications and source records attributed to M Kikuchi.

At least 181 records · Page 10Linked to original sources

Serum midkine levels are increased in patients with various types of carcinomas.

The level of expression of midkine (MK), a heparin-binding growth factor, is increased in many types of human carcinomas. An enzyme-linked immunoassay, which utilizes a combination of rabbit and chicken antibodies revealed that serum MK level in the controls (n = 135) was 0.154 +/- 0.076 (mean +/- SD) ng ml(-1)with an apparent cut-off value as 0.5 ng ml(-1). Serum MK level was significantly elevated in the cancer patients (n = 150) (P< 0.001); 87% of the patients showed levels of more than 0.5 ng ml(-1). All ten types of cancer examined showed a similar profile of serum MK level. There was no or weak correlation between C-reactive protein level, a marker of inflammation, and serum MK level. Furthermore, in case of gastric carcinoma and lung carcinoma, patients with stage I carcinoma already showed elevated serum MK levels. The present results indicated that serum MK could serve as a general tumour marker with a good potential for clinical application.

Adult↗

Soy isoflavone aglycones are absorbed faster and in higher amounts than their glucosides in humans.

Isoflavones are contained in soybean or soy foods in two chemical forms, i.e., aglycones and glucosides. We investigated the difference in the absorption of soy isoflavone aglycones and glucosides in humans. After a single, low dose intake (0.11 mmol), the highest isoflavone concentrations in plasma were reached 2 and 4 h after ingestion of aglycones and glucosides, respectively; subjects were four men (41 y old) and four women (45 y old). The highest plasma concentration after aglycone intake was more than two times greater than that after glucoside ingestion. In a similar manner, we then compared the plasma isoflavone concentration profiles after intake of a single, high dose of isoflavones (1.7 mmol) in eight subjects (four men, 40 y old; four women, 47 y old) and found the highest plasma concentration after aglycone intake was more than five times higher than that after glucoside intake. In both high and low dose intake tests, the plasma concentration of genistein was significantly higher than that of daidzein despite the similar levels of intake. After long-term (4 wk) intakes (0.30 mmol/d), we also measured the plasma concentration of isoflavones (eight men, 45 y old). After 2 and 4 wk, these concentrations remained >100% higher after ingestion of aglycones than of glucosides. The isoflavone aglycones were absorbed faster and in greater amounts than their glucosides in humans. Isoflavone aglycone-rich products may be more effective than glucoside-rich products in preventing chronic disease such as coronary heart disease.

Absorption↗

Isoflavone aglycone-rich extract without soy protein attenuates atherosclerosis development in cholesterol-fed rabbits.

The antiatherogenic effect of soy protein with intact isoflavones is well established, but the effects of isoflavones without soy protein have not been determined. We investigated the antiatherogenic effect of an isoflavone aglycone-rich extract (containing 429.4 mg/g isoflavone aglycones) without soy protein from fermented soy in cholesterol-fed rabbits. We fed 12-wk-old New Zealand white male rabbits diets containing 1 g/100 g cholesterol with 0, 0.33 or 1 g/100 g isoflavone aglycones for 8 wk. We also fed the rabbits a diet containing 1 g/100 g cholesterol with 1.09 g/100 g soy saponin-rich extract, a component other than isoflavone aglycones in the isoflavone aglycone-rich extract. Controls did not consume cholesterol, isoflavone aglycones or saponins. The isoflavone aglycone- and saponin-rich extracts did not affect the serum lipid profile of cholesterol-fed rabbits. The serum concentration of daidzein in its conjugated form was significantly higher in the high isoflavone group than in the low isoflavone group. The level of cholesteryl ester hydroperoxide (ChE-OOH) induced by CuSO(4) in plasma in the high isoflavone group was significantly less than that in the cholesterol group, and the ChE-OOH levels of LDL in the low and high isoflavone groups were significantly less than those in the cholesterol group. The ChE-OOH levels in plasma and LDL in the saponin group did not differ from the cholesterol group. In the aortic arch, the cholesterol concentration was significantly lower in the high isoflavone group, and malondialdehyde concentration was significantly lower in the low and high isoflavone groups compared with the cholesterol group; however these concentrations in the saponin group did not differ from those in the cholesterol group. The atherosclerotic lesion area of the aortic arch was significantly lower in the isoflavone groups (26.3% lower in the low isoflavone group and 36.9% lower in the high isoflavone group) than in the cholesterol group. The lesion areas were not different in the soy saponin and cholesterol groups. Immunohistochemical analysis revealed fewer oxidized LDL-positive macrophage-derived foam cells in atherosclerotic lesions in the aortic arch of isoflavone groups compared with that of the cholesterol group. These results suggest that the antioxidative action of isoflavones and their antioxidative metabolites inhibit the oxidation of LDL, thereby exerting an antiatherosclerotic effect.

Animals↗

Isolation and characterization of a 60 kDa 2,4-D-binding protein from the shoot apices of peach trees (Prunus persica L.); it is a homologue of protein disulfide isomerase.

To obtain a candidate auxin-binding protein (ABP), a soluble 60 kDa protein was isolated from an extract of shoot apices of peach trees (Prunus persica L.) by affinity chromatography on a 2,4-dichlorophenoxyacetic acid (2,4-D)-linked Sepharose4B column. The 60 kDa polypeptide, designated Pp60, was purified as a single band on SDS-PAGE by column chromatography. Its dissociation constant (Kd) for [14C]-2,4-D was calculated to be 3.5 x 10(-5) M. The binding of Pp60 for [14C]-2,4-D was inhibited by naphthalene-1-acetic acid (NAA) and p-chlorophenoxyisobutyric acid (PCIB) as well as 2,4-D. Indole-3-acetic acid (IAA) had little effect on the binding. These results suggested that Pp60 is a protein that has an affinity for 2,4-D, NAA, and PCIB in vitro. The partial amino acid sequences of Pp60 showed high homology to those of protein disulfide isomerase (EC 5.3.4.1). Immunoblot analysis demonstrated that Pp60 exists ubiquitously in shoots and leaves. In fruit, expression of Pp60 is restricted at an early stage of development.

2,4-Dichlorophenoxyacetic Acid↗

Histologic and immunohistologic findings and prognosis of 40 cases of gastric large B-cell lymphoma.

It has been considered that gastric large B cell lymphoma mainly consists of mucosa-associated lymphoid tissue lymphoma (MALToma) with large cell transformation. However, debate continues about the cell lineage. We analyzed 61 operated cases of gastric B cell lymphoma, mainly focusing on 40 cases of diffuse large cell lymphoma (DLCL). Immunohistologically, two cases were classified as CD10-positive follicular lymphoma, 19 cases were low-grade MALToma, 11 CD10-negative DLCL with a component of low-grade MALToma (high-grade MALToma), 12 CD10-positive DLCL, and 17 CD10-negative DLCL without MALToma (pure DLCL). Lymphoepithelial lesion (LEL) was found in all -cases of high-grade MALToma, and in eight of these its invasion was confined to the mucosa and submucosa. Expression of Bcl-6 was detected in two cases of high-grade MALToma. Only two cases of CD10-positive DLCL had large cell LEL, and seven cases showed tumor invasion beyond the submucosa. All 12 cases were positive for Bcl-6, and a delicate meshwork of CD35 (Ber-MAC-DRC)-positive follicular dendritic cells was detected in eight cases. Pure DLCL of all 17 cases reached the proper muscle layer or more, and expression of Bcl-6 was detected in 10 cases. For patients with pure DLCL, overall survival was significantly (p <0.05) worse than those of high-grade MALToma and CD10-positive DLCL by Kaplan-Meier and log-rank methods. Clinical staging and Bcl-6 expression were also good prognostic factors in patients with DLCL. Three groups of gastric DLCL each had unique histologic findings, immunohistologic characteristics, and prognosis.

Aged↗

Cutaneous CD30 (Ki-1)-positive anaplastic large cell lymphoma preceded by Hodgkin's disease.

A 38-year-old female was diagnosed as Hodgkin's disease of the axillar lymph nodes, nodular sclerosis type, as evidenced by the presence of Reed-Sternberg cells positive for CD30 and CD15 and negative for CD3, CD20, and CD45. She achieved complete remission after combination chemotherapy. Two years later, she noticed a red papule on her public area without any lymph node involvement. The biopsy specimens showed diffuse proliferation of large-sized atypical lymphoid cells positive for CD30 and CD45, and negative for CD3, CD20 and CD15. These findings were mostly compatible with CD30 (Ki-1)-positive anaplastic large cell lymphoma (Ki-1 lymphoma). Our case is considered to be cutaneous Ki-1 lymphoma preceded by Hodgkin's disease.

Adult↗

Molecular identification of a human carcinoma-associated glycoprotein antigen recognized by mouse monoclonal antibody FU-MK-1.

Mouse monoclonal antibody FU-MK-1, raised against a human gastric adenocarcinoma, recognizes an antigen (termed MK-1 antigen) present on the majority of carcinomas. The present study aimed to identify the MK-1 molecule and to establish its relationship to other carcinoma antigens. Immunoprecipitation studies of human tumor cell lines revealed that FU-MK-1 recognizes a monomeric membrane glycoprotein with two forms, 40 kDa (major form) and 42 kDa (minor form), and with a molecular mass of 35 kDa following treatment with the N-glycosylation inhibitor tunicamycin. The partial amino acid sequence of a main fragment of the MK-1 molecule obtained by spontaneous cleavage under hypotonic conditions was examined, and the 17 contiguous NH2-terminal amino acids were found to be identical with residues 81-97 of the 314-residue GA733-2 protein [Szala et al.; Proc. Natl. Acad. Sci. USA, 87, 3542-3546 (1990)]. Hence, the GA733-2 cDNA was cloned and the specificity of FU-MK-1 was confirmed using four recombinant forms of the GA733-2 antigen expressed in COS-1 cells. Immunoprecipitation with FU-MK-1 of the cell lysate transfected with the full-length GA733-2 cDNA revealed two bands corresponding to those obtained from the tumor cell lines. FU-MK-1 also precipitated three other recombinant proteins consisting of amino acids 1-265, 1-201, and 1-139 of the GA733-2 protein, respectively. Furthermore, immunoblotting analysis indicated that FU-MK-1 binds to a small fragment (6 kDa) generated from a tumor cell line under hypotonic conditions, suggesting that the FU-MK-1 epitope exists on the distal 6-kDa peptide of the extracellular domain of the GA733-2 molecule. We thus conclude that the MK-1 antigen is the GA733-2 antigen, which is currently being used as a target in clinical trials with monoclonal antibodies.

Amino Acid Sequence↗

Intraperitoneal PACAP administration decreases blood glucose in GK rats, and in normal and high fat diet mice.

PACAP is an islet peptide that serves as an endogenous amplifier of glucose induced insulin secretion. Furthermore, we has recently found that PACAP also potentiates insulin stimulated glucose uptake in adipocytes. Therefore, an antidiabetic action of PACAP is possible. In the present study, we examined the effect of PACAP treatment of the hyperglycemia in GK rats, an animal model of type 2 diabetes, and in high fat fed C47BL/6J mice, an animal model for glucose intolerance. GK rats housed with normal diet exhibited a normal level of blood glucose until three weeks old but significant hyperglycemia at eight weeks. When GK rats were treated with daily PACAP38 (i.p. injection, 6 pmol/kg) from age three weeks, development of hyperglycemia was prevented. In high fat fed mice, i.p. administration of PACAP27 for five (25 nmol/kg twice daily) reduced plasma glucose levels to 6.9 +/- 0.2 mmol/l compared to 8.1 +/- 0.2 mmol/l in saline injected animals (p < 0.001) without altering baseline insulin levels. We conclude that PACAP reduces circulating glucose in animal models of type 2 diabetes and glucose intolerance. The mechanism of this action needs to be established.

Animals↗

Hyperglycemia contributes insulin resistance in hepatic and adipose tissue but not skeletal muscle of ZDF rats.

To determine the contribution of hyperglycemia to the insulin resistance in various insulin-sensitive tissues of Zucker diabetic fatty (ZDF) rats, T-1095, an oral sodium-dependent glucose transporter (SGLT) inhibitor, was administered by being mixed into food. Long-term treatment with T-1095 lowered both fed and fasting blood glucose levels to near normal ranges. A hyperinsulinemic euglycemic clamp study that was performed after 4 wk of T-1095 treatment demonstrated partial recovery of the reduced glucose infusion rate (GIR) in the T-1095-treated group. In the livers of T-1095-treated ZDF rats, hepatic glucose production rate (HGP) and glucose utilization rate (GUR) showed marked recovery, with almost complete normalization of reduced glucokinase/glucose-6-phosphatase (G-6-Pase) activities ratio. In adipose tissues, decreased GUR was also shown to be significantly improved with a normalization of insulin-induced GLUT-4 translocation. In contrast, in skeletal muscles, the reduced GUR was not significantly improved in response to amelioration of hyperglycemia by T-1095 treatment. These results suggest that the contribution of hyperglycemia to insulin resistance in ZDF rats is very high in the liver and considerably elevated in adipose tissues, although it is very low in skeletal muscle.

Adipocytes↗

High cardiac angiotensin-II-forming activity in infarcted and non-infarcted human myocardium.

The aims of this study were to compare human cardiac angiotensin-II-forming activity (AIIFA) between the intact area of control autopsy hearts without cardiac disease (n = 10) and the infarcted or non-infarcted area of autopsy hearts with myocardial infarction (MI, n = 7) and to determine responsible angiotensin-II-forming enzymes. Cardiac total and chymase-dependent AIIFAs were significantly higher in the infarcted and non-infarcted myocardium than those in non-MI heart, while angiotensin-converting enzyme-dependent AIIFA increased only in the infarcted myocardium. The density of chymase antibody-positive mast cells in the non-infarcted area of MI heart correlated positively with total or chymase-dependent AIIFA. Augmented AIIFA was also detected in the left atrium of post-MI hearts. Our results indicated that cardiac angiotensin II formation could be activated in the infarcted as well as in non-infarcted myocardium of the post-MI human heart.

Adult↗

Effects of scopolamine on interhemispheric EEG coherence in healthy subjects: analysis during rest and photic stimulation.

The present study of coherence analysis, in 16 healthy male volunteers, aged 24-31 years, showed that the administration of 0.25 mg of scopolamine significantly reduced interhemispheric coherence in the delta and beta-1 bands in the resting state. Scopolamine also caused a significant increase both in EEG coherence during PS and in PS-related coherence reactivity in the beta band. In addition, this compound significantly reduced total WMS scores. These findings suggest that, in addition to causing cognitive impairments, central cholinergic dysfunction can alter interhemispheric functional connectivity under both nonstimulus and stimulus conditions.

Adult↗

Effect of normal aging upon interhemispheric EEG coherence: analysis during rest and photic stimulation.

The present study was conducted to examine and compare interhemispheric EEG coherence at rest and during photic stimulation (PS; 5, 10 and 15 Hz) in 30 younger subjects aged 22.1 +/- 2.2 (mean +/- S.D.) and 25 elderly subjects aged 56.8 +/- 4.9. The elderly subjects had significantly lower coherence in the resting EEG for the delta, theta, alpha-3, beta-1 and beta-2 frequency bands. In contrast, EEG analysis during PS showed that elderly subjects had significantly higher coherence in the frequency corresponding to PS at 15 Hz. In addition, when we examined the changes in coherence from the resting state to the stimulus condition (i.e., coherence reactivity), elderly subjects had significantly higher coherence reactivity to PS at 15 Hz. These findings suggest a low interhemispheric functional connectivity in elderly subjects under non stimulus conditions and a high connectivity during photic stimulus.

Adult↗

Structures of new ceramides from the fruit bodies of Grifola frondosa.

Four new phytosphingosine-type ceramides, (2S,3S,4R)-2-[(2'R)-2'-hydroxydocosanoylamino]-1,3,4-octadecane triol (1), (2S,3S,4R)-2-[(2'R)-2'-hydroxytricosanoylamino]-1,3,4-octadecan etriol (2), (2S,3S,4R)-2-[(2'R)-2'-hydroxypentacosanoylamino]-1,3,4-octadec anetriol (3) and (2S,3S,4R)-2-[(2'R)-2'-hydroxyhexacosanoylamino]-1,3,4-octadeca netriol (4), have been isolated from the fruit bodies of Grifola frondosa. The structures of the new compounds were elucidated on the basis of their spectral data.

Ceramides↗

Sterol constituents from two edible mushrooms, Lentinula edodes and Tricholoma matsutake.

Two new sterols, (22E)-23-methylergosta-5,7,22-trien-beta-ol (1) and 5alpha,6alpha-epoxy-(22E)-ergosta-8,14,22-triene -3beta,7alpha-diol (2), have been isolated from two edible mushrooms, Lentinula edodes and Tricholoma matsutake, respectively, together with twelve known ones (3-14). The structures of the new compounds were elucidated on the basis of their spectral data.

Agaricales↗

Incidence of atrial flutter and atrial fibrillation in patients with implanted physiological pacemakers.

Atrial flutter (AF) is a troublesome arrhythmia for patients with an implanted pacemaker. Although it has recently become possible to eliminate AF by radiofrequency catheter ablation (RF-CA), the incidence of AF before and after pacemaker implantation has not been clarified. The present study was conducted with 123 consecutive patients (69.3+/-11.6 (SD) years old) implanted with pacemakers, excluding patients who had chronic atrial fibrillation (AFib) when the pacemaker was implanted; 69 patients with atrioventricular (AV) block and 54 patients with sick sinus syndrome (including 29 patients with bradycardia-tachycardia syndrome). All patients were implanted with physiological pacemakers. The follow-up period was 4.7+/-1.9 years. In 11 of the 123 patients (8.9%), AF was observed before pacemaker implantation and the incidence was significantly higher in patients with sick sinus syndrome than in those with AV block (16.7 vs 2.9%, p<0.01). Nine of the 29 patients with bradycardia-tachycardia syndrome (31%) had AF. After physiological pacemaker implantation, AF recurred in 9 of the 11 patients, and AF was newly observed in 1 patient. Thus, 10 of the 123 patients (8.1%) had AF after physiological pacemaker implantation. Recurrence of AF was not suppressed by physiological pacing. Thirty of the 123 patients had AFib before implantation of a pacemaker and its occurrence was reduced by physiological pacing (from 24.4% to 12.2%, p<0.05). The incidence of AFib in patients with AF was significantly higher than in those without AF (90.0 vs 5.3%, p<0.001). In conclusion, the recurrence of AF is not prevented by physiological pacing and is closely related to the occurrence of AFib. RF-CA should be considered in patients who have AF before pacemaker implantation.

Aged↗

Efficacy of atrioventricular sequential pacing and diastolic mitral regurgitation in patients with intrinsic atrioventricular conduction.

The efficacy of a short atrioventricular (AV) delay in patients with dilated cardiomyopathy has been reported, but there are deleterious effects of right ventricular pacing. Diastolic mitral regurgitation (MR) is observed in patients with elevated left ventricular end-diastolic pressure and can be induced by prolonging the AV delay in patients with DDD pacemakers. The critical PQ interval that induces diastolic MR may represent the upper limit of the optimal PQ interval. The efficacy of AV sequential pacing and diastolic MR were studied in 11 patients (68.3+/-13.7 (SD) years old) with intrinsic AV conduction and with implanted DDD pacemakers. Cardiac output (CO) and pulmonary capillary wedge pressure (PCWP) were measured by Swan-Ganz catheter and transmitral flow was recorded by pulsed Doppler echocardiography. AV delay was prolonged stepwise by 25 ms starting from 65 ms. Pacing rate was fixed at 70-80 beats/min. In 6 of the 11 patients, diastolic MR was observed under atrial pacing and the critical PQ interval for the appearance of diastolic MR was 0.22+/-0.04 s. CO was increased from 3.8+/-0.8 to 4.3+/-0.9 L/min (p<0.05) and PCWP was decreased from 7.5+/-2.8 to 5.5+/-1.6 mmHg (p<0.05) by shortening the AV delay till the diastolic MR disappeared. On the other hand, in 5 of the 11 patients, diastolic MR was not observed, and CO (4.2+/-0.5 to 4.3+/-0.5L/min, ns) and PCWP (5.8+/-4.6 to 5.4+/-3.9 mmHg, ns) were not improved by AV sequential pacing. In conclusion, cardiac function may be improved by AV sequential pacing and setting the AV delay under the critical PQ interval for the appearance of diastolic MR when the diastolic MR is observed. However, AV sequential pacing may be either ineffective or even deleterious for patients in whom diastolic MR is not observed.

Aged↗

Angiodestruction and tissue necrosis of skin-involving CD56+ NK/T-cell lymphoma are influenced by expression of cell adhesion molecules and cytotoxic granule and apoptosis-related proteins.

We compared the expression of cell adhesion molecules (CAMs), cytotoxic granule proteins, and apoptosis-related proteins by immunohistology and in situ terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick end labeling (TUNEL) of 10 cases of cutaneous CD56+ NK/T cell lymphoma with and 6 cases without angiodestruction. Lymphoma cells in cases with angiodestruction frequently expressed CAMs CD2, CD11a, and CD49d and their ligands CD58, CD54, and CD106 and were positive for CD122 and cytotoxic granule proteins TIA1, perforin, and granzyme B. Lymphoma cells in cases without angiodestruction mostly were negative for CD2, CD58, CD54, CD106, and TIA1 and weakly positive for perforin and granzyme B. In the TUNEL method, mean apoptotic indices (AI) for cases with angiodestruction showed a higher percentage than those without angiodestruction. CD95L, CD95, apoptosis-induced cysteine protease CPP32, apoptosis-promoting protein Bax, and proliferating marker (MIB1) frequently were positive in the lymphoma cells of cases with angiodestruction, but there was no expression of apoptosis-inhibitor protein Bcl2. In most cases without angiodestruction, lymphoma cells were positive for CD95L and Bax and negative for CD95, CPP32, and MIB1. CAMs and the 3 cytotoxic granule proteins and an apoptosis pathway might be important factors in the paracrine and autocrine mechanisms of tissue necrosis in cutaneous CD56+ NK/T cell lymphoma.

Aged↗