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Biomedical subjects

M Kikuchi

Publications and source records attributed to M Kikuchi.

At least 289 records · Page 16Linked to original sources
PubMed1999

A fiber-optic measurement system of light scattering to evaluate embryo viability: model experiment using a latex sphere suspension and mouse embryos.

In this study, we tested the efficacy of a fiber-optic light scattering system developed by us to measure mitochondrial size and particle density in embryos in order to establish a non-invasive method of evaluating human embryo viability for in vitro fertilization and embryo transfer. Particle size was determined by comparing the measured angular distribution of the light scattering intensity with that of the theoretical distribution using a 1.0 micron latex sphere suspension and mouse embryos. The measured light scattering pattern of the latex suspension was found to agree closely with the theoretically derived pattern. The measured light scattering pattern of the mouse embryo was similar to the calculated pattern of spheres, the diameter of which was equivalent to that of the mitochondria. Therefore, the measured light scattering is thought to be derived mainly from the mitochondria in the embryo. The relationship between light scattering intensity and latex particle density was also examined in order to estimate the detectable range of mitochondrial particle density. Since the detectable range of the particle density obtained in our study (1.4 x 10(6) - 1.4 x 10(11) particles/ml) was greater than the known mitochondrial particle density in human embryos (1.0 x 10(9) - 1.0 x 10(11) particles/ml), we believe that this mitochondrial particle density can be measured using our system. We concluded that it is possible to use our simple system as a non-invasive method for evaluating human embryo viability.

Animals↗
PubMed1999

[Cytokine imbalance in critically ill patients: SIRS and CARS].

It remains difficult to treat severely ill patients, especially those who have sepsis and subsequent multiple organ dysfunction syndrome. We propose the hypothesis that the pathophysiology in the sequential sepsis and multiple organ dysfunction syndrome may be strongly related to the imbalance between inflammatory cytokines and antiinflammatory cytokines induced for the host defense to active neutrophils and endothelial cells. Thus we attempted to develop cytokine modulation therapy to normalize the cytokine balance in the host defense system. In this review, we elucidate the relationship between cytokine imbalance and SIRS/CARS in patients with severe burn injury. Furthermore, we examine the possible usage of G-CSF to amplify neutrophil function, and clarify the reasons why various innovative therapies against sepsis have failed.

Critical Illness↗
PubMed1999

[Shock and acute organ dysfunction].

Multiple trauma, hemorrhage, and sepsis may produce various kinds of shock, and such a host as shock could not be controlled and may easily fall into multiple organ dysfunction. Although those mechanisms on the pathogenesis of these sequential inflammatory responses have been clarified recently, the clinical outcome of such patients suffering from severe sepsis and multiple organ dysfunction is still very low. This inflammatory response against the insult shows a sequential manner; cardiovascular system failure, renal system failure, respiratory system failure, central nervous system failure, and finally, hepatic failure. However, the host response to the insult is a kind of defense against the invasion, and the clinical goal might be to stabilize hemodynamic system, metabolic system, and immunologic system. To achieve hemodynamic homeostasis, we use catecholamines and blood transfusion to improve the oxygen supply to important organs and enhance tissue repair. For metabolic homeostasis, early administration of hyperalimentation may be needed, either parenterally or enterally. Enteral feeding may also provided a route for bacterial translocation. To achieve immunologic homeostasis, prophylactic antibiotic administration and metabolic support may be required and should also protect against infection as a secondary invasion. This review explains these mechanisms in terms of the relationship between shock and organ dysfunction and the general features of clinical management.

Anti-Bacterial Agents↗
PubMed1999

Application of low-intensity ultraviolet irradiation to the treatment for pharmacological vasoconstriction via a percutaneous transluminal approach.

We applied low-power ultraviolet (UV) laser irradiation via a thin flexible optical fiber to an in vivo model of vasospasm using an intravascular transluminal approach. The surgically exposed left femoral arteries of a rabbit were constricted by norepinephrine. A quartz fiber of 400 microm in diameter was introduced into the artery via the right common carotid artery through a 2.5F catheter. The femoral artery lumen was then irradiated with a helium-cadmium laser (wavelength 325 nm, output power 8 mW) through the fiber for 30 s. The UV irradiation increased the mean luminal diameter by 85% in comparison to the precontracted state, while the increase was only 45% in a sham operation. A histopathologic examination revealed no thermal damage and an intact internal elastic lamina. These results suggest that intravascular transluminal irradiation with a low-power UV laser may thus have potentially clinical applications to reverse acute arterial vasospasm.

Angiography↗
PubMed1998

Cerebrosides A and C, sphingolipid elicitors of hypersensitive cell death and phytoalexin accumulation in rice plants.

When plants interact with certain pathogens, they protect themselves by generating various chemical and physical barriers called the hypersensitive response. These barriers are induced by molecules called elicitors that are produced by pathogens. In the present study, the most active elicitors of the hypersensitive response in rice were isolated from the rice pathogenic fungus Magnaporthe grisea, and their structures were identified as cerebrosides A and C, sphingolipids that were previously isolated as inducers of cell differentiation in the fungus Schizophyllum commune. Treatment of rice leaves with cerebroside A induced the accumulation of antimicrobial compounds (phytoalexins), cell death, and increased resistance to subsequent infection by compatible pathogens. The degradation products of cerebroside A (fatty acid methyl ester, sphingoid base, and glucosyl sphingoid base) showed no elicitor activity. Hydrogenation of the 8E-double bond in the sphingoid base moiety or the 3E-double bond in the fatty acid moiety of cerebroside A did not alter the elicitor activity, whereas hydrogenation of the 4E-double bond in the sphingoid base moiety led to a 12-fold decrease in elicitor activity. Furthermore, glucocerebrosides from Gaucher's spleen consisting of (E)-4-sphingenine and cerebrosides from rice bran mainly consisting of (4E,8E)-4,8-sphingadienine and (4E,8Z)-4,8-sphingadienine showed no elicitor activity. These results indicate that the methyl group at C-9 and the 4E-double bond in the sphingoid base moiety of cerebrosides A and C are the key elements determining the elicitor activity of these compounds. This study is the first to show that sphingolipids have elicitor activity in plants.

Anti-Infective Agents↗
PubMed1998

Different subcellular distribution and regulation of expression of insulin receptor substrate (IRS)-3 from those of IRS-1 and IRS-2.

Adipocytes contain three major substrate proteins of the insulin receptor, termed IRS-1, IRS-2, and IRS-3. We demonstrated that IRS-1 and IRS-2 are located mainly in the low density microsome (LDM) fraction and are tyrosine phosphorylated in response to insulin stimulation, leading to phosphatidylinositol (PI) 3-kinase activation. In contrast, IRS-3 is located mainly in the plasma membrane (PM) fraction and contributes to PI 3-kinase activation in the PM fraction. The different cellular localizations of IRS proteins may account for the mechanism of insulin resistance induced by a high fat diet, considering that PI 3-kinase activation in the LDM fraction is reportedly essential for the translocation of GLUT4 in adipocytes. High fat feeding in rats increased both protein and mRNA levels of IRS-3 but decreased those of IRS-1 and IRS-2 in epididymal adipocytes. As a result, selective impairment of insulin-induced PI 3-kinase activation was observed in the LDM fraction, whereas PI 3-kinase activation was conserved in the PM fraction. This is the first report showing that different IRS proteins function in different subcellular compartments, which may contribute to determining the insulin sensitivity in adipocytes.

Adipocytes↗
PubMed1998

Random integration of HTLV-1 provirus: increasing chromosomal instability.

Adult T-cell leukemia/lymphoma (ATLL) is a neoplasm of mature helper (CD4) T-lymphocytes. Human T-cell lymphotropic virus type-I (HTLV-I) is etiologically considered to cause ATLL. It has been suggested that HTLV-I integrates its provirus into random sites in host chromosomal DNA after infection. Clonal integration has been observed in patients with ATLL, including smoldering, chronic and acute leukemia states. Almost all cases with ATLL demonstrate clonal chromosome abnormalities, with karyotypes being very complicated in both number and structure. However, there are no specific karyotype abnormalities in ATLL. In order to examine the role of HTLV-I in the pathogenesis of ATLL, we investigated whether or not HTLV-I randomly integrates and whether the integration site in the human genome is associated with any chromosomal abnormality. We analyzed 18 cases with ATLL, which included 15 cases with acute states, two cases with chronic states and one case with a smoldering state. In four of the 18 cases, the HTLV-I provirus integrated into the 9th chromosome, while in three cases, it integrated into the 1st or 10th chromosome. However, the integrated site in the chromosome varied in each case and the random integration was considered to be true. All 15 cases with acute ATLL had complicated chromosomal abnormalities and two cases with chronic and smoldering ATLL showed simple abnormal karyotypes, while one case with chronic ATLL showed a normal karyotype. In 15 of the 18 cases, the chromosomes with HTLV-I integration showed abnormalities. In particular, in two cases with simple chromosome abnormalities, HTLV-I integrated into the abnormal chromosome, but not into the normal chromosome. The HTLV-I proviral integration thus seems to be associated with chromosome abnormalities. In the multistage leukemogenesis of ATLL, these findings indicate that HTLV-I integration might play an important role in the induction of chromosomal instability.

Adult↗
PubMed1998

Simultaneous determination of nicotinic acid and its metabolites in rat urine by micellar electrokinetic chromatography with photodiode array detection.

Nicotinic acid, nicotinamide and their possible metabolites were successfully separated within 17 min by micellar electrokinetic chromatography using 50 mM borate buffer (pH 9.0) containing 150 mM sodium dodecyl sulfate as the running buffer. Calibration curves for all compounds showed good linearity in a range of 5 microg/ml and 250 microg/ml with good correlation. The present method did not require any clean-up procedures and made it possible to determine all metabolites without interference on a photodiode array detector. Urine samples collected from Wistar male rats were analyzed after high-dose oral or intravenous administration of nicotinic acid or nicotinamide. Metabolic pathways of nicotinic acid in male Wistar rats are also discussed.

Animals↗
PubMed1998

Effects of intranasal administration of recombinant murine interferon-gamma on murine acute myocarditis caused by encephalomyocarditis virus.

BACKGROUND: Viral myocarditis has been strongly implicated in the pathogenesis of dilated cardiomyopathy as well as acute myocarditis. Among the antiviral therapies, interferons (IFNs) have been widely studied and become very important in clinical practice. METHODS AND RESULTS: To investigate the possibilities of IFN therapy in viral myocarditis, we analyzed the effects of recombinant murine interferon (mIFN)-gamma and natural mIFN-alpha/beta by the intranasal and intramuscular routes on the development of acute murine myocarditis caused by encephalomyocarditis virus. Both mIFN-gamma and mIFN-alpha/beta treatment by either route significantly increased the survival rate; none of the mIFN-gamma-treated mice died. The effect of mIFN-gamma was significantly greater than that of mIFN-alpha/beta. Furthermore, intranasal administration of mIFN-gamma significantly suppressed virus replication and inflammation in the heart. CONCLUSIONS: Our data demonstrate that IFN therapy, especially intranasal administration of IFN-gamma, dramatically improved the prognosis of acute murine viral myocarditis by suppressing virus replication and raises the possibility of antiviral therapy with IFN-gamma in patients with acute myocarditis.

Administration, Intranasal↗
PubMed1998

Detection of chromogranin A mRNA in small cell lung carcinoma using a new, highly sensitive in situ hybridization method with a non-radioisotope oligonucleotide probe.

BACKGROUND: Immunoreactivity for chromogranin A (Cg A) is associated with the presence of neurosecretory granules in tumor cells, but immunohistochemical staining for Cg A may be absent in small cell lung carcinoma (SCLC), which has only a few secretory granules. Localization of Cg A mRNA is a useful indicator of the site of synthesis of a particular protein and possibly the rate of synthesis, and it is not dependent on posttranslation events within the cells. However, it is difficult to detect the low levels of mRNA copies using the standard non-radioisotope (RI) oligonucleotide probe. METHODS: The authors analyzed Cg A mRNA in 20 cases of SCLC in formalin fixed, paraffin embedded tissue using a new, highly sensitive in situ hybridization method that was developed from the maximized immunohistochemistry (ImmunoMax) method. They also investigated Cg A mRNA in nonsmall cell lung carcinoma (NSCLC), including ten cases each of adenocarcinoma and squamous cell carcinoma of the lung. RESULTS: All examined SCLC tissues showed a positive reaction for Cg mRNA. No NSCLC specimens showed any positive reaction for Cg A mRNA. CONCLUSIONS: The detection of Cg A mRNA using the new, highly sensitive in situ hybridization method with a non-RI oligonucleotide probe can be used to characterize neuroendocrine differentiation of lung tumors even when the Cg A protein is not detected by immunohistochemistry. The authors believe this is a first step toward better diagnosis and treatment for patients with SCLC.

Adult↗
PubMed1998

Effect of SA4503, a novel sigma1 receptor agonist, against glutamate neurotoxicity in cultured rat retinal neurons.

We examined the effects of sigma1 receptor agonists against glutamate-induced neurotoxicity in cultured retinal neurons. Primary cultures obtained from fetal rat retinas (16-19 d gestation) were used. The neurotoxic effect of glutamate was quantitatively assessed using the trypan blue exclusion method. A brief exposure of retinal cultures to glutamate (500 microM) led to delayed neuronal cell death. The glutamate-induced neurotoxicity was inhibited by (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo-[a,b]-cyclohepten-5 ,10-imine hydrogen maleate (MK-801). The sigma1 receptor agonists, 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)-piperazine dihydrochloride (SA4503) and (+)-pentazocine at a concentration range of 0.1 approximately 100 microM reduced the glutamate-induced neurotoxicity in a dose-dependent manner. In addition, the neuroprotective effects of both SA4503 and (+)-pentazocine were antagonized by co-treatment with N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]ethylamine monohydrochloride (NE-100), a putative sigma1 receptor antagonist. These findings suggest that sigma1 receptor agonists protect retinal cells against glutamate-induced neurotoxicity.

Analgesics, Opioid↗
PubMed1998

Integrated and episomal forms of Epstein-Barr virus (EBV) in EBV associated disease.

Epstein-Barr virus (EBV) is known to be linear in viral particles but EBV circularizes into an episomal form after infection. Recently, the presence of integrated EBV DNA has been reported. We investigated EBV integration into the human genome in EBV-associated disease using Southern blotting. One hundred four cases in which the presence of EBV was confirmed by Southern blotting with EBV-W probes were thus analyzed with left- and right-hand end probes of linear EBV. Integrated EBV was demonstrated in 11 of 104 cases; five of 14 cases with B cell lymphoma (36%), one of 12 cases with nasopharyngeal carcinomas (8%), four of 31 cases with natural killer (NK) leukemia/lymphoma (13%) and one of 11 cases with chronic EBV infection (9%). However, none of the 24 T cell lymphoma, seven Hodgkin's disease, or five acute EBV infection cases showed integrated EBV. In addition, seven of the 11 cases with EBV integration (five B cell lymphoma and two NK leukemia/lymphoma) showed only an integration form, however, the other four (two NK leukemia/lymphoma, one nasopharyngeal carcinoma and one chronic EBV infection) showed both integrated and episomal forms. The integrated form was frequently found in B cell lymphoma and especially in high grade B cell lymphoma. Fluorescence in situ hybridization (FISH) was performed in two cases (NK and B cell lymphoma), which represented integrated EBV in Southern blotting and the integration form was confirmed in both. However, it is still uncertain as to whether or not the EBV integration site is directly associated with chromosomal abnormality.

Blotting, Southern↗
PubMed1998

Successful treatment of a patient with cardiac lymphoma who presented with a complete atrioventricular block.

A patient with primary cardiac lymphoma, which is very rare, generally is regarded to have a poor prognosis. We herein report a patient with cardiac lymphoma who was treated successfully by systemic chemotherapy and radiotherapy using a pacemaker to control the complete atrioventricular (A-V) block. A 70-year-old man had a syncope caused by a complete A-V block. An echocardiogram, a computed tomographic scan, and magnetic resonance imaging of his chest showed a cardiac tumor. At this time, a biopsy of the cardiac tumor disclosed malignant lymphoma (diffuse large cell type, B cell type). The patient was thus treated with systemic chemotherapy and radiotherapy and, as a result, achieved a complete remission with a disappearance of the A-V block. Recently, several successful outcomes involving primary cardiac lymphoma have been reported because of the progress in diagnostic techniques including echocardiography, computed tomographic scanning, and magnetic resonance imaging, as well as improvement in the therapy of malignant lymphoma. Our clinical experience indicated that an early and accurate diagnosis combined with the appropriate therapy can thus help in obtaining a long survival in patients with primary cardiac lymphoma.

Aged↗
PubMed1998

Calcium-binding and structural stability of echidna and canine milk lysozymes.

For echidna and canine milk lysozymes, which were presumed to be the calcium-binding lysozymes by their amino acid sequences, we have quantitated their calcium-binding strength and examined their guanidine unfolding profiles. The calcium-binding constants of echidna and canine lysozymes were determined to be 8.6 x 10(6) M(-1) and 8.9 x 10(6) M(-1) in 0.1 M KCl at pH 7.1 and 20 C, respectively. The unfolding of decalcified canine lysozyme proceeds in the same manner as that of alpha-lactalbumin, through a stable molten globule intermediate. However, neither calcium-bound nor decalcified echidna lysozyme shows a stable molten globule intermediate. This unfolding profile of echidna lysozyme is identical to that of conventional lysozymes and pigeon egg-white lysozyme, avian calcium-binding lysozyme. This result supports the suggestion of Prager and Jolles (Prager EM, Jolles P. 1996. Animal lysozymes c and g: An overview. In: Jolles P, ed. Lysozymes: Model enzymes in biochemistry and biology. Basel-Boston-Berlin: Birkhauzer Verlag. pp 9-31) that the lineage of avian and echidna calcium-binding lysozymes and that of eutherian calcium-binding lysozymes diverged separately from that of conventional lysozymes.

Animals↗