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Biomedical subjects

Y Endo

Publications and source records attributed to Y Endo.

At least 145 records · Page 8Linked to original sources

Quantification of viral ribonucleic acid in plasma of cats naturally infected with feline immunodeficiency virus.

OBJECTIVE: To assess plasma viral RNA concentration in cats naturally infected with feline immunodeficiency virus (FIV). ANIMALS: 28 FIV-infected cats. PROCEDURE: Cats were categorized into 1 of the 3 following stages on the basis of clinical signs: asymptomatic (nonclinical) carrier (AC; n = 11), acquired immunodeficiency syndrome-related complex (ARC; 9), or acquired immunodeficiency syndrome (AIDS; 8). Concentration of viral RNA in plasma (copies per ml) was determined by use of a quantitative competitive polymerase chain reaction (QC-PCR) assay. Total lymphocyte count, CD4+ cell and CD8+ cell counts, and the CD4+ cell count-to-CD8+ cell count ratio were determined by use of flow cytometry. RESULTS: Plasma viral RNA concentration was significantly higher in cats in the AIDS stage, compared with cats in AC and ARC stages. Most (5/7) cats in the AIDS stage had low total lymphocyte, CD4+ cell, and CD8+ cell counts. CONCLUSIONS AND CLINICAL RELEVANCE: Concentration of plasma viral RNA is a good indicator of disease progression in FIV-infected cats, particularly as cats progress from the ARC to the AIDS stage. Determination of CD4+ and CD8+ cell counts can be used as supportive indicators of disease progression.

Animals↗

Comparisons of effects of raw and gelatinized sago and tapioca starches on serum and liver lipid concentrations in rats.

Effects of raw and gelatinized sago and tapioca starches on serum and liver lipid concentrations were compared in rats fed a cholesterol-enriched diet. Total serum cholesterol and the atherogenic index in the rats fed raw sago starch showed a statistically significant decrease and tendency to decrease, respectively, when compared with those of rats fed raw tapioca starch. Both the serum total cholesterol and atherogenic index in the rats fed gelatinized sago starch showed a tendency to decrease when compared with those of rats fed gelatinized tapioca starch. Serum triacylglycerol concentrations in the rats fed raw sago starch were significantly lower than those in the rats fed raw tapioca starch. The apparent digestibility of raw sago starch was lower than that of tapioca starch. The oval shapes of undigested raw sago starch granules collected from feces remained almost unchanged in shape, but had some holes and scrapes on their surfaces. The shape surfaces of undigested raw tapioca starch collapsed, thereby not retaining their original granule shapes. On the other hand, the amylose contents in the raw and gelatinized sago starches were higher than those in the raw and gelatinized tapioca starches. These results suggested that a decrease or a tendency to decrease in serum total cholesterol levels and atherogenic indexes in raw or gelatinized sago starch-fed rats compared to those of raw or gelatinized tapioca starch-fed rats, and a decrease in serum triacylglycerol concentrations in raw sago starch-fed rats compared to those of raw tapioca starch-fed rats, were due to the lower digestibility and higher amylose content of sago starch.

Amylases↗

Clinical significance of S100A4 and E-cadherin-related adhesion molecules in non-small cell lung cancer.

S100A4 has been implicated in the malignant phenotype of tumor cells, including cell motility, but the biological function is hardly known. A recent study suggests that S100A4-induced invasiveness in malignant tumor cells is partially caused by down-regulation of E-cadherin. To clarify the clinical significance of S100A4 and its association with E-cadherin-mediated cell-to-cell adhesion system, we examined their protein expressions in non-small cell lung cancer (NSCLC) specimens using immunohistochemical techniques. Expression of S100A4 was observed in 81 (60%) of 135 NSCLCs and correlated with progression of the pathological T factor (p<0.001), lymph node metastasis (p<0.005), and poor survival (p<0.05). Reduced expression of E-cadherin, alpha-catenin, and beta-catenin was observed in 64% (87 of 135), 50% (43 of 86), and 58% (50 of 86) of the specimens tested, respectively. The expression of E-cadherin closely correlated with differentiation and inversely with that of S100A4. Among these adhesion-associated molecules we found that alpha-catenin appeared to reflect most strikingly the presence of lymph node metastasis and the short survival periods of NSCLC patients. Furthermore, patients who showed S100A4-positive/alpha-catenin-negative expression had a significantly shorter survival than the patients with S100A4-negative/alpha-catenin-positive expression. These results indicate that S100A4, as well as alpha-catenin, plays a role in the progression and metastasis of NSCLCs and that simultaneous immunohistochemical detection of their expression may be useful to define a subpopulation of lung cancer patients with a possible poor prognosis.

Aged↗

Fatal Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis with clonal karyotype abnormality.

We report a case of Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH) with clonal karyotype abnormality. A 5-year-old boy was admitted to our hospital with persistent high-grade fever, hepatomegaly, and pancytopenia. Laboratory data disclosed a coagulation abnormality and severe liver damage. Clonal proliferation of EBV-infected cells was detected in the bone marrow by Southern hybridization, and bone marrow cells exhibited clonal chromosomal abnormality. Although the patient was treated with immunochemotherapy according to the HLH94 protocol, the disease recurred during the induction therapy, and the patient died of disseminated intravascular coagulopathy. Considering this aggressive and fatal clinical course, it is important to take intensive therapeutic measures if karyotype abnormality is noted in the treatment of EBV-HLH patients.

Bone Marrow Cells↗

Continuous monitoring of change in hemodilution during water immersion in humans: effect of water temperature.

BACKGROUND: The present study was designed to examine whether water temperature during head-out immersion (HOI) modifies hemodilution dynamics. METHODS: We made continuous measurements of blood density (rho(b)) during HOI at 3 different water temperatures; the lower critical (32 degrees C), neutral (34.5 degrees C), and upper critical (36 degrees C) temperatures in 6 healthy male volunteers. Blood was withdrawn continuously from the antecubital vein for measurement of rho(b) during 60 min of water immersion with a 10-min control period before the immersion. The density was measured with the mechanical oscillator technique. Hematocrit (Hct), plasma density (rho(p)), and osmolality were measured at 5-min intervals. Erythrocyte density (rho(e)) was calculated from rho(b), rho(p) and Hct. Cardiac output and BP were measured to calculate total peripheral resistance. RESULTS: Hct, rho(b), and rho(p) decreased rapidly in the first 20-25 min of immersion and were maintained at a reduced level during immersion. Plasma volume calculated from rho(p) and Hct increased with the rho(b) reduction. These immersion-induced changes were independent of these water temperatures. Plasma osmolality and rho(e) remained constant throughout the experimental period in the three temperature conditions, indicating that the increase in plasma volume and hence hemodilution was induced by an isotonic fluid shift from extravascular space. The total peripheral resistance increased inversely in proportion to the water temperature during HOI. CONCLUSION: In the present condition, water temperature did not modify the net transcapillary fluid transfer during HOI in the presence of the temperature dependent increase in vascular tone.

Adult↗

Antimetastatic and antitumor effects of 2,4-diamino-6-(pyridine-4-yl)-1,3,5-triazine (4PyDAT) on the high lung metastatic colon 26 tumor in mice.

The therapeutic potential of a diaminotriazine, 2,4-diamino-6-(pyridine-4-yl)-1,3,5-triazine (4PyDAT), was investigated in a metastatic model using the mouse colon 26 carcinoma variant (Co26Lu), which preferentially metastasizes to the lung of mouse. The compound had a moderate antimetastatic activity as well as antitumor activity, without toxicity to the host, when administered orally. In the cytotoxicity test in vitro, 4PyDAT showed very weak direct cytotoxicity against the Co26Lu cell line, Co26Lu(F55) (IC50 < or = 1000 microM). Less microcapiral formation on tumors were observed for the treated group with a hemorrhage than the control group under microscopy. 4PyDAT significantly inhibited the production of urokinase-type plasminogen activator (u-PA) in Co26Lu(F55) cells. These results suggest that the antimetastatic and antitumor activities of 4PyDAT are due in part to inhibition of angiogenesis, rather than direct antiproliferative action on the tumor cells. 4PyDAT may become a lead compound to develop antitumor triazine derivatives based on antiangiogenic action.

Animals↗

[Intra-arterial infusion chemotherapy in combination with microwave hyperthermia for cancer of head of pancreas and liver metastasis--a case of 16 years survival].

Our experience of arterial infusion chemotherapy combined with regional hyperthermia in the treatment of non-resectable pancreatic cancer was presented. A patient with cancer in the pancreatic head with accompanying extensive metastasis in both hepatic lobes was treated by sub selective aortic infusion of 5-FU and MMC with microwave hyperthermia. Both the cancer in the pancreatic head and the liver metastasis showed complete remission for 16 years.

Antineoplastic Combined Chemotherapy Protocols↗

Estrogenic antagonists bearing dicarba-closo-dodecaborane as a hydrophobic pharmacophore.

Dicarba-closo-dodecaboranes (carboranes), which have spherical geometry and hydrophobicity, are applicable as a hydrophobic pharmacophore of biologically active molecules. We have designed and synthesized estrogenic antagonists based on the structure of the potent agonist 1-hydroxymethyl-12-(4-hydroxyphenyl)-1,12-dicarba-closo-d odecaborane, which we have developed. The compounds showed potent antagonistic activity in luciferase reporter gene assay using COS-1 cells transfected with rat ER alpha-expression plasmid and an appropriate reporter plasmid.

Animals↗

Structure-activity study of estrogenic agonists bearing dicarba-closo-dodecaborane. Effect of geometry and separation distance of hydroxyl groups at the ends of molecules.

Dicarba-closo-dodecaboranes (carboranes), which have spherical geometry and hydrophobicity, are applicable as a hydrophobic pharmacophore of biologically active molecules. We have investigated structure-activity relations based on the structure of the potent estrogenic agonist, 1-hydroxymethyl-12-(4-hydroxyphenyl)-1,12-dicarba-closo-d odecaborane, which we have previously reported. The geometry and separation distance of the phenolic and alcoholic hydroxyl groups play a critical role in the appearance of biological activity.

Animals↗

A new member of the GTPase superfamily that is upregulated in highly metastatic cells.

Two sublines of B16 melanoma cells, F10 and BL6, are metastatic after intravenous injection, but only BL6 cells are metastatic after subcutaneous injection. We found a new member of the GTPase superfamily, namely TIB929, which displayed an induction of expression in BL6 cells. It conserved three consensus sequences for GTP-binding site motifs and showed a significant homology to the yeast Gtr2 gene throughout the coding sequence. TIB929 was expressed ubiquitously in human tumor cells, with a marked expression in highly metastatic cells. TIB929 was mapped on mouse chromosome 4D, syntenic to human chromosome 1p. The results suggested an involvement of TIB929 in malignant progression.

Amino Acid Sequence↗

Emergence of a highly pathogenic simian/human immunodeficiency virus in a rhesus macaque treated with anti-CD8 mAb during a primary infection with a nonpathogenic virus.

Although simian/human immunodeficiency virus (SHIV) strain DH12 replicates to high titers and causes immunodeficiency in pig-tailed macaques, virus loads measured in SHIV(DH12)-infected rhesus monkeys are consistently 100-fold lower and none of 22 inoculated animals have developed disease. We previously reported that the administration of anti-human CD8 mAb to rhesus macaques at the time of primary SHIV(DH12) infection resulted in marked elevations of virus loads. One of the treated animals experienced rapid and profound depletions of circulating CD4(+) T lymphocytes. Although the CD4(+) T cell number partially recovered, this monkey subsequently suffered significant weight loss and was euthanized. A tissue culture virus stock derived from this animal, designated SHIV(DH12R), induced marked and rapid CD4(+) cell loss after i.v. inoculation of rhesus monkeys. Retrospective analyses of clinical specimens, collected during the emergence of SHIV(DH12R) indicated: (i) the input cloned SHIV remained the predominant virus during the first 5-7 months of infection; (ii) variants bearing only a few of the SHIV(DH12R) consensus changes first appeared 7 months after the administration of anti-CD8 mAb; (iii) high titers of neutralizing antibody directed against the input SHIV were detected by week 10 and persisted throughout the infection; and (iv) no neutralizing antibody against SHIV(DH12R) ever developed.

Amino Acid Sequence↗

A new class of enzyme acting on damaged ribosomes: ribosomal RNA apurinic site specific lyase found in wheat germ.

A new enzyme, which we named ribosomal RNA apurinic site specific lyase (RALyase), is described. The protein was found in wheat embryos and has a molecular weight of 50 625 Da. The enzyme specifically cleaves the phosphodiester bond at the 3' side of the apurinic site introduced by ribosome-inactivating proteins into the sarcin/ricin domain of 28S rRNA. The 3' and 5' ends of wheat 28S rRNA at the cleavage site are 5'-GUACG-alpha-hydroxy-alpha, beta-unsaturated aldehyde and pGAGGA-3', demonstrating that the enzyme catalyzes a beta-elimination reaction. The substrate specificity of the enzyme is extremely high: it acts only at the apurinic site in the sarcin/ricin domain of intact ribosomes, not on deproteinized rRNA or DNA containing apurinic sites. The amino acid sequences of five endopeptidase LysC-liberated peptides from the purified enzyme were determined and used to obtain a cDNA sequence. The open reading frame encodes a protein of 456 amino acids, and a homology search revealed a related rice protein. Similar enzyme activities were also found in other plants that express ribosome-inactivating proteins. We believe that RALyase is part of a complex self-defense mechanism.

Amino Acid Sequence↗

Characterization of the human dihydropyrimidinase-related protein 2 (DRP-2) gene.

The genes within the dihydropyrimidinase-related protein (DRP) family, were originally identified in humans by their homology to dihydropyrimidinase (DHP). Four members of this gene family, DRP-1, -2, -3 and -4, are expressed mainly in the fetal and neonatal brains of mammals and chickens, and have been implicated as intracellular signal transducers in the development of the nervous system. We isolated the human DRP-2 gene, and determined its transcriptional start site and exon/intron organization. The gene spanned more than 62 kb, and contained 14 exons with lengths ranging from 62 bp to 2606 bp. The transcriptional start site was determined by an RNase protection assay and 5' rapid amplification of cDNA ends (RACE), and a highly GC-rich promoter was identified that contained possible regulatory elements such as a TATA box, CAAT box and three GC boxes. Comparison of the phase and position of intron insertions within the human DRP-2 gene with those within DRP-1, DHP and two Caenorhabditis elegans DRP/DHP homologs, indicated that DRPs are more conserved in their exon/intron organization than DHP.

Amidohydrolases↗

Therapeutic advantage of angiotensin converting enzyme inhibitors in chronic glomerulonephritis.

Hypertension in chronic progressive renal disease is a major clinical problem leading to renal function loss. We studied the influence of ambulatory blood pressure (ABP) and the effect of hypertension therapy on renal function in 116 patients with chronic glomerulonephritis. Patients were subdivided as hypertensive, normotensive and hypotensive according to the level of ABP and age. Hypotensive subjects showed improvement of renal function and normotensive subjects showed slower rate of progression of renal function loss than hypertensives, suggesting the adequate level of ABP was 100-125/55-75 mm Hg in patients less than 40 years old, 100-135/60-80 mm Hg in patients 40-60 years old, and 105-140/60-85 mm Hg in patients over 60 years, respectively. The renal protection of calcium antagonists was associated with achieving lower blood pressure levels, whereas the blood pressure level did not affect progression of renal function in patient treated with angiotensin converting enzyme (ACE) inhibitor. ACE inhibitor, but not calcium antagonists, showed a reduction of urinary protein excretion. Thus, the mechanisms of renal protection were different between ACE inhibitors and calcium antagonists.

Adolescent↗

A long-term stress exposure impairs maze learning performance in rats.

To elucidate hippocampal dysfunctions following chronic stress exposure, we evaluated the effect of chronic stress on maze learning performance, as assessed by a radial eight-arm maze task. In the 12-week stress sessions, male rats in the stress group were exposed to the stress of a 15-min immersion in cold water once a day and, rats in the control group were slightly handled. Rats in the stress group performed significantly poorly during the acquisition period (P < 0.01) and required more trials to attain at least seven correct choices in the first eight choices for five consecutive trials (P < 0.05). Together with our previous findings that chronic stress exposure damages the hippocampus histologically, we concluded that chronic stress exposure resulted in an impairment of maze learning performance, probably due to hippocampal damages.

Animals↗

Protein kinase C modulators bearing dicarba-CLOSO-dodecaborane as a hydrophobic pharmacophore.

The size and position of a hydrophobic moiety on a benzolactam skeleton, which reproduces the active conformation and biological activity of teleocidins, play an important role in the appearance of the activity. We have designed and synthesized benzolactams bearing dicarba-closo-dodecaborane. These compounds showed potent binding affinity to protein kinase C, providing a further example of the application of carborane as the hydrophobic pharmacophore of biologically active molecules.

Boron Compounds↗