Biomedical subjects

K Honda

Publications and source records attributed to K Honda.

At least 109 records · Page 6Linked to original sources

PubMed2001

[Clinical significance of measuring inferior vena cava dimension in patients with acute exacerbation of chronic heart failure].

OBJECTIVES: This study determined the clinical significance of measuring the inferior vena cava dimension in patients with heart failure. METHODS: The subjects were 373 patients admitted due to acute exacerbation of chronic heart failure. The relationships were examined between inferior vena cava dimension in the end-expiratory phase on admission and in the stable state and etiology of heart failure, age, New York Heart Association (NYHA) functional classification in the stable state (before exacerbation), body weight, grade of tricuspid regurgitation, left ventricular end-diastolic dimension and left ventricular ejection fraction measured by two-dimensional echocardiography in the stable state and on admission, severity of lung congestion (Killip's classification) on admission, and clinical course during treatment. RESULTS: The inferior vena cava dimension was not correlated with etiology, age, NYHA functional classification, body weight, left ventricular end-diastolic dimension or left ventricular ejection fraction, but was correlated with the grade of tricuspid regurgitation (r = 0.78, p < 0.0001 in the stable state, r = 0.60, p < 0.0001 and on admission). The severity of lung congestion did not correlate with inferior vena cava dimension on admission or the increase in inferior vena cava dimension. The increase in body weight on admission was correlated with the increase in inferior vena cava dimension (r = 0.83, p < 0.0001), but did not correlate with inferior vena cava dimension on admission. Tricuspid regurgitation grade and inferior vena cava dimension were restored to the stable state when body weight reached stable state after treatment in patients (n = 202) with inferior vena cava dimension increased by over 5 mm on admission. CONCLUSIONS: Inferior vena cava dimension in patients with heart failure is correlated with the tricuspid regurgitation grade in the stable state and at acute exacerbation. The increase in inferior vena cava dimension between stable and exacerbated states, but not the actual value, is clinically useful to evaluate patients with acute exacerbation of chronic heart failure.

Chronic Disease↗

PubMed2001

[Intermittent administration of 5-FU and isovorin to patients with advanced and recurrent colon cancer].

We attempted a new regimen of intermittent administration of 5-FU and low-dose Isovorin (F.I) to four patients with advanced and recurrent colon cancer. A partial response (PR) was achieved in two of four patients who had evaluable lesions for this treatment. We observed few side effects among these patients. Only one patient among four showed grade 1 neuropathy after two administrations of this chemotherapy. However, after a two-week pause in administration, the neuropathy disappeared and we could continue the therapy. This patient with multiple liver metastases achieved a partial response. Other patients had no side effects such as bone marrow suppression or digestive symptoms. This intermittent F.I treatment might be an effective and promising therapy with few side effects even for patients with poorer conditions.

Aged↗

PubMed2001

Studies on mechanisms of low emetogenicity of YM976, a novel phosphodiesterase type 4 inhibitor.

YM976 is a novel and selective inhibitor of phosphodiesterase type 4 (PDE4) with a different chemical structure from rolipram. Orally administered YM976 showed anti-inflammatory activity (ED(50) = 2.8 mg/kg) similar to rolipram (3.5 mg/kg). On the other hand, the emetogenicity of YM976, one of the main adverse effects of PDE4 inhibitors, was lower (maximal non-emetic dose = 10 mg/kg) than that of rolipram (1 mg/kg). The reasons for this low emetogenicity of YM976 remain unclear, and the present study endeavored to elucidate the mechanisms. Candidates for the possible mechanisms included 1) PDE4 subtype selectivity, 2) binding affinity for HAR-conformation, and 3) brain penetration. YM976 exhibited affinity for high affinity for rolipram-conformation (HAR-conformation) (IC(50) = 2.6 nM) identical to that of rolipram (1.2 nM), and failed to show significant selectivity for the individual PDE4 subtype. These results suggested that neither subtype selectivity nor the affinity for HAR-conformation may be related to the low emetogenicity of YM976. YM976 showed a minor effect on reserpine-induced hypothermia, in contrast to rolipram. To estimate brain penetration, we then measured cAMP contents in peripheral tissues (peritoneal macrophages) and in the brain. YM976 increased the cAMP content of peritoneal macrophages, but caused no significant increase in brain cAMP levels, while rolipram elevated the cAMP content of both tissues at the same dose. In conclusion, YM976 shows an apparent dissociation between its anti-inflammatory effects and emetogenicity, perhaps because of the poor brain penetration.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2001

DNA testing of Klinefelter's syndrome in a criminal case using XY chromosomal STR multiplex-PCR.

We report genetic typing of Klinefelter's syndrome applied to casework in forensic DNA testing. In this case, by using extracted DNA from body samples (muscle and bones), we could identify two distinct X alleles in two out of three X-STR loci (HPRTB and ARA), in addition to Y alleles (DYS390, DYS393). The extra X was found to have originated from father, and the victim turned out to have 47XXY Klinefelter's syndrome. The victim was a 30-year-old male, born from relatively elderly parents as a second child. His father was a severe alcoholic and had been malnourished for more than 20 years at the moment of his birth. He exhibited slight mental retardation as a child, and belonged to a criminal group as an adult. The method presented here was useful to accurately diagnose sex chromosomal abnormality instead of conventional chromosomal analysis and Xg blood group typing. A subtype of this syndrome, 48 XXXY or mosaic, for example, could be identified if the intensity of the overlapped X bands were calculated.

Adult↗

PubMed2001

Inverse correlation of thioredoxin expression with estrogen receptor- and p53-dependent tumor growth in breast cancer tissues.

Estrogen receptor (ER) and p53 are important transcription factors in the growth regulation of tumor cells in breast cancer. We reported previously that thioredoxin (TRX) regulates the DNA binding activities of ER and p53 in vitro. The expression of pS-2, a trefoil factor, is also correlated with that of ER. To clarify the regulation mechanism of tumor growth in breast cancer, here we investigated the expression of TRX, ER, pS-2, and p53 and the mitotic index (MI) in 147 breast cancer tissues using immunohistochemical analysis. Of 123 TRX+ cases, ER+ cases (n = 62) showed a higher pS-2 score and lower MI than did ER- cases (n = 61). Furthermore, p53- cases (no mutation in p53; n = 76) also showed a lower MI than did p53+ cases (n = 47). There was no significant correlation between pS-2 and ER, MI and ER, or p53 and MI in the TRX- group. Among the ER+ and p53- cases (ER+/p53- group; n = 61), MI was lower in the TRX+ group (n = 46) than in the TRX- group (n = 15). However, in all other groups (n = 86) with abnormalities in the immunohistochemical expression of either p53 or ER, there was no significant correlation between MI and TRX expression. In the TRX+ and ER +/p53- group (n = 46), histological grading was lower than that in all other groups (n = 101). These findings suggest that TRX expression is linked to the ER- and p53-dependent regulation of tumor growth in breast cancer. In addition, TRX expression in ER+ and p53 intact (wild-type p53+) groups may mean better prognosis than in other conditions.

Adult↗

PubMed2001

Tubular osteopontin expression in patients with ANCA-associated glomerulonephritis.

OBJECTIVE: To elucidate the role of osteopontin (OPN) in monocyte recruitment in crescentic glomerulonephritis, we investigated immunohistochemical localization of OPN in the kidney and its correlation with clinical and histopathologic parameters in biopsy specimens of patients with myeloperoxidase antineutrophil cytoplasmic autoantibody- (MPO-ANCA) associated glomerulonephritis. METHODS: Twelve patients with MPO-ANCA-associated glomerulonephritis were enrolled in this study. Clinical parameters such as creatinine clearance and urinary protein excretion of each patient were obtained at the time of biopsy. Paraffin-embedded sections were used for immunohistochemical staining using the LSAB method. Five cortical interstitial fields randomly selected at original magnification x 200 were assessed using a computer-assisted color image analyzer. Tubular OPN expression was assessed as the percentage of positive area in the tubulointerstitium. Double immunofluorescent staining using antibodies against OPN and alpha(v)beta3 was performed. RESULTS: In all of the cases studied, OPN was occasionally localized within the glomeruli, and expressed slightly in proximal tubular epithelium and significantly in distal tubular epithelium. Tubular OPN expression tended to be promoted in the interstitium infiltrating by numerous monocytes/macrophages. The extent of tubular OPN expression was positively correlated with serum ANCA titers and urinary OPN concentrations. Enhanced alpha(v)beta3 expression appeared in the distal tubular epithelium expressing OPN. CONCLUSION: These results suggest that inducible expression of OPN and alpha(v)beta3 in the tubular epithelium seems to be associated with interstitial moncyte infiltration and subsequent tubulointerstitial changes in human MPO-ANCA-associated glomerulonephritis.

Adult↗

PubMed2001

[Acute onset of tuberculous meningoencephalitis presenting with symmetric linear lesions in the bilateral thalamus: a case report].

A 18-year-old woman was admitted to our hospital because of high fever and headache. Nuchal stiffness was present, and a CSF examination showed lymphocyte-domonant pleocytosis and a decreased level of glucose. Although antibiotics, aciclovir and an antimycotic drug were administered, disturbance of consciousness, involuntary movements, and pyramidal tract signs appeared. Soon after the medications were changed to antituberculous medicines, the meningoencephalitis started to subside, and was finally cured. Judging from the clinical findings, the CSF findings, the effectiveness of antituberculous medicines, an elevated ADA level in CSF, and positive conversion in tuberculin tests, the final diagnosis was made as tuberculous meningoencephalitis. At the severest stage of the disease, a brain MRI showed symmetric, linear lesions without the effect of Gd-enhancement in the bilateral thalamus, which thereafter disappeared along with the healing of the illness. From all these things, we conclude that thalamic and other parenchymal lesions should be kept in mind in case of acute tuberculous meningoencephalitis.

Acute Disease↗

PubMed2000

Protection of cultured spinal motor neurons by estradiol.

Estrogens have been reported to exert neuroprotection in the brain, but there have been no reports of such neuroprotection in spinal motor neurons, the neurons selectively involved in amyotrophic lateral sclerosis (ALS). In this study, we demonstrated that 17beta-estradiol and its biologically inactive stereoisomer, 17alpha-estradiol, prevented glutamate- and nitric oxide (NO)-induced selective motor neuronal death observed in primary cultures of the rat spinal cord. The dose of estradiols required for motor neuron protection was greatly reduced by co-administration with glutathione. The results of this study shows that estradiol protects spinal motor neurons from excitotoxic insults in vitro, and may have application as a treatment for ALS.

Animals↗

PubMed2000

Primary CD30/Ki-1 positive anaplastic large cell lymphoma of skeletal muscle with der(17)t(1;17)(q11;p11).

CD30/Ki-1 positive anaplastic large cell lymphoma (Ki-1 ALCL) frequently exhibits extranodal disease and chromosomal t(2;5)(p23;q35). An 11-year-old girl presented with an intramuscular tumor of the right upper arm. Tumors of the chest wall, left arm and leg, hepatomegaly, pleural effusion, and enlarged lymph nodes then developed. The intramuscular tumor and pleural effusion showed a diffuse infiltration of large atypical cells with abundant amphophilic cytoplasms. The tumor cells were positive for CD30, CD2, CD45RO, and p80, but were negative for other T-cell, B-cell, and myeloid cell antigens. She was diagnosed as having Ki-1 ALCL with a T-cell origin. Cytogenetic studies showed an abnormal karyotype including a der(17)t(1;17)(q11;p11). She received seven cycles of intensive chemotherapy followed by an autologous peripheral blood stem cell transplantation, and has been in complete remission for more than two years. The primary involvement of skeletal muscle is quite uncommon in ALCL, and an abnormal karyotype including t(1;17)(q11;p11) has not been reported previously. Since a high frequency of aberrations of 1p36/1q12 or 17p13.3 was detected in sarcoma cells, the presence of suppressor genes is suggestive in these sites.

Child↗

PubMed2000

Abnormal expression of BRCA1 and BRCA1-interactive DNA-repair proteins in breast carcinomas.

Breast cancer is one of the most common malignancies among women. The molecular mechanisms involved in breast carcinogenesis, however, remain to be elucidated. Although somatic mutation of BRCA1 is rare, BRCA1 protein expression is reduced in about 30% of sporadic breast carcinomas (Yoshikawa et al., Clin. Cancer Res., 5:1249-1261, 1999), indicating its possible involvement even in sporadic breast carcinogenesis. Among the BRCA1-interactive proteins are hRAD51 (a human homologue of Escherichia coli rec A protein), BARD1 (BRCA1-associated RING domain 1) and p53, all of which are involved in DNA repair. We have analyzed the expression patterns of the hRAD51, BARD1 and p53 proteins in five breast cancer cell lines, including a BRCA1-deficient cell line, and in 179 breast cancer tissue samples from Japanese women, including 113 sporadic, 47 hereditary (i.e., BRCA1 status unknown), and 19 BRCA1-associated cases. Of the 179 breast carcinomas, fifty-four (30%) exhibited reduced hRAD51 expression, and sixty-two (35%) exhibited p53 overexpression. On the other hand, reduced expression level of BARD1, and of hMSH2 and hMLH1, which are components of DNA mismatch-repair pathway and are involved in colorectal carcinogenesis, was observed respectively in only 10 (6%), 8 (5%) and 3 (2%) cases. The overall frequency of sporadic breast carcinomas with abnormal expression of either BRCA1 or the BRCA1-interactive proteins was 67% (76/113). These results indicate that there may be an important role for the BRCA1-associated DNA-repair pathway, not only in BRCA1-associated breast carcinomas, but also in sporadic breast carcinomas.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Quantitative ultrasonic tissue characterization can identify high-risk atherosclerotic alteration in human carotid arteries.

BACKGROUND: Recently, ultrasonic tissue characterization of the composition of plaques has been performed in a quantitative fashion on the basis of integrated backscatter (IBS) analysis, but most of those studies have used high-frequency ultrasound to obtain microscopic images. METHODS AND RESULTS: We performed B-mode measurement and IBS signal analysis with acoustic densitometry with a 7.5-MHz linear-array transducer in freshly excised human aortas (n=58) (normal, atheromatous, and fibrous tissue) obtained at autopsy. Atheromatous and fibrous tissue had a similar intima-media thickness (IMT), but the IBS value in atheromatous specimens was lower than that in fibrous specimens. We further applied this method to human carotid ultrasonography. The subjects were young (80 regions), middle aged with 1 or no coronary risk factors (low risk) (120 regions), middle aged with >/=2 coronary risk factors (high risk) (240 regions), or elderly (80 regions) or were patients with myocardial infarction (MI) with multivessel disease (90 regions). The IMT was similar in middle-aged, elderly, and MI subjects. In contrast, the IBS value was significantly higher in elderly subjects and lower in high-risk middle-aged and MI subjects compared with that in low-risk middle-aged subjects. The percent of regions diagnosed as atheromatous (IBS less than mean minus 2-SD value of IBS in young subjects) was 11% in low-risk middle-aged subjects, 29% in high-risk middle-aged subjects, and 63% in the MI group. CONCLUSIONS: In conjunction with conventional B-mode imaging, IBS analysis with carotid ultrasonography appeared to provide prognostic information to identify a high-risk group with systemic atherosclerosis, which could lead to coronary heart disease in individuals with early-stage disease.

Adult↗

PubMed2000

The contribution of the median preoptic nucleus to renal sympathetic nerve activity increased by intracerebroventricular injection of hypertonic saline in the rat.

The median preoptic nucleus (MnPO) of the hypothalamus is involved in the osmotic control of neurohypophysial hormone release and drinking behavior. At the same time, renal sympathetic nerves exert multiple effects on renal functions such as regulating renal blood flow and urinary sodium excretion. We made the hypothesis that the MnPO may also regulate body fluid balance by exerting an influence on renal sympathetic nerve activity (RSNA). In this study we examined the effect of electrical stimulation of the MnPO on RSNA and the contribution of the MnPO to the change of RSNA induced by intracerebroventricular injection of hypertonic saline in the male Wistar rat. Electrical stimulation of the MnPO and the paraventricular nucleus of the hypothalamus (PVN) elicited an increase in RSNA. This increase of RSNA elicited by electrical stimulation of the MnPO was reduced by microinjections (100 nl) of 10% lidocaine or 4 mM cobaltous chloride (a synaptic transmission blocking agent) bilaterally into the PVN. Both RSNA and the mean arterial pressure (MAP) were increased by the injection of 1.5 M NaCl into the third ventricle, although heart rate (HR) was not significantly changed. These responses of RSNA and MAP were diminished by microinjection of 10% lidocaine (100 nl) into the MnPO. Our results suggest that the MnPO is involved in body fluid regulation not only by controlling vasopressin secretion and water intake but also by modulating central sympathetic outflow which regulates body fluid balance through an effect on the kidney.

Anesthetics, Local↗

PubMed2000

Degradation of human Aurora2 protein kinase by the anaphase-promoting complex-ubiquitin-proteasome pathway.

Human Aurora2 was originally identified by its close homology to yeast IPL1 and fly aurora, which are key regulators of chromosome segregation and a family of serine/threonine kinases. Here we demonstrate that the Aurora2 protein is degraded rapidly after G2/M phase release in mammalian cells. Aurora2 protein has a rapid turnover rate with a half-life of approximately 2 h. In eukaryotic cells, the ubiquitin-proteasome pathway is the major mechanism for the targeted degradation of unstable proteins. The treatment of mammalian cells with proteasome inhibitors blocks Aurora2 degradation. Furthermore, Aurora2 is polyubiquitinated in vivo and in vitro using anaphase-promoting complex (APC). These results demonstrate that Aurora2 protein is turned over through the APC-ubiquitin-proteasome pathway. Oncogene (2000) 19, 2812 - 2819

Anaphase-Promoting Complex-Cyclosome↗

PubMed2000

Phosphatidylinositol 3-kinase mediates neuroprotection by estrogen in cultured cortical neurons.

It has been shown that estrogen replacement in menopausal women is effective in slowing down the progression of cognitive impairment in Alzheimer's disease. Although recent studies have demonstrated the neuroprotective effects of estrogen, the precise mechanism of neuroprotection has not been elucidated. In the present study, we show that the phosphatidylinositol 3-kinase (PI3-K) cascade is involved in the neuroprotective mechanism stimulated by estrogen. Exposure to glutamate reduced the viability of rat primary cortical neurons. Pretreatment with 10 nM 17beta-estradiol significantly attenuated the glutamate-induced toxicity. This neuroprotective effect of 17beta-estradiol was blocked by co-administration with LY294002, a selective PI3-K inhibitor, but not by co-administration with PD98059, a selective mitogen activated protein kinase kinase inhibitor. Pretreatment with ICI182780, a specific estrogen receptor antagonist, also blocked the neuroprotection. Immunoblotting assay revealed that treatment with 17beta-estradiol induced the phosphorylation of Akt/PKB, an effector immediately downstream of PI3-K. These results suggest that PI3-K mediates the neuroprotective effect of 17beta-estradiol against glutamate-induced neurotoxicity.

Animals↗

PubMed2000

Involvement of M3 muscarinic receptors of the spinal cord in formalin-induced nociception in mice.

Subcutaneous injection of formalin into a paw of mice caused two distinct phases of licking and biting, first phase (1-5 min) and the second phase (7-30 min) after the injection. The muscarinic antagonist atropine (0.1-10 ng, i.t.) and the M(3) receptor antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) (0.1-20 ng, i.t.) inhibited the second phase of this response, whereas higher doses of atropine (20-100 ng, i.t.) did not cause inhibition. The M(1) muscarinic receptor antagonist pirenzepine (10-100 ng, i.t.) did not inhibit either the first or the second phase response, but a high dose of pirenzepine (1000 ng, i.t.) tended to inhibit the second phase response. On the other hand, the M(2) muscarinic receptor antagonist 11-¿(2-[(diethylamino)methyl]-1-piperidinyl¿acetyl)-5, 11-dihydro-6H-pyrido(2,3-b)(1,4)benzodiazepine-6-one (AF-DX116; 10-1000 ng, i.t.) had no effect on either the first or the second phase of response. The opioid receptor antagonist naloxone did not affect the 4-DAMP-induced anti-nociceptive response. The i.t. injection of the acetylcholinesterase inhibitor neostigmine (25 ng) significantly inhibited only the second phase. The acetylcholine (ACh) depletor hemicholinium-3 (HC-3) (1 microg, i.t.) completely abolished the 4-DAMP-induced anti-nociceptive response. The ACh content of the spinal cord was significantly increased 14 min after formalin injection. This significant increase in the ACh content was inhibited by pretreatment with 4-DAMP (10 ng, i.t.). These results suggest that endogenous ACh in the spinal cord acts as a transmitter anti-nociception, and that ACh release regulated by presynaptic M(3) muscarinic receptors in the spinal cord is involved in the second phase of nociception induced by formalin.

Acetylcholine↗

PubMed2000

Novel substrate specificity of a membrane-bound beta-glycosidase from the hyperthermophilic archaeon Pyrococcus horikoshii.

A beta-glycosidase gene homolog of Pyrococcus horikoshii (BGPh) was successfully expressed in Escherichia coli. The enzyme was localized in a membrane fraction and solubilized with 2.5% Triton X-100 at 85 degrees C for 15 min. The optimum pH was 6.0 and the optimum temperature was over 100 degrees C, respectively. BGPh stability was dependent on the presence of Triton X-100, the enzyme's half-life at 90 degrees C (pH 6.0) was 15 h. BGPh has a novel substrate specificity with k(cat)/K(m) values high enough for hydrolysis of beta-D-Glcp derivatives with long alkyl chain at the reducing end and low enough for the hydrolysis of beta-linked glucose dimer more hydrophilic than aryl- or alkyl-beta-D-Glcp.

Amino Acid Sequence↗

PubMed2000

Large deletion of the X-linked lymphoproliferative disease gene detected by fluorescence in situ hybridization.

The X-linked lymphoproliferative disease (XLP) is an inherited immunodeficiency characterized by an abnormal responses to infection with Epstein-Barr virus (EBV), resulting in fatal infectious mononucleosis, hypogammaglobulinemia, virus-associated hemophagocytic syndrome, and malignant lymphoma. Mutations in the gene coding for a T cell-specific SLAM-associated protein (SAP) have been recently identified in XLP patients. We report on a 1-year-old boy representing fulminant hemophagocytic syndrome. He developed high fever, lymphadenopathy, hepatosplenomegaly with liver dysfunction, and pancytopenia with marrow hemophagocytosis. EBV DNA was abnormally increased in the blood. Polymerase chain reaction failed to amplify SAP mRNA and genomic DNA products from the patient' As peripheral blood. A large deletion of the SAP gene was confirmed by fluorescence in situ hybridization (FISH). FISH analysis also disclosed that the patient's mother was a carrier. We conclude that FISH can be useful in the diagnosis of XLP with large deletions of the SAP gene and its carrier state.

Carrier Proteins↗

PubMed2000

HLA-DQB1 and HLA-DPB1 genotypes in severe preeclampsia.

OBJECTIVE: To clarify whether there are susceptible HLA-DQB1 or HLA-DPB1 alleles in women with preeclampsia. METHODS: The frequency of HLA-DQB1 and HLA-DPB1 alleles was analyzed in 47 women with previous severe preeclampsia and compared with that in 85 normal fertile women. The types of HLA-DQB1 and HLA-DPB1 alleles were assessed using a polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: The frequency of HLA-DQB1*04 allele in previously preeclamptic women was 21.3% (20 of 94 loci) and in the controls was 11.2% (19 of 170 loci). Thus, the HLA-DQB1*04 allele frequency was significantly higher in preeclamptic women compared with controls (P <.05 by chi(2) test, OR 2.15, 95% confidence interval 1.08, 4.27). The frequency of other HLA-DQB1 alleles and all HLA-DPB1 alleles was not significantly different between groups. The incidence of homozygosity of HLA-DQB1 or HLA-DPB1 alleles in preeclamptic women was not significantly different compared with that of normal fertile women. CONCLUSION: These data suggest that women who have the HLA-DQB1*04 allele might be susceptible to preeclampsia.

Adult↗