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Biomedical subjects

H Okada

Publications and source records attributed to H Okada.

At least 163 records · Page 9Linked to original sources
PubMed2000

Circulating bronchoepithelial cells expressing mRNA for surfactant protein A in patients with pulmonary fibrosis.

There are several unsolved clinical findings in patients with idiopathic pulmonary fibrosis (IPF); (i) predominance of fibrosis in the lower lung fields, (ii) digital clubbing, and (iii) patchy distribution of pulmonary fibrosis. To explain these unsolved problems, we hypothesized that regenerated or premature bronchoepithelial cells may circulate in the blood in patients with IPF. To prove this, we performed the reverse transcriptase-polymerase chain reaction (RT-PCR) for cytokeratin 19 (CK19) and pulmonary surfactant protein A (SPA) in peripheral blood in patients with IPF and pulmonary fibrosis associated with collagen vascular disorders. In addition, 20 patients with chronic pulmonary emphysema as a disease control and 19 normal volunteers were also evaluated for the existence of circulating bronchoepithelial cells. RT-PCR analysis showed that CK19 was expressed in 12 of 38 blood samples (31.6%) of IPF and pulmonary fibrosis associated with collagen vascular disorders, seven of 20 (35.0%) blood samples of chronic pulmonary emphysema, and four of 19 (21.1%) blood samples of normal volunteers. mRNA for SPA was positive in eight of 38 (21.1%) blood samples of IPF. In contrast, SPA expressing cells were not detected in any blood samples obtained from patients with chronic pulmonary emphysema or normal volunteers. This evidence suggests that there were some circulating bronchoepithelial cells expressing mRNA for SPA in peripheral blood of patients with IPF and pulmonary fibrosis associated with collagen vascular disorders.

Adult↗
PubMed2000

Inhibition of apoptosis in cultured immature rat Leydig cells by human chorionic gonadotropin associated with Bcl-2 mRNA expression.

Bcl-2 is the first identified negative regulator of apoptotic cell death. When the level of Bcl-2 mRNA in rat whole testes was examined in the present study, it gradually decreased in rats from 2.5 to 9 weeks old. We also examined the effect of human chorionic gonadotropin (hCG) on apoptosis and the level of Bcl-2 mRNA expression in immature Leydig cells in vitro. When the cells were cultured with serum free media (SFM), Bcl-2 mRNA levels gradually decreased. On the other hand, the level of Bcl-2 mRNA in cells treated with 50 ng/ml of hCG decreased at 6 h, but increased after 12 h. At 24 h, the level of Bcl-2 mRNA in the treated cells was almost the same as that of control cells (time = 0). At 12 h after the addition of various concentrations (from 0.1-1000 ng/ml) of hCG, Bcl-2 mRNA levels increased in a dose-dependent manner. An analysis of DNA fragmentation showed that treatment with hCG prevents the apoptosis of immature Leydig cells. Our findings suggest that Bcl-2 mRNA may be related to the programmed cell death of immature rat Leydig cells in vitro, which are inhibited by hCG.

Animals↗
PubMed2000

Influence of the timing of initiating antihypertensive therapy in hypertensive rats with renal failure.

The important contribution of hypertension to the progression of renal failure is well realized. However, it have been less discussed which drugs are suitable for the different stages of progressive renal failure. The present study examined the effects of timing of antihypertensive therapy using calcium channel blocker and angiotensin converting enzyme inhibitor in 5/6 nephrectomized spontaneously hypertensive rats (SHRs). Forty male 6 week old SHRs were divided into 5 groups (n=8 in each group), and they were placed on a high salt diet after 5/6 nephrectomy. Group 1, high salt diet without any drug. Group 2 received 0.2 mg/kg/day of amlodipine and group 3 received 0.2 mg/kg/day of enalapril mixed in the high salt diet from week 6 respectively. Similarly group 4 received the same doses of amlodipine, and group 5 received the same doses of enalapril from week 10. Each drug protected from increasing blood pressure in 4 groups, and no significant difference was observed between the effects of amlodipine and enalapril. Proteinuria was reduced with both drugs. In histopathological evaluation, glomerulosclerosis was controlled only in group 2, and arterio/olosclerosis was significantly suppressed in all treated groups except group 5. From these results, both amlodipine and enalapril are renal protective in early stage of renal failure with hypertension. However, in advanced stage of renal failure, amlodipine is superior in its renal protective effect.

Amlodipine↗
PubMed2000

A 2D/3D hybrid PET scanner with rotating partial slice-septa and its quantitative procedures.

This paper presents a PET scanner capable of acquiring projection data in three-dimensional (3D) and two-dimensional (2D) modes simultaneously. The scanner has rotating partial slice-septa, and coincidence events are stored as 2D data or as 3D data depending on whether the lines of response are collimated by the septa or not. 68Ge/Ga rod sources can be set on the rotating septa, and a transmission scan for attenuation correction is performed in the 2D mode. The scanner allows simultaneous 3D-emission/2D-transmission scanning or post-injection transmission scanning with little cross-talk. A blank scan for detector normalization is also performed with the rotating rod sources in the 2D mode, from which we can derive the normalizing factors in both modes. The 3D/2D difference method is available for scatter correction, even in a dynamic study where the source distribution is changing. A 'summation method' is proposed as a new image reconstruction algorithm, in which the high- and low-frequency components of images are reconstructed from the 3D and 2D data respectively. In this method, most of the scatter contribution in the 3D data is removed by high-pass filtering, not by subtracting estimated scatter distribution, and hence the method is expected to be robust for scatter from outside the axial field of view. Computer simulations revealed that the rotating partial septa offer a single-scatter to true ratio similar to that of the conventional full septa if the depth of the partial septa is properly lengthened, with a small increase in multiple scattering.

Algorithms↗
PubMed2000

Significance of human testicular mast cells and their subtypes in male infertility.

The mast cell populations in the human testis were examined using immunohistochemical techniques in five fertile volunteers and 12 patients with obstructive azoospermia, seven patients with idiopathic azoospermia, and 30 patients with varicocele. The number of mast cells per seminiferous tubular section was significantly increased (P < 0.05) in the men with idiopathic azoospermia. In the normal testes, mast cells containing only tryptase were the predominant subtype. In the patient groups, the predominant subtype of mast cell was shifted to that containing both tryptase and chymase. The average number of mast cells containing both tryptase and chymase per seminiferous tubular section was significantly increased (P < 0.05) compared with the controls in patients with obstructive azoospermia, idiopathic azoospermia, and varicocele. The number of mast cells containing only tryptase was not increased in infertile men. The selective expansion of the mast cell population containing both tryptase and chymase may be related to spermatogenetic disorders and testicular fibrosis.

Adult↗
PubMed2000

Expression of interleukin-15 in human endometrium and decidua.

In human endometrium, cytokines and growth factors that vary periodically during the menstrual cycles have been suggested to play various roles in uterine function. In the present study, differential gene expression in human endometrium between the proliferative and the secretory phases was investigated by using a human cDNA expression array system. Human interleukin (IL)-15 was identified as an up-regulated transcription product during the secretory phase, in comparison with the proliferative phase, and therefore its expression in human uterus was examined by Northern blot analysis. In human endometrium, expression of IL-15 mRNA significantly increased during the secretory phase compared with the proliferative phase (P < 0.01). The most abundant expression of IL-15 mRNA during the menstrual cycle was observed in the midsecretory phase. In the first trimester pregnancy, the expression of IL-15 mRNA in the decidua was significantly higher than that in the chorionic villi (P < 0.01). By using an in-vitro decidualization with human endometrial stromal cells, it was demonstrated that the expression of IL-15 mRNA is up-regulated during progesterone-induced decidualization. These results suggest that IL-15 plays a role in uterine function during pregnancy, as well as during the menstrual cycle.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Vitamin B6 supplementation can improve peripheral polyneuropathy in patients with chronic renal failure on high-flux haemodialysis and human recombinant erythropoietin.

BACKGROUND: High-flux haemodialysis (HD) has recently been vigorously promoted as a novel standard, and it can indeed efficiently reduce the occurrence of most uraemic symptoms due to middle molecular toxins and/or underdialysis. However, some symptoms remain problematical, particularly peripheral polyneuropathy (PPN). One of the possible reasons for this is that the patients may have low concentrations of some nutrients, e.g. vitamin B(6), necessary for normal peripheral neuron function. METHODS: Predialysis serum pyridoxal-5'-phosphate (P5P) level was determined in 36 chronic HD patients who were undergoing high-flux HD and receiving human recombinant erythropoietin. Among them, 26 patients suffered from PPN. Prior to supplementation, these 26 patients were examined and their neurological symptoms were ranked according to our PPN symptom score. Vitamin B(6) (60 mg/day) was randomly prescribed to 14 of them, and vitamin B(12) (500 microg/day) was prescribed to the others. After 4 weeks, all the patients were re-examined. RESULTS: We found that predialysis serum P5P levels of HD patients with PPN were not significantly lower than those of matched HD patients without PPN. Nonetheless, it was demonstrated that supplementation with vitamin B(6) for 4 weeks significantly increased the predialysis level of P5P and dramatically attenuated PPN symptoms compared with initial symptoms. No improvement was observed in response to vitamin B(12) supplementation. CONCLUSION: This result suggests that although vitamin B(6) deficiency could not be demonstrated in patients with chronic renal failure on high-flux HD, vitamin B(6) supplementation was effective in improving PPN symptoms of various aetiologies, possibly because of vitamin B(6) resistance to PPN in these patients.

Chronic Disease↗
PubMed2000

Marked reduction of mortality in salt-loaded Dahl salt-sensitive rats by the new, selective endothelin ETA receptor antagonist, J-105859.

OBJECTIVE: To examine the chronic effects of a newly synthesized, potent and selective endothelin (ET) ETA receptor antagonist, J-1 05859, on mortality in salt-loaded Dahl salt-sensitive (DS) rats and to confirm the potential of this compound as an ETA antagonist METHODS: Vehicle and J-105859 were administered to salt-loaded DS rats for 12 weeks. Throughout the experimental period, blood pressure was measured continuously using a telemetry system and the survival rate was determined. The surviving animals were subsequently sacrificed and autopsy was performed. Binding and functional assays were also carried out to characterize J-1 05859. RESULTS: The Ki values of J-1 05859 for cloned human ETA and ETB were 0.025 and 48 nmol/l, respectively. J-105859 inhibited ET-1-induced contractions in rabbit iliac artery (pA2 = 10.08) and BQ-3020 (ETB agonist)-induced contractions in pulmonary artery (pA2 = 7.63). The pressor response to intravenous (i.v.) ET-1 (0.5 nmol/kg) was significantly inhibited by J-1 05859 at a dose of 0.03 mg/kg i.v. Chronic treatment with J-1 05859 [0.1 and 1 mg/kg per day orally (p.o.)] from the prehypertensive stage decreased the mortality of salt-loaded DS rats and markedly inhibited the development of brain lesions. The survival rates in the control and J-1 05859 (0.1 and 1 mg/kg per day) groups were 34, 80 and 100%, respectively. Development of hypertension was markedly inhibited at a dose of 1 mg/kg per day. CONCLUSION: J-105859 is a selective, potent, orally active ETA-selective antagonist ETA antagonists may reduce morbidity as well as mortality in salt-sensitive hypertension.

Alkanes↗
PubMed2000

CPR-Total (TAFI and activated TAFI) levels in plasma/serum of hemophiliacs.

Arginine carboxypeptidase (CPR) is a single-chain plasma protein generated during coagulation from a precursor (proCPR). proCPR is the same molecule as thrombin activable fibrinolysis inhibitor (TAFI), which retards fibrin clot lysis in vitro and most likely modulates fibrinolysis in vivo. In this study, the amount of CPR-total, which includes proCPR (TAFI) and CPR (activated TAFI), in hemophiliac patients was evaluated using a newly developed enzyme linked immunosorbent assay (ELISA). The amount of CPR-total in plasma or serum of most of the hemophiliac patients was in the range of healthy individuals. There was no significant difference in hemophiliac patients with or without HIV-1 infection. However, two out of the 74 hemophiliac patients showed a significantly high level. The upregulation of CPR-total might contribute to compensate for inefficient coagulation in some hemophiliac individuals.

Enzyme Activation↗
PubMed2000

Inhibition of HIV-1 infection by an intramolecular antisense peptide to T20 in gp160.

Antisense amino acids are amino acids which can be translated from the corresponding anti-codons of a sense amino acid. Antisense peptides encoded by the noncoding DNA strand have a tendency to interact with each other. We have demonstrated that antisense peptide sequences are present intramolecularly, and these may contribute to the folding and maintenance of the tertiary structure of a protein. T20 is a synthetic peptide with an amino acid sequence in the gp41 of HIV-1 and has been demonstrated to be a potent inhibitor of HIV-1 infection. We searched for intramolecular peptide sequences which are antisense to portions of T20. A synthetic peptide (TA-1L) consisting of amino acids 84 to 97 of gp160, which contains an antisense peptide sequence (TA-1) to T20, was shown to inhibit HIV-1(IIIB) infection of MT-4 cells. Interaction of these antisense peptides could be involved in sustaining HIV-1 infectivity. The TA-1L site, which exists in the C1 domain of gp160, is highly homologous among strains of HIV-1, especially at TA-1 and in the amino acids flanking the C terminus. Although the TA-1 sites of 18 out of 30 HIV-1 strains were antisense to the T20 region, those of the remaining 12 strains, including HIV-1(MN), were not. However, TA-1L inhibited infection by HIV-1(MN), which has no antisense peptide in T20 corresponding to TA-1, although the inhibitory effect was weaker. TA-1L may thus also interfere with the gp160 interaction with CD4, which has an antisense sequence to TA-1.

Amino Acid Sequence↗
PubMed2000

The IgM antibody level against ganglioside GM2 correlates to the disease status of HIV-1-infected patients.

HIV-1 infection induces the expression of high level of GM2 ganglioside on infected cells and IgM antibody (Ab) against GM2 can cause complement (C)-mediated cytolysis of HIV-1-infected cells. Since GM2 is immunogenic in human, we proposed that an anti-GM2 IgM Ab may be produced by some HIV-1-infected patients and the titer of this Ab might provide some insight into the progress of the disease. On this premise, the amount of IgM Ab against GM2 was determined in 124 HIV-1-infected patients and 111 seronegative donors. As expected, the anti-GM2 IgM Ab titers of the patients was significantly higher than that of the seronegative donors while the total IgM levels remained unchanged. In addition, we determined the CD4+ cell count and the HIV-RNA load in the HIV-1-infected patients. The results showed a positive correlation between the anti-GM2 IgM Ab titer and CD4+ cell count but a negative correlation between the anti-GM2 IgM Ab titer and HIV-RNA load. These suggest that anti-GM2 IgM Ab induced and/or enhanced by HIV-1 infection causes C-mediated cytolysis of HIV-1-infected cells in vivo to a certain extent, and may help lower the plateau level of the HIV-RNA load. Therefore, the amount of IgM Ab against GM2 may be related to the prognosis of HIV-1 infected patients.

CD4 Lymphocyte Count↗
PubMed2000

Molecular cloning and partial characterization of rat procarboxypeptidase R and carboxypeptidase N.

Carboxypeptidase R (EC 3.4.17.20) (CPR) and carboxypeptidase N (EC 3.4.17.3) (CPN) cleave carboxy-terminal arginine or lysine residues from biologically active peptides such as kinins or anaphylatoxins in the circulation thereby regulating their activities. Although CPN is present in a stable active form in plasma, CPR is generated from proCPR, a plasma zymogen, by proteolytic enzymes such as thrombin, thrombin-thrombomodulin complex and plasmin. We have isolated rat proCPR and CPN cDNA clones which can induce enzymatic activities in culture supernatants of the transfected cells. mRNA of proCPR was detected only in rat liver by Northern hybridization and showed hepatocyte-specific expression. Expression of proCPR mRNA was enhanced following LPS injection, indicating that proCPR production is increased under inflammatory conditions.

Animals↗
PubMed2000

Antibody to heat shock protein can be used for early serological monitoring of Helicobacter pylori eradication treatment.

Infection with Helicobacter pylori induces humoral immune responses against various antigens of the bacterium. Heat shock proteins (hsps) are immunodominant antigens in various diseases including H. pylori infection. In the present study, we measured the anti-hsp antibody titers in 42 patients with H. pylori-infected peptic ulcers during a bacterial eradication study. The patients were treated with a proton pump inhibitor and antimicrobial agents to eradicate the organism. Their sera were obtained at pretreatment and at 1 month and 6 months after the eradication therapy. The titers of immunoglobulin G antibodies to the H. pylori hsp, whole-cell lysate, and urease (30-kDa subunit) antigens in serum were measured by a capture enzyme-linked immunosorbent assay. The levels of H. pylori hsp60 antibodies in sera collected 1 month after treatment had declined significantly, even when changes in the titers of antibodies to whole-cell and urease antigens were not apparent. These results suggest that measurement of antibodies to H. pylori hsp60 in serum is useful for the early monitoring of the effectiveness of eradication therapy.

Adult↗
PubMed2000

Detection of significant bacteriuria by automated urinalysis using flow cytometry.

A new flow cytometry-based automated urine analyzer, the UF-50, was evaluated for its ability to screen urine samples for significant bacteriuria. One hundred eighty-six urine specimens from patients attending an outpatient clinic of a university-based hospital were examined. The results obtained with the UF-50 were compared with those obtained by conventional quantitative urine culture. The UF-50 detected significant bacteriuria with a sensitivity of 83.1%, a specificity of 76.4%, a positive predictive value of 62.0%, a negative predictive value of 90.7%, and an accuracy of 78.5%. These results are comparable to those obtained by previously reported screening procedures. Besides detecting significant bacteriuria, the UF-50 can also perform routine urinalysis, including measurement of concentrations of red blood cells, white blood cells, epithelial cells, and casts, within 70 s. This capability renders this new flow cytometry-based urine analyzer superior to previously reported rapid screening methods.

Bacteria↗
PubMed2000

Clinicopathological features of gastric mucosa associated lymphoid tissue (MALT) lymphomas: high grade transformation and comparison with diffuse large B cell lymphomas without MALT lymphoma features.

AIMS: To investigate the clinicopathological differences among gastric low grade MALT lymphomas (low MALT), large B cell lymphomas with low grade components (secondary high grade MALT lymphomas, high MALT), and diffuse large B cell lymphomas without low grade features (primary high grade MALT lymphomas, DLL). METHODS: Clinicopathological and morphological characters of 126 gastric lymphoma cases were studied: 82 cases of low MALT lymphoma including 40 that were surgically resected, 17 cases of high MALT lymphoma including 13 surgically resected, and 27 cases of DLL including 12 surgically resected. RESULTS: Age ranges were as follows: low MALT lymphoma, 34 to 85 years (mean 59.9); high MALT lymphoma, 53 to 88 years (mean 68.5); DLL, 29 to 83 years (mean 62.3). The average age for low and high MALT lymphomas was significantly different (p < 0.05), but there were no differences in other comparisons. There was a female predominance of low MALT lymphoma patients (female to male ratio, 47/35), while for high MALT patients the ratio was almost even (8/9), and for DLL patients there was a male predominance (11/16). Examination of surgically resected material showed that MALT lymphomas had a wider distribution in the gastric wall than DLL. CONCLUSIONS: The findings suggest that at least some of the high grade gastric lymphomas, especially in patients younger than the fifth decade, do not originate from high grade transformation of low MALT lymphomas. It seems to take about one decade at least for high grade transformation of low MALT lymphomas.

Adult↗
PubMed2000

Osteopontin expressed by renal tubular epithelium mediates interstitial monocyte infiltration in rats.

In this study, we have shown that intravenously administered antisense oligodeoxynucleotide (ODN) was demonstrated to be taken up by tubular epithelium, after which it blocked mRNA expression of target genes in normal and nephritic rats. Therefore, we injected osteopontin (OPN) antisense ODN to Goodpasture syndrome (GPS) rats every second day between days 27 and 35, the time when renal OPN expression increased and interstitial monocyte infiltration was aggravated. In parallel to blockade of tubular OPN expression, this treatment significantly attenuated monocyte infiltration and preserved renal plasma flow in GPS rats at day 37, compared with sense ODN-treated and untreated GPS rats. No significant changes were observed in OPN mRNA level by RT-PCR and histopathology of the glomeruli after ODN treatment, which was compatible with an absence of differences in the urinary protein excretion rate. In conclusion, OPN expressed by tubular epithelium played a pivotal role in mediating peritubular monocyte infiltration consequent to glomerular disease.

Animals↗