Biomedical subjects

M Okada

Publications and source records attributed to M Okada.

At least 37 records · Page 2Linked to original sources

PubMed2005

Effect of the adenovirus E1A gene on nitric oxide production in alveolar epithelial cells.

This study determined the effect of the adenovirus E1A gene on nitric oxide (NO) production in alveolar epithelial (A549) cells. E1A-positive A549 cells (E1A transfectants), E1A-negative A549 cells (control transfectants) and untransfected A549 cells were placed in 96-well tissue culture plates. After stimulation with lipopolysaccharide (LPS) or cytokine mixture (CM), the biochemical reaction products of NO (nitrite and nitrate) in the culture medium were measured by chemiluminescence. The inducible (iNOS) and the endothelial (eNOS) isoforms of nitric oxide synthase (NOS) protein expression were examined by Western blotting. iNOS mRNA expression was examined by Northern blotting and RT-PCR. CM-induced NO production by E1A-positive A549 cells was significantly lower than that of E1A-negative cells (p < 0.0001). LPS stimulation failed to enhance NO production in both cell types. CM induced iNOS protein expression in E1A-negative A549 cells, but not in E1A-positive cells. eNOS protein expression was constitutive and was not affected by CM stimulation, LPS stimulation or E1A. CM induced iNOS mRNA expression in E1A-negative A549 cells, but not in E1A-positive cells. In conclusion, the adenovirus E1A gene suppressed NO production through transcriptional control of the iNOS gene in A549 cells. This inhibition of NO production may enable the virus to persist in human tissue, since NO is an antiviral effector of the innate immune system.

Adenovirus E1A Proteins↗

PubMed2005

Increased serum concentrations of tissue inhibitor of metalloproteinase-1 in COPD patients.

Matrix metalloproteinase (MMP)-9 and tissue inhibitors of metalloproteinase (TIMP)-1 concentrations are increased in the sputum of asthma and chronic bronchitis patients, and are thought to be related to airflow obstruction. However, serum concentrations of these enzymes have not been clearly evaluated in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to examine the serum concentrations of these enzymes in COPD and asthmatic patients in order to determine their relationship with airway obstruction. Serum samples were obtained from 72 patients with COPD: 66 control subjects and 26 patients with asthma. Smoking histories of control subjects were matched with those of COPD patients. Serum concentrations of TIMP-1 and MMP-9 were determined by ELISA. The circulating TIMP-1 concentration was significantly higher in stable COPD patients than in control and asthmatic subjects, and was significantly negatively correlated with forced expiratory volume in one second/forced vital capacity in COPD patients. The molar ratio between MMP-9 and TIMP-1 was significantly lower in COPD patients than in control subjects. In patients with COPD, the serum TIMP-1 concentration was significantly increased during disease exacerbation. In conclusion, the current findings suggest that serum tissue inhibitors of metalloproteinase-1 concentration can be used as a serum marker of airway obstruction and exacerbation in chronic obstructive pulmonary disease patients.

Adrenal Cortex Hormones↗

PubMed2005

A Japanese family with Alport syndrome associated with esophageal leiomyomatosis: genetic analysis of COL4A5 to COL4A6 and immunostaining for type IV collagen subtypes.

BACKGROUND: In some families, X-linked Alport syndrome (AS) is associated with diffuse leiomyomatosis. We describe clinical, pathologic and molecular-genetic findings in a Japanese family with this inheritance mode of AS in association with leiomyomatosis. PATIENT: AS was diagnosed in a one-year-old boy with recurrent aspiration pneumonia caused by esophageal stenosis from leiomyomatosis. Diagnosis was confirmed by electron microscopy coupled with type IV collagen chain subtype staining in a renal biopsy specimen. His mother, who exhibited esophageal leiomyomatosis and is heterozygous for AS, showed a discontinuous staining pattern for collagen alpha5(IV) chain along the epidermal basement membrane in a skin biopsy specimen. Genetic analysis in the boy revealed the deletion of the first two exons of COL4A6 together with deletion of the 5' end of COL4A5. Despite administration of cyclosporin A, massive proteinuria has persisted in the boy, although renal function otherwise remains normal. CONCLUSION: Identification of an AS patient during infancy is extremely rare. Clinical manifestations, including macroscopic hematuria, cataracts and leiomyomatosis caused by the large deletion involving COL4A5 to COL4A6, led to early presentation with AS.

Collagen Type IV↗

PubMed2004

Modification of human 5-HT(2C) receptor function by Cys23Ser, an abundant, naturally occurring amino-acid substitution.

A human serotonin (5-HT)(2C) receptor gene polymorphism leads to the substitution of cysteine for serine at codon 23 (Cys23Ser); the frequency of the Ser23 allele in unrelated Caucasians is approximately 0.13. In the present study, we assessed whether Cys23Ser could affect receptor function. The two alleles were functionally compared following expression in COS-7 cells. The constitutive activity of the receptor in an in situ reconstitution system was also evaluated following expression of each allele in Sf9 cells. Using radioligands, Ser23-expressed membranes showed reduced high-affinity binding to meta-chlorophenylpiperazine (m-CPP) and 5-HT. Although the amplitude of the 5-HT-induced intracellular Ca(2+) peak did not differ between the alleles, Ser23 required higher 5-HT concentrations to elicit the same response. These differences might be due to more extensive desensitization in the Ser23 form. In the in situ reconstitution system, the 5-HT(2C) receptor displayed considerable constitutive activity, with the Ser23 allele being significantly higher in this regard than the Cys23 form. After prolonged serum deprivation in order to resensitize the receptor, four of the 15 cells expressing Ser23 showed abnormally higher m-CPP-induced sensitivity of the Ca(2+) response. These results indicate that the Ser23 allele may be constitutively more active than Cys23. Thus, Ser23 appears to be an abundant candidate allele capable of directly influencing inter-individual variation in behavior, susceptibility to mental disorder, and response to drugs including atypical antipsychotic and some antidepressant drugs that are potent 5-HT(2C) inverse agonists or antagonists.

Amino Acid Substitution↗

PubMed2004

Concentrations and fluxes of chloronaphthalenes in sediment from Lake Kitaura in Japan in past 15 centuries.

The concentrations of 63 congeners of chloronaphthalene (CN; polychlorinated naphthalenes, PCNs) in dated on approximately 500 B.C. to 2000 sediment core from the Lake Kitaura in Japan have been quantified by HRGC/HRMS after double column HPLC fractionation. Sediment from the Lake Kitaura showed a time-dependent pattern in distribution of CNs since the approximately 500 B.C. Starting from the 1910s the total CNs content increased accelerating from the 1960s, and, in parallel, the pattern of CN congeners has changed with a substantial increase in contribution from the penta, hexa, hepta, and octaCN. The total CNs content normalized to dry weight of sediment peaked out in the layer dated on 1984-1985, and next nearly two-fold decreased with further gradually decreasing concentration in 1987-2000. An occurrence of tri and tetraCNs in deep sediment layers corresponded to preindustrial synthesis and use of CNs seems to be connected to relatively greater water solubility and mobility in the pore water of those CN homologue groups. Based on CN congener pattern and results of multivariate analysis three main layers were separated in the sediment core. Starting from 1981 the emission sources related to combustion marker congeners become substantial contributors to flux of annually deposited CNs, while relative significance of the evaporative source marker congeners decreased after 1985. The annual flux of CNs into sediments of the Lake Kitaura was 0.073-0.31 pg/cm2 before 1926, increased to 5.5-14 pg/cm2 in 1963-1970 and next sharply increased to 50-107 pg/ cm2 in 1971-1985, and after that decreased to 17 pg/cm2 in 1997-2000.

Chlorine Compounds↗

PubMed2004

Non-surgical approach to advanced chronic periodontitis: a 17.5-year case report.

This 17.5-year longitudinal case report details the treatment of advanced chronic periodontitis in a female patient commencing at 34 years of age. The woman was provided with periodontal care comprising of temporary fixation, scaling and root planing, intra-pocket irrigation using a root canal syringe and regular supervised maintenance. The patient presented with a 10-year history of bleeding gums. Therapy conducted in general practice had included simple curettage and irrigation. However, these treatments proved unsuccessful and the patient often changed dentists seeking better treatment. She presented to the University Dental Hospital, for diagnosis and treatment of her periodontal conditions after her mandibular lateral incisor had exfoliated. On presentation a purulent exudate could be expressed from all of the pockets. All anterior teeth, excluding the maxillary canines, demonstrated +2 to +3 mobility. The patient did not want any surgical treatment or her teeth extracted. It was decided to treat the patient conservatively without surgery. By postponing extraction, the authors were in a better position to determine the prognosis of the remaining teeth after the infection was under control. Although six teeth were extracted during the 17.5 years, this case report suggests that a non-surgical approach is a viable option while maintaining regular visits for periodontal care.

Adult↗

PubMed2004

A boy with Japanese Dent's disease exhibiting abnormal calcium metabolism and osseous disorder of the spine: defective megalin expression at the brushborder of renal proximal tubules.

We encountered a 16-year-old boy with Japanese Dent's disease who exhibited renal insufficiency and an osseous disorder of the spine. Proteinuria first was noted at the age of 2 years. At 13 years, the patient underwent analysis of the CLCN5 gene, which identified missense mutation (I524K) in exon 10. During follow-up, a marked increase in urinary beta2-microglobulin was associated with mild deterioration of renal function. At the age of 15 years, hypocalcemia (7.5 mg/dl) accompanied by an increased plasma concentration of alkaline phosphatase was first detected. At that time, plasma concentration of 25(OH)D3 and 1'alpha25(OH)2D3 were low accompanied by a high plasma parathyroid hormone concentration. A renal biopsy specimen revealed tubulointerstitial alterations including mononuclear cell infiltration, partial fibrosis and focal glomerular sclerosis. Immunofluorescence revealed weak, discontinuous staining of megalin along the brushborder of renal proximal tubules. Western blotting demonstrated decreased urinary excretion of megalin. Thus, clinical manifestations and prognosis may vary in Japanese Dent's disease. Reduced megalin expression may have disturbed calcium homeostasis, leading to osseous disorder in our patient.

Adolescent↗

PubMed2004

[Technical points of venous reconstruction for disorders of the superior vena cava].

In recent years, the number of patients with disorders of the superior vena cava due to mediastinal tumors such as malignant thymoma, teratoma and hilus type of lung cancer is now increasing in Japan. For those patients, we have tried to do venous reconstruction for the disorders of the superior vena cava (SVC) due to malignant mediastinal tumors. By these combined surgical procedures such as resection of malignant tumor and SVC reconstruction, curability and longevity of the life were apparently recognized. However, it is very important to select patients of which resection of tumor and venous reconstruction can be carried out by several kinds of examinations such as computed tomography (CT), magnetic resonance angiography (MRA) and venography. There are 3 kinds of reconstruction such as direct suture and patch grafting, as well as bypass grafting with ringed e-PTFE (expanded-polytetrafluoloethylene) prosthetic graft except for endovascular interventions of which number of patients is still few. On the other hand, bypass grafting is also effective for high intracranial pressure with syncope for the patients whose tumors could not be resected, because of huge tumor and diffuse invasion.

Blood Vessel Prosthesis↗

PubMed2004

Effects of alpha-linked galactooligosaccharide on adjuvant-induced arthritis in Wistar rats and type II collagen-induced arthritis in DBA/1J mice.

alpha-Linked galactooligosaccharide (alpha-GOS) has been reported to change the composition of enteric microflora. In the present study, the antiarthritic effect of alpha-GOS was evaluated by employing adjuvant-induced arthritis (AIA) in Wistar rats and type II collagen-induced arthritis (CIA) in DBA/1J mice. The animals were given alpha-GOS orally. This substance had beneficial effects on both clinical signs, such as erythema and swelling of the limbs, and histopathological findings in the hind paw joints in a dose-dependent manner. alpha-GOS reduced the plasma nitrite/nitrate (NOx) level in rats with AIA. In the cell culture system employing peritoneal macrophages from rats with AIA, alpha-GOS enhanced interleukin-1 production without lipopolysaccharide stimulation in a dose-dependent manner, suggesting that alpha-GOS stimulates peritoneal macrophages through modulation of enteric microflora. Since alpha-GOS modulates the composition of the enteric microflora, the antiarthritic effects of alpha-GOS could be partly attributable to its immunomodulating activity. Thus, alpha-GOS is a potential functional food for the treatment of human rheumatoid arthritis.

Animals↗

PubMed2003

L523S, an RNA-binding protein as a potential therapeutic target for lung cancer.

Approaches to vaccine-based immunotherapy of human cancer may ultimately require targets that are both tumour-specific and immunogenic. In order to generate specific antitumour immune responses to lung cancer, we have sought lung cancer-specific proteins that can be targeted for adjuvant vaccine therapy. By using a combination of cDNA subtraction and microarray analysis, we previously reported the identification of an RNA-binding protein within the KOC family, L523S, to be overexpressed in squamous cell cancers of the lung. We show here that L523S exhibits significant potential for vaccine immunotherapy of lung cancer. As an oncofetal protein, L523S is normally expressed in early embryonic tissues, yet it is re-expressed in a high percentage of nonsmall cell lung carcinoma. The specificity of L523S expression in lung cancer was demonstrated by both mRNA and protein measurements using real-time PCR, Western blot, and immunohistochemistry analyses. Furthermore, we show that immunological tolerance of L523S is naturally broken in lung cancer patients, as evidenced by detectable antibody responses to recombinant L523S protein in eight of 17 lung pleural effusions from lung cancer patients. Collectively, our studies suggest that L523S may be an important marker of malignant progression in human lung cancer, and further suggest that treatment approaches based on L523S as an immunogenic target are worthy of pursuit.

Biomarkers, Tumor↗

PubMed2003

Septicaemia and arthritis in pigs experimentally infected with Pasteurella multocida capsular serotype A.

Twenty-five caesarean-derived, colostrum-deprived (CDCD) pigs and 18 specific pathogen-free pigs, aged 8 to 14 weeks, were inoculated intranasally or intratracheally with Pasteurella multocida capsular serotype A, isolated from a severe pneumonic lesion in a growing pig. The pigs were killed for necropsy on day 6 or 14 post-inoculation (PI) or, in the case of the only fatally infected animal, examined at the time of death. One CDCD pig, inoculated intratracheally with 5 ml of a bacterial suspension containing 1.7x10(9) colony-forming-units/ml, died of septicaemia on day 1 PI. Histological lesions such as severe pleuropneumonia, thrombi in glomerular capillaries, haemorrhage of the spleen, and abscesses in the tonsillar crypts were observed. The organism was recovered from a number of sites and its antigens were detected immunohistochemically in the pneumonic lesions, blood vessels of the tissues, and tonsillar crypts in the dead pig. Pneumonia, pleural adhesions and suppurative arthritis in the extremital joints were observed grossly in 3/29, 8/29 and 7/29 intratracheally inoculated pigs, respectively. In intranasally inoculated pigs, no macroscopical abnormalities were seen; histologically, however, exudative bronchopneumonia and fibrinous pleurisy were observed in 9/14 and 4/14 pigs, respectively. No significant changes were seen in the tissues of uninfected control pigs. The organism was recovered from the lesions and P. multocida type A antigen was demonstrated immunohistochemically. The organism was rarely recovered from the liver, spleen or lymph nodes (bronchopulmonary or mesenteric). The results suggest that P. multocida capsular serotype A alone can cause not only pneumonia in pigs but also septicaemia or arthritis.

Animals↗

PubMed2003

The characteristics of the bacterial community structure and population dynamics for phosphorus removal in SBR activated sludge processes.

The characteristics of the bacterial community structure and population dynamics for phosphorus removal in activated sludge were investigated using laboratory-scale sequencing batch reactor (SBR) activated sludge processes fed with four different carbon sources. Phosphorus removal activity, quinone profile of the activated sludge and isolated bacterial strains were monitored. An enhanced phosphorus removal activity was accompanied by the increase in ubiquinone-9 (Q-9). The relationships between phosphorus removal activity and Q-9 contents of the isolated bacterial strains were dependent neither on the organic substrates nor on the species of isolated bacterial strains. The enhanced phosphorus removal capability of activated sludge seemed to be due to the increase in the populations of bacteria with activity of phosphorus removal, i.e. species succession of bacteria in activated sludge ecosystems, rather than the increase in the phosphorus removal capability of phosphorus removal bacteria. Not only Acinetobacter but also Pseudomonas identified from isolated strains were regarded as representative polyphosphates-accumulating organisms and predominant species to the whole of bacterial population in activated sludge for phosphorus removal.

Acinetobacter↗

PubMed2003

Edg-8 receptors are preferentially expressed in oligodendrocyte lineage cells of the rat CNS.

The messenger RNA for endothelial differentiation gene 8 receptors is known to be expressed almost exclusively in the rat CNS, but the nature of the expressing cells has not been defined. Using an antibody specific for endothelial differentiation gene 8, we investigated the immunohistochemical localization of endothelial differentiation gene 8 receptors in the rat CNS. Immunopositive staining was detected in a subset of glial cells distributed throughout the brain and spinal cord, including both gray and white matter, but not in the dorsal root ganglion. The distribution and morphological similarity in comparative immunostaining for endothelial differentiation gene 8 and various glial markers suggested that endothelial differentiation gene 8 is preferentially expressed in NG2-positive oligodendrocyte progenitor cells in adult rat brains. Counts of endothelial differentiation gene 8-positive cells and NG2-positive cells in the forebrain revealed that a subset of NG2-positive cells was endothelial differentiation gene 8-positive, and that the ratio of endothelial differentiation gene 8-positive cells to NG2-positive cells varied from region to region. In 17-day-old embryonic brains, the endothelial differentiation gene 8 distribution was similar to that of an oligodendrocytic marker, 2',3'-cyclic nucleotide 3'-phosphodiesterase. These data suggest that endothelial differentiation gene 8 receptors are preferentially expressed in oligodendrocyte lineage cells including oligodendrocyte progenitor cells and immature/maturating oligodendrocytes in rat CNS, and that they might have important functions in oligodendrocytic maturation and myelination.

Animals↗

PubMed2003

Endothelial damage caused by cytomegalovirus and human herpesvirus-6.

Infection with cytomegalovirus (CMV) or human herpesvirus-6 (HHV-6) may have a role in vascular endothelial damage after bone marrow transplantation (BMT). In total, 41 patients who underwent BMT were classified into four groups (12, 10, 7, and 12 patients who were infected with both CMV and HHV-6, CMV alone, HHV-6, and neither virus, respectively). Levels of thrombomodulin, plasminogen activator inhibitor-1, and cyclic GMP were 7.5+/-1.7 FU/ml, 76.4+/-24.1 ng/ml, and 9.51+/-1.1 pmol/ml, respectively, in the patients with both viruses, while the respective values were 2.9+/-0.67 FU/ml, 33.8+/-8.09 ng/ml, and 2.90+/-1.4 pmol/ml in patients infected with CMV alone, 4.8+/-0.96 FU/ml, 47.7+/-9.21 ng/ml, and 5.48+/-0.55 pmol/ml in patients with HHV-6 alone, and 1.6+/-0.39, 17.5+/-7.88 ng/ml, and 0.45+/-0.3 in those with neither virus. All three markers were significantly higher in the three groups with at least one virus than in the uninfected patients (P<0.05), and were also higher in patients with HHV-6 alone than in those with CMV alone (P<0.05). These results suggest that infection by CMV or HHV-6 causes vascular endothelial injury, with HHV-6 having a stronger effect than CMV, and combined infection having a stronger effect than either virus alone. Such viral infection may be a cause of thrombotic microangiopathy after BMT.

Acyclovir↗

PubMed2003

Influence of Helicobacter pylori on platelets after bone marrow transplantation from unrelated donors.

This study was performed to clarify the influence of Helicobacter pylori on the platelet count in patients undergoing bone marrow transplantation (BMT) from unrelated donors. Of 23 consecutive patients undergoing BMT from unrelated donors, the H. pylori antibody test did not change from before conditioning until recovery of the platelet count in 15 patients. These patients were classified into H. pylori antibody-positive (n=8) and -negative (n=7) groups. In the H. pylori antibody-positive group, the platelet count exceeded 20 x 10(9)/l significantly faster after BMT, than in the H. pylori antibody-negative group. When myelosuppression was most severe, the interleukin-6 (IL-6) level was significantly higher in the positive group than in the negative group (67.0+/-10.6 vs 9.9+/-2.4 pg/ml, P<0.05). In addition, the thrombopoietin level was significantly lower in the positive group than in the negative (510.1+/-313.9 vs 3209.1+/-2006.7 pg/ml, P<0.01). These data suggest that H. pylori infection accelerates recovery of the platelet count after BMT from unrelated donors, possibly by stimulating IL-6 production.

Adult↗

PubMed2003

Prognostic value of cyclic GMP in patients undergoing allogeneic bone marrow transplantation after conditioning with total body irradiation.

This study was performed to investigate whether measurement of cyclic GMP (cGMP), a marker for nitric oxide production, before and after allogeneic bone marrow transplantation (BMT) with total body irradiation (TBI) conditioning was of prognostic value. cGMP levels were monitored in 23 consecutive patients who received TBI as conditioning for BMT, and were compared with the outcome. cGMP became positive during the aplastic phase after BMT in 12 patients. In nine of these 12 patients, cGMP level decreased during the recovery phase. Eight of the nine patients survived, one dying after relapse. In three other patients, the cGMP level continued to increase even during the recovery phase and they died of severe complications. cGMP became positive on day 0 of BMT and during the leukocyte recovery phase after BMT in two and seven of the 23 patients, respectively. Subsequently, all patients died of severe complications. The two patients who were negative for cGMP both before and after BMT survived without complications. These results suggest that monitoring cGMP from early after BMT may be useful for predicting outcome and that it may be a useful prognostic marker.

Adolescent↗

PubMed2003

Effects of combination therapy with a luteinizing hormone-releasing hormone agonist and chlormadinone acetate on rat prostate weight and plasma testosterone levels.

We investigated whether the combination of chlormadinone acetate (CMA) and a luteinizing hormone releasing hormone (LH-RH) agonist, leuprorelin acetate (leuprorelin), more markedly decreased ventral prostate and seminal vesicle weights and plasma sex hormone levels in male rats. Four weeks after administration of 0.28, 0.84 or 2.8 mg/kg of leuprorelin, ventral prostate weights significantly decreased (53.8, 54.4 and 64.1%) and the plasma testosterone levels significantly lowered, but not dose-dependently. After repetitive administrations of 3 and 30 mg/kg/day of CMA, the rates of ventral prostatic atrophy were 37.1 and 65.9%, respectively. Although there was no change in the plasma testosterone level at 3 mg/kg, 30 mg/kg of CMA significantly decreased the level. A combination of leuprorelin (0.28 mg/kg) and CMA (3 or 30 mg/kg) more potently induced ventral prostatic and seminal vesicle atrophy than leuprorelin alone. Furthermore, a combination of leuprorelin and CMA (30 mg/kg) more markedly decreased the plasma testosterone level. According to the pharmacokinetic data for CMA in male rats, the doses of CMA correspond to the clinical dose. These findings suggest that combination therapy with an LH-RH agonist and CMA is more useful than therapy with the agonist alone in the treatment of prostate cancer.

Androgen Antagonists↗

PubMed2003

Muscle architectural characteristics in young and elderly men and women.

The purpose of this study was to compare the muscle architectural characteristics, i. e., muscle thickness, pennation angle, fascicle length, of four different groups comprising a total of 121 men and 190 women, divided according to sex and age (i. e., 20 - 39 yrs and 60 - 85 yrs). Muscle thickness and pennation angles of the vastus lateralis (VL), medial gastrocnemius (MG), long head of triceps brachii (TB) muscles were measured by B-mode ultrasonography, and fascicle length was estimated. Men had significantly greater relative muscle thickness (to limb length) than women, but not for MG. Relative muscle thickness of VL was significantly greater in younger subjects than in elderly (men; p < 0.001, women; p < 0.001), although there were no significant differences in relative muscle thickness of MG and TB between younger and elderly subjects. Men had significantly greater pennation angles than women, but not for MG in elderly subjects. The pennation angle of VL was significantly greater in younger subjects than in elderly (men; p < 0.001, women; p < 0.001), although there were no significant differences in pennation angles of MG and TB between younger and elderly subjects. Women had longer relative fascicle lengths (to limb length) of VL than men (p = 0.048 for younger, p = 0.028 for elderly). These results suggest that the decrease of thickness of the vastus lateralis muscle with aging is significant, and that there is the gender difference in the fascicle length of the vastus lateralis muscle.

Adult↗