Biomedical subjects

H Maeda

Publications and source records attributed to H Maeda.

At least 343 records · Page 19Linked to original sources

PubMed1998

Improved nitric oxide detection using 2,3-diaminonaphthalene and its application to the evaluation of novel nitric oxide synthase inhibitors.

A specific and sensitive detection method for nitric oxide (NO) in living cells and tissue culture systems is required in the search for novel NO synthase (NOS) inhibitors. We have improved a fluorometric determination with 2,3-diaminonaphthalene (DAN) by the addition of 2-phenyl-4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl (PTIO) as an oxidant to form NO2 from NO. This method is 3 times more sensitive than that without PTIO, and is suitable for examining the NOS-inhibitory activity of large numbers of test compounds using a 96-well microplate reader. The improved method was applied to N-monomethyl-L-arginine (L-NMMA) as a known inhibitor and the derivatives of 2-phenyl-1,2-benzisoselenazol-3(2H)-one as teat compounds in order to investigate the effect of these compounds on NO production from activated rat aortic smooth muscle cells. The results obtained indicate that this method is suitable for the rapid assay of large numbers of test compounds.

2-Naphthylamine↗

PubMed1998

Interlocking intramedullary nail method for the treatment of femoral and tibial fractures in cats and small dogs.

We have developed an interlocking intramedullary nail method for the treatment of femoral and tibial fractures and used this method for the treatment of 7 cats and 6 dogs with these fractures. The interlocking nails, with a diameter of 4-6 mm and length of 60-140 mm, have holes at 10 mm intervals for screwing. The nail placed on the insertion device was inserted into the marrow cavity from the end of the fractured bone in the usual procedures for intramedullary fixation, then fixed by screws at the distal and proximal ends with a jig which was also attached to the insertion device. Animals were able to bear weight on the treated legs within three days, and the prognosis was excellent.

Animals↗

PubMed1998

Non-invasive blood pressure measurements in cats: clinical significance of hypertension associated with chronic renal failure.

The systolic, mean and diastolic pressures as well as the heart rate were measured using the oscillometric method, on a total of 104 cats (60 cats in the normal group, and 44 in the renal disease group) which were brought into Azabu University Animal Hospital. The blood pressure in the normal group was systolic: 115.4 +/- 10.1 mmHg, mean: 96.2 +/- 12.2 mmHg, and diastolic: 73.7 +/- 10.7 mmHg. Although no difference in heart rate, the renal disease group showed significantly (p < 0.05) higher values for systolic, mean, and diastolic pressure when compared with the normal group. Moreover, when plasma renin activity, angiotensin I and II, and aldosterone concentrations were measured in other cats (11 normal and seven with chronic renal failure), all cats with chronic renal failure showed significantly (p < 0.05) higher values than the normal group. It is, therefore, indicated that hypertension due to stimulating renin-angiotensin-aldosterone system may have manifested in cats with renal dysfunction.

Animals↗

PubMed1998

Human matrix metalloprotease activation by insults of bacterial infection involving proteases and free radicals.

We found that human matrix metalloproteases (MMPs) may be processed from their proenzyme forms (proMMP) to their active forms by two new and unique mechanisms: Firstly, by bacterial proteases such as Pseudomonas elastase and Vibrio cholerae protease, which cleave off the N-terminal autoinhibitory domain (so-called cysteine switch) from proMMPs. The second mechanism depends on free radical generation by activated polymorphonuclear leukocytes (PMNs). In this case, peroxynitrite (ONOO-) or nitrogen dioxide radical (.NO2), the reaction products of either superoxide (O2.-) or molecular oxygen (O2) and nitric oxide (.NO), are the key reactants. Both O2.- and .NO are generated by activated macrophages and PMNs as a result of immunologic responses involving various proinflammatory cytokines. .NO2 or ONOO- seems to interact with a single cysteine residue in the propeptide autoinhibitory domain, or so-called cysteine switch of proMMPs, thus transforming proMMPs into their active conformation. Furthermore, reactive oxygen species are known to inactivate the alpha1-protease inhibitor (alpha1-PI), a potent neutrophil elastase inhibitor in plasma. In addition, we found that such radicals activate MMPs which degrade and inactivate alpha1-PI by proteolysis. Thus, the activation of MMPs, accompanied by the inactivation of alpha1-PI, will bring about enhanced proteolytic damage to the matrix tissues of the infected sites by both MMPs and elastase.

Bacterial Proteins↗

PubMed1998

Rheumatoid arthritis associated with diffuse panbronchiolitis.

Diffuse panbronchiolitis (DPB) is a distinct clinicopathologic entity, which is characterized by chronic recurrent sinopulmonary infection and inflammation. We describe 3 patients with rheumatoid arthritis (RA) associated with DPB and consider that DPB is one of the bronchopulmonary manifestations associated with RA.

Aged↗

PubMed1998

Effect of emeriamine, an inhibitor of fatty acid oxidation, on metabolic fate of a geometrical isomer of linoleic acid in perfused rat liver.

To estimate the relative significance of exogenous vs. endogenous fatty acids in increasing hepatic triacylglycerol secretion following an inhibition of fatty acid oxidation by emeriamine, livers from 2-d-fasting rats were perfused with or without an inhibitor in the presence of a geometrical isomer of linoleate (linolelaidic acid, trans,trans-9,12-octadecadienoic acid). Emeriamine added to the perfusion medium at 2 h of the recirculating perfusion period caused immediate and complete cessation of ketone body production while it increased triacylglycerol and cholesterol secretion by the liver without affecting uptake of exogenous linolelaidic acid. The increase in the triacylglycerol secretion by emeriamine was accompanied by a marked increase in the proportion of linolelaidic acid in this lipid molecule in the perfusate and in the liver. The calculated amounts of exogenous linolelaidate, compared with those of endogenous fatty acids in the secretory triacylglycerol, suggested that the former compared with the latter contributes more to the drug-mediated increase in triacylglycerol secretion. This drug caused a marked reduction of mitochondrial carnitine palmitoyltransferase activity in perfused liver. These results suggest that a blockade of fatty acid oxidation by emeriamine, through an inhibition of carnitine palmitoyltransferase, diverts predominantly the exogenous free fatty acids from oxidation to the esterification pathway and subsequently stimulates the synthesis and secretion of triacylglycerol-rich lipoproteins.

3-Hydroxybutyric Acid↗

PubMed1998

Free radicals in viral pathogenesis: molecular mechanisms involving superoxide and NO.

The importance of free radical molecular species in the pathogenesis of various viral diseases has been increasingly recognized in recent years. Oxygen radicals such as superoxide (O2-) and hydroxyl radical (.OH) have been implicated as possible pathogenic molecules in viral disease pathogenesis. Much attention has been given to another simple inorganic radical [nitric oxide (NO)] in the host's defense mechanism and pathogenesis of virus infection. The NO synthesis pathway, in particular, the inducible isoform of NO synthase (iNOS), is expressed in different viral diseases via induction of proinflammatory cytokines such as interferon-gamma. iNOS produces an excessive amount of NO for a long time compared with other constitutive isoforms of NOS (i.e., neuronal NOS and endothelial NOS). Recent studies indicate that NO and O2- are produced in excess during the host's defense responses against various intruding microbes. Reactive nitrogen oxide species such as peroxynitrite (ONOO-) and NOx (NO2 and N2O3) are produced in biological systems through the reaction of NO with either O2- or O2. Among these reactive nitrogen species, ONOO- and its biological actions are of considerable interest in that ONOO- causes oxidation and nitration of amino acid residues of proteins and guanine of DNA, lipid peroxidation, and DNA cleavage. Because the ONOO- is formed via a diffusion-limited fast reaction of NO and O2-, it may be a dominant nitrogen oxide species during the host's defense reactions, when both NO and O2- are produced in excess. Thus, understanding the role of NO and oxygen radical generation in virus infections will provide insight into not only viral pathogenesis but also the host-pathogen interaction in microbial infections at a molecular level.

Animals↗

PubMed1998

A novel dosage approach for evaluation of SMANCS [poly-(styrene-co-maleyl-half-n-butylate) - neocarzinostatin] in the treatment of primary hepatocellular carcinoma.

We report a Phase I/II clinical trial of poly-(styrene-co-maleyl-half-n-butylate)-neocarzinostatin (SMANCS) for intra-arterial treatment of hepatoma. Early patients received 4 or 8 mg SMANCS dissolved in Lipiodol; later patients were treated according to tumour size and degree of filling achieved. SMANCS/Lipiodol drained rapidly from normal liver but was retained within tumour interstitium. Tumour nodules filled with SMANCS/Lipiodol usually stabilised and often regressed. No UICC criteria-defined responses were achieved, partly due to difficulties of filling several lesions simultaneously. Signs of therapeutic activity suggest a more extensive clinical study is warranted.

Abdominal Pain↗

PubMed1998

[Renal hemangiopericytoma: report of a case].

A 34-year-old house wife presented with a right renal mass detected by work-up for epigastralgia. The mass located in the right renal sinus was round and approximately 3 cm in diameter. Although the tumor was well enhanced with contrast medium on CT scan, it was hypovascular on the early arterial phase of renal angiography. Translumbar radical nephrectomy was performed on suspicion of the right renal cell carcinoma. The tumor was solid and hard and, the cut surface of the tumor was homogenously colored pale pink. Microscopically it was hemangiopericytoma arising in the renal sinus, composed of well-developed pericytes and capillaries with so-called staghorn configuration, with invasion of hilar renal vein. Immunohistochemically, the hemangiopericytes were strongly positive for CD34, but negative for factor VIII associated antibodies. To our knowledge, the present patient is the 6th case in the Japanese literature and the first case with incidentally detected renal hemangiopericytoma.

Adult↗

PubMed1998

Benefits of induced sputum for the evaluation of therapeutic efficacy in patients with bronchial asthma.

Airway inflammation is a major factor in the pathogenesis of asthma. Inducing sputum by hypertonic saline is a noninvasive method of assessment of the airway inflammation in asthmatic patients. To investigate sputum induction as a method for assessing airway inflammation and to evaluate the effect of inhaled beclomethasone dipropionate (BDP) in asthmatic patients, we examined the bronchial hyperresponsibility (BHR), pulmonary function and differential cell counts in induced sputum of the patients before and after BDP therapy. In asthmatic patients, the percentage of eosinophils in induced sputum was significantly higher than that in non-asthmatic subjects. Ten patients with atopic asthma (four men and six women; mean [+/- SD] age, 30.5 +/- 12.4 years) participated. Their mean percentage of eosinophils (% eosinophils) in induced sputum fell from 22.9 +/- 7.2% to 13.9 +/- 8.3% (p < 0.05) by 3 months of BDP treatment. The percentage of eosinophils in induced sputum before BDP treatment was significantly correlated with the ratio of the forced expiratory volume in one second to the forced vital capacity (FEV1%) at baseline (r = -0.75, p < 0.05), but not with log Dmin at baseline (p = 0.18). The change in FEV1% between at baseline and post-treatment correlated significantly with the change in the sputum eosinophil percentage (r = -0.79, p < 0.01). In addition, there was a significant correlation between the change of log Dmin and the change of the sputum eosinophil percentage (r = -0.64, p < 0.05). In conclusion, analysis of induced sputum is a safe, noninvasive, repeatable and useful method to assess the clinical condition of bronchial inflammation in patients with bronchial asthma.

Administration, Inhalation↗

PubMed1998

Telomerase activity in rheumatoid synovium correlates with the mononuclear cell infiltration level and disease aggressiveness of rheumatoid arthritis.

OBJECTIVE: To determine whether the presence of telomerase activity in synovial tissues could provide insights into the pathogenesis of rheumatoid arthritis (RA). METHODS: Synovial tissue samples obtained from patients with RA or osteoarthritis (OA) were examined for telomerase activity using the telomeric repeat amplification protocol (TRAP). RESULTS: Telomerase activity was detected in over half the RA synovial tissues (14/25, 56%) but in no OA synovial tissue samples (0/15). Telomerase activity was detected in the mononuclear cells isolated from telomerase-positive RA synovial tissue, but not in cultured adherent cells. In RA synovial tissue with positive telomerase activity mononuclear cell infiltration levels were increased (p < 0.001). In addition, patients with RA with positive telomerase activity had undergone joint operations at an earlier age (p = 0.030) and more often (p = 0.023) compared to those without telomerase activity. CONCLUSION: Telomerase activity in RA synovial tissue is likely derived from infiltrating mononuclear cells and may be involved in the pathogenesis of RA. Clinically, the presence of telomerase activity in RA may be an indicator of a more aggressive phenotype.

Aged↗

PubMed1998

[Metastatic renal tumor originating from lung cancer: a case report].

A 45-year-old house-wife, who had undergone surgical treatment for lung adenocarcinoma 2 years previously, presented with a left renal mass detected by follow-up CT. During 7 months of observation, it rapidly enlarged from 1 cm to 3 cm in maximum diameter. Although the short doubling time (40 days) suggested that the tumor was metastatic, abdominal urtrasonography, angiography and CT scan did not exclude primary renal cell carcinoma. Left nephrectomy was performed. Histologically, the tumor proved to be metastasis from the previous lung adenocarcinoma. She has been alive with pulmonary recurrence 13 months after nephrectomy. The doubling time of the tumor may be one of the key factors in differentiating a metastatic renal tumor from a primary carcinoma.

Adenocarcinoma↗

PubMed1998

[Recent advances in research on SMANCS].

During the past five years we observed many advances in the study of the polymer drug, "SMANCS". This first polymeric drug was approved by the Japanese Ministry of Health and Welfare in 1994 as a drug for primary liver cancer, in which the arterial injection of oily formulation in Lipiodol (a lipid contrast medium) is the standard procedure. The advantage of this tactic is the most extraordinary cancer targeting efficiency with the least systemic side effect and very prolonged slow release of SMANCS. The mechanism of tumor selective accumulation of SMANCS and polymeric drugs in general is discussed in view of the so called-EPR (enhanced permeability and retention) effect of solid tumor. The mode of action of SMANCS at the cellular level seems to accompany the generation of superoxide radical which damages DNA; strand break and modification of guaninine by 8-hydroxylguanine. Immunological potentiation involves either the cellular (M phi, T-cell, NK-cell) or molecular level (induction of cytokines, including interferon gamma). The in vivo effect of SMANCS is most pronounced in the tumor vessels where more concentrated SMANCS is accessible due to the EPR effect, and perhaps the generation of O2.-. Nitric oxide generated by both inducible form of NO synthase (iNOS) by the infiltrated macrophages and NOS of endothelial cells, and superoxide from SMANCS will readily react to form peroxynitrite (O2- + NO-->ONOO-), which is a very potent cytotoxic molecule and will damage (nitrate and oxidize) DNA and proteins. Thus, tissue damage and vascular injury or collapse will be the principle tumor toxic mechanism of SMANCS at tissue level. The dose of SMANCS (or grade I-IV tumor filling) and tumor regression parallel each other, and a profile of AFP-value and technical issues of SMANCS/Lipiodol administration intraarterially are also discussed.

Animals↗

PubMed1998

[Distribution of retinal sensitivity with blue on yellow perimetry in ocular hypertension].

We evaluated the visual field pattern with Blue-on-Yellow perimetry in 22 eyes of 22 persons with ocular hypertension. Another series of 20 normal eyes served as controls. All the subjects underwent central field perimetry with a Humphrey automated perimeter (Model 640) using White-on-White targets. Blue-on-Yellow perimetry was performed within one week later. Both groups showed no difference in White-on-White perimetry, but the ocular hypertensive group showed a diffuse reduction in central sensitivity to Blue-on-Yellow perimetry by an average of 2.5 dB compared with the controls. These findings show the possibility that ocular hypertension causes fragility of the blue-yellow transmission system including the blue cones.

Adult↗

PubMed1998

Prevention of ornithine cytotoxicity by proline in human retinal pigment epithelial cells.

PURPOSE: To investigate the relationship between ornithine-delta-aminotransferase (OAT) deficiency and ornithine accumulation and the specific degeneration of retinal pigment epithelial (RPE) cells in gyrate atrophy. METHODS: Human RPE cells, human hepatoma cells, and human fibroblast cells were treated with 5-fluoromethylornithine (5-FMOrn), a specific irreversible inhibitor of OAT. Ornithine cytotoxicity was determined by using a [3H]thymidine incorporation assay and immunohistochemical staining for cytokeratin. The effects of various metabolites of ornithine and arginine, such as creatine, creatine phosphate, I-delta 1-pyrroline-5-carboxylic acid (L-P5C), and proline, which may be deficient in gyrate atrophy on RPE cell damage by ornithine, were determined by the same procedures. RESULTS: When the human RPE cells, HepG2 hepatoma cells, and WI-38 fibroblast cells were treated with 0.5 mM 5-FMOrn for 30 minutes, which inactivated OAT, ornithine exhibited severe time- and dose-dependent inhibition of DNA synthesis in the human RPE cells but not in the HepG2 hepatoma cells or WI-38 fibroblast cells. The inhibition of DNA synthesis was accompanied by drastic changes in morphologic appearance, disorganization of the cytoskeleton, and cell death. Ornithine or 5-FMOrn alone did not exhibit such cytotoxicity to the RPE cells. Proline prevented the cytotoxicity of ornithine. CONCLUSIONS: These findings suggest that an elevated level of ornithine combined with an increased sensitivity to ornithine as a result of OAT deficiency may be crucial to the specific RPE degeneration in gyrate atrophy. They suggest also that abnormalities of proline metabolism may be involved in the progress of gyrate atrophy.

Arginine↗

PubMed1998

[A case report of neoadjuvant intra-arterial injection chemotherapy combined with peripheral blood stem cell reinfusion in an advanced breast cancer patient].

A seventy-one year-old woman suffered from Stage IIIb advanced breast cancer complicated with direct thoracic invasion and skin eruption. An indwelling intra-arterial catheter was inserted into the subclavian artery for the administration of anti tumor agents. After three courses of neoadjuvant chemotherapy combined with G-CSF and/or PBSCT reinfusion, the breast cancer revealed a remarkable size reduction and was absent from direct thoracic and pectoral muscle, invasion within the physical status and visual analysis by CT scan. Thereafter, the patient underwent a radical mastectomy. In the pathological findings of the operation specimen, despite a remarkable tumor collapse, the microscopic invasion remained in the shallow layer of the pectoral muscle. Thus, the patient should be given additional postoperative irradiation. The patients has had six months of stable tumor-free survival since the mastectomy.

Aged↗

PubMed1998

Differential effects of chronic administration of the antidepressants amitriptyline and rolipram on adenylyl cyclase activity.

Significant increases were observed in guanylylimidodiphosphate- and fluoride-stimulated adenylyl cyclase activities in synaptic membrane preparations from rat cerebral cortex subsequent to the repeated administration of rolipram and amitriptyline. The potency of GppNHp-dependent inhibition of adenylyl cyclase was decreased by chronic treatment with rolipram but not by amitriptyline treatment. These findings suggest that chronically administered rolipram and amitriptyline share the augmentation of adenylyl cyclase activity by different actions on post-receptor signaling.

Adenylyl Cyclases↗

PubMed1998

Free-to-total prostate specific antigen ratio in clinical staging of prostate cancer.

The value of the free-to-total serum prostate-specific antigen (f/t PSA) ratio was compared with that of the total prostate specific antigen (tPSA) value for the prediction of clinical stage in patients with prostate cancer. The f/t PSA ratio was obtained from the frozen sera of 56 untreated patients with histologically proven BPH and 78 patients with prostate cancer. The clinical stage was organ-confined in 36, locally advanced in 20 and metastatic in 22 patients. Serum levels of free PSA (fPSA) and tPSA were determined using a chemiluminescent enzyme immunoassay. The f/t PSA ratio was calculated by dividing the fPSA value by the tPSA value and was compared with tPSA and fPSA in the correlation with clinical stage via the Spearman rank correlation test. Patients with prostate cancer had a significantly lower f/t PSA ratio than patients with BPH. The f/t PSA ratio did not differ between patients with clinically localized and metastatic cancer. tPSA and fPSA reflected the clinical stage and the extent of bone metastasis more accurately than the f/t PSA ratio. The extent of bone metastasis had no effect on the PSA ratio. The f/t PSA ratio had no additional value in clinical staging compared to tPSA. Our study suggests that the f/t PSA ratio does not reflect tumor load.

Aged↗