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Biomedical subjects

M Ohta

Publications and source records attributed to M Ohta.

At least 199 records · Page 11Linked to original sources

Joint effects of HMG-CoA reductase inhibitors and eicosapentaenoic acids on serum lipid profile and plasma fatty acid concentrations in patients with hyperlipidemia.

HMG-CoA reductase inhibitors reduce serum total cholesterol concentrations and the risk of coronary heart disease in patients with hypercholesterolemia. Recently, it has been reported that patients with combined hyperlipidemia are also at risk of coronary heart disease. However, HMG-CoA reductase inhibitor therapy alone does not sufficiently reduce serum triglyceride concentrations. Epidemiological and clinical evidence has shown that fish oil can lower plasma lipid levels, especially triglycerides. Consequently, we investigated the effects of the combination of HMG-CoA reductase inhibitors and eicosapentaenoic acid, a major component of fish oil, on hyperlipidemia. We administered 900-1,800 mg/day of the ethyl ester of eicosapentaenoic acid to patients with hyperlipidemia who had been treated with HMG-CoA reductase inhibitors for 30 +/- 6 months (means +/- SE). Serum total cholesterol and triglyceride concentrations were significantly decreased 3 months after the administration of eicosapentaenoic acid (from 5.63 +/- 0.23 mmol/l to 5.02 +/- 0.20 mmol/l, P < 0.05; from 2.07 +/- 0.41 mmol/l to 1.08 +/- 0.17 mmol/l, P < 0.01, respectively). Serum high-density lipoprotein-cholesterol concentrations were significantly increased after the treatment (from 1.23 +/- 0.12 mmol/l to 1.34 +/- 0.13 mmol/l, P < 0.05). Plasma eicosapentaenoic acid concentrations and the ratio to arachidonic acid in plasma were also significantly increased 3 months after the treatment (from 101.9 +/- 8.1 mg/l to 181.8 +/- 23.9 mg/l, P < 0.001; from 0.640 +/- 0.075 to 1.211 +/- 0.170, P < 0.001, respectively). These results suggested that the combination therapy of HMG-CoA reductase inhibitors and eicosapentaenoic acid was effective for patients with hyperlipidemia.

Aged↗

Detection and differentiation of Aino and Akabane Simbu serogroup bunyaviruses by nested polymerase chain reaction.

Reverse transcription-polymerase chain reaction (RT-PCR) and nested PCR were developed to detect and differentiate Aino (AINO) and Akabane (AKA) virus S RNA. Two pairs of AINO- and AKA-specific primers for nested PCR were synthesized and examined for their capacity to amplify PCR products using 7 Simbu serogroup viruses isolated in Japan and Australia. RT- and nested PCR using AKA-specific primers amplified cDNA from Tinaroo virus RNA as well as homologous RNA. Nested PCR products were differentiated by Hph I and Bst EII digestion. Peaton (PEA) virus S cDNA was also amplified using AINO- specific primers. The nested PCR products of PEA virus were not digested by 3 restriction enzymes (Ava II, Eco RI and Hae II), whereras those of AINO virus were digested as expected. Using this technique, AINO and AKA viruses were detected at concentrations as low as 10(-3) plaque-forming units (PFU) and 10(-5) PFU, respectively, in a supernatant of virus-infected cells. It was possible to detect AINO and AKA genome from various tissues of experimentally infected mice, and also the AKA nested PCR products from serum samples from sentinel cattle naturally infected with AKA virus. The present nested PCR appears a simple, rapid and valuable method for diagnosing AINO and AKA infection.

Animals↗

Functional imaging in periventricular nodular heterotopia with the use of FDG-PET and HMPAO-SPECT.

We analyzed the interictal [18F]fluoro-2-deoxy-D-glucose positron emission tomography (FGD-PET) and single photon emission computed tomography with technetium-99m-hexamethyl-propyleneamine oxime (HMPAO-SPECT) in two epileptic patients with periventricular nodular heterotopia (PNH). In both cases, we found both the glucose metabolism and the perfusion of PNH to be almost identical to those of the normal cerebral cortex. The metabolic activity and perfusion in the heterotopic gray matter in a subependymal white matter area probably represent the glucose metabolism and perfusion of the abnormally located gray matter rather than a subclinical ictal phenomenon. FDG-PET and HMPAO-SPECT were thus found to be a useful complement to magnetic resonance imaging in the evaluation of PNH.

Adult↗

Results of laparoscopic splenectomy for immune thrombocytopenic purpura.

BACKGROUND: Laparoscopic splenectomy has been demonstrated to be technically feasible and safe for the treatment of immune thrombocytopenic purpura (ITP), hereditary spherocytosis, and Hodgkin's disease. PATIENTS AND METHODS: The study comprised 76 consecutive patients with chronic ITP who were admitted to our hospital from 1968 to 1997 and underwent splenectomy; 35 patients underwent a laparoscopic splenectomy, and 41 had open surgery. RESULTS: Laparoscopic splenectomy involved minimal incision, and a significantly lower frequency of analgesia was required for postoperative abdominal pain (1.4 versus 3.3); postoperative hospital stay was shorter (9.6 versus 20.1 days, P <0.05). Operative time was significantly longer for the laparoscopic surgery (204.5 versus 99.8 minutes, P <0.01), but blood loss was less (154.4 versus 511.7 g, P <0.01). During the present study (range 3.8 to 80 months), accumulative nonrecurrence rate was 67.9% in 5 years after surgery, which is similar to that of the previous open splenectomy. CONCLUSIONS: Laparoscopic splenectomy can become an alternative therapeutic modality in the treatment of ITP.

Adult↗

Impaired learning and memory in OLETF rats without cholecystokinin (CCK)-A receptor.

Cholecystokinin (CCK) is one of the most abundant neurotransmitter peptides in the brain. As OLETF rats lack CCK-A receptor because of a genetic abnormality, we examined whether learning and memory were impaired in these animals using an elevated eight-arm radial maze. After the completion of a radial maze study, the animals were sacrificed for histological examination of the brain. In some animals, long-term potentiation (LTP) in the hippocampus was measured. In the radial maze, the level of activity (seconds/entry) and the time remaining in the arms were significantly longer in OLETF rats. The number of errors was also significantly higher, and that of the correct choices was significantly lower in OLETF rats compared to the controls (LETO rats). The LTP of the population spike was significantly lower in the OLETF than in the LETO rats. No histological abnormalities were observed. From these observations, we concluded that learning and memory functions were impaired in the OLETF rats.

Animals↗

Angiographic and histologic effects of fundus photodynamic therapy with a hydrophilic sensitizer (mono-L-aspartyl chlorin e6).

PURPOSE: To demonstrate the efficacy of the photosensitizer mono-L-aspartyl chlorin e6 (NPe6) in closing choroidal vessels at low energy levels, that tissue uptake and clearance are rapid, and that low concentrations of drug are needed to achieve clinical effects. DESIGN: Experimental animal study. ANIMALS: Pigmented rabbits and Japanese monkeys were used in this study. METHODS: Using a modified 664-nm diode laser, the fundi of pigmented rabbits and Japanese monkeys were irradiated after intravenous administration of NPe6 (2-100 mg/kg). Time from injection to irradiation varied from 5 to 15 minutes, and duration of exposure varied from 1 to 10 seconds. Power output at the corneal surface was either 3.6 or 5.9 mW. Animals were examined by indirect ophthalmoscopy and fluorescein angiography at 2 hours and 7 days after treatment. After enucleation 7 days after treatment, specimens were prepared for light and electron microscopy. MAIN OUTCOME MEASURES: Angiographic evidence of occlusion and histopathologic evidence of retinal damage. RESULTS: Both clinical and histopathologic examination demonstrated effects on the choroidal vasculature and the retinal pigment epithelium, including necrosis of endothelial cells and occlusion in choroidal vessels, particularly within the choriocapillaris, at low energy levels. Overlying neurosensory retina was minimally affected. Fluorescein angiography of lesions treated with 2 mg/kg and laser fluence of 2.3 to 7.5 J/cm2 showed a normal appearance 2 hours after treatment, which changed to early hypofluorescent and later hyperfluorescent lesions 7 days after treatment. In contrast, those animals receiving the 10-mg/kg dose and laser fluence of 0.46 to 0.75 J/cm2 showed marked hypofluorescence of choroidal lesions and occlusion of retinal vessels 7 days after treatment. CONCLUSIONS: Effective occlusion of normal choroidal vessels was achieved at 2 mg/kg using 2.3 to 7.5 J/cm2 or at 10 mg/kg using 0.46 to 0.75 J/cm2 with minimal injury to overlying neurosensory retina.

Animals↗

Cerebrospinal fluid cytokine levels and dexamethasone therapy in bacterial meningitis.

OBJECTIVES: cerebrospinal fluid (CSF) levels of interleukin (IL)-1 beta and tumor necrosis factor (TNF) alpha were measured to assess the effect and application of dexamethasone (Dex) therapy for bacterial meningitis. METHODS: associations between clinical findings and CSF parameters were first investigated, and prognosis was compared between 25 patients with Dex and 12 without Dex therapy. RESULTS: patients with the presence of disturbed consciousness showed higher CSF levels of TNF alpha (mean: 3015 pg/ml) or protein (mean: 215 mg/dl) than those without it (both, P < 0.O5). Simultaneous increase of TNF alpha (> 1000 pg/ml) and protein (> 100 g/dl) was observed in 80%, of patients with profoundly disturbed consciousness. Patients with Dex therapy presented higher TNF alpha/protein levels at diagnosis than those without Dex therapy (P < 0.05). Despite worse conditions at diagnosis, only one of 14 Dex-treated patients whose initial CSF TNF alpha levels exceeded 1000 pg/ml developed deafness. On the other hand, two of four patients without Dex therapy who had the same TNF alpha level suffered from psychomotor retardation. The differences in the frequency of sequelae between those with and without Dex therapy were significant in patients showing high TNF alpha level (P < O.05), but not in those showing high CSF levels of IL-1 beta or protein. The logistic regression analysis indicated that high CSF protein level (P < O.0001), or no Dex therapy (P=0.0001) was the independent risk factor for sequelae. CONCLUSIONS: although the study number was small, our observations suggested that CSF TNF alpha/protein levels reflected the neurologic severity, and implied that early Dex therapy might be beneficial for patients with prominently high TNF alpha levels.

Adolescent↗

Production and characterization of monoclonal antibodies that recognize bovine Kit receptor.

Kit receptor is a transmembrane tyrosine kinase that is the receptor for stem cell factor (SCF). The extracellular domain of bovine Kit receptor (boKit) was produced by a baculovirus expression system. Six monoclonal antibody (MAb) clones designated as bK-1 to bK-6 were obtained upon immunization of mice with the recombinant protein. Immunoprecipitation and flow cytometric analysis indicated that all of the MAbs specifically bound to boKit expressed in COS-7 cells transfected with boKit cDNA. Four of the six MAbs neutralized the biological activity of recombinant bovine SCF, whereas the other two did not. The boKit-positive and boKit-negative cell fractions were sorted from cryopreserved bovine bone marrow cells by the use of MAb bK-1. Colony formation assays indicated that the cells which were able to grow in response to bovine SCF were enriched in the boKit-positive fraction. These MAbs would be valuable in studying possible boKit-positive cell species such as bovine hematopoietic cells, and in defining the biological role of Kit receptor in cattle.

Animals↗

Influence of TNF microsatellite polymorphisms (TNFa) on age-at-onset of insulin-dependent diabetes mellitus.

The TNF-alpha gene is located in the HLA region and has been implicated in the pathogenesis of Type I (insulin-dependent) diabetes mellitus (IDDM). We investigated the frequency of TNFa microsatellite alleles in 76 young-onset IDDM patients, 65 adult-onset IDDM patients, and 90 control subjects. We also examined the association of these TNFa alleles with HLA-DRB1 alleles, HLA-class I alleles, and TNF-alpha production. The frequency of the TNFa2 and TNFa9 alleles was increased in the young-onset IDDM patients compared to control subjects, but the increased frequency of TNFa2 was not significant after the correction for the number of comparisons was made. We did not find any association of TNFa2 or TNFa9 with any of the HLA-DRB1 alleles. In contrast, the frequency of the TNFa13 allele was decreased in both the young-onset and the adult-onset IDDM patients compared to the control subjects, but the difference lost significance after the correction was made in the adult-onset IDDM. The TNFa13 allele was strongly associated with DRB1*1502. Patients with TNFa2 or TNFa9 had greater TNF-alpha production, while those positive for TNFa13 had lower TNF-alpha production than patients with non-TNFa2, a9, and a13 alleles. These results suggest that TNFa polymorphisms are associated with age-at-onset of IDDM and influence the inflammatory process of pancreatic beta cell destruction in the development of IDDM.

Adolescent↗

Dose escalation and pharmacokinetic study of a humanized anti-HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer.

We conducted a phase I pharmacokinetic dose escalation study of a recombinant humanized anti-p185HER2 monoclonal antibody (MKC-454) in 18 patients with metastatic breast cancer refractory to chemotherapy. Three or six patients at each dose level received 1, 2, 4 and 8 mg kg(-1) of MKC-454 as 90-min intravenous infusions. The first dose was followed in 3 weeks by nine weekly doses. Target trough serum concentration has been set at 10 microg ml(-1) based on in vitro observations. The mean value of minimum trough serum concentrations at each dose level were 3.58 +/- 0.63, 6.53 +/- 5.26, 40.2 +/- 7.12 and 87.9 +/- 23.5 microg ml(-1) respectively. At 2 mg kg(-1), although minimum trough serum concentrations were lower than the target trough concentration with a wide range of variation, trough concentrations increased and exceeded the target concentration, as administrations were repeated weekly. Finally 2 mg kg(-1) was considered to be sufficient to achieve the target trough concentration by the weekly dosing regimen. One patient receiving 1 mg kg(-1) had grade 3 fever, one at the 1 mg kg(-1) level had severe fatigue defined as grade 3, and one at 8 mg kg(-1) had severe bone pain of grade 3. No antibodies against MKC-454 were detected in any patients. Objective tumour responses were observed in two patients; one receiving 4 mg kg(-1) had a partial response in lung metastases and the other receiving 8 mg kg(-1) had a complete response in soft tissue metastases. These results indicate that MKC-454 is well tolerated and effective in patients with refractory metastatic breast cancers overexpressing the HER2 proto-oncogene. Further evaluation of this agent with 2-4 mg kg(-1) weekly intravenous infusion is warranted.

Antibodies, Monoclonal↗

Occlusal contact area, occlusal pressure, bite force, and masticatory efficiency in patients with anterior disc displacement of the temporomandibular joint.

The occlusal contact area, occlusal pressure, bite force, and masticatory efficiency were measured in 48 patients with anterior disc displacement (ADD) of the temporomandibular joint (TMJ). The results were compared with those of 30 normal controls without TMJ dysfunction. The values of occlusal contact area, bite force, and masticatory efficiency measured in patients with ADD were significantly smaller than those measured in the controls, although there was no difference in occlusal pressure between the two groups. The results of the measurements of 22 patients with ADD with reduction were also compared with those of 26 patients with ADD without reduction. There was no difference in any measurement between these patients subgroups. The analysis of occlusal contact area, bite force, and masticatory efficiency appeared to be useful methods in documenting the fact that masticatory function was impaired in patients with ADD of the TMJ.

Adenosine Triphosphate↗

Effect of candesartan cilexetil (TCV-116) in rats with chronic renal failure.

BACKGROUND: Inhibition of the renin-angiotensin system by both angiotensin II type 1 receptor antagonists (AT1As) and angiotensin I-converting enzyme inhibitors (ACEIs) shows renoprotective effects in rats with chronic renal failure when treatment is started in the early phase of renal injury. In this study, we examined the renal protective effects of candesartan cilexetil (TCV-116), an AT1A, and enalapril, an ACEI, in the progressive phase of renal injury in 5/6 nephrectomized rats. METHODS: Candesartan cilexetil (1 mg/kg/day) and enalapril (10 mg/kg/day) were orally administered once a day for 4 weeks (the short-term experiment) or 16 weeks (the long-term experiment) to 5/6 nephrectomized rats beginning 15 weeks after the nephrectomy, that is, after they had already showed marked proteinuria. RESULTS: In vehicle-treated rats, proteinuria, glomerulosclerosis, and interstitial fibrosis developed. Moreover, enhanced expression of transforming growth factor-beta1 (TGF-beta1) in the injured glomeruli was observed. These adverse changes progressed with time, and in the short-term experiment, both drugs inhibited them. In the long-term experiment, the progressive proteinuria and the elevation of blood pressure were similarly attenuated by both drugs. However, candesartan cilexetil significantly inhibited the progression of glomerulosclerosis, the expression of TGF-beta1, and interstitial fibrosis, whereas enalapril did not. CONCLUSION: These results indicate that candesartan cilexetil shows potent and long-term preventive effects against the progression of previously developed renal injury.

Angiotensin Receptor Antagonists↗

Rapid detection of the gene of Legionella pneumophila using the fluorescence polarization with the asymmetric PCR.

We attempted the rapid detection method of Legionella pneumophila by the asymmetric PCR and the fluorescence polarization. Eleven extracted DNAs from L. pneumophila serogroup 1 to approximately 6, L. bozemanii, L. dumoffii, L. gormanii, L. micdadei, and Pseudomonas aeruginosa were amplified by asymmetric PCR, and the polarization of those products were measured. Only the polarization of L. pneumophila serogroup 1 to approximately 6 rose within a few minutes after the beginning of measurement. The sensitivity to L. pneumophila using this method was 10(3) cells.

Animals↗

Growth conditions of and emetic toxin production by Bacillus cereus in a defined medium with amino acids.

The growth and emetic toxin (cereulide) production of Bacillus cereus strains in defined culture media were studied. We found that a fully synthetic medium (CADM) allowed the production of emetic toxin and the addition of glucose enhanced it. By subtracting each amino acid from CADM, we found that only three amino acids, valine, leucine and threonine, were essential for growth and toxin production by B. cereus. The addition of high levels (50 mM) of leucine, isoleucine and glutamic acid decreased the toxin production. Other amino acids had no effect at this concentration.

Amino Acids↗

Antibacterial activities of new synthetic divalent cation chelators.

A series of new synthetic ligand compounds which chelate divalent cations was examined for the antibacterial activities of the compounds. Only 2 of 14 synthetic chelators, 9-trans-anthryl-1, 4, 8, 11-tetraaza-tetradecane (No. 6) and bis(2-pyridyl)methylamine (No. 13) showed antibacterial activities, whereas none of the diamines, hydrophilic triamines nor tetramines showed antibacterial activities. Chelators No. 6 and No. 13 inhibited the growth of both Gram-negative and -positive bacteria at doses of 25-200 microg/ml, comparable to those of common antibiotics such as polymixin B, fosfomycin and macrolides. Ethylenediaminetetraacetate (EDTA) potentiated these antibacterial activities, whereas an inhibitory effect of Mg2+ on the MICs of these chelators was observed. Moreover, these chelators enhanced the leakage of periplasmic beta-lactamase. It is therefore suggested that chelators No. 6 and No. 13 disrupt both the membranes and cytoplasmic functions of bacteria, resulting in cell death.

Anthracenes↗

Prophylaxis of local vascular graft infection with levofloxacin incorporated into albumin-sealed dacron graft (LVFX-ALB Graft).

An animal model was used to assess the efficacy of levofloxacin (LVFX) incorporated into albumin (ALB)-sealed Dacron (LVFX-ALB) graft for the prevention of vascular graft infections caused by Staphylococcus aureus. Under general anesthetic, an interposition graft was placed into dog carotid artery. On completion of the operation, 0.1 ml of normal saline containing 10(7) colony-forming units (CFU) of a slime-producing S. aureus was inoculated directly onto the graft. After 1 day, the samples were sterilely harvested. The antibacterial activity of LVFX into the LVFX-ALB graft was evaluated by colony counting in bacterial cultures and by the fluorescent antibody method staining bacteria adhesion to the grafts. LVFX-ALB grafts had a lower infection rate than the control grafts (1/4, 10(2) CFU vs 4/4, 1.50 x 10(5)+/-1.38 x 10(5)CFU (mean+/-SE)). In an immunostaining study, LVFX-ALB grafts had small fluorescent areas showing S. aureus adhesion, while fluorescence was observed over the entire surface of the control grafts. Therefore, LVFX-ALB presumably had a bactericidal action and adhesive prevention against inoculated S. aureus. LVFX-ALB may be useful in preventing graft infections during and immediately after vascular reconstruction.

Albumins↗

Are autoantibodies against Lewis antigens involved in the pathogenesis of Helicobacter pylori-induced peptic ulcers?

We examined whether anti-Lewis x (Le(x)) and y (Le(y)) autoantibodies affect the pathogenesis of Helicobacter pylori-induced peptic ulcers. Of 11 patients with peptic ulcers, 10 patients had both anti-Le(x) and -Le(y) immunoglobulin G (IgG) antibodies, and 1 patient had only anti-Le(x) antibody. After successful eradication, we measured the serum titer of anti-Le(x) and -Le(y) antibodies. Six patients had a reduction of the titers of anti-Le(x) and/or -Le(y) antibodies, whereas no notable changes were detected in 5 patients in the follow-up. This result suggests that anti-Le(x) and -Le(y) autoantibodies had no critical role in the development of H. pylori-induced peptic ulcer.

Autoantibodies↗