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Biomedical subjects

K Iwamoto

Publications and source records attributed to K Iwamoto.

At least 91 records · Page 5Linked to original sources

[Type III procollagen N-terminal aminopeptide and type IV collagen 7S in pleural effusion fluid].

The mechanism of pleural fibrosis in malignant and inflammatory pleural effusion remains unclear. We measured the levels of type III procollagen N-terminal amino peptide (PIIIP) and type IV collagen 7S in patients who had pleural effusion and lung carcinoma, and in others who had inflammatory diseases (parapneumonic and tuberculous pleuritis). The PIIIP level and the PIIIP/type IV collagen 7S ratio in patients with malignant pleural effusion were significantly lower than those in patients with inflammatory pleural effusion (p < 0.01), but the levels of type IV collagen 7S did not differ. The ratio of PIIIP to type IV collagen 7S was higher in patients with tuberculous pleuritis than in those with parapneumonic pleuritis (p < 0.05). These data indicate that pleural fibrotic adhesion may be accelerated in inflammatory pleural effusion because of elevated production of type III collagen; basement membrane injury in malignant and inflammatory pleural effusion may be caused by similar damage. We conclude that a high level of PIIIP and a high PIIIP/type IV collagen 7S ratio may indicate the presence of inflammatory pleuritis, and that the latter may indicate the presence of tuberculous pleuritis.

Aged↗

[A case of porencephaly with mirror movements: pathophysiological investigation by using long-latency long-loop reflex and dipole tracing method].

We report a 42-year-old left-handed woman with congenital right hemiparesis and bilateral mirror movements in the hands. She had a porencephaly of the left hemisphere and the brain MRI demonstrated cortical and subcortical defect of the left hemisphere from Brodmann's area 6 to 40 including the left motor cortex. By electrical stimulation of the left median nerve at the wrist, N20 of the somatosensory evoked potential was recorded in the right postcentral gyrus by using the dipole tracing method. Long-loop reflexes from the bilateral thenar muscles were recorded and their latencies were almost the same. The stimulation of the right median nerve did not evoke N20, nor long-loop reflex. These electrophysiological findings suggest that the reorganization of the motor system made the right motor cortex to innervate bilateral hands, and caused bilateral mirror movements. In other words, the mirror movements managed to relieve the paralysis of the right hand though the damage of the left motor cortex was present. In the previous literature we are able to find hypotheses regarding the mechanism of mirror movements in congenital hemiparesis. Here we discussed about the reorganization of the motor system in the damaged brain.

Cerebral Cortex↗

Isolation and primary culture of rat cerebral microvascular endothelial cells for studying drug transport in vitro.

To establish the cerebral microvascular endothelial cell (CMEC) culture system for animals commonly utilized in in vivo studies, we developed a method for isolation and culture of rat CMECs, and the model system was used in preliminary in vitro transport experiments. The isolated rat brains were minced. After an incubation with dispase, a fraction of microvessels was obtained by the dextran gradient. The tissue was filtered and dissociated using collagenase/dispase. After the enzyme treatment, the microvessels were layered onto the top of Percoll gradient and centrifuged for purification. Specific enzyme activities of alkaline phosphatase and gamma-glutamyltransferase in the preparations gradually increased as the isolation process progressed. The isolated cells reached confluence after 5-7 days in culture. The cultured cells had Factor VIII-related antigen and an uptake of acetylated-low density lipoprotein labeled with 1,1'-dioctadecyl-3,3, 3',3'-tetramethyl-indocarbocyamine perchlorate (Dil-Ac-LDL). In the transport studies, thawed cells after several months under -80 degrees C were used. The cultured cells after the freezing preservation also had CMEC characteristics, the same as the cells seeded immediately after isolation. The permeability of [14C]-mannitol, an impermeable marker for blood-brain barrier, was considerably reduced when the cell monolayer was present. The transport of [3H]3-O-methyl-D-glucose was significantly inhibited by the unlabeled compound. Furthermore, 2,4-dinitrophenol, an uncoupler of oxidative phosphorylation, significantly diminished the transport of [3H]L-proline. These results indicated that the cell monolayer obtained in the present study could be applicable to drug transport studies through the blood-brain barrier in vitro.

3-O-Methylglucose↗

Saturable transport of valproic acid in rat choroid plexus in vitro.

In order to obtain in vitro evidence for a specific transport system of valproic acid (VPA) at the blood-cerebrospinal fluid (CSF) interface, the uptake of VPA by isolated rat choroid plexus was investigated. The uptake clearance of [3H]VPA decreased with the increase of the unlabeled VPA concentration in the incubation medium. Kinetic analysis yielded an apparent Km of 10.0 mM, Vmax of 0.0871 mumol s-1 g-1 and Kns, a permeability coefficient of the nonsaturable component, of 6.85 microL s-1 g-1, indicating that both saturable and nonsaturable systems may contribute to VPA uptake by choroid plexus. Organic anions, penicillin G, p-aminohippurate, salicylate, and probenecid significantly inhibited VPA uptake by choroid plexus. We suggest that VPA translocation through choroidal membrane is partly operated by the organic anion transport system. A significant decrease of VPA uptake induced by 2,4-dinitrophenol, stilbenedisulfonate, and hypothermia (10 degrees C) indicates the involvement of an energy-dependent, carrier-mediated transport system. These results demonstrate that VPA is actively transported through the rat choroidal epithelium via a saturable system probably shared by organic anions.

4-Chloromercuribenzenesulfonate↗

Synthetic cationic amphiphile for liposome-mediated DNA transfection with less cytotoxicity.

A cationic peptide amphiphile comprising an L-alanine residue interposed between a charged head group and a double-chain segment, N,N-dihexadecyl-N alpha-[6-(trimethylammonio)- hexanoyl]-L-alaninamide bromide (NC5Ala2C16), was synthesized and used to prepare sonicated liposomes. We examined the efficiency of this liposome in gene transfer according to the transient expression of chloramphenicol acetyltransferase (CAT). This cationic liposome reagent facilitates efficient DNA transfection in COS-7 cells. We determined the optimum conditions for NC5Ala2C16 liposome-mediated transfection. The optimal amounts of the amphiphile and plasmid DNA were determined to be about 100 micrograms and 10 micrograms per 35-mm dish, respectively. The activity of this liposome was greater than that of commercial reagents, lipofectin, and N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethyl-ammonium methylsulfate (DOTAP), and it was less toxic than lipofectin and DOTAP in COS-7 cells.

Animals↗

[Traumatic atlanto-occipital dislocation: a case report with survival].

We reported a case of a patient who survived anterior atlanto-occipital dislocation. A seven-year-old girl was admitted to our hospital due to disturbed consciousness after being involved in a traffic accident. With gradual improvement of consciousness, she showed bilateral abducens nerve palsy, quadriparesis and cervical instability. Lateral plain film showed anterior atlanto-occipital dislocation. MRI showed severe compression of the cervical cord and disruption of supporting ligaments of the cervicomedullary junction. After 4 months, cervical instability continued and posterior fixation was carried out with bone grafts. Her postoperative course was uneventful.

Accidents, Traffic↗

Pancreatic beta-cell-specific targeted disruption of glucokinase gene. Diabetes mellitus due to defective insulin secretion to glucose.

Mice carrying a null mutation in the glucokinase (GK) gene in pancreatic beta-cells, but not in the liver, were generated by disrupting the beta-cell-specific exon. Heterozygous mutant mice showed early-onset mild diabetes due to impaired insulin-secretory response to glucose. Homozygotes showed severe diabetes shortly after birth and died within a week. GK-deficient islets isolated from homozygotes showed defective insulin secretion in response to glucose, while they responded to other secretagogues: almost normally to arginine and to some extent to sulfonylureas. These data provide the first direct proof that GK serves as a glucose sensor molecule for insulin secretion and plays a pivotal role in glucose homeostasis. GK-deficient mice serve as an animal model of the insulin-secretory defect in human non-insulin-dependent diabetes mellitus.

Alternative Splicing↗

A mutation in the beta 3-adrenergic receptor gene is associated with obesity and hyperinsulinemia in Japanese subjects.

The Trp 64 Arg mutation in the beta 3-adrenergic receptor (beta 3AR) gene was investigated in 350 Japanese subjects. This mutation was not associated with non-insulin-dependent diabetes mellitus (NIDDM). In 191 subjects without NIDDM, body mass index (BMI) was significantly higher in subjects homozygous for this mutation than in those homozygous for the normal allele (24.7 +/- 1.4 vs 22.1 +/- 0.2 kg/m2, p = 0.009). Moreover, the frequency of the mutant allele in obese subjects (BMI > 26.4) was significantly higher than that in non-obese subjects (BMI < 22) (0.37 vs 0.15, p = 0.009). The presence of this mutation was also accompanied by significantly higher fasting (p = 0.000) and 2 hrs (p = 0.018) serum insulin levels during an oral glucose tolerance test. The beta 3AR may be one of the loci contributing to obesity and hyperinsulinemia/insulin resistance in Japanese subjects.

Adult↗

No evidence for mutations in a putative subunit of the beta-cell ATP-sensitive potassium channel (K-ATP channel) in Japanese NIDDM patients.

The ATP-sensitive K channel (K-ATP channel) in pancreatic beta cells is believed to play a crucial role in glucose-stimulated insulin release. We investigated whether defects in the recently cloned gene for a putative subunit of this channel (KATP-2) could be a cause of diabetes in Japanese patients. The coding region of this beta-cell type channel gene was investigated in 192 diabetics with a family history of the disorder by single-stranded conformational polymorphism (SSCP) analysis. Two silent polymorphisms were found and confirmed by sequencing, but no missense or nonsense mutations were detected. The allele frequency of the polymorphisms was compared with 96 control subjects without a family history of the disease, and no clear difference was found. These results indicate that genetic defects of the KATP-2 channel may not be a major cause of diabetes in Japan.

Adult↗

Diethylstilbestrol revisited: a review of the long-term health effects.

PURPOSE: To review the literature on the long-term health effects of exposure to diethylstilbestrol (DES) among women prescribed DES during pregnancy (DES mothers), among their children exposed inutero to the drug (DES sons and daughters) and among the progeny of these exposed sons and daughters (DES grandchildren). DATA SOURCES: English-language articles were identified through MEDLINE and CANCERLIT searches and through review of the bibliographies of identified articles. STUDY SELECTION: All human studies relevant to long-term health effects of exposure to DES were reviewed. DATA EXTRACTION: Descriptive data on existing DES cohorts were extracted from early publications. Risk estimates for health effects were extracted from published reports. DATA SYNTHESIS: An estimated 5 to 10 million Americans received DES during pregnancy or were exposed to the drug in utero. Exposure to DES has been associated with an increased risk for breast cancer in DES mothers (relative risk, < 2.0) and with a lifetime risk of clear-cell cervicovaginal cancer in DES daughters of 1/1000 to 1/10,000. The association between DES exposure and testicular cancer in DES sons remains controversial. Exposure to DES has also been linked to reproductive tract abnormalities in DES sons and daughters that consist of immune system disorders and psychosexual effects. No evidence for transgenerational effects currently exists. Recommendations for screening persons exposed to DES are reviewed. CONCLUSIONS: Further research is needed to define long-term health effects related to DES exposure. Such research would provide a basis for counseling persons exposed to DES and would further understanding of environmental and pharmacologic compounds similar to DES.

Animals↗

Effect of ultraviolet-A (UV-A) light on growth, photosynthetic activity and production of biopterin glucoside by the marine UV-A resistant cyanobacterium Oscillatoria sp.

We have isolated a marine planktonic cyanobacterium Oscillatoria sp. NKBG 091600 which is resistant to ultraviolet-A (UV-A) irradiation. In response to UV-A irradiation this cyanobacterium produces high levels of a UV-A absorbing compound which was identified previously as biopterin glucoside. Here, we have investigated the effect of UV-A light intensity on growth, biopterin glucoside production and photosynthetic activity. Oscillatoria sp. NKBG 091600 could grow at UV-A intensities of up to 800 microW/cm2 and at 300 microW/cm2 could grow as well as in the absence of UV-A irradiation. In addition, pre-culture of cells with UV-A protected cells from UV-A induced inhibition of photosynthetic activity. Detection of biopterin glucoside levels in irradiated cells by HPLC demonstrated that after 10 h there was a rapid increase in biopterin glucoside content. This increase was dependent on the intensity on the intensity of the UV-A irradiation.

Biopterins↗

beta-Carbolinium cations, endogenous MPP+ analogs, in the lumbar cerebrospinal fluid of patients with Parkinson's disease.

We measured beta-carbolinium cations (BC+s) endogenous analogs of the N-methyl-4-phenylpyridinium ion (MPP+), in the lumbar CSF of 22 patients with idiopathic Parkinson's disease (PD) and 11 age-matched controls without any symptoms of parkinsonism. Among the BC+s, 2,9-diemethylnorharmanium cation (2,9-Me2NH+), the most potent neurotoxicant that mirrors MPP+ in mitochondria toxicity, was present in 12 patients with PD but not in controls. Although the 2-monomethylated beta-carbolinium cations (2-MeBC+s), which were present in almost all subjects, registered a slightly higher level in PD patients than in controls, the difference was not significant. The total BC+ content, sum of 2-MeBC+ and 2,9-Me2NH+ levels, was significantly higher in PD patients than in controls. The 2-MeBC+ contents significantly increased with the progression of the PD, but 2,9-Me2NH+ decreased as the disease exacerbated, although levels varied within a wide range. The present results strongly support the hypothesis that "bioactivated" BC+s, especially 2,9-Me2NH+s, may be the endogenous causative factors underlying PD.

1-Methyl-4-phenylpyridinium↗

Radiofrequency catheter ablation for atrioventricular node reentry tachycardia with multiple slow atrioventricular node pathways.

Catheter ablation was attempted in 2 patients with atrioventricular node reentry tachycardia which showed fast, intermediate and slow anterograde atrioventricular node pathways. Radiofrequency currents were applied within a restricted area of the tricuspid annulus between the His bundle and the ostium of the coronary sinus where presumed slow pathway potentials were identified. Elimination of both the intermediate and the slow pathways, with preservation of anterograde and retrograde fast pathway conduction, was achieved in both patients.

Aged↗

Differential significance of nitric oxide in hypotensive mechanisms of acetylcholine and histamine in dogs.

The nitric oxide synthase inhibitor, NG-nitro-L-arginine, suppressed hypotensive response to acetylcholine, but not to histamine, in pentobarbital-anesthetized dogs. Infusions of acetylcholine increased plasma cyclic GMP levels, while histamine infusions did not. These results indicate that there is an apparent difference in the contributions of nitric oxide to the hypotensive mechanisms of acetylcholine and histamine.

Acetylcholine↗

Isolation of cylindrospermopsin from a cyanobacterium Umezakia natans and its screening method.

In 1987 a cyanobacterium (blue-green alga) Umezakia natans was isolated from Lake Mikata, Fukui, Japan, as a new member of the family of Stigonemataceae. The crude extract of U. natans showed hepatotoxicity to mice, from which a toxic compound was isolated. The toxin was identical in all respects to a recently reported hepatotoxin, cylindrospermopsin, isolated from an Australian tropical cyanobacterium Cylindrospermopsis raciborskii. Because cylindrospermopsin causes fatty liver and central necroses in mice and is suspected of being an agent causing human hepatoenteritis, its monitoring in drinking water supplies has been required. So a rapid screening method including four steps, extraction, clean-up, separation, and determination, has been proposed for cylindrospermopsin. A combination of a clean-up using HP-20 and C18-cartridge, and HPLC with photodiode array detector made it possible to establish a screening method for the toxin. The established method was applied to five samples and cylindrospermopsin was traced in one of them.

Alkaloids↗

Immunomodulatory effects of three macrolides, midecamycin acetate, josamycin, and clarithromycin, on human T-lymphocyte function in vitro.

The effect of three macrolide antibiotics, midecamycin acetate, josamycin, and clarithromycin, on human T-cell function was investigated in vitro. Midecamycin acetate and josamycin suppressed the proliferative response of peripheral blood mononuclear cells stimulated by polyclonal T-cell mitogens at concentrations between 1.6 and 8 micrograms/ml. At higher concentrations (40 to 200 micrograms/ml), all these drugs showed a marked inhibitory effect. At concentrations of 1.6 to 40 micrograms/ml, these drugs suppressed interleukin-2 (IL-2) production induced by mitogen-stimulated T cells, but not the expression of IL-2 receptor (CD25), in a dose-dependent manner. Therefore, the suppressive action on T-lymphocyte proliferation seems to be based on the ability of these drugs to inhibit IL-2 production by T cells. The drug also inhibited mixed lymphocyte reaction at the same concentrations. Combined treatment with these macrolides and the known immunosuppressants such as FK506 and cyclosporin A resulted in an increased inhibition of T-cell proliferation. The immunomodulatory properties of the antibiotics may have clinical relevance for modulation of the immune response in transplant patients and in patients with inflammatory diseases.

Adjuvants, Immunologic↗