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Biomedical subjects

K Kaneko

Publications and source records attributed to K Kaneko.

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

Randomly amplified polymorphic DNA analysis of Erysipelothrix spp.

The usefulness of randomly amplified polymorphic DNA method (RAPD) to identify each species of genus Erysipelothrix and for epidemiological analysis of this genus was studied. Eighty-one strains and 18 random primers were tested. Among the tested primers, the primers NK51 (GGTGGTGGTATC) and NK6 (CCCGCGCCCC) produced noticeable results. The primer NK51 revealed four species-specific RAPD patterns. Of the 66 strains of E. rhusiopathiae, 64 had the same unique band of 884 bp. Of the 12 strains of E. tonsillarum, 11 produced a 1,265-bp band. In addition, two strains, previously thought to be E. rhusiopathiae, produced the 1,265-bp band, suggesting that they had been misclassified. One strain of E. tonsillarum produced the 884-bp band, suggesting that it too was E. rhusiopathiae. The E. rhusiopathiae strain of serovar 13 produced a 650-bp band, and the strain of serovar 18 produced a clear 420-bp band as well as three weak bands of 1,265, 918, and 444 bp. The primer NK6 revealed 14 RAPD patterns that were not serovar specific. However, different patterns were produced among strains of the same serovar showing that the RAPD method is able to identify the genetic variations of strains of this genus and can rapidly and easily differentiate strains of the same serovar. Based on these results, we concluded that the RAPD method with primers NK51 and NK6 is a rapid and reliable method to identify the species of this genus; we also concluded that this method might be a useful tool for the epidemiological analysis of the Erysipelothrix species.

Erysipelothrix↗
PubMed2000

Dominant-negative inhibition of prion formation diminished by deletion mutagenesis of the prion protein.

Polymorphic basic residues near the C terminus of the prion protein (PrP) in humans and sheep appear to protect against prion disease. In heterozygotes, inhibition of prion formation appears to be dominant negative and has been simulated in cultured cells persistently infected with scrapie prions. The results of nuclear magnetic resonance and mutagenesis studies indicate that specific substitutions at the C-terminal residues 167, 171, 214, and 218 of PrP(C) act as dominant-negative, inhibitors of PrP(Sc) formation (K. Kaneko et al., Proc. Natl. Acad. Sci. USA 94:10069-10074, 1997). Trafficking of substituted PrP(C) to caveaola-like domains or rafts by the glycolipid anchor was required for the dominant-negative phenotype; interestingly, amino acid replacements at multiple sites were less effective than single-residue substitutions. To elucidate which domains of PrP(C) are responsible for dominant-negative inhibition of PrP(Sc) formation, we analyzed whether N-terminally truncated PrP(Q218K) molecules exhibited dominant-negative effects in the conversion of full-length PrP(C) to PrP(Sc). We found that the C-terminal domain of PrP is not sufficient to impede the conversion of the full-length PrP(C) molecule and that N-terminally truncated molecules (with residues 23 to 88 and 23 to 120 deleted) have reduced dominant-negative activity. Whether the N-terminal region of PrP acts by stabilizing the C-terminal domain of the molecule or by modulating the binding of PrP(C) to an auxiliary molecule that participates in PrP(Sc) formation remains to be established.

Animals↗
PubMed2000

Renal amyloidosis in recessive dystrophic epidermolysis bullosa.

BACKGROUND: Although it is known that renal amyloidosis may complicate several dermatoses, recessive dystrophic epidermolysis bullosa (RDEB) complicated by nephropathy has been thought to be rare. We, however, had seen a young adult with RDEB who died of renal failure due to systemic amyloidosis. OBJECTIVE: A retrospective study was performed in order to investigate the incidence and etiology of renal amyloidosis in RDEB. METHODS: Routine urinalysis, serum amyloid A protein (SAA) and creatinine levels were repeatedly determined in 11 patients with RDEB (mean age 17.7 years, range 5-28, 7 males, 4 females). Nephropathy was defined as the presence of both proteinuria and hematuria with red blood cell casts. RESULTS: Seven out of 9 generalized RDEB patients had nephropathy including 3 cases with end-stage renal disease (2 died within 2 years from the onset of nephropathy), while 2 patients with localized RDEB did not. Levels of SAA were significantly higher in patients with nephropathy than those in patients without nephropathy (p<0.05). CONCLUSION: Nephropathy is a common and serious complication of RDEB. Renal amyloidosis may play an important role in its etiology. We recommend that patients with RDEB should be periodically screened for nephropathy due to amyloidosis by urinalysis and measuring SAA levels.

Adolescent↗
PubMed2000

Complex organization in multicellularity as a necessity in evolution.

By introducing a dynamical system model of a multicellular system, it is shown that an organism with a variety of differentiated cell types and a complex pattern emerges through cell-cell interactions even without postulating any elaborate control mechanism. Such an organism is found to maintain a larger growth speed as an ensemble, by achieving a cooperative use of resources, than do simple homogeneous cells, which behave "selfishly." This suggests that the emergence of multicellular organisms with complex organization is a necessity in evolution. According to our theoretical model, there initially appear multipotent stem cells, which undergo stochastic differentiation to other cell types. With development and differentiation, both the chemical diversity and the complexity of intra-cellular dynamics are decreased, as a general consequence of our system. Robustness of the developmental process is also confirmed.

Biological Evolution↗
PubMed2000

Evolution of genetic codes through isologous diversification of cellular states.

Evolution of genetic codes is studied as change in the choice of enzymes that are used to synthesize amino acids from the genetic information of nucleic acids. We propose the following theory: the differentiation of physiological states of a cell allows for a choice of enzymes, and this choice is later fixed genetically through evolution. To demonstrate this theory, a dynamical systems model consisting of the concentrations of metabolites, enzymes, amino acyl tRNA synthetase, and tRNA - amino acid complexes in a cell is introduced and studied numerically. It is shown that the biochemical states of cells are differentiated by cell-cell interactions, and each differentiated type starts to use a different synthetase. Through the mutation of genes, this difference in the genetic code is amplified and stabilized. The relevance of this theory to the evolution of non-universal genetic code in mitochondria is suggested. The present theory is based on our recent theory of isologous symbiotic speciation, which is briefly reviewed. According to the theory, phenotypes of organisms are first differentiated into distinct types through the interaction and developmental dynamics, even though they have identical genotypes; later, with mutation in the genotype, the genotype also differentiates into discrete types, while maintaining the "symbiotic" relationship between the types. Relevance of the theory to natural as well as artificial evolution is discussed.

Biological Clocks↗
PubMed2000

Open problems in artificial life.

This article lists fourteen open problems in artificial life, each of which is a grand challenge requiring a major advance on a fundamental issue for its solution. Each problem is briefly explained, and, where deemed helpful, some promising paths to its solution are indicated.

Artificial Intelligence↗
PubMed2000

Protein kinase C modulates Ca2+-activated K+ channels in cultured rat mesenteric artery smooth muscle cells.

The electrical and pharmacological properties of protein kinase C (PKC) and its effect on the single Ca2+-activated K+ channel (Kca-channel) in the cultured smooth muscle cells of rat mesenteric artery were studied using a patch-clamp technique. The Kca-channel had a slope conductance of 151+/-7 pS (mean+/-S.E.) in symmetrical 142 mm K solutions. The high conductance K+ channel, applied to the outer side of membrane patches, was potently inhibited by charybdotoxin (0.1 microM) and tetraethylammonium (0.5 microM), but not by apamin (0.4 microM). In cell-attached patches, bath application of phorbol 12-myristate 13-acetate (PMA, 2 microM), a PKC activator, inhibited the activity of the Kca-channel in the presence of the Ca2+ ionophore, A 23187 (10 microM). This inhibition was reversed by subsequent application of staurosporine (1 nM), a PKC inhibitor. Application of 1-oleoyl-2-acetylglycerol (OAG, 30 microM), another PKC activator, also inhibited the A 23187-induced activation of the K+ channel, and this inhibition was reversed by staurosporine. In inside-out patches, bath application of PKC (0.2 munits), in the presence of ATP (1 mM) and PMA (1 microM), inhibited the K+ channel. These results indicate that protein kinase C inhibits the Ca2+-activated K+ channel of mesenteric artery smooth muscle cells in the rat.

Adenosine Triphosphate↗
PubMed2000

Anti-cancer activities of pyrazolo[1,5-a]indole derivatives.

The structure activity relationship (SAR) in the anti-cancer activities of pyrazolo[1,5-a]indole derivatives was investigated, and the following conclusions were obtained: 1) N(1)-quaternarization is essential for anti-cancer activity, 2) the size and polarity of the 2-substituent is crucial for in vitro activity which allows further investigation in an in vivo test, 3) the effect of the 4-substituent on the activity is minor compared with the other two factors.

Antineoplastic Agents↗
PubMed2000

Haemorrhagic lumbar synovial cyst. A cause of acute radiculopathy.

A total of 254 cases of synovial cysts of the spine have been reported in the English literature, but only eight have been associated with haemorrhage. We describe a 55-year-old man with acute radiculopathy resulting from haemorrhage involving a synovial cyst at a lumbar facet joint. Traumatic factors could have caused bleeding around or into the synovial cyst. Treatment by resection of the cyst and evacuation of the haematoma led to complete neurological recovery.

Acute Disease↗
PubMed2000

C-reactive protein as a prognostic marker in lymphocytic myocarditis.

The prognosis of patients with lymphocytic myocarditis (LM) is poor with the combined endpoint of death or transplant in the Myocarditis Treatment trial being 56% at 5 years. Physicians often have difficulty determining the prognosis in an individual patient. Patients with LM may have ongoing myocardial inflammation. We evaluated the ability of a serum marker of inflammation to predict prognosis in patients with LM. Serum concentrations of C-reactive protein (CRP) were measured in patients with LM. Thiry-one patients with clinical and histologic evidence of LM were evaluated. Patients with coronary artery disease, and idiopathic dilated and secondary cardiomyopathies were excluded. Overall mortality and morbidity from congestive heart failure was assessed at 28 days. The mean plasma CRP concentrations in the five patients who died within the 28-day follow-up period were significantly higher than in those patients who survived (17.4 +/- 5.6 vs 5.9 +/- 3.3 mg/ml, p < 0.05). The CRP concentration was positively correlated with plasma levels of lactic dehydrogenase and the New York Heart Association functional class. Routine measurement of CRP may be a useful tool for determining the prognosis in patients with LM.

Adolescent↗
PubMed2000

No toxicity caused by organ accumulation of CPT-11 on multiple injections under clinical regimens in rats.

We investigated the accumulation of CPT-11 and its metabolite (SN-38) in various organs and toxicities on multiple injections of CPT-11 under clinical regimens in SD rats. CPT-11 (16.7 mg/kg equivalent to 100 mg/m2) was administered intravenously by a single injection, or by multiple injections in 1 course (once a week for three consecutive weeks) or 3 courses (1 course repeated 3 times at intervals of 2 weeks). There was no tendency for CPT-11 and SN-38 to accumulate in any organs regardless of the number of injections. Treatment-related changes were not observed in the general condition, body weight, hematology, biochemistry, and organ weights. Histopathological changes induced by CPT-11 were not persistent and the rats made a rapid recovery after the administrations. From these results, it is suggested that there is no toxicity caused by accumulation of CPT-11 and its active metabolite, SN-38, in organs under clinical regimens in rats.

Animals↗
PubMed2000

Long-term (14 years) effect of LDL apheresis on obstructive changes in aortocoronary saphenous-vein bypass grafts in a case of heterozygous familial hypercholesterolemia with the LDL receptor proline664 to leucine mutation.

A 61-year-old Japanese woman with heterozygous familial hypercholesterolemia (FH), type 2 diabetes mellitus and coronary artery disease underwent coronary artery bypass grafting (CABG) utilizing a saphenous vein graft at the age of 46, in June 1984, 6 months before low density lipoprotein (LDL) apheresis was started. She had received LDL apheresis every two weeks, along with combined drug treatment since the age of 47 (December 1984). She had bilateral xanthelasma and Achilles tendon xanthomas. Her fasting baseline serum total cholesterol and triglyceride level were 464 mg/dl and 57 mg/dl, respectively at the age of 47 when she visited our hospital for the first time. Analysis of the genomic DNA from the patient revealed heterozygous amino acid substitution of Leu for Pro664 in the LDL receptor gene. She was diagnosed as type 2 diabetes mellitus at the age of 53. Combined treatment in the steady state yielded a pretreatment LDL cholesterol level of 230+/-14 mg/dl and a posttreatment level of 57+/-7.6. All grafts were widely patent after as long as 14 years since CABG, suggesting that LDL apheresis combined with drug therapy is highly effective in preventing the occlusion of bypass grafts in a patient with heterozygous FH and type 2 diabetes mellitus.

Aorta↗
PubMed2000

Bilirubin adsorption therapy and subsequent liver transplantation cured severe bilirubin encephalopathy in a long-term survival patient with Crigler-Najjar disease type I.

Crigler-Najjar disease (CN) type I is characterized by persistent unconjugated hyperbilirubinemia from birth. The male patient here was diagnosed with this disease as a neonate and had been treated by phototherapy. At age 16 he suddenly developed generalized convulsions, followed by impaired cognitive function. The serum level of bilirubin was extremely high (total bilirubin: 41.7 mg/dl) and there were no other detectable causes responsible for the metabolic encephalopathy. He received bilirubin adsorption therapy several times, and the bilirubin encephalopathy improved in response to the fall in the serum level of bilirubin. After this he underwent a successful liver transplantation in Australia, and recovery of his mental faculties was satisfactory. Within the subsequent 3 years epileptic abnormal discharges on the electroencephalogram disappeared. Phototherapy alone can not prevent the rise in the serum level of bilirubin in adolescent or adult patients with CN type I, therefore such patients tend to experience life-threatening bilirubin encephalopathy. To save patients with the acute onset type of bilirubin encephalopathy, sufficient bilirubin adsorption followed by liver transplantation appears to be the most recommended therapeutic approach.

Adsorption↗
PubMed2000

Establishment of a visible peritoneal micrometastatic model from a gastric adenocarcinoma cell line by green fluorescent protein.

To establish a visible peritoneal micrometastatic model, an enhanced green fluorescent protein (EGFP) expressing plasmid vector was transfected into the gastric cancer cell line, MKN-45. Highly expressing EGFP cells were injected into the peritoneal cavity of nude mice. Then, the peritoneum and abdominal organs were harvested and observed on days 1, 4 and 7. Fluorescence stereomicroscopy identified peritoneal micrometastases that had been undetected by stereomicroscopy. Micrometastases as small as a single cell are detectable in this model. This peritoneal micrometastatic model should be a useful tool for research on metastasis of gastric cancer.

Adenocarcinoma↗
PubMed2000

[Nose bleeds and nitric oxide in the nose].

Most of the nitric oxide (NO) in expiratory air is produced by the nose and its accessory sinuses, and nasal allergies related to NO have been often reported. In the present study, we postulated that nose bleeds may be somehow related to reactive oxygen species. The expression of NO synthase (NOS) by the nasal mucosa was evaluated using the RT-PCR method, and the concentration of NO in air expired through the nose was measured. The activity of superoxide dismutase, which scavenges superoxide anions, was also evaluated. The genetic expression of iNOS was observed in the nasal mucosa, and a significantly lower level of expression was noted in subjects with a nosebleed, compared to that of the controls. This result was interpreted as indicating a decrease in NO levels as a result of the nosebleed, leading to an elevation in blood pressure. Transient elevations in blood pressure caused by oxidative stress may lead to the rupture of nasal vessels if hypertension preexists. Serum levels of superoxide dismutase increased significantly in subjects with nose bleeds. This finding might be related to the activity of the superoxide anion, which is released in large amounts during nose bleeds. Serum superoxide dismutase levels increase in response to the high concentration of superoxide anions. The concentration of NO in air expired through the nose was significantly lower in subjects with nose bleeds, compared to that of the control subjects. We suggest that NO production decreases in subjects experiencing nose bleeds and that this reduction is induced by preexisting hypertension and injury from reactive oxygen species, contributing to the resulting nose bleed.

Adult↗
PubMed2000

[Effect of stellate ganglion block on human retinal blood flow].

PURPOSE: The effect of stellate ganglion block (SGB) on human retinal blood flow was evaluated. METHODS: We measured the diameter of the retinal artery and vein, and retinal venous flow rate by laser speckle retinal blood flow meter simultaneously in 11 eyes of 11 normal volunteers. RESULTS: The reliable data from 9 eyes of 9 person were used for analysis. SGB did not change the blood pressure, heart rate, retinal arterial diameter, or venous diameter. However SGB increased retinal blood velocity significantly from 9.9 +/- 1.6 (mean +/- standard deviation) mm/s to 11.1 +/- 1.5 mm/s (p < 0.01). Intraocular pressure decreased from 12.3 +/- 2.1 (mean +/- standard deviation)mmHg to 9.4 +/- 2.2 mmHg after SGB (p < 0.01). There was no relationship between the change of ocular perfusion pressure and that of retinal venous blood velocity. CONCLUSION: SGB increased the retinal venous blood velocity without changing the retinal vessel diameter.

Adult↗
PubMed2000

Studies of the metabolism of alpha-tocopherol stereoisomers in rats using [5-methyl-(14)C]SRR- and RRR-alpha-tocopherol.

We investigated the distribution and metabolism of SRR-alpha-tocopherol (SRR-alpha-Toc), synthetic alpha-Toc compared with RRR-alpha-Toc, in rats after a single oral administration of 2 mg (20 microCi) SRR- and RRR-alpha-[5-methyl-(14)C]Toc. In the liver, there was no difference in the recovery of radioactivity until 12 h after administration, and it reached a maximum of 4.4% of the dose after 12 h, but in other tissues, radioactivity derived from RRR-alpha-Toc was clearly higher than that derived from SRR-alpha-Toc after 12 h. For 96 h after administration, urinary excretions of SRR-alpha-Toc were 7.8% of the dose and significantly greater than that of RRR-alpha-Toc, which was 1.3% of the dose. On the other hand, total fecal excretions of SRR- and RRR-alpha-Toc were 87.6% and 83.0%, respectively. Therefore, radioactivity in the urine was assumed to have transferred out of the liver. Furthermore, the urine samples were hydrolyzed with 3 N methanolic HCl and analyzed by high performance liquid chromatography (HPLC) and liquid chromatography/mass spectrometry. The results showed that about 73% of the total radioactivity injected into HPLC was found to be 2,5,7, 8-tetramethyl-2-(2'-carboxyethyl)-6-hydroxy chroman (alpha-CEHC), as well as RRR-alpha-Toc. Thus, there is no difference between SRR-alpha-Toc and RRR-alpha-Toc in metabolic pathways, and it is suggested that SRR-alpha-Toc discriminated in the liver is rapidly metabolized by the liver and excreted as the conjugate of alpha-CEHC in the urine.

Animals↗