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Biomedical subjects

H Kojima

Publications and source records attributed to H Kojima.

At least 91 records · Page 5Linked to original sources
PubMed2001

Insulin production in a neuroectodermal tumor that expresses islet factor-1, but not pancreatic-duodenal homeobox 1.

We studied a 60-yr-old female with a brain tumor who showed severe symptoms of hypoglycemia (plasma glucose, 2.2 mmol/L) and hyperinsulinemia (1.28 nmol/L) after radiotherapy. The cystic brain tumor contained proinsulin and insulin at concentrations of 13.6 and 1.22 nmol/L, respectively. Immunohistochemical studies showed the tumor cells were ectodermal in origin but not endodermal, based on three diagnostic features of neuroectodermal tumors 1) pseudorosette formation noted under light microscopy, 2) finding of a small number of dense core neurosecretory granules on electron microscopy, and 3) positive immunostaining for both neuronal specific enolase and protein gene product 9.5. These cells also expressed the transcription factor, neurogenin-3, NeuroD/beta 2, and islet factor I, which are believed to be transcription factors in neuroectoderm as well as in pancreatic islet cells, but not pancreatic-duodenal homeobox 1, Pax4, or Nkx2.2. In addition, they did not express glucagon, somatostatin, or glucagon-like peptide-1. Our results show the presence of proinsulin in an ectoderm cell brain tumor that does not express the homeobox gene, pancreatic-duodenal homeobox 1, but expresses other transcription factors, i.e. neurogenin3, NeuroD/beta 2, and islet factor-1, which are related to insulin gene expression in the brain tumor.

Antigens, Differentiation↗
PubMed2001

Passive targeting of doxorubicin with polymer coated liposomes in tumor bearing rats.

The purpose of this study was to reveal the effectiveness of the polymer coated liposomes as a carrier of the anticancer drug doxorubicin in intravenous administration. The size controlled doxorubicin-loaded liposomes (egg phosphatidylcholine : cholesterol = 1:1 in molar ratio) were coated with hydrophilic polymers (polyvinyl alcohol; PVA and hydroxypropylmethylcellulose; HPMC) having a hydrophobic moiety in the molecules (PVA-R, HPMC-R). The existence of a thick polymer layer on the surface of the polymer coated liposomes was confirmed by measuring the change in particle size and the amount of polymer on the liposomal surface. The polymer coating effects on the tumor accumulation of the drug encapsulated in the liposomes were evaluated in Walker rat carcinoma 256 cell bearing rats. The doxorubicin-loaded liposomes coated with PVA-R and HPMC-R showed higher drug accumulation into the tumor site by prolonging the systemic circulation in tumor-bearing rats. The targeting efficiency of the polymer coated liposomes calculated with the total and tumorous clearance of the drug was ca. 5 times larger than that of non-coated liposomes. We ascertained that polymers having a hydrophobic moiety in the molecule such as PVA-R and HPMC-R are suitable materials for modifying the surfaces of the doxorubicin-loaded liposome to improve its targeting properties.

Animals↗
PubMed2001

Mutation analysis of the feedback inhibition site of aspartokinase III of Escherichia coli K-12 and its use in L-threonine production.

Aspartokinase III (AKIII), one of three isozymes of Escherichia coli K-12, is inhibited allosterically by L-lysine. This enzyme is encoded by the lysC gene and has 449 amino acid residues. We analyzed the feedback inhibition site of AKIII by generating various lysC mutants in a plasmid vector. These mutants conferred resistance to L-lysine and/or an L-lysine analogue on their host. The inhibitory effects of L-lysine on and heat tolerance of 14 mutant enzymes were examined and DNA sequencing showed that the types of mutants were 12. Two hot spots, amino acid residue positions 318-325 and 345-352, were detected in the C-terminal region of AKIII and these enzyme regions may be important in L-lysine-mediated feedback inhibition of AKIII. Feedback resistant lysC relieved on L-threonine hyper-producing strain, B-3996, from reduced L-threonine productivity by addition of L-lysine, and furthermore increased L-threonine productivity even when no addition of L-lysine. It suggested that the bottleneck of L-threonine production of B-3996 was AK and feedback resistant lysC was effective because of the strict inhibition by cytoplasmic L-lysine.

Amino Acid Sequence↗
PubMed2001

Ideal cue combination for localizing texture-defined edges.

Many visual tasks can be carried out by using several sources of information. The most accurate estimates of scene properties require the observer to utilize all available information and to combine the information sources in an optimal manner. Two experiments are described that required the observers to judge the relative locations of two texture-defined edges (a vernier task). The edges were signaled by a change across the edge of two texture properties [either frequency and orientation (Experiment 1) or contrast and orientation (Experiment 2)]. The reliability of each cue was controlled by varying the distance over which the change (in frequency, orientation, or contrast) occurred-a kind of "texture blur." In some conditions, the position of the edge signaled by one cue was shifted relative to the other ("perturbation analysis"). An ideal-observer model, previously used in studies of depth perception and color constancy, was fitted to the data. Although the fit can be rejected relative to some more elaborate models, especially given the large quantity of data, this model does account for most trends in the data. A second, suboptimal model that switches between the available cues from trial to trial does a poor job of accounting for the data.

Contrast Sensitivity↗
PubMed2001

Primary pineal melanocytic tumor. Case report.

A primary melanocytic lesion arising from the pineal gland is very rare. The authors report a case of primary pineal melanocytic tumor with dissemination to the right hippocampus in a 50-year-old woman who presented with memory disturbance. Magnetic resonance (MR) imaging revealed a mass that was hyperintense on T1-weighted and hypointense on T2-weighted MR images. The pineal tumor was removed subtotally via the occipital transtentorial approach, and the patient underwent whole-brain irradiation. Results of histological examination revealed that the tumor predominantly consisted of atypical cells with scanty melanin pigment and some necrotic foci. The strongly pigmented areas of the tumor contained well-differentiated cells similar to those of melanocytoma. An ultrastructural study demonstrated evidence of a mature type of melanosome. The patient died 11 months after surgery and radiotherapy (1.7 years after the onset of symptoms). The autopsy findings demonstrated tumor invasion into the parenchyma through the leptomeningeal space and the ventricular wall. The tumor was diagnosed as being malignant, and it was finally concluded that the atypical cells in the tumor were probably responsible. This pineal melanocytic tumor exhibited a wide spectrum of differentiation, ranging from highly malignant melanoma to well-differentiated melanocytoma, which may have contributed to the patient's relatively long survival period. The biological behavior and morphological characteristics of this tumor appear to be similar to those of other pineal parenchymal lesions.

Fatal Outcome↗
PubMed2001

Pathological mechanism and three-dimensional structure of cerebral dissecting aneurysms.

OBJECT: The goal of this study was to investigate the pathological mechanism and precise three-dimensional (3D) structure of cerebral dissecting aneurysms in association with their clinical course. METHODS: Nine aneurysm specimens were excised from eight patients. Of the nine aneurysms, seven arose from the vertebral artery, one from the anterior cerebral artery, and one from the superior cerebellar artery. Eight aneurysms were accompanied with subarachnoid hemorrhage (SAH) and one with infarction. Seven aneurysms were obtained at autopsy and two were obtained during surgery (trapping and bypass). All nine aneurysms were sectioned into serial axial slices measuring 5 to 10 microm in thickness. Taking each slice as an element, we reconstructed the 3D structure of the aneurysm. The true lumen communicated with a pseudolumen through the disrupted portion of the internal elastic lamina (IEL) in all nine aneurysms. The ruptured portion was located just above the disrupted IEL. Two aneurysms had an exit back into the true lumen. but the other seven had no such exit. CONCLUSIONS: The primary mechanism by which a cerebral dissecting aneurysm is created is by the sudden disruption of the IEL. The plane of dissection extends through the media. The majority of aneurysms have one entrance into the pseudolumen (entry-only type). This type is associated with an unstable clinical course. Some cerebral dissecting aneurysms have both an entrance and exit (entry-exit type). This type of aneurysm occasionally contains a constant flow of blood through the pseudolumen and is clinically more stable than entry-only aneurysms.

Adult↗
PubMed2001

Heated scallop-shell powder slurry treatment of shredded cabbage.

The main component of scallop-shell powder is calcium carbonate (CaCO3). Through heat treatment, CaCO3 in the shell is converted to CaO, which exhibits antibacterial activity. The disinfecting effect of heated scallop-shell powder on shredded cabbage was investigated for various powder concentrations (0.1 to 1.0 g dm(-3)) and treatment temperatures (10 to 40 degrees C). Scallop-shell powder treatment was found to reduce the aerobic bacteria count in cabbage, with increasing effectiveness at higher powder concentrations and treatment temperatures. Coliforms were completely eliminated within 5 min with as little as 0.1 g dm(-3) powder treatment. During storage at 4 degrees C, aerobic bacterial counts did not increase after powder treatment, whereas counts increased with water-washing or sodium hypochlorite treatment at 200 microg dm(-3). The inactivation pattern of bacterial cells in shredded cabbage involved an accelerated decline followed by an extended tail at powder concentrations of 0.1 and 0.5 g dm(-3). We postulate that a fraction of bacterial cells in the initial population becomes tolerant to the shell powder. A proposed model accurately predicts the reducing bacterial counts on shredded cabbage by scallop-shell powder treatment. The decrease in the L-ascorbic acid content of shredded cabbage was approximately 20 to 30% for scallop-shell powder treatment at 0.1 and 0.5 g dm(-3) (20 degrees C), which is almost identical to that by sodium hypochlorite treatment at 200 micorg dm(-3).

Bacteria, Aerobic↗
PubMed2001

[Shwachman syndrome].

Explore the source record for details and available documents.

Exocrine Pancreatic Insufficiency↗
PubMed2000

A convenient NMR method for in situ observation of aerobically cultured cells.

We observed P31-NMR signals of intracellular phosphorylated metabolites, i.e. ATP, NAD(H) and UDPG, in the aerobically cultured cells of AJ13375 (a derivative of E. coli K-12) without a cell culture circulating system, which needs much more cells. Each NMR spectrum of 40 ml cell-culture was obtained with a 25 mm Phi sample tube mini-fermenter equipped with a pH electrode and three supply routes for O2 gas, aqueous ammonia and glucose. Spectra were measured at 15-min intervals. When glucose in the culture medium was consumed, P31-NMR signals of ATP disappeared first and then those of ADP decreased to below the limit of detection. The intracellular concentration of ATP was estimated to be approximately 7 mM.

Adenosine Triphosphate↗
PubMed2000

Determination and bioimaging method for nitric oxide in biological specimens by diaminofluorescein fluorometry.

A simple and sensitive assay and a cellular bioimaging method for nitric oxide (NO) were developed using a novel diaminofluorescein DAF-FM and its diacetate. DAF-FM is converted via an NO-specific mechanism to an intensely fluorescent triazole derivative. For the measurement of NO, the triazole derivative of DAF-FM was determined by reversed-phase high-performance liquid chromatography with fluorescence detection. In the presence of 1 microM DAF-FM, the concentrations of NOR-1, an NO donor, in the range of 2-200 nM were linearly related to the fluorescence intensity. This sensitive NO assay enabled us to detect the spontaneous and substance P-induced NO release from isolated porcine coronary arteries, both of which were dependent entirely on the NO synthase activity in vascular endothelial cells. We also obtained fluorescence images of cultured smooth muscle cells of the rat urinary bladder after loading with DAF-FM diacetate. In the cells pretreated with cytokines, the fluorescence intensity increased with time after DAF-FM loading. This increase in the fluorescence intensity was blocked by prior treatment of the muscle cells with an NO synthase inhibitor, N(G)-nitro-l-arginine methyl ester. Therefore, the present novel diaminofluorescein fluorometry should be useful not only for sensitive NO assay, but also for NO imaging in a variety of biological specimens.

Animals↗
PubMed2000

Relationship between serum cholesterol levels and meta-chlorophenylpiperazine-induced cortisol responses in healthy men and women.

We investigated the effect of cholesterol on serotonergic receptor function in 20 healthy male and 10 healthy female subjects using cortisol responses to meta-chlorophenylpiperazine (m-CPP) neuroendocrine challenge tests. M-CPP, a metabolite of the antidepressant trazodone, has been widely used in psychopharmacology research as a probe of serotonin function. In the human brain, m-CPP binds both to various serotonergic receptors, mainly 5-HT(2C), and to alpha(2)-adrenoceptors. After an overnight fast, the subjects received m-CPP (0.5 mg/kg) or identical placebo capsules orally in a randomized, double blind, crossover design. Blood was obtained for measurement of cholesterol and cortisol. In some analyses, especially in males, there were significant positive correlations between serum cholesterol levels and cortisol responses. These findings suggest the possibility that serum cholesterol levels may be positively associated with serotonergic receptor function. The existence of such an association may provide an explanation for reported increases in depression, suicide and violence in individuals with low or lowered cholesterol.

Adult↗
PubMed2000

Development of a time-resolved fluorometric detection system using diffusion-enhanced energy transfer

A novel detection system using both emission energy transfer and time-resolved fluorometry (TRF) was developed, with a europium chelate as the energy donor and a novel fluorophore SNR1, excitable with long-wavelength light corresponding to europium emission, as the energy acceptor. When the donor and acceptor molecules were mixed in solution, energy transfer was observed without direct attachment of the donor and the acceptor, via a diffusion-enhanced energy-transfer mechanism. Thus, the acceptor emission can be detected as a long-lifetime fluorescence in TRF. When the fluorescence properties of the acceptor molecule are changed by interaction with an enzyme or other bioactive molecule, the change can be detected as a long-lived sensitized emission. If we develop or select suitable acceptor molecules, this simple and convenient system should be applicable to a wide variety of bioactive molecules. Since it is based on TRF, it can be used for high-resolution assay.

Journal Article↗
PubMed2000

Oral administration of tetrahydrobiopterin prevents endothelial dysfunction and vascular oxidative stress in the aortas of insulin-resistant rats.

We have reported that a deficiency of tetrahydrobiopterin (BH(4)), an active cofactor of endothelial NO synthase (eNOS), contributes to the endothelial dysfunction through reduced eNOS activity and increased superoxide anion (O(2)(-)) generation in the insulin-resistant state. To further confirm this hypothesis, we investigated the effects of dietary treatment with BH(4) on endothelium-dependent arterial relaxation and vascular oxidative stress in the aortas of insulin-resistant rats. Oral supplementation of BH(4) (10 mg. kg(-1). d(-1)) for 8 weeks significantly increased the BH(4) content in cardiovascular tissues of rats fed high levels of fructose (fructose-fed rats). Impairment of endothelium-dependent arterial relaxation in the aortic strips of the fructose-fed rats was reversed with BH(4) treatment. The BH(4) treatment was associated with a 2-fold increase in eNOS activity as well as a 70% reduction in endothelial O(2)(-) production compared with those in fructose-fed rats. The BH(4) treatment also partially improved the insulin sensitivity and blood pressure, as well as the serum triglyceride concentration, in the fructose-fed rats. Moreover, BH(4) treatment of the fructose-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, nuclear factor-kappaB and activating protein-1, which were increased in fructose-fed rats. The BH(4) treatment of control rats did not have any significant effects on these parameters. These results indicate that BH(4) augmentation is essential for the restoration of eNOS function and the reduction of vascular oxidative stress in insulin-resistant rats.

Administration, Oral↗
PubMed2000

Phylogenetic relation of lungfish indicated by the amino acid sequence of myelin DM20.

The cDNA of lungfish Protopterus annectens myelin DM20 was cloned, and the complete amino acid sequence of Protopterusannectens DM20 was deduced. When five possible phylogenetic trees were tested for the DM20 sequences, the maximum likelihood method supported tree 1 [((tetrapods, lungfish), coelacanth), zebrafish, shark] or tree 5 [(tetrapods, lungfish), (coelacanth, zebrafish), shark]. Both tree 1 and tree 5 indicate that lungfish is phylogenetically the closest to tetrapods among the living fishes.

Amino Acid Sequence↗
PubMed2000

Biodistribution of liposomes and C3 fragments associated with liposomes: evaluation of their relationship.

The biodistribution of liposomes with two different kind phospholipids (hydrogenated egg phosphatidylcholine and egg phosphatidylcholine) plus cholesterol (CHOL) were investigated after intravenous administration to rats. Elimination of liposomes from blood circulation was affected by the lipid composition. It appeared that the inclusion of CHOL in liposomes accelerates the rate of liposome uptake by liver, resulting in rapid elimination of liposomes. The amount of C3 fragments bound to liposomes was quantitatively determined to assess the contribution of the complement system to liposome accumulation into organs and liposome destabilization in vivo and in vitro. The amount of bound C3 fragments was directly proportional to CHOL content, and the amount was also proportional to the CLh, CLs as well as CLrel. This relationship suggests that the complement system is responsible for the elimination of liposomes from blood circulation, presumably as a consequence of opsonization by C3 fragments and assembly of membrane attack complex (MAC) onto liposomes. In addition, substitution of cholesteryl methyl ether into the liposome formulation for CHOL significantly diminished not only the binding of C3 fragments but also the CLh, CLs and CLrel, resulting in increased mean resident time (MRT) of the liposomes. This result suggests that the hydroxyl-group on CHOL is a binding site for C3 fragments on the liposomes and that CHOL in a liposome formulation promotes the accumulation of liposomes into the liver and spleen, probably due to their uptake by phagocytic cells, and impairs the stability of the liposomes in blood circulation, via a mechanism involving the complement system.

Animals↗
PubMed2000

Polymer coating of liposomes with a modified polyvinyl alcohol and their systemic circulation and RES uptake in rats.

The objective of this study was to evaluate the in vivo characteristics of liposomes coated with a polyvinyl alcohol having a long alkyl chain at the end of the molecule (PVA-R) as an injectable drug carrier for passive targeting of drugs. A fluorescence marker, cholesteryl-anthracene-9-carboxylate, was incorporated into the liposomes to detect their concentration in the plasma and organs. The small unilamellar liposomes (100 nm in diameter) with various lipid compositions, such as the different cholesterol contents or the different charges, were prepared by the hydration method followed by sonication and coated with PVA or PVA-R by just mixing the resultant liposomal suspensions with the polymer solutions. The circulation and distribution of the liposomes were tested with their intravenous administration in rats. The PVA-R-coated liposomes showed significantly higher circulation compared to that of non-coated ones in any liposomal formulation tested. The prolonged circulation of PVA-R-coated liposomes was attributed to their fewer uptake in liver and spleen. The extent in improvement in the in vivo characteristics were well interpreted by the hydrophobicity of liposomes and their coating amount of PVA-R. It was also demonstrated that the liposomes having a positive and a negative charge, which showed the completely different circulating profiles, showed almost the same profile by coating with PVA-R. When the liposomes were coated with PVA the improvement in blood circulation was much less in any cases, although coating layer of PVA was detected. These results confirm that not only the hydrophilic property but the sterically stabilizing effect of the coating layer is important to prolong the circulation of the particulate drug carriers with less RES uptake, and the PVA-R having a hydrophobic moiety at the end of the molecule of PVA is a suitable material for the coating of liposomes.

Animals↗