Biomedical subjects

K Hatanaka

Publications and source records attributed to K Hatanaka.

At least 55 records · Page 3Linked to original sources

PubMed2000

Asymmetric Mannich-Type Reactions of Aldimines with a Chiral Acetate.

We introduce here a strategy that enables effective addition of lithium enolates of acetates to aldimines. The new method depends strongly on the use of o-alkoxy (or o-fluoro) aniline-derived aldimines which have been found to have a potential effect on the enolate addition. This scope was expanded to the asymmetric process using the chiral acetate. A Lewis acid additive has a complementary role in the pronounced activation of imine functionalities.

Journal Article↗

PubMed2000

Effect of acute treatment with YM992 on extracellular norepinephrine levels in the rat frontal cortex.

The effects of acute treatment with (S)-2-[[(7-fluoroindan-4-yl)oxy]methyl]morpholine monohydrochloride (YM992), venlafaxine, fluoxetine and citalopram on extracellular norepinephrine levels were examined in the rat frontal cortex by in vivo microdialysis. YM992 (3, 10, 30 mg/kg, i.p.) dose-dependently increased extracellular norepinephrine levels (3-fold at 10 mg/kg, 5. 5-fold at 30 mg/kg). While venlafaxine and 30 mg/kg fluoxetine also produced significant increases in norepinephrine levels, 30 mg/kg citalopram had no effect. The combined administration of MDL100,907 (a selective 5-HT(2A) receptor antagonist) and citalopram did significantly increase norepinephrine levels compared with either saline or citalopram treatment. Therefore, a synergistic effect due to 5-HT reuptake inhibition and 5-HT(2A) receptor antagonism of YM992 may partly contribute to the increase of extracellular norepinephrine levels. YM992 enhances the neurotransmission of not only 5-HT system but also norepinephrine, and as such may have a preclinical profile different from that of a selective serotonin reuptake inhibitor.

Analysis of Variance↗

PubMed2000

Effect of acute treatment with YM992 on extracellular serotonin levels in the rat frontal cortex.

(S)-2-[[(7-fluoroindan-4-yl)oxy]methyl]morpholine monohydrochloride (YM992) is a novel putative antidepressant exhibiting both selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibition and 5-HT(2A) receptor antagonism. In vivo microdialysis revealed that a single treatment with YM992 (3, 10, 30 mg/kg i.p.) dose-dependently increased extracellular 5-HT levels in the rat frontal cortex. Fluoxetine, citalopram and venlafaxine also produced significant increases in 5-HT levels at doses of 10-30 mg/kg. However, the increase in 5-HT levels induced by YM992 was significantly larger than increases elicited by these three compounds at 30 mg/kg. The combined administration of R-(+)-alpha-(2, 3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidine-methanol (MDL100,907) (a selective 5-HT(2A) receptor antagonist) and citalopram produced no additional increase in 5-HT levels compared with citalopram treatment alone. YM992 moderately enhanced [3H]5-HT release from rat cerebral cortex synaptosomes using different mechanisms than p-chloroamphetamine. In comparison, 10-microM fluoxetine markedly induced 5-HT release in vitro, while citalopram and venlafaxine had no noticeable effect on release. YM992 produces a more robust increase of 5-HT levels acutely than other antidepressants in vivo and the effect may be due to 5-HT releasing properties of the drug.

Analysis of Variance↗

PubMed2000

Effect of cytochrome c on the linoleic acid-degrading activity of porcine leukocyte 12-lipoxygenase.

Hemoproteins are known to have quasilipoxygenase activity that converts linoleic acid (LA) to its hydroperoxides. However, it is not still clear whether, like lipoxygenases, hemoproteins can produce LA hydroperoxides when the LA is part of a mixture containing many different saturated and unsaturated fatty acids. In this study, we found that such hemoprotein as cytochrome c (Cyt c) did not produce LA hydroperoxides from the phospholipase A(2) (PL-A(2)) hydrolysis products of egg yolk phosphatidylcholine (PC). We also found that traces of hydroperoxides and a high concentration of the target unsaturated fatty acid (LA) needs to be present in a fatty acid mixture before the quasi-lipoxygenase activity of Cyt c becomes apparent. We also attempted to elucidate how Cyt c interact with porcine leukocyte 12-lipoxygenase (12-LOX). Hemoproteins are known to possess pseudo-lipohydroperoxidase activity, and can remove the hydroperoxides of unsaturated fatty acids from a reaction mixture. However, we found that Cyt c catalyzed the reaction by which hydroperoxides degrade LA, and thus enhanced the LA-degrading activity of 12-LOX. This hemoprotein-induced promotion of the ability of 12-LOX to degrade LA was observed even when the reaction mixture contained many different saturated and unsaturated fatty acids.

Animals↗

PubMed2000

Postmortem changes in cytochrome c oxidase activity in various organs of the rat and in human heart.

Cytochrome c oxidase (COX), a mitochondrial enzyme, is inactivated by cyanide or carbon monoxide (CO) intoxication. To test whether cytochrome c has potential as an indicator of these toxins in cadavers, we measured COX activity in the main organs of the rat, and in the human heart, at various times after death. Each tissue sample or organ was homogenized and the COX activity in the mitochondrial fraction was measured using ferrous cytochrome c as the substrate. COX activity was significantly higher in rat brain, heart and kidney than in lung and liver from 0 to 4 days after death. The loss of COX activity was significantly slower in the brain and heart than in the lung, liver and kidney. Most importantly, COX activity correlated with the time-since-death for each of the rat organs we tested (r2=0.70-0.95), but for the human heart (r2=0.47). It may be possible that COX activity is likely to be a useful indicator of the time-since-death, and is worth pursuing as an indicator of the tissue cyanide and CO content.

Adolescent↗

PubMed2000

Onset of rigor mortis is earlier in red muscle than in white muscle.

Rigor mortis is thought to be related to falling ATP levels in muscles postmortem. We measured rigor mortis as tension determined isometrically in three rat leg muscles in liquid paraffin kept at 37 degrees C or 25 degrees C--two red muscles, red gastrocnemius (RG) and soleus (SO) and one white muscle, white gastrocnemius (WG). Onset, half and full rigor mortis occurred earlier in RG and SO than in WG both at 37 degrees C and at 25 degrees C even though RG and WG were portions of the same muscle. This suggests that rigor mortis directly reflects the postmortem intramuscular ATP level, which decreases more rapidly in red muscle than in white muscle after death. Rigor mortis was more retarded at 25 degrees C than at 37 degrees C in each type of muscle.

Adenosine Triphosphate↗

PubMed2000

Synthesis of sulfated colominic acids and their interaction with fibroblast growth factors.

Colominic acid, an alpha (2-->8)-linked poly(sialic acid), was sulfated and characterized by NMR spectroscopy. During sulfation, the secondary hydroxyl group at C-4 had almost the same reactivity as the primary hydroxyl group at C-9, while the secondary hydroxyl group at C-7 was hardly substituted. Analysis by molecular modeling suggested that the lack of substitution at C-7 was due to a steric hindrance. A mobility shift assay indicated that FGF-2 bound to the sulfated colominic acid. Synthetic sulfated colominic acid potentiated the mitogenic activity of FGFs for fibroblasts in the same manner as heparin. Sulfated colominic acid with a low degree of sulfation was able to potentiate FGF activity. Regardless of the degree of sulfation, sulfated colominic acid-induced cytotoxicity was not observed. It was suggested that the carboxyl groups in sulfated colominic acid cooperate with the sulfate groups to reinforce the interaction with FGFs and to reduce the cytotoxicity of sulfated colominic acids.

3T3 Cells↗

PubMed2000

Meloxicam inhibits prostaglandin E(2) generation via cyclooxygenase 2 in the inflammatory site but not that via cyclooxygenase 1 in the stomach.

We studied the effects of meloxicam on prostanoid levels, both in the inflammatory site in rat carrageenin-induced pleurisy and in the rat stomach injected with 1 mol/l NaCl solution, to clarify the relationship between its low gastric toxicity and its relative cyclooxygenase (COX) 2 selectivity. NS-398 (3 mg/kg), a highly selective COX-2 inhibitor, and meloxicam (3 mg/kg) exhibited anti-inflammatory effects in the pleurisy model. Prostaglandin (PG) E(2) thromboxane (TX) B(2) and 6-keto-PGF(1alpha) were detectable in the inflammatory site. Anti-inflammatory doses of NS-398 and meloxicam each suppressed the intrapleural PGE(2) level at 5 h as potently as piroxicam (3 mg/kg) as aspirin (100 mg/kg), both of which are nonselective COX inhibitors. NS-398 was much less potent than the other three in suppressing the levels of TXB(2) and 6-keto-PGF(1alpha). These results suggest that PGE(2) may be produced mainly via COX-2 in this model and that meloxicam may inhibit COX-2 in the inflammatory site. Piroxicam completely inhibited the increase in gastric PGE(2) induced by administering 1 mol/l NaCl solution into the rat stomach. Nimesulide (3 mg/kg), another selective COX-2 inhibitor, however, never affected this increase, suggesting that the gastric PGE(2) may be produced via COX-1. The anti-inflammatory dose of meloxicam caused statistically nonsignificant suppression of the PGE(2) level, by approximately 50%. These results suggest that the potent anti-inflammatory effect of meloxicam, accompanied with low gastric toxicity, may be related to its relative selectivity for COX-2 over COX-1.

6-Ketoprostaglandin F1 alpha↗

PubMed2000

A modification of Mayer's tannic acid-ferric chloride staining method for demonstrating cellular membranous systems for light microscopy.

To observe cellular membranous systems under a light microscope, we modified Mayer's tannic acid-ferric chloride stain method by adding a treatment with hematoxylin after the original procedure. We used the modified tannic acid-ferric chloride (MTA-Fe) stain method to examine kidneys, liver, heart, trachea, epididymides and other organs of rats and dogs. The MTA-Fe stain clearly demonstrated the basement membrane, brush border, basolateral invaginations and cell processes in the kidneys which enabled easy differentiation of the S1 and S3 segments of proximal convoluted tubules. Our technique also demonstrated hepatic cell membranes and bile canaliculi in the liver, cross striations and longitudinal traveling of myofibrils in the heart, cilia of the epithelial cells in the trachea, and stereocilia and terminal bars in the epididymis. The MTA-Fe stain is a convenient method to visualize cellular membranous systems even for light microscopy. The stain has the advantages of using no toxic materials, simple and easy technique, little variation of staining results, and little fading for several months after staining.

Animals↗

PubMed2000

[Occurrence of angioimmunoblastic T-cell lymphoma six months after onset of Lyme disease].

A 68-year-old man, who had suffered a tick bite one week previously, consulted his home doctor because of fever and an erythematous rash around the bite scar. He underwent a skin biopsy, and Borrelia garinii was detected, from which Lyme disease was diagnosed. He received amoxicillin for two weeks and his symptoms disappeared. After 6 months he noticed swelling of his cervical, axillary and inguinal lymph nodes. A biopsy sample was taken from a left cervical lymph node, and this revealed angioimmunoblastic T-cell lymphoma. The patient achieved a complete remission after chemotherapy. The relationship between Lyme disease and lymphoma is discussed.

Aged↗

PubMed1999

Dopamine D4-like binding sites labeled by [3H]nemonapride include substantial serotonin 5-HT2A receptors in primate cerebral cortex.

Dopamine D4-like binding sites are abundant in human cerebral cortex as detected by [3H]nemonapride. The extremely low density of D4 mRNA in human cerebral cortex is inconsistent with the high amount of D4-like binding sites. To investigate the nature of the D4-like receptors, [3H]nemonapride binding sites in the nonhuman primate cerebral cortex were characterized. Although [3H]nemonapride binding sites were D4-like, displaceable by clozapine but not raclopride, [3H]nemonapride binding was not displaced by selective D4 antagonists but was displaced by the selective 5-HT2A antagonist MDL100907. Using [3H]ketanserin as a 5-HT2A ligand, nemonapride showed high affinity for monkey (Ki = 10.4 nM) and cloned human (Ki = 9.4 nM) 5-HT2A receptors, while its affinity for rat receptors was lower (Ki = 140 nM). The present study demonstrates that cerebral cortical D4-like binding sites labeled by [3H]nemonapride in nonhuman primates consist of a very small portion of D4, but a substantial portion of 5-HT2A receptors. The unexpectedly high affinity of nemonapride for primate 5-HT2A receptor suggests reconsidering previous data from other studies using [3H]nemonapride, particularly those on D4-like receptors.

Animals↗

PubMed1999

Expression and function of cyclooxygenase-2 in mesothelial cells during late phase of rat carrageenin-induced pleurisy.

We have previously shown that the inducible isoform of the cyclooxygenases, COX-2, is strongly expressed in pleural exudate leukocytes early (between 3 and 7 hr after irritation) during rat carrageenin-induced pleurisy. The present study further examined COX-2 expression and disclosed that mesothelial cells expressed COX-2 later (12 to 24 hr after irritation) in this model. A COX-2 inhibitor, nimesulide, lowered the intrapleural level of 6-keto-PGF1alpha and inhibited hyperplasia of the pleural matrix, suggesting that COX-2 expressed in mesothelial cells may play a role in the synthesis of extracellular matrix through formation of PGI2.

Animals↗

PubMed1999

A 'keyhole lesion' gunshot wound in an adipocere case.

A corpse completely converted into adipocere and showing two adjacent bone defects--a typical gunshot entrance wound and a keyhole lesion--is reported. Postmortem changes, a comminuted fracture of the cranial base, and destruction of the bullets made it impossible to determine the direction of fire through the keyhole lesion. Gunshot wounds may show various atypical forms, including keyhole lesions, and especially in old corpses, the distinction between an entrance wound and an exit wound can be very difficult, even if a careful complete autopsy is performed.

Journal Article↗

PubMed1999

In vitro phototoxicity of new quinolones: production of active oxygen species and photosensitized lipid peroxidation.

To elucidate photosensitization potentials of new quinolone antibacterial agents, production of active oxygen species and peroxidation of squalene after ultraviolet A exposure were investigated. Production of singlet oxygen and/or hydrogen peroxide was estimated by bleaching of p-nitroso-N,N-dimethylaniline. Lomefloxacin showed the greatest ability to produce active oxygen species, and this ability was reduced by the addition of the singlet oxygen quencher sodium azide. Ciprofloxacin and fleroxacin also had strong activity. Photosensitized peroxidation of squalene was evaluated by measurement of thiobarbituric acid-reactive substances. Lomefloxacin was the strongest sensitizer, followed by fleroxacin and ciprofloxacin. These results suggest that certain new quinolones are involved in phototoxicity via the mechanism of active oxygen species.

Anti-Infective Agents↗

PubMed1999

[New quinolone versus vancomycin/tobramycin for intestinal sterilization in patients who undergo allogeneic bone marrow transplantation].

The frequency of infection in recipients of allogeneic bone marrow transplants (BMT) who received oral new quinolones (NQ) was compared with that in BMT recipients who were given oral vancomycin/tobramycin (V/T). Between 1984 and 1997, our hospital treated 79 patients with V/T and 90 patients with NQ. Number of febrile days, duration of intravenous antibiotics administration, and frequency of documented infections were statistically the same for both groups. However, the frequency of grampositive bacterial infections, especially staphylococcal infections, was slightly higher in patients receiving NQ than in patients receiving V/T (p = 0.12). Of the patients who received NQ, those who underwent unrelated donor BMT procedures were generally febrile for slightly longer periods than those who underwent related donor BMT procedures (p = 0.10). These results suggest that oral NQ is as effective as oral V/T for the prevention of serious gramnegative bacterial infections in patients who undergo BMTs.

Administration, Oral↗

PubMed1999

[CT evaluation of pulmonary metastases: usefulness in comparison with chest radiography].

The purpose of this study was to evaluate the usefulness of follow-up CT for screening pulmonary metastases, in comparison with chest radiography (CXR). Two hundred sixty CT examinations performed on 200 patients with known malignancy formed the basis of the study. One hundred sixty-five metastatic nodules were detected from 52 CT examinations in 36 patients. The detectability of these nodules on CXR was relatively good, but it was better on CT, which detected more nodules of smaller size, those overlying the mediastinum or hilus, and those showing ground-glass attenuation. As for the relationship between treatment and pulmonary metastases, pulmonary metastases treated surgically were detected on CXR in all patients. Pulmonary metastases showed a tendency to recur within one year after the initial treatment. The author concluded that routine CT to screen occult lung metastases in every patient with malignancy is not cost-effective. However, CT may be added at the start of the initial treatment and within one year thereafter, particularly for patients with lung cancer.

Adult↗

PubMed1998

Effects of helical structures formed by the binding arms of DNAzymes and their substrates on catalytic activity.

As a part of our efforts to clarify structure-function relationships in reactions catalyzed by deoxyribozymes (DNAzymes), which were recently selected in vitro , we synthesized various chimeras and analyzed the kinetics of the corresponding cleavage reactions. We focused on the binding arms and generated helices composed of binding arms and substrates that consisted of RNA and RNA, of RNA and DNA or of DNA and DNA. As expected for the rate limiting chemical cleavage step in reactions catalyzed by DNAzymes, a linear relationship between log( k cat) and pH was observed. In all cases examined, introduction of DNA into the binding helix enhanced the rate of chemical cleavage. Comparison of CD spectra of DNAzyme. substrate complexes suggested that higher levels of B-form-like helix were associated with higher rates of cleavage of the substrate within the complex. To our surprise, the enhancement of catalytic activity that followed introduction of DNA into the binding helix (enhancement by the presence of more B-form-like helix) was very similar to that observed in the case of the hammerhead ribozymes that we had investigated previously. These data, together with other observations, strongly suggest that the reaction mechanism of metal-ion-dependent DNAzymes is almost identical to that of hammerhead ribozymes.

Base Sequence↗

PubMed1998

Determination of interactions between structured nucleic acids by fluorescence resonance energy transfer (FRET): selection of target sites for functional nucleic acids.

We previously developed a method for monitoring the integrity of oligonucleotides in vitro and in vivo by quantitating fluorescence resonance energy transfer (FRET) between two different fluorochromes attached to a single oligonucleotide. As an extension of this analysis, we examined changes in the extent of FRET in the presence or absence of target nucleic acids with a specific sequence and a higher-ordered structure. In this system FRET was maximal when probes were free in solution and a decrease in FRET was evidence of successful hybridization. We used a single-stranded oligodeoxyribonucleotide labeled at its 5'-end and its 3'-end with 6-carboxyfluorescein and 6-carboxytetramethylrhodamine, respectively. Incubation of the probe with a single-stranded complementary oligonucleotide reduced the FRET. Moreover, a small change in FRET was also observed when the probe was incubated with an oligonucleotide in which the target site had been embedded in a stable hairpin structure. The decrease in the extent of FRET depended on the length of the stem region of the hairpin structure and also on the higher-ordered structure of the probe. These results indicate that this spectrofluorometric method and FRET probes can be used to estimate the efficacy of hybridization between a probe and its target site within highly ordered structures. This conclusion based on changes in FRET was confirmed by gel-shift assays.

DNA↗