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Biomedical subjects

H Komatsu

Publications and source records attributed to H Komatsu.

At least 73 records · Page 4Linked to original sources

Neural selectivity for hue and saturation of colour in the primary visual cortex of the monkey.

In the inferior temporal (IT) cortex of monkeys, which has been shown to play a critical role in colour discrimination, there are neurons sensitive to a narrow range of hues and saturation. By contrast, neurons in the retina and the parvocellular layer of the lateral geniculate nucleus (pLGN) encode colours in a way that does not provide explicit representation of hue or saturation, and the process by which hue- and saturation-selectivity is elaborated remains unknown. We therefore tested the colour-selectivity of neurons in the primary visual cortex (V1) and compared it with those of pLGN and IT neurons. Quantitative analysis was performed using a standard set of colours, systematically distributed within the CIE (Commission Internationale de l'Eclairage)-xy chromaticity diagram. Selectivity for hue and saturation was characterized by analysing response contours reflecting the overall distribution of responses across the chromaticity diagram. We found that the response contours of almost all pLGN neurons were linear and broadly tuned for hue. Many V1 neurons behaved similarly; nonetheless, a considerable number of V1 neurons had clearly curved response contours and were selective for a narrow range of hues or saturation. The relative frequencies of neurons exhibiting various selectivities for hue and saturation were remarkably similar in the V1 and IT cortex, but were clearly different in the pLGN. Thus, V1 apparently plays a very important role in the conversion of colour signals necessary for generating the elaborate colour selectivity observed in the IT cortex.

Animals↗

Serum glutathione S-transferase alpha as a measure of hepatocellular function following prolonged anaesthesia with sevoflurane and halothane in paediatric patients.

We studied the effects of prolonged anaesthesia (4.3-7.7 h) with sevoflurane and halothane on hepatic function in 14 paediatric patients. Hepatic function was assessed using serum concentrations of liver-specific glutathione S-transferase alpha (GSTA) before and 0, 3 and 15 h after the end of anaesthesia. A transient significant increase in GSTA over baseline was observed in the sevoflurane group, but not in the halothane group, and the difference between the groups was not significant. These data suggest that, although statistically insignificant, the use of sevoflurane for prolonged anaesthesia in paediatric patients is more likely than halothane to be involved in damage to hepatic function.

Analysis of Variance↗

Antibiotic susceptibility of bacteria detected from the root canal exudate of persistent apical periodontitis.

Intracanal exudates in persistent endodontic cases were sampled for detecting bacteria using a preculture method, and the antibiotic susceptibility of the bacteria identified was examined. Twelve species were recovered from 15 cases. The species most commonly detected were alpha-Streptococcus and Enterococcus. The results of the antibiotic susceptibility tests revealed that Enterococcus was highly resistant to antibiotics tested, especially to cephalosporin products. Enterococcus is known as one of the bacteria that show multidrug resistance. In cases of prolonged endodontic treatment, a specific antibiotic prescription would play an important role for efficient treatment. Collecting data about antibiotic susceptibility could be helpful. Identification, however, take approximately 2 wk and a further study to develop the method that rapidly informs us about the antibiotic susceptibility that might be needed.

Anti-Bacterial Agents↗

Long-term outcome of chronic hepatitis B in adolescents or young adults in follow-up from childhood.

BACKGROUND: It has not yet been defined whether children with chronic hepatitis B are likely to develop severe liver disease in the future. The purpose of this study was to evaluate the evolution of chronic hepatitis B acquired in childhood. METHOD: Fifty-two children in the age range of 0 to 15 years who were positive for hepatitis B surface antigen and hepatitis B e antigen in serum for at least 6 months were enrolled in this study. In the majority of the 52 children, hepatitis B virus infection was acquired by perinatal transmission. All 52 showed abnormal liver function test findings for more than 6 months before enrollment, and the subjects were followed up longitudinally for 3 to 22 years (mean, 11 years). They are now more than 15 years of age (15-27 years old). RESULTS: During the follow-up period, 26 (50%) children had spontaneous seroconversion to anti-hepatitis B e. Serum levels of alanine aminotransferase normalized in these 26 children. In one child of these children, hepatocellular carcinoma developed at the age of 21 years, 16 years after seroconversion, although his liver function profiles remained normal. The other 26 children remained hepatitis B e antigen positive, most with unchanged biochemical features. Sixteen (62%) children among these 26 children were treated with interferon-alpha. Eleven (69%) children had seroconversion to anti-hepatitis B e within the first year after the cessation of therapy. Hepatocellular carcinoma developed in 1 of these 11 children at the age of 16 years, 6 years after interferon therapy. Thus, hepatocellular carcinoma developed in two children in an anti-hepatitis B e positive phase. CONCLUSION: All children carrying hepatitis B surface antigen should be observed carefully to monitor the possible development of hepatocellular carcinoma, especially in the antihepatitis B e-positive phase after spontaneous seroconversion or even after interferon treatment.

Adolescent↗

Suppression by flavonoids of cyclooxygenase-2 promoter-dependent transcriptional activity in colon cancer cells: structure-activity relationship.

Cyclooxygenase-2 (COX-2) plays an important role in carcinogenesis. Investigation of the suppressive action of twelve flavonoids of different chemical classes on the transcriptional activity of the COX-2 gene in human colon cancer DLD-1 cells using a reporter gene assay have revealed quercetin to be the most potent suppressor of COX-2 transcription (IC50 = 10.5 microM), while catechin and epicatechin showed weak activity (IC50 = 415.3 microM). Flavonoids have three heterocyclic rings as a common structure. A structure-activity study indicated that the number of hydroxyl groups on the B ring and an oxo group at the 4-position of the C ring are important in the suppression of COX-2 transcriptional activity. A low electron density of the oxygen atom in the hydroxyl group of the A ring was also important. Further examination of the role of the hydroxyl group in the A ring showed that bromination of resacetophenone to give 3,5-dibromo-2,4-dihydroxyacetophenone resulted in a 6.8-fold increase in potency for suppressing COX-2 promoter activity. These results provide a basis for the design of improved suppressors of COX-2 transcriptional activity.

Acetophenones↗

Use of microvascular Doppler sonography in aneurysm surgery on the anterior choroidal artery.

Anterior choroidal artery (AChA) syndrome is still one of the most serious complications of the clipping of internal carotid artery aneurysms. No monitoring method can detect ischemia in the area of the AChA during surgery. This artery may be obstructed when a clip is applied to the neck of the aneurysm, and patency is sometimes difficult to confirm by microscopy because of the artery's small size and site of origin (usually behind the internal carotid artery as viewed surgically). However, microvascular Doppler sonography (MVDS) can detect flow instantaneously even in such a small vessel. In our series, AChA syndrome occurred in three of 19 patients treated for AChA aneurysm before the introduction of MVDS, but only one of 19 patients treated with the aid of this device. In that patient, one of the two AChA branches was intentionally sacrificed by applying a clip to the prematurely ruptured aneurysm. MVDS detected hypoperfusion of the AChA after clipping in five other patients, and so the clip was readjusted to preserve AChA flow. Use of MVDS is very effective to prevent inadvertent injury to the AChA during aneurysm surgery on this artery.

Adult↗

[Laser photocoagulation for choroidal neovascularization developed in a patient with optic disc drusen and angioid streaks].

BACKGROUND: Optic disc drusen accompanied by angioid streaks is rarely seen in Japan. Laser photocoagulation for choroidal neovascularization (CNV) in patients with angioid streaks is controversial. CASE: A 45-year-old woman presented with bilateral papilledema. Clinical examination revealed optic disc drusen and angioid streaks. During the follow-up period, juxtapapillary CNV developed in both eyes. CNV in the right eye developed progressively towards the fovea and was eventually treated by laser, but the CNV in the left eye regressed spontaneously. CONCLUSION: These are the first precise clinical records on optic disc drusen with angioid streaks to be reported. The outcome of laser treatment for CNV in this case was favorable, because alteration of Bruch's membrane was mild, in the form of angioid streaks.

Angioid Streaks↗

[Supplement of ulinastatin on renal function after cardiopulmonary bypass].

The effects of Miraclid (ulinastatin) on renal tubular function after open thorax surgery under cardiopulmonary bypass were investigated. On the 3rd day after open thorax surgery, which had lasted more than 127 min under cardiopulmonary bypass, the levels of urinary ulinastatin in the Miraclid group and control (without Miraclid) were 170 IU.mg Cr-1 and 95 IU.mg Cr-1, respectively. In the Miraclid group, 300,000 units.day-1 of Miraclid was administrated for three postoperative days. N-acetyl-beta-d-glucosaminidase in urine as a marker of tubular function rose significantly on the seventh postoperative day in the control group but not in patients with Miraclid group. These data suggested that Miraclid 300,000 units.day-1 was needed to protect renal tubular function and more than that dose was needed to prevent the deterioration of renal function after open thorax surgery after cardiopulmonary bypass lasting more than 127 min.

Acute Kidney Injury↗

[Successful treatment of relapsed and refractory acute promyelocytic leukemia with arsenic trioxide (As2O3)].

It has been shown that arsenic trioxide (As2O3) may induce hematologic remissions in patients with acute promyelocytic leukemia (APL) refractory to all-trans retinoic acid (ATRA). We reported on a patient with ATRA and drug-resistant APL that was successfully treated with As2O3. The patient had been given a diagnosis of typical APL and was treated with ATRA and chemotherapy for 12 months. He achieved complete remission (CR), but leukemia relapsed with 43% APL cells in the bone marrow in the 16th month of treatment. ATRA and cytarabine plus daunorubicin were administered; however, the APL cells in the bone marrow increased to 97.2%. As2O3 was initiated intravenously, and bone marrow showed a decrease of APL cells (6.7%) and a partial differentiation after 9 days. The patient received idarubicin (IDA) and steroid pulse because of the development of ATRA-like syndrome, and achieved CR 37 days after the initiation of As2O3. He received an additional 2 courses of As2O3 with IDA, and is in CR. These results demonstrated the therapeutic efficacy of As2O3 in treating ATRA and drug-resistant APL.

Adult↗

HPLC analysis of dental resin composites components.

Five uncured commercial dental resin composites (two bis-glycidyl methacrylate based products and three non-bis-glycidyl methacrylate based products) were examined for contamination with bisphenol A, which is a known xenobiotic. After the samples were processed with acetonitrile for extraction of their components, high performance liquid chromatography analysis was performed and the eluted peaks were fractionated for comparison using UV spectra. The results suggested that all the resin composites tested were contaminated with bisphenol A or its derivatives. Theoretically, bisphenol A is not a component of dental resin composite, but it could remain as an impurity of the composite during the synthesis of Bis-GMA. The results suggest that it is necessary to investigate the ability of this impurity and its derivatives in dental resin composites to cause estrogenic effects, as well as to evaluate the release of the impurity from cured resin composites.

Benzhydryl Compounds↗

Reactive oxygen species are involved in the apoptosis induced by nonsteroidal anti-inflammatory drugs in cultured gastric cells.

We previously reported the induction of apoptotic DNA fragmentation by nonsteroidal anti-inflammatory drugs (NSAIDs) in cultured rat gastric cells, and indicated that prostaglandin-synthesis is only marginally involved in the apoptotic process. In the present study, we examined whether the generation of reactive oxygen species is critically involved in NSAID-induced apoptosis. Indomethacin, sodium diclofenac, flurbiprofen, zaltoprofen, etodolac, but not mofezolac, enhanced apoptotic DNA fragmentation and mRNA expression for cyclooxygenase-2 in AGS cells, a cell line derived from human gastric epithelium. The apoptotic effect of indomethacin was then confirmed by fluorescent staining of the cells with annexin V. Apoptotic DNA fragmentation induced by indomethacin and flurbiprofen was suppressed by incubation of the cells with the anti-oxidants pyrrolidine dithiocarbamate, diphenyleneiodonium chloride, and N-acetyl-L-cysteine. These two NSAIDs also enhanced release from the cells of 8-isoprostane, a nonenzymatic product by free-radical-mediated peroxidation of arachidonic acid. Further, lucigenin chemiluminescence showed that the intracellular production of reactive oxygen species increased in cells treated with indomethacin. The present data thus indicate a crucial association between the generation of reactive oxygen species and NSAID-induced apoptosis in gastric epithelial cells.

Anti-Inflammatory Agents, Non-Steroidal↗

Coalescence of Lipid Emulsions in Floating and Freeze-Thawing Processes: Examination of the Coalescence Transition State Theory.

Lipid emulsions, triacylglycerol droplets covered with single surface monolayers of phospholipid in aqueous medium, were prepared by high-pressure emulsification and successive ultracentrifugation. Egg yolk phosphatidylethanolamine did not stabilize triolein (TO) droplets in aqueous medium. Phosphatidylcholine (PC) of various long fatty acyl chains dispersed TO and tricaprylin (TC) well in aqueous medium as emulsion droplets of 110 nm. After ultracentrifugation, however, oil separation was observed in the floating creamy layer of TO/dioleoyl-PC emulsions. Dioleoyl-PC contains two bulky unsaturated fatty acyl chains, as well as oleoyl chains, and it has a lower spontaneous curvature than egg PC. Egg PC and dipalmitoyl-PC gave stably dispersed emulsion droplets of TO even after the freeze-thawing (F-T) procedure. On the other hand, TO/egg PC emulsion droplets containing cholesterol of 83 mol% PC and TC/egg PC emulsion droplets coalesced after the F-T procedure. Cholesterol and a medium chain triacylglycerol, TC, were distributed into the surface PC monolayers and occupied an appreciable fraction of the surface area. These neutral lipids have small polar groups and thus decrease the mean spontaneous curvature of surface lipids. The relationship between the droplet coalescence and the spontaneous curvature was discussed on the basis of the coalescence transition state theory recently developed by Kabalnov et al. in 1996. In addition, effects of maltose on the emulsion coalescence in the freeze state were briefly discussed. Copyright 1999 Academic Press.

Journal Article↗

Potent antitumor activity of MS-247, a novel DNA minor groove binder, evaluated by an in vitro and in vivo human cancer cell line panel.

We synthesized a novel anticancer agent MS-247 (2-[[N-[1-methyl-2-[5-[N-[4-[N,N-bis(2-chloroethyl) amino] phenyl]] carbamoyl]-1H-benzimidazol-2-yl] pyrrol-4-yl] carbamoyl] ethyldimethylsulfonium di-p-toluenesulfonate) that has a netropsin-like moiety and an alkylating residue in the structure. We evaluated antitumor activity of MS-247 using a human cancer cell line panel coupled with a drug sensitivity database and subsequently using human cancer xenografts. The average MS-247 concentration required for 50% growth inhibition against a panel of 39 cell lines was 0.71 microM. The COMPARE analysis revealed that the differential growth inhibition pattern of MS-247 significantly correlated with those of camptothecin analogues and anthracyclins, indicating that MS-247 and the two drug groups might have similar modes of action. MS-247 exhibited remarkable antitumor activity against various xenografts. A single i.v. injection of MS-247 significantly inhibited the growth of all 17 xenografts tested, which included lung, colon, stomach, breast, and ovarian cancers. In many cases, MS-247 was more efficacious than cisplatin, Adriamycin, 5-fluorouracil, cyclophosphamide, VP-16, and vincristine and was almost comparable with paclitaxel and CPT-11; these are the most clinically promising drugs at present. MS-247 was noticeably more effective than paclitaxel (in HCT-15) and CPT-11 (in A549, HBC-4, and SK-OV-3). The toxicity of MS-247, indicated by body weight loss, was reversible within 10 days after administration. The MS-247 mode of action showed DNA binding activity at the site where Hoechst 33342 bound, inhibited topoisomerases I and II (as expected by the COMPARE analysis) blocked the cell cycle at the G2-M phase, and induced apoptosis. These results indicate that MS-247 is a promising new anticancer drug candidate to be developed further toward clinical trials.

Animals↗

Functional reconstitution of a heteromeric cyclic nucleotide-gated channel of Caenorhabditis elegans in cultured cells.

The tax-4 and tax-2 genes of Caenorhabditis elegans are essential for normal olfaction, gustation, and thermosensation, suggesting that they have a role in sensory transduction. The predicted products of these genes are similar to the cyclic nucleotide-gated (CNG) channel subunits used in vertebrate vision and olfaction: TAX-4 is highly related to those alpha subunits, while TAX-2 is most closely related to the beta subunits of the rod phototransduction channels. TAX-4 has previously been shown to form a highly sensitive cGMP-gated channel when expressed in human HEK293 cells. Here we show that TAX-4 and TAX-2 form a heteromeric channel when expressed in HEK293 cells, but TAX-2 does not form a channel on its own. Since these genes are expressed in the same neurons, most of the native channels in C. elegans are likely to be hetero-oligomers of TAX-4 and TAX-2 subunits, with TAX-4 as the alpha subunit and TAX-2 acting as a modifying beta subunit. The heteromeric TAX-4/TAX-2 channel is 25-fold less sensitive to cGMP than the TAX-4 channel, but it remains highly selective for cGMP over cAMP. The heteromeric channel and the TAX-4 homomeric channel differ in their blockage by divalent cations and in their single channel properties. These results suggest that cGMP is used as the second messenger during sensory signal transduction in C. elegans, and that distinct roles for alpha and beta subunits of CNG channels are conserved in vertebrate and invertebrate signal transduction.

Animals↗

New hyperprolactinemia and anovulation model in common marmoset (Callithrix jacchus) and effect of cabergoline.

We aimed to develop an anovulation model, using sulpiride-induced hyperprolactinemia in common marmosets. The serum prolactin level gradually increased during the twice-daily administration of sulpiride and reached a plateau after 4 days. Sulpiride produced as big a response at 10 mg kg(-1) as at 50 mg kg(-1). In this study, the length of the ovarian cycle was approximately 30 days in normal common marmosets. Serum progesterone and estradiol levels showed no consistent change during the first 2 months of treatment with sulpiride. When treatment with sulpiride had been continued for more than 2 months, serum progesterone and estradiol levels fell to within the range seen in the follicular phase of the normal cycle and absence of ovulation was recognized by laparoscopy. A single oral administration of cabergoline (at doses between 0.01 and 0.1 mg kg(-1)) dose dependently reduced the elevated serum prolactin level. Bromocriptine (at an oral dose of 10 mg kg(-1)) also reduced the serum prolactin level at 4 and 8 h after its administration. With bromocriptine, the prolactin level had recovered at 24 h, but with cabergoline at doses of 0.05 mg kg(-1) or more, it had still not recovered at 48 h. In anovulatory common marmosets, oral administration of cabergoline at a daily dose of 0.05 mg kg(-1) restored ovarian function and resulted in ovulation in 100% of the group (following a reduction in the serum prolactin level). Bromocriptine at a daily oral dose of 10 mg kg(-1) resulted in ovulation in 67% of the group, but this dose was about 200 times higher than the dose of cabergoline. We could produce an anovulatory model induced by sulpiride repeatedly administered over a long time period. It is suggested that, in this anovulatory model in common marmosets, cabergoline has a potent and long-lasting action as a dopamine D2 receptor agonist, and thus could be a useful drug for the treatment of galactorrhea and hyperprolactinemic amenorrhea and/or anovulation.

Animals↗

Alcohol-induced biphasic inhibition of myosin subfragment 1 K-EDTA-ATPase.

Butanol-induced inhibition of K-EDTA-ATPase of myosin subfragment 1 proceeded by biphasic kinetics, consisting of rapid and slow inactivations. The extent of the rapid inactivation, which was estimated by extrapolating the process of slow inactivation to zero time of the incubation period, was saturated with butanol concentration. Recovery of activity by dilution in the rapid phase indicates that the rapid process is reversible. The slow inactivation was concomitant with a partial denaturation of the 50 kDa domain of S1, which was detected by limited tryptic digestion. Other alcohols (methanol, ethanol, propanol and hexanol) also inhibited the K-EDTA-ATPase in the rapid phase. The Ki decreased with an increase in the number of methylene groups of alcohol. When K-EDTA-ATPase activity in the rapid phase was plotted against viscosity, surface tension or dielectric constant, the curves were different for each of the various alcohol solutions. The rapid inactivation appears to be caused by a binding of the alkyl group to S1, rather than by solvent effects. The kinetics of rapid butanol inhibitions indicate that butanol reduces the maximum activity of ATPase but enhances an apparent affinity of S1 with ATP. These indications suggest that alcohol stabilizes S1.KATP intermediate. The rapid K-EDTA-ATPase inhibition was observed at the same alcohol concentration where S1 Mg-ATPase was activated.

1-Butanol↗

Refined structure of orthorhombic lysozyme crystallized at high temperature: correlation between morphology and intermolecular contacts.

The structure of orthorhombic hen egg-white lysozyme (HEWL) crystallized at 310 K has been refined at 1.7 A resolution. Large displacements of the side-chain atoms with respect to the tetragonal structure were observed in many places, in contrast to small displacements of the main-chain atoms. A chloride-ion binding site was observed at an interface of two molecules, but at a different position to the binding site in the tetragonal form. The analysis of intermolecular contacts in the crystal has shown the presence of three independent intermolecular contacts which are called macrobonds A, B and C. Arginine side chains are frequently involved in these macrobonds, suggesting that the high frequency of this residue in HEWL may be a possible reason for the multiple polymorphs of this protein. The crystal forms were determined using a light-reflecting device on a four-circle diffractometer. Correlations between crystal forms and the three-dimensional macrobond networks were interpreted in terms of their components in various crystallographic planes, making use of approximate strengths of hydrogen-bond and van der Waals interatomic forces.

Animals↗