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Biomedical subjects

K Kato

Publications and source records attributed to K Kato.

At least 163 records · Page 9Linked to original sources

Elevated serum-soluble Fas ligand in histiocytic necrotizing lymphadenitis.

Recent studies have indicated that Fas and perforin-based mechanisms seem to induce apoptosis in histiocytic necrotizing lymphadenitis (HNL). In this study, we evaluated the serum levels of soluble Fas ligand (sFasL) in 30 HNL patients using paired sera. Elevations in sFasL levels were detected in 9 patients in the active stage. In the convalescent stage, the levels of sFasL decreased to an undetectable degree after 2 weeks. These findings indicate the possibility that sFasL plays an important role in the constitutional symptoms and pathogenesis of HNL and, furthermore, that it can act as a surrogate marker of the disease activity.

Adolescent↗

Glucose-induced hyperproliferation of cultured rat aortic smooth muscle cells through polyol pathway hyperactivity.

AIMS/HYPOTHESIS: The protein kinase C (PKC), platelet-derived growth factor (PDGF) and polyol pathway play important parts in the hyperproliferation of smooth muscle cells, a characteristic feature of diabetic macroangiopathy. The precise mechanism, however, remains unclear. This study investigated the relation between polyol pathway, protein kinase C and platelet-derived growth factor in the development of diabetic macroangiopathy. METHODS: Smooth muscle cells were cultured with 5.5 or 20 mmol/l glucose with or without an aldose reductase inhibitor, epalrestat, or a PKC-beta specific inhibitor, LY333531. Protein kinase C activities, the expression of PKC-beta II isoform and PDGF-beta receptor protein, free cytosolic NAD+:NADH ratio, the contents of reduced glutathione, and proliferation activities were measured. RESULTS: Smooth muscle cells cultured with 20 mmol/l glucose showed statistically significant increases in protein kinase C activities, the expression of PKC-beta II isoform and PDGF-beta receptor protein, and proliferation activities, compared with smooth muscle cells cultured with 5.5 mmol/l glucose. Although epalrestat and LY333531 inhibited protein kinase C activation induced by glucose to the same degree, the effects of epalrestat on proliferation activities and expression of the PDGF-beta receptor were more prominent than those of LY333531. Epalrestat improved the glucose-induced decrease in free cytosolic NAD+:NADH ratio and reduced glutathione content, but LY333531 did not. The increased expression of membranous PKC-beta II isoform was normalized by epalrestat. CONCLUSION/INTERPRETATION: These observations suggest that polyol pathway hyperactivity contributes to the development of diabetic macroangiopathy through protein kinase C, PDGF-beta receptor, and oxidative stress, and that an aldose reductase inhibitor has a therapeutic value for this complication.

Aldehyde Reductase↗

An insulator element from the sea urchin Hemicentrotus pulcherrimus suppresses variation in transgene expression in cultured tobacco cells.

Specialized DNA sequences known as insulators protect genes from both the positive and negative influences of nearby chromatin. Many insulators have been identified in various species; however, few function in multiple species. We have shown that an insulator from the Ars (arylsulfatase) gene of the sea urchin Hemicentrotus pulcherrimus functions in plant cells. Normally, expression of an introduced chimeric GUS gene is inactivated in approximately 30% of transformed tobacco BY2 clones. Transgenes containing the Ars insulator, however, were expressed in all transformed tobacco BY2 cells. The insulator did not affect the copy number, the chromosomal position of transgene integration or maximum expression levels. These results suggest that the insulator functions to suppress the variation normally associated with transgene expression in tobacco BY2 cells.

Animals↗

Melatonin's gastroprotective and antistress roles involve both central and peripheral effects.

Systemic administration of melatonin (5 to 20 mg/kg) has been reported to inhibit the induction of acute gastric mucosal lesions by stress or ischemia-reperfusion in rats. We recently demonstrated that intracisternal (i.c.) melatonin at low doses (1 to 100 ng) dose-dependently decreased acid and pepsin outputs in rats. The aim of the present study was to further investigate the peripheral and central roles of melatonin in gastric mucosal defense. Using a radioimmunoassay, we measured melatonin concentrations in the plasma and cerebrospinal fluid (CSF) of the cisterna magna in rats subjected to water immersion restraint stress and given intraperitoneal (i.p.) or i.c. injection of melatonin. Water immersion restraint stress was followed by a significant duration-related increase in peripheral plasma melatonin levels; the stress similarly produced a time-dependent increase in the extent of gastric mucosal lesions. Administration of melatonin (1 or 10 mg/kg, i.p., or 100 ng/10 microl, i.c.) significantly reduced the extent of stress-induced gastric damage, by 46%, 67%, and 54%, respectively. The effective i.c. dose of melatonin was at least 10,000-fold smaller than the effective i.p. dose. Melatonin levels in plasma and CSF after the i.p. injection of melatonin at 10 mg/kg were dramatically higher than those after the i.c. injection of vehicle or 100 ng of melatonin. Our results suggest that the peripheral gastroprotective action of melatonin should be investigated with due regard to these central effects.

Animals↗

Discriminant analysis of prognostic factors for malignant fibrous histiocytoma in soft tissue.

We prospectively followed 32 patients with soft-tissue malignant fibrous histiocytoma (MFH). Parameters were age; sex; tumor size, location, and depth; operative method; chemotherapy; radiotherapy; and histology. Patients with recurrence or metastases due to MFH within 6 months after the initial operation were separated from those without these characteristics by discriminant analysis with statistically significant difference. The order of influential functions was histology, depth of tumor, operative method, and sex. Male patients with deep-seated storiform-pleomorphic type MFH, receiving less comprehensive surgery, had the greatest risk of local recurrence or early metastases. We have to pay particular attention to patients with these factors and perform adequate surgery, because local recurrence and metastases were found to be closely related, and to have a great influence on the prognosis of this disease. Discriminant analysis to separate patients with MFH recurrence or metastases within 6 months after the initial operation from those without these characteristics is worthwhile for prognostic assessment.

Adult↗

Survey of antibiotic resistance in Pseudomonas aeruginosa by The Tokyo Johoku Association of Pseudomonas Studies.

Pseudomonas aeruginosa resistance (minimum inhibitory concentration [MIC], > or =16 microg/ml defined as resistant) to meropenem, imipenem, panipenem, piperacillin, ceftazidime, cefozopran, cefoperazone, sulbactam/cefoperazone, amikacin, and tobramycin, as well as cross-resistance profiles, were investigated in P. aeruginosa strains isolated at eight hospitals in the Johoku area, Tokyo, during November 1998. Overall, 8.3% of isolates were imipenem-resistant and 4.6% were ceftazidime-resistant. However, the incidence of antibiotic-resistant P. aeruginosa was distinctly different at each hospital. P. aeruginosa resistance to imipenem ranged from (MIC) 1 to 64 microg/ml (MIC90 32 microg/ml), and its resistance to ceftazidime ranged from 2 to more than 128 microg/ml (MIC90, 64 microg/ml). Meropenem (MIC range, < or =0.25 to 16 microg/ml) was more active than panipenem (MIC range, 2 to 64 microg/ml). Cefozopran was more active than piperacillin, cefoperazone, or sulbactam/cefoperazone, but many strains were resistant to cefoperazone (17/57). Our analysis found cross-resistance to many beta-lactams, but the degree of cross-resistance was very variable.

Anti-Bacterial Agents↗

Axial length and refractive error in X-linked retinoschisis.

PURPOSE: To examine the relationship between axial length and refractive error in patients with X-linked retinoschisis. DESIGN: To determine whether the hypermetropia frequently found in patients with X-linked retinoschisis is axial hypermetropia. METHODS: The axial length and refractive error were measured in 29 right eyes of 29 patients. The patients were divided into two groups: a juvenile group with ages <13 years (12 eyes) and an adult group with ages > or =13 years (17 eyes). The axial length of the right eye of 30 adult men without eye diseases whose refractive error ranged from +/- 1.0 diopter served as controls. RESULTS: In the adult patient group, the refractive error was significantly more hypermetropic and the axial length was significantly shorter than was the normal adult group (P <.001). CONCLUSION: These results strongly suggest that the hypermetropia in patients with X-linked retinoschisis is axial hypermetropia.

Adolescent↗

UV-irradiation-induced DNA immobilization and functional utilization of DNA on nonwoven cellulose fabric.

Immobilization of double-stranded DNA onto nonwoven cellulose fabric by UV irradiation and utilization of DNA-immobilized cloth were examined. The immobilized DNA was found to be stable in water, with the maximum amount of fabric-immobilized DNA being approximately 20 mg/g of nonwoven fabric. The DNA-immobilized cloth could effectively accumulate endocrine disruptors and harmful DNA intercalating pollutants, such as dibenzo-p-dioxin, dibenzofuran, biphenyl, benzo[a]pyrene and ethidium bromide. Additionally, DNA-immobilized cloth was found to bind metal ions, such as Ag+, Cu2+, and Zn2+. The maximum amounts of bound Ag+, Cu2+, and Zn2+ onto DNA-immobilized cloth (1 g) were approximately 5, 2, and 1 mg, respectively. DNA-immobilized cloth containing Ag+ showed antibacterial activity against Escherichia coli and Staphylococcus aureus. DNA-immobilized cloth without metal ion and with Cu2+ or Zn2+ did not show antibacterial activity. These results suggest that immobilized DNA imparts useful functionality to cloth. DNA-immobilized cloth prepared by UV irradiation has potential to serve as a useful biomaterial for medical, engineering, and environmental application.

Cellulose↗

Antiviral activity of NMSO3 against adenovirus in vitro.

NMSO3, a sulfated sialyl lipid, was evaluated for its efficacy against adenovirus (AdV) in vitro. The median effective concentration (50% effective concentration, EC(50)) of NMSO3 against replication of AdV type 2 (AdV2), type 4 (AdV4), type 8 (AdV8) and type 37 (AdV37) was 0.21-0.71 microg/ml in HEp-2 cells and 1.01-1.41 microg/ml in MKN-28 cells. The EC(50) values of NMSO3 were lower than those of HPMPC and ddC, which were also evaluated. NMSO3 exhibited minimal cytotoxicity against HEp-2 cells and MKN-28 cells, both for which the median cytotoxic concentration (50% cytotoxic concentration, CC(50)) was more than 1000 microg/ml. NMSO3 was the most potent and selective anti-AdV compound of those examined. NMSO3 inhibited AdV infection of HEp-2 cells only when present during the virus adsorption period. A virus binding assay using radiolabeled AdV4 revealed that NMSO3 inhibited viral binding to the HEp-2 cells. NMSO3 itself bound to the virus particles, but not to the HEp-2 cell membrane. Thus, the mechanism of anti-AdV activity by NMSO3 involves inhibition of virus adsorption to cells by NMSO3 binding to viral particles.

Adenoviridae↗

Anterior cingulate activity during pain-avoidance and reward tasks in monkeys.

We recorded single neuronal activities in the anterior cingulate cortex of monkeys while they were performing discriminative pain-avoidance and reward tasks: a prediction cue was presented for 0.5-1.5 s, followed by a red or green discrimination cue (1:1, random) for 1.0 s; painful stimuli were presented if the monkey failed to respond during the red cue; a reward was given, subsequent to a cued 1 s delay, if the monkey responded after the green cue. Among 775 neurons recorded, 196 neurons showed significant activity during one or more observation periods; 36 during the prediction period; 77 during the discrimination period; 41 during the delay period; 85 during the response period; 40 during the pre-reward period; and 15 during the reward-ingestion period. Of 77 neurons activated during the discrimination period, 47 showed exclusive activity either during the red (34) or during the green (13) cue: of 85 neurons activated during the response period, 64 showed exclusive activity either for pain-avoidance (37) or obtaining a reward (27). Control experiments confirmed that the neuronal activity could not be attributed to simple visual or motor processes. The results suggest that some anterior cingulate neurons are involved with anticipation of, and response selection for, imminent events.

Action Potentials↗

Polysynaptic excitatory pathways induce heterosynaptic depression in the rat auditory cortex.

Short-term plasticity, the effect of a preceding synaptic response on the following response in a pair, in layers II/III of the rat auditory cortex slice after application of repetitive stimuli to layer IV, was investigated using a multichannel extracellular recording system. Paired-pulse depression, which is induced to a moderate degree in standard artificial cerebrospinal fluid, was markedly facilitated in the presence of bicuculline, a GABA(A) receptor antagonist, concurrent with the emergence of a polysynaptic component of the EPSP (polyEPSP) in the first response in a pair. This depression (bicuculline-facilitated synaptic depression, BFSD) was maximal at the minimum interval tested (50 ms), reduced as the interval was increased, and persisted beyond an interval of 2 s. The occurrence of BFSD was dependent on the presence of a polyEPSP regardless of the presence of the monosynaptic component of the EPSP, indicating that BFSD is induced by a heterosynaptic mechanism. D-AP5, an NMDA receptor antagonist, partially eliminated polyEPSPs and reversed BFSD. These results suggest that activation of polysynaptic excitatory pathways induces a heterosynaptic depression in the range of a few seconds and that NMDA receptor activity is involved in this heterosynaptic depression.

2-Amino-5-phosphonovalerate↗

Left ventricular mass index increases in proportion to the progression of diabetic nephropathy in Type 2 diabetic patients.

The aim of our cross-sectional case-control study was to evaluate the mechanism of increased cardiac morbidity and mortality in Type 2 diabetic patients with normo-, micro-, and macroalbuminuria. Twenty-nine Type 2 diabetic patients with normoalbuminuria (group N), 19 patients with microalbuminuria (group M1), and seven patients with macroalbuminuria (group M2) were investigated. Groups were not significantly different concerning age, sex and diabetes duration. All patients took their normal medication throughout the study and had no clinical evidence of heart disease. Left ventricular mass index (LVMI) and systolic function were determined by echocardiography. As to the elevation of urinary albumin excretion levels, LVMI was significantly elevated, 101.4+/-20 gm(-2) of group N, 119.5+/-29 gm(-2) of group M1, and 141.9+/-27 gm(-2) of group M2. The prevalence of left ventricular hypertrophy (LVH) was significantly higher in group M2 (100%), and M1 (58%), as compared with group N (24%), but was not significantly different between groups M1 and M2. The body mass index and systolic blood pressure were significant independent predictors of LVMI by multiple regression analysis. In conclusion, the mechanism of the link between albuminuria and cardiovascular mortality was suggested to be LVH.

Albuminuria↗

Human adrenomedullin gene delivery protects against cardiovascular remodeling and renal injury.

We investigated the potential roles of adrenomedullin (AM) in cardiovascular and renal function by somatic gene delivery. We showed that a single intravenous injection of the human AM gene under the control of cytomegalovirus promoter/enhancer induces a prolonged delay in blood pressure rise for several weeks in spontaneously hypertensive rats, Dahl salt-sensitive, DOCA-salt, and two-kidney one-clip hypertensive rats as compared to their respective controls injected with a reporter gene. Expression of the human AM transcript was identified in the heart, kidney, lung, liver and aorta of the rat after adenovirus-mediated AM gene delivery by RT-PCR followed by Southern blot analysis. Immunoreactive human AM levels were measured in rat plasma and urine following AM gene delivery. AM gene delivery induced significant reduction of left ventricular mass in these hypertensive animal models. It also reduces urinary protein excretion and increases glomerular filtration rate, renal blood flow and urinary cAMP levels. AM gene transfer attenuated cardiomyocyte diameter and interstitial fibrosis in the heart, and reduced glomerular sclerosis, tubular disruption, protein cast accumulation and renal cell proliferation in the kidney. In the rat model with myocardial ischemia/reperfusion injury, AM gene delivery significantly reduced myocardial infarction, apoptosis, and superoxide production. Furthermore, local AM gene delivery significantly inhibited arterial thickening, promoted re-endothelialization and increased vascular cGMP levels in rat artery after balloon angioplasty. Collectively, these results indicate that human AM gene delivery attenuates hypertension, myocardial infarction, renal injury and cardiovascular remodeling in animal models via cAMP and cGMP signaling pathways. These findings provide new insights into the role of AM in cardiovascular and renal function.

Adenoviridae↗

Membranous proliferation of lens epithelial cells on acrylic, silicone, and poly(methyl methacrylate) lenses.

PURPOSE: To determine whether intraocular lens (IOL) material influences the membranous proliferation of lens epithelial cells (LECs) on the anterior surface of the IOL. SETTING: Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan. METHODS: This prospective study included 87 eyes of 87 consecutive patients who had cataract surgery with IOL implantation. Patients were randomly assigned to receive a single-piece poly(methyl methacrylate) (PMMA) IOL, a 3-piece silicone IOL, or a 3-piece acrylic IOL. Postoperatively, the IOL optic was examined by slitlamp microscopy at 1 and 10 days and 1, 2, and 3 months to determine the incidence, duration, and extent of membranous LEC proliferation. The optic was also examined at 6, 9, and 12 months if proliferation persisted. RESULTS: Thirteen eyes were excluded from analysis because of incomplete coverage of the IOL rim by the anterior capsule margin; 74 remaining eyes were studied. All patients obtained good postoperative visual acuity (20/25 or better). Incidence (P =.0024) and duration (P =.0002) of membranous LEC proliferation with the acrylic IOL was greater than with the other 2 types. Proliferation on the acrylic IOL was more extensive than on the PMMA IOL 10 days postoperatively (P <.05) and on the silicone IOL at 10 days (P <.01) and 1 month (P <.01). However, LEC proliferation on the 3 types of IOLs usually decreased by the third postoperative month, and proliferation did not disturb visual acuity. CONCLUSIONS: The material of an IOL influenced membranous proliferation of LECs on its anterior surface. Proliferation on the acrylic IOL persisted longer than on the other 2 types but did not cause visual symptoms.

Acrylic Resins↗

Glistening formation in an AcrySof lens initiated by spinodal decomposition of the polymer network by temperature change.

PURPOSE: To examine the effect of temperature change on the structural alteration and glistening formation in an AcrySof intraocular lens (IOL). SETTING: Department of Chemical Science and Engineering, Faculty of Engineering, Kobe University, Kobe, Japan. METHODS: The equilibrium water content of a Wagon-Wheel-packaged AcrySof IOL was determined at various temperatures by the gravimetrical method. Alterations in the microscopic structure of the lens were analyzed in situ with a reflecting microscope without staining, while the temperature of the lens was changed at different rates. RESULTS: Microvacuoles of 1.0 to 20.0 microm formed in the bulk of a swollen AcrySof IOL as the temperature decreased. The morphology of the vacuoles was similar to that of glistening particles observed in vivo. The size and density of the glistening-like vacuoles varied depending on the magnitude and rate of the temperature decrease. The glistening-like vacuoles were imprinted in the bulk of the IOL during the preceding cooling process in aqueous humor. CONCLUSIONS: Glistenings formed in the bulk of an AcrySof IOL as the medium temperature decreased. The mechanism may involve spinodal decomposition of the swollen polymer network, which initiates the formation of microvacuoles consisting of water and loosely packed network chains.

Acrylic Resins↗

Nitric oxide synthase-I containing cortical interneurons co-express antioxidative enzymes and anti-apoptotic Bcl-2 following focal ischemia: evidence for direct and indirect mechanisms towards their resistance to neuropathology.

Neuronal nitric oxide-I is constitutively expressed in approximately 2% of cortical interneurons and is co-localized with gamma-amino butric acid, somatostatin or neuropeptide Y. These interneurons additionally express high amounts of glutamate receptors which mediate the glutamate-induced hyperexcitation following cerebral injury, under these conditions nitric oxide production increases contributing to a potentiation of oxidative stress. However, perilesional nitric oxide synthase-I containing neurons are known to be resistant to ischemic and excitotoxic injury. In vitro studies show that nitrosonium and nitroxyl ions inactivate N-methyl-D-aspartate receptors, resulting in neuroprotection. The question remains of how these cells are protected against their own high intracellular nitric oxide production after activation. In this study, we investigated immunocytochemically nitric oxide synthase-I containing cortical neurons in rats after unilateral, cortical photothrombosis. In this model of focal ischemia, perilesional, constitutively nitric oxide synthase-I containing neurons survived and co-expressed antioxidative enzymes, such as manganese- and copper-zinc-dependent superoxide dismutases, heme oxygenase-2 and cytosolic glutathione peroxidase. This enhanced antioxidant expression was accompanied by a strong perinuclear presence of the antiapoptotic Bcl-2 protein. No colocalization was detectable with upregulated heme oxygenase-1 in glia and the superoxide and prostaglandin G(2)-producing cyclooxygenase-2 in neurons. These results suggest that nitric oxide synthase-I containing interneurons are protected against intracellular oxidative damage and apoptosis by Bcl-2 and several potent antioxidative enzymes. Since nitric oxide synthase-I positive neurons do not express superoxide-producing enzymes such as cyclooxygenase-1, xanthine oxidase and cyclooxygenase-2 in response to injury, this may additionally contribute to their resistance by reducing their internal peroxynitrite, H(2)O(2)-formation and caspase activation.

Animals↗

Glycine reduces novelty- and methamphetamine-induced locomotor activity in neonatal ventral hippocampal damaged rats.

The use of neonatal ventral hippocampal nVH lesioned rats is well established in animal models of schizophrenia. Moreover, the dysfunction of N-methyl-D-aspartate (NMDA) neurotransmission may play a crucial role in the pathophysiology of schizophrenia. To examine the effect of glycine (GLY) in this animal model, we compared the effects of GLY (0.8 and 1.6 g/kg, IP) on locomotor activity induced by a novel environment (NOVEL) and methamphetamine (MAP, 1.5 mg/kg, IP) in lesioned and sham-operated rats. Compared with sham rats, GLY significantly reduced NOVEL- and MAP-induced locomotor activity in lesioned rats (p <.001 and p <.05, respectively). It is suggested that GLY attenuated nVH-induced hyperactivity, and that this effect was evident both in the presence and absence of MAP. The nVH lesions may result in a form of hyperactivity that differs from normal locomotion in the degree to which it is highly sensitive to regulation by GLY.

Animals↗