Biomedical subjects

N Mori

Publications and source records attributed to N Mori.

At least 73 records · Page 4Linked to original sources

PubMed2001

AS-924, a novel, orally active, bifunctional prodrug of ceftizoxime: physicochemical properties, oral absorption in animals, and antibacterial activity.

AS-924 is an oral prodrug of the antibiotic ceftizoxime (CTIZ), a parenteral use cephalosporin. This novel prodrug, produced by esterifying CTIZ with a lipophilic pivaloyloxymethyl (POM) group and introducing a water soluble L-alanyl group, is expected to increase the bioavailability and thereby, augment the antibacterial activity of CTIZ in vivo compared with existing prodrugs. To study the effect of the L-alanyl group in AS-924 on its bioavailability, the plasma concentration profiles of CTIZ in dogs were examined following the dosing of AS-924 and CTIZ-POM, in powder form, after pretreatment with the antacid ranitidine, and following the dosing of AS-924 after pretreatment with a gastrointestinal motility stimulant metoclopramide or suppressant scopolamine butylbromide. The absorption rate of AS-924 was constant under these different conditions due to its unique balance of lipophilicity and water solubility. CTIZ is as antibacterially active as pre-existing oral cephalosporins against Gram-positive clinical isolates, while being more active against all Gram-negative isolates-particularly Enterobacteriaceae and Haemophilus influenzae. A simulation model for the eradication profile of bacteria in computer programmed pharmacokinetic (PK) system was carried out to study the antibacterial action of CTIZ in human. CTIZ was proven to eradicate Streptococcus pneumoniae and H. influenzae effectively, while cefpodoxime (CPOD), the active moiety of CPOD proxetil, eradicated S. pneumoniae, but not H. influenzae. These results confirm that, AS-924 is a potent oral antibiotic and would be expected to be clinically effective and efficient.

Administration, Oral↗

PubMed2001

Effect of antacid pretreatment on the pharmacokinetics of AS-924, a novel ester-type cephem antibiotic--comparison with cefteram-pivoxil.

The effect of pretreatment with ranitidine, an antacid, on the absorption of AS-924, a novel prodrug-type cephem antibiotic derived from ceftizoxime (CTIZ), was examined in eight healthy adult male volunteers by the cross-over method, using cefteram-pivoxil (CTER-PI) as the control drug. The C(max) and area under the concentration (AUC) values and cumulative urinary excretion rate (0-24 h) of cefteram (CTER) after administration of CTER-PI decreased by 32, 38 and 37%, respectively, in the ranitidine pretreatment group whereas those of AS-924 were not affected by the antacid. The urinary levels of pivaloyl-carnitine determined to evaluate the solubility of these antibiotics in the gastrointestinal tract suggested that this was not affected by ranitidine. These results indicate that the absorption of CTER-PI was affected by pretreatment with ranitidine largely due to inactivation of this antibiotic in the gastrointestinal tract at high pH rather than to a decrease in solubility. In contrast, isomerization of AS-924 was hardly induced by the elevation of pH, thus demonstrating that AS-924 was less likely to be affected by pretreatment with antacids.

Absorption↗

PubMed2001

Effects of the quantity of water and milk ingested concomitantly with AS-924, a novel ester-type cephem antibiotic, on its pharmacokinetics.

The effect of the quantity of water ingested concomitantly with drugs, on the absorption of AS-924, a novel prodrug-type cephem antibiotic, was studied in five healthy adult volunteers by a cross-over method, using cefteram-pivoxil (CTER-PI) as the control drug. In addition, the effect of milk on the absorption of AS-924 was also investigated. The absorption of CTER-PI was significantly reduced when administered together with 30 ml of water compared with its absorption when administered together with 150 ml of water, whereas no such reduction was found in the case of AS-924. Ingestion of milk did not significantly affect the absorption of AS-924. These results confirm that absorption of AS-924 after oral administration is not likely to be affected by the quantity of water taken concomitantly with the drug, nor by milk.

Administration, Oral↗

PubMed2001

The association between obstetric complications and childhood-onset schizophrenia: a replication study.

BACKGROUND: Many previous studies have shown that individuals who develop schizophrenia in adult life are more likely than normal controls to have a history of obstetric complications (OCs) at birth. However, little attention has been paid to the involvement of OCs in the risk of developing childhood-onset schizophrenia (COS). In our earlier report, we found an association between OCs and the development of COS. In this study, we determined whether the association could be replicated in another, independent set of patients with COS. METHODS: OCs, birth weight and gestational age were retrospectively assessed in 35 children, aged between 14 and 15 years old (average 15.4 years), who met the DSM-III-R criteria for schizophrenia, and in age- and gender-matched controls (children with anxiety disorders). RESULTS: The COS patients showed significantly greater scores in all of the three measures of OCs according to the Parnas et al. scale compared to controls. Moreover, individuals exposed to OCs were about 3.2 times (odds ratio = 3.22; 95% confidence interval, 1.1-9.8) more likely to develop schizophrenia than those without a history of OCs. The mean birth weight was significantly lower in schizophrenics than in controls (P < 005). The frequency of prematurity signs with weight < 2500 g was significantly higher in schizophrenics than in controls (P < 0.05). CONCLUSION: Repeatedly reported association between OCs and adult-onset schizophrenia have also been demonstrated in patients with COS. This suggests that there may be a continuity between childhood- and adult-onset schizophrenia.

Adolescent↗

PubMed2001

Human T-cell leukemia virus type I tax protein induces the expression of anti-apoptotic gene Bcl-xL in human T-cells through nuclear factor-kappaB and c-AMP responsive element binding protein pathways.

Human T-cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T-cell leukemia (ATL), which is an aggressive form of human T-cell malignancy. The viral protein, Tax, immortalizes human T-cells and inhibits various types of apoptosis, and is thought to play crucial roles in the development of ATL. We have recently demonstrated that Tax induces the constitutive expression of the anti-apoptotic protein, Bcl-xL, in a mouse T-cell line. The mouse, however, is not a natural host of HTLV-I, and HTLV-I does not induce this malignancy in mice. We thus examined whether Tax also activates the expression of Bcl-xL in human T-cells. Expression of Tax in a human T-cell line, Jurkat, induced the expression of the Bcl-xL gene, but did not significantly affect the expression of the other apoptosis-related genes, Bcl-2 and Bax. Transient transfection assays showed that Tax stimulated human Bcl-xL promoter activity in Jurkat cells. Deletion of the two potential nuclear factor (NF)-kappaB binding sites in the human Bcl-xL promoter significantly decreased Tax-induced transactivation. In addition to NF-kappaB, Tax activates transcription through the c-AMP responsive element binding protein (CREB). Tax mutants segregating these two pathways showed that both the NF-kappaB and CREB pathways of Tax are required for maximum activation of a human Bcl-xL promoter, nevertheless, NF-kappaB alone was sufficient for that of a mouse Bcl-xL promoter. Northern blot analysis showed that all the human T-cell lines expressing Tax had higher levels of Bcl-xL mRNA than HTLV-I-uninfected ones. Furthermore, the sample from one patient with ATL expressed higher levels of Bcl-xL mRNA compared with levels from uninfected peripheral blood mononuclear cells. Our results suggest that Tax induces the expression of Bc-xL through the NF-kappaB and CREB pathways in HTLV-I-infected human T-cells, and then inhibits apoptosis, and such inhibition is necessary for the infected cells to advance to the leukemia in vivo.

Apoptosis↗

PubMed2001

Interleukin-2-dependent but not independent T-cell lines infected with human T-cell leukemia virus type 1 selectively express CD45RO, a marker for persistent infection in vivo.

Human T-cell leukemia virus type 1 (HTLV-1) is an etiologic agent of adult T-cell leukemia. HTLV-1 is exclusively detected in CD45RO+ T-cells in infected individuals, but CD45RO is weakly expressed in HTLV-1-transformed T-cell lines in vitro. The aim of this study was to investigate the role of CD45RO in the persistent HTLV-1 infection in vivo. Flow cytometry showed that only two out of eight interleukin(IL)-2-independent HTLV-1-transformed T-cell lines expressed CD45RO, whereas all five IL-2-dependent ones expressed CD45RO, and the level of expression was higher in IL-2-dependent than in IL-2-independent cells. The high CD45RO expression in IL-2-dependent cell lines was not due to IL-2, since IL-2 had little effect on the expression of CD45RO in T-cell lines. Using western blotting, we showed that IL-2-dependent HTLV-1-transformed T-cell lines expressed a lower level of expression of the viral transcriptional regulatory protein Tax than IL-2-independent ones, and that the level of expression correlated inversely with that of CD45RO. However, the expression of Tax in one HTLV-1-negative T-cell line little affected the expression of CD45RO, suggesting that Tax at least alone does not suppress the expression of CD45RO in HTLV-1-infected T-cell lines, and that other viral or cellular factor(s) are probably involved in such suppression. Our results suggest that CD45RO+ Tax-low IL-2-dependent T-cell lines in vitro correspond to the persistent HTLV-1-infected cells in vivo, and HTLV-1-infected cells in vivo are immortalized in IL-2-dependent manner.

Cell Line↗

PubMed2001

Differences of symptoms and standardized weight index between patients with early-onset and late-onset anorexia nervosa.

OBJECTIVE: There have so far been no studies that directly compared clinical features between patients with early- and late-onset anorexia nervosa (AN). METHOD: We identified 64 patients with DSM-III-R AN. We defined individuals as an early-onset group, who had an age of onset before 14 years (N = 31), and the remaining as a late-onset group (N = 33). The clinical symptoms, body weight and weight index, were compared between the two groups. Subjects were dichotomized into those with extremely low weight and those remaining. We compared the proportion of the patients with extremely low weight between the two groups. RESULTS: The rates of 'self-induced vomiting' and 'purging' were significantly lower in a group of patients with early-onset AN than in those with late-onset AN. There were significantly fewer subjects with extremely low weight in early-onset than in late-onset AN group. CONCLUSION: We found clear differences in clinical features between early- and late-onset AN groups.

Adolescent↗

PubMed2001

Near-infrared irradiation stimulates cutaneous wound repair: laboratory experiments on possible mechanisms.

BACKGROUND/AIMS: Several physical agents such as low-energy lasers have been used in the treatment of chronic skin ulcers. This study was performed to investigate potential effects of a newly-developed, specific near-infrared light source on wound repair. METHODS: Cultured human keratinocytes, endothelial cells and fibroblasts were exposed to the light, and the production of transforming growth factor (TGF)-beta1 and matrix metalloproteinase (MMP)-2 was examined by enzyme immunoassay, zymography and reverse transcription polymerase chain reaction. Incisional wounds were created in ICR and db/db diabetic mice and the effect of irradiation on wound closure was followed photographically. RESULTS: The TGF-beta1 and MMP-2 content of the medium of cultured cells was significantly elevated after irradiation. The amount of MMP-2 mRNA extracted from irradiated fibroblasts was also upregulated. Negative results in thermal controls suggested that the action of the light was athermic in nature. In animal models, the rate of wound closure was significantly accelerated by repeated exposures. CONCLUSION: Near-infrared irradiation potentially enhances the wound healing process, presumably by its biostimulatory effects.

Animals↗

PubMed2001

The effects of dentate granule cell destruction on behavioural activity and Fos protein expression induced by systemic methamphetamine in rats.

1. We destroyed dentate granule cells unilaterally or bilaterally by means of intrahippocampal injection of colchicine in rats. Subsequently, we observed behavioural changes following the intraperitoneal injection of 2 mg kg(-1) methamphetamine or saline, in addition to quantitatively assessing Fos protein expression in several brain regions, including the medial prefrontal cortex, cingulate cortex, piriform cortex, dorsal striatum, and nucleus accumbens. 2. Bilaterally lesioned animals, when administered saline, showed a marked increase in locomotor activity compared with those of non-lesioned animals. With respect to the methamphetamine response, bilateral destruction resulted in a marked enhancement of locomotor activity, while the unilateral destruction led to a marked increase in rotation predominantly contralateral to the lesioned side, with no identifiable change in locomotor activity. 3. Bilaterally lesioned animals, when administered saline and having undergone an immunohistological examination, showed a marked increase in Fos expression in both sides of the nucleus accumbens. Bilaterally lesioned animals administered methamphetamine showed a marked increase in Fos expression in the right and left sides of all regions tested. Unilaterally lesioned animals administered methamphetamine showed a significant and bilateral enhancement in Fos expression in the medial prefrontal and cingulate cortices, and a marked and unilateral (ipsilateral to the lesioned side) enhancement of Fos protein in the piriform cortex, dorsal striatum, and nucleus accumbens. 4. The present findings suggest that dentate granule cells regulate methamphetamine-associated behavioural changes through the function of widespread areas of the brain, mostly the nucleus accumbens.

Animals↗

PubMed2001

Kit(+) melanocytes seem to contribute to melanocyte proliferation after UV exposure as precursor cells.

Melanogenesis caused by UV exposure is characterized by proliferation and differentiation of functioning melanocytes in epidermis. Recently, the existence of precursor melanocytes in normal skin was proposed immunohistochemically. Thus, this precursor melanocyte seems to proliferate and differentiate into mature pigmented melanocytes after UV exposure. To elucidate how these processes occur, we examined C57BL mouse epidermal sheets after UV exposure immunohistochemically. In normal epidermis, TRP-1(+) cells and Kit(+) cells were easily identified and the cellularities were 41.0 and 31.7 cells per mm(2), respectively. Only a few Mitf(+) cells and no TRP-2(+) cells were observed. On the first day after UV exposure, Mitf(+) cells and TRP-2(+) cells appeared, whereas the numbers of TRP-1(+) cells and Kit(+) cells decreased. Some Kit+ cells also expressed Mitf, but no TRP-1 and Mitf double positive cells were seen. In this period, some Mitf(+) cells were labeled with BrdU. The next day, Mitf(+) cells and TRP-2(+) cells increased to the maximum cellularity, and they decreased thereafter and disappeared on the seventh day. An increase of TRP-1(+) cells was first identified on the fifth day after UV exposure, and reached a cellularity four times as great as that of the normal control on the fourteenth day. The subepidermal injection of Kit antibody attenuated the increase of Mitf+ cells and TRP-1(+) cells. These findings suggested that precursor cells that reside in the skin, first differentiated into Mitf(+) and TRP-2(+) melanocytes by the activation of the Kit receptor, then become mature TRP-1(+) melanocytes after UV exposure.

Animals↗

PubMed2001

Helicobacter pylori-mediated transcriptional regulation of the human beta-defensin 2 gene requires NF-kappaB.

Human beta-defensin 2 (hBD-2) is an antimicrobial peptide involved in host defence against bacterial infection in epithelial tissues. Its levels are dramatically increased after bacterial infection. The involvement of NF-kappaB in Helicobacter pylori-mediated induction of hBD-2 promoter activity was examined. A luciferase reporter plasmid containing the hBD-2 promoter extending from -2110 base pairs to -1 was transiently expressed in MKN45 cells, and promoter activity was determined after incubation with H. pylori for 6 h. Deletion or mutation of the NF-kappaB site at -208 abolished activation of the hBD-2 promoter. Only H. pylori strains carrying a cag pathogenicity island (PAI) induced activation of the NF-kappaB site of the hBD-2 promoter gene. By gel retardation analyses, H. pylori increased NF-kappaB binding to hBD-2 promoter gene sequences. Supershift analysis demonstrated that whereas H. pylori activated NF-kappaB p65-p65 and p50-p50 homodimers, and the p65-p50 heterodimer of NF-kappaB, only the p65-p65 homodimer bound to the NF-kappaB site of the hBD-2 promoter. Thus, specific NF-kappaB proteins are important cis-elements for induction of hBD-2 gene transcription by H. pylori.

Cell Line↗

PubMed2001

Effects of prolonged strenuous exercise on plasma levels of atrial natriuretic peptide and brain natriuretic peptide in healthy men.

BACKGROUND: Now that marathon racing is growing in popularity, many thousands of enthusiastic athletes are participating in various ultramarathons all over the world each year. However, it remains controversial whether such a sport contributes to the promotion of health. The occurrence of transient cardiac dysfunction and irreversible myocardial injury has been reported in association with such exercise in healthy individuals. Brain natriuretic peptide (BNP) is a cardiac hormone, as is atrial natriuretic peptide (ANP), and its measurement has been widely used for clinical evaluation of cardiac dysfunction. However, little is known about the response of plasma BNP to prolonged strenuous exercise. We hypothesized that confirmation of minimal cardiac dysfunction or myocardial injury may be made by measurements of plasma BNP. METHODS: Levels of plasma ANP, BNP, catecholamines, blood lactate, and serum cardiac troponin T (cTnT) were determined before and after a 100-km ultramarathon in 10 healthy men to examine the effects of the exercise on levels of ANP and BNP and correlations between the natriuretic peptides and cTnT as a marker for myocardial damage. RESULTS: Whereas all variables significantly increased after the race, increased levels of ANP and BNP were most strongly correlated with increases in cTnT levels. The cTnT level after the race was greater than the upper reference limit in 9 of 10 men. CONCLUSIONS: Such exercise significantly increased ANP and BNP levels in healthy men, and the increases could be partially attributed to myocardial damage during the race.

Adult↗

PubMed2001

Chordoid meningioma. A case report.

We report on a 62-year-old woman without Castleman's syndrome diagnosed with chordoid meningioma. A white, encapsulated brain tumor was located in the parietal lobe of the left hemisphere of the cerebrum, adhered to the dura, and was separated from the cerebrum. The tumor revealed a multilobular arrangement of two types of neoplastic cells, and the surrounding myxoid stroma was separated by incomplete fibrous septa. Neoplastic cells consisted of myxomatous and meningothelial cells. The former made up about four-fifths of the tumor, had a vacuolar cytoplasm, and were arranged in a chordoma-like cord pattern. They were floating in myxoid stroma. The latter had an eosinophilic spindle or epithelioid cytoplasm and were disposed in lobules. Coarse eosinophilic materials positive for periodic acid-Schiff stain were deposited among them. Transitional cells between two types of cells were also observed. Both neoplastic cells were positive for vimentin and Leu-7 (CD57) in their cytoplasm, and were consistently negative for epithelial membrane antigen, S-100 protein, and cytokeratin.

Chordoma↗

PubMed2001

Arterial blood supply to the auditory cortex of the chinchilla.

Utilizing optical imaging we identified and named the arteries that supply the primary auditory cortex in the chinchilla (Chinchilla laniger). The primary auditory cortex is located 2-3 mm caudal to the medial cerebral artery and is supplied by it. Using corrosion casts and scanning electron microscopy we visualized the capillary networks in the auditory cortex and found regional variations in the densities of the capillary bed. We hypothesize that the uneven capillary densities observed in the auditory cortex correspond to neurologically more active areas.

Animals↗

PubMed2001

Effects of actinomycin D on fetal growth in rats.

OBJECTIVE: The goal of this study was to determine the effects of actinomycin D on fetal growth and prostaglandin dehydrogenase activity and to determine whether these effects could be obtained by administering extracts of fetal calf serum (SS-094). METHODS: Actinomycin D (7 microg/100 g body weight) was injected intraperitoneally on days 11 and 12 of pregnancy to induce growth restriction in rats. In another group, SS-094 was given (0.1 ml/100 g body weight) on days 12, 15, 17 and 19 of pregnancy, following the administration of actinomycin D. Placental prostaglandin dehydrogenase (PGDH) activity was measured on days 15 and 21 of pregnancy. Statistical analysis was performed by ANOVA and Dunnet's test. RESULTS: In the group injected with actinomycin D, fetal weight was significantly restricted (on day 15; p < 0.05; on day 21; p < 0.01), compared to the controls, and this restriction was successfully reversed by SS-094. PGDH activity in the placenta was significantly (p < 0.01) decreased in growth-restricted rats and remained low even after fetal weight recovered. CONCLUSIONS: Growth restriction in pregnant rats was successfully induced by actinomycin D, and SS-094 reversed this restriction. It does not seem that prostaglandin metabolism in the placenta is responsible for growth restriction.

Analysis of Variance↗

PubMed2001

Localization of neuronal growth-associated, microtubule-destabilizing factor SCG10 in brain-derived raft membrane microdomains.

Raft is a mobile membrane subdomain enriched in sphingolipid and cholesterol and also various signaling molecules. Previous observation suggested that brain-derived rafts contain tubulin but that rafts of non-neural origin do not. We hypothesized that SCG10, one of the neuronal growth-associated proteins (nGAPs), might be a neuron-specific molecule that anchors tubulin to neuronal rafts, and we explored biochemically its subcellular localization, interaction with tubulin, and effects on microtubule dynamics. In postnatal rat brain extracts, SCG10 was recovered mostly in membrane-associated fractions, and at least half was included in the raft fraction that was also enriched in GAP-43 and NAP-22. SCG10-enriched brain rafts also contained tubulin, and chemical cross-linking experiments revealed that SCG10 was closely associated with tubulin. In addition, SCG10 was able to inhibit polymerization of tubulin. These results indicate that SCG10 is a component of neuronal rafts as are other nGAPs, and suggest that SCG10 may be involved in signaling events in membranes for cytoskeletal reorganization around neuronal rafts.

Animals↗

PubMed2001

Renal protective effects of chronic exercise and antihypertensive therapy in hypertensive rats with chronic renal failure.

OBJECTIVES: Patients with chronic renal failure are restricted to mild physical activity and tend to a lack of exercise. However, there have been few reports regarding the influence of chronic exercise on the progression of renal disease. Similarly, there are few animal models concerned with the effect of exercise training on improving renal function. Therefore, we assessed the renal effects of moderate chronic treadmill exercise in a remnant kidney model of spontaneously hypertensive rats (SHR) with chronic renal failure. We also assessed the effects of exercise and antihypertensive therapy on renal function. DESIGN AND METHODS: Eight-week-old SHR were subjected to 5/6 nephrectomy by removal of the left kidney and excision of two-thirds of the right kidney. The rats were divided into four groups: (i) no exercise (Non-EX); (ii) moderate exercise with treadmill running (20 m/min, 0 grade incline for 60 min) (EX); (iii) EX with an angiotensin converting enzyme (ACE) inhibitor, enalapril (2 mg/kg per day, i.p.); and (iv) EX with an angiotensin receptor antagonist, losartan (5 mg/kg per day, i.p.), for 4 weeks. RESULTS: Chronic EX significantly attenuated the increase in proteinuria (P < 0.01) and significantly protected against increases in the index of glomerular sclerosis (IGS). Both enalapril and losartan with EX significantly decreased blood pressure (P < 0.001), and further decreased the IGS. In the stepwise multiple regression analysis, only antihypertensive drug remained in the model as a significant predictor of IGS (P < 0.0001). In contrast, exercise, antihypertensive drug and mean systolic blood pressure (weeks 1-4) remained in the model as a significant predictors of mean proteinuria (weeks 1-4) (all P < 0.0001). CONCLUSIONS: These results suggest that exercise does not worsen renal function and has renal-protective effects in this model of rats. Moreover, the antihypertensive therapy has additional renal-protective effects in this model of rats.

Angiotensin Receptor Antagonists↗

PubMed2001

Structural comparison of three types of staphylococcal cassette chromosome mec integrated in the chromosome in methicillin-resistant Staphylococcus aureus.

The beta-lactam resistance gene mecA of Staphylococcus aureus is carried by a novel mobile genetic element, designated staphylococcal cassette chromosome mec (SCCmec), identified in the chromosome of a Japanese methicillin-resistant S. aureus (MRSA) strain. We now report identification of two additional types of mecA-carrying genetic elements found in the MRSA strains isolated in other countries of the world. There were substantial differences in the size and nucleotide sequences between the elements and the SCCmec. However, new elements shared the chromosomal integration site with the SCCmec. Structural analysis of the new elements revealed that they possessed all of the salient features of the SCCmec: conserved terminal inverted repeats and direct repeats at the integration junction points, conserved genetic organization around the mecA gene, and the presence of cassette chromosome recombinase (ccr) genes responsible for the movements of SCCmec. The elements, therefore, were considered to comprise the SCCmec family of staphylococcal mobile genetic elements together with the previously identified SCCmec. Among 38 epidemic MRSA strains isolated in 20 countries, 34 were shown to possess one of the three typical SCCmec elements on the chromosome. Our findings indicated that there are at least three distinct MRSA clones in the world with different types of SCCmec in their chromosome.

Amino Acid Sequence↗