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Biomedical subjects

S Kuwahara

Publications and source records attributed to S Kuwahara.

At least 19 recordsLinked to original sources
PubMed2004

Evaluation of electrochemically generated ozone for the disinfection of water and wastewater.

Effective wastewater treatment is critical to public health and well-being. This is especially true in developing countries, where disinfection of wastewater is frequently inadequate. People who live in these areas may benefit from wastewater disinfection using ozone. This study evaluated the ability of a new electrochemical process of ozone generation, which produced ozone continuously at high pressure and concentration by the electrolysis of water, to disinfect tap water and secondarily treated wastewater. Inactivation of Klebsiella terrigena, Escherichia coli, MS2 bacteriophage and poliovirus 1 was evaluated first in reverse osmosis (RO) treated water. Inactivation of K. terrigena (6-log), E. coli (6-log), MS2 (6-log) and poliovirus 1 (>3-log) was observed after 1 min of ozonation in a 1 L batch reactor. Experiments were then performed to assess the microbiological impact of disinfection using ozone on secondarily treated municipal wastewater. The effect of ozonation on wastewater was determined for total and faecal coliforms, bacteriophages and heterotrophic plate count (HPC) bacteria. Electrochemical ozone generators provided an effective, rapid and low-cost method of wastewater disinfection. Based on the results of this research, electrochemically generated ozone would be well suited to remote, small-scale, disinfection operations and may provide a feasible means of wastewater disinfection in developing countries.

Developing Countries↗
PubMed2002

Influence of parents' oral health behaviour on oral health status of their school children: an exploratory study employing a causal modelling technique.

OBJECTIVES: The aim of this study was to examine the simultaneous interrelationships between parents' oral health behaviour and the oral health status of their school children. SAMPLE AND METHODS: Subjects comprised 296 pairs of parents (mother or father) and their children at an elementary school in Hiroshima. The child's dental examination was performed using the World Health Organization (WHO) caries diagnostic criteria for decayed teeth (DT) and filled teeth (FT). The Oral Rating Index for Children (ORI-C) was used for the child's gingival health examination. Hiroshima University Dental Behavioural Inventory (HU-DBI) was used for the assessment of the parents' oral health behaviour. A parent-child behavioural model was tested by the linear structural relations (LISREL) programme. RESULTS: There was a significant correlation between DT and ORI-C (r = - 0.168; P < 0.01). Correlation was found between ORI-C and oral health behaviour in children (OHB-C) (r = 0.182; P < 0.01). OHB-C was significantly associated with the HU-DBI (r = 0.251; P < 0.001). The hypothesized model after some revisions was found to be consistent with the data (chi(2) = 1.3, d.f. = 6, P = 0.97; Goodness of Fit Index = 0.999). Parents' oral health behaviour affected their children's oral health behaviour (P < 0.001). Children's oral health behaviour affected their DT through its effect on gingival health level. Parents' oral health behaviour also had a significant direct effect on their children's DT (P < 0.05). Children's grade affected both DT and their oral health behaviour. CONCLUSIONS: Parents' oral health behaviour could influence their children's gingival health and dental caries directly and/or indirectly through its effect on children's oral health behaviour.

Adult↗
PubMed2001

Synthesis, structure-activity relationships, and pharmacokinetic profiles of nonpeptidic alpha-keto heterocycles as novel inhibitors of human chymase.

We designed nonpeptidic chymase inhibitors based on the structure of a peptidic compound (1) and demonstrated that the combination of a pyrimidinone skeleton as a P3-P2 scaffold and heterocycles as P1 carbonyl-activating groups can function as a nonpeptidic chymase inhibitor. In particular, introduction of heterobicycles such as benzoxazole resulted in more potent chymase-inhibitory activity. Detailed structure-activity relationship studies on the benzoxazole moiety and substituents at the 2-position of the pyrimidinone ring revealed that 2r (Y-40079) had the most potent chymase-inhibitory activity (K(i) = 4.85 nM). This compound was also effective toward chymases of nonhuman origin and showed good selectivity for chymases over other proteases. Pharmacokinetic studies in rats indicated that 2r was absorbed slowly after oral administration and showed satisfactory bioavailability (BA) (T(max) = 6.0 +/- 2.3 h, BA = 19.3 +/- 6.6%, t(1/2) = 35.7 +/- 13.3 h). In conclusion, 2r is a novel, potent, and orally active chymase inhibitor which would be a useful tool in elucidating the pathophysiological roles of chymase.

Animals↗
PubMed2001

Synthesis, structure-activity relationships, and pharmacokinetic profiles of nonpeptidic difluoromethylene ketones as novel inhibitors of human chymase.

Potent human chymase inhibitors with high enzymatic selectivity and satisfactory metabolic stability were obtained by replacing the Val-Pro (P3-P2) dipeptide portion of the previously described inhibitor 1 with a nonpeptidic pyrimidinone skeleton. The potency of the novel compounds was further enhanced by the introduction of carbamoyl-substituted difluoromethylene ketone moieties. The most potent chymase inhibitor of the newly created series was 2u (Y-40018), which had a K(i) of 2.62 nM. Compound 2u possessed high selectivity for human chymase since it lacked significant activity toward other representative human proteolytic enzymes. Moreover its strict specificity for human chymase suggested that 2u strongly inhibited human and canine chymases but not rat and mouse ones. Pharmacokinetic studies in rats and dogs indicated that 2u was absorbed rapidly after oral administration and had satisfactory bioavailability in these experimental animal species (rat, 17%; dog, 32%). In conclusion, 2u is a novel, potent, and orally active chymase inhibitor which would prove very useful in revealing the precise roles of the latter in various pathophysiological processes.

Animals↗
PubMed2001

A novel (Pro79Thr) mutation in the FKHL7 gene in a Japanese family with Axenfeld-Rieger syndrome.

PURPOSE: To report the ocular and genetic findings of a Japanese family with Axenfeld-Rieger syndrome associated with a novel Pro79Thr mutation in the FKHL7 gene. METHODS: Observational case series. Genomic DNA of patients from a family with Axenfeld-Rieger syndrome was extracted from leukocytes, and exons of the FKHL7 gene were amplified by polymerase chain reaction for direct sequencing. RESULTS: Molecular genetic analysis disclosed that one Japanese family with Axenfeld-Rieger syndrome had a heterozygous C to A transversion in the first nucleotide at codon 79, designated Pro79Thr mutation in the FKHL7 gene. CONCLUSION: Considering this novel Pro79Thr mutation together with previously reported findings, it is indicated that the clinical features of Axenfeld-Rieger syndrome may depend on the portion of the FKHL7 gene affected by the mutation, although more case reports are needed to clarify genotype-phenotype correlations of the FKHL7 gene.

Adult↗
PubMed2001

Non-peptidic inhibitors of human chymase. Synthesis, structure-activity relationships, and pharmacokinetic profiles of a series of 5-amino-6-oxo-1,6-dihydropyrimidine-containing trifluoromethyl ketones.

Chymase possesses a wide variety of actions, including promotion of angiotensin II production and histamine release from mast cells. However, due to a lack of effective inhibitors featuring both high inhibitory activity and high metabolic stability, the pathophysiological role of chymase has not been fully elucidated. We designed non-peptidic inhibitors based on the predicted binding mode of the peptidic chymase inhibitor Val-Pro-Phe-CF3 and demonstrated that the Val-Pro unit is replaceable with a (5-amino-6-oxo-2-phenyl-1,6-dihydro-1-pyrimidinyl)acetyl moiety. Structure-activity relationship studies revealed that phenyl substitution at the 2-position of the pyrimidinone ring is indispensable for high activity. The most potent compound 1h (Ki = 0.0506 microM) is superior in potency to the parent peptidic inhibitor Val-Pro-Phe-CF3 and has good selectivity for chymase over other proteases. The related analogue 1e was orally absorbed and maintained high plasma levels for at least 2h. These results suggest that the derivatives reported here could be developed as agents for treatment of chymase-induced disease.

Animals↗
PubMed2001

In vitro absorption and metabolism of nobiletin, a chemopreventive polymethoxyflavonoid in citrus fruits.

The polymethoxyflavonoid (PMF), nobiletin (NOB), specifically occurs in citrus fruits, and is currently believed to be a promising anti-inflammatory and antitumor promoting agent. In the present study, we investigated the in vitro absorption and metabolism of NOB and compared them with those of the polyhydroxyflavonoid (PHF), luteolin (LT). NOB preferentially accumulated in a differentiated Caco-2 cell monolayer, which is a model for small intestinal epithelial cells, while LT did not. Treatment of NOB with a rat liver S-9 mixture led to the formation of 3'-demethyl-NOB, while that of LT did not. We thus suggest that PMFs including NOB have properties distinct from those of general flavonoids for absorption and metabolism in vitro.

Animals↗
PubMed2001

Synthesis of southern (C1'-C11') and eastern (C8-C18) fragments of pamamycin-607, an aerial mycelium-inducing substance of Streptomyces alboniger.

Synthesis of the southern C1'-C11' and eastern C8-C18 fragments of pamamycin-607, an aerial mycelium-inducing substance of Streptomyces alboniger, was achieved. The southern fragment was synthesized by using the Evans aldol reaction and cis-selective iodoetherification as the key steps in a 9.6% overall yield (7 steps). The eastern fragment was constructed via the Julia coupling reaction and cis-selective iodoetherification in a 3.0% overall yield (8 steps from the known epoxide).

Furans↗
PubMed2001

The cycle of the seminiferous epithelium in the greater Japanese shrew mole, Urotrichus talpoides.

Spermatogenesis and acrosomal formation in the greater Japanese shrew mole, Urotrichus talpoides, were studied by light microscopy. On the basis of acrosomal changes, morphology of spermatid head, nuclear shape, appearance of meiotic figures, location of spermatid and period of spermiation, the cycle of the seminiferous epithelium was classified into 12 stages, and developing spermatids could be divided into 15 steps. The mean relative frequencies of stages from I to XII were 10.9, 8.7, 9.8, 7.3, 8.5, 10.3, 12.5, 8.7, 5.8, 5.4, 5.1 and 7.1%, respectively. Similar to the case in the musk shrew, the spermatid nucleus of the greater Japanese shrew mole remained in the middle region of the seminiferous epithelium and only the acrosome extended towards the basement membrane. The elongation of the acrosome, however, was not prominent. The proacrosomal vesicle first appeared in stage II and then one large and round granule was seen in stage III. The acrosomal vesicle became flattened on the surface of the nucleus in stage IV. Spreading of the acrosomic system has been recognized from stage VII. In stage VII, spermiation occurred. In stage IX, the spermatid nucleus began to elongate. Elongation and condensation of the nucleus were clearly observed in stage X. In stage XII, pachytene spermatocytes divided into diplotene spermatocytes. In stage XII, meiotic figures and secondary spermatocytes were observed.

Acrosome↗
PubMed2001

Chronic subdural hematoma with vasogenic edema in the cerebral hemisphere--case report.

An 80-year-old male with a history of hypertension presented with chronic subdural hematoma manifesting as progressive consciousness disturbance and left hemiparesis. T1-weighted and fluid attenuation inversion recovery (FLAIR) magnetic resonance imaging showed a fresh hematoma in the right subdural space with a midline shift of 15 mm. FLAIR and diffusion-weighted imaging showed a hyperintense area in the right paraventricular white matter compressed by the hematoma. Apparent diffusion coefficients (ADCs) corresponding to the hyperintense area in the central area of the affected cerebral hemisphere on FLAIR images were measured before and one month after the operation. The motion probing gradient was applied in the right-left direction to the body axis. Since the central area in the cerebrum includes nerve fibers perpendicular to the direction of the gradient, the measured ADC appeared to be anisotropic. Preoperative ADC in the right paraventricular white matter was anisotropic and greater than in age-matched normal subjects, so the edema was identified as the vasogenic type. The edema in the right paraventricular white matter resolved promptly with improvement of the midline shift and normalization of the ADC.

Aged↗
PubMed2001

Successful treatment of a ruptured enlarged infundibular widening of the posterior communicating artery--case report.

A 67-year-old female with a history of hypertension and cerebral infarction presented with subarachnoid hemorrhage (SAH) (Hunt and Kosnik grade 4). Brain computed tomography (CT) revealed a clot dominantly on the right (Fisher's classification Group 4). Cerebral angiography showed funnel-shaped widenings at the origins of the bilateral posterior communicating arteries. The maximum diameter of the widening was greater than 3 mm, so this widening was called an enlarged infundibular widening. Angiography showed a small bulge protruding posterolaterally from the wall of the right enlarged infundibular widening, and the right posterior communicating artery arose from the apex of the enlarged infundibular widening. Based on the findings of the brain CT and cerebral angiography, the diagnosis was SAH due to rupture of the right enlarged infundibular widening. Approximately 12 hours after the onset, the clot was evacuated through the right pterional approach. Bleeding from the small bulge of the right enlarged infundibular widening occurred intraoperatively, so a right-angled ring clip was applied parallel to the right internal carotid artery to obliterate the rupture point. Postoperatively, she was discharged without neurological deficit, and follow-up CT showed no other new infarction. We recommend clipping rather than wrapping or coating for similar cases of ruptured enlarged infundibular widening.

Aged↗
PubMed2001

Cryptococcal meningoencephalitis presenting with an unusual magnetic resonance imaging appearance--case report.

A 61-year-old female with a past history of gastric cancer presented with altered mental status, a few seizures, and low-grade fever. Lumbar puncture revealed elevated cerebrospinal fluid (CSF) pressure, lymphocytic pleocytosis, elevated protein level, remarkably decreased glucose level, and presence of cryptococcal antigen. Cryptococcus neoformans was identified by India ink staining and culture of CSF. The patient was given antifungal agents intravenously and intrathecally. CSF findings improved and C. neoformans could not be detected in CSF one month after the onset. Cerebral sulcal hyperintensity was identified in the bilateral frontal and parietal lobes on fluid-attenuated inversion recovery (FLAIR) magnetic resonance (MR) imaging one month after the onset, but no leptomeningeal enhancement was detected in the affected sulci on T1-weighted MR imaging. The sulcal hyperintensity on FLAIR imaging developed in the bilateral temporal and occipital lobes 2 months after the onset. CSF findings obtained by lumbar puncture were within the normal range except for pressure. However, neurological deterioration and reconfirmation of C. neoformans in CSF indicated recurrent cryptococcal inflammation. The sulcal hyperintensity on FLAIR imaging may indicate a high CSF protein concentration in the subarachnoid space. Such cerebral sulcal hyperintensity is an unusual MR imaging finding of cryptococcal meningoencephalitis, and may be an early sign of procrastinating process or recurrent inflammation even if the findings of CSF obtained by lumbar puncture are normal.

Diagnosis, Differential↗
PubMed2001

[A case of cerebral venous thrombosis with reversible brain parenchymal lesions: usefulness of diffusion weighted imaging and measurement of apparent diffusion coefficient].

A 47-year-old man with a history of thrombophlebitis of his left leg for several years presented with a mild left hemiparesis and ipsilateral hypesthesia. Magnetic resonance imaging showed subacute thrombosis of the superior sagittal sinus and a cortical vein of the right cerebral hemisphere. A linear hyperintense area was found in the white matter of the right postcentral gyrus on T 2- and diffusion weighted axial imagings on the 7 days after the onset. The patient was treated conservatively, and his clinical course was uneventful. His neurological dysfunctions recovered within approximately three weeks after the onset. The white matter lesion in the right postcentral gyrus also disappeared one month later. The apparent diffusion coefficients (ADCs) in the white matter of the pre- and postcentral gyrus were measured bilaterally on the ADC mapping imaging. In the subacute stage, the ADC values in the white matter of the right pre- and postcentral gyrus were 0.50 x 10(-3) mm2/sec and 0.91 x 10(-3) mm2/sec, respectively. The %ADC indicating the ratio of ADC value of the lesion to that of the contralateral brain tissue was calculated. The %ADCs in the white matter of the pre- and postcentral gyrus were 64.9% and 124.5% respectively. In the chronic stage, the ADC values in the white matter of the right pre- and postcentral gyrus were 0.96 x 10(-3) mm2/sec and 0.99 x 10(-3) mm2/sec, and the %ADCs improved to 106.7% and 106.5% respectively. The lesions in the white matter of the right pre- and postcentral gyrus were reversible. The former was thought to be mainly ascribed to cellular edema and the latter was vasogenic edema. The present case showed when %ADC of the ischemic lesion in cerebral venous thrombosis was higher than 60%-70%, conservative therapy alone is sufficient effective for the improvement of neurological deficits.

Cerebral Veins↗
PubMed2001

[A high aged case of herpes simplex viral encephalitis associated with progressive cerebral white matter lesion].

An 80-year-old male without abnormal past medical history presented with coma, general seizures, and fever subsequent to abnormal behavior. The pressure of the cerebrospinal fluid(CSF) elevated(13.5-20.5 cm H2O), and CSF examination revealed pleocytosis with predominant mononuclear cells(80-879/mm3) and elevated protein level(32-130 mg/dl). DNAs of herpes simplex virus(HSV) type 1 and 2 in CSF were not confirmed by polymerase chain reaction method in the acute phase. The HSV(type 1) antibody(HSV-1 Ab) ratio of serum to CSF(= [serum HSV-1 Ab]/[CSF HSV-1 Ab]) was 0.98 and HSV-1 Ab index(= [CSF HSV-1 Ab]/[serum HSV-1 Ab] divided by [CSF albumin]/[serum albumin]) was 62.4. Initial fluid attenuated inversion recovery(FLAIR) (TR/TE/TI = 6,882/110/1,700 msec) axial magnetic resonance(MR) imaging showed hyperintensity in the subfrontal area, inferomedial portions of the temporal lobes, cingulate gyri, and insular cortices bilaterally. Meningoencephalitis caused by HSV-1 was diagnosed based on the values of HSV-1 Ab ratio of serum to CSF(less than 20), of HSV-1 Ab index(larger than 1.91), and the findings of MR imaging. Diffuse white matter lesions manifesting hyperintensity on FLAIR imaging in the bilateral frontal and temporal lobes close to the affected cortices developed approximately six weeks after the onset despite administration of antiviral agent and steroid. The lesion extensively involved the white matter of the bilateral frontal and temporal lobes finally. The initial value of myelin basic protein(MBP) in CSF was 0.9 ng/ml (normal value: less than 4 ng/ml). Subsequent measurement of MBP in CSF about two, six weeks, two, three, and six months after the onset showed a marked increase of 233.9 ng/ml followed by a gradual decrease of 25.4 ng/ml, 18.4 ng/ml, 7.4 ng/ml and 4.3 ng/ml, respectively. Therefore, demyelination of the lesion in the cerebral white matter was suggested by the chronological change in FLAIR imaging and MBP in CSF.

Aged↗
PubMed2000

Seasonal changes in the hypothalamo-pituitary-testes axis of the Japanese wood mouse (Apodemus speciosus).

Seasonal changes in the hypothalamo-pituitary-testes axis of the Japanese wood mice (Apodemus speciosus) were studied. The testes, epididymis, pituitary and hypothalamus were compared between mice in the breeding season (July) and non-breeding season (October) using morphological techniques, and the plasma testosterone level was evaluated by enzyme immunoassay. Significant differences in these tissues were observed between the breeding season and the non-breeding season. Specifically, differences in the non-breeding season included 1) a decline in testicular and epididymal weights, arrest of spermatogenesis and decrease of serum testosterone concentration; 2) a decrease in the number of luteinizing hormone (LH)-, follicle stimulating hormone (FSH)-, prolactin (PRL)-, and growth hormone (GH)-immunoreactive cells, and decrease in the size of FSH, PRL, and GH-immunoreactive cells; and 3) an increase in the size of gonadotropin-releasing hormone (GnRH)-immunoreactive neurons. Our findings indicate that the male adult Japanese wood mouse exhibits unique seasonal changes in the hypothalamo-pituitary-testes axis which are not found in laboratory mice.

Animals↗
PubMed2000

Inhibitory effect of citrus nobiletin on phorbol ester-induced skin inflammation, oxidative stress, and tumor promotion in mice.

The intake of citrus fruits has been suggested as a way to prevent the development of some types of human cancer. Nitric oxide (NO) is closely associated with the processes of epithelial carcinogenesis. We attempted a search for NO generation inhibitors in Citrus unshiu. The active constituent was traced by an activity-guiding separation. NO and superoxide (O2-) generation was induced by a combination of lipopolysaccharide and IFN-gamma in mouse macrophage RAW 264.7 cells, and by 12-O-tetradecanoylphorbol-13-acetate (TPA) in differentiated human promyelocyte HL-60, respectively. Expression of inducible NO synthase and cyclooxygenase 2 proteins were detected by Western blotting. The in vivo anti-inflammatory and antitumor promoting activities were evaluated by topical TPA application to ICR mouse skin with measurement of edema formation, epidermal thickness, leukocyte infiltration, hydrogen peroxide production, and the rate of proliferating cell nuclear antigen-stained cells. As a result, nobiletin, a polymethoxyflavonoid, was identified as an inhibitor of both NO and O2- generation. Nobiletin significantly inhibited two distinct stages of skin inflammation induced by double TPA application [first stage priming (leukocyte infiltration) and second stage activation (oxidative insult by leukocytes)] by decreasing the inflammatory parameters. It also suppressed the expression of cyclooxygenase-2 and inducible NO synthase proteins and prostaglandin E2 release. Nobiletin inhibited dimethylbenz[a]anthracene (0.19 micromol)/TPA (1.6 nmol)-induced skin tumor formation at doses of 160 and 320 nmol by reducing the number of tumors per mouse by 61.2% (P < 0.001) and 75.7% (P < 0.001), respectively. The present study suggests that nobiletin is a functionally novel and possible chemopreventive agent in inflammation-associated tumorigenesis.

Animals↗
PubMed2000

In vitro activities of a new lipopeptide antifungal agent, FK463, against a variety of clinically important fungi.

The in vitro antifungal activity and spectrum of FK463 were compared with those of amphotericin B, fluconazole, and itraconazole by using a broth microdilution method specified by National Committee for Clinical Laboratory Standards document M27-A (National Committee for Clinical Laboratory Standards, Wayne, Pa., 1997). FK463 exhibited broad-spectrum activity against clinically important pathogens including Candida species (MIC range, <==0.0039 to 2 microg/ml) and Aspergillus species (MIC range, <==0.0039 to 0.0313 microg/ml), and its MICs for such fungi were lower than those of the other antifungal agents tested. FK463 was also potently active against azole-resistant Candida albicans as well as azole-susceptible strains, and there was no cross-resistance with azoles. FK463 showed fungicidal activity against C. albicans, i.e., a 99% reduction in viability after a 24-h exposure at concentrations above 0.0156 microg/ml. The minimum fungicidal concentration (MFC) assays indicated that FK463 was fungicidal against most isolates of Candida species. In contrast, the MFCs of FK463 for A. fumigatus isolates were much higher than the MICs, indicating that its action is fungistatic against this species. FK463 had no activity against Cryptococcus neoformans, Trichosporon species, or Fusarium solani. Neither the test medium (kind and pH) nor the inoculum size greatly affected the MICs of FK463, while the addition of 4% human serum albumin increased the MICs for Candida species and A. fumigatus more than 32 times. Results from preclinical in vitro evaluations performed thus far indicate that FK463 should be a potent parenteral antifungal agent.

Antifungal Agents↗