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Biomedical subjects

H Oikawa

Publications and source records attributed to H Oikawa.

At least 19 recordsLinked to original sources
PubMed2004

Prevention of critical telomere shortening by oestradiol in human normal hepatic cultured cells and carbon tetrachloride induced rat liver fibrosis.

BACKGROUND AND AIM: Significant telomere shortening of hepatocytes is associated with replicative senescence and a non-dividing state in chronic liver disease, resulting in end stage liver failure and/or development of hepatocellular carcinoma. To prevent critical telomere shortening in hepatocytes, we have focused on oestrogen dependent transactivation of the human telomerase reverse transcriptase (hTERT) gene as a form of telomerase therapy in chronic liver disease. METHODS: We examined expression of hTERT mRNA and its protein, and telomerase activity (TA) in three human normal hepatic cell lines (Hc-cells, h-Nheps, and WRL-68) before and after treatment with 17beta-oestradiol. The effects of exogenous oestradiol administration were examined in a carbon tetrachloride (CCl(4)) induced model of liver fibrosis in rats. RESULTS: Expression of hTERT mRNA and its protein was upregulated by oestradiol treatment. Telomere length decreased in Hc-cells and h-Nheps with accumulated passages whereas with long term oestradiol exposure it was greater than without oestradiol. The incidence of beta-galactosidase positive cells, indicating a state of senescence, decreased significantly in oestradiol treated cells in comparison with non-treated cells (p<0.05). TA in both male and female rats with CCl(4) induced liver fibrosis was significantly higher with oestradiol administration than without (p<0.05). Long term oestradiol administration markedly rescued the hepatic telomere from extensive shortening in both male and female rats. CONCLUSION: These results suggest that oestradiol acts as a positive modulator of the hTERT gene in the liver. Oestrogen dependent transactivation of the hTERT gene is a new strategy for slowing the progression of chronic liver disease.

Animals↗
PubMed2004

Genetic analysis of crown size in the first molars using SMXA recombinant inbred mouse strains.

Tooth crown size may be determined by both genetic and environmental factors. The aim of this study was to identify quantitative trait loci (QTLs) affecting dental crown size and determine whether there is genetic independence between upper and lower teeth, using SMXA recombinant inbred strains of mice. Mesiodistal and buccolingual crown diameters (MD and BL, respectively) of the upper and lower first molars (M(1) and M(1), respectively) were measured. For each trait, mean values of substrains showed a continuous spectrum of distribution. Genome-wide scan detected QTLs exceeding suggestive threshold levels for MD of M(1) (chromosomes 7, 13, and 17), BL of M(1) (chromosomes 8 and 13), MD of M(1) (chromosomes 7 and 13), and BL of M(1) (chromosomes 3 and 15). These findings suggest that tooth crown size is controlled by multiple genes, and that there is some independence of genetic control between M(1) and M(1).

Animals↗
PubMed2002

Synthesis of specific protein phosphatase inhibitors, tautomycin and tautomycetin toward structure-activity relationship study.

The recent progress in synthetic and SAR studies of the specific protein phosphatase inhibitors tautomycin and tautomycetin is reviewed. This article covers the total synthesis of tautomycin and synthetic studies of the spiroketal and the anhydride segments and tautomycetin, and SAR studies on PP inhibition and apoptosis-inducing activity of tautomycin.

Antifungal Agents↗
PubMed2001

Tautomycetin is a novel and specific inhibitor of serine/threonine protein phosphatase type 1, PP1.

Here we isolated tautomycetin, TC, and examined its phosphatase inhibitory activity. Recently we have reported that the left-hand moiety of tautomycin, TM, and the right one containing the spiroketal are essentially required for inhibition of protein phosphatase, PP, and induction of apoptosis, respectively. TC is structurally almost identical to TM except that TC is lacking the spiroketal, which has the potential apoptosis-inducing activity. TC specifically inhibited PP1 activity, IC50 values for purified PP1 and PP2A enzymes being 1.6 and 62 nM, respectively, whereas the IC50 values of TM were 0.21 and 0.94 nM, respectively. These results demonstrate that TC is the most specific PP1 inhibitor out of over 40 species of natural phosphatase inhibitors reported, strongly suggesting that TC is a novel powerful tool to elucidate the physiological roles of PP1 in various biological events.

Animals↗
PubMed2001

Disorganised unilateral cerebellar folia: a mild form of cerebellar cortical dysplasia?

We describe MRI findings in two patients with disorganised foliation of one cerebellar hemisphere, with folia running vertically rather than horizontally. The thickness of individual folia and corticomedullary interdigitations were normal. These patients have no cerebellar neurological deficit. This rare abnormality is probably a maldevelopment of the hemispheric part of the posterior lobe of the developing cerebellum, and no clinical significance can be elicited.

Adult↗
PubMed2001

The circuit of Papez in mesial temporal sclerosis: MRI.

We looked at abnormalities in the circuit of Papez in patients with the mesial temporal sclerosis (MTS). We reviewed the MRI studies of 15 patients with probable MTS, seeking changes in the fornix, mamillary body, mamillothalamic tract, thalamus and cingulate and parahippocampal gyri. We correlated any abnormalities with each other and with clinical severity. Atrophy and/or signal change in one or more structures in the circuit of Papez were found in five patients. They involved the parahippocampal gyri in all five, the fornices in four, mamillary bodies in three, the thalamus in two and the cingulate gyrus in one. Changes in the fornix, mamillary body, thalamus or cingulate gyrus were always accompanied by hippocampal and parahippocampal atrophy. The patients with abnormalities of the circuit of Papez did not have more severe epilepsy than those without. Changes in the parahippocampal gyrus, including the entorhinal cortex and subiculum, in which forniceal fibres originate, may be crucial in causing abnormalities more distally in the circuit.

Adolescent↗
PubMed2001

Total synthesis of (+)-albicanol and (+)-albicanyl acetate.

The drimane sesquiterpenes, (+)-albicanol (2) and (+)-albicanyl acetate (3), were synthesized from an optically active bicyclic diol [(+)-1] that had been obtained via the recently developed optical resolution of a general synthetic intermediate for drimane sesquiterpenes. The crucial step in the previous syntheses was markedly improved by the modified Wittig methylenation of a silyloxy ketone (7). The high overall yield (77% in 4 or 5 steps from (+)-1) by this total synthesis makes it possible to synthesize the other biologically active drimane sesquiterpenes.

Ketones↗
PubMed2001

NMR determination of the absolute configuration of a macrophomate synthase inhibitor by using an axial chiral reagent.

Macrophomate synthase catalyzes an extraordinary four-step transformation from oxalacetate and 2-pyrone to macrophomic acid by an intermolecular Diels-Alder reaction. The absolute configuration of the most potent macrophomate synthase inhibitor; (-)-2-carboxylmethyl-1-methoxybicyclo[2.2.2]oct-5-ene-2-carboxylic acid, was determined to be (1S, 2R, 4R) by using an axial chiral reagent.

Carboxylic Acids↗
PubMed2000

Detailed reaction mechanism of macrophomate synthase. Extraordinary enzyme catalyzing five-step transformation from 2-pyrones to benzoates.

Macrophomate synthase from the fungus Macrophoma commelinae IFO 9570 is a Mg(II)-dependent dimeric enzyme that catalyzes an extraordinary, complex five-step chemical transformation from 2-pyrone and oxalacetate to benzoate involving decarboxylation, C-C bond formation, and dehydration. The catalytic mechanism of the whole pathway was investigated in three separate chemical steps. In the first decarboxylation step, the enzyme loses oxalacetate decarboxylation activity upon incubation with EDTA. Activity is fully restored by addition of Mg(II) and is not restored with other divalent metal cations. The dissociation constant of 0.93 x 10(-)(7) for Mg(II) and atomic absorption analysis established a 1:1 stoichiometric complex. Inhibition of pyruvate formation with 2-pyrone revealed that the actual product in the first step is a pyruvate enolate, which undergoes C-C bond formation in the presence of 2-pyrone. Incubation of substrate analogs provided aberrant adducts that were produced via C-C bond formation and rearrangement. This strongly indicates that the second step is two C-C bond formations, affording a bicyclic intermediate. Based on the stereospecificity, involvement of a Diels-Alder reaction at the second step is proposed. Incubation of the stereospecifically deuterium-labeled malate with 2-pyrones in the presence of malate dehydrogenase provided information for the stereochemical course of the reaction catalyzed by macrophomate synthase, indicating that the first decarboxylation provides pyruvate (Z)-[3-(2)H]enolate and that dehydration at the final step occurs with anti-elimination accompanied by concomitant decarboxylation. Examination of kinetic parameters in the individual steps suggests that the third step is the rate-determining step of the overall transformation.

Benzoates↗
PubMed2000

The correlation between spontaneous and radiation-induced apoptosis in T3B bladder cancer (histological grade G3), and the precedence between the two kinds of apoptosis for predicting clinical prognosis.

PURPOSE: The correlation between the frequency of spontaneous and radiation-induced apoptosis, and the precedence between those for predicting prognosis were studied at clinical level. METHODS AND MATERIALS: Twenty-one patients (mean age, 65.8 years; 16 men and 5 women) with bladder cancer (transitional cell carcinoma Grade 3, T3bN0M0, Stage IIIb) underwent intraoperative radiotherapy: single 30-Gy 12-MV electron beam irradiation to bladder, followed by total cystectomy 6 h after irradiation. The specimens of pretreatment and irradiated bladder cancer were assayed for apoptosis, using TUNEL staining with counter staining of hematoxylin. The apoptotic index (AI) was calculated by dividing the number of apoptotic cells by the total number of cells and multiplying by 100. The Pearson's linear fitting was used to test the correlation between spontaneous and radiation-induced apoptosis. The Kaplan-Meier product-limit estimation was used for overall survival (OS) and freedom from recurrence (FFR). The precedence between spontaneous and radiation-induced apoptosis for predicting the clinical prognosis was estimated using the proportional hazard regression. RESULTS: The mean AI of spontaneous and radiation-induced apoptosis was 1.18 +/- 0.16 and 2.63 +/- 0.45, respectively, which was significantly different. There was strong correlation between spontaneous and radiation-induced apoptosis (r(2) = 0.864, adjusted r(2) = 0.857). Radiation-induced apoptosis was estimated by equation: y (radiation-induced apoptosis) = 2.67 x (spontaneous apoptosis) -0.52. However, the proportional hazard regression test indicated that only spontaneous apoptosis was significant for predicting OS and FFR (&z.sfnc;t&z.sfnc; > 0.2), but radiation-induced apoptosis was not. CONCLUSION: Estimating AI in radiation-induced apoptosis from AI in spontaneous apoptosis is possible. However, spontaneous apoptosis is more accurate in predicting clinical prognosis.

Aged↗
PubMed2000

Quantitative analysis of pulmonary neuroendocrine cell distribution of the fetal small airways using double-labeled immunohistochemistry.

Pulmonary neuroendocrine cells (PNECs) are supposed to play an essential role in development of fetal lung and neonatal respiratory adaptation. Some previous studies have suggested the close relation between PNECs and sudden infant death syndrome (SIDS). To investigate how PNECs distribute to the thermal bronchioli of fetal lung may be a clue to clarify this relation. Since it is difficult to distinguish bronchiole from alveolus in fetal lung, we performed double immunostaining with antibody against chromogranin A (CGA) and alpha-smooth muscle actin (SMA) which can make clear distinction between them. In this study, formalin-fixed, paraffin-embedded lung tissues from 18 autopsy cases from 16 to 28 weeks of gestation were assessed. CGA immunopositive cells were counted and the length of basement membranes of terminal bronchioli was measured with computed image analyzer. Density of PNECs was expressed as the number of immunopositive cells per millimeter of basement membrane. Terminal bronchiole stained with SMA was clearly distinguished from alveolus at 16 weeks. With gestational age, CGA immunopositive PNECs were gradually increased in 2 folds by the 25th week. After that, their density wasn't changed significantly until termination. It is suggested that PNECs in terminal bronchiole was playing an important role in morphogenesis of alveolar ducts and alveolar sacks.

Actins↗
PubMed2000

Pulmonary neuroendocrine cell distribution in sudden infant death syndrome.

The density of pulmonary neuroendocrine cells (PNECs) in 21 sudden infant death syndrome (SIDS) cases, 19 controls, and 25 fetuses was studied morphometrically. Formalin-fixed, paraffin-embedded lung samples were immunostained with antibody against chromogranin A (CGA). The percentage of PNEC-positive airways and the density of PNECs in each airway were calculated in all cases. The density of PNECs was expressed as the number of cells per millimeter of basement membrane. The percentage of PNEC-positive airways reached nearly 100% by term and did not change significantly until 12 months of age in both the SIDS cases and the controls. The density of PNECs also showed a rapid increase in the saccular stage fetus and had its peak of about 4 cells/mm around birth. The density of PNECs, including the standard deviation, was higher in SIDS cases than in controls. The uneven distribution of PNECs may affect respiratory control in SIDS victims.

Journal Article↗
PubMed2000

Patterns and mechanisms of pedestrian injuries induced by vehicles with flat-front shape.

To clarify the difference between flat-front vehicles and bonnet-front vehicles with regard to the patterns and mechanisms of vehicle-induced pedestrian injuries, we investigated 101 cases of pedestrians who were struck by the front of a vehicle. There were 33 flat-front vehicle collision cases and 68 bonnet-front vehicle collision cases. The frequency of chest injuries in flat-front vehicle collisions (30.3%) was significantly higher than that in bonnet-front vehicle collisions (11.8%). Lower leg fractures were more common in bonnet-front vehicle collisions than in flat-front vehicle collisions. Although head injuries were common in both cases, the mechanisms of these injuries differed. The pedestrians who were struck by flat-front vehicles tended to sustain more severe injuries at lower impact speeds. All of these results stem from the difference in the front shape of the two types of vehicle. Pedestrians who are struck by the front of flat-front vehicles receive the impact force to the trunk, particularly the chest, at the initial impact and are thrown out forward after the impact, because the front of these vehicles is perpendicular to the road.

Journal Article↗
PubMed2000

Photosynthetic production of microalgal biomass in a raceway system under greenhouse conditions in Sendai city.

The photosynthetic productivities of the marine microalgae Chlorophyta sp. and freshwater microalgae Chlorella sp. were investigated in a raceway system under greenhouse conditions in Sendai city. The system was constructed with a surface area of 0.986 m2 and equipped with paddle wheels (8 fins). The semicontinuous batch culture experiment was carried out for 4 months from June to October 1998 in Sendai city. The productivity of Chlorophyta sp. was ranged from 4 to 13 g.m(-2).d(-1) and the average was 8.2 g.m(-2).d(-1), which corresponded to the photosynthetic efficiency of 4.15% (PAR). The productivity of Chlorella sp. was ranged from 7 to 21 g.m(-2).d(-1) and the average was 13.2 g.m(-2).d(-1), which corresponded to the photosynthetic efficiency of 6.56% (PAR). These results indicate that stable microalgal cultivation with comparatively high photosynthetic efficiency could be obtained in a raceway system under greenhouse conditions in Sendai city located in the northern part of Japan.

Journal Article↗
PubMed2000

Intracranial low-grade chondrosarcoma with hyperostosis of the skull: a case report.

We describe a case of intracranial chondrosarcoma in a 46-year-old woman. The preoperative diagnosis was meningioma as plain radiography and computed tomography of the head revealed a tumor with discrete calcifications predominantly in the right frontoparietal region and hyperostosis of the inner table of the skull overlying the tumor. However, the tumor was histologically composed of cartilaginous tissue without meningiomatous differentiation and the final diagnosis was a low-grade chondrosarcoma based on its histological appearance and size, together with the radiologic images. Intracranial chondrosarcoma occurring above the skull base is extremely rare and 19 cases were found in our literature review. Intracranial chondrosarcoma showing hyperostosis of the skull has not been reported in the cases. The discussion includes its differential diagnosis, origin, and clinical behavior.

Chondrosarcoma↗