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Biomedical subjects

H Oikawa

Publications and source records attributed to H Oikawa.

At least 19 recordsLinked to original sources
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

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↗
PubMed2000

Macrophomate synthase: characterization, sequence, and expression in Escherichia coli of the novel enzyme catalyzing unusual multistep transformation of 2-pyrones to benzoates.

Macrophoma commelinae isolated from spots on leaves of Commelina communis has the ability to transform 5-acetyl-4-methoxy-6-methyl-2-pyrone (1) to 4-acetyl-3-methoxy-5-methylbenzoic acid (macrophomic acid, 2). This biotransformation includes the condensation of the 2-pyrone ring with a C3-unit precursor to form a substituted benzoic acid. We optimized conditions for induction of enzyme activity in M. commelinae, identified oxalacetate as a C3-unit precursor with cell extract, and purified the novel enzyme, macrophomate synthase. Oxalacetate inhibited the enzyme activity at a concentration higher than 5 mM, and magnesium chloride stimulated the enzyme activity. Kinetic analyses gave K(m) of 1.7 mM for 1 at 5 mM oxalacetate, K(m) of 1.2 mM for oxalacetate at 5 mM 1, and k(cat) of 0.46 s(-1) per subunit. Pyruvate was a weak substrate, with K(m) of 35.2 mM and k(cat) of 0.027 s(-1) at 5 mM 1. We cloned and sequenced a cDNA encoding the macrophomate synthase. The cDNA of 1,225 bp contained an open reading frame that encoded a polypeptide of 339 amino acid residues and 36,244 Da, the sequence of which showed no significant similarity with known proteins in a homology search with BLAST programs. Transformed E. coli cells carrying the cDNA encoding the mature protein of macrophomate synthase overproduced macrophomate synthase under the control of the T7 phage promoter induced by IPTG. The purified enzyme showed the same values of K(m) and optimum pH as the native macrophomate synthase.

Amino Acid Sequence↗
PubMed2000

Potent inhibition of macrophomate synthase by reaction intermediate analogs.

Potent inhibitors for macrophomate synthase, which has recently been found to catalyze a highly unusual five-step chemical transformation, were explored. Among 11 oxalacetate analogs tested, only three analogs had moderate to relatively strong inhibitory activities (I50 1.3-8.1 mM). On the other hand, among 35 bicyclic intermediate analogs synthesized, two diacids were found to be the most potent inhibitors (I50 0.80, 0.84 mM) which had a much higher affinity than that of the natural substrate 2-pyrone. (-)-Enantiomers of the diacids showed 30 times stronger activity (I50 0.34, 0.41 mM) than (+)-ones. The I50/Km values (0.20, 0.24) showed their potent inhibitions. Competitive inhibitions were observed in two representative inhibitors.

Binding, Competitive↗
PubMed2000

Substrate diversity of macrophomate synthase catalyzing an unusual multistep transformation from 2-pyrones to benzoates.

Macrophomate synthase, which we have recently purified, catalyzes an unusual multistep transformation from 5-acetyl-4-methoxy-6-methyl-2-pyrone to 4-acetyl-3-methoxy-5-methyl-benzoic acid (macrophomic acid). To investigate the substrate diversity of the enzyme, 40 analogs of 2-pyrone were prepared and their relative efficiency was examined in the enzymatic conversions. The experimental results reveal the structural requirements of the substrates and the rough size of the enzyme active site, and eliminate the ambiguity caused by contamination by other enzymes in the whole-cell experiments.

Benzoates↗
PubMed2000

[Intranet-based integrated information system of radiotherapy-related images and diagnostic reports].

PURPOSE: To use an intranet technique to develop an information system that simultaneously supports both diagnostic reports and radiotherapy planning images. METHODS: Using a file server as the gateway a radiation oncology LAN was connected to an already operative RIS LAN. Dose-distribution images were saved in tagged-image-file format by way of a screen dump to the file server. X-ray simulator images and portal images were saved in encapsulated postscript format in the file server and automatically converted to portable document format. The files on the file server were automatically registered to the Web server by the search engine and were available for searching and browsing using the Web browser. RESULTS: It took less than a minute to register planning images. For clients, searching and browsing the file took less than 3 seconds. Over 150,000 reports and 4,000 images from a six-month period were accessible. Because the intranet technique was used, construction and maintenance was completed without specialty. CONCLUSION: Prompt access to essential information about radiotherapy has been made possible by this system. It promotes public access to radiotherapy planning that may improve the quality of treatment.

Computer Communication Networks↗
PubMed2000

Focal nodular hyperplasia of the liver: direct evidence of circulatory disturbances.

Focal nodular hyperplasia of the liver is a lesion characterized by a well-circumscribed region of hyperplastic liver parenchyma and contains a stellate fibrous scar. The lesion is thought to be because of liver-cell hyperplasia that is caused by focal circulatory disturbances. We describe here a pediatric case of this lesion that provided direct histopathologic evidence of circulatory disturbances. We identified arterial and portal thrombi, as well as recanalization of arteries in the nodule. Hepatic necrosis was also seen in the lesion. We speculate that thrombosis of the hepatic artery and/or portal vein was the cause of hepatic necrosis and that reperfusion following hepatic arterial recanalization resulted in nodule formation. Although there was no stellate scar present in our case, the presence of bile ductular proliferation at the periphery of the nodule was helpful in distinguishing this lesion from adenoma and hepatocellular carcinoma. The early stage of nodular formation may explain the lack of a stellate scar in our case. The patient was treated earlier with actinomycin D and vincristine following surgical excision of Wilms' tumor. It is possible that such chemotherapy contributed to thrombosis in our case.

Antineoplastic Agents↗
PubMed1999

The spiroketals containing a benzyloxymethyl moiety at C8 position showed the most potent apoptosis-inducing activity.

The spiroketals containing a benzyloxymethyl moiety at the C8 position showed the most potent apoptosis-inducing activity, whereas its analogous compounds lacking any substituent at C8 or possessing ones other than the benzyloxymethyl moiety at C8 were all much less active. These results strongly suggest an important role of the benzyloxymethyl moiety linked to the C8 oxygen atom.

Apoptosis↗