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Biomedical subjects

T Ohtsuka

Publications and source records attributed to T Ohtsuka.

At least 235 records · Page 13Linked to original sources

A new series of natural antifungals that inhibit P450 lanosterol C-14 demethylase. I. Taxonomy, fermentation, isolation and structural elucidation.

A new series of antifungal antibiotics, Ro 09-1470 and its 6 congeners were isolated from the fermentation broth of Penicillium sp. NR6564. Their structures were determined as tetrahydropyran derivatives with an alkenyl side chain on the basis of their spectroscopic and physico-chemical properties. Among these compounds, Ro 09-1470 and Ro 09-1545 possessing a glycyl N-substituted glycyl ester residue had high antifungal activity. Ro 09-1469, one of the congeners, was found in the fermentation broth of several strains of Aspergillus sclerotiorum Huber.

Antifungal Agents↗

[Resection of a mediastinal teratoma that perforated the lung and combined with aspergilloma in the tumor cyst].

We hereby report a rare case of a mature type teratoma that perforated the lung and combined with aspergilloma in the tumor cyst. The patient was a 48-year-old female, who complained of coughing and sputum. The chest roentogenography and chest CT suggested aspergilloma. The patient was operated upon. From the intraoperative and pathological findings, a mature type mediastinal teratoma was found to have perforated the bronchus and lung, and combined with aspergilloma in the cyst of the tumor. The tumor was resected, the drainage bronchus was closed. The mediastinal teratoma and aspergilloma have not recurred for two years and four months since the operation.

Aspergillosis↗

[MRI findings of moyamoya disease in children].

Magnetic resonance imaging (MRI) findings were evaluated in two cases with moyamoya disease. A twelve-year-old girl and a five-year-old boy were admitted to our hospital with the complaints of transient ischemic attack. They were diagnosed as having moyamoya disease by cerebral angiogram. MRI clearly presented cerebral infarction by T2-weighted imaging and multiple small round or tortuous hypo_signal areas around the basal ganglia by proton density weighted imaging. These findings were consistent with moyamoya vessels shown by cerebral angiogram. Moyamoya vessels were visualized more clearly on proton density weighted imaging than on T1-weighted imaging. MRI is less invasive than cerebral angiogram and repeated safely. It might play an important role in a follow-up study of morphological changes on moyamoya vessels.

Age Factors↗

[Cavernoplasty for pulmonary aspergillosis associated with restrictive ventilatory impairment].

Nine patients were diagnosed as suffering from localized pulmonary aspergillosis associated with restrictive ventilatory impairment. Eight cases reportedly received a combination of thoracoplasty and cavernoplasty, while one case received only cavernoplasty. The following postoperative courses were observed in these nine patients: of the eight patients having combined thoracoplasty and cavernoplasty, seven patients were cured as the result of successful cavity closures. Cavernotomy was required for the remaining patient whose cavity failed to close. An attempt was made to close the cavity of the one patient reported to have only cavernoplasty, but the cavity failed to close on the first attempt. The cavity was successfully closed in a later attempt using thoracoplasty. Although the application of thoracoplasty and cavernoplasty is useful and safe to the treatment of patients being unable to undergo resection and/or having pulmonary dysfunction, it is very important to reduce the number of ribs being resected because pulmonary function may be more worsened after operation. A combination of extraperiosteal detachment and cavernoplasty seems to be a useful alternative. A lower limitation of the postoperative ventilation function, evaluated as a ratio of FEV1.0/VCpr is thought to be 20%.

Adult↗

[A case report of cervical disc hernia presenting fecal incontinence evoked by walking; spinal intermittent rectal dysfunction].

Intermittent clinical manifestations, the representative one of which is claudication, can be classified into two types; neurogenic and vasculogenic. Although cauda equina lesions are well known as a neurogenic cause, spinal disorders, especially cervical or thoracic cord lesions, have been paid more attention to by several authors recently. We encountered a 42-year-old man with cervical soft disc hernia and ossification of longitudinal ligament, who showed intermittent rectal dysfunction evoked by walking. This peculiar clinical manifestation successfully disappeared after surgical decompression of the spinal cord. Such an interesting case has not been reported in the world literature. The patient was admitted because of numbness in both hands. Neurological examinations on admission showed neither motor weakness nor abnormally increased tendon reflex. Hypesthesia and hypalgesia were noticed below the Th4 dermatome on both sides. Adding to those symptoms, he complained of fecal incontinence evoked by walking 100 meters. This rectal dysfunction became gradually worse. At last he showed fecal incontinence after walking only 10 meters. This was ten days after his admission. Myelogram and computed tomographic scan revealed a cervical soft disc hernia at the C5/6 level and findings of OPLL at the C5 and C6 level. Anterior cervical approach for OPLL and soft disc was used for bone graft insertion from the C4 to the C7 vertebral body. The rectal dysfunction completely disappeared after the operation. The possible mechanisms of intermittent rectal dysfunction evoked by walking were discussed.

Adult↗

[Changes in plasma histamine concentrations following food challenges in children with food allergy].

This study was undertaken to determine whether the measurement of plasma histamine concentrations after food challenges provides an additional predictive marker for the diagnosis of food allergy. In 13 patients who were positive to food antigen-specific IgE, 21 oral food challenges were performed. In 5 non-atopic subjects (controls), 5 oral food challenges were performed in the same way. Plasma histamine concentration was measured by RIA before the challenges and 5, 15, 30, 60, 120, 240 min afterwards. Significant rises in plasma histamine concentrations were observed 120 and 240 min after the challenges in the group of patients who were positive to food challenges. The late onset of the plasma histamine elevation suggests that antigenic macromolecules are absorbed from the small intestine and then reach the target tissues where mast cells release histamine. Even in the group of patients who were negative to food challenges, the peak concentration of the plasma histamine in each patient was significantly higher than it was before challenge. No significant change in plasma histamine concentrations was observed after the challenges in the controls. The results confirmed the strong connection between food allergy and the elevation of plasma histamine concentration, and furthermore they implied the existence of allergic reaction in patients who are negative to food challenges as well as in those who are positive to food challenges. Therefore, plasma histamine concentration following food challenges might be useful markers in the detection of food allergy.

Adolescent↗

[Intraparenchymal granulocytic sarcoma in acute monocytic leukemia; case report].

Granulocytic sarcoma of the parenchyma of the brain present in a patient with acute monocytic leukemia, and its unusual course during treatment, is described. Four years after diagnosis of acute monocytic leukemia, a 24-year-old man developed severe headache during its remission period. The CT scan showed large intraparencymal mass in the right frontal lobe, which was partially removed and diagnosed as granulocytic sarcoma. Following the operation, radiation in total dose of 35.5 Gy was given to the whole brain, and there was also left intraventricular administration of methotrexate (MTX) and cytosine arabinoside (ara-C). The treatment resulted in the complete disappearance of the intraparenchymal mass apart from small calcifications. Five months later, the patient redeveloped severe headache with consciousness disturbance. CT scan revealed marked swelling in the left cerebral hemisphere with irregular contrast-enhanced areas. The patient died of brain herniation in spite of conservative therapy. Photomicroscopic findings of the left cerebral hemisphere proved the presence of "disseminated leukoencephalopathy" and the absence of tumor cells. On the other hand, the right frontal lesion consisted of no tumor cells but scar tissues. This unusual feature of the CT scan in the terminal stage might be caused by combination with the effect of highly concentrated MTX in the left cerebral hemisphere because of the increased permeability of the ependym and the relatively high radiosensitivity in the non-affected left cerebral hemisphere.

Adult↗

Stimulation of superoxide anion production in guinea pig polymorphonuclear leukocytes by hypotonic conditions in combination with protein kinase C activators.

Conditions for superoxide anion (O2-) production were examined in guinea pig polymorphonuclear leukocytes (PMNL). When PMNL were suspended in the hypotonic medium, O2- production was significantly enhanced by concurrent treatment with low concentrations of 1-oleoyl-2-acetylglycerol (OAG), a cell-permeable protein kinase C activator. Such hypotonicity or OAG alone had little effect on the production. Other protein kinase C activators also markedly enhanced O2- production in combination with hypotonicity, but not in the isotonic medium. Protein kinase C inhibitors, H-7 and staurosporine, dose-dependently inhibited the production. These observations indicate that protein kinase C participates in such synergistic O2- production with hypotonicity. Phosphorylation of 46-kDa protein(s), which was commonly enhanced in paralleled with an activation of NADPH oxidase in guinea pig PMNL, was increased by treatment with 10 microM OAG, but the phosphorylation was little altered by hypotonic treatment. Intracellular calcium concentration, arachidonate release, and 1,2-diacylglycerol and phosphoinositide concentrations were slightly altered by hypotonic treatment. A change in phosphatidate (PA) production in PMNL was induced by hypotonic treatment either by itself or in combination with OAG treatment. These results suggest that the combination of cell membrane changes by hypotonic treatment accompanied by the increase in PA and 46-kDa protein phosphorylation by protein kinase C provides the conditions required for a marked increase in O2- production. Hypotonicity may be a good tool for studying the mechanism of priming in the activation of NADPH oxidase.

Animals↗

Identification of a botulinum C3-like enzyme in bovine brain that catalyzes ADP-ribosylation of GTP-binding proteins.

A novel enzyme activity was found in bovine brain cytosol that transfers the ADP-ribosyl moiety of NAD to proteins with Mr values of 22,000 and 25,000. The substrates were the same GTP-binding proteins serving as the substrate of an ADP-ribosyltransferase C3 which was produced by a type C strain of Clostridium botulinum. The brain enzyme was partially purified from the cytosol and had a molecular mass of approximately 20,000 on a gel filtration column. The brain endogenous enzyme displayed unique properties similar to those observed with botulinum C3 enzyme. The enzyme activity was markedly stimulated by a protein factor that had been initially found in the cytosol as an activator for botulinum C3-catalyzed ADP-ribosylation (Ohtsuka, T., Nagata, K., Iiri, T., Nozawa, Y., Ueno, K., Ui, M., and Katada, T. (1989) J. Biol. Chem. 264, 15000-15005). The activity of the brain enzyme was also affected by certain types of detergents or phospholipids. The substrate of the brain enzyme was specific for GTP-binding proteins serving as the substrate of botulinum C3 enzyme; the alpha-subunits of trimeric GTP-binding proteins which served as the substrate of cholera or pertussis toxin were not ADP-ribosylated by the endogenous enzyme. Thus, this is the first report showing an endogenous enzyme in mammalian cells that catalyzes ADP-ribosylation of small molecular weight GTP-binding proteins.

ADP Ribose Transferases↗

Comparative study of affective disorders in three Asian countries. II. Differences in prevalence rates and symptom presentation.

This study used standardized diagnostic criteria and method to investigate both prevalence rates and nature of symptoms of depressive disorders in three Asian centres--Nagasaki, Shanghai and Seoul. Of the patients who visited a psychiatric clinic in each of the 3 centres for the first time, over 20% suffered from depression. Unlike previous reported prevalence rates for Asian countries, these results suggest that rates in Asia may not be much lower than those reported in Western countries. Although prevalence rates of depression were similar in all 3 centres, differences in symptoms were noted.

Adolescent↗

Cyclothiazomycin, a novel polythiazole-containing peptide with renin inhibitory activity. Taxonomy, fermentation, isolation and physico-chemical characterization.

Cyclothiazomycin is a novel renin inhibitor produced by Streptomyces sp. NR0516. It was isolated from fermentation broth by extraction with butyl alcohol, QAE-Toyopearl column chromatography and preparative HPLC. Cyclothiazomycin, which was determined to be a unique polythiazole-containing bicyclic peptide, exhibited inhibitory activity against human plasma renin with IC50 being 1.7 microM.

Angiotensin I↗

[Mitral valve disease with pulmonary hypertension: two surgical cases].

Two surgical cases of mitral valve disease with severe pulmonary hypertension were reported, in which pulmonary hypertensive crisis (PHC) was a really serious problem to be treated. The first case (60-year-old woman) had atrial fibrillation and her pulmonary artery pressure was 68/32 mmHg (Pp/Ps = 0.63) and mean pulmonary wedge pressure was 26 mmHg with a high v wave (46 mmHg). PHC developed immediately after the cessation of artificial cardiopulmonary bypass, and intraaortic balloon pumping was performed. However, it was difficult to wean from the assist circulation, and then PGE1 and isoproterenol were given into the pulmonary artery and epinephrine and norepinephrine were given into the left atrium, and we succeeded in weaning from the assist circulation. The second case (58-year-old woman) had high pulmonary artery pressure (86/37 mmHg) and the Pp/Ps was 0.73. According to the experience of the first case, prevention of PHC started during cardiopulmonary bypass, giving PGE1, nitroglycerin and torazoline into the pulmonary artery. This led to the easy weaning from cardiopulmonary bypass. PHC may be seen even in cases of acquired valvular disease, and the prevention is mandatory for uneventful surgery.

Cardiopulmonary Bypass↗

[A case of leptomeningeal carcinomatosis: demonstration of CA19-9 and CEA positive malignant cells in the CSF and particular elevation of CA19-9 level in the CSF].

A 44-year-old male was admitted for diplopia, headache and gait disturbance. Neurological examination revealed the meningeal irritation sign, the Vth, VII, VIth, IXth and the Xth nerve palsies and cerebellar ataxia of all four limbs. Laboratory studies carried out on the day of admission demonstrated the elevation of serum levels of both tumor markers, carbohydrate 19-9 (CA19-9) and carcinoembryonic antigen (CEA). The estimated serum concentrations of CA19-9 and CEA were 39.4 U/ml and 81.1 ng/ml, respectively. The cerebrospinal fluid (CSF) contained 9 cells/mm3 which consisted of the mixture of malignant cells with appearance strongly suggestive of poorly differentiated adenocarcinoma and of hemosiderinphagocytizing macrophages. Detection of both CA19-9 and CEA in the tumor cells in the CSF was undertaken by the avidin biotinylated peroxidase complex method by use of monoclonal antibodies against each marker. As the results the following findings were obtained. Namely, although all the tumor cells isolated from the CSF were found to contain both tumor markers, CA19-9 and CEA, there was found a difference in the concentration ratio in CSF vs serum between the markers. The estimated concentration of CA19-9 (61.4 U/ml) in CSF was approximately 1.6 times higher than that in serum. On the other hand, the CSF concentration of CEA remained constantly very low (1.1 ng/ml) as compared with that in the serum throughout the whole course of the disease. In response to intrathecal administration of cytarabine and brain irradiation, the CSF cytological findings became normal and concomitant decrease in the concentration of CA19-9 was demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

A diacylglycerol kinase inhibitor, R 59 022, potentiates superoxide anion production and 46-kDa protein phosphorylation in guinea pig polymorphonuclear leukocytes.

A diacylglycerol (DG) kinase inhibitor, R 59 022, potentiated superoxide anion (O2-) production in guinea pig polymorphonuclear leukocytes (PMNL) induced by N-formyl-methionyl-leucyl-phenylalanine (FMLP). R 59 022 also potentiated O2- production induced by 1-oleoyl-2-acetylglycerol, a permeable DG. However, the production induced by phorbol 12-myristate 13-acetate (PMA), a direct activator for protein kinase C, was not potentiated by R 59 022. R 59 022 by itself had no significant effects on unstimulated O2- production. The potentiation of FMLP-induced O2- production by R 59 022 was correlated closely with increased formation of DG and decreased formation of phosphatidic acid, a product of DG kinase. R 59 022 had no effect on the breakdown of phosphoinositides. Phosphorylation of 46-kDa protein(s) by protein kinase C was also examined in relation to O2- production in PMNL. In coincidence with the increase in O2- production, the phosphorylation was potentiated by R 59 022 in the response to FMLP, but not in the response to PMA. In addition, staurosporine, a protein kinase C inhibitor, inhibited increases in both O2- production and phosphorylation of the 46-kDa protein(s) after PMA stimulation. Similar inhibitory effects of staurosporine were also observed upon stimulation with FMLP, irrespective of the presence of R 59 022. These results indicate that retention of DG as a result of the inhibition of further metabolism induces marked stimulation of O2- production via protein kinase C activation in PMNL. These results also provide further evidence for the close relationship between 46-kDa protein phosphorylation by protein kinase C and stimulation of O2- production in PMNL.

Alkaloids↗

Dipalmitoylphosphatidylcholine (L-alpha-lecithin) stimulates phospholipase A2 activity in human amnion.

In order to investigate the mechanism of dipalmitoylphosphatidylcholine (DPPC, L-alpha-lecithin) stimulation of the prostaglandin E (PGE) production of the amniotic membrane, effects of DPPC (50-800 micrograms/ml) on phospholipase A2 (PLA2), phospholipase C (PLC), PG endoperoxide synthase, and PGE synthase activities of human amniotic membrane were studied. Only PLA2 activity was increased by DPPC, suggesting that lecithin, the major surfactant component, increases the PGE production of the amniotic membrane by activating PLA2.

1,2-Dipalmitoylphosphatidylcholine↗

[Recurrence of endometrial cancer and its pathological factors].

The number of patients with uterine endometrial cancer has increased in recent years in Japan. The studies on the prognostic factors of endometrial cancer, however, have not been made in detail as compared with those on the prognostic factors of cervical cancers. We have therefore investigated retrospectively the prognoses of 94 cases with endometrial cancer treated in our clinic from 1973 to 1984. Out of 31 cases (32.9%) with recurrence, 13 cases were at the Stage I and II, and the recurrence ratios were 11.4% for Stage Ia, 18.2% for Stage Ib and 31.3% for Stage II. The prognosis of endometrial carcinoma appears to depend on the endocervical involvement of the cancer. Five prognostic factors for Stage I and II endometrial cancers analyzed here are as follows; (1) histologic differentiation (grade), (2) size (diameter) of the primary tumor, (3) myometrial invasion, (4) vascular invasion, (5) lymphnode metastasis. (1) The recurrence ratio was 15.0% in the well differentiated (Grade 1) group, 25.0% in the moderately differentiated (Grade 2) group, 27.3% in the poorly differentiated (Grade 3) group, and 12.5% in adenoacanthoma. (2) The ratio of recurrence was 2.9% with less than 3 cm diameter, 24% with 3-6 cm diameter, and 30% with greater than 6 cm diameter in tumor size. (3) The ratio of recurrence was 2.9% with less than 1/3, 24% with 1/3-2/3, and 30% with greater than 2/3 myometrial invasion. (4) The ratio of recurrence was 43.8% with vascular invasion, and 5.6% without it. (5) The ratio of recurrence was 75% with lymphnode metastasis, and 8.8% without it.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

Synergism between platelet-activating factor and diacylglycerol in the induction of superoxide anion production in guinea pig polymorphonuclear leukocytes.

The superoxide anion (O2-) production of guinea pig polymorphonuclear leukocytes (PMNL) by platelet-activating factor (PAF) was greatly enhanced by the addition of 1-oleoyl-2-acetylglycerol (OAG), even at low concentrations of OAG at which O2- production was little induced. The enhanced production was biphasic, depending on concentrations of PAF. One was saturable at a lower concentration range of PAF and probably mediated through a putative PAF receptor-islet-activating protein-sensitive GTP-binding protein (G protein) pathway. Another was increased in a concentration-dependent manner at a higher concentration range of PAF and apparently mediated through both receptor-G protein-dependent and -independent pathways. These results suggest that at least two types of action of PAF are involved in the synergistic stimulation of O2- production by PAF and OAG in PMNL.

Animals↗