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Biomedical subjects

K Ohtani

Publications and source records attributed to K Ohtani.

At least 217 records · Page 12Linked to original sources

Improved preparation of T-2 toxin-protein conjugates.

T-2 toxin (T-2) was converted into T-2 hemisuccinate (T-2 HS), T-2 hemiglutarate (T-2 HG) and T-2 hemiphthalate (T-2 HP), and conjugated with bovine serum albumin (BSA), ovalbumin (OVA) and keyhole limpet haemocyanin (KLH) using carbodiimide under various conditions. The recovery of T-2 conjugated proteins and the amount of T-2 bound were largely dependent on the amount of coupling reagent, pH, reaction temperature, buffer and reaction time. In regard to T-2 derivatives binding with a protein, T-2 HG was the most efficient, followed by T-2 HS and then T-2 HP. With regard to T-2 to protein binding, KLH was the most efficient, followed by BSA and then OVA. To promote T-2-protein binding, phosphate-buffered saline was more effective than cacodylate buffer. Within a pH range of 5.5-7.0, weakly acidic conditions were more efficient than neutral conditions for promoting T-2-protein binding.

Animals↗

Cerebral blood flow during ACTH therapy: especially diurnal changes within the first week of therapy.

Changes in cerebral blood flow (CBF) were evaluated in children with epilepsy treated with adrenocorticotrophic hormone (ACTH) by the Doppler ultrasound method. The average maximal blood velocity (A/L) and maximal end-diastolic blood velocity (d) of the internal carotid artery, as indices of CBF, significantly decreased during ACTH therapy. These values had already decreased at 30 minutes after the first injection of ACTH and were hardly restored 24 hours later just before the next injection. Such changes repeatedly occurred for the first four days of therapy so that the reductions in the A/L and d values proceeded in a stepwise manner. These values became minimum at around one week after initiation of the therapy and then gradually increased, returning to the original levels by the 8th week of therapy. Investigation of the changes in cerebral metabolism seemed to be the next step for elucidation of the mechanism underlying the CBF reduction during ACTH therapy.

Adrenocorticotropic Hormone↗

Atypical form of Menkes kinky hair disease with mitochondrial NADH-CoQ reductase deficiency.

A male infant with an atypical form of Menkes kinky hair disease showed mitochondrial NADH-CoQ reductase (complex I) deficiency in a femoris muscle biopsy. His clinical features consisted of hypotonicity of the upper limbs, hyper-reflexia of the lower extremities, abnormal hair and fine myoclonic movement of the hands. The serum levels of copper and ceruloplasmin were just below normal range, and the copper concentration in fibroblastic cells was much increased (101.2 ng/mg of protein). The occurrence of this case suggests that there may be a mild form of Menkes disease with a NADH-CoQ reductase deficiency or other mitochondrial enzyme defects.

Atrophy↗

Application of an enzyme-linked immunosorbent assay for screening of T-2 toxin-producing Fusarium spp.

Culture filtrates of Fusarium species were subjected without clean-up procedures to an indirect competitive enzyme-linked immunosorbent assay with anti-T-2 toxin monoclonal antibody. Fusarium sporotrichioides, F. poae, F. tricinctum, and F. culmorum strains were positive for T-2 toxin, with a minimum detection limit of 5 pg per assay (100 pg/ml of culture filtrate), and the assay data correlated well with the gas-liquid chromatographic data.

Antibodies, Monoclonal↗

12-O-tetradecanoylphorbol-13-acetate induces the enhancer function of human T-cell leukemia virus type I.

Phorbol esters were employed in studies on the molecular mechanism of the induction of expression of human T-cell leukemia virus type I (HTLV-I) by a tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). Experiments using the chloramphenicol acetyltransferase (CAT) system showed that CAT expression directed by the long terminal repeat (LTR) of HTLV-I was induced by TPA, but not by 4 alpha-phorbol-12,13-didecanoate, which is not an activator of protein kinase C, and that like other known enhancers, irrespective of its position and orientation, a 230-bp fragment in the U3 region of the HTLV-I LTR confers susceptibility to induction by TPA.

Deltaretrovirus↗

Identification of two distinct elements in the long terminal repeat of HTLV-I responsible for maximum gene expression.

Human T-cell leukemia virus type I has a unique sequence, pX, between env and the 3' long terminal repeat (LTR). One of its products, p40, activates gene expression directed by the LTR in a trans-acting manner. We have analysed the mechanism of this trans-activation mediated by p40 in human T cells co-transfected with a plasmid expressing p40 using the transient CAT gene expression. We identified two distinct elements in the LTR which are involved in maximum gene expression. The first was present in a 230-bp fragment upstream from TATA box in the U3 region and behaved as a classical enhancer. This region was also shown to be responsible for trans-activation by p40. This element alone together with functional p40 could direct the gene expression at only approximately 10% of the level achieved by the complete LTR and p40. The second element was present within a 300-bp fragment downstream from the RNA start site and profoundly enhanced the gene expression in a way independent from trans-activation mechanism. This enhancement was observed only when the element was located immediately downstream from the RNA start site without orientation preference. These two elements participate independently in the enhancement of gene expression.

Base Sequence↗

Comparison of brain imaging and neuropathology in cases of trisomy 18 and 13.

A comparative study of intracranial imaging and brain pathology in cases of trisomy 18 and 13 was performed. Computed tomography (CT) and ultrasonography (US) revealed disproportional dilatation of the lateral ventricles, a wide Sylvian fissure and a large extracerebellar space with a small cerebellum in each case. In addition, it was characteristic that the occipital poles of the cerebrum protruded in the infero-posterior direction in trisomy 18, and the pontine basis was relatively wide in trisomy 13. The brain pathology in trisomy 18 and 13 demonstrated that the large extracerebellar space is due to the cerebellar dysplasia and protruding occipital poles, the wide Sylvian fissures due to the temporal lobes or external capsular dysplasia, and the relatively wide pontine basis due to meningeal glioneuronal heterotopia. Thus, the characteristic intracranial image in trisomy 18 and 13 suggest microdysgenesis of the brain and might be useful for understanding the pathological structure of the central nervous system in these conditions.

Abnormalities, Multiple↗

Functional and morphometrical maturation of the brainstem auditory pathway.

The correlation between the functional and morphological maturation of the auditory pathway was studied in preterm and term infants, children and adults. As to the auditory brainstem response (ABR), peak latencies and I-V interpeak latencies (central transmission) gradually decreased during the third trimester and the first 2 years postnatally. The calculated pontine auditory conduction velocity (PACV) showed dramatic development, which may indicate a more precise auditory function. The PACV value at the age of 2-4 years was almost the same as that of adults. In a histomorphometrical study, the density of nerve cells in the cochlear nucleus and the inferior colliculus was found to decrease with age, that in the inferior colliculus decreasing more slowly. Myelination in the lateral lemniscus proceeded from the late fetal to the infantile period, and the myelin sheaths of large diameter increased mainly in the infantile period. Thus, on studying ABR in combination with the quantitative histomorphometrical investigation, the development of PACV was found to be related to the maturation of nerve cells in the upper nuclei corresponding to each latency as well as myelination of small and large fibers in the auditory pathway. PACV, which can be calculated by studying ABR and magnetic resonance imaging, may be used to assess more accurately the brainstem function in individual patients.

Adolescent↗

[The effects of FUT-175 (nafamostat mesilate) on blood coagulation and experimental disseminated intravascular coagulation (DIC)].

FUT-175 is a newly synthesized serine protease inhibitor. In the present study, we investigated the effects of FUT-175 on blood coagulation and experimental DIC. The effects on coagulation were examined in vitro by measuring the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) of rat plasma in the presence of FUT-175. FUT-175 exhibited remarkable anticoagulative effects to prolong APTT at a plasma concentration of 3 x 10(-7) M, PT at 1 x 10(-5) M and TT at 3 x 10(-5) M. The anticoagulative effect of FUT-175 at 1 x 10(-6) M on APTT was almost similar to that of heparin at 0.3 U/ml or that of gabexate mesilate at 1 x 10(-3) M. Experimental DIC was induced by a four-hr sustained intravenous infusion of endotoxin. FUT-175 was administered intraperitoneally prior to the injection of endotoxin or infused intravenously with endotoxin. As a result, the prolongation of APTT and PT, the decreases of fibrinogen level, platelet counts and complement level, and the increase of FDP were remarkably improved by FUT-175. Furthermore, glomerular fibrin deposits were reduced by the infusion of FUT-175. These results indicate that FUT-175, having a potent inhibitory effect on blood coagulation, is clinically applicable to therapy for DIC.

Animals↗

[Effects of RU38486, an antiprogesterone agent, on endometrium, fertilized ovum and serum sex steroid levels in rats].

Effects of antiprogesterone RU38486 were studied in rats. The synthetic compound effectively (100%) inhibited implantation when administered on day 2 as well as on day 4 postconception (2.5mg/kg, in glycerol). This treatment, however, did not alter circulating estradiol and progesterone levels. Fertilized ovum yielded on day 4 from the uterine cavity showed normal morphology including adequate progress in cell division. A light microscopic study of the endometrium showed decreased cytoplasmic vacuole formation but estrogenic effects were apparently preserved. These data suggest that administration of RU38486 immediately after conception could successfully prevent implantation without altering early luteotropic functions in rats. Also the high dose of the compound was found to have no significant toxic effects on fertilized ovum, indicating that the anticonceptional action of RU38486 mainly functions at the uterine endometrial level.

Animals↗

A study of anti-progestational compound RU38486 action on the estrogen-induced enlargement of the rat pituitary gland.

Long term administration of estradiol to intact and ovariectomized female rats caused enlargement of the pituitary gland. This process was partially antagonized in intact animals when antiprogestational compound RU38486 was given concomitantly. In ovariectomized rats, however, this effect of RU38486 was not apparent. Since administration of the compound to ovariectomized animals did not alter estrogen-receptor translocation or estrogen induced hypervascularity in the pituitary gland, this inhibitory effect of RU38486 seems not to be exerted through estrogen-receptor binding antagonism but rather due to a progesterone receptor blockade at the hypothalamic-pituitary axis.

Adenoma↗

[Peripheral sensory neuropathy produced by a megadose of vitamin B6].

Clinical cases of sensory neuropathy produced by a megadose of vitamin B6 have been reported in English literatures. We investigated the ordinary daily dosage and maximal dose of vitamin B6 widely adopted in Japan, and the amount of vitamin B6 per unit (per tablet, capsule or ampule) available in our medical practice. We concluded that in Japan it is very rare to administer such a large dose of vitamin B6 that produced sensory neuropathy described in the literatures. In our experimental study, Sprague-Dawley rats were intraperitoneally given a total amount of 14,000 mg/kg of body weight of pyridoxine hydrochloride in ten separate doses. They developed an ataxic gait. The occurrence of the degeneration of nerve cell bodies and peripheral axons of lumbar primary sensory neurons were histologically demonstrated. Although in Japan no clinical cases of neuropathy produced by a megadose of vitamin B6 have been reported to our knowledge, it is necessary to be aware of the possible occurrence of such neuropathy among patients with polyneuropathy of unknown etiology or who have been receiving vitamin B6 for a long time.

Animals↗