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Biomedical subjects

S Ohta

Publications and source records attributed to S Ohta.

At least 487 records · Page 27Linked to original sources

Characterization of a taxol-resistant human small-cell lung cancer cell line.

Taxol is a novel anticancer agent with activity against a broad range of tumors. It has a unique ability to stabilize polymerized tubulin into microtubule bundles within the cell. We have established a taxol-resistant human small-cell lung cancer cell line (H69/Txl) by exposing H69 cells to stepwise increases in taxol concentration. The resistance of H69/Txl cells to taxol was 4.7-fold that of the original H69 cells: the IC50 values for H69 and H69/Txl were 113.7 +/- 56.54 nM and 538.7 +/- 214.7 nM by the tetrazolium dye assay, respectively. Removal of the drug from the medium resulted in a 38% decrease in the growth rate of H69/Txl as compared with that in the presence of 30 nM taxol, suggesting that the growth of H69/Txl was partially dependent on taxol. H69/Txl showed higher sensitivity to vinca alkaloids such as vindesine, vincristine and vinblastine than the parental H69. There was no significant difference in intracellular [3H]taxol content between H69 and H69/Txl cells. No MDR-1 mRNA was detected in H69/Txl by the reverse transcription polymerase chain reaction. There was no significant difference of total and polymerized tubulin content between H69 and H69/Txl cells. Altered mobility of one of the alpha-tubulin isoforms in H69/Txl was revealed by using isoelectric focusing and Western blotting with anti-alpha-tubulin antibody. In H69, two alpha-tubulin isoforms were observed, whereas three were evident in H69/Txl, two of them comigrating with the isoforms of H69 and the other being more acidic. We observed the increased acetylation of alpha-tubulin in H69/Txl cells as compared with that in H69 cells. The acetylation of alpha-tubulin may be responsible for the taxol resistance and/or taxol-dependent growth of H69/Txl.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

An early-onset case of multiple sclerosis with thalamic lesions on MRI.

We present here an early-onset case of multiple sclerosis (MS) with thalamic lesions. The patient first experienced an episode of ataxic gait at 2 years 3 months of age, with spontaneous remission within 1 month. At 5 years 4 months, she was admitted because of cerebellar ataxia, oculomotor restriction and feeding difficulty. Magnetic resonance imaging (MRI) showed multiple well-defined lesions in the white matter of the cerebellum, mid-brain, periventricle and right frontal lobe. Cerebrospinal fluid (CSF) showed a mild elevation of both immunoglobulin G (IgG) and myelin basic protein (MBP). Serum anti-myelin antibody was also positive, although leukocytosis and elevation of C-reactive protein were not found. Methylprednisolone pulse therapy relieved symptoms within 2 weeks and the abnormal MRI and CSF findings gradually improved. At 6 years 6 months of age, she incurred a third episode of cerebellar ataxia and disturbance of consciousness. Magnetic resonance imaging revealed recurrence and extension of the previous lesions as well as new lesions in the thalamus and internal capsule. CSF IgG and MBP level showed a higher elevation than in the second episode. The combination of the cerebellar, brain-stem, cerebral and thalamic lesions with remission and exacerbation, supported by MRI and CSF findings, allowed the diagnosis of clinically definite MS to be made. This is one of the youngest cases of MS yet described, with the first attack occurring at 27 months of age. In addition, this case is unique for the involvement of the gray matter in the thalamus.

Age Factors↗

Mechanisms of vasodilation of cerebral vessels induced by the potassium channel opener nicorandil in canine in vivo experiments.

BACKGROUND AND PURPOSE: Nicorandil, a potent antianginal agent characterized as a potassium channel opener, could produce cerebrovascular dilation in in vitro studies. Our aim was to investigate the pharmacologic response to the topical application of nicorandil on the vasomotor tone of pial vessels in vivo. To elucidate its mechanism, we also studied the inhibitory action of methylene blue and glibenclamide against nicorandil-induced vasodilation. METHODS: In 14 dogs prepared with a parietal cranial window, we administered five different concentrations of nicorandil solution (10(-7), 10(-6), 10(-5), 10(-4), and 10(-3) mol/L) under the window and measured pial arterial and venular diameters. After pretreating pial vessels with either 10(-5) mol/L methylene blue or 10(-5) mol/L glibenclamide, we examined inhibitory action after the application of 10(-5) mol/L nicorandil. In additional experiments with 9 dogs, we evaluated the effects of nitroglycerin and cromakalim on pial vessels in the absence or presence of 10(-5) mol/L methylene blue and 10(-5) mol/L glibenclamide, respectively. RESULTS: Nicorandil produced significant, concentration-dependent dilation of pial vessels (P < .05). Methylene blue blocked nicorandil-induced dilation, whereas glibenclamide only attenuated such action of nicorandil. Nitroglycerin and cromakalim also produced a concentration-dependent increase in pial arteriolar and venular diameters (P < .05), and those effects were blocked in the presence of methylene blue or glibenclamide, respectively. CONCLUSIONS: Our in vivo study demonstrates that topical application of nicorandil dilates both pial arterioles and venules in a concentration-dependent manner and suggests that the mechanisms of such actions are most likely due to both cyclic GMP-mediated vascular smooth muscle dilation and the regulation of K+ flux.

Administration, Topical↗

Synthetic approaches to 3-amino-1,4-naphthoquinone-2-carboxylic acid derivatives and photochemical synthesis of novel 1,4,5,10-tetrahydro-5,10-dioxo-2H-naphth[2,3-d][1,3]oxazine derivatives.

Synthesis of 3-alkylamino-1,4-naphthoquinone-2-carboxylic acid (2) was attempted. Although 3-(1-piperidinyl)-1,4-naphthoquinone-2-carboxylic acid (2a) was not obtained, probably because of its instability, the esters (18a, b) of 2a could be prepared. 2-Alkylamino-3-hydroxymethyl-1,4-naphthoquinones (9a-g) were photochemically cyclized to the 1,4,5,10-tetrahydro-5,10-2H-naphth[2,3-d][1,3]oxazines (19a-g), containing a novel heterocyclic ring system in moderate yields. Anti-bacterial activity of the prepared compounds was weak or insignificant.

Anti-Bacterial Agents↗

Correlation between zeta-potential of a cell in a new cationic disinfectant solution and minimum inhibitory concentration of the disinfectant.

In the previous paper, we described the synthesis of new quaternary ammonium slats with antimicrobial activity: N-alkyl-N-2-hydroxyethyl-N,N-dimethylammonium butyl phosphate (4) and N-alkyl-N-(2-hydroxy-3-phenoxy)-propyl-N,N-dimethylammonium butyl phosphate (5). In this study, we examined the relationship between the MIC (minimum inhibitory concentration) of these new cationic disinfectants, 4 (six compounds) and 5 (three compounds), and the xi-potential against Escherichia coli in solutions of these compounds. The MIC values of these disinfectants against E. coli were highly correlated with the concentration that induced electric charge inversion (xi-potential=0) of E. coli from negative to positive.

Disinfectants↗

[Protective effects of sesamol and its related compounds on carbon tetrachloride induced liver injury in rats].

Sesamol is a kind of antioxidant and exists in sesame oil. This paper describes the protective effect of sesamol against carbon tetrachloride (CCl4)-induced liver injury in rats. Sesamol had a significant effect in case of intraperitoneal, subcutaneous and oral administration. In order to examine the relationship between the chemical constitution of sesamol and its protective effect, the protective effects of 20 kinds of sesamol related compounds against liver injury induced by CCl4 were investigated in rats. Consequently, significant protective effects were found in methylenedioxybenzene, isosafrole, safrole, methylenedioxyaniline and methylenedioxyacetophenone. These five compounds had a methylenedioxy group had protective effects, it was considered that the protective effects of the methylenedioxy group were influenced by substituent groups on 4 position of methylenedioxy phenyl compounds. In addition, sesamol, methylenedioxybenzene and isosafrole showed significant protective effects against cholestasis induced by CCl4.

Animals↗

[Study on new anti-rust disinfectants. III. Effect of alkyl chain length of N-alkyl-N-(2-hydroxy-3-phenoxy)propyl-N,N-dimethylammonium butyl phosphate on the antibacterial activity].

New anti-rust quaternary ammonium salts such as N-alkyl-N-(2-hydroxy-3-phenoxy)propyl-N,N-dimethylammonium butyl phosphate (5) [alkyl homologues are octyl (5a), decyl (5b), dodecyl (5c), tetradecyl (5d), hexadecyl (5e), and octadecyl (5f)] were synthesized in order to find the relationship between the alkyl length and the antibacterial activities. N-Alkyl-N-(2-hydroxy-3-phenoxy)propyl-N,N-dimethylammonium chloride (6) [alkyl homologues are dodecyl (6c), tetradecyl (6d), hexadecyl (6e)] were used as standard compounds in the quantitative analysis. 5c and 6c showed antibacterial activities and these activities were nearly equal to that of benzalkonium chloride (BAC), but, the activities shown by 5e, 5f and 6e were insufficient. 5c-e, showed excellent anti-rust effects, but 6c-e showed insufficient effects, because the former had a butyl phosphate anion and the latter had a chloride anion as a counter ion. 5a, b were insoluble in water. 5c showed a cloud point at 61.5 degrees C and 5d showed a cloud point at 72.0 degrees C at a 10% concentration in water. This phenomenon is similar to those of non-ionic surfactants. 5e was freely soluble in water.

Bacteria↗

Characterization of Haemophilus paragallinarum isolated in the Philippines.

In 1989 and 1990, we isolated five strains of Haemophilus paragallinarum in the Philippines. Serological studies were done on three of these isolates. The results of haemagglutination, reactability to monoclonal antibodies and cross immunization with standard strains showed that they belonged to serotypes A, B and C respectively. This is the first report on the isolation of H. paragallinarum and on a related serological study in the Philippines.

Animals↗

Large cystic cavernous angioma of the cerebellum--case report.

A 40-year-old female presented with gait disturbance and dysarthria. Computed tomography revealed a large cystic tumor in the cerebellar vermis with a mural nodule located in the deepest portion of the cyst. The magnetic resonance (MR) imaging appearance suggested cavernous angioma. The solid nodule was completely removed through the suboccipital approach. The cyst was filled with transparent yellowish fluid which showed positive Froin's sign. The histological diagnosis of the mural nodule was cavernous angioma. The cyst wall consisted of gliosis and contained no angiomatous tissues. Postoperative MR imaging demonstrated that the nodule was totally removed and the cyst size was reduced. The neurological deficits improved postoperatively. The mechanism of formation of the large cyst was assumed to be repeated peritumoral hemorrhage.

Adult↗

Chronic subdural hematoma associated with middle fossa arachnoid cysts--three case reports.

Three patients with chronic subdural hematoma associated with middle fossa arachnoid cyst were treated by irrigating the hematoma through burr holes, because the symptoms were considered mainly due to increased intracranial pressure caused by the subdural hematoma. The symptoms disappeared immediately afterwards, so no surgery for the middle fossa arachnoid cyst was done. The patients were followed by magnetic resonance imaging. No subdural hematoma recurred during a postoperative period of 11 months to 2.5 years, and the arachnoid cyst reduced in size in two patients. We recommend irrigation of the subdural hematoma as the initial procedure of choice for such cases.

Adolescent↗

Changes in Ca(++)-ATPase activity in smooth-muscle cell membranes of the canine basilar artery with experimental subarachnoid hemorrhage.

Changes in Ca(++)-adenosine triphosphatase (ATPase) activity in the plasma membrane of smooth-muscle cells in the basilar arteries of dogs with experimental subarachnoid hemorrhage (SAH) were examined. The study methods included electron microscopic histochemistry and bioassay of the enzyme that exports cytoplasmic Ca++ to extracellular spaces. The Ca(++)-ATPase activity in the basilar artery increased significantly in response to the application of vasoconstrictive agents (prostaglandin F2 alpha and a phorbol ester), but decreased significantly 24 hours after experimental SAH, inversely with basilar artery contraction. Dogs that had undergone two arterial blood injections (double SAH) exhibited a further decrease in Ca(++)-ATPase activity as well as persistent contraction of the basilar artery for a longer period (at least 7 days) than was seen in animals with a single arterial blood injection. Bioassay of the enzyme also demonstrated a decrease in vascular Ca(++)-ATPase activity in dogs subjected to double SAH. These findings suggest that the early occurrence of and long-lasting decrease in Ca(++)-ATPase activity in dogs with experimental SAH induces a persistent disturbance of Ca++ homeostasis and indicates that damage to the plasma membrane in the cerebral arterial smooth-muscle cells proceeds to myonecrosis after SAH.

Animals↗

Isolation, characterization and functional activity of human marrow stromal progenitors in hemopoiesis.

In conclusion, monoclonal antibody STRO-1 has proven to be an extremely valuable reagent for the identification, isolation and functional characterization of human bone marrow stromal cell precursors. We were able to isolate CFU-F free of contaminating hemopoietic progenitors and are beginning to construct a detailed picture of their cell surface phenotype and have developed assays to examine the conditions required for their growth and differentiation. In the future, we hope to determine whether multipotential stromal stem cells exist in human bone marrow and to establish culture conditions that selectively promote self-renewal or development along any of a number of stromal cell lineages. Such cells would be an ideal target for gene therapy and may provide a means of treating disorders of the hemopoietic system with a suspected stromal etiology, such as aplastic anemia. We have recently succeeded in generating bone cells from STRO-1+ marrow cells (Gronthos et al, in preparation) and thus marrow stromal cell precursors may also find application in the treatment of other disorders such as those of the osteogenic system. For the present, these must remain tantalizing possibilities.

Adult↗

[A case of ANCA-associated rapidly progressive glomerulonephritis with oral aphtha and erythema nodosum].

We reported a case of a 22-year old female with a microscopic form of polyarteritis nodosa (PN) who initially manifested Behçet's disease-like symptoms, such as fever, arthralgia, oral aphtha and erythema nodosum, and rapidly progressive glomerulonephritis (RPGN). On admission, her urinalysis showed active nephritic syndrome and her renal function rapidly deteriorated; serum creatinine levels elevated from 1.2 to 3.9 mg/dl within 2 weeks. Skin biopsy specimens from erythema showed panniculitis. Accordingly, she was treated with daily 30 mg of oral prednisolone and three-day intravenous pulse therapy of 1000 mg of methylprednisolone twice. After treatment, skin eruption and oral aphtha disappeared, and the serum creatinine level improved to 1.2 mg/dl. Percutaneous renal biopsy performed on the 28th day showed focal necrotizing glomerulonephritis and hyalinosis of small arteries. Immunofluorescence studies showed only trace stainings for IgG, IgA and beta lc. Electron microscopic findings revealed fusion of the foot process and swelling of endothelial cells, but no dense deposits. Anti-neutrophil cytoplasmic antibody (ANCA) was positive for IgG class with a 40-fold titer by indirect immunofluorescence test and showed a cytoplasmic pattern combined with high urinary IL-8 level (280.1 pg/ml). We diagnosed this case as a microscopic form of PN. ANCA titer and urinary IL-8 correlated positively with the disease activity, and were finally below 8-fold and 58.6 pg/ml, respectively after resolution of RPGN for 42 months. In this case, ANCA was useful not only for differential diagnosis of the patients with systemic vasculitis and crescentic glomerulonephritis, but also for evaluation of the disease activity.

Adult↗

[Evaluation of cerebral circulation and cerebrovascular CO2 reactivity with transcranial Doppler ultrasonography].

We examined the cerebrovascular CO2 reactivity (K) determined by measurements of the middle cerebral artery blood flow velocity (Vm) with transcranial Doppler ultrasonography (TCD) in 24 anesthetized patients. The relationship between Vm and mean arterial blood pressure (mBP) showed a linear regression in each constant level of PaCO2. The exponential curve with an exponent of 0.0399 mmHg-1 was found to be the best fit to the plotted data of Vm against PaCO2 during normotension of 90 mmHg. The following equation was used to evaluate K from the two flow values, because the calculated K value would be logically constant, i.e., an exponent of Vm/PaCO2 exponential curve: K (mmHg-1) = delta lnVm/delta PaCO2 = (lnVm(1) - lnVm(2)/(PaCO2(1) - PaCO2(2)). The validity of K values could be enhanced under conditions of the delta PaCO2 > or = 12.5 mmHg and the variation in arranged mBP < or = 30 mmHg. This methodology with TCD can be used to correlate changes in cerebral blood flow and provide much benefit for the evaluation of cerebrovascular CO2 reactivity.

Adult↗

[Recovery from unconsciousness following severe hemodilution and hypotension caused by intraoperative massive hemorrhage: a case report].

A 75-year-old female with a history of cerebral infarction fell into sudden hypotension (mean blood pressure of around 46 mmHg) and severe anemia (hematocrit < or = 10%; minimum hemoglobin concentration of 2.0 g.dl-1) of approximately one hour due to massive hemorrhage during surgical removal of pheochromocytoma originated in the right adrenal gland. Nevertheless, she recovered from the unconsciousness after over 9 hours postoperatively. It is suggested that major reasons for her escaping from the brain damage, in spite of the low cerebral perfusion pressure, might be the decreased cerebral oxygen consumption due to the intraoperative mild hypothermia (31.5 degrees C) and the avoidance due to hemodilution of the extremely low cerebral blood flow.

Adrenal Gland Neoplasms↗

[Effects of hemodilution on cerebral arterial blood flow velocity and cerebrovascular CO2 reactivity].

We investigated the effects of normovolemic hemodilution on the mean blood flow velocity of the middle cerebral artery (Vm) and the cerebrovascular CO2 reactivity (K-value) by transcranial doppler sonography in ten patients undergoing elective surgeries. Vm during hemodilution (Hct of 24%) significantly increased for 8% in normocarbia (PaCO2 of 40 mmHg) and for 15% in hypocarbia (PaCO2 of 30 mmHg), compared with that in prehemodilution (Hct of 33%), at the range of mean blood pressure < or = 90 mmHg. However, in hypercarbia (PaCO2 of 50 mmHg), there were no significant differences in Vm between during hemodilution and in pre-hemodilution. K-values during hemodilution were significantly lower than those in pre-hemodilution at the same hypotensive range. These findings suggest that moderate hemodilution may elicit the compensatory increase of cerebral blood flow by cerebrovascular dilation and therefore induce no disturbance for normal cerebral hemodynamics.

Adult↗

[An autopsy case of hereditary cerebellar atrophy (Holmes-type) with mental symptoms and rhythmic skeletal myoclonus].

We report on the clinicopathological findings in autosomal recessive hereditary cortical cerebellar atrophy of the Holmes type (H-CCA). Although based on the patient's family tree we cannot rule out the possibility of sex-linked recessive hereditary disease, both clinically and pathologically we differentiated this case from sex-linked recessive hereditary cortical cerebellar atrophy, in which lesions are widely distributed and associated with a variety of symptoms, since the major clinical feature was cerebellar ataxia, and the major lesions were limited to the olivocerebellar system. The patient's initial symptom was a motor disturbance in the upper extremities at the age of 16. This was followed by chronic progression of his symptoms, with cerebellar ataxia becoming the major symptom. The patient died unexpectedly at 40 years of age as a result of choking caused by misswallowing. The total period of observation was 24 years. The clinical features in this case were juvenile onset at age 16 with motor disorders of the upper extremities, followed by cerebellar ataxia, mental symptoms, mainly consisting of personality changes, and associated rhythmic skeletal myoclonus (RSM). Even though the patient died in the middle stage of the disease, pathologically there were extensive lesions in the olivocerebellar system, i.e., extensive degeneration not only of Purkinje cells but of granular cells and the molecular layer, and the distribution of the lesions was characteristic, with more extensive degeneration in the neocerebellum than in the paleocerebellum.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Anti-bacillus substance in the marine sponge, Hyatella species, produced by an associated Vibrio species bacterium.

The bacterial isolate, M22-1, belonging to the genus Vibrio was obtained from an homogenate of the sponge, Hyatella sp. The bacterium was cultured in marine agar and was found to produce an anti-Bacillus compound. The substance was chemically identified as a peptide antibiotic, an andrimid. The same substance was found in the sponge extract, suggesting that the active component was synthesized by the associated microorganism.

Animals↗