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Biomedical subjects

T Sekimoto

Publications and source records attributed to T Sekimoto.

At least 37 records · Page 2Linked to original sources

Evidence for lysine 80 as general base catalyst of leucine dehydrogenase.

To elucidate the functional role of the lysyl residue highly conserved in NAD(P)(+)-dependent amino acid dehydrogenases, Lys-80 of leucine dehydrogenase from Bacillus stearothermophilus has been mutated into Ala, Arg, or Gln. All of the mutant enzymes had markedly reduced activities in the oxidative deamination, whereas the Michaelis constants for substrate and coenzyme did not change significantly upon the mutation, except for a 10-30-fold increase in Km values for alpha-keto-iso-caproate in the Ala and Gln mutants. The pH profiles of kinetic parameters of the mutants considerably differed from those of the wild type, in which two ionizable groups with pKa values of 8.9 and 10.7 must be unprotonated for catalysis and protonated for substrate binding, respectively. Combined with the analyses of solvent isotope effect and inhibition by substrate analogs, these results unequivocally show that the epsilon-amino group of Lys-80 participates in catalysis as a general base, assisting the nucleophilic attack of a water molecule to the substrate alpha-carbon atom. Furthermore, the Ala mutant was markedly stimulated by primary amines depending on the pKa and molecular volume, suggesting that in the Ala mutant the added amines can partially replace the general base function of Lys-80 in the wild type enzyme.

Amines↗

[A case of cervical vagus neurinoma with hypoglossal palsy].

Cervical vagus neurinoma with hypoglossal palsy is extremely rare and only one case has been reported so far in Japan. A 52-year-old female complained of dysarthria. She has hypoglossal palsy with left-deviated tongue and the left half of her tongue was markedly atrophic. Cervical mass was not palpable and she had no other complaint such as hoarseness or dysphagia. CT scan and MRI revealed a tumor at a caudal part of the left jugular foramen. A hypoglossal canal was intact. Cerebral angiography demonstrated arterio-venous dissociation but vascular formation or tumor stain was not revealed. The tumor was totally removed by transpetrosal approach. The vagus nerve became thicker above C2 level and changed into the yellowish tumor with clear margin. The hypoglossal nerve was compressed between the tumor and an occipital bone. The authors think this is why hypoglossal palsy appeared. Histologically, the tumor was neurinoma. Clinical symptoms, diagnosis, and treatment were discussed.

Cranial Nerve Diseases↗

[Prognostic significance of nuclear DNA content in breast cancer].

The relationship between nuclear DNA content determined by cytofluorometry in the primary focus of breast cancer and the survival rate was analyzed to clarify the prognostic significance of nuclear DNA content in breast cancer. The relationships of the ploidy pattern and the frequency of polyploid cells (4c or above) with the survival rate were studied in patients who underwent extended radical mastectomy and were comparable in the clinical stage and other prognostic factors. The survival rate was significantly lower in those of the non-diploid type showing no prominent peak at 2c or those in whom the frequency of polyploid cells was more than 30% than in those of the diploid type with a prominent peak at 2c or those showing few polyploid cells, even when the disease stage (Stage II by TNM classification and stage III by Tnm classification), histological lymph node metastasis (n (+), n1 beta), and histological type (papillotubular carcinoma, scirrhous carcinoma) were identical. From these findings, nuclear DNA content is considered to be a parameter of the malignancy of breast cancer and to have clinical significance as an important prognostic factor.

Breast Neoplasms↗

[Clinical significance of measurement of nuclear DNA content in breast cancer].

Nuclear DNA content measured by a cytofluorometric method was investigated to evaluate its clinical significance in 73 cases with breast cancer which had extended radical mastectomy. Many cases of D type (diploid type) which had a prominent peak at the 2c region (control DNA content of lymphocytes) were safe indications for modified radical mastectomy. Bone recurrence was significantly more frequent in D type than in N type (non-diploid type) which did not have a prominent peak at the 2c region. Because D type had high positive rate of hormone receptors, endocrine therapy might be effective for many cases. Local or lung recurrence was more common in cases with N type which had a significant low cumulative survival rate compared with D type and especially N type 4c-3 of which over 4c cells more than 30% had the poorest prognosis. Therefore, multidisciplinary treatment composed of extended operation, radiation and chemotherapy was necessary to improve the prognosis of breast cancer patients with N type 4c-3. It was concluded that the measurement of nuclear DNA content in breast cancer might be useful for decision of therapy suitable for each case based on malignancy grading.

Breast Neoplasms↗

[A case of transorbital intracranial foreign bodies due to windshield impact].

A case of transorbital intracranial foreign bodies due to windshield impact was reported. A 17-year-old man was admitted to our department after he had his face injured in a traffic accident. He was fully conscious, and had no neurological deterioration except for a disturbance in his left external ocular movement. Plain skull X-rays and a plain CT revealed foreign bodies in the left orbit and the left frontal lobe. Combined surgery, through the orbit and the subfrontal approach, was performed to remove many foreign bodies (crushed windshield glass). His external ocular movement returned to normal postoperatively. There were no complications of meningitis and liquorrhea, and he was discharged without any neurological deficiency. The law, enacted in 1988, obliges the use of high penetration resistant (H.P.R.) laminated windshield in all new cars in Japan. But many motor cars equipped with partially enhanced windshields are still in use. It should be noted that partially enhanced windshields cause more severe injuries than H.P.R. laminated ones.

Accidents, Traffic↗

[Malignancy grading in breast cancer as assessed by nuclear DNA content].

The relationship between nuclear DNA content measured by cytofluorometry and the prognostic factors, especially the histological lymph node metastasis was investigated in patients with breast cancer. Nuclear DNA content was measured in 82 cases to evaluate its clinical significance concerning the malignancy grading. Histograms of DNA content were classified into two basic ploidy patterns based on presence or absence of a prominent peak at the 2c (diploid) region. D type (diploid type) which had a prominent peak at the 2c region resembled the histogram pattern of normal cells more closely than N type (non-diploid type). The rate of lymph node metastasis of N type (57.4%) was significantly higher than that of D type (28.6%) (p less than 0.05). The rate of lymph node metastasis of N type was higher than D type regardless of the tumor size or histological types. The five year cumulative survival rate of D type (91.7%) was significantly higher than that of N type (68.2%) (p less than 0.05). Despite the lymph node metastasis, the survival rate of D type was higher than that of N type. From a view point of the relationship between nuclear DNA content and lymph node metastasis, breast cancers of D type might be much safer indications for modified radical mastectomy. From this study, it was suggested that the measurement of nuclear DNA content of the breast cancer would bring the important informations about the malignancy grading and decision of the operative procedure.

Adult↗

[A case of pleomorphic xanthoastrocytoma].

A case of pleomorphic xanthoastrocytoma (Kepes) is reported. This patient was a 12-year-old boy with a history of convulsive seizure. Neurological examination on admission showed no abnormality. Plain CT scan revealed a well defined low density area with calcification in the right frontal lobe. A part of peripheral portion of low density area were well enhanced with contrast media. At operation, there was a cyst containing xanthochromic fluid in the right frontal lobe. A part of cyst well near the cerebral surface was reddish hard. Total removal of nodular tumor and subtotal removal of the cyst wall were performed. He has been doing well for these 3 years following craniotomy and has no deficit without CT evidence of recurrent tumor. Histologically the tumor cells displayed marked pleomorohism. However either necrosis or mitosis were not seen. Frequently these cells had vacuolated or foamy cytoplasm. There were many of the giant cells and multinucleated cells. In some area, these tumor cells were surrounded by a fine network of reticulin fibers. Electron microscopically the tumor cells were occasionally filled with glial filament and lipid granules were seen. Immunoperoxidase technique revealed GFAP in the cytoplasm of the tumor cells. This case was considered to be pleomorphic xanthoastrocytoma first proposed by Kepes.

Astrocytoma↗

Sources of extramitochondrial corticoidogenic cholesterol in the adrenal cortex.

Intracellular sources of extramitochondrial corticoidogenic cholesterol in bovine, rat and hamster adrenocortical cells were examined in vitro by comparing the species differences in the effects of various inhibitors on the adrenocorticotropic hormone (ACTH)-induced corticoidogenesis. The inhibitors were ML-236B (3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor), W-7 (N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide; calmodulin inhibitor), dichlorvos (O,O-dimethyl-2,2-dichlorovinyl phosphate; organic phosphorylation inhibitor), chloroquine [7-chloro-4-4-diethylamino-1-methyl-butylamino) quinoline; lysosomal enzyme inhibitor) and cycloheximide (protein synthesis inhibitor). During 2 to 3 hr incubation periods, the ACTH-induced corticoidogenesis was not inhibited by ML-236B (100 microM) in the bovine and rat adrenocortical cells. In the hamster adrenocortical cells, ML-236B (100 microM) did not affect the ACTH-induced corticoidogenesis during the initial 1 hr incubation periods; but thereafter, the ACTH-induced corticoidogenesis during the subsequent 2 hr incubation periods was completely blocked by ML-236B. The ACTH-induced corticoidogenesis was inhibited by W-7 (up to 25 microM) in the bovine and rat adrenocortical cells, but this was not the case in the hamster cells. Chloroquine (up to 400 microM) inhibited the ACTH-induced corticoidogenesis in the adrenocortical cells of three different species, but the hamster adrenal cells were much more vulnerable than the bovine and rat cells. The ACTH-induced corticoidogenesis in the adrenocortical cells of three different species were equally inhibited by cycloheximide (up to 1 mM).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗

[Photoradiation therapy of experimental brain tumor].

Malignant tumors retain hematoporphyrin to a much greater extent than do normal tissues and can be destroyed by exposure to light. To utilize this mechanism in the treatment of malignant brain tumor, we investigated the antitumor effect of photoradiation on rat and mouse glioma, utilizing hematoporphyrin administration and cold light irradiation. In vitro study of rat glioma (EA285), the tumor cells which were exposed to hematoporphyrin and light irradiation showed marked degeneration in a short time, though no change was found in the control groups of hematoporphyrin administration alone and of light irradiation alone. The subcutaneously transplanted gliomas of rat and mouse also showed the growth inhibition after treatment of hematoporphyrin and light irradiation, though they grew up again. Histological degeneration by this treatment reached about 7 mm depth in the tumor. It was made clear that the effect on gliomas was induced by photosensitization and not by heat. From these results it is concluded that photoradiation therapy would be a great means for adjuvant therapy for malignant brain tumor.

Animals↗

[Spontaneous epidural hematoma--report of two cases].

We report two cases of spontaneous epidural hematoma associated with the hemorrhagic diathesis and the paranasal sinusitis. Case 1: A 31-year-old man with a history of subtotal gastrectomy because of gastric cancer. He complained of headache at left temporal region, but CT scan showed no abnormal finding. After about 12 hours, he was found in comatose state. Emergency CT scan showed left epidural hematoma. He had the thrombocytemia and hemorrhagic diathesis which were supposed to be the side effect of the chemotherapy or DIC. Although the epidural hematoma was removed at emergency, he died 5 days after the operation, because of severe brain swelling. Case 2: A 34-year-old woman with a history of paranasal sinusitis. At 3 weeks after her fourth delivery, she had a headache and a right orbital swelling. She was admitted to the otorhinolaryngologist under the diagnosis of the acute paranasal sinusitis and orbital phlegmone. After admission, the level of consciousness became worse, she was given neurosurgical consultation. Angiogram showed right temporal mass lesion. At operation, the epidural hematoma was found and evacuated. She was discharged without any neurological deficits.

Adult↗

Possible involvement of Ca2+-calmodulin system in cyclic AMP action in cholesterol ester hydrolytic response to ACTH in bovine adrenocortical cells.

In order to elucidate the relationship between cyclic AMP and the Ca2+-calmodulin system in the steroidogenic response to adrenocorticotropic hormone (ACTH), the effects of calmodulin inhibitors (trifluoperazine and W-7) on cortisol production and cellular cholesterol ester hydrolysis induced by ACTH or dibutyryl cyclic AMP in bovine adrenocortical cells were examined in the absence of extracellular Ca2+. These calmodulin inhibitors inhibited not only the cortisol production and the cholesterol ester hydrolysis induced by ACTH in the absence of extracellular Ca2+, but also inhibited the dibutyryl cyclic AMP-induced cortisol production and the cholesterol ester hydrolysis in the absence of extracellular Ca2+. These results suggested the possibility that cyclic AMP action was mediated by the Ca2+-calmodulin system in the activation process of cellular cholesterol ester hydrolysis in the steroidogenic response to ACTH.

Adrenal Cortex↗