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Biomedical subjects

K Toda

Publications and source records attributed to K Toda.

At least 181 records · Page 10Linked to original sources

Membrane-bound respiratory system of Enterobacter cloacae strain HO1 grown anaerobically with chromate.

Chromate has been demonstrated to be an electron acceptor in the respiratory chain of anaerobically grown Enterobacter cloacae strain HO1. By using potentiometric titration and low temperature spectroscopy, the spectral absorption of the anaerobic membrane vesicles of this organism in the presence of chromate was resolved into six peaks at 548, 549, 550, 555, 556, and 558 nm in the alpha band of the reduced minus oxidized spectra. The spectra elicited by chromate are attributed to cytochromes c548, c549, c550, b555, b556, and b558. Among these cytochromes, c548 was found to be specifically involved in electron transfer to chromate.

Anaerobiosis↗

Modulatory effects of interferon-gamma on the fibronectin receptor function of squamous cell carcinoma cells in vitro.

We previously showed that the in vivo invasion of a squamous cell carcinoma induced by the intradermal injection of tumor cells was significantly delayed after the IFN-gamma-producing gene transfer to tumor cells. With respect to the mechanism of the delayed invasion, it was suggested that the IFN-gamma might inhibit the adhesion of the cells to extracellular matrices (ECM) and the subsequent locomotion. Thus, we examined the effect of IFN-gamma on the adhesion of Pam-T cells to ECM. The attachment of Pam-T cells to fibronectin (FN) was significantly higher than that to laminin (LN), collagen type I (COL I) or collagen type IV (COL IV) substrata. The attachment to FN was significantly enhanced specifically by the IFN-gamma-treatment of the cells, although the attachment to LN, COL I or COL IV was not altered by IFN-gamma. Neither IFN-alpha nor IFN-beta had any effect on the attachment of Pam-T cells to FN. When Pam-T cells were treated with IFN-gamma together with a neutralizable anti-IFN-gamma antibody, this enhancement was completely abolished. Moreover, the attachment of IFN-gamma-treated Pam-T cells as well as non-treated cells to FN was blocked by the synthetic peptide Arg-Gly-Asp-Ser (RGDS), but not by the control peptide Arg-Gly-Glu-Ser. Based on these results, we conclude that IFN-gamma specifically enhances the adhesiveness of Pam-T cells to FN substrata by the modulation of integrin activity.

Amino Acid Sequence↗

Morphological characterization of hemangiomatous tumors derived from a novel murine vascular endothelial cell line (F-2).

Hemangiomatous tumors were induced in Balb/c nude mice by inoculating F-2 cells (5 x 10(6)) from a novel tumorigenic murine endothelial cell line which had been established and maintained in our laboratories. These tumors were morphologically investigated in the course of development. Subcutaneous hemorrhage was observed at the inoculation site within 12 hours after the injection of F-2 cells, followed by development of skin tumors of various sizes at the same sites. They were dome-shaped, glossy surfaced, black, soft tumors. Mice finally died of massive blood loss due to internal and/or external hemorrhage (on day 10-77). Light microscopically, F-2 cells formed aggregates immediately after inoculation and then branched into a network of channels and cysts containing erythrocytes. Thereafter, spongiform structures composed of various sizes of cysts appeared with subsequent formation of a single large blood-filled cyst lined by one or two layers of thin cells. Under an electron microscope, F-2 cells, possessing large amounts of cytoplasm, formed narrow spaces which were occasionally incomplete with ambiguous basal lamina at the early stages. However, later, in large cysts, they became attenuated, tightly connected, and produced complete lumen surrounded by a basal lamina. Immunohistological demonstration of H-2 K, D antigen showed that tumors induced by F-2 cells mainly consisted of the inoculated F-2 cells. These results indicate that F-2 presents a good experimental system for investigation of vascular endothelial cell tumorigenesis and differentiation.

Animals↗

Computed tomographic findings in relation to event-related potentials during visual discrimination tasks in patients with multiple cerebral infarcts.

Event-related potentials were recorded for 29 patients with multiple cerebral infarcts (MCI) (mean age, 65.7 years) during visual discrimination tasks to clarify the relationship between computed tomographic findings (CT) and P300 component. P300 latency in patients with MCI was significantly longer than that of 15 age-matched normal subjects (mean age, 65.4 years), although no significant difference was found in P300 amplitude between the two groups. There was a significant negative correlation between P300 latency and mental status as determined by the Hasegawa's Dementia Scale. Significant correlation was also found between P300 latency and the degree of ventricular dilatation or severity of periventricular lucency (PVL) on CT scan. P300 latency was not significantly correlated with the number of infarcts. P300 latency in patients with MCI thus appears related to the severity of PVLs and degree of ventricular dilatation in addition to mental status.

Cerebral Ventriculography↗

Cerebral blood flow and event-related potential in patients with multiple cerebral infarcts.

Cerebral blood flow and P300, a long-latency, positive component of the scalp-recorded, event-related potential (ERP), were measured in 26 patients with multiple cerebral infarcts (mean age, 65.0 years). Compared with age-matched normal subjects, patients with multiple cerebral infarcts had significantly lower cortical blood flow values and had prolongation of the P300 latency. There was a significant correlation between the P300 latency and the mean cortical blood flow values in patients with multiple cerebral infarcts. These results suggest that, in patients with multiple cerebral infarcts, the cognitive impairment associated with change of the ERP may be related to reduction of cortical blood flow.

Aged↗

[Cognitive processes in Parkinson's disease--an event-related potential analysis].

Event-related potentials (ERPs) occurring in response to attended and unattended stimuli were studied in 31 patients with Parkinson's disease (mean age: 66.9 years), 9 patients with Alzheimer's disease (mean age: 73.6 years) and 37 normal subjects (mean age: 47.5 years). Of the 31 patients with Parkinson's disease, 6 met the criteria for dementia in DSM-III-R. ERPs were recorded during the performance of visual discrimination tasks using three kinds of stimuli: frequent non-target (62%), infrequent non-target (19%) and infrequent target (19%) stimuli. The P3a and P3b were identified as the components of the P3 (P300) responses to infrequent non-target stimuli and infrequent target stimuli. Both the P3a and P3b latencies were significantly prolonged with normal aging. Nine of the Parkinson's disease patients showed a P3b latency above the 95% confidence limit of the age estimated regression line, while only one patient showed a prolonged P3a latency. There was no significant correlation between the P3a and P3b latencies in the patients with Parkinson's disease, although a significant correlation was found in the normal subjects. There was a significant correlation between the P3b latency and Hasegawa's dementia scale (HDS) score although the P3a latency showed no correlation with HDS score. These results indicate that the P3a and P3b components have some differences. In demented patients with Parkinson's disease, the P3b latency was significantly longer than that in 15 age-matched normal subjects, although no significant difference was found in the P3a latency. On the other hand, patients with Alzheimer's disease showed a significant prolongation of both P3a and P3b latencies compared to the age-matched normal subjects. Furthermore, there was a significant difference in P3a latency between demented patients with Parkinson's disease and those with Alzheimer's disease. There were no significant differences in any of the amplitudes among these three groups. These results suggest that the automatic processing stage, as reflected by P3a, may be less impaired than attentional controlled processing reflected by P3b in patients with Parkinson's disease, and further indicate that there may be some differences in the changes of the cognitive process between patients with Parkinson's disease and those with Alzheimer's disease.

Aged↗

Fiberoptic ductoscopy of the breast: a new diagnostic procedure for nipple discharge.

A fiberoptic ductoscopy system was successfully developed by means of which we were able to observe the duct cavity of the breast. Two kinds of silicafiberscopes with outer diameters 0.80 and 0.45 mm were used in the present study. Fiberoptic ductoscopy was applied to 52 ducts in 46 patients with nipple discharge for whom no tumor was palpable; the intraductal appearance could be observed in 47 ducts from 41 patients (90.3%). Fourteen ducts from 13 patients were operated upon and were histologically diagnosed as carcinoma (four cases), intraductal papilloma (nine ducts from eight patients) and mastitis (one case). The internal surface of a normal duct was lustrous and smooth. Cancer growing on the surface of a duct wall appeared white and was slightly elevated, forming a bridging structure. The intraductal papillomas formed intraductal solid nodules, being yellow in most cases and red at the site of hemorrhage. Fiberoptic ductoscopy can be used to recognize the growth of minute intraductal lesions in cases of nipple discharge. Clinical endoscopic diagnosis for minute intraductal lesions will make an important contribution to the early detection of cancer and the evaluation of nipple involvement in intraductal carcinoma.

Breast Neoplasms↗

Fc epsilon receptor II/CD23-positive lymphocytes in atopic dermatitis. I. The proportion of Fc epsilon RII+ lymphocytes correlates with the extent of skin lesion.

Cells expressing Fc receptors for IgE (Fc epsilon RII) were identified in the peripheral blood from patients with atopic dermatitis and with eczematous dermatitis, and normal non-atopic subjects by using monoclonal antibodies to human lymphocyte Fc epsilon RII, and to lymphoid cell-surface antigens by immunofluorescence staining. Based on the extent of the dermatitis patients were classified as severe (greater than 50% skin surface involved), moderate (50-10%) and mild (less than 10%). Patients with severe and moderate atopic dermatitis had 5.9% and 5.7% Fc epsilon RII+ peripheral blood mononuclear cells (PBMC), respectively, that were significantly higher than percentages in mild atopic dermatitis patients (2.6%), severe to moderate eczematous dermatitis patients (2.3%), mild eczematous dermatitis patients (2.2%) and normal individuals (1.7%)(0.05 greater than P). In severe and moderate atopic dermatitis patients, 10% of Fc epsilon RII+ PBMC were T cells that preferentially expressed CD8, and the remainder B cells and monocytes. Fc epsilon RII+ T cells comprised 1% of peripheral T cells, while half or more of peripheral B cells expressed Fc epsilon RII. In mild atopic dermatitis patients, eczematous dermatitis patients and normal subjects. Fc epsilon RII were expressed exclusively on 25-35% of peripheral B cells. Short-term treatment and long-term follow-up of atopic dermatitis patients revealed that changes in the skin condition were related closely to fluctuations in the proportion of Fc epsilon RII+ PBMC. Total serum IgE levels and atopic respiratory allergy did not influence the percentage of Fc epsilon RII+ PBMC. These findings suggest that the percentage of Fc epsilon RII+ PBMC reflects the extent of atopic dermatitis.

Adolescent↗

Lichen sclerosus et atrophicus, morphea, and coexistence of both diseases. Histological studies using lectins.

Histological studies using three lectins, lens culinaris agglutinin, soybean agglutinin, and Ulex europaeus agglutinin-I, were carried out in a case of coexistent lichen sclerosus et atrophicus and morphea, five cases of morphea, and two cases of lichen sclerosus et atrophicus. The lectin staining patterns of the formaldehyde-fixed epidermis of patients with morphea were not different from those of normal epidermis, but epidermis of patients with lichen sclerosus et atrophicus showed different staining patterns. Lens culinaris agglutinin stained the basal and the spinous layers of the normal epidermis and that of patients with morphea but stained only the basal cells of the epidermis from patients with lichen sclerosus et atrophicus; epidermal Ulex europaeus agglutinin binding was observed only in the cases of lichen sclerosus et atrophicus. Moreover, in the patient with coexistent diseases, the morphea lesion showed the staining profiles of morphea and the lichen sclerosus et atrophicus lesion showed the staining patterns of lichen sclerosus et atrophicus, respectively.

Adolescent↗

[Effect, recurrence and prognosis of intra-arterial infusion chemotherapy with anticancer agents for advanced breast cancer--especially, the significance of tumor blood vessels].

Between January 1977 and March 1991, 86 patients of Stage III and Stage IV breast cancer were treated by intra-arterial infusion chemotherapy (IAIC) in Sapporo Medical College. The 5- and 10-year overall survival rates of Stage III b were: infusion group 53.1% and 53.1%, non infusion group 50.1% and 16.7%, respectively. A significant difference was seen in the 10-year survival rate (p less than 0.05). The 5- and 10-year overall survival rate of Stage III b histologically effective group was 67.3% and non-effective group 31.8%. A significant difference was seen between these two groups (p = 0.0241). A significant difference was seen between n2 positive Stage III b infusion group and non-infusion group in 7-year survival rate (p less than 0.01). The ischemic effect on tumor cells by degeneration changes of the blood vessels was important for the histological effect. Pre-operative angiography helped in the choice of anticancer agents. The sufficient adjuvant chemo-endocrine therapy will assure a good prognosis for IAIC-treated Stage III b breast cancer patients.

Antineoplastic Combined Chemotherapy Protocols↗

Human poly(ADP-ribose) polymerase gene. Cloning of the promoter region.

The promoter region of the poly(ADP-ribose) polymerase gene has been isolated using a Sau3AI genomic library derived from human leukocyte. It lacks typical transcriptional regulatory elements such as TATA and CAAT boxes, but it contains two potential Sp1 binding sites and three putative AP-2 binding elements. The region up to nucleotide position-99 in relation to the predominant transcriptional initiation site exhibits promoter activity as judged by chloramphenicol acetyltransferase assay and the activity is enhanced both by cAMP and by phorbol ester. Northern blot and Western blot analyses have revealed that expression of the polymerase gene is also stimulated by both of these compounds in cultured HeLa cells. Southern blot hybridization of genomic DNA separately digested with various endonucleases gives a discrete single band in each case when the 5'-untranslated region of the polymerase cDNA is used as a probe. These results indicate that poly(ADP-ribose) polymerase is encoded by a unique gene whose expression is regulable by cAMP and by phorbol ester.

Amino Acid Sequence↗

Cloning and expression of a cDNA for human cytochrome P-450aldo as related to primary aldosteronism.

A cDNA clone encoding human aldosterone synthase cytochrome P-450 (P-450aldo) has been isolated from a cDNA library derived from human adrenal tumor of a patient suffering from primary aldosteronism. The insert of the clone contains an open reading frame encoding a protein of 503 amino acid residues together with a 3 bp 5'-untranslated region and a 1424 bp 3'-untranslated region to which a poly(A) tract is attached. The nucleotide sequence of P-450aldo cDNA is 93% identical to that of P-450(11) beta cDNA. Catalytic functions of these two P-450s expressed in COS-7 cells are very similar in that both enzymes catalyze the formation of corticosterone and 18-hydroxy-11-deoxycorticosterone using 11-deoxycorticosterone as a substrate. However, they are distinctly different from each other in that P-450aldo preferentially catalyzes the conversion of 11-deoxycorticosterone to aldosterone via corticosterone and 18-hydroxycorticosterone while P-450(11)beta substantially fails to catalyze the reaction to form aldosterone. These results suggest that P-450aldo is a variant of P-450(11)beta, but this enzyme is a different gene product possibly playing a major role in the synthesis of aldosterone at least in a patient suffering from primary aldosteronism.

Amino Acid Sequence↗

Structural and functional characterization of human aromatase P-450 gene.

The gene encoding aromatase P-450 (CYP XIX) has been isolated from two types of human genomic DNA libraries. It spans at least 70 kb and consists of 10 exons. The translational initiation site and the termination site are located in exon 2 and exon 10, respectively. The promoter region of the gene contains a TATA box, a CAAT box and two putative AP-1 binding sites beginning at -28, -83, -55 and -68 bp, respectively, from the transcriptional initiation site. In addition, a palindromic nucleotide sequence is observed between -209 and -196 and two types of repetitious hexanucleotide (consensus: AATGAA and CCATAAGG) are also present within the regions between -485 and -433 and between -358 and -331. Transient expression studies of chloramphenicol acetyltransferase constructs bearing various lengths of 5'-flanking region of the gene show that the region between -500 and -243 contains negative cis-acting element(s), whereas the region between -242 and -183 is required for efficient transcriptional activity. Northern blot analysis demonstrates that the expression of aromatose P-450 gene is remarkably stimulated by treatment of cells with 12-O-tetradecanoyl-phorbol 13-acetate. By chloramphenicol acetyltransferase assay the region up to nucleotide position -242 relative to the transcriptional initiation site is shown to participate in the transcriptional responsiveness to this phorbol ester.

Amino Acid Sequence↗

Cloning of cDNA and genomic DNA for human cytochrome P-45011 beta.

A full-length cDNA clone encoding steroid 11 beta-hydroxylase (P-45011 beta) has been isolated from a cDNA library derived from human adrenal tumor. The insert of the clone contains an open reading frame encoding a protein of 503 amino acid residues together with a 4 bp 5'-untranslated region and a 576 bp 3'-untranslated region to which a poly(A) tract is attached. The promoter region of the P-450(11) beta gene has also been isolated from a genomic library derived from human pre-B cells. It contains a TATA box, a putative cAMP-responsive element, several repeated sequences and two sequence elements similar to the consensus sequence for binding of AP-1. A transient expression assay in Y-1 adrenal tumor cells demonstrates that the promoter activity is remarkably enhanced by treatment of the cells with cAMP. In addition, analysis using deletion mutants containing various lengths of the 5'-flanking region of the gene suggests that several cis-acting elements participate in transcriptional regulation of human P-450(11) beta gene.

Adrenal Gland Neoplasms↗

Establishment and characterization of a tumorigenic murine vascular endothelial cell line (F-2).

A new murine cell line, designated F-2, was established from an ultraviolet light-induced tumor which developed on the back skin of a BALB/c x C57BL/6 F1-nu/nu nude mouse. More than 1 x 10(5) F-2 cells injected into nude mouse skin produced rapidly developing hemangiomatous lesions. F-2 had a 14-h doubling time under 10% fetal calf serum-containing Dulbecco's modified Eagle's medium culture conditions without any cell growth factor supplementation, and it showed "cobblestone" appearance at confluency. F-2 was able to rapidly differentiate on Matrigel with resultant fine network structure and tubule formation. Ultrastructural observations of the tubule demonstrated that the F-2 cells were connected to each other by intermediate junctions and arranged to form spaces, but that no Weibel-Palade bodies were found in the cytoplasm. F-2 also showed the active uptake of fluorescent-labeled acetylated low-density lipoprotein at 37 degrees C but not at 4 degrees C, and it showed prominent binding to the lectin, Griffonia simplicifolia I agglutinin. The addition of fibroblast growth factor did not facilitate the growth of F-2 cells. These findings strongly suggest that F-2 is a transformed cell line with tumorigenicity and vascular endothelial cell properties, and it may be useful in the study of vascular tumor biology.

Animals↗

Non-reciprocal facilitation of trigeminal motoneurons innervating jaw-closing and jaw-opening muscles induced by iontophoretic application of serotonin in the guinea pig.

Effects of iontophoretically applied serotonin (5-HT) and its antagonist, methysergide (MS), on masseter (a jaw-closer, MA.MNs) and anterior digastric motoneurons (a jaw-opener, AD.MNs) were studied in paralyzed guinea pigs, chloralose-anesthetized or decerebrate. Unitary activity was recorded with multibarrel capillary electrodes from MA.MNs and AD.MNs identified by antidromic spikes evoked by stimulation of the masseter and anterior digastric nerves, respectively. Under chloralose anesthesia, both MA.MNs and AD.MNs were almost quiescent, and application of 5-HT alone induced no changes in discharge of either of them. However, iontophoretically applied 5-HT increased the frequency of discharge induced by iontophoretic application of glutamate in 26 of 34 MA.MNs (76%) and 17 of 30 AD.MNs (59%) tested. MS depressed the glutamate-induced activity in 17 MA.MNs and 3 AD.MNs, respectively, in which 5-HT exerted a facilitatory effect on the glutamate-induced activity. In decerebrate preparations, the firing index of spikes of MA.MNs monosynaptically evoked by stimulation of the trigeminal mesencephalic nucleus was increased by 5-HT and decreased by MS. 5-HT also enhanced the discharge of MA.MNs induced by a ramp-and-hold stretch of the masseter muscle. We conclude that 5-HT alone does not excite either MA.MNs or AD.MNs, but potentiates the effect of excitatory inputs to them: 5-HT exerts a modulatory facilitatory action on trigeminal motoneurons.

Action Potentials↗

Chromate-resistance in a chromate-reducing strain of Enterobacter cloacae.

Resistance to toxic hexavalent chromium (chromate: CrO4(2)) in Enterobacter cloacae strain HO1, isolated from an activated sludge sample, was investigated under aerobic and anaerobic conditions. Decreased uptake of 51CrO4(2-) in E. cloacae strain HO1 was observed under aerobic conditions, when compared with a standard laboratory E. cloacae strain (IAM 1624). Under anaerobic conditions E. cloacae strain HO1 was able to reduce hexavalent chromium to the less toxic trivalent form. When E. clocacae strain HO1 was grown with nitrate anaerobically, the cells were observed to lose simultaneously their chromate-reducing ability and chromate-resistance under anaerobic conditions.

Anaerobiosis↗