Biomedical subjects

T Okuda

Publications and source records attributed to T Okuda.

At least 145 records · Page 8Linked to original sources

PubMed1997

Modulation of renal hemodynamics by IGF-1 is absent in spontaneously hypertensive rats.

We recently reported that attenuation of vasoactive agent-induced calcium signal and cell contraction of mesangial cell by insulin-like growth factor 1 (IGF-1), observed in normal mesangial cells, is totally abolished in spontaneously hypertensive rat (SHR) mesangial cells. This phenomenon might be related to the well-known aberrant regulation of SHR glomerular hemodynamics. Since it has been reported that in vivo IGF-1 infusion increases renal plasma flow (RPF) and glomerular filtration rate (GFR), we examined whether the modulation of renal function by IGF-1 is altered in SHR. We performed in vivo renal clearance studies using eight-week-old SHR and control Wistar Kyoto rats (WKY) before and after IGF-1 (5 micrograms/kg) infusion into the left renal artery for 20 minutes. Mean arterial pressure was not affected by IGF-1 in both WKY and SHR. In WKY, IGF-1 increased GFR and RPF, and decreased renal vascular resistance (RVR). However, GFR, RPF, and RVR were not altered by IGF-1 in SHR, while systemic infusion of angiotensin II antagonist, CV-11974, increased GFR and RPF. The present data show that the modulation of renal hemodynamics by IGF-1 is absent in SHR. This might be related the pathophysiology of the development of hypertension.

Animals↗

PubMed1997

Internal tandem duplication of the FLT3 gene is preferentially seen in acute myeloid leukemia and myelodysplastic syndrome among various hematological malignancies. A study on a large series of patients and cell lines.

In this study, we examined a large number of patients to clarify the distribution and frequency of a recently described FLT3 tandem duplication among hematopoietic malignancies, including 112 acute myelocytic leukemia (AML), 55 acute lymphoblastic leukemia (ALL), 37 myelodysplastic syndrome (MDS), 20 chronic myelogenous leukemia (CML), 30 non-Hodgkin's lymphoma (NHL), 14 adult T cell leukemia, 15 chronic lymphocytic leukemia (CLL) and 38 multiple myeloma (MM). We also evaluated 71 cell lines derived from 11 AML, 31 ALL, two hairy cell leukemia, three acute unclassified leukemia, 10 CML, 12 NHL including six Burkitt's lymphoma, and two MM. Using genomic PCR of exon 11 coding for the juxtamembrane (JM) domain and first amino acids of the 5'-tyrosine kinase (TK) domain, this length mutation was found only in AML (22/112, 20%) and MDS (1/37). According to the FAB subclassification, they were 5/18 (28%) of M1, 4/29 (14%) of M2, 3/17 (18%) of M3, 6/24 (25%) of M4, 4/20 (20%) of M5 and 1/9 of refractory anemia with excess of blast in transformation. In the various cell lines examined, this abnormality was determined in only one derived from AML and never found in other hematological malignancies. The sequence analysis of the abnormal PCR products revealed that 23 of 24 showed internal tandem duplication with or without insertion of nucleotides. In one AML, insertion and deletion without duplication was determined. All 24 lengthened sequences were in-frame. Duplication takes place in the sequence coding for the JM domain and leaves the TK domain intact. In conclusion, we emphasize that the length mutation of FLT3 at JM/TK-I domains were restricted to AML and MDS. Since all these mutations resulted in in-frame, this abnormality might function for the proliferation of leukemic cells.

Acute Disease↗

PubMed1997

Evaluation of acceleration plethysmograms in dermatology--efficacy of lipo PGE1 preparations against herpes zoster and neuralgia following herpes.

Reports published in recent years indicate that administration of lipo PGE1 is effective against herpes zoster and neuralgia following herpes. However, there are presently no standards to objectively assess efficacy. We therefore looked into the possibility of achieving this goal by using an acceleration plethysmograph. The results showed a significant difference in the rate of change of pulse waves after initiation of drip infusion as compared to before drip infusion among the effective group, the control group, and the non-effective group. This method appears to be useful to objectively assess both the analgesic effects of lipo PGE1 and the efficacy of drugs in general, based on data analysis. Our results suggest that investigations using this method may be able to predict the therapeutic effects of vasodilators and analyze hemodynamic disorders of the skin.

Alprostadil↗

PubMed1997

Analysis of hyperplastic foci in livers with hepatocellular carcinomas by flow cytometry and AgNOR staining.

The phase S ratio in cell cycles were analyzed in livers with hyperplastic foci (HPF) and in livers without HPF by nuclear DNA determinations using flow cytometry, and by staining with argyrophilic proteins of the nucleolar organizer region (AgNOR). Flow cytometric analysis was done on 50 fresh frozen specimens of livers resected from 50 patients with hepatocellular carcinoma (HCC). Paraffin sections from the same patients were analyzed using AgNOR staining. There were 25 cases each with and without HPF. We examined the stage of fibrosis and the grade of inflammatory activity according to the modified Scheuer and Desmet scale. The incidence of HCC recurrence among these patients was also studied. The average phase S ratio of the livers of the patients with HPF was 6.5 +/- 3.2%, and that of the livers of the patients without HPF was 4.0 +/- 2.5%. The ratio differed significantly between the two groups (P < 0.01). The average AgNOR score for HPF lesions of the HPF-positive cases was 1.60 +/- 0.34, that for non-HPF lesions in the HPF-positive cases was 1.29 +/- 0.12, and that for the HPF-negative cases was 1.19 +/- 0.14. Significant differences were found between the average AgNOR scores for HPF lesions of the HPF-positive cases and the non-HPF lesions of the HPF-positive cases (P < 0.01), as well as between the non-HPF lesions in the HPF-positive cases and the HPF-negative cases (P < 0.05). Severe fibrosis (stage 3) and cirrhosis (stage 4) were found in 76% of HPF-positive cases and 48% of HPF-negative cases. The livers of HPF-positive patients were significantly more cirrhotic than those of HPF-negative patients (P < 0.05). The association between HPF and the inflammatory grade was not significant (P > 0.05). The incidence of HCC recurrence among HPF-positive cases was significantly higher than that among the HPF-negative cases (P < 0.05). The average phase S ratio of the recurrent HPF-positive patients was 7.48 +/- 3.48%, significantly higher than that of HPF negative cases (5.57 +/- 3.06%, P < 0.05). Hyperplastic foci of the liver was shown to be a highly proliferative lesion. The proliferative activity of the non-HPF lesions in the HPF-positive patients was also higher than that of the HPF-negative patients. Hyperplastic foci tended to be present in cirrhotic livers, but it was not associated with the grade of inflammatory activity of the liver. Hyperplastic foci may represent an important predictor of recurrence after hepatic resection.

Adult↗

PubMed1997

[Properties of extracellular products produced by group A streptococci isolated from patients with streptococcal toxic shock syndrome].

Extracellular products of group A streptococci isolated from patients with streptococcal toxic shock syndrome (STSS) were examined. The outline of the discussion of the 3 products are as follows; streptolysin O (SLO), proteinase and erythrogenic toxin. SLO and proteinase showed a relatively large amount of products more than erythrogenic toxin. SLO produced by group A streptococci isolated from the patient with STSS had an isoelectric point (pI) of 6.0 and a molecular weight of 64,000 and showed hemolytic activity in the presence of 2-mercaptoethanol (2-ME). Furthermore, the hemolytic activities of all components were inhibited by gamma-globulin and cholesterol. Proteinase had pIs of 8.7 and 8.9, and a molecular weight of 21,000. These data suggest that STSS clinical criteria probably reflects a characteristic of a large amount of products of individual S. pyogenes isolates.

Bacterial Proteins↗

PubMed1997

Contents of resveratrol, piceid, and their isomers in commercially available wines made from grapes cultivated in Japan.

The presence of resveratrol (3,5,4'-trihydroxystilbene) and its beta-glucoside, piceid (resveratrol-3-beta-D-glucopyranoside), together with their isomers in wine appears to be one of the beneficial factors conferring a protective effect against cardiovascular disease through red wine ingestion. A total of 42 red and white wines was collected in areas from Hokkaido to Kyushu in Japan. The wines were fractionated with a C18 Sep-pak cartridge, and the active principles were eluted with ethyl acetate. Crude trans- and cis-piceid were extracted from a Chinese medicine, 'Kojohkon' (Polygonum cuspidatum), and their retention times and UV absorption were confirmed by HPLC. trans- and cis-Resveratrol, and trans- and cis-piceid were analyzed in a short C18 HPLC column, and cis-resveratrol was quantified from the amount of cis-isomer converted from authentic trans-resveratrol that had been treated by UV irradiation. The content of piceid is shown as the resveratrol equivalent. The average content of total stilbene compounds was 4.37 mg/liter in red wines, while only 0.68 mg/liter in white wines. Red wines made from Pinot noir, Merlot, and Zweigeltrebe grapes all had a high resveratrol content.

Chromatography, High Pressure Liquid↗

PubMed1997

TMC-2A, -2B and -2C, novel dipeptidyl peptidase IV inhibitors produced by Aspergillus oryzae A374. I. Taxonomy of producing strain, fermentation, and biochemical properties.

TMC-2A(1), -2B (2) and -2C (3), novel dipeptidyl peptidase IV (DPIV) inhibitors, were isolated from the fermentation broth of Aspergillus oryzae A374. TMC-2A, -2B and -2C inhibited rat kidney DPIV with IC50 value of 8.1 microM, 17 microM, and 20 microM, respectively, as well as human DPIV prepared from mononuclear cells and adenocarcinoma cells. TMC-2 compounds inhibited only DPIV among the proteases tested, indicating their high selectivity for DPIV. The kinetic analyses revealed that TMC-2A was an uncompetitive inhibitor. Taxonomy and fermentation of the producing strain are also described.

Animals↗

PubMed1997

T2 shortening in the visual cortex: effect of aging and cerebrovascular disease.

PURPOSE: To evaluate the effect of aging and cerebrovascular disease on T2 shortening in the visual cortex at MR imaging. METHODS: MR images of 72 neurologically normal subjects (45 men and 27 women, 35 to 92 years old) and 32 (13 men and 19 women, 54 to 92 years old) with cerebrovascular disease were evaluated retrospectively. On T2-weighted spin-echo images, the signal intensity of the visual, motor, and sensory cortices was divided into three grades and compared with the signal intensity of the frontal subcortical white matter. RESULTS: Decreased signal intensity (grade III) was rarely seen in the visual and sensory cortices of the neurologically normal subjects who were less than 60 years old. The signal intensity of the motor cortex decreased rapidly after the age of 50 years. At 61 to 70 years of age, 53% of these subjects had grade III intensity, and at age 71 years or older, 94% had reached grade III. The frequency of progression from grade I to grade III was lower in the visual cortex than in the motor cortex; 22% of these subjects had grade III appearance at age 61 to 70 years, and at age 71 years older, 56% had reached grade III. In patients with cerebrovascular disease who were older than 60 years of age, the frequency of grade III signal intensity in the visual cortex was almost equal to that in the neurologically normal subjects. CONCLUSIONS: T2 shortening in the visual cortex is frequently seen in neurologically normal older persons. These findings are compatible with a previously reported histochemical study of normal iron deposition in the visual cortex. Cerebrovascular disease has no effect on T2 shortening in the visual cortex.

Adult↗

PubMed1997

CT and MR findings of denervated tongue after radical neck dissection.

PURPOSE: To describe the CT and MR findings in the denervated tongue after a radical neck dissection. METHODS: We retrospectively evaluated the radiologic findings in seven patients who had hypoglossal paralysis following radical neck dissection. None of the patients had clinical or radiologic evidence of tumor recurrence. RESULTS: The side of the tongue operated on showed low density on CT scans. At MR imaging, denervated tongues were clearly seen as hyperintense relative to muscle on T2-weighted images; on T1-weighted images, the signal was hypointense to hyperintense, representing increased extracellular water or fatty degeneration. CONCLUSION: In patients who have undergone a neck dissection for a malignant process, abnormal imaging findings in the tongue not only might indicate a recurrence of tumor involving the hypoglossal nerve but also suggest the possibility of postoperative change. Our findings emphasize the importance of the denervated tongue in differentiating inflammatory from neoplastic diseases of the the tongue.

Adult↗

PubMed1997

MR of epidermoids with a variety of pulse sequences.

PURPOSE: To assess the usefulness of fluid-attenuated inversion recovery (FLAIR) and constructive interference in steady state (CISS) sequences in depicting epidermoid tumors. METHODS: Six patients with surgically confirmed epidermoid tumors in the subarachnoid space were examined with T1-weighted MR imaging with a spin-echo sequence, and with T2- and proton density-weighted imaging with a fast spin-echo sequence, a FLAIR sequence, and a CISS sequence. In the qualitative analysis, three observers compared the five sequences for visibility of tumors and presence of artifacts. A quantitative analysis was also performed by measuring the contrast-to-noise ratio. RESULTS: On visual assessment, the FLAIR sequence depicted all tumors as hyperintense relative to cerebrospinal fluid. The CISS sequence depicted all tumors as hypointense relative to cerebrospinal fluid and was considered to show tumor extension better than the FLAIR sequence. At quantitative analysis, the mean contrast-to-noise ratios of tumor to cerebrospinal fluid on T1-, T2-, and proton density-weighted images, and on FLAIR and CISS sequences were 2.85, 3.41, 4.42, 16.13, and 20.23, respectively. The contrast-to-noise ratios for the FLAIR and CISS sequences were significantly higher than those for the T1-, T2-, and proton density-weighted sequences. The contrast-to-noise ratio was not significantly different between FLAIR and CISS sequences, although the CISS sequence was slightly superior. CONCLUSION: CISS and FLAIR sequences depicted epidermoid tumors in the subarachnoid spaces better than conventional spin-echo images did. The CISS sequence produced a relatively constant contrast between the tumors and less artifactual interference.

Adolescent↗

PubMed1996

High-performance liquid chromatography using on-line solid-phase extraction: determination of furosemide in human serum.

An on-line solid-phase extraction technique based on column switching (heart-cutting) was developed for direct injection analysis of furosemide in human serum. In order to minimize the influence of deterioration in pre-treatment column efficiency, which was caused by protein precipitation with repeated injections of serum, furosemide was completely enriched at the top of the analytical column by ion-pair formation with tetra-n-butylammonium ion during heart-cutting. The robustness of the established on-line solid-phase extraction system was confirmed under routine conditions. As a result, almost comparable chromatograms could be obtained even though 50 repeated injections of a 100-microliter volume of serum were carried out using one pre-treatment column. The linearity of the calibration curves was demonstrated by the correlation coefficient which was greater than 0.99999 (5-1000 ng/ml). The relative errors and C.V. of quality control samples were within 4.00 and 5.88%, respectively (furosemide concentrations: 5, 100 and 1000 ng/ml).

Chromatography, High Pressure Liquid↗

PubMed1996

Quantitation of a new potent angiotensin II receptor antagonist, TCV-116, and its metabolites in human serum and urine.

A sensitive high-performance liquid chromatographic (HPLC) method is described for the determination of a new potent antihypertensive agent, TCV-116, and its two metabolites (M-I and M-II) in human serum or urine. After pre-treatment of the specimens, the analytes were determined using a column switching technique, except for the metabolites in urine which were determined by gradient elution mode HPLC. The quantitation limits for TCV-116, M-I and M-II were all 0.5 ng/ml in serum, and 0.5, 10 and 110 ng/ml in urine, respectively. The methods were applied to clinical trials of TCV-116.

Angiotensin II↗

PubMed1996

High-performance liquid chromatographic determination of pioglitazone and its metabolites in human serum and urine.

A high-performance liquid chromatographic (HPLC) method for the simultaneous determination of pioglitazone and its metabolites (M-I to M-V) in human serum and urine was developed. The method for serum involved the solid-phase and liquid-liquid extraction. Urine with and without enzymatic hydrolysis using beta-glucuronidase was treated with liquid-liquid extraction. The compounds in the extract were analyzed using HPLC with UV detection at 269 nm. The detection limits of pioglitazone, M-I, M-II, M-III, M-IV, and M-V in serum were 0.01-0.05 micrograms/ml, those in urine were 0.1-0.5 micrograms/ml, and those in urine after enzymatic hydrolysis were 0.3-0.5 micrograms/ml, respectively. The method was applied to the clinical trials of pioglitazone.

Calibration↗

PubMed1996

AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis.

The AML1-CBF beta transcription factor is the most frequent target of chromosomal rearrangements in human leukemia. To investigate its normal function, we generated mice lacking AML1. Embryos with homozygous mutations in AML1 showed normal morphogenesis and yolk sac-derived erythropoiesis, but lacked fetal liver hematopoiesis and died around E12.5. Sequentially targeted AML1-/-es cell retained their capacity to differentiate into primitive erythroid cells in vitro; however, no myeloid or erythroid progenitors of definitive hematopoietic origin were detected in either the yolk sac or fetal livers of mutant embryos. Moreover, this hematopoietic defect was intrinsic to the stem cells in that AML1-/-ES cells failed to contribute to hematopoiesis in chimeric animals. These results suggest that AML1-regulated target genes are essential for definitive hematopoiesis of all lineages.

Animals↗

PubMed1996

Characteristic histologic features of human hepatocellular carcinoma with mutant p53 protein.

To characterize hepatocellular carcinoma (HCC) cells with mutant (m) p53 protein histologically, we examined 68 main nodules and 20 accessory lesions of 72 patients with HCC who underwent hepatic resection between October 1990 and September 1993. Some sections were fixed in periodate-lysine-paraformaldehyde, embedded in OCT compound, and stained with the mouse monoclonal antibody PAb1801 to m-p53 protein by the immunoperoxidase technique with avidin-biotin complexes. Other sections were fixed in 20% buffered formalin, embedded in paraffin, and stained with the mouse monoclonal antibody DO-1 to m-p53 protein in the same way. Lesions in which cells had nuclei stained for m-p53 protein were defined as being positive for the protein; 25 of the 68 main nodules and 14 of the 20 accessory lesions were positive. Large main nodules were more likely to be positive than small ones. Microscopic examination showed that a larger proportion of poorly differentiated main nodules than well differentiated nodules were positive. Larger proportions of main nodules with extracapsular invasion, septa, portal thrombi, or intrahepatic metastases were positive than main nodules without these features. Accessory lesions that seemed to be metastatic were almost all positive, but few accessory lesions that seemed to be of multicentric occurrence were positive. Our results suggest that lesions with m-p53 protein had a high grade of malignancy and metastasized readily.

Adult↗

PubMed1996

The effect of ovariectomy on the temporomandibular joints of growing rats.

PURPOSE: This investigation studied the effects of ovariectomy, on the temporomandibular joints (TMJ) of young rats. MATERIALS AND METHODS: Four-week-old female Wistar rats were ovariectomized and killed at the intervals of 1, 2, 4, and 8 weeks postoperatively. Histomorphometric study of the TMJ was performed in a synchronous manner with an age-matched sham-operated control group. The serum levels of estrogen, calcitonin, and C-terminus parathyroid hormone were also determined. RESULTS: In the sham-operated control group, the serum levels of estrogen and calcitonin increased with age. An increase of the bone volume, with a concomitant increase of the osteoid surface, was observed at 12 weeks. Thickness of the articular soft tissue was decreased with increasing age. In the ovariectomized animals, serum estrogen was not detected during the experiment. A biphasic change in the parathyroid hormone level, with decreases at 1 and 2 weeks after the ovariectomy and increases at 4 and 8 weeks postoperatively, was observed, whereas a constant value was noted in the calcitonin level. Thickness of the articular soft tissue was increased in the anterior and central portions of the condyle at 1, 2, and 4 weeks after the ovariectomy, whereas no appreciable changes were observed in the posterior portion. The bone volume was decreased during the experiment, particularly in the posterior portion. An osteophyte in the anterior region was also observed 8 weeks postoperatively. CONCLUSIONS: Estrogen deficiency in rats during puberty predisposes to alterations of the TMJ through changes in serum calcitonin and parathyroid hormone levels.

Analysis of Variance↗

PubMed1996

Molecular Diagnostics in Pediatric Acute Lymphoblastic Leukemia.

Remarkable progress has been made in identifying the molecular lesions involved in the pathogenesis of pediatric acute lymphoblastic leukemia. Efforts to clone the genes involved in chromosomal translocations have led to the isolation of a number of novel proto-oncogenes. The biochemical characterization of the encoded products has helped to elucidate important regulatory pathways involved in cellular differentiation, proliferation, or control of cell death, and has helped to define how alterations in these pathways contribute to leukemogenesis. In addition, these efforts have led to the development of molecular-based assays for the identification of the specific molecular lesions. Clinical application of these assays has rapidly led to the realization that molecular lesions can identify distinct patient subgroups with predictable clinical features and responses to therapy. In this review, the emerging role of molecular diagnostics in the clinical management of pediatric patients with acute lymphoblastic leukemia is discussed.

Journal Article↗

PubMed1996

Mechanism of acceleration of wound healing by basic fibroblast growth factor in genetically diabetic mice.

To elucidate the role of basic fibroblast growth factor (bFGF) in the wound healing process, we investigated the ability of the factor to modulate an inflammatory reaction at the wound site and to influence endothelial cells and fibroblasts in vitro. A single, topical application of bFGF to a full-thickness wound of genetically diabetic mice caused an increase in the volume of wound exudate in a dose-dependent manner. bFGF induced the infiltration of a large number of leukocytes in the wound exudate. Transforming growth factor-beta (TGF-beta) positive cells, such as macrophages, monocytes and fibroblasts, appeared in the granulation tissue in bFGF-treated diabetic mice. These phenomena were comparable to those in normal animals, suggesting that the treatment with bFGF restored the inflammatory response in wound healing of diabetic mice. The effects of bFGF on cell proliferation, migration and angiogenesis were histologically recognized as shown in enhanced granulation tissue formation and neovascularization. It is suggested that bFGF promotes the recruitment of inflammatory cells into the wound site to induce a cascade reaction of growth factors including TGF-beta in a wound healing process, and so would accelerate wound healing.

Animals↗