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Biomedical subjects

A Kubo

Publications and source records attributed to A Kubo.

At least 127 records · Page 7Linked to original sources
PubMed1998

[Evaluation of the safety and clinical feasibility of exercise 99mTc-MIBI SPECT using one day protocol--multicenter phase III clinical trial report].

We evaluated the safety and clinical usefulness of the same day protocol of exercise 99mTc-MIBI SPECT in 107 patients with heart diseases. No adverse event was observed except for one case of transient hypotension caused by the exercise. More than 95% of stress images and all of the rest images were judged as "Excellent" or "Good" in image quality. Overall sensitivity was 84.3% in detecting coronary artery disease, and no statistical difference was observed between the results obtained with Re-Ex and Ex-Re protocols. The examination was "Quite Effective" or "Effective" in diagnostic efficacy in 96.2% of the cases. We concluded that the same day protocol is a safe and useful method for diagnosing myocardial ischemia, which provides high image quality and valuable information.

Adult↗
PubMed1997

Biodistribution of iodine-125 labeled monoclonal antibody/interleukin-2 immunoconjugate in athymic mice bearing human tumor xenografts.

BACKGROUND: Some vasoactive drugs have been studied in the hope of altering the vascular permeability and/or blood of tumors to enhance monoclonal antibody (MoAb) uptake. The pretreatment of interleukin-2 (IL-2), one of the vasoactive reagents, produced a generalized vascular permeability, but its function was not tumor specific. Conversely, MoAb/IL-2 immunoconjugates were developed that selectively alter the vasopermeability of tumors. In the current study the authors evaluated whether radiolabeled anti-carcinoembryonic antigen (CEA) MoAb, ZCE025/IL-2 immunoconjugate, specifically can enhance delivery of iodine-125 (I-125) to tumor sites. METHODS: ZCE025 was conjugated with IL-2, and the conjugate then labeled with I-125. Biodistribution studies were performed in athymic mice bearing CEA-producing human tumor (MKN45) xenografts. Mice were injected with I-125-ZCE025/IL-2 conjugate, and I-125 activities in the organs, including blood and tumor, were investigated at 1, 3, and 5 days after injection. Vascular permeability of the organs, including tumors, also was studied by using I-131 labeled mouse serum albumin in three groups. RESULTS: I-125 labeled ZCE025/IL-2 conjugate destroyed its lymphokine-activated killer cell (LAK) activation, but retained a minimum of 75% of the antibody binding reactivity. Biodistribution of I-125-ZCE025/IL-2 conjugate showed increased uptake of I-125 in tumor by a factor of 1.5, 4.2, and 4.1 compared with I-125-ZCE025 on Days 1, 3, and 5, respectively. In contrast, I-125 distribution was not enhanced in any organs except the tumor. Vascular permeability studies demonstrated that the physiologic effect of IL-2 was tumor specific in the mice that received the I-125-ZCE025/IL-2 conjugate. CONCLUSIONS: These studies indicate that the administration of radiolabeled MoAb/IL-2 double conjugate may enhance the therapeutic potential of radiolabeled MoAb without any pretreatment with IL-2 or repeated injection of MoAb.

Animals↗
PubMed1997

Determination of FAD-binding domain in flavin-containing monooxygenase 1 (FMO1).

The flavin-containing monooxygenases (FMOs) are a family of flavoenzymes and contain one molecule of FAD per monomer. In order to demonstrate where FMO interacts with FAD, four mutants for the rat liver FMO1 protein were expressed in yeast and characterized. All four mutants were immunochemically similar to the unmodified form, although the contents of FAD in all four mutants were much lower than that in the unmodified form. Interestingly, the mutant generated by changing the first glycine of the proposed FAD-binding domain (GxGxxG) to alanine revealed catalytic activities, but was lower than those seen with the unmodified form. The conversion of the first glycine to alanine markedly increased and decreased the Km and Vmax values for imipramine N-oxidation, respectively. The other three mutants (RFMOm2, RFMOm3, and RFMOm4) were catalytically inactive. Our results suggest that three glycines, especially the second and third glycines, in the proposed FAD-binding domain were necessary for FMO to show catalytic activities. Using RFMOm1 and the unmodified form, the effects of n-octylamine on the activity of FMO1 were investigated. The activities of both wild-type and RFMOm1 enzymes for all of the compounds examined were enhanced by n-octylamine. The Km and Vmax values of both RFMOm1 and the unmodified form for imipramine N-oxidation were lowered and raised by n-octylamine, respectively.

Animals↗
PubMed1997

Isolation of a promoter region in mouse cytochrome P450 3A (Cyp3A16) gene and its transcriptional control.

An 11.5 kb fragment of the mouse Cyp3a16 gene containing the 5' flanking region was isolated from the lambda DASHII mouse genomic library. A part of the 5' flanking region and the first exon of Cyp3a16 gene were sequenced. S1 mapping analysis showed the presence of two transcriptional initiation sites. The first exon was completely identical to Cyp3a16 cDNA. The identity of 5' flanking sequences between Cyp3a16 and Cyp3a11 genes was about 69%. A typical TATA box and a basic transcription element (BTE) were found as seen with other CYP3A genes from various animal species Moreover, some putative transcriptional regulatory elements were also found in addition to the sequence motif seen for the formation of Z-type DNA. To examine the transcriptional activity of Cyp3a11 gene, DNA fragments in the 5'-flanking region of the gene were inserted front of the luciferase structural gene, and the constructs were transfected in primary hepatocytes. The analysis of the luciferase activity indicated that the region between -146 and -56 was necessary for the transcription of CYP3a16 gene.

Animals↗
PubMed1997

Radiotherapy for centrally recurrent cervical cancer of the vaginal stump following hysterectomy.

PURPOSE: This study was performed to establish the classification and the treatment modality for recurrent cervical cancer of the vaginal stump after hysterectomy. PATIENTS AND METHODS: Ninety patients with centrally recurrent cervical cancer of the vaginal stump following hysterectomy were treated with high-dose-rate intracavitary brachytherapy with or without external irradiation. The intervals between primary surgery and vaginal recurrences varied from 3 months to 36 years. Tumor size of the vaginal stump was determined by bimanual rectovaginal examination at the time of recurrence and was classified into three groups, i.e., small (no palpable tumor), medium (less than 3 cm), and large (3 cm or more). RESULTS: The 10-year survival rates for all patients were 52%. Survival was greatly influenced by the tumor sizes of the vaginal stump. The 10-year survival rates of patients with small, medium, and large size tumors were 72, 48, and 0%, respectively. All patients with large size tumors died within 5 years. Of 90 patients, 75 (83%) were determined by physical examination to be free of tumor on at least one visit within 2 months of the completion of treatment (CR). The remaining 15 patients (17%) had physical findings suggestive of residual tumor (Residual). The overall 10-year survival rate for all patients with CR was 63%, compared with 10% for the patients with Residual (P < 0.0001). The incidences of distant metastases of the patients with or without local failure were 55 and 13%, respectively (P < 0.0001). The patients with local failure had significantly higher incidence of metastases. Most patients with small size tumor were treated with brachytherapy alone, and the survival rates of these patients were not improved by combination with external irradiation. CONCLUSION: These results suggest that tumor size was a significant prognostic factor for recurrent cervical cancer of the vaginal stump. Patients with small size tumors were recommended to be treated with brachytherapy alone.

Adult↗
PubMed1997

Effect of dibutyryl cyclic AMP on plasma renin activity in normal men and patients with primary aldosteronism.

Dibutyryl cyclic AMP (DBcAMP) directly stimulates the release of renin from the juxtaglomerular (JG) cells in vitro. We investigated the effect of DBcAMP on plasma renin activity (PRA) in 6 normal men and in 8 patients with primary aldosteronism (PA). A 20-min infusion of 0.33 mg/kg/min of DBcAMP significantly increased PRA in normal men, but had little effect on PRA in patients with PA. Infusion of DBcAMP significantly reduced the blood pressure and the levels of serum sodium and potassium in normal men and the patients with PA. Infusion of DBcAMP significantly increased urine volume in normal men, but not in patients with PA. Urinary excretion of sodium increased in both groups after the infusion of DBcAMP. Thus, DBcAMP did not stimulate renin release in patients with PA, suggesting that the chronic excess production of aldosterone suppresses the release of renin from JG cells.

Adult↗
PubMed1997

Granulocyte colony-stimulating factor receptor expression on human transitional cell carcinoma of the bladder.

Receptors for granulocyte colony-stimulating factor (G-CSFRs) have been confirmed on the cell surfaces of several non-haematopoietic cell types, including bladder cancer cells. This observation has naturally led to the hypothesis that the expression of G-CSFR on these cells may enhance their growth by G-CSF. In this study, the expression of G-CSFR was determined in both established human bladder cancer cell lines and primary bladder cancers. We studied five different human bladder cancer cell lines (KU-1, KU-7, T-24, NBT-2 and KK) and 26 newly diagnosed bladder tumours. G-CSFR mRNA expressions on cultured cell lines were determined using the reverse transcriptase polymerase chain reaction (RT-PCR) method. Furthermore, the G-CSFR binding experiments on the cultured cell lines were conducted using the Na(125)I-labelled G-CSF ligand-binding assay method. Moreover, the G-CSFR mRNA expressions on primary bladder tumour specimens were assessed using the in situ RT-PCR method. Three out of the five cultured cell lines (KU-1, NBT-2 and KK) exhibited G-CSFR mRNA signals when the RT-PCR method was used. The G-CSFR binding experiments showed an equilibrium dissociation constant (K[d]) of 490 pM for KU-1, 340 pM for NBT-2 and 103 pM for KK cells. With in situ RT-PCR, the tumour cells of 6 out of 26 primary bladder tumour specimens (23.1%) presented positive G-CSFR mRNA signals. Thus, in this study, G-CSFR expression was frequently observed on bladder cancer cells. Therefore, the clinical use of G-CSF for patients with bladder cancer should be selected with great care.

Carcinoma, Transitional Cell↗
PubMed1997

Constitutive production of multiple cytokines and a human chorionic gonadotrophin beta-subunit by a human bladder cancer cell line (KU-19-19): possible demonstration of totipotential differentiation.

Bladder cancer cells have been shown to secrete a variety of factors that are not related to cells of urothelial origin. The histogenesis of these tumour developments is uncertain, and a variety of theories have been previously reported. In the present manuscript, we identify the factors constitutively produced by a human bladder cancer cell line (KU-19-19) that was found to produce beta human chorionic gonadotrophin (beta-hCG), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 1alpha (IL-1alpha), interleukin 6 (IL-6) and interleukin 8 (IL-8). The cells were obtained from a case of metastatic carcinoma that was originally diagnosed to be a grade 3 (WHO classification), invasive transitional cell carcinoma of the bladder. On microscopic observation, the cultured cells exhibited an epithelial appearance with vacuole formation in their cytoplasm. Ultrastructural observations revealed relatively marked microvilli and a tight junction. Significant amounts of beta-hCG, G-CSF, GM-CSF, IL-1alpha, IL-6 and IL-8 concentrations in the supernatant from cultured cells were demonstrated by enzyme-linked immunosorbent assays, while the expression of mRNA of these marker proteins in cancer cells was also significantly exhibited by reverse transcription polymerase chain reaction (RT-PCR). In addition, the expression of G-CSF receptor and IL-6 receptor mRNA was also shown by RT-PCR. Xenograft transplantability using nude mice was observed in association with the presence of severe neutrophilia in the peripheral blood. These results indicate that this cell line appears to be an effective model for the study of transitional cell carcinoma of the bladder with multipotent differentiation potentials.

Aged↗
PubMed1997

Bone mineral density after surgical treatment for Graves' disease.

Restoration of bone loss associated with thyrotoxicosis follows normalization of thyroid function. However, the extent of bone loss and restoration remain controversial. To clarify whether bone recovery is complete, we examined lumbar and femoral bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) in 14 thyrotoxic premenopausal women with Graves' disease and 31 premenopausal women treated for Graves' disease by subtotal thyroidectomy who had been in remission for at least 3 years. In the remission group, to exclude the influence of subclinical hyperthyroidism, thyrotropin (TSH) levels were followed and subjects with low levels excluded. Thus, all 31 subjects had normal thyroid hormone levels with transiently or persistently elevated TSH levels post-thyroidectomy. Data from the two study groups were compared with those from healthy premenopausal controls matched for age, height and weight. Mean lumbar (anterior-posterior and lateral), femoral neck, and trochanter BMDs were significantly lower in the thyrotoxic group than in controls (p < .05, all four BMDs). Mean lumbar (anterior-posterior), femoral neck and trochanter BMDs were significantly higher in the remission group than in controls (p < 0.05, all three BMDs). At the time of DXA, the 31 remission subjects showed a significant positive correlation between lumbar BMD and TSH (p < 0.05) and a significant negative correlation between femoral neck BMD and free triiodothyronine (FT3) (p < 0.05). These observations suggest: (1) in premenopausal women, bone loss associated with thyrotoxicosis due to Graves' disease is present but is fully restored when remission is reached after subtotal thyroidectomy; (2) subclinical hypothyroidism after subtotal thyroidectomy may result in higher BMD than that of controls.

Absorptiometry, Photon↗
PubMed1997

Antisense oligodeoxynucleotide complementary to platelet-derived growth factor A-chain messenger RNA inhibits the arterial proliferation in spontaneously hypertensive rats without altering their blood pressures.

OBJECTIVE: To evaluate the effects of the antisense oligodeoxynucleotide (ODN) to platelet-derived growth factor (PDGF) A-chain messenger RNA (mRNA) on the growth of cardiovascular organs in hypertension. DESIGN: 15-Mer antisense ODN complementary to the initiation codon region of rat PDGF-A chain mRNA and non-sense ODN of identical proportion but with a random order of bases relative to that of antisense ODN were synthesized with a DNA synthesizer. METHODS: We examined the effects of the antisense ODN on the growth of vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats, and on the expression of PDGF A-chain mRNA by reverse transcription and polymerase chain reaction and PDGF A-chain protein by Western blot analysis in vitro. We evaluated the distribution of 32P-labeled antisense ODN and examined the effects of the antisense ODN on the growth of cardiovascular organs in vivo. RESULTS: The antisense ODN reduced the basal DNA synthesis of VSMC from SHR significantly, but did not do so in cells from Wistar-Kyoto rats. Mutations in the antisense ODN sequence reduced the ODN-induced inhibition of DNA synthesis. Addition of serum or transforming growth factor-beta 1 increased the DNA synthesis in the SHR-derived VSMC that was inhibited by the antisense ODN. The antisense ODN inhibited the production of PDGF A-chain protein, but not of the PDGF A-chain mRNA. The injection of 32P-antisense ODN in vivo led to a greater accumulation of radioactivity in the aorta than in other organs. Infusion of antisense ODN for 28 days did not alter the systolic blood pressure appreciably in rats of either strain. However, in SHR, it reduced markedly the elevated DNA content, [3H]-thymidine uptake, and incorporation of [3H]-thymidine into aortic DNA, and suppressed the production of aortic PDGF A-chain protein. These results indicated that the PDGF A-chain is involved in the exaggerated growth of VSMC from SHR by which inhibition of the translation of PDGF A-chain mRNA to the protein with antisense ODN occurs in vitro, and that antisense ODN to PDGF A-chain suppresses the exaggerated arterial proliferation in SHR without altering the high blood pressure in vivo. CONCLUSION: These results imply that inhibition of the final responsible growth factor PDGF A-chain by antisense ODN can suppress the arterial proliferation in hypertension without altering the blood pressure, suggesting that the arterial proliferation in hypertension is independent of the high blood pressure in part, and that antisense therapy could be feasible for treating hypertension.

Animals↗
PubMed1997

Direct detection by PCR of Escherichia coli O157 and enteropathogens in patients with bloody diarrhea.

Direct detection of Escherichia coli O157 and foodborne pathogens associated with bloody diarrhea were achieved using polymerase chain reaction (PCR) after the preparation of DNA from stool specimens using the microspin technique. PCR was compared with cultivation and toxin production tests with respect to the efficiency of detection of each pathogen; E. coli O157, Vibrio parahaemolyticus, Salmonella serovar Enteritidis and Campylobacter jejuni. Detection of some or all of the above pathogens in clinical stool specimens was achieved using PCR. The minimum number of cells required for the detection of the above pathogens by PCR was 10(1) CFUs/0.5 g of stool sample. PCR was completed within 6 hr. The above pathogens were also detected in cultivation and toxin production tests. Partial purification of the template DNA using the microspin technique was essential for the elimination of PCR inhibitors from the DNA samples. This PCR method is an accurate, easy-to-read screening method for the detection of Shiga-like toxin producing E. coli O157 and enteropathogens associated with bloody diarrhea in stool specimens.

Bacteria↗
PubMed1997

[Changes in patterns of morbidity over 10 years among elderly patients with stroke who were treated in a rehabilitation unit].

We examined changes in outcomes among elderly patients with stroke who were admitted to the rehabilitation unit of our hospital from April, 1985 to March, 1995. During that period, 933 patients (489 men and 444 women, average age 71.3 years) were admitted and received physical therapy. During those 10 years, the average age of the patients increased, functional status with regard to sitting up and walking worsened, and the incidence of urinary incontinence at the time of discharge increased. In contrast, the percentage of patients discharged to home (50 to approximately 60%), the degree of impairment of lower extremities, and the onset-to-admission interval (3 to 4 months) did not change.

Aged↗
PubMed1997

Scatter and attenuation correction in technetium-99m brain SPECT.

UNLABELLED: We propose a practical method for scatter and attenuation compensation in 99mTc-ECD brain SPECT using a simultaneous emission CT (ECT) and transmission CT (TCT) acquisition system that includes the following major components: (a) triple-headed SPECT gamma camera equipped with fanbeam collimators; (b) external line sources containing 99mTc placed at the focal lines of the collimators; and (c) scatter correction by the triple-energy-window (TEW) method. METHODS: Projection images were obtained over a 360 degrees rotation scan. After acquisition, scatter correction was performed using the TEW method, which corrected scattered photons pixel by pixel in the projection data. Scatter-corrected ECT images were compensated for attenuation using the TCT images with Chang's iterative method, and were converted to activity concentration (kBq/ml) images by obtaining a cross-calibration scan. After validating this method with phantom studies, it was applied to clinical brain imaging using a combination of 925 MBq 99mTc-ECD as a radiopharmaceutical and 222 MBq 99mTc as an external source. ECT and TCT data were acquired separately or simultaneously. RESULTS: SPECT quantification and image quality were improved by performing this correction. The activity concentration images obtained with the simultaneous acquisition were almost identical to those obtained with the separate acquisition. CONCLUSION: This method was clinically practical and cost-effective for reconstructing quantitative 99mTc brain SPECT images.

Brain↗
PubMed1997

[Prognostic factors of cervical carcinoma treated with postoperative radiotherapy].

We analyzed 119 patients with cervical carcinoma treated by postoperative radiotherapy from 1983 to 1993. Five- and 10-year survival rates of all patients were 77% and 67%, respectively. The 10-year survival rates for stage I (54 patients) and stage II (65 patients) were 76% and 58%, respectively. Ten-year survival rate for patients with both deep stromal invasion and lymph node metastasis was 37% which was much lower than in those without them (more than 90 %), indicating that they seemed to be factors related to poor prognosis. The results of multivariate analysis showed that the number of metastatic lymph nodes was the most important prognostic factor. Leg edema and intestinal and urinary insufficiency as late complications of postoperative radiotherapy occurred at low incidences and were well tolerated.

Adult↗