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Biomedical subjects

K Okubo

Publications and source records attributed to K Okubo.

At least 181 records · Page 10Linked to original sources
PubMed1996

Radical prostatectomy for clinically localized prostate cancer: local tumor extension and prognosis.

BACKGROUND: This study was performed to evaluate the frequency of local tumor extension and its effect on disease progression after radical prostatectomy. METHODS: The study consisted of 66 consecutive men who underwent radical prostatectomy for clinically localized prostate cancer without any prior hormonal therapy. Cases were stratified according to pathologic findings. Sites of capsular penetration were also evaluated. RESULTS: The overall incidences of lymph node metastases, seminal vesicle invasion, capsular penetration, and positive surgical margin were, respectively, 23%, 32%, 55% and 35%. The disease progression rate in patients with positive lymph nodes differed significantly from that in those without nodal metastases (P < 0.0001). Although seminal vesicle invasion, capsular penetration, or positive surgical margin had an adverse effect on prognosis, the difference in progression missed statistical significance, when patients with positive lymph node metastases were excluded. The most common site of capsular penetration was posterolateral, in the area of the neurovascular bundle. CONCLUSIONS: Extraglandular tumor extension and positive surgical margins are common features of radical prostatectomy specimens. A nerve-sparing operation should be performed selectively and with great caution. The markedly adverse effect of lymph node involvement on progression must be accounted for when evaluating other variables relating to progression.

Aged↗
PubMed1996

Pros-Eight transurethral radiofrequency thermotherapy for benign prostatic hyperplasia: preliminary clinical results.

BACKGROUND: We have developed a new transurethral thermotherapy device using 8MHz radiofrequency (RF) for the treatment of patients with symptomatic benign prostatic hyperplasia (BPH). We report the safety and effectiveness of the initial clinical experience with this device. METHODS: Sixty patients with symptomatic BPH were subjected to a single 1-hour treatment under local anesthesia. The treatment device uses extracorporeal RF capacitive heating in combination with radiative heating and conductive cooling of the urethra. RESULTS: In the 49 patients evaluable at 3 months, the mean International Prostate Symptom Score decreased from 17.8 to 13.1 (P < 0.0001) and the Quality of Life score decreased from 4.4 to 3.4 (P < 0.0005). Maximum flow rate increased from 8.1 to 9.7 mL/s (P < 0.05) at 3 months. Overall effectiveness by Homma's response criteria was as follows; excellent 4.1%, good 10.2%, fair 38.8% and poor 46.9%. Side effects were minimal. Gross hematuria was seen in 3 patients and erosion of the external urethral meatus was seen in 2 patients, but none had urinary retention. CONCLUSIONS: In this initial clinical trial, transurethral RF thermotherapy was safe and resulted in modest symptomatic improvement. Further investigations for optimizing the treatment protocol seem warranted.

Aged↗
PubMed1996

Aromatase and estrogen 2-hydroxylase activities of human placental microsomes in pregnancy-induced hypertension.

2-Hydroxylation is one of the major metabolic pathways of estrogens and is believed to be catalyzed by a form of cytochrome P450. Recently it has been reported that estrogen 2-hydroxylase activity in human placenta is catalyzed by aromatase. Some investigators suggested the effect of catechol estrogen on human placental steroidogenesis which may be related to pregnancy-induced hypertension (PIH) through the inhibition of catechol-O-methyltransferase (COMT) activity. In order to better understand the interrelationship between placental aromatase and estrogen 2-hydroxylase activities in PIH patients, both activities were evaluated in the PIH placentas. Human placental microsomes obtained from PIH patients were incubated with [1 beta-3H]androstenedione or [2-3H]estradiol in the presence of NADPH. Aromatase and estrogen 2-hydroxylase activities were assessed by the tritium water method. The immunosuppression patterns of both activities due to monoclonal antiaromatase cytochrome P450 antibody (MAb3-2C2) were studied. Estrogen 2-hydroxylase activity was significantly higher in PIH placentas (4.7 +/- 0.9 pmol/min/mg protein, n = 7) than in normal placentas (3.0 +/- 0.7 pmol/min/mg protein, n = 7). When the PIH placental microsomes were subjected to immunosuppression by 1 to 100 micrograms IgG of MAb3-2C2, estrogen 2-hydroxylase activity was suppressed by 94 to 65% whereas aromatase activity was strongly suppressed by 72 to 17%, respectively. From our results of high estrogen 2-hydroxylase activity in PIH placentas, it is assumed that there is a different estrogen catalyzing mechanism in PIH placentas.

Antibodies, Monoclonal↗
PubMed1996

[Effects of pulmonary rehabilitation in patients with chronic respiratory failure].

To evaluate the effects of pulmonary rehabilitation in patients with chronic respiratory failure, 43 patients with stable chronic respiratory failure were enrolled in a pulmonary rehabilitation program. The program included education, instruction in diaphragmatic breathing, respiratory muscle training, and exercise training (walking and riding a stationary bicycle). Patients were divided into 2 groups by the lowest SpO2 during a 12-minute-walk test done before rehabilitation: lowest SpO2 < 90% (Group A, 32 patients) and lowest SpO2 > or = 90% (Group B, 11 patients). In group A, SpO2 during exercise training was maintained over 90% by O2 inhalation, by load reduction, or by maintaining a slower walking speed. During 2 months of rehabilitation, the distance walked in 12 minutes and the maximum distance walked with an SpO2 > or = 90% significantly increased in both groups, but PaO2, VC, and FEV1 increased only in group A. In group A, the patients with chronic obstructive pulmonary disease had significant increases in PaO2, VC, and FEV1, but those with old tuberculosis sequelae had significant increases in PaO2 only. Pulmonary rehabilitation in patients with chronic respiratory failure may not only increase exercise tolerance but may also improve arterial oxygenation and pulmonary function.

Aged↗
PubMed1996

A gene expression profile of human corneal epithelium and the isolation of human keratin 12 cDNA.

PURPOSE: To describe the quantitative and qualitative aspects of gene expression in human corneal epithelium and to discover novel cornea-specific genes. METHODS: A 3'-directed cDNA library was constructed with messenger RNA prepared from normal human corneal epithelial cells, and inserts in 1069 randomly chosen clones were sequenced. These sequences were compared with each other to determine the frequency of appearance and were searched against GenBank for identification. The resultant expression profile, a list of gene species and their recurrences, reflected the composition of mRNA in the cornea. Recurrently appearing sequences, representing abundant transcripts, were compared with sequences in expression profiles obtained from seven other tissues and from those in dbEST to discover cornea-specific genes. RESULTS: The expression profile of human corneal epithelium showed that the most abundant transcript in this tissue was that for apolipoprotein J. Altogether 62 genes were suggested to be very active, including calcyclin, alpha-enolase, keratin 3, connexin 43, and 12 novel genes. The expression of four of these 12 novel genes seemed to be limited to cornea because they were not found in seven other expression profiles nor in dbEST. Full-length cDNA corresponding to one of these (GS8025), isolated from a separately made cDNA library, contained open reading frame highly homologous to mouse keratin 12, which is known to be cornea specific. CONCLUSIONS: An expression profile of corneal epithelium provides probes to monitor physiological and pathologic conditions of this tissue in terms of gene expression. Furthermore, by comparing this profile with those of other tissues, probes to isolate genes uniquely transcribed in corneal epithelium are determined. These genes are assumed to carry unique functions for this tissue and are candidate genes for inherited diseases that manifest only in cornea. As an example, human cornea-specific keratin was isolated, and partial cDNA sequences for three more cornea-specific genes were presented.

Adult↗
PubMed1996

Band 3 protein: physiology, function and structure.

Band 3 protein is a typical polytropic membrane protein and mediates the exchange of the cellular HCO3- with CI- in plasma, which has been known as the "Chloride Shift". Owing to the "Chloride Shift", red blood cells can discriminate the metabolically active cells from inactive cells and deliver oxygen particularly to metabolically active tissues that produce carbon dioxide. Thus, band 3 protein is a sensor for metabolically active tissues and no excess oxygen is supplied to tissues as far as oxygen is delivered by red blood cells. In this chapter, we review the physiological role of the anion exchange mediated by band 3 protein and our work concerning the structure and function relationship in band 3 protein, that, is, affinity labeling of the active center for the anion exchange with pyridoxal phosphate, conformational change during the anion exchange process, examination of fidelity of hydropathy prediction on band 3 protein, and phosphoenolpyruvate transport mediated by band 3 protein and its clinical application.

Amino Acid Sequence↗
PubMed1995

Monitoring cell physiology by expression profiles and discovering cell type-specific genes by compiled expression profiles.

A gene expression profile is the list showing the expressed gene species and the abundance of their transcripts in a given cell or tissue. This list is made by constructing 3'-directed cDNA libraries consisting of only the 3'-termini of mRNA and sequencing randomly selected clones from such libraries: genes are identified by the sequences, and the composition of mRNA, which reflects gene activities, is measured from the frequency of appearance of the gene transcripts. For practical reasons, the number of sequenced clones has been limited to approximately 1000 per library at present, but the resulting profile covers almost all highly or moderately expressed genes, along with many less active genes. We constructed expression profiles from the HL60 human promyelocytic cell line and two of its derivatives, granulocytoids induced by DMSO and monocytoids induced by TPA. In HL60, a significant fraction of the abundantly expressed genes was for protein synthesis. Upon induction, these genes were partially or totally silenced; transcripts for proteins that characterize the granulocytes and monocyte-macrophages became abundant. By compiling and comparing different expression profiles, genes can be categorized into those expressed in diverse cell types and those active only in limited cell types. Although at present, the number of expression profiles that can be compiled is limited and this categorization is applicable only to abundantly expressed genes, 13 novel genes that may represent granulocyte- or monocyte-specific functions have been discovered.

Base Sequence↗
PubMed1995

Structure, sequence and location of the UQCRFS1 gene for the human Rieske Fe-S protein.

We have identified and studied the chromosomal location of the human Rieske Fe-S protein-encoding gene UQCRFS1. Mapping by hybridization to a panel of monochromosomal hybrid cell lines indicated that a UQCRFS1 partial cDNA was derived from either chromosome 19 or 22. By screening a human chromosome 19 specific genomic cosmid library with a probe from this cDNA sequence, we identified a corresponding cosmid. Portions of this cosmid were sequenced directly. The exon, exon:intron junction and flanking sequences verified that this cosmid contains the genomic locus. Fluorescent in situ hybridization (FISH) was performed to localize this cosmid to chromosome band 19q12.

Amino Acid Sequence↗
PubMed1995

High incidence of a polymorphic variant of erythrocyte membrane protein, Band 3-Memphis, on a western Japanese island.

Band 3 is the major membrane protein of erythrocytes, which binds membrane skeletal proteins, glycolytic enzymes, and hemoglobin and transports various kinds of anions. Band 3-Memphis is a variant of Band 3, the amino terminal fragment of which depicts a slow electrophoretic mobility on sodium dodecyl sulfate-polyacrylamide gel. The frequency of Band 3-Memphis varies among populations, with a higher frequency among the Japanese. We investigated the frequency of Band 3-Memphis in a western Japanese island which is relatively isolated from the main islands, finding that the frequency of Band 3-Memphis of the inhabitants of this island is significantly higher than the frequency of the Japanese based on the survey in Kyushu Island. This indicates that there may be differences of population in the frequency of Band 3-Memphis in Japan and that Band 3-Memphis may be a good marker to genetically differentiate each population.

Anion Exchange Protein 1, Erythrocyte↗
PubMed1995

A saponin conjugated with 2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one from Dolichos lablab.

A new 2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one (DDMP)-conjugated saponin, lablab saponin I, was isolated from the hypocotyl of hyacinth bean (Dolichos lablab). The structure was elucidated by 1H NMR and 13C NMR spectroscopy and chemical techniques as 3-O-[alpha-L-rhamnopyranosyl- (1-->2)-beta-D-galactopyranosyl(1-->2)-beta-D-glucuronopyranosyl(1 -->)]-22-O- [2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one(2'-->)]-3 beta, 22 beta, 24-trihy-droxyolean-12-en-28-al. SOD (superoxide dismutase)-like activity depended upon the DDMP group and the aldehyde group (C-28) of the aglycone was observed in the order of lablab saponin I > glutathione > soyasaponin beta g > maltol. The soybean saponin Bb, lacking the DDMP moiety was found not to exhibit the SOD-like activity.

Carbohydrate Conformation↗
PubMed1995

Evaluation of cases with combined bronchoplasty and pulmonary arterioplasty for the treatment of lung cancer.

Bronchoplasty and pulmonary angioplasty(PA-plasty) have been performed in recent years for lung cancer invading the bronchus and pulmonary artery. We evaluated the results and complications in patients who underwent such operations. There were 23 cases of bronchoplasty performed between 1988 and October 1993. Of these 23 cases, 9 underwent PA-plasty with bronchoplasty. There were 8 males and 1 female (mean 65.6 year-old). There were 8 patients with primary lung cancer(sq 5, ad 1, la 1, and sm 1) and 1 with metastatic lung tumor of colon cancer. One patient was in p-stage II, 6 in p-stage III, and 1 in p-stage IV. Seven patients underwent right upper lobectomy, 1 did the right upper and middle bilobectomy, and 1 did a left upper lobectomy. Bronchoplasty was performed using sleeve resection in 8 patients, and a wedge resection in 1 patient. PA-plasty was performed using sleeve resection and end to end anastomosis in 2 cases, and using side wall resection and plasty in 7 patients after clamp. Of 9 patients in whom both broncho- and PA-plasty were performed, there was one with the resected bronchial stump of cancer-positive. Total resection of the cancer was possible in the remaining 8 patients. Postoperative complications included 2 pneumonia, 2 empyema, and 1 each, acute cardiac failure, pulmonary thrombus, and chylothorax. The patients with empyema required re-operation using omentopexy or thoracoplasty. Long-term results showed that 2 patients died because of recurrence. Another patient died of respiratory failure. The remaining 6 patients were alive without any evidence of cancer. Pneumonectomy was avoided and the combination of PA-plasty and bronchoplasty was performed instead. However, the incidence of postoperative complications was high, indicating that utmost care must be exercised in the postoperative management of these patients.

Adenocarcinoma↗
PubMed1995

Treatment of Pancoast tumors. Combined irradiation and radical resection.

Eighteen patients underwent combined preoperative irradiation and radical resection for a Pancoast tumor at the Department of Thoracic Surgery, Chest Disease Research Institute, Kyoto University between 1977 and 1993. Four patients were applied a full radiation dose of 50-70 Gy and fourteen patients were applied a reduced dose of 33-40 Gy preoperatively. Eleven of these fourteen were applied a supplemental dose postoperatively up to a total dose of at least 50 Gy. Fourteen lobectomies, three partial resections, and one pneumonectomy were performed with combined resection of chest wall or adjacent structures: rib in 14, vertebra in 4, brachiocephalic vein in 3, subclavian artery in 2, spinal nerve in 3, sympathetic truncus in 2, phrenic nerve in 2 cases. Chest walls were reconstructed with marlex mesh in 5 patients, and two subclavian arteries and one brachiocephalic vein were repaired with artificial grafts. In 13 patients complete resections were achieved, but in the other 5 only incomplete resections leaving residual tumor were achieved. Incomplete resections consisted of 4 positive stumps at the brachial plexus of the apex and one aortic involvement by a metastatic lymph node. There was one operative death. Median survival was 21.6 months and the 5-year-survival rate was 38.5% for all 18 patients. In the complete resection group 5-year-survival was 56.4%, but in the incomplete-resection group 0%, showing a significantly more favorable result for the complete resection group. It is considered that evidence of incomplete resection influences the prognosis and that particularly tumor invasion to the brachial plexus may serve as a limiting factor for surgery.

Adult↗
PubMed1995

A 96-kDa glycyrrhizin-binding protein (gp96) from soybeans acts as a substrate for casein kinase II, and is highly related to lipoxygenase 3.

A 96-kDa glycyrrhizin (GL)-binding protein (gp96) was purified to apparent homogeneity from an aqueous extract of soybeans by means of successive DEAE-cellulose column chromatography, gel filtration on Superdex 200pg, GL-affinity column chromatography, and ion-exchange chromatography on a Mono S column (HPLC). The protein was identified as a GL-binding protein since it specifically binds to [3H]GA. Moreover, it is a lipoxygenase (an enzyme that catalyzes the oxygenation of unsaturated fatty acids) since (i) it displays lipoxygenase (LOX) activity at pH 6.5; (ii) it is recognized on Western blot analysis by antibodies against LOX-1 and LOX-2; and (iii) the sequence of the N-terminal 21 amino acid residues (SNDVYLPRDEAFGHLKSSDFL) of a 42-kDa fragment (p42) proteolytically generated from gp96 is identical to a sequence of soybean LOX-3. In addition, GL, glycyrrhetinic acid (GA) and soyasaponin beta g slightly inhibited LOX activity of the purified gp96 fraction, whereas oGA (a GA derivative) greatly inhibited its activity. Furthermore, CK-II catalyzed phosphorylation of gp96 was stimulated significantly by GL at doses between 1 and 10 microM, but this phosphorylation was inhibited completely by 50 microM GL. All these results taken together suggest that (i) gp96 purified from soybeans as a GL-binding protein belongs to the LOX family; and (ii) triterpenoid saponins, including GL, are involved in the regulation of the activities of CK-II and LOXs in plants, such as soybeans and roots of liquorice, which contain large quantities of saponins.

Amino Acid Sequence↗
PubMed1995

A structural study of the carboxyl terminal region of the human erythrocyte band 3 protein.

Two peptides derived from the carboxyl terminal region of the human erythrocyte band 3 protein were identified as fragments releasable from cell membranes on trypsin digestion. These peptides, Asn-880-Lys-892 and Ala-893-Val-911-COOH, however, were resistant to trypsin, unless the cell membranes had been treated with high concentrations of NaOH. This suggests that the carboxyl terminal region is located in situ within the native band 3 molecule. Unlike in the cases of other portions of the band 3 protein, such as Gly-647-Arg-656, Ser-731-Lys-743, and Tyr-818-Lys-826, the release of the carboxyl terminal region was not inhibited by pretreatment of erythrocytes with 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), indicating that there is no major structural difference in the carboxyl terminal portion between the outward and inward facing forms. The carboxyl terminal region of the band 3 protein has a negative charge cluster. In the middle of the negative charge cluster, consensus sequences, Val-Asp-X-X-X-Leu-Asp-Ala-Asp-Asp and Thr-Phe-Asp-Glu (TFDE), were found in the carboxyl terminal regions of aquaporin CHIP and glucose transporter 1, respectively. The sequence, TFDE, exists in the highly amphipathic 11-residue sequence of glucose transporter 1, and this amphipathic sequence has been suggested to promote normal membrane insertion of polytopic membrane proteins such as glucose transporter 1 and serine chemoreceptor. The role of the carboxyl terminal region of the band 3 protein is discussed.

Alanine↗
PubMed1995

Disulfide bond-forming reaction using a dimethyl sulfoxide/aqueous HCl system and its application to regioselective two disulfide bond formation.

Disulfide bond formation in S-acetamidomethyl (Acm) cysteine-containing peptides by successive treatments with silver trifluoromethanesulfonate (AgOTf) and dimethyl sulfoxide (DMSO)/aqueous HCl is described. An S-Acm cysteine was found to be quantitatively converted into cysteine by deprotection of the Acm group with AgOTf followed by DMSO/aqueous HCl treatment. Under these reaction conditions, no significant side reactions were observed with oxidation-sensitive amino acids such as Met, Tyr and Trp. Oxytocin and a Trp-containing peptide, urotensin II, were prepared by this method. Furthermore, regioselective two disulfide bond formation was found to be feasible by the combination of air oxidation and the AgOTf-DMSO/HCl system. This strategy has been successfully applied to the syntheses of tachyplesin I and endothelin I, which have two disulfide bonds and a Trp residue in the molecule.

Amino Acid Sequence↗
PubMed1995

Interstitial laser coagulation for benign prostatic hyperplasia: preliminary clinical results.

We report our early experience in the clinical application of interstitial laser coagulation of the prostate (ILCP) in the treatment of benign prostatic hyperplasia (BPH). Neodymium: YAG laser energy is transmitted via a specially designed interstitial thermotherapy light-guide. The light guides were inserted transurethrally into each lobe of the prostate by direct puncture, under direct visualization. The prostatic urethra is preserved during the procedure. From December 1993 to March 1994, 37 patients with symptomatic BPH were treated with ILCP. Treatment outcome was evaluated by the International Prostatic Symptom Score (I-PSS), flow rate, postvoided residual urine volume and quality of life score. Significant improvement in I-PSS and peak flow rate was observed at 3 months: I-PSS decreased from a mean of 19.3 to 10.4, and the peak flow rate increased from a mean of 7.2 to 9.4 ml/sec (p < 0.0001). The mean postvoided residual urine volume significantly decreased from 91 to 47 ml (p < 0.01). Two days after ILCP the serum prostate-specific antigen had increased by 860%, evidence of the significant tissue damage produced by laser irradiation. The quality of life score significantly decreased from a mean of 4.8 to 2.1 (p < 0.0001). No serious side-effects were observed. The early clinical results suggest that ILCP is safe and effective as a treatment of BPH and is less invasive than some other methods.

Aged↗
PubMed1995

Lymphocyte subsets of the nasal mucosa in perennial allergic rhinitis.

T cells have been considered to play a primary role in IgE-mediated atopic diseases, yet little is known about the T-cell subsets in the nasal mucosa of patients with perennial allergic rhinitis. To elucidate the characteristics of T cells at the site of allergic inflammation, we analyzed the proportions, phenotypes, stages of differentiation, and distribution of T-cell subsets in the nasal mucosa of 15 patients with house-dust-mite perennial allergic rhinitis (PAR) and 14 patients with chronic infective rhinitis (CIR), using flow cytometry and immunohistochemistry. We also examined the T-cell subsets in the peripheral blood (PBL) in conjunction with those of the nasal mucosa in 10 patients with PAR and in nine patients with CIR. Our results revealed no obvious difference in the percentage of nasal CD3+ T cells, CD8+ T cells, and alpha beta T cells in the PAR and CIR patients. In contrast, CD4+ T cells (p < 0.05), CD3+4-8- double-negative T cells, (p < 0.01), and gamma delta T cells (p < 0.01) were significantly increased in the nasal mucosa of PAR patients. A majority of the CD4+ T cells in the nasal mucosa of PAR patients coexpressed the CD45RO surface molecule, and a predominant proportion of CD4+ T cells in the nasal coexpressed the CD45RO surface molecule, and a predominant proportion of CD4+ T cells in the nasal epithelium were CD45RO+. The ratio of CD4+ CD45RO+:CD4+ CD45RA+ T cells in the allergic patients' nasal mucosa was significantly greater than that in autologous peripheral blood (p < 0.01). The proportion and stages of activation and differentiation of T-cell subsets in the allergic patients' nasal mucosa were independent of those in the peripheral blood. An increase in the proportion of natural killer (NK) cells was observed in the nasal mucosa of CIR patients. Taken together, our results suggest that nasal T cells exhibit distinct patterns of distribution, differentiation, and activation in different inflammatory conditions of the nose. PAR is characterized by a selective increase in CD4+ memory T cells, CD3+4-8- double-negative T cells, B cells, and gamma delta T cells in the nasal mucosa. The increase in CD4+ memory T cells in the allergic nasal epithelium may have critical implications in the pathogenesis of PAR.

Adult↗