Biomedical subjects

K Okubo

Publications and source records attributed to K Okubo.

At least 91 records · Page 5Linked to original sources

PubMed2000

[Improvement in the regimen for combined CDDP and CPT-11 chemotherapy].

UNLABELLED: Combination therapy with cisplatin (CDDP) and irinotecan hydrochloride (CPT-11) is expected to be effective against refractory tumors. The antitumor effect of CPT-11 is believed to depend on the area under the concentration-time curve (AUC) of SN 38, which is a metabolite of the prodrug CPT-11. Of the major adverse effects of CPT-11, leukopenia is dependent on the AUC of CPT-11 and severe diarrhea is believed to be dependent on the peak concentration (Cmax) of SN 38. Considering these properties of CPT-11, we investigated the administration of a new regimen. METHOD: The subjects were patients with gynecological cancer who consented to intra-arterial [IA] infusion. The patients received CDDP (30 mg/m2 over 2 hours) concurrently with CPT-11 (40 mg/m2 over 24 hours) at 2-week intervals. Plasma concentrations of platinum and CPT-11 were measured before and after administration. To prevent binding of SN 38 to the large intestinal mucosa, we performed 1) alkalization, 2) detoxification of SN 38, and 3) clearance of the large intestine. RESULT: 1) A decrease in tumor diameter or negative conversion on cytology and reduced tumor marker levels were observed in patients receiving IA infusion. 2) No serious adverse reactions occurred, except grade 3 diarrhea in one patient given infusion at the initial dose. 3) The rate of conversion from CPT-11 to SN 38 was about 10%, which was higher than the 3% rate after standard 90-minute intra-venous [i.v.] infusion. 4) In the patients treated with IA infusion, CPT-11 levels in venous blood were one thirty-third of those in arterial blood. 5) Regarding the venous blood concentration of platinum when CDDP (30 mg/m2) was administered, the AUC of free platinum in patients given IA infusion was about 2.5 times that after i.v. infusion. CONCLUSION: The IA infusion treatment produced a good clinical response with good compliance.

Adenocarcinoma↗

PubMed2000

Clinical significance of micrometastases in axillary lymph nodes assessed by reverse transcription-polymerase chain reaction in breast cancer patients.

We evaluated the clinical significance of micrometastases in axillary lymph nodes (AxLNs) of breast cancer patients for prediction of prognosis. Archived formalin-fixed paraffin-embedded AxLN specimens from 129 node-negative breast cancer patients diagnosed by routine H&E staining between 1986 and 1990 were subjected to carcinoembryonic antigen-specific reverse transcription-PCR analysis. Micrometastases were detected in 40 of 129 (31.0%) node-negative breast cancer patients. After a median follow-up period of 105.6 months, log-rank test analysis indicated that 10-year disease-free and overall survival rates by Kaplan-Meier methods were significantly better in patients without micrometastases than in patients with micrometastases [disease-free survival, 87.6% versus 66.1% (P = 0.0008); overall survival, 93.7% versus 67.8% (P = 0.0024)]. The presence of micrometastases in AxLNs was revealed by multivariate analyses to be an independent and significant predictor of clinical outcome. The hazard ratio was 3.992 (95% confidence interval, 1.293-12.323; P = 0.0161) for relapse and 4.293 (95% confidence interval, 1.043-17.675; P = 0.0436) for cancer-related death. The molecular staging of AxLNs using reverse transcription-PCR is useful for prediction of clinical outcome in early-stage breast cancer patients and can provide a powerful and sensitive complement to routine histopathological analysis.

Adult↗

PubMed2000

[The significance of magnetic resonance cholangiopancreatography in acute cholecystitis].

To clarify the significance of magnetic renonance cholangiopancreatography (MRCP) in the acute phase of acute cholecystitis, MRCP was carried out in forty-five patients with acute cholecystitis in their acute phase. The MR pericholecystic high signal was observed in 38 of the 45 patients (84%). Enlargement of the gallbladder, presence of gallstones, and impacted stones was seen in 71%, 53%, and 18%, respectively. The MR pericholecystic high signal was classified into four categories: type 0, not observed; type 1, a liner high signal; type 2, a band-like high signal; type 3, a radiating high signal. In patients who showed a type 3 MR pericholecystic high signal, 91% required percutaneous transhepatic gallbladder drainage, and most of the gallbladders were diagnosed as necrotic cholecystitis by histology. The accuracy of MRCP for the diagnosis of choledocholithiasis was 96%. It was suggested that MRCP for patients with acute cholecystitis in the acute phase provides useful information for planning the treatment.

Acute Disease↗

PubMed1999

Cloning and characterization of a novel human gene encoding a zinc finger protein with 25 fingers.

This study reports cloning and characterization of a human cDNA encoding a novel human zinc finger protein, ZFD25. ZFD25 cDNA is 6118 bp long and has an open reading frame of 2352 bp that encodes a 783 amino acid protein with 25 C2H2-type zinc fingers. The ZFD25 cDNA also contains a region with high sequence similarity to the Krüppel-associated box A and B domain in the 5'-untranslated region, suggesting that ZFD25 belongs to the Krüppel-associated box zinc finger protein family. The ZFD25 gene was localized to chromosome 7q11.2. Northern blot analysis showed that ZFD25 was expressed in a wide range of human organs. In cultured endothelial cells, the mRNA level was decreased upon serum starvation.

Amino Acid Sequence↗

PubMed1999

Analysis of chemical modification of RNA from formalin-fixed samples and optimization of molecular biology applications for such samples.

Formalin-fixed archival samples are known to be poor materials for molecular biological applications. We conducted a series of experiments to understand the alterations in RNA in fixed tissue. We found that formalin-fixed tissue was resistant to solubilization by chaotropic agents. However, proteinase K completely solubilized the fixed tissue and enabled the extraction of almost the same amount of RNA as from a fresh sample. The extracted RNA did not show apparent degradation. However, as reported, successful PCR amplification was limited to short targets. The nature of such 'fixed' RNA was analyzed using synthetic homo-oligo RNAs. The heterogeneous increase in molecular weight of the RNAs, measured by MALDI-TOF mass spectrometry, showed that all four bases showed addition of mono-methylol (-CH(2)OH) groups at various rates. The modification rate varied from 40% for adenine to 4% for uracil. In addition, some adenines underwent dimerization through methylene bridging. The majority of the methylol groups, however, could be removed from bases by simply elevating the temperature in formalin-free buffer. This demodification proved effective in restoring the template activity of RNA from fixed tissue. The improvement in PCR results suggested that more than half of the modification was removed by this demodification.

Animals↗

PubMed1999

Genomic organization and chromosomal localization of the human cathepsin L2 gene.

Cathepsin L2 is a recently described cysteine proteinase with high sequence homology to cathepsin L and other members of the papain superfamily of cysteine proteinases. Its expression is regulated in a tissue-specific manner and is high in thymus, testis and cornea. In the present study, the entire gene sequence, including 5' and 3' flanking region, and chromosomal localization of human cathepsin L2 were determined. The gene spans approximately 6.4 kb and consists of eight exons and seven introns. Genomic organization was similar to human cathepsin L and more than 50% similarity was found between the first introns of cathepsin L and L2, suggesting that they diverged late in evolution. The transcription initiation site, determined by primer extension, was 198 nucleotides from the first ATG. The 5' flanking region lacks a TATA box but has one SP1 site. The gene was mapped to chromosome 9q21-22 by fluorescence in situ hybridization and the distance from cathepsin L was determined to be 15 cM by compiling radiation hybrid mapping results with a genetic map.

Base Sequence↗

PubMed1999

Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity.

We isolated the human adipose-specific and most abundant gene transcript, apM1 (Maeda, K., et al., Biochem. Biophys. Res. Commun. 221, 286-289, 1996). The apM1 gene product was a kind of soluble matrix protein, which we named adiponectin. To quantitate the plasma adiponectin concentration, we have produced monoclonal and polyclonal antibodies for human adiponectin and developed an enzyme-linked immunosorbent assay (ELISA) system. Adiponectin was abundantly present in the plasma of healthy volunteers in the range from 1.9 to 17.0 mg/ml. Plasma concentrations of adiponectin in obese subjects were significantly lower than those in non-obese subjects, although adiponectin is secreted only from adipose tissue. The ELISA system developed in this study will be useful for elucidating the physiological and pathophysiological role of adiponectin in humans.

Adiponectin↗

PubMed1999

Bronchoalveolar carcinoma: clinical, radiologic, and pathologic factors and survival.

BACKGROUND: The principal feature of bronchoalveolar carcinoma is that it spreads along airways or aerogenously with multifocality, but many issues are unresolved. METHODS: We studied 119 patients with pathologically confirmed bronchoalveolar carcinoma. Symptoms, smoking status, radiologic findings, the size of tumor, operative procedures, and complications were reviewed. We studied the pathologic features: presence or absence of aerogenous spread, patterns of growth, cell type, nuclear grade, mitosis, rate of bronchoalveolar carcinoma in adenocarcinoma, and lymphocyte infiltration. The correlation among clinical, radiologic, and pathologic findings was examined, and the factors affecting survival were analyzed. RESULTS: Symptomatic patients had more infiltrative radiographic features, and asymptomatic patients tended to have more mass-like features (P <.0001). Tumors with radiographically infiltrating lesions tended to have mucinous histologic features (P =.006). Tumors with mass lesions by radiograph tended to have nonmucinous and sclerosing histologic features (P =.003). Aerogenous spread was seen in 94% of specimens. The presence of a variety of cell types suggested multiple clonal origin. The overall survival in those patients undergoing resection was 69.1% at 5 years and 56.5% at 10 years. The significant factors affecting survival were radiologic presence of a mass or infiltrate, pathologic findings of the presence of sclerosis, association with a scar, the rate of bronchoalveolar carcinoma in adenocarcinoma, lymphocyte infiltration grade, nodal involvement, and status of complete resection. Mitosis or nuclear grade of tumor cells did not correlate with survival. CONCLUSIONS: Bronchoalveolar carcinoma showed good overall survival with appropriate surgical procedures. Certain radiologic or pathologic findings correlated with survival. These findings may enhance the ability to predict long-term survival.

Adenocarcinoma, Bronchiolo-Alveolar↗

PubMed1999

Voiding function of orthotopic ileal neobladder in women.

OBJECTIVES: Although the advent of orthotopic lower urinary reconstruction in women is a major achievement in the evolution of urinary diversion, the mechanism of voiding dysfunction remains incompletely understood. We report on the voiding function of ileal neobladder in 12 female patients. METHODS: A neobladder was constructed using an ileal segment. Voiding function was evaluated in terms of voiding pattern and continence. Chain cystography was performed postoperatively to detect the existence of urethral angulation. Median follow-up was 33.2 months (range 8.4 to 77.4). RESULTS: Of the 1 2 patients, 10 (83.3%) achieved excellent daytime continence, and 6 (50%) had nighttime incontinence despite regular voiding during the night. Three patients (25%) sometimes or often performed self-catheterization because of difficulty in urinating. One patient (8.3%) was unable to void and required regular intermittent catheterization. Chain cystogram revealed urethral angulation in the 3 patients with difficulty in urinating or hypercontinence. CONCLUSIONS: An orthotopic neobladder can be constructed in women with excellent functional results. Urethral angulation appears to be one of the main mechanisms for voiding dysfunction, and further studies on the functional anatomy of the female urethra are needed to improve the voiding function of the orthotopic neobladder in women.

Aged↗

PubMed1999

Complexed prostate-specific antigen and its volume indexes in the detection of prostate cancer.

OBJECTIVES: To evaluate complexed prostate-specific antigen (cPSA), cPSA density (cPSAD), and cPSA adjusted for the transition zone volume (cPSA-TZ) in comparison with the free-to-total PSA ratio (F/T PSA) and free-to-complexed PSA ratio (F/C PSA) as a means of diagnosing prostate cancer. METHODS: Transition zone volume was determined in 137 of 142 men who underwent systematic sextant biopsies and had total PSA (tPSA) values between 4.1 and 10.0 ng/mL. cPSAD and cPSA-TZ were calculated by dividing the cPSA value by the whole prostate volume and the transition zone volume, respectively. RESULTS: Of the 137 men, 23 (16.8%) had prostate cancer. cPSA predicted the biopsy outcome better than tPSA, F/T PSA, or F/C PSA, although the difference was not significant. A cutoff value of 4.1 ng/mL for cPSA provided a specificity of 42% and a sensitivity of 87%. A combination of cPSA and F/C PSA maintained a sensitivity of 83% and gave an increased specificity of 54%. In a subgroup of 65 patients with smaller prostate volumes (less than 45 mL), the diagnostic value of cPSA-TZ was remarkably increased. A cutoff value of 0.31 for cPSA-TZ provided a sensitivity of 93% and a high specificity of 72%. CONCLUSIONS: cPSA was more specific than tPSA and F/T PSA. As a component of F/C PSA, free PSA could provide additional value to cPSA. cPSA-TZ and cPSAD could be better indicators for prostate cancer than cPSA.

Aged↗

PubMed1999

Isomers and homologues of L-glutamic acid 5-n-butyl ester as promoters of sediment formation in raw soy sauce.

Soy sauce was found to contain promoters of sediment formation at 60 degrees C, one of which has previously been identified as L-glutamic acid 5-n-butyl ester. Isomers and homologues of L-glutamic acid 5-n-butyl ester (n-propyl, isopropyl, n-butyl, isobutyl, and sec-butyl esters of L-glutamic acid) were synthesized using 80% (w/w) sulfuric acid as a catalyst and identified by 1H-NMR and the ninhydrin test. The yields of L-glutamic acid 5-n-propyl, isopropyl, n-butyl, isobutyl, and sec-butyl esters from 10 g L-glutamic acid were 25, 101, 72, 130, and 134 micromol, respectively. For maximum sediment formation in 1 ml soy sauce, 1.2, 8.6, 22.0, 22.0, and 26.5 micromol/ml of n-butyl, n-propyl, isobutyl, sec-butyl, and isopropyl esters were respectively required. Sediment-forming activity was not observed with L-glutamic acid and L-glutamic acid 5-methyl, ethyl and tert-butyl esters.

Journal Article↗

PubMed1999

Changes in resistive index following extracorporeal shock wave lithotripsy.

BACKGROUND: Extracorporeal shock wave lithotripsy (ESWL) has replaced most surgical and endourologic forms of therapy for upper urinary tract stone disease. Despite its proved safety and efficacy, its adverse effects on renal function are still to be identified. A newer diagnostic technique, color Doppler ultrasonography, has brought a new insight into renal function. It enables precise evaluation of the renal vascular supply. Changes in intrarenal vascular resistance after ESWL were studied with Doppler ultrasound techniques. METHODS: In 70 consecutive patients the resistive index (RI) was measured at an interlober artery before and 30 min after ESWL in the treated and contralateral kidneys. In 17 patients, a follow-up Doppler study was performed 1 week after ESWL. RESULTS: In the treated kidneys, the RI significantly increased from 0.656+/-0.053 (mean +/- SD) at baseline to 0.682+/-0.053 (P<0.0001). There was no significant correlation of increase in RI with patient age (r = 0.010) or with pre-ESWL blood pressure (r = 0.002). Elderly patients (> or =60 years old, n = 31) had higher RI levels on baseline than younger patients (<60 years old, n = 39). In 18 of the 31 (58.1%) elderly cases the RI were elevated to greater than 0.7, indicating pathologic changes. In younger patients, only 9 (23.1%) experienced increase in RI up to 0.7 or greater. The contralateral untreated kidneys showed significant change in RI before (0.664+/-0.045) and after (0.679+/-0.049) lithotripsy in elderly patients (P<0.005). A follow-up Doppler study showed that the mean RI returned to pretreatment levels after 1 week. CONCLUSIONS: Because of higher RI levels on baseline, elderly patients have a higher risk of post-ESWL renal tissue damage than younger patients. Clinical implication of RI change in the contralateral kidneys in this study remains to be answered. The measurement of changes in RI with Doppler ultrasound techniques after ESWL may provide useful information for clinical diagnosis of renal tissue damage.

Adolescent↗

PubMed1999

Urinary undiversion for pelvic actinomycosis: a long-term follow up.

BACKGROUND: A 43-year-old woman who had been using intrauterine contraceptive devices for the past 10 years underwent an emergency operation for bowel and urinary obstruction. METHODS/RESULTS: Frozen section analysis showed undifferentiated adenocarcinoma. Incomplete tumorectomy, ileal resection, partial cystectomy, colostomy and bilateral ureterocutaneostomy were palliatively performed. Postoperatively, periodic acid-Schiff and Grocott-Gomori methenamine tests revealed Actinomyces and the final diagnosis was pelvic actinomycosis. Treatment with penicillin G administered intravenously relieved her symptoms and the lesion was dramatically improved. The patient underwent colostomy closure and urinary undiversion. CONCLUSIONS: Five years after urinary undiversion, the patient's renal function has been maintained and she can void without incontinence and dysuria.

Actinomycosis↗

PubMed1999

Patient-reported quality of life after radical prostatectomy for prostate cancer.

BACKGROUND: Increasingly, quality of life (QOL) assessments are receiving greater attention in the management of malignancies, including prostate cancer. We evaluated the impact of radical prostatectomy on patient QOL 12 months or longer after surgery. PATIENTS AND METHODS: We evaluated the impact of radical prostatectomy on QOL in 60 patients with prostate cancer. The patients comprised two groups: the first group (n = 32) was evaluated 12 months or longer after radical prostatectomy; the second group (n = 28) was evaluated while awaiting radical prostatectomy. General health-related QOL was measured with the European Organization for Research and Treatment of Cancer Prostate Cancer QOL Questionnaire. Sexual function was assessed with the Sapporo Medical University Sexual Function Questionnaire. A newly developed instrument assessing urinary function was prepared only for the postoperative group. RESULTS: No differences between the two groups were seen in comparisons of general health-related QOL subscales. Men who underwent surgery reported significant deterioration in sexual function (decreased quality of erection, decreased sexual activity and decreased satisfaction with sex life) than those awaiting surgery. Of the 32 postoperative patients, 26 (81%) did not use pads at all, five (16%) used one or fewer pads per day due to occasional spotting and only one patient (3%) used two to four pads per day to deal with urine dripping. Twenty-six postoperative patients (81%) stated that, given the choice, they would undergo radical prostatectomy again. CONCLUSIONS: General health-related QOL does not appear to be compromised following radical prostatectomy. Patients are willing to accept some morbidity for a perceived survival benefit. Although minimal urinary dysfunction was reported, most patients were dissatisfied with postoperative sexual function. In preoperative counselling, greater emphasis should be placed on the risk of postoperative impotence.

Aged↗

PubMed1999

Expression profile of active genes in mouse lymph node high endothelial cells.

High endothelial venules (HEV) allow rapid and selective lymphocyte trafficking from the blood into secondary lymphoid tissues. Here we report the expression profile of active genes in mouse high endothelial cells (HEC). HEC were first purified from mouse lymph nodes (LN) by magnetic cell sorting with MECA-79 mAb and a 3'-directed cDNA library that faithfully represents the composition of mRNA was constructed. A total of 1495 cDNA sequences were obtained from randomly selected clones. Based on their sequence identity, they were grouped into 754 different species [gene signatures (GS)] of which 335 GS were identified in GenBank. Among the previously identified genes, expression of several endothelial cell surface molecules including endoglin and ICAM-1 was detected in HEC. Comparison of the gene expression profile with that of purified CD31(+) flat endothelial cells identified several molecules, such as KC chemokine and Duffy antigen/receptor for chemokines, that are known to be selectively expressed in activated endothelial cells or post-capillary venules. Interestingly, mac25/TAF, which is known to be expressed specifically in tumor vessels and implicated in the regulation of cell adhesion, was highly and selectively expressed in HEC in mouse LN, suggesting that it may participate in regulating HEC-specific functions. Comparison with the expression profiles obtained from 35 different cell types showed at least 22 GS that were apparently specific to HEC. Our results illustrate the expression differences between HEC and CD31(+) flat endothelial cells, and will be useful for the identification and characterization of genes specific for HEC.

Animals↗

PubMed1999

Pharmacologic characterization of FR172516: a new combined calcium channel-blocking and beta-adrenoceptor-blocking agent.

The pharmacologic characterization of FR172516, a new combined calcium channel-blocking and beta-adrenoceptor-blocking agent, was studied and compared with amlodipine in receptor-binding assay and in vivo studies. In the binding assay, Ki values of FR172516 for calcium channel and beta-receptor were 29.3 nM and 44.1 nM, respectively. In the in vivo studies with pithed rats, FR172516 shifted the dose-response curves of isoproterenol in heart rate to the right, suggesting that this compound has a antiadrenoceptor effect in vivo. The hypotensive effect of FR172516, which could be mainly attributed to its calcium channel-blocking action, was compared with that of amlodipine in normotensive Wistar rats (NTRs), spontaneously hypertensive rats (SHRs), and renal hypertensive dogs (RHDs). FR172516 showed more potent hypotensive action than amlodipine when administered intravenously to NTRs, and apparent bradycardia was seen only with FR172516. In SHRs, FR172516 showed a long-lasting hypotensive action and dose-dependently decreased heart rate, whereas amlodipine scarcely affected heart rate. In RHDs, oral administration of FR172516 once daily for 5 days decreased blood pressure without reflex tachycardia or an increase of plasma renin activity. On the other hand, amlodipine, in the dose at which hypotensive effects equipotent to those of FR172516 were observed, produced apparent reflex tachycardia and concomitant increase of plasma renin. These results indicate that FR172516 has a potent long-lasting antihypertensive effect without activating sympathetic tone by calcium channel-blocking and beta-adrenoceptor-blocking actions.

Adrenergic beta-Antagonists↗

PubMed1999

Expression profiling by iAFLP: A PCR-based method for genome-wide gene expression profiling.

The availability of comprehensive sets of genes has prompted the researchers to carry out systematic collection of gene expression data. RT-PCR has the highest specificity and sensitivity for transcript detection among all available methods. Low throughput, especially when quantitative data are desired, has precluded RT-PCR from genome-wide application. Here we report a PCR-based expression profiling method, introduced amplified fragment length polymorphism (iAFLP), that has the same specificity and sensitivity as RT-PCR and a throughput level comparable to that of DNA-microarray hybridization. In this method, restricted ends of total cDNAs from six sources were ligated with adaptors having various length of short insertions to a common sequence (polymorphic adaptors). Amplification of a pool of these differentially adapted cDNAs with a gene-specific primer and an adaptor primer allows us to quantitate the abundance of any transcript in six mRNA sources. Using three different primer colors this technique allows quantitation of expression of 864 genes across six different sources per day with a single autosequencer, which is comparable to the throughput of microarray analysis in terms of number of genes x number of sources.

Animals↗

PubMed1999

Isolation of Orientia tsutsugamushi from patients in Shikoku and finding of a strain which grows preferentially at low temperatures.

Three strains of Orientia tsutsugamushi were isolated from patients in Anan City, Tokushima Prefecture. The strains were identified as Karp type by analyses of reactivities with type-specific monoclonal antibodies. One strain, Okazaki, was isolated in L cells cultivated at 31 C, but not in cells at 36 C or in mice. This strain showed better growth at 31 C than 36 C. This is the first report of an O. tsutsugamushi strain which grows preferentially at low temperatures.

Aged↗