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Biomedical subjects

K Okubo

Publications and source records attributed to K Okubo.

At least 145 records · Page 8Linked to original sources

Serum Soluble Interleukin-2 Receptor Levels in Patients with Breast Cancer.

Preoperative levels of serum soluble interleukin-2 receptor (1L-2R) were examined in 37 patients with breast cancer. We investigated the correlations of serum soluble IL-2R levels with various factors such as stage grouping, lymph node metastasis, distant metastasis, tumor size, histophthological type, estrogen receptor (ER), progesterone receptor (PgR) and CA 15-3. Serum soluble 1L-2R levels were measured with an enzyme-linked immunosorbent assay. Levels of serum soluble 1L-2R in the patients with stage III and IV breast cancer were significantly higher than those in the normal controls, and patients with stage I and II breast cancer. Preoperative levels of serum soluble IL-2R in patients with T3 and T4 were also significantly higher than those in patients with T1 and T2. Serum levels of IL-2R in patients with distant metastasis were also significantly higher than those in patients without distant metastasis. Moreover, serum levels of soluble IL-2R in patients with higher CA 15-3 were significantly higher than those in patients with normal CA 15-3 levels. We conclude that preoperative serum soluble IL-2R levels in patients with breast cancer may be a valuable parameter, especially in evaluating whether they have distant metastasis or not.

Journal Article↗

Amelioration of ischemia-reperfusion injury by human thioredoxin in rabbit lung.

Human thioredoxin is a polypeptide with thiol groups, possessing reducing activity, which is proved to have the ability to reduce active oxygens. This study evaluated the effect of human thioredoxin on the ischemia-reperfusion lung injury and the roles of human thioredoxin on active oxygens by chemiluminescence examination. The left hilum of the lung of Japanese white rabbits was occluded for 110 minutes and then reperfused for 90 minutes. Ten, 30, 60, and 90 minutes after reperfusion the right hilum was occluded for 5 minutes and the pulmonary functions of the left lung were examined. The animals were divided into four groups, three ischemia groups and a sham group (without occlusion; n = 6). The ischemia groups received human thioredoxin, 60 mg/kg (n = 10), N-acetylcysteine, 150 mg/kg (n = 7), or saline solution (control, n = 10) during reperfusion. Three rabbits in the human thioredoxin group and the control group were used to measure active oxygens with a cypridina luciferin analog. An additional group of reperfused lungs (n = 3) that were given superoxide dismutase after 110 minutes of ischemia was established to identify chemiluminescence examination. Compared with the sham group, reperfusion after 110 minutes of ischemia produced a significant lung injury in the control group. Among the ischemia groups, the human thioredoxin group showed significantly higher arterial oxygen tension at 30, 60, and 90 minutes after reperfusion than the control group, although there was no significant difference between the N-acetylcysteine and control groups. Histologically, intraalveolar exudation, interstitial thickening, and cellular infiltration were seen in the control group, whereas in the thioredoxin group alveolar structure was well preserved. In the measurement of active oxygens the chemiluminescence in the human thioredoxin group was less than that in the control group and as little as that in the group administered superoxide dismutase. We concluded human thioredoxin attenuated ischemia-reperfusion injury by involving active oxygens in rabbit lungs.

Acetylcysteine↗

Prostate specific antigen adjusted for the transition zone volume as an indicator of prostate cancer.

PURPOSE: We compared prostate specific antigen (PSA) adjusted for the transition zone volume with PSA and PSA density with regard to value in diagnosing prostate cancer in men with intermediate PSA levels of 4.1 to 10.0 ng./ml. in a community based urology practice. MATERIALS AND METHODS: Between October 1994 and May 1996, PSA transition zone was obtained from 92 of 94 men who underwent systematic sextant biopsies and had a PSA value between 4.1 and 10.0 ng./ml. PSA transition zone, calculated by dividing the PSA value by the volume of the transition zone of the prostate, was compared with PSA and PSA density via the receiver operating characteristic (ROC) curves. RESULTS: Of the 92 men 12 (13.0%) had prostate cancer. ROC curve analysis demonstrated that PSA transition zone and PSA density predicted the biopsy outcome significantly better than PSA (p <0.05 and p <0.01, respectively). In a subset of 59 men with normal digital rectal examination PSA transition zone predicted the biopsy outcome better than PSA density, although without significant difference. With a cutoff value of 0.3 PSA transition zone had a sensitivity of 75% and a specificity of 54%. CONCLUSIONS: PSA transition zone is more specific than PSA in distinguishing benign from malignant disease in men with intermediate PSA levels of 4.1 to 10.0 ng./ml., especially in those with normal digital rectal examination. Further study is necessary to discuss whether PSA transition zone is superior to PSA density.

Aged↗

Autoantibody reactive with the human general transcription factor TFIIF in sera from patients with autoimmune disorders.

Transcription factor (TF) IIF, a heteromeric protein composed of two subunits, RAP30 and RAP74, is required for both specific initiation and elongation of mRNA synthesis by RNA polymerase II. We have identified high titre of specific autoantibodies against the RAP74 subunit of TFIIF in sera from patients with systemic lupus erythematosus (SLE) as well as those with rheumatoid arthritis (RA), periarteritis nodosa (PN), Sjögren's syndrome (SS), dermatomyositis (DM), and mixed connective tissue disease (MCTD) by Western blot or immunoprecipitation. The epitopes recognized by autoantibodies were shown to be preferentially clustered at the central charged region. Anti-RAP74 autoantibody was shown to suppress the activity of TFIIF-stimulated elongation of mRNA synthesis by RNA polymerase II. It is concluded that some patients with autoimmune disorders develop specific autoantibodies against the RAP74 subunit of TFIIF.

Adult↗

Proteolytic cleavage sites of band 3 protein in alkali-treated membranes: fidelity of hydropathy prediction for band 3 protein.

To assess the fidelity of hydropathy prediction for band 3 protein, we determined the cleavage sites of the protein and the portions of the protein tightly bound to the membrane lipid bilayer by means of in situ proteolytic digestion. For the removal of all anticipated hydrophilic connector loops from membranes, we had to denature the band 3 protein molecule in situ by alkali treatment. When the alkali-treated membranes were digested with trypsin, chymotrypsin, and pepsin, the majority of the anticipated transmembrane portions remained in the membrane fraction. However, five anticipated transmembrane portions were released into the supernatant fraction. Thus, the first, second, third, sixth and tenth anticipated transmembrane portions, in accordance with the hydropathy prediction, were released into the supernatant with the proteolytic digestion method. This indicates that these anticipated transmembrane portions are not bound with the boundary lipids although the hydrophobicity of these portions is comparable to that of the portions experimentally remaining in the membrane fraction. It is conceivable that the membrane peptide portions of band 3 protein could be classified into at least two categories, i.e. one bound to the boundary lipids and the other free from the boundary lipids. Approximately 90% of the transmembrane domain of the band 3 protein are recovered in either the supernatant fraction or the membrane fraction. The fidelity of hydropathy prediction for polytopic membrane proteins and the nature of the membrane embedded peptide portions are discussed.

Amino Acid Sequence↗

Prospective evaluation of prostate specific antigen density and systematic biopsy for detecting prostate cancer in Japanese patients with normal rectal examinations and intermediate prostate specific antigen levels.

PURPOSE: To improve the specificity of cancer detection in patients with normal digital rectal examination and intermediate prostate specific antigen (PSA) level, PSA density has been recommended, with biopsy based on a PSA density of 0.15 or more. PSA density is reportedly higher in Japanese men than in white men, because of physiological differences between the 2 races. We prospectively evaluated PSA density as a discriminator of prostate cancer in Japanese men. MATERIALS AND METHODS: We evaluated prospectively 60 consecutive men with normal digital rectal examinations and serum PSA levels of 4.1 to 10.0 ng./ml. enrolled during a 17-month period. All patients underwent transrectal ultrasound guided sextant biopsies, regardless of calculated PSA density and transrectal ultrasound findings. Serum PSA levels were determined by IMx assay. RESULTS: Overall, 8 of 60 men (13%) had prostate cancer. There was no significant difference in mean PSA between those with positive and those with negative biopsies, but the difference was significant in the mean PSA density (mean 0.24 and 0.15, respectively, p < 0.01). Receiver operating characteristics curves for PSA and PSA density demonstrated superior benefit for PSA density in this patient population. A reference PSA density value of 0.19 was chosen because it showed the highest sum of sensitivity and specificity, which gave a sensitivity of 75%, a specificity of 87%, a positive predictive value of 46% and a negative predictive value of 96%. CONCLUSIONS: The results suggest that PSA density improves the specificity of cancer detection in men with a normal digital rectal examination and an intermediate PSA level. Although further study with a larger patient population is needed to obtain a best-fit value, an optimal PSA density cutoff seems to be higher than that recommended in the literature from western countries. Because of possible racial differences in serum PSA and prostate volume, the role of PSA density in Asian men should be studied independently.

Aged↗

Three cases of pyogenic sacro-iliitis, and factors in the relapse of the disease.

Pyogenic sacro-iliitis (PS) is a rare disease in childhood. Three cases of PS are reported that were difficult to diagnose. Scintigraphy and magnetic resonance imaging (MRI) were useful for diagnosis. One patient suffered from an episode of relapse. Seventeen other cases of PS were reviewed in the literature to investigate the incidence of abnormal imaging findings and various factors in disease relapse. It was found that the incidence of abnormal findings by scintigraphy was significantly higher than that by computed tomography (P = 0.0057). The duration of intravenous antibiotic administration of the relapse group (14.7 +/- 4.7 days) was significantly shorter than that of the non-relapse group (24.3 +/- 10.7 days; P = 0.0376). The statistical analysis suggested that intravenous antibiotic administration is necessary at least for 20 days to prevent a relapse of PS.

Adolescent↗

Nerve-sparing retroperitoneal lymph node dissection for metastatic testicular cancer.

BACKGROUND: Nerve-sparing techniques are used during retroperitoneal lymph node dissection (RPLND) in patients with early stage testicular cancer to preserve postoperative ejaculatory function. Indications for the procedures have been extended to patients with a postchemotherapy retroperitoneal residual mass without compromising the efficacy of surgery. We report 6 cases diagnosed with metastatic testicular cancer who underwent nerve-sparing RPLND. METHODS: Between January 1994 and March 1996, 6 patients with metastatic testicular cancer underwent nerve-sparing RPLND. Five of these patients received primary chemotherapy and a retroperitoneal residual mass. Four patients underwent complete bilateral RPLND and 2 underwent unilateral template surgery. RESULTS: After a mean follow-up of 18.7 months (range, 8 to 34), there have been no local recurrences and 5 (83%) patients report antegrade ejaculation. CONCLUSION: Nerve-sparing RPLND is applicable for selected patients with metastatic testicular cancer without increasing the risk of local recurrence. Ejaculatory function is preserved in the majority of patients, contributing to the improvement of the quality of life in men who require such surgery.

Adolescent↗

Value of systematic transition zone biopsy in the detection of prostate cancer.

BACKGROUND: We evaluated routine transition zone biopsies for the detection of prostate cancer. METHODS: Systematic sextant transrectal biopsies, including 2 systematic transition zone biopsies (sextant biopsy group), were performed on 196 consecutive patients. Biopsies were based on indications from digital rectal examination and/or a serum PSA level greater than 4.0 ng/mL. During the same period, 21 patients with persistently elevated PSA levels and earlier negative systematic biopsies also had the sextant biopsy (re-biopsy group). The sextant biopsy group was compared with 124 cases in our previous cancer detection program who had systematic quadrant biopsies targeted to the peripheral zone (quadrant biopsy group). RESULTS: Between the sextant and quadrant biopsy groups, the difference in rate of cancer detection was not significant statistically. Of the sextant biopsy group, 64 (33%) demonstrated malignancy, including 9 (4.6%) with cancer found exclusively in the peripheral zone and 55 (28%) both in the peripheral and transition zones. No cancer was found exclusively in the transition zone. Of the re-biopsy group, all 4 cancers (19%) were detected in the transition zone, 2 of them exclusively in the transition zone. CONCLUSION: Routine transition zone biopsies did not increase the detection rate of prostate cancer. Systematic transition zone biopsies proved useful to the patients with persistently elevated PSA values and negative results in previous systematic peripheral zone biopsies.

Aged↗

A novel neurological disorder with progressive CNS calcification, deafness, renal tubular acidosis, and microcytic anemia.

Progressive calcification of the brain and the spinal cord at early infantile onset was observed in two siblings. They showed growth failure, psychomotor deterioration, deafness, vestibular dysfunction, microcytic hypochromic anemia, abnormal ratios of lymphocyte subpopulations, and slightly decreased bicarbonate on blood gas analysis. Distal renal tubular acidosis was demonstrated in one of them. Carbonic anhydrase II activity was normal. This new hereditary disease might have a defect in a molecule that is present in brain, spinal cord, kidney and hematocytes and is involved in H+/HCO3- production or transport.

Acidosis, Renal Tubular↗

Recovery of diaphragmatic function in awake sheep after two approaches to thoracic surgery.

Video-assisted thoracoscopic surgery (VATS) is replacing thoracotomy, but no study has addressed the extent or duration of VATS-induced diaphragmatic alteration. We hypothesized that VATS would impair diaphragmatic function less and return diaphragmatic function faster than thoracotomy. In eight sheep, sonomicrometers were randomly implanted on the right costal diaphragm via VATS or thoracotomy. Diaphragmatic resting length, shortening fraction, and respiratory function were measured weekly during quiet breathing (QB) and CO2 rebreathing for 4 wk. For VATS, shortening fraction was smallest on postoperative days 1 (POD 1) (6.4 +/- 3.4 and 12.9 +/- 8.7% during QB and 10% CO2 rebreathing, respectively) and 7 (6.3 +/- 3.4 and 16.9 +/- 4.0% during QB and 10% CO2 rebreathing, respectively) and recovered by 3 wk (13.2 +/- 1.8 and 28.9 +/- 8.0% during QB and 10% CO2 rebreathing, respectively). For thoracotomy, shortening fraction at 10% CO2 rebreathing was smaller on PODs 1, 7, 14 (15.9 +/- 7.1, 13.6 +/- 5.4, and 19.0 +/- 6.9%) than on POD 28 (29.9 +/- 8.2%), but not during QB on POD 1 or 7 (7.5 +/- 3.8 and 3.4 +/- 2.6%) compared with POD 28 (10.7 +/- 8.7%). Shortening fraction did not differ between surgeries. There was no group difference in minute ventilation, respiratory rate, transdiaphragmatic pressure, or esophageal and gastric pressures. In conclusion, although shortening fraction recovered faster for VATS, this translated into insignificant functional differences.

Animals↗

Management of eyelid sebaceous carcinomas.

We retrospectively studied 14 patients confirmed histopathologically to have eyelid sebaceous carcinoma during 1986-1994. We removed all tumors totally with frozen section controls and performed reconstruction either by primary apposition or transposition flaps. We observed recurrence in 5 patients (35.7%) in whom a surgical margin of either 1 or 3 mm was taken but none in those with a 5-mm surgical margin. At least 5 mm of normal tissue around the tumor should be removed considering the metastatic potential of these tumors.

Adenocarcinoma, Sebaceous↗

[Intrarenal bacillus Calmette-Guerin therapy for carcinoma in situ of the upper urinary tract].

PURPOSE: We performed intrarenal bacillus Calmette-Guerin (BCG) instillation for carcinoma in situ (CIS) of the upper urinary tract. Its efficacy and safety are evaluated. MATERIAL AND METHODS: Eight patients (6 men and 2 women, median age of 63.7 years) diagnosed as upper urinary tract carcinoma in situ were studied. One had bilateral upper urinary tract CIS. Thus, 9 units of upper urinary tract were treated with BCG instillation. Diagnostic criteria of upper urinary tract CIS were: 1. positive voided urinary cytology, 2. negative multiple random biopsy of the bladder and the prostatic urethra, 3. negative radiographic studies, 4. two serial positive cytologies in selective ipsilateral urine sampling. The BCG solution was administered weekly by retrograde ureteral catheterization under local anesthesia and instillation during one hour. Second course instillation was performed when 1st course was not effective. RESULTS: Of 9 renal units 7 (78%) had normalization of the urinary cytology at the end of the 1st course BCG therapy. One patient with CIS of the bilateral upper tract had negative cytology of the unilateral unit, and underwent the contralateral nephroureterectomy because of persistent positive urinary cytology and coincidental renal cell carcinoma. One patient did not have negative cytology even after three courses of BCG instillation and is now under observation. During the procedure, high fever and bladder irritative symptom were observed in 6 out of the 8 patients (75%) and 4 (50%), respectively. CONCLUSIONS: Although longer followup and further experience with intrarenal BCG are required, this treatment is considered to be effective and safe for upper tract CIS.

Aged↗

Constitutive mRNA and immunoreactivity for IL-2 in human nasal mucosa.

BACKGROUND: The nasal mucosa is the initial site in the upper airway of host defence against antigenic challenge in the form of airborne allergens, irritants, toxins and infectious agents, and yet little is known about nasal mucosal cytokine expression and function. We hypothesized that IL-2 might play a role in immunocompetence of the upper airway. METHODS: IL-2 immunoreactivity was measured by ELISA in nasal secretions and by Western blot. Immunohistochemistry and electron microscopy were performed on turbinated tissue. mRNA for IL-2 was evaluated by RTPCR and Southern hybridization. RESULTS: IL-2 immunoreactivity was demonstrated by Western blot and quantitated by an enzyme immunoassay. Immunohistochemical and electron microscopy analysis of turbinate tissue revealed interstitial staining for IL-2. By RTPCR, IL-2 message was evident in 5/5 atopics and 5/5 non-atopics. IL-2 message was expressed in all subjects by Southern hybridization to an internal probe after PCR. CONCLUSION: This study has demonstrated constitutive expression of IL-2 protein and mRNA in the upper airway of healthy individuals. The further characterization of cytokines in the upper airway could provide useful insights into immune regulation at the mucosal level.

Base Sequence↗

Osteonectin (SPARC) expression in human liver and in cultured human liver myofibroblasts.

Osteonectin/SPARC is a glycoprotein involved in the regulation of cell shape, adhesion, migration, and proliferation. It also has complex effects on extracellular matrix synthesis and turnover. We found that osteonectin mRNA was very abundant in a human liver myofibroblast library. Using Northern and Western blot, immunoprecipitation, and radioimmunoassay, we found that cultured liver myofibroblasts actively secreted osteonectin. Myofibroblasts are very rare in normal liver but proliferate during liver fibrosis where they synthesize extracellular matrix components. Thus, we studied the distribution of osteonectin in normal and fibrotic human liver using in situ hybridization. Osteonectin mRNA expression was weak in normal liver but very high in fibrotic liver within fibrous septae and scattered sinusoidal cells. Serial sectioning and double staining experiments with an antibody to smooth muscle alpha-actin showed that osteonectin transcripts were mostly co-localized with myofibroblasts. In conclusion, osteonectin is highly expressed in human liver myofibroblasts in culture as well as in human liver fibrosis in vivo. The many biological properties of osteonectin make it a candidate effector of human liver fibrogenesis.

Actins↗

An expression profile of genes in human retina and isolation of a complementary DNA for a novel rod photoreceptor protein.

PURPOSE: To characterize expression patterns of active genes in human retina, and to isolate novel genes that are uniquely expressed in this tissue. METHODS: A 3'-directed complementary DNA (cDNA) library that faithfully represents the composition of messenger RNA (mRNA) was constructed with an mRNA preparation from a cadaveric human retina. A total of 925 3' terminal sequences were collected by sequencing randomly selected clones, of which 789 were regarded as representing chromosomally coded genes (gene signatures [GS]). GS were compared with each other and searched against GenBank. The resulting expression profile, listing gene species and their frequency, represents the composition of mRNA in the retina. By comparing this expression profile with those obtained from 10 other source cells or tissues, genes uniquely active in the retina were discovered, including some not previously described. A full-sized cDNA corresponding to one of these was isolated and sequenced. Its expression was analyzed by multitissue Northern hybridization and in situ hybridization to the retina specimen. It was then mapped on human chromosomes. RESULTS: In the expression profile, 108 genes were detected recurrently, suggesting that they are very active. Fifty-five of them were identified in GenBank, including the most abundant opsin gene and several other genes for phototransduction. Among the remaining novel and active genes, 19 were considered unique to retina on the basis of their representation status in other expression profiles and in dbEST. One of these was identified as a gene that encodes a novel secretory protein expressed in a rod photoreceptor that maps to chromosome 18p11.3. CONCLUSIONS: The expression profile of active genes in the retina represents the composition of mRNA, which reflects the relative activities of genes in this tissue. A comparison of this expression profile with those obtained with other tissues resulted in isolation of a novel cDNA specifically expressed in the rod photoreceptor. It is anticipated that additional novel genes that are uniquely active in the neural retina may be obtained with the same strategy, leading to further clarification of the biologic or physiological characteristics of this tissue.

Amino Acid Sequence↗