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Biomedical subjects

Y Yasunaga

Publications and source records attributed to Y Yasunaga.

At least 19 recordsLinked to original sources

Transition zone biopsy in the detection of prostate cancer.

OBJECTIVE: About 25% of all prostate cancers occur in the transition zone (TZ). We analyzed the impact of 4 systematic TZ and 2 systematic apex (AP) biopsies in addition to systematic sextant biopsies in an effort to establish the diagnostic importance of early prostate cancer. METHODS: One hundred and thirty patients underwent systematic transperineal multipoint prostate biopsy (biopsy of 12 sites, including 4 TZ and 2 AP biopsies). RESULTS: Forty-one of 130 men (31.5%) had biopsy specimens positive for cancer, and cancer originated in the TZ alone in 4 of these 41 patients (9.8%). Fourteen patients underwent radical retropubic prostatectomy. We compare the pathological findings of radical prostatectomy specimens and biopsy results. Prostate cancers predicted to be stage T(2c) by TZ biopsy were all classified as pT(2c) or greater. CONCLUSIONS: Routine TZ biopsy does not substantially increase the prostate cancer detection rate; however, it can be useful in patients who require repeat biopsy.

Aged↗

Rotational acetabular osteotomy for advanced osteoarthrosis secondary to dysplasia of the hip. Results at 6-11 years postoperatively.

Clinical and radiological studies were done on the results of rotational acetabular osteotomy for advanced osteoarthrosis secondary to dysplasia of 29 adult hips followed up for 6 to 11 years postoperatively (mean 8 years). Clinical evaluation by Merle d'Aubigne and Postel's system showed improvement from a preoperative mean of 12.8 to a follow-up mean of 14.8, with aggravation being observed in 8 joints. Radiologically, this procedure produced adequated improvement regarding femoral head coverage, but improvement in joint congruency could not necessarily be obtained due to joint deformity and progression of arthrosis, with aggravation of joint congruency being observed in 6 joints. The most important factor influencing the postoperative results of this procedure was postoperative joint congruency. If the postoperative joint congruency is satisfactory, with the joint congruent index being more than 6.0, progression of arthrosis can be prevented in the long term by this procedure, even in advanced cases.

Acetabulum↗

Morphological and functional restoration of parietal cells in helicobacter pylori associated enlarged fold gastritis after eradication.

BACKGROUND/AIM: Helicobacter pylori infections are associated with hypochlorhydria in patients with pangastritis. It has previously been shown that eradication of H pylori leads to an increase in acid secretion in H pylori associated enlarged fold gastritis, suggesting that H pylori infection affects parietal cell function in the gastric body. The aim of this study was to evaluate the effects of H pylori infection on parietal cell morphology and function in hypochlorhydric patients. PATIENTS/METHODS: The presence of H pylori infection, mucosal length, and inflammatory infiltration were investigated in six patients with enlarged fold gastritis and 12 patients without enlarged folds. Parietal cell morphology was examined by immunohistochemistry using an antibody against the alpha subunit of H(+),K(+)-ATPase and electron microscopy. In addition, gastric acid secretion and fasting serum gastrin concentration were determined before and after the eradication of H pylori. RESULTS: In the H pylori positive patients with enlarged fold gastritis, fold width, foveolar length, and inflammatory infiltration were increased. In addition, the immunostaining pattern of H(+), K(+)-ATPase was less uniform, and the percentage of altered parietal cells showing dilated canaliculi with vacuole-like structures and few short microvilli was greatly increased compared with that in H pylori positive patients without enlarged folds. After eradication, fold width, foveolar length, and inflammatory infiltrates decreased and nearly all parietal cells were restored to normal morphology. On the other hand, altered parietal cells were negligible in H pylori negative patients. In addition, the basal acid output and tetragastrin stimulated maximal acid output increased significantly from 0.5 (0.5) to 4.1 (1.5) mmol/h and from 2.5 (1.2) to 13.8 (0.7) mmol/h (p<0.01), and fasting serum gastrin concentrations decreased significantly from 213.5 (31.6) to 70.2 (7.5) pg/ml (p<0.01) after eradication in patients with enlarged fold gastritis. CONCLUSION: The morphological changes in parietal cells associated with H pylori infection may be functionally associated with the inhibition of acid secretion seen in patients with enlarged fold gastritis.

Adult↗

[A case of crossed fused kidney with simple ureterocele].

A 32-year-old man consulted Osaka National hospital with chief complaints of dysuria and macrohematuria. DIP and CT revealed that the right kidney deviated to the lower pole of the left kidney and they fused together. The right ureter crossed over the supine. The calcified shadow existed in the lower end of the left ureter with cobra head image. He had no external anomalies. Under diagnosing crossed fused kidney (inverted L shaped) complicated the left ureterocele with a stone, transurethral incision of ureterocele (TUI) was performed. We made transverse incision and extracted stone, 7 mm in size (calcium oxalate 96% and calcium phosphate 4%). Three months later after the operation, IVP, CG and VCG revealed the down-sized ureterocele and no VUR. Crossed renal ectopia complicated many anomalies about 50%. Among them anomalies of the urinary tract was most frequent about 30%. But crossed renal ectopia with ureterocele wasn't reported so far in Japanese literature.

Adult↗

Prognostic factors of renal cell carcinoma: a multivariate analysis.

BACKGROUND AND OBJECTIVES: To establish appropriate therapeutic modalities for renal cell carcinoma (RCC), informations on the factors affecting prognosis of patients are essential. For this purpose, multivariate analysis including a large set of variables is necessary. METHODS: Prognostic significance of 14 clinical factors and 19 histologic factors including counting of silver-stained nucleolar organizer regions (AgNORs) were evaluated in 96 patients. Age of patients ranged from 41 to 85 (median 59) yr with a male to female ratio of 4:1. The tumors were staged based on the TNM classification as follows: 7 in stage I, 58 in stage II, 15 in stage III, and 11 in stage IV. RESULTS: The overall and metastasis-free survival rates in all patients were 80.1% and 72.7%, respectively. Multivariate analysis using Cox's proportional hazards model performed on the factors proved to be significant at the univariate analysis. Univariate analysis revealed four clinical factors including presence of macroscopic hematuria, symptoms such as pain and palpable abdominal mass, anemia, and adjuvant therapy, and nine histologic factors, including AgNOR count, to be significant for survival. Multivariate analysis showed that anemia, pathological stage, and AgNOR count were independent factors for overall survival of patients. The AgNOR count, in particular, is the only predictive factor for metastasis-free survival. CONCLUSIONS: Among various clinicopathological factors, anemia, pathological stage, and AgNOR count are significant prognosticators of RCC. The AgNOR count is also predictive factor for metastasis-free survival.

Adult↗

Analgesic effect of mofezolac, a non-steroidal anti-inflammatory drug, against phenylquinone-induced acute pain in mice.

The oral administration of mofezolac, [3,4-di(4-methoxyphenyl)-5-isoxazolyl]acetic acid, resulted in the suppression of writhing induced by the intraperitoneal injection of phenyl-p-benzoquinone (phenylquinone, PQ) in mice. The analgesic activity of mofezolac was almost as potent as that of indomethacin, and more potent than that of sodium diclofenac, zaltoprofen, NS-398, and etodolac when their 50% effective doses were compared. The in vitro inhibitory activity of mofezolac against ovine cyclooxygenase (COX)-1 was also more potent than that of any other non-steroidal anti-inflammatory drugs (NSAIDs) tested, whereas the activity of mofezolac against COX-2 was relatively weak. A Western analysis revealed COX-1 to be constitutively expressed, whereas COX-2 was hardly expressed until 30 min after the PQ-injection in the peritoneal cells. Because the writhing terminated within 30 min after PQ-injection, the prostaglandins involved in the induction of writhing seem to be derived from COX-1. These data thus indicate that potent analgesic activity of mofezolac against the present model to be more closely related to its potent inhibitory activity against COX-1 but not against COX-2.

Analgesics↗

Utility of immunohistochemical detection of high molecular weight cytokeratin for differential diagnosis of proliferative conditions of the prostate.

BACKGROUND: Differential diagnosis of adenocarcinoma from other proliferative conditions in the prostate is often problematic. Immunohistochemistry using an antibody (34 beta E12) to high molecular weight cytokeratin, specifically present in basal cells of the prostate, could clearly demonstrate the presence or absence of these cells in the proliferating glands and thus provide an important clue in cancer diagnosis. METHODS: To examine the utility of immunostaining using 34 beta E12, we examined 88 equivocal lesions. Twenty lesions with apparently benign and malignant features were added as controls. We compared the morphologic features of these lesions with their immunoreactivities toward 34 beta E12 on a personal computer display following storage on the MICROPHOT-FXA system. RESULTS: Proliferating glands in all 20 benign lesions had 34 beta E12-reactive basal cells, but none of the malignant lesions did. The equivocal lesions were categorized on morphologic grounds into 2 groups: possibly benign and possibly malignant. Forty-five (51.1%) of the 88 equivocal lesions, were positive for 34 beta E12. These included 35 of the 45 (77.8%) possibly benign lesions and 10 of the 43 (23.3%) possibly malignant lesions. Among the equivocal lesions, 10 considered possibly benign on morphologic grounds showed negative reactivities, and 10 considered possibly malignant showed positive reactivities. Even through comparison on the computer display, no difference in morphology could be discovered between the negative and positive lesions in either group. CONCLUSION: Immunohistochemical procedures using 34 beta E12 are indispensable in the diagnosis of equivocal prostate lesions.

Adenocarcinoma↗

Different patterns of p53 mutations in prostatic intraepithelial neoplasia and concurrent carcinoma: analysis of microdissected specimens.

Prostatic intraepithelial neoplasia (PIN) is characterized by intraluminal proliferation of epithelial cells and can be divided into high-grade (HGPIN) and low-grade (LGPIN) lesions. HGPIN is regarded as the most likely precursor of prostatic carcinoma (PCA). Microdissected DNA selectively extracted from paraffin-embedded sections of 29 cases of PCA and 1 benign prostatic hypertrophy were analyzed for p53 mutation by single-strand conformation polymorphism (SSCP) of polymerase chain reaction (PCR)-amplified DNA fragments followed by direct sequencing. These patients had received total prostatectomy (27 cases) or transurethral resection (3 cases). Under direct microscopic observation, DNA was microdissected from 108 lesions: 67 lesions from 22 cases of PIN (55 HGPIN and 12 LGPIN), 29 from 22 cases of PCA, and 12 from 11 cases of adjoining benign glands. Analysis revealed 13 mutations in 10 lesions from six cases. All 13 were point mutations: 7 missense, 5 silent, and 1 nonsense. Mutations were detected in 3 cases (14%) of PIN and 5 cases (25%) of PCA. PIN lesions with p53 mutations were all categorized as HGPIN. Neither LGPIN nor benign glands adjoining PIN and/or PCA had mutations. Two PIN and one PCA lesion in each of two cases had mutations that were different from each other. G-to-A transition was the commonest mutation pattern. The current findings showed that HGPIN, but not LGPIN, and PCA are similar with regard to p53 mutation. The diverse patterns of p53 mutation among HGPIN and PCA lesions suggested multiclonal development of prostatic precancerous lesions.

Amino Acid Substitution↗

Incidence of prostatic intra-epithelial neoplasia in Osaka, Japan.

High-grade prostatic intra-epithelial neoplasia (HGPIN) is the most likely precancerous lesion for prostatic carcinoma. A high incidence of its association with cancer has been reported in Western countries. On the other hand, information regarding its incidence is limited in Japan, where the mortality due to prostate cancer is much lower. We reviewed 53 clinical stage T2 or T3 prostatic cancers of Japanese patients living in Osaka, Japan (mean age, 67.2 years). These cases were subdivided into a pre-operatively non-castrated group (34 cases) and a medically or surgically castrated group (19 cases). HGPIN was found in 27 cases. The incidence of HGPIN was significantly lower in the castrated group (21.0%) compared with the non-castrated group (67.6%). In the non-castrated group, patient age, pathological stage, Gleason score, tumor size and serum prostate-specific antigen showed no significant correlation with HGPIN. Advanced pathological stage and tumor size tended to decrease the incidence of HGPIN, although this was not statistically significant. When the study group was limited to stage T2 tumors of the non-castrated group, the incidence of HGPIN was 81.0%. HGPIN in Japan may also be clinically and etiologically significant as a precursor of clinical cancer.

Aged↗

Cancer risk after renal transplantation in Japan.

Excess of cancer in patients receiving renal transplantation is well-known in Western countries, but information in Japan remains limited. Our study examined whether excess risk is found in patients receiving renal transplantation in Japan. Between 1970 and 1995, 1155 males and 589 females underwent renal transplantation in 6 hospitals, and a total of 12,982 person-years of observation was accumulated. Malignancies developed in 2.6% of patients; O/E ratio was 2.78. Median interval from renal transplantation to tumor development was 58 months. The interval in the patients receiving medication with cyclosporine-A (CyA) (median, 42.5 months) was significantly shorter than that with non-CyA (median, 95.5 months). Median age at the diagnosis of malignancy was 40 years, which is much younger than that in the general population. Relative risk was highest in renal cancer, followed by thyroid cancer, malignant lymphoma and uterine cancer. A distribution of malignancies was different from that reported from Western countries. These findings showed the excess risk of malignancies in Japan with renal transplants, especially in male patients, similar to that observed in Western countries, though the types of malignancy were different.

Adolescent↗

Malignant lymphoma of the kidney.

BACKGROUND: Primary renal lymphoma (PRL) is a rare disease, making information including etiologic factors for PRL extremely limited. METHODS: Clinical and pathologic findings of PRL in Japan are presented and compared with those from Western countries. The presence of Epstein-Barr virus (EBV) genomes in the tumor was also evaluated. Eight cases of PRL were collected from a review of the "Annual of the Pathological Autopsy Cases in Japan (1976-1992)". These cases fulfilled the following criteria: (1) presence of renal mass without extrarenal lymphomatous involvement at admission and (2) absence of a leukemic blood picture. For histologic and immunohistochemical studies, 10% formalin-fixed and paraffin-embedded histologic specimens were used. Presence of Epstein-Barr virus (EBV) genome was examined by polymerase chain reaction (PCR) and in situ hybridization (ISH). RESULTS: There were five males and three females; age at admission ranged from 15 to 79 years (median 57 yr). Abdominal and/or flank pain were the most common presenting symptoms. No particular past history was present in any of the patients. Histologically, tumor cells in all cases showed a diffuse pattern of proliferation: large cell type in six cases, mixed cell type and small lymphocytic type in 1 each. Immunohistochemistry revealed B-cell nature of lymphoma cells in all cases. Neither PCR nor ISH showed the presence of EBV genome in any cases. CONCLUSIONS: PRL is non-Hodgkin's lymphoma of predominantly large cell type with a B-cell immunophenotype. EBV etiology is unlikely in PRL.

Adolescent↗

Rotational acetabular osteotomies: a rabbit model.

We investigated the morphological changes in the articular cartilage after rotational acetabular osteotomy in 16 adolescent rabbits. Radiological and histological studies were conducted at 12 and 24 weeks postoperatively. The radiological evaluations at 12 and 24 weeks showed significantly increased femoral head coverage. No cases of osteonecrosis of the acetabulum or femoral head nor narrowing of the joint space was observed. The histology of the articular cartilage at 12 weeks postoperatively showed cloning and hypercellularity of the chondrocytes in the medial portion of the acetabular roof, indicating remodelling due to the increased weight-bearing stress caused by the osteotomy. The histology at 24 weeks postoperatively showed less cloning of the chondrocytes, indicating that the remodelling process in the articular cartilage induced by this procedure was almost complete at 24 weeks. Degeneration of the articular cartilage was not observed within 24 weeks of the operation.

Acetabulum↗

Mucosal interleukin-1 beta production and acid secretion in enlarged fold gastritis.

BACKGROUND: We have previously shown that eradication of Helicobacter pylori increases acid secretion in H. pylori-associated enlarged fold gastritis. AIM: To investigate whether locally produced interleukin-1 beta is possibly involved in the inhibition of acid secretion in H. pylori gastritis. METHODS: IL-1 beta release from the gastric body mucosa was determined by short-term culture of biopsy specimens in 13 patients with enlarged fold gastritis (all H. pylori-positive), five H. pylori-positive and 10 H. pylori-negative patients without enlarged folds. The acid-inhibitory effect of locally produced IL-1 beta was examined by [14C]-aminopyrine uptake assay using isolated rabbit gastric glands. RESULTS: IL-1 beta release was significantly greater in patients with enlarged fold gastritis, significantly correlated with both basal and tetragastrin-stimulated acid outputs in the H. pylori-positive patients (r = -0.591 and r = -0.641, respectively; P < 0.01), and significantly decreased with concomitant increases in acid secretions after eradication of H. pylori. [14C]-aminopyrine uptake was inhibited by IL-1 beta in a dose-dependent manner. CONCLUSIONS: Increased production of IL-1 beta caused by H. pylori infection is possibly involved in the inhibition of acid secretion in enlarged fold gastritis.

Adult↗

Production of the immunosuppressive cytokine interleukin-10 by Epstein-Barr-virus-expressing pyothorax-associated lymphoma: possible role in the development of overt lymphoma in immunocompetent hosts.

Malignant lymphomas frequently develop in the pleural cavity of patients with long-standing pyothorax. Thus, the term pyothorax-associated lymphoma (PAL) has been proposed for this type of tumor. Most PALs are diffuse lymphomas of B cell type and contain Epstein-Barr virus (EBV) DNA. We have established two lymphoma cell lines from the biopsy specimens of PAL cases, OPL-1 and OPL-2. Both cell lines contain EBV DNA, but only OPL-1 expresses EBV nuclear antigen 2, which works as a target molecule for the cell-mediated immune response. As systemic immunodeficiency is unlikely to be present in PAL patients, PAL from which OPL-1 derived was not expected to be fully developed. In this study, we examined the expression of immunosuppressive factors in OPLs. Only OPL-1, not OPL-2, expressed interleukin-10 (IL-10) mRNA and secreted IL-10 into culture supernatant. Both OPL-1 and OPL-2 expressed transforming growth factor (TGF)-beta 1 mRNA; however, neither expressed latent TGF-beta-binding protein mRNA at a detectable level by Northern blot analysis. Because TGF-beta expresses its functions in cooperation with latent TGF-beta-binding protein, the biological functions of TGF-beta 1 could be negligible. Neither cell line expressed at a detectable level EBV BCRF-1 mRNA, a viral gene product that is partly homologous to human IL-10 and shares biological activities of IL-10. Although IL-10 is reported to promote the growth of activated or neoplastic B cells, OPL-1 did not respond to human recombinant IL-10 by growing faster. As OPL-1 expresses a target antigen for the host cytotoxic T-cell response, the production of an immuno-suppressive cytokine, IL-10, might contribute to the development of overt lymphoma by inducing locally immunosuppressive circumstances. The present study suggests that an immunosuppressive cytokine plays a role in lymphomagenesis of immunocompetent patients.

Animals↗

Role of an immunosuppressive cytokine, interleukin-10, in the development of pyothorax-associated lymphoma.

Malignant lymphoma frequently develops in the pleural cavity of the patients with long-standing pyothorax. Thus, the term pyothorax-associated lymphoma (PAL) has been proposed for this type of tumor. Most of PALs are diffuse lymphoma of B cell type and contain Epstein-Barr virus (EBV) DNA. We have established two lymphoma cell lines from the biopsy specimens of PAL cases, OPL-1 and OPL-2. Both cell lines contain EBV DNA, but only OPL-1 expresses Epstein-Barr virus nuclear antigen 2 (EBNA2) that works as a target molecule for cell-mediated immune response. In this study, we examined the expression of immunosuppressive factors in OPLs. Only OPL-1, not OPL-2, expressed interleukin-10 (IL-10) mRNA and secreted IL-10 into culture supernatant. Both OPL-1 and OPL-2 expressed transforming growth factor (TGF) beta 1 mRNA, however, neither expressed latent TGF beta binding protein (LTBP) mRNA at detectable level by Northern blot analysis. Because TGF beta expresses its functions in cooperation with LTBP, the biological functions of TGF beta 1 could be negligible. Neither cell lines expressed EBV BCRF1 mRNA at detectable level, a viral gene product which is partly homologous to human IL-10 and shares biological activities of IL-10. Since OPL-1 shows weaker proliferative activity than OPL-2 and expresses viral antigens, the production of an immunosuppressive cytokine, IL-10, might contribute to the development of overt lymphoma. The present study suggested that immunosuppressive cytokine plays a role in lymphomagenesis of immunocompetent patients.

DNA, Viral↗

Alterations of the p53 gene in occupational bladder cancer in workers exposed to aromatic amines.

Epidemiologic studies have revealed an increased risk for development of transitional cell carcinoma (TCC) among dye workers/painters occupationally exposed to aromatic amines such as benzidine, beta-naphthylamine, orthotoluidine, and aniline. In the present study, p53 gene mutations in 26 patients with bladder lesions occupationally exposed to aromatic amines were examined by single-strand conformation polymorphism analysis of PCR-amplified DNA segments, followed by direct sequencing. All were male, and age at admission ranged from 43 to 75 (median 66) years. Twenty-nine biopsy specimens were from primary lesions; 17 (61%) of these lesions were from TCC including one carcinoma in situ (CIS); 11 were from dysplasia; and 1 was taken from normal-looking transitional epithelium adjoining TCC. TCC lesions included 12 with low-grade (Grade 1 or 2) and 5 with high-grade (Grade 3 or CIS) changes. Twenty-four recurrent lesions were biopsied in 16 patients: TCC was found in 12 lesions (50%), CIS in 1 (4%), and dysplasia in 11 (46%). All lesions were localized within the submucosa except for two, which invaded into the muscle layers. PCR-single-strand conformation polymorphism analysis demonstrated that mutations (a) occurred in both dysplasia and in normal-looking epithelium, in addition to TCC lesions; (b) were at different sites in the p53 gene in concurrent or metachronous lesions; and (c) occurred in exon 5 in approximately 70% of lesions, especially at codons 151 and 152. C to T transitions were predominantly seen. These findings clearly show differences in the pattern of p53 mutation in occupational versus nonoccupational bladder lesions. Because both common and unique point mutations were found in p53 in concurrent and metachronous lesions, our results suggest that the multifocality of occupational bladder cancer arises both from multiple clonal lesions (field change) and from the dissemination of a single clone.

Adult↗

Oxidative stress increases gene expression of heparin-binding EGF-like growth factor and amphiregulin in cultured rat gastric epithelial cells.

We investigated the effects of oxidative stress on mRNA levels of heparin-binding epidermal growth factor-like growth factor (HB-EGF) and amphiregulin (AR) in rat gastric epithelial RGM1 cells. In response to stimulation with hydrogen peroxide (100-400 microM), gene expression of HB-EGF and AR increased in a dose-dependent manner, peaked at 3 h, and returned to the base line at 7 h. Hydrogen peroxide-induced HB-EGF and AR gene expression was blocked by pretreatment with an antioxidant N-acetyl-cysteine. In addition, it was significantly inhibited by pretreatment with EGF receptor-specific tyrphostin AG1478, but not by depletion of protein kinase C. These data indicate that oxidative stress upregulates expression of EGF-related polypeptides and the possible involvement of EGF receptor in this process.

Acetylcysteine↗