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Biomedical subjects

J Kawamura

Publications and source records attributed to J Kawamura.

At least 91 records · Page 5Linked to original sources

Characterization of semenogelin II and its molecular interaction with prostate-specific antigen and protein C inhibitor.

The serine protease, prostate-specific antigen (PSA), its protein substrates, semenogelin (Sg) I and II, and protein C inhibitor (PCI) have been described as components of human seminal plasma. PCI was found to inhibit the PSA-catalyzed degradation of insoluble coagula Sg I + II by forming a PSA-PCI complex. Digestion of seminal coagula with PSA released PCI and PSA-PCI complex from the coagula into a soluble phase, suggesting the presence of active PCI binding to the coagula. To investigate the molecular interaction of Sg with PSA and PCI, we purified Sg II from seminal coagula as a soluble form and found that Sg II is glycosylated with heterogeneous carbohydrate moieties. Sg II bound to the solid-phase complex of diisopropylfluorophosphate (iPr2FP) and PSA with an apparent dissociation constant (kd) of 41 nM and to PCI with a Kd of 28 nM. The binding of Sg II to iPr2P-PSA was not affected by PCI and that of Sg II to PCI was not affected by iPr2P-PSA, suggesting that Sg II forms a ternary complex with PSA and PCI. The bindings of Sg II to both iPr2P-PSA and PCI were influenced by pH, ionic strength, heparin, dextran sulfate, and divalent cations, particularly by Zn2+. Treatment of Sg II with heparinase, heparitinase, N-glycanase, or with O-glycanase following sialidase did not affect the binding of Sg II to iPr2P-PSA and PCI. These findings suggested that PCI bound to Sg in seminal vesicles regulates the PSA-catalyzed degradation of Sg in seminal plasma, and that the binding of PCI and PSA to Sg is modulated by several factors such as pH, ionic strength, divalent cations, and heparin-like substances in seminal plasma.

Amino Acid Sequence↗

Influence of diethylstilbestrol, Leuprolelin (a luteinizing hormone-releasing hormone analog), Finasteride (a 5 alpha-reductase inhibitor), and castration on the lobar subdivisions of the rat prostate.

The effects of various means of interfering with androgen action on rat coagulating gland, ventral prostate, lateral type 1 prostate, lateral type 2 prostate, and dorsal prostate were examined morphologically and quantitatively by assessing DNA content, wet weight, protein content, and zinc concentrations. Adult male Sprague-Dawley rats were subjected to 2 weeks of interfering with androgen action by treatment with Leuprolelin (a luteinizing hormone-releasing hormone analog), Finasteride (a 5 alpha-reductase inhibitor), or diethylstilbestrol (DES), or by physical castration. For all prostatic lobes, inhibition of 5 alpha-reductase elicited the smallest reduction in prostatic wet weight, DNA and protein contents, and zinc concentration. The most profound reductions in all parameters were elicited by castration. Treatments with DES and Leuprolelin gave intermediate effects with DES being the more effective in reducing all parameters in all prostatic lobes. Morphological changes elicited by all forms of androgen blockade were reduction of epithelial height, relative increase of connective tissue, reduction in ductal diameter, length, and number. The order of effectiveness of the various treatments on morphological features was as described above. While all forms of androgen blockade elicited similar effects throughout the prostate, differences in response to all forms of interference with androgen action were observed in different lobes of the prostate with regard to wet weight, DNA and protein contents, and zinc concentration as well as morphological effects. Regressive changes at the morphological level were particularly striking in the coagulating gland and ventral prostate, and indistinct in the lateral type 2 prostate. Prostatic zinc concentration in both normal and androgen-deprived rats was the highest in the lateral type 2 prostate and was reduced by interfering with androgen action to the greatest extent in the dorsolateral prostate (lateral type 1 and type 2, and dorsal prostate). The distribution of zinc correlated with the expression of metallothionein, which was detected by immunocytochemistry only in the lateral type 2 prostate of both normal and androgen deprived rats. Intraprostatic heterogeneity of zinc and metallothionein expression emphasizes interlobar differences in biological function within the rat prostate. The mechanism of development of regional heterogeneity within the prostate may shed light on the pathogenesis of prostatic proliferative diseases (prostatic hyperplasia and prostatic cancer) that initially owe their development to focal changes within large cell populations.

5-alpha Reductase Inhibitors↗

Evidence of stem cells in the adult prostatic epithelium based upon responsiveness to mesenchymal inductors.

Ductal tips approximately 300 microM in length from adult rat dorsal (DP), lateral type 1 (L1), and lateral type 2 (L2) prostates were combined with mesenchyme from the embryonic urogenital sinus (UGM), neonatal seminal vesicle (SVM), or neonatal bulbourethral gland (BUGM) and grafted underneath the renal capsule of syngeneic male hosts. Following 1 month of in vivo growth, all tissue recombinants formed large masses of prostatic ductal tissue, which represented massive growth of the original population of prostatic epithelial cells. Examination of secretory protein expression in these tissue recombinants indicated that each mesenchyme influenced secretory function in the adult prostatic epithelium in a characteristic way. SVM maintained expression of DP-1 and probasin in prostatic ducts of DP, L1, and L2, which normally express these proteins. BUGM induced expression of C3 in prostatic ducts of the DP, L1, and L2, which normally do not express C3. UGM induced the expression of DP-1, probasin, and C3 in prostatic ducts from all dorsal-lateral lobes. Mesenchymal induction of massive epithelial growth, new ductal branching morphogenesis, and change in prostatic lobe identity are indicative of the presence of stem cells in adult prostatic epithelium because high proliferative capacity, tissue regeneration, and pluripotency (change in functional differentiation) are hallmarks of stem cells.

Androgen-Binding Protein↗

Interphase cytogenetics of prostate cancer: fluorescence in situ hybridisation (FISH) analysis of Japanese cases.

No numerical aberration of chromosomes that might be specific for prostate cancer has so far been established. We used fluorescence in situ hybridisation (FISH) with centromere-specific probes for chromosomes 7, 8, 17, X and Y to establish the distribution of centromere copy numbers in frozen-stored or freshly prepared samples of benign prostate hypertrophy (BPH) and to detect numerical aberrations of these chromosomes in 28 prostate cancers from Japanese men. There was no significant difference in the data of centromere copy numbers between fresh and frozen-stored tissue. The most common aberration in prostate cancers was a gain of chromosome 8 (57%), with numerical aberration of chromosome 7 being the second most frequent anomaly (50%). Numerical aberration of chromosome 7 is most significantly associated with a higher Gleason score (GS) (P < 0.005) or with lymph node metastasis (P < 0.001). Numerical aberration of several chromosomes, including chromosomes 7 and/or 8, was common in aggressive prostate cancers. Loss of chromosome Y was detected in only 4% of cases. FISH analysis thus proved to be a useful method for detecting numerical aberrations of individual chromosomes, with application to touch preparations of frozen-stored tissue having the advantage of exact sampling of cancer foci. The results suggest that numerical aberration of chromosome 7 is associated with aggressive tumour behaviour and poor prognosis of patients with prostate cancer. The association between genetic change and chromosomal abnormality should be studied in detail.

Centromere↗

Bromocriptine therapy in early-stage Parkinson's disease.

We evaluated bromocriptine monotherapy during the early stage of Parkinson's disease (Hoehn and Yahr stage I or II). Of the 120 patients registered as participants in this trial, 96 were studied. The follow-up period was 48 weeks. For the first 24 weeks they were all placed on bromocriptine with or without anticholinergic drugs; for the second 24 weeks, 75 of them were still kept on the same medication, with 21 requiring additional levodopa. Clinically, the former group showed a good response to the bromocriptine monotherapy, while the latter responded poorly to it (requiring in addition levodopa). We think that Parkinson's disease encompasses a heterogeneous group of patients of whom about 75% are well treated by bromocriptine alone at the early stages of the illness.

Antiparkinson Agents↗

Prognostic factors of peripheral blood lymphocyte subsets in patients with renal cell carcinoma.

In 76 patients with renal cell carcinoma (RCC) we assessed the therapeutic effects of interferon-alpha (IFN-alpha) and the outcome of curative resection by analyzing changes in peripheral blood lymphocyte subsets to try to find prognostic indices. The percentage of activated CD8-positive cells present in blood samples before IFN-alpha therapy was significantly higher in progressive disease (PD) patients who died within 8 months than in PD patients who survived for more than 18 months. The high percentage of activated CD8-positive cells present in postoperative blood samples was the most remarkable characteristic in patients in which RCC recurred. Multivariate analysis showed that the percentage of activated CD8-positive cells in postoperative blood samples was the only predictor of recurrence (hazard ratio 1.29, p value 0.02). Thus, the high percentage of activated CD8-positive cells in postoperative blood samples is, therefore, a useful indicator of poor prognosis.

Antineoplastic Agents↗

Immune reactions associated with cerebral amyloid angiopathy.

BACKGROUND AND PURPOSE: Cerebral amyloid angiopathy (CAA) occasionally coexists with cerebral vasculitis. An immune system may influence deposition or degradation of the amyloid in cerebral blood vessels. The purpose of this study was to elucidate immune reactions associated with CAA. METHODS: In 11 elderly patients with sporadic CAA, 2 patients with Icelandic familial CAA, and 2 patients with CAA and granulomatous angiitis, the cerebrovascular amyloid proteins and infiltrating inflammatory cells were analyzed immunohistochemically. RESULTS: In both sporadic CAA (beta-protein amyloid angiopathy) and Icelandic familial CAA (cystatin C amyloid angiopathy), leptomeningeal and cortical vessels were associated with an increase or activation of monocyte/macrophage lineage cells. In the cases of CAA with granulomatous angiitis, the vascular amyloid was of beta-protein and associated with infiltration of many monocyte/macrophage lineage cells, which included multinucleated giant cells containing the amyloid in the cytoplasm as well as T cells composed of CD4+ and CD8+ subsets. Amyloid P component, which was reported to be a common component of amyloid deposits and to prevent phagocytic proteolysis of amyloid fibrils of beta-protein, was negative for the vascular amyloid in a case of CAA with granulomatous angiitis but positive in the others. CONCLUSIONS: In both the beta-protein and cystatin C amyloid angiopathies, cerebrovascular amyloid deposition was associated with an increase or activation of monocyte/macrophage lineage cells. Prominent reactions of monocyte/macrophage lineage cells admixed with CD4+ and CD8+ T cells (granulomatous angiitis) were occasionally associated with beta-protein angiopathy. In some of these cases, the absence of amyloid P component might be related to pathogenesis of the granulomatous reaction.

Aged↗

[Prostate cancer screening in total health care check--using serum PSA and AUA score].

From April 1994 to February 1995, we studied prostate cancer screening at Shakaihoken Hazu Hospital and Health Care Center. Among 1,838 men, over 55, who had taken the total health care check, 857 applicants had had prostate cancer screening, using serum PSA (Delia kit; normal range < 11.7 ng/ml) and AUA voiding symptom score and bothersome score. According to the serum PSA level, they were divided into 4 groups, 11 with 8 ng/ml or more indicating requirement of further examination, 29 with 4-8 ng/ml indicating requirement of observation, 100 with less than 4 ng/ml and AUA score (approximately more than 10) indicating voiding disturbance and the other 717 were normal; Of 11 further examined cases, 6 applicants underwent random biopsy. We found 3 with prostate cancer (0.35%).

Aged↗

[A case of leiomyoma of the urinary bladder associated with transitional cell carcinoma].

We report a case of leiomyoma of the urinary bladder associated with transitional cell carcinoma. A 60-year-old-male was referred to our hospital because of the complaint of dysuria and for detailed examination of left hydronephrosis. Drip infusion pyelography revealed left uretero-vesico junction stenosis. Flexible cystoscopy revealed benign prostatic hypertrophy and epithelial bladder tumor at the bladder neck and left ureteral orifice. The tumor was histologically diagnosed as TCC (transitional cell carcinoma). M-VAC chemotherapy (methotrexate 30 mg/m2, day 1, 15, 22, vinblastine 3 mg/m2, day 1, 15, 22, adriamycin 30 mg/m2, day 2, cisplatin 70 mg/m2, day 2) was performed as a neoadjuvant chemotherapy. However, since pelvic MRI revealed tumor invasion in to the muscle area, total cystoprostatourethrectomy and ileal conduit were done. Pathological examination of the tumor of left ureteral orifice revealed TCC, G2, INF beta, pT1, ly0, v(-), pN0, PM0. The tumor in the bladder neck was histologically diagnosed as submuscosal type leiomyoma. No cases of leiomyoma of the urinary bladder associated with transitional cell carcinoma have been reported in Japan.

Carcinoma, Transitional Cell↗

[A clinical study of renal cell carcinoma with extension into the inferior vena cava].

Nineteen patients with renal cell carcinoma with tumor extension into the inferior vena cava (IVC) were investigated between January, 1973 and March, 1994. The patients were between 50 and 78 years old with a mean of 65.9 years. The male to female ratio was 1.7 to 1. Thirteen tumors were on the right side and 6 on the left side. In 12 patients, both nephrectomy and removal of the tumor thrombus were performed. The survival rate in the operated group was 60% at 5 years. Histologically, 7 cases were diagnosed as clear cell subtype and 5 cases as granular cell subtype. From this study, an extended operative intervention such as radical nephrectomy combined with tumor thrombectomy of the IVC with or without cavectomy was suggested in the case of renal cell carcinoma without any other metastatic lesions and histopathologically of the clear cell subtype.

Aged↗

[Two cases of giant condyloma of the penis treated with penis-sparing methods].

Herein, we report two cases of giant condyloma of the penis treated with penis-sparing methods. In the first case, the papillomatous tumor disappeared with topical use of fluorouracil ointment. In the second case, the tumor was treated with topical use of fluorouracil or bleomycin hydrochloride, followed by the resection of tumor. Giant condylomas reported in the recent 13 years are reviewed and methods of treatment discussed.

Administration, Topical↗

[Postoperative sore throat--a comparison of standard cuff, gas-barrier cuff and Brandt anesthesia tube cuff].

Excessive intracuff pressure due to nitrous oxide diffusion into the cuff can damage the tracheal mucosa. Several endotracheal tubes have been developed (Trachelon gas barrier type tube, Brandt Anaesthesia tube) to limit nitrous oxide-related intracuff pressure increase. We investigated whether the incidence of postoperative sore throat could be reduced by using these tubes. Endotracheal intubation was performed in 37 adult female patients with either a standard tube (group S, n = 14), a gas barrier type tube (group G, n = 11), or a Brandt tube (group B, n = 12). All patients were interviewed 16-30 h postoperatively by anesthesiologist who did not know which tube had been used. The increase of intracuff pressure was significantly lower in group G (7.6 +/- 5.1 mmHg, mean +/- SD) and in group B (3.4 +/- 1.7 mmHg) than that in group S (24.0 +/- 9.5 mmHg). The incidence of postoperative sore throat was not significantly different among the groups, 36% (5/14) in group S, 45% (5/11) in group G, and 33% (4/12) in Group B. This incidence did not correlate with intracuff pressure increase. In conclusion, specially manufactured endotracheal tubes to limit excessive intracuff pressure did not effectively attenuate the incidence of postoperative sore throat in this patient population.

Adult↗

Keratinocyte growth factor (KGF) can replace testosterone in the ductal branching morphogenesis of the rat ventral prostate.

Prostatic growth occurs through ductal elongation and branching into the mesenchyme. Ductal branching morphogenesis in the prostate is elicited by androgens via mesenchymal-epithelial interactions mediated by paracrine influences from mesenchyme. The role of keratinocyte growth factor (KGF) was investigated in the developing prostate as KGF has been suggested to be a paracrine acting factor. KGF transcripts were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in neonatal rat ventral prostates (VPs) in vivo, in VPs cultured in vitro, and in isolated VP mesenchyme. KGF receptor was detected in VP's by RT-PCR and was localized specifically to the epithelium by in situ hybridization. KGF was investigated as a potential paracrine mediator during androgen-induced prostatic development by examining neonatal rat VPs cultured for 6 days under serum-free conditions using a basal medium supplemented only with insulin and transferrin. When testosterone (10(-9) to 10(-8) M) was added to the basal medium, VPs grew and underwent ductal branching morphogenesis similar to that in situ. Neutralization of endogenous KGF with a monoclonal antibody to KGF (anti-KGF) or a soluble KGF receptor peptide inhibited androgen-stimulated VP growth (DNA content) and reduced the number of ductal end buds after 6 days of culture. When KGF (50 or 100 ng/ml) was added to the basal medium in the absence of testosterone, VP growth and ductal branching morphogenesis were stimulated. The number of ductal end buds was about 70% of that obtained with an optimal dose of testosterone (10(-8)M), and DNA content of VP's cultured with 100 ng/ml KGF was equivalent to that of glands cultured with testosterone. The stimulatory effect of KGF was partially blocked by cyproterone acetate, a steroidal anti-androgen. These data imply that KGF plays an important role as a mesenchymal paracrine mediator of androgen-induced epithelial growth and ductal branching morphogenesis in the rat VP.

Animals↗

[Endorectal magnetic resonance imaging for staging of prostatic cancer].

We retrospectively studied the staging accuracy of endorectal magnetic resonance imaging (MRI) using a surface coil for 14 localized prostatic cancers resected by retropubic radical prostatectomy. The prostatic tumor in the peripheral zone was mostly demonstrated as a low signal intensity on the T2 weighted image, and prostatic capsular invasion was indicated as an interruption of prostatic capsule, irregularity of glandular margins, and a low signal intensity of periprostatic venous plexus on the T2 weighted image. The seminal vesicular invasion was seen as a high signal intensity on the enhanced T1 weighted image, and a low signal intensity on the T2 weighted image. The clear prostatic zonal anatomy was demonstrated on the T2 weighted image. The accuracies of clinical staging in endorectal MRI and transrectal ultrasound examination (TRUS) were 79% and 57%, respectively. Also, the accuracies of seminal vesicular invasion in endorectal MRI and TRUS were 93% and 57%, respectively. The endorectal MRI revealed more accurately the seminal vesicular invasion than TRUS (p = 0.038), but there was no significant difference in the accuracy of detecting prostatic capsular invasion between endorectal MRI (79%) and TRUS (71%). The reduction of prostatic volume after 4 months of endocrine neoadjuvant therapy (LH-RH agonist) was compared in each prostatic intraglandular zone with the T2 weighted image. The total prostatic reduction rate was 43.2%. The reduction rate in the peripheral zone (64.8%) was more than two-fold that (29.7%) in the central gland (transition zone + central zone). The endorectal MRI may greatly contribute to the local staging of prostatic cancer, especially to the diagnosis of seminal vesicular invasion.

Gadolinium DTPA↗

[Usefulness of 99mTc-DTPA renography and diuretic renography in predicting successful stone discharge following outpatient ESWL in patients with a single ureteral stone].

We analyzed the 99mTc-DTPA renogram with and without diuresis to predict the possibility of stone discharge on the outpatient basis by renogram patterns. Between October, 1993 and December, 1995, 99mTc-DTPA renography was performed in 79 patients with a single ureteral stone. The 99mTc-DTPA renogram pattern was classified into the three types of normal function, obstruction and lower function patterns and the complete stone discharge rate was 93, 63 and 25%, respectively. In addition, diuretic renography using Furosemide was performed in patients with an obstruction pattern and the three renogram patterns of return to the normal curve, a diuretic response and no response were obtained; the complete stone discharge rate was 44, 65.3 and 93%, respectively. From this study, patients with a single ureteral stone with a normal pattern on the regular DTPA renogram and patients with no response pattern on the diuretic renogram, even if in such patients an obstructive pattern was seen on the regular DTPA renogram, seem to be a good candidate for obtaining a high rate of a stone discharge with extracorporeal shock wave lithotripsy (ESWL) treatment in the outpatients basis.

Diuretics↗

[Effect of pamidronate and interferon-alpha on bone and lung metastases and hypercalcemia in a patient with renal cell carcinoma].

Pamidronate is a second generation bisphosphonate used for treating tumor-induced hypercalcemia and for preventing the development of new bone metastasis. A 47-year-old man with renal cell carcinoma was admitted in our institution because of hypercalcemia with multiple metastasis in bone, lung and lymph nodes. After embolization of the right renal artery, the patient was treated with pamidronate and interferon-alpha. Intravenous pamidronate significantly reduced bone pain and normalized the serum calcium level. The pulmonary metastasis responded to interferon therapy after 2 months of therapy. Radical nephrectomy was then carried out. Paraaortic lymph nodes were found to be necrosed completely. Ossification of osteolytic lesions was observed after two months of therapy and metastatic lesions in the lung showed complete remission (CR) after six months of therapy.

Antineoplastic Agents↗