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Biomedical subjects

M Iwamura

Publications and source records attributed to M Iwamura.

At least 55 records · Page 3Linked to original sources

[A case of fulminant hepatitis caused by antiandrogen, flutamide in a patient with prostate cancer].

Luteinizing hormone-releasing hormone analogue, 3.6 mg goserelin acetate and flutamide, 375 mg per day were used to treat metastatic prostate cancer in a 66-year-old male. Marked increase in serum aminotransferases and total bilirubin levels was noted after 7 weeks of treatment. The enzyme levels returned to normal at 2 months following discontinuation of the treatment. Though incidences of severe hepatotoxicity are rare (0.003-0.18%), cases of flutamide-induced death have been reported. Careful monitoring of patients is mandatory while administering flutamide.

Aged↗

Acyloxycoumarinylmethyl-caged cAMP, the photolabile and membrane-permeable derivative of cAMP that effectively stimulates pigment-dispersion response of melanophores.

Two acyloxycoumarinylmethyl-caged cAMPs (ACM- and PCM-cAMP) have been synthesized using a silver (I) oxide promoted method. Introduction of the acyloxy group to the 7-position on the coumarin ring not only enhanced the membrane permeability but diminished the photolability of the coumarin-cage. Because intracellular enzymatic hydrolysis of the 7-acyloxy group would produce the 7-hydroxy moiety which is more hydrophilic and photolabile, application of acyloxycoumarinylmethyl-caged cAMPs in biological studies would be expected to be efficient. Thus, the effect of extracellularly applied ACM- and PCM-cAMP had been investigated using the motile response of fish melanophores. After irradiation, a significant enhancement in the motility responses was observed. The observed magnitudes of the dispersions are comparable to that of Bt2cAMP/AM which is known as a membrane permeable cAMP derivative.

1-Methyl-3-isobutylxanthine↗

Microsatellite instability in transitional cell carcinoma of the urinary tract and its relationship to clinicopathological variables and smoking.

To determine whether microsatellite instability is involved in the development of transitional cell carcinoma (TCC) of the urinary tract, a microsatellite instability assay was carried out using PCR with 9 microsatellite loci. Thirty-eight TCC samples (30 patients with bladder cancer, 5 with renal pelvic tumors and 3 with ureteral tumors) and 1 lymph node with metastasis were examined. Microsatellite instability was found in 8 of 38 tumors examined, and 3 showed alterations in more than 2 microsatellite loci. All 8 tumors were beyond grade 2 and stage pT2 advanced tumors. Stages pT1-2 and pT3-4 patients differed significantly. Microsatellite instability was greater in smokers than non-smokers, but the differences were not significant. Microsatellite instability in TCC of the urinary tract is rare in superficial tumors but more common in invasive tumors. Microsatellite alterations would thus appear to occur, and possibly be importantly involved, in the tumorigenesis of urinary tract TCC.

Carcinoma, Transitional Cell↗

Risk of progression and dying of clinically localized prostate cancer in Japan.

Study was made of the conservative management of 107 men with clinically localized prostate cancer. Distant metastasis developed more frequently in patients with poorly differentiated tumors than in those with well- and moderately differentiated counterparts (P < 0.01). Poorly differentiated histology was strongly associated with cancer-specific death (P < 0.01). The progression-free and cancer-specific survival of patients with stage T1a disease was significantly better than that of patients with stages T1b, T2a-b, and T2c tumors (P < 0.05). Available data clearly demonstrate that prostate cancer is a progressive disease when managed conservatively. Long-term follow-up data indicate the natural history of prostate cancer not to differ significantly according to race, despite noteworthy differences in prevalence and mortality. Patients with localized prostate cancer would be candidates for expectant therapy if they had lower-grade tumors and a life expectancy of 10 years or less. For patients with a 10-year or greater life expectancy and any grade of disease definitive therapy should be applicable.

Aged↗

Alteration of the hormonal bioactivity of parathyroid hormone-related protein (PTHrP) as a result of limited proteolysis by prostate-specific antigen.

OBJECTIVES: To discover whether the proteolytic activity of prostate-specific antigen (PSA) affects the structure and function of parathyroid hormone-related protein (PTHrP), as both are abundant components of human seminal plasma. METHODS: The ability of PTHrP to act as a substrate was studied by incubating a synthetic polypeptide, consisting of 34 amino acid residues of the amino-terminal domain of PTHrP, with purified PSA. The incubate was then analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, high-pressure liquid chromatography separation, amino-terminal peptide sequencing, and mass spectrometry. The physiologic effect of the proteolytic activity of PSA on PTHrP was studied by measuring any alteration in PTHrP (1-34)-induced elevation of cyclic adenosine monophosphate (cAMP) production by UMR-106 rat osteosarcoma cells in culture. All cell culture experiments were performed with PSA and PTHrP (1-34) at physiologic concentrations. RESULTS. Our data show that PSA proteolytically cleaves PTHrP (1-34) after either residue 22 or 23, generating three peptide fragments. Both cleavages occur carboxy terminally of a phenylalanine residue. The cAMP production in rat osteosarcoma cells, induced by the amino-terminal portion of PTHrP (1-34), as a result of its structural similarity with parathyroid hormone (PTH), was abated by PSA in a dose- and time-dependent fashion. In contrast, heat-inactivated PSA had no effect on cAMP production. CONCLUSIONS: Our study demonstrates that PTHrP is a substrate for PSA. The cleavage of the amino-terminal portion of PTHrP completely disrupts its ability to interact with the PTH/PTHrP receptor and thus inhibits its PTH-like activity. The proteolytic processing of PTHrP by PSA may play an important role in the post-translational/post-secretional regulation of prostatic PTHrP activities, which are believed to include regulation of prostate growth and differentiation.

Amino Acid Sequence↗

Deoxyribonucleic acid ploidy status as no basis for pathologic stage prediction in clinically resectable prostate cancer.

OBJECTIVES: Assessment of deoxyribonucleic acid (DNA) ploidy status of a tumor as a means for predicting pathologic stages in prostate cancer. METHODS: DNA ploidy of each focus of a cancer in 70 radical prostatectomy specimens was determined by nuclear image analysis. DNA ploidy was compared with the pathologic features of tumors. RESULTS: One hundred three individual cancers in 70 patients were used for DNA ploidy analysis. Of these, 39 (38%) were diploid and 64 (62%), nondiploid. DNA ploidy was weakly correlated with increase in tumor volume (P = 0.049) but not tumor grade. The relationship between DNA content and extraprostatic spread was not statistically significant. Increase in tumor volume and grade promoted extraprostatic spread more than nondiploidy, as shown by multivariate analysis. CONCLUSIONS: The incidence of a nondiploid cell population in a tumor focus in prostate cancer is essentially the same, at least for Americans and Japanese. DNA ploidy of a tumor cannot serve as a means of pathologic stage prediction in clinically resectable prostate cancers, contrary to many previous studies. Thus, DNA content analysis would be of no use for deciding on the treatment strategy of prostate cancer.

DNA, Neoplasm↗

A non-randomized comparative study of visual laser ablation and transurethral resection of the prostate in benign prostatic hyperplasia.

BACKGROUND: Transurethral resection of the prostate (TURP) has been the preferred surgical treatment for benign prostatic hyperplasia (BPH) for the past 50 years. Alternative methods for treating BPH such as visual laser ablation (VLAP) have been established during the past decade. In order to assess the safety and efficacy of VLAP, this alternative method was performed using a Urolase fiber and neodymium: yttrium-aluminum-garnet laser, and compared to results obtained in patients treated with TURP for BPH. METHODS: In this non-randomized comparative study, 100 BPH patients were equally split between treatment with VLAP or TURP, and their cases compared. The efficacy was assessed using an International Prostate Symptom Score, urinary flow rates, post-void residual urinary volume and an estimated prostate volume. RESULTS: There was a clinically significant improvement in all parameters in both groups. In the VLAP and TURP groups, 92.0% and 81.6%, 90.2% and 86.2 and 93.1% and 100.0% were categorized as effectively-treated cases at 3, 6 and 12 months post-operatively, respectively. No severe side effect was seen in VLAP group. The total and post-operative lengths of hospitalization in the VLAP group were shorter, but the duration of post-operative bladder irrigation was longer in these patients. CONCLUSIONS: Although TURP remains the standard surgical treatment for BPH, VLAP is associated with less morbidity and the clinical outcome is similar compared to patients treated with TURP. VLAP in conjunction with TURP may result in less risk of postoperative urinary retention and vesical irritability.

Aged↗

Synthesis, photoreactivity and cytotoxic activity of caged compounds of L-leucyl-L-leucine methyl ester, an apoptosis inducer.

L-Leucyl-L-leucine methyl ester (Leu-Leu-OMe), an apoptosis inducer in natural killer cells and macrophages, was caged with trans-o-hydroxycinnamoyl (3a-d), trans-o-mercaptocinnamoyl (4) and o-nitrobenzyl derivatives (5a, b), and the photochemical reactivity of these derivatives in phosphate-buffered saline containing 1% dimethyl sulfoxide and their immunological properties were studied. All of the derivatives exhibited absorption at wavelengths longer than the UVB region. Although 3a-d and 4 were expected to isomerize to a cis isomer, which then cyclizes intramolecularly to give Leu-Leu-OMe and a coumarin derivative, cyclization efficiency was not satisfactory except for 3a. However, 3a itself caused necrosis (cell swelling) of U937 cells (a myeloid cell line). In contrast, 5a and b released Leu-Le-OMe quickly and efficiently and did not affect U937 cells. Although irradiated 5b induced necrosis, irradiated 3a and 5a induced apoptosis in these cells, as evidenced by a decrease in cell size.

Apoptosis↗

Cervical discitis associated with spinal epidural abscess caused by methicillin-resistant staphylococcus aureus.

A 53-year-old male developed fever, nuchalgia, shoulder pain, and sore throat after a partial sigmoidectomy. He suffered sudden onset of quadriplegia about 5 days later. Magnetic resonance (MR) imaging indicated the characteristic appearance of C5-6 intervertebral disc herniation. However, anterior discectomy showed that he had cervical discitis associated with spinal epidural abscess. Continuous pus drainage from the abscess and vigorous antibiotic therapy were undertaken after surgery. He improved and could walk with assistance. MR imaging with gadolinium can be useful in diagnosing pyogenic spinal infection (epidural abscess, osteomyelitis, and discitis), but care should be taken in MR image interpretation since spinal epidural abscess associated with discitis may mimic disc herniation. Axial MR images are important to distinguish this rare disease from other cervical disorders.

Abscess↗

[Renal cell carcinoma associated with circumferential "ring-like" calcification].

A 37-year-old man was found to have large calcification in the left kidney in a health check. This calcification has not changed in size during 3 years with computerized tomographic (CT) studies. However, a suspicious lesion for a malignant tumor with the calcification was suggested by a magnetic resonance image (MRI) study. Thus, the patient underwent tumor enucleation and the histology showed the mixed typed renal cell carcinoma. Although it remains controversial, partial nephrectomy or tumor enucleation would be considered in a case of renal cell carcinoma with calcification, which is usually considered to have a favorable prognosis compared to that of a tumor without a calcification.

Adult↗

[A case of solitary metastasis from renal cell carcinoma to the thyroid gland].

A case of solitary metastasis with renal cell carcinoma to the thyroid gland is presented. The patient was a 54-year-old man found to have an abnormal mass in the neck. He had a past history of radical nephrectomy orignating from the right renal cell carcinoma 5 years earlier (pT2N0M0, G2 > 3, alveolar type, clear cell subtype). Ultrasonography revealed a tumor mass in the right hemithyroid gland. Right hemithyroidectomy was performed on April 19, 1995. Histopathologically, the removed thyroid tumor showed clear cell carcinoma. The possibility of a primary thyroid tumor was ruled out by immunohistochemical thyroglobulin staining, and the present case was thus diagnosed as of metastatic thyroid tumor of renal cell carcinoma. The present case is the 12th case of thyroid solitary metastasis of renal cell carcinoma reported in Japan to date.

Carcinoma, Renal Cell↗

[Renal cell carcinoma in childhood: a case report].

A case of renal cell carcinoma (RCC) in a teenage patient is reported. A 13-year-old girl visited our hospital with the complaint of dyspnea and right abdominal mass. CT scan and chest X-P revealed a right renal tumor with multiple lung metastasis. Wilms' tumor was suspected and a combination chemotherapy consisting of actinomycin D and vincristin was performed. Since the tumor was insensitive to these agents, open biopsy was done. The pathological findings showed clear cell renal cell carcinoma. Despite the administration of alpha interferon, 5-FU and cimetidine, the disease was progressive and the patient died 5 months after diagnosis. It is important to consider the possibility of renal cell carcinoma in teenage patients with a renal mass, since more than 40% of the renal tumors in this age group are renal cell carcinomas.

Adolescent↗

[A case of spontaneous rupture of renal leiomyosarcoma].

A 53-year-old female visited our out-patient department complaining of right flank pain. Ultrasonography revealed a solid mass lesion in the lower pole of the right kidney and further evaluation was scheduled. A few days later, she suddenly felt pain at the abdominal enlarged mass. Computed tomographic (CT) scan revealed a huge retroperitoneal mass with heterogenous density. Spontaneous rupture of renal tumor was suspected and emergency nephrectomy was performed. The ruptured tumor was pale, elastic firm and invaded directly to the duodenum. Histopathological findings revealed fibrous cells with frequent nuclear mitosis. Smooth muscle actin was identified immunohistochemically. Therefore, the tumor was diagnosed as leiomyosarcoma. The patient died 2 months after operation due to perforation of the intestine.

Actins↗

Synthesis of caged compounds of L-leucyl-L-leucine methyl ester, an apoptosis inducer, and their cytotoxic activity.

In this study, we newly synthesized caged compounds of L-leucyl-L-leucine methyl ester and examined their photochemical and immunological properties. From the viewpoints of solubility in phosphate-buffered saline containing 1% dimethyl sulfoxide as well as photoreactivity, we chose two caged compounds, 1 and 2, for study. Upon irradiation, L-leucyl-L-leucine methyl ester with a trans-o-hydroxycinnamoyl group (1) releases L-leucyl-L-leucine methyl ester quite slowly, whereas L-leucyl-L-leucine methyl ester with an o-nitrobenzyl group (2) releases L-leucyl-L-leucine methyl ester quickly. Both irradiated compounds induced apoptosis of U937 cells, as evidenced by a decrease in cell size, although 1 itself caused necrosis (cell swelling) of these cells.

Antineoplastic Agents↗

Genomic instability of microsatellite repeats in prostate cancer: relationship to clinicopathological variables.

Sixty-six patients with prostatic adenocarcinoma were screened for somatic instability at 8 microsatellite marker loci on 5 chromosomes. Differences in unrelated microsatellites for tumor and normal DNA were detected in 13 (19.7%) patients. Only extraglandular spread (nodal involvement and distant metastasis) was found to show significant association with somatic instability after controlling for other clinicopathological variables (P < 0.05). Microsatellite instability may possibly occur during the early stages of neoplastic transformation in a subset of prostate cancer rather than as a late event. This may be related to a phenotype with growth advantage. The frequency of this mutator phenotype is much higher in the United States than Japan, reflecting racial differences in the molecular tumorigenesis of this malignancy.

Adenocarcinoma↗

Immunohistochemical localization of parathyroid hormone-related protein in prostatic intraepithelial neoplasia.

Parathyroid hormone-related protein (PTHrP) is a regulatory protein hormone that has been associated with normal fetal growth and differentiation as well as fetal calcium regulation. Parathyroid hormone-related protein has been implicated in a variety of carcinomas as a major factor in the development of humoral hypercalcemia of malignancy and may also play a role as an autocrine growth factor. In a previous immunohistochemical study we found that all prostatic adenocarcinomas (CAP) express PTHrP. In the current study, we evaluated PTHrP in prostate intraepithelial neoplasia (PIN) in radical prostatectomy specimens. A validated mouse monoclonal antibody, 9H7, raised against fragment 109-141 of the carboxy-terminus of PTHrP was used for immunostaining. The results generally showed negative to weak staining of normal and hyperplastic tissue and strong staining in PIN. The staining intensity was further evaluated by computer based image analysis. The relative optical density in PIN (9.24 +/- 9.05) was significantly (P = .008) higher than that in normal gland (.00 +/- 3.6). These findings suggest that PTHrP may be involved in the pathogenesis of prostatic dysplasia, and its immunohistochemical evaluation may have diagnostic use in the evaluation of PIN.

Adenocarcinoma↗

High intensity focused ultrasound for benign prostatic hyperplasia.

BACKGROUND: Transurethral resection of the prostate (TURP) has been the gold standard of treatment for patients with symptomatic benign prostatic hyperplasia (BPH). The present paper discusses the safety and effectiveness of transrectal high intensity focused ultrasound (HIFU) for treating patients with symptomatic BPH. METHODS: HIFU was conducted on 28 patients with BPH. At one, three and six months after treatment, all patients were examined for parameters including International Prostate Symptom Scores (I-PSS), Quality of Life (QOL) inquiry, uroflowmetry, and transrectal ultrasound for determining prostate volume. RESULTS: I-PSS and QOL showed statistically significant improvement at one, three, and six months postoperatively (P < 0.0001-0.005, Wilcoxon signed-rank test). Ten of 28 (35.7%), 13 of 28 (46.4%), and 6 of 15 (40.0%) cases were categorized as effective cases with HIFU treatment at one, three, and six months follow-up. CONCLUSIONS: Focused ultrasound is an exciting new technology by which tissue can be destroyed at a site distant from the source of energy without damage to surrounding tissue. Clinical experience with alternative power settings, more accurate spacing of treatment lesions, and further development of HIFU machines may improve the results. Longer follow-up of patients with further clinical evaluation of HIFU is necessary to define the efficacy of this technique.

Aged↗