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Biomedical subjects

K Kunimi

Publications and source records attributed to K Kunimi.

At least 19 recordsLinked to original sources

Identification of the human sperm protein that interacts with sperm-immobilizing antibodies in the sera of infertile women.

OBJECTIVE: To identify the target antigen of sperm-immobilizing antibodies present in the circulation of infertile women. DESIGN: Laboratory research. SETTING: Academic research laboratory. PATIENT(S): Twenty-nine infertile women with sperm-immobilizing antibodies, 22 infertile women with other disorders, and 20 fertile women. INTERVENTION(S): Titers of antibodies to the sperm protein, rSMP-B, were determined by ELISA using as substrate the synthetic peptide segment (rSMP-230) that corresponds with the hydrophilic domain of rSMP-B. Tests for sperm immobilization and zona pellucida penetration were performed using the human IVF system. MAIN OUTCOME MEASURE(S): Human sera with sperm-immobilizing activity were assayed for the presence of antibodies to rSMP-230. Polyclonal antibodies to rSMP-230 were assessed for the same biologic activities as sperm-immobilizing antibodies. RESULT(S): Antibodies to rSMP-230 were detected in 10 (34%) of 29 sera obtained from women with immunologic infertility. In contrast, only one serum sample (2%) from women without sperm-immobilizing activity had a low titer of antibodies to rSMP-230. Polyclonal antibodies to rSMP-230 completely immobilized human sperm in the presence of complement and blocked sperm penetration across the zona pellucida. CONCLUSION(S): The human sperm protein, rSMP-B, probably is the target antigen of sperm-immobilizing antibodies.

Adult↗

Expression of messenger RNAs for membrane-type 1, 2, and 3 matrix metalloproteinases in human renal cell carcinomas.

PURPOSE: Three different membrane-type matrix metalloproteinases (MT1, 2, and 3-MMP) that can activate proMMP-2 (progelatinase A) are thought to play an important role in invasion and metastasis by various human carcinomas. To further clarify this role, we examined mRNA expression of MT-MMPs in human renal cell carcinomas. MATERIALS AND METHODS: mRNA was extracted from 25 clinical specimens of renal cell carcinoma and 23 specimens of normal renal parenchyma remote from the tumor. Reverse transcription polymerase chain reaction (RT-PCR) using specific primers was performed, and PCR products were hybridized to 32P-labeled internal probes and analyzed by a bioimage analyzer. RESULTS: MT1, 2, and 3-MMP mRNA expression in carcinomas was significantly higher than in normal parenchyma. In terms of the pathologic stage, MT1-MMP mRNA expression in pT2 and pT3 tumors was significantly higher than those in pT1 tumors. Although the sample size was small, it was evident that MT3-MMP mRNA expression in clear cell subtype renal cell carcinomas was higher than in the group of tumors including the granular cell subtype. CONCLUSIONS: These three MT-MMPs may play an important role in the pathogenesis of human renal cell carcinoma, and MT1-MMP in particular is important in invasion by carcinoma cells. It is interesting that the expression of MT3-MMP was higher in carcinomas, especially clear cell carcinoma, than in normal parenchyma, so that MT3-MMP may provide a clue an understanding of the molecular mechanism of carcinogenesis in human kidney.

Carcinoma, Renal Cell↗

[Renal cell carcinoma recurrence in the mediastinum lymph node 19 years after nephrectomy: a case report].

A 62-year-old male, who had undergone right nephrectomy to treat renal cancer 19 years earlier, was recently referred to our hospital to receive a detailed examination and treatment of mediastinal lymph node swelling. Biopsy of the swollen lymph nodes allowed a diagnosis of renal cell carcinoma (alveolar type, clear cell subtype, GI) to be made. The pathological features of his tumor were consistent with those of the renal tumor resected 19 years previously. Because there was a high probability of further growth of the swollen mediastinal lymph nodes and consequent high probability of compression of the superior vena cava, we performed mediastinal lymph node excision. Immediately after surgery, prophylactic interferon therapy was started. To date, five cases (including the present case) in which renal tumors recurred more than 15 years after surgical treatment have been reported in Japan.

Carcinoma, Renal Cell↗

beta-Microseminoprotein/prostatic secretory protein is a member of immunoglobulin binding factor family.

Human seminal plasma contains a factor that binds human IgG, designated as immunoglobulin binding factor (IgBF). Under reducing condition IgBF interacts with anti-Leu-11b, a murine monoclonal antibody raised against human FcgammaRIII/CD16. IgBF shows no binding activity under non-reducing condition. Three components having IgBF activity were separated by HPLC and their amino acid sequences determined. The main IgBF showed structural identity to beta-microseminoprotein (beta-MSP), prostatic secretory protein of 94 amino acids (PSP94) and beta-inhibin. The slight variation in the reported sequences of these proteins has been attributed to analytical error. In the present study the molecular masses of main IgBF and beta-MSP/PSP94 were found to be identical by mass spectrometry. In addition, a large component of IgBF and a shorter beta-MSP consisting of 93 amino acids were identified. The binding of beta-MSP for human IgG and anti-Leu-11b antibody is demonstrable only under reducing condition, determined by Western blot analysis. The present data clearly show that IgBF is a family composed of at least three isoforms. One of the members is beta-MSP/PSP94. This family should be designated as IgBF.

Amino Acid Sequence↗

Effects of MK-801 on bladder overactivity in rats with cerebral infarction.

PURPOSE: Our objective was to evaluate the underlying mechanisms of neurogenic voiding dysfunction following cerebral infarction. MATERIALS AND METHODS: The left middle cerebral artery (MCA) was occluded using 4-0 monofilament nylon thread in male S-D rats. Cystometric examination was performed in unanesthetized and urethane-anesthetized rats through a catheter chronically implanted in the dome of the bladder. RESULTS: Bladder capacity of unanesthetized or urethane anesthetized rats was significantly reduced just after occlusion of the left MCA; 2 weeks after the occlusion, the capacity was less than half that in sham-operated rats. Intravenous administration of N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 to the unanesthetized sham-operated rats led to a marked dose-dependent decrease in bladder capacity. Its administration to unanesthetized rats with cerebral infarction resulted in a slight decrease in bladder capacity. In the urethane-anesthetized state, the bladder capacity of the rats with cerebral infarction was significantly increased by MK-801, 0.1 mg./kg., without inhibiting the contraction pressure or increasing the amount of residual urine. A high dose (1 mg./kg.) of MK-801 was required to increase the bladder capacity of sham-operated rats. This led to an inhibition of contraction pressure and an increase in residual urine. CONCLUSION: Results in urethane anesthetized rats indicate that NMDA glutamatergic transmission is important in the overactivity of the bladder following a cerebral infarction. This model is useful in studying the neurogenic voiding dysfunction observed in patients with cerebrovascular disease.

Anesthesia↗

Chemotherapy of metastatic testicular germ cell tumors: relationship of histologic response to size reduction and changes in tumor markers.

BACKGROUND: Although testicular germ cell tumor is one of the most curable cancers, approximately 20% of advanced cases remain incurable. In this study we investigate factors that may predict a poor response to standard chemotherapeutic regimens and thus allow earlier initiation of more aggressive measures. METHODS: We analyzed the records of 19 patients with metastatic testicular germ cell tumors (8 seminomas and 11 nonseminomas). Sixteen patients underwent surgical exploration for residual tumors following chemotherapy, and the histological findings on the resulting specimens were correlated with reductions in tumor size observed on computed tomography and with changes in tumor marker levels. RESULTS: Complete necrosis was obtained in 10 of 12 lesions that shrank by at least 80%, while continued existence of teratoma or cancer was confirmed in 9 of 11 lesions with smaller size reductions. An initial human chorionic gonadotropin-beta subunit (HCG-beta) level more than 100 times the upper limit of normal appeared to predict poor histological response (teratoma/cancer) to chemotherapy. Slow fall (prolonged half-life) of tumor markers during chemotherapy also correlated with poor histological response. CONCLUSION: Factors which predict poor histological response of tumors to chemotherapy include size reduction less than 80%, initial HCG-beta levels more than 100 times the upper limit of normal, and prolonged half-life of tumor markers (placental alkaline phosphatase, alpha-fetoprotein and HCG-beta).

Antineoplastic Combined Chemotherapy Protocols↗

Expression and tissue localization of membrane-types 1, 2, and 3 matrix metalloproteinases in human urothelial carcinomas.

PURPOSE: Three different membrane-type matrix metalloproteinases (MT1, 2, 3-MMP) which can activate proMMP-2 (progelatinase A) are thought to have an important role in various human carcinoma invasions and metastases. We examined the mRNA expression of MT-MMPs and the tissue immunolocalization of MT1-MMP in human urothelial carcinomas. MATERIALS AND METHODS: mRNA was extracted from 27 clinical urothelial carcinomas and 10 normal urothelial mucosa tissues remote from the tumor. RT-PCR using specific primers was performed, and PCR products were hybridized to 32P-labeled internal probes and analyzed by a bioimage analyzer. Immunolocalization was studied using a monoclonal antibody against MT1-MMP (114-6G6). RESULTS: MT1-MMP and MT2-MMP mRNA expressions in urothelial carcinomas were significantly higher than those in the normal mucosa. In contrast, MT3-MMP mRNA was little expressed in both tissues, and the amount of MT3-MMP mRNA appeared to be much lower than MT1-MMP and MT2-MMP in the tissue samples. In terms of the tumor multiplicity, MT1-MMP and MT2-MMP mRNA expressions in the group of multiple tumors were significantly higher than those in the solitary tumor group. The carcinoma cells were immunostained for MT1-MMP predominantly in invasive and superficial carcinoma cells. The immunoreactivity was more intense in the invasive type than in the superficial type. CONCLUSIONS: It is suggested that MT1-MMP and MT2-MMP play an important role in the development of human urothelial carcinomas and reflect some aspects of the pathogenesis of multifocal occurrence. In spite of the possible contribution to the invasive and metastatic phenotype, MT1-MMP mRNA and its product are thought to be expressed already in the clinical superficial stage in some cases of this tumor type.

Carcinoma, Transitional Cell↗

Telomerase activity in human urothelial tumors.

Telomerase is a ribonucleoprotein that synthesizes telomeric DNA onto chromosomal ends by using an RNA component as a template. Telomerase extends the telomeric repeats, which prevents telomere shortening during cell division, contributes to chromosomal stability, and, possibly, leads to immortalization of the cells. The telomerase activity in 22 urothelial tumors, including 13 bladder cancers, 8 ureter cancers, and 1 renal pelvic cancer, as well as in 12 adjacent normal tissues, was examined with the use of a nonradioisotope polymerase chain reaction (PCR)-based telomeric repeat amplification protocol assay. Different levels of telomerase activity were detected in the urothelial tumors. No significant activity was observed in normal adjacent tissues; however, two cases exhibited weak activity. Nine tumors retained positive telomerase signals after 100-fold dilution of extracts, which suggests that these tumors express high levels of telomerase activity. These findings indicate that telomerase activation may be a critical step in the pathogenesis of urothelial tumors. Unexpectedly, no significant correlation was observed between high levels of telomerase expression and the clinicopathologic features of the tumors, including clinical stage, pathologic grade, tumor multiplicity, and status of recurrence.

Adenocarcinoma↗

Trends in clinical outcome of transitional cell carcinoma of the ureter: have the results improved?

We divided 53 consecutive patients with transitional cell carcinoma of the ureter into two groups. Group A consisted of patients treated in the 1970s and group B of patients treated in the 1980s. Clinical features and outcomes were compared between the groups. Group B patients saw an increased use of new diagnostic modalities, including antegrade pyelography, computed tomography, and bone scintigraphy. Regional lymphadenectomy was added to the operative routine in group B and combined chemotherapy, using methotrexate, vinblastine, adriamycin and cisplatinum, the most effective regimen at present, was used in 9 patients in group B and no patients in group A. In spite of new diagnostic modalities and treatments, the survival rate for ureteral cancer failed to improve from the 1970s to the 1980s.

Aged↗

Urodynamic effects of intravesical instillation of lidocaine in patients with overactive detrusor.

PURPOSE: We evaluated the effects of intravesical administration of lidocaine on the overactive detrusor in patients with spinal cord injury and cerebrovascular disease. MATERIALS AND METHODS: Cystometry was performed before and 15 minutes after intravesical instillation of 20 ml. of 1 and/or 4% lidocaine in 48 patients with spinal cord injury and 67 with cerebrovascular disease. RESULTS: A significant increase in bladder capacity was observed following administration of 1 and 4% lidocaine in patients tested longer than 1 year after spinal cord injury. However, no significant increase was noted even with 4% lidocaine in those tested within 1 year after injury. A significant increase in bladder capacity was observed in patients with cerebrovascular disease with 4 but not 1% lidocaine. When comparing the percent increase in bladder capacity obtained with 4% lidocaine in the 2 groups, patients with spinal cord injury showed a significantly greater increase than those with cerebrovascular disease (91.6 versus 31.9%, respectively). Detrusor contractions disappeared in 37.5 versus 5.4% of patients, respectively. CONCLUSIONS: Intravesical administration of lidocaine appears to be useful in differentiating detrusor hyperactivity caused by lesions of the spinal cord versus those of the brain.

Administration, Intravesical↗

Melanotic neuroectodermal tumor of infancy in the epididymis. Case report and literature review.

We report a case of melanotic neuroectodermal tumor that originated in the right epididymis of a 4-month-old Japanese male and review reports of similar cases. Since we could not exclude malignant disease preoperatively, we performed a radical orchiectomy. Histopathological and immunohistochemical studies revealed features characteristic of a melanotic neuroectodermal tumor. Imaging studies showed no distant metastases.

Epididymis↗

Point mutation of the p53 gene is an infrequent event in untreated prostate cancer.

The p53 gene is known to be one of the frequently altered tumor suppressor genes, involved in the oncogenesis of a wide spectrum of human malignant tumors. We investigated mutational events of the p53 gene in 18 clinically untreated prostate cancers. Direct sequencing analysis demonstrated that 1 of 18 cases harbored point mutation in the highly conserved transcript region. The case showed CAT at codon 273 instead of wild-type CGT, substituting the encoded amino acid form histidine to arginine. The case had previously revealed homozygous loci on 17p, including the p53 locus, by restriction fragment length polymorphism analysis. The other 17 cases harbored neither mutation nor small deletion. It is concluded that point mutation of the p53 gene is a infrequent event in the oncogenesis of untreated prostate cancer.

Base Sequence↗

[Molecular staging of hematogenous microdissemination of prostate cancer cells].

We have used a reverse transcriptase-polymerase chain reaction assay for prostate specific antigen (PSA) expression to detect hematogenous microdissemination in patients with prostate cancer. Thirty-nine consecutive patients with prostate cancer were surveyed. Nineteen patients (48.7%) were positive for PSA-expressing cells in this assay. Positivity rates by stage were as follows: stage A1-0/1, A2-0/2, B-2/6, C-2/9, D0-3/3, D1-1/4, D2-11/14. In clinically organ-confined cancers with a positive assay result, two stage C patients subsequently developed bone metastasis, while two stage B patients who were positive had no evidence of disease progression. In patients with a negative assay result, 3 of the 3 stage A, 3 of the 4 stage B, and 6 of the 7 stage C patients did not develop hematogenous dissemination during the follow-up period. Molecular assay for hematogenous microdissemination of prostate cancer cells provides an opportunity for earlier detection of disseminated disease and may have prognostic value.

Humans↗

Radiofrequency capacitive hyperthermia combined with irradiation or chemotherapy for patients with invasive bladder cancers.

To assess the immediate therapeutic clinical efficacy and long-term outcome, hyperthermia in combination with irradiation or chemotherapeutic agent was used in 46 patients with invasive bladder cancer. Radiohyperthermia (RH) was employed in 19 cases and chemohyperthermia (CH) in 27 cases. Complete response (CR) was obtained in 5 and partial response (PR) in 15 of the 46 cases. One-year survival rates by the Kaplan-Meier method were 65.0% in the CR/PR group and 46.2% in the no change (NC)/progressive disease (PD) group. Five-year survival rates were 43.8% and 18.3%, showing no difference in survival rate between the CR/PR group and the NC/PD group The overall median survival period for the CR/PR group without metastasis was 61.6 months compared to 32.3 months for the NC/PD group without metastasis (P < 0.05).

Adult↗

Topical anaesthesia for bladder biopsies and cautery: intravesical lidocaine versus caudal anaesthesia.

A total of 62 patients were randomized to receive bladder biopsy and cautery with either topical lidocaine anaesthesia or caudal anaesthesia. The patients were asked to describe the level of pain experienced during the procedure on a scale from 0 (no pain) to 5 (unbearable pain). In 29 patients receiving topical lidocaine anaesthesia, the mean value was 1.6 at cold-cup biopsies and 2.7 at cautery, which were considered to be tolerable for the patients. On the other hand, in 33 patients who had biopsies and cautery with caudal anaesthesia, the mean values were 0.8 and 1.0, respectively, which were significantly lower than those in patients receiving topical anaesthesia (p < 0.01). Serum lidocaine levels were measured in 5 patients at 15 minutes from the beginning of biopsies, and were negligible. These results revealed that caudal anaesthesia provided more effective pain relief, although most patients could tolerate biopsy and cautery with topical lidocaine anaesthesia. The technique of topical anaesthesia is very simple and no side effects were observed. We thus conclude that topical lidocaine anaesthesia is useful and safe for bladder biopsies and cautery in most cases.

Administration, Intravesical↗

Comparative clinical features of stage A1 and stage A2 prostate cancers. Is the concept of stage A changing from the current status?

We surveyed the comparative clinical features of patients with stage A1 and stage A2 prostate cancer. Preoperatively, prostate specific antigen (PSA) level was elevated in 50.0% of stage A2 patients as compared to 18.2% of stage A1 patients. Compared to low positivity of prostatic acid phosphatase in 12.5% of stage A2 and in 0% of stage A1, PSA was more sensitive to the presence of incidental carcinoma. During the observation period (mean 35.7 months) no stage A patient died of cancer. No evidence of the disease showed significantly higher rate, and death without cancer was significantly lower in stage A1.

Acid Phosphatase↗

Refractory haemospermia: any predictive factors?

A total of 56 patients with haemospermia were reviewed. Twenty-four patients suffered from prolonged haemospermia for more than 1 month or recurrent haemospermia (refractory group). In 32 patients haemospermia disappeared within a month (non-refractory group). Patient age in the refractory group was significantly higher than that in the non-refractory group (p < 0.05). Clinical symptoms other than haemospermia, white blood cell counts in the semen, expressed prostatic secretion and urine after prostatic massage, and transrectal ultrasonography findings were studied in both groups, with no significant differences found in any of these parameters. We concluded that, among these clinical findings, only patient age is a predictive factor for refractory haemospermia.

Adolescent↗

Is CIS of the ureter responsible for skipped lymph node metastasis? A case report.

A case of skipped lesion of lymph node metastasis of left ureteral tumour with concurrent carcinoma in situ in the affected ureter is presented. Postoperatively, lymph node metastasis was de novo detected in the left retrocrural and renal hilar regions on CT scan, although only the obturator lymph node was histologically metastatic among the regional lymph nodes completely dissected. The possible explanations of this rare metastatic mode are discussed.

Carcinoma in Situ↗