Kazuto Kunimi

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.

Transrectal Ultrasonography of the Prostate and Seminal Vesicles with Hemospermia

Transrectal ultrasonography was performed in 46 patients with hemospermia. Abnormal findings in the prostate and seminal vesicles, including prostatic stones, benign prostatic hyperplasia, prostatitis, and dilatation and calculi of the seminal vesicles, were observed in 34 patients (73.9%). However, no malignant lesions were found in the prostate or seminal vesicles. Transrectal ultrasonography was a useful and noninvasive procedure to investigate the causes of hemospermia. Furthermore, transrectal ultrasonography could demonstrate latent diseases and exclude malignancy of the prostate and seminal vesicle in patients with hemospermia.

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.

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.

Spectroscopic study of haematoporphyrin oligomers in tumour tissue

Fluorescence spectra of modified haematoporphyrin (Hp) oligomers (of mean molecular weights 3000, 5000 and 12000) and Photofrin II in tumour tissue were semi-quantitatively measured by a reflection method. Characteristic peaks of the emission spectra, obtained by excitation at 370 nm, appeared at 677 nm and also at 634 and 695 nm. The intensity ratio of the emission band (677 nm) to the other emission bands (633 nm) increased in accordance with increases in the oligomer molecular weight. The integral intensity of the fluorescence emission spectra of oligomer 3000 (i.e., the pentamer of Hp in tumour tissue) was about two times greater than that of Photofrin II.The solutions extracted from the tumour tissues following injection of these porphyrins were analysed by fluorescence spectrophotometry. The integral fluorescence intensity of the pentamer solution was about three times larger than that of the Photofrin II solution. The extracted solution was fractionated by high-pressure liquid chromatography (HPLC), and the fluorescence of each fraction was measured by fluorescence spectrophotometry. The chromatography fraction of each oligomer had the same long elution time and a single sharply peaking fraction. The fluorescence spectrum pattern of the eluted oligomer fraction showed a shoulder at 677 nm and the same spectrum as that in the extraction solvent before injection. The fraction corresponding to dihaematoporphyrin ether (DHE) or its dissociated molecules showed a new emission peak at 647 nm in addition to the other monomer emission bands.From these spectroscopic analyses it was considered that Photofrin II and Hp oligomers had a tendency to aggregate in tumour tissue and that the pentamer was more readily incorporated in tumour tissue than was Photofrin II. Accordingly, it was concluded that the modified oligomers were stable compounds and that these oligomers—especially the one consisting of 5±2 molecules of Hp—were effectively incorporated into, and accumulated within, tumour tissue. It is suggested that the oligomer may be useful as an indicator of tumour localization.

Studies of effects of anticancer agents in combination with/without hyperthermia on metastasized human bladder cancer cells in chick embryos using the polymerase chain reaction technique

Cultivated T24 cells derived from a human bladder cancer were inoculated into the chorioallantoic membrane vein of chick embryos. Hyperthermic treatment was performed following injection of anticancer agents 3 days after the inoculation of the T24 cells. DNA samples were obtained from the livers of the chick embryos, and the polymerase chain reaction technique was used to amplify a DNA fragment specific to the human β-globin gene. The Southern hybridization method was used to evaluate the inhibitory effects of anticancer agents in combination with/without hyperthermia on T24 cells metastasized to the liver. The hyperthermia exerted an inhibitory effect on the growth of the T24 cells in the livers of the chick embryos, and this was dependent on the thermal dose. The antitumor effects of hyperthermia performed at 42.5° C for 20 min and at 43.0° C for 10 min were evidenced by 69.2% an 82.0% inhibition of the growth of the metastasized T24 cells, respectively, as compared with the growth of untreated T24 cell. Hyperthermia performed at 42.5° C for 10 min alone produced 26.7% tumor growth inhibition, and these conditions for hyperthermia were subsequently used as a criterion for evaluating the effects of its combination with various anticancer agents. Adriamycin (20 μg/egg) alone, mitomycin C (10 μg/egg) alone, carboplatin (10 μg/egg) alone, and cisplatin (10 μg/egg) alone produced 13.5%, 58.9%, 27.3%, and 29.1% tumor growth inhibition, respectively. Adriamycin and mitomycin C applied in combination with hyperthermia showed additive inhibitory effects on the growth of the metastasized T24 cells in this chick embryo model.

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.

Magnetic resonance imaging of bladder hemangioma

An 18-year-old woman with a bladder hemangioma is described. The tumor had a low signal intensity with multilocular pattern on T1-weighted magnetic resonance (MR) images and high signal intensity on T2-weighted MR images. MR images were useful in evaluating tumor character and its extent.

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.

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.