Arterial stiffness is increased in young women with endometriosis.

Endometriosis is a chronic gynaecological disorder that is accompanied by inflammation and oxidative stress. Atherosclerosis has a long subclinical progression in arteries of children and young adults decades before overt clinical manifestations of the disease. In this study, we determined arterial stiffness by measuring brachial-ankle pulse wave velocity (baPWV) in women with endometriosis to assess the presence of subclinical atherosclerosis. We also measured markers of inflammation and oxidative stress in women with endometriosis. baPWV in women with endometriosis aged over 30 years was significantly higher than that in women without endometriosis aged over 30 years (p < 0.05), but not in women aged less than 30. Serum high-sensitivity C-reactive protein level in women with endometriosis was significantly higher than that in controls (p < 0.05). Young women with endometriosis show significantly increased arterial stiffness, suggesting that women with endometriosis need to be cautious of the future onset of atherosclerosis.

Difference in the ratio of high-molecular weight (HMW) to total adiponectin and HMW adiponectin in late post-menopausal women.

OBJECTIVE: High-molecular weight (HMW) isoform level and HMW ratio have been shown to be better predictors of insulin sensitivity and metabolic syndrome than total adiponectin level.We examined the changes in circulating levels of HMW adiponectin and ratios of HMW to total adiponectin in women during the menopausal transition. METHODS: We conducted a cross-sectional study in 217 healthy women and divided them into 4 stages: 58 women in pre-menopausal, 69 women in perimenopausal, 62 women in early post-menopausal and 28 women in late post-menopausal phase. Serum levels of total adiponectin and HMW adiponectin were measured by an enzyme-linked immunosorbent assay. RESULTS: In late post-menopausal women, HMW adiponectin level was significantly higher than that in peri-menopausal women and the HMW to total adiponectin ratio was significantly lower than that in early post-menopausal women. In peri-menopausal women, HMW adiponectin level was significantly lower than that in pre-menopausal women and HMW to total adiponectin ratio was significantly lower than the ratios in pre-menopausal and early post-menopausal women. CONCLUSION: The ratio of HMW to total adiponectin is low in late post-menopausal women, though both levels of total and HMW adiponectin were high after menopause in our cross-sectional study.

A gene near the D3F15S2 site on 3p is expressed in normal human kidney but not or only at a severely reduced level in 11 of 15 primary renal cell carcinomas (RCC).

Renal Cell Carcinoma (RCC) has been associated with the loss of heterozygosity at several loci on the short arm of chromosome 3 (3p). We have previously found that one of these loci, D3F15S2 (pH3H2) was lost in 76% of the tumor cells derived from heterozygous donors (Kovacs, G., Erlandsson, R., Boldog, F., Ingvarrsson, S., Müller-Brechlin, R., Klein, G. & Sümegi, J. (1988), Proc. Natl. Acad. Sci., 85, 1571-5). More recently we have identified a putative CpG island in the vicinity of D3F15S2, suggesting that DNA sequences in or around this site may have coding potential (Boldog, F., Erlandsson, R., Klein, G. & Sümegi, J. (1989). Cancer Genet. Cytogenet., 42, 295-306). The screening of a human placenta cDNA library with DNA probes derived from D3F15S2 has led to the isolation of several cDNA clones. They identified a 2.9 Kb long message in human placenta and kidney. In total RNA from 11 of 15 primary RCCs the gene expression was reduced to less than 20% compared to eight normal kidneys. This low level of expression may be due to contaminating normal tissue. In the remaining 4 tumors the expression varied from 24-51% compared to normal kidney. To facilitate reference, the gene was provisionally designated as 'RIK'. It was expressed in the HEK 293, one osteosarcoma (HOS), two carcinoma (COLO320 and QDMT), and three Burkitt lymphoma lines (BL2, BL29 and BL31). It was not expressed in one Burkitt lymphoma (DG75) and two EBV transformed lymphoblastoid cell lines (LCL) (NAD-20 and Cherry).

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.

Experimental-study of radiofrequency capacitive hyperthermia on transplanted tumor.

The in vivo effects of radiofrequency capacitive hyperthermia combined with cis-diammine-dichloroplatinum (CDDP) were studied using nude mice bearing a subcutaneous graft of KK-47 cells derived from human bladder cancer. Tumor growth curve was obtained by measuring the transplanted tumor volume for 21 consecutive days after the treatment. After the treatment, the tumor was removed and examined light-microscopically. Tumor growth was inhibited for 21 days after chemotherapy, hyperthermia, or chemohyperthermia, as compared with the control group. Comparing the chemohyperthermia group with the other groups, it was found that tumor reduction rate was greater in the former group than those in other groups tested. With respect to the combined chemohyperthermic treatment, hyperthermia significantly enhanced the anti-tumor efficacy of CDDP.

Lack of mutation at codon 12 of the C-h-ras oncogene in 51 human sarcomas assessed by PCR-rflp.

Mutations of the ras genes in codons 12, 13 or 61 make them oncogenic. There are several methods to determine the point mutations in the ras family. In an attempt to do so in a sensitive and time saving manner we have checked a total of 51 sarcomas (14 bone tumors and 37 soft tissue tumors) for mutations in codon 12 of the c-H-ras oncogene. First we amplified a 100 bp fragment covering this codon and then performed RFLP analysis after digestion with restriction endonuclease Msp I. We did not find mutations in any of the tumors. Our results, may reinforce previous data on the fact that ras genes do not play an important role in tumorigenesis of sarcomas.

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.

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 beta-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 degrees C for 20 min and at 43.0 degrees 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 degrees 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 micrograms/egg) alone, mitomycin C (10 micrograms/egg) alone, carboplatin (10 micrograms/egg) alone, and cisplatin (10 micrograms/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.

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.

Combined treatment of radiofrequency capacitive hyperthermia for urological malignancies.

During the period from April 1984 to July 1993, we investigated the clinical efficacy of local hyperthermia used to treat 110 patients with urological malignancies. We investigated the long-term outcome of 40 (36.4%) responders who exhibited an immediate, partial or better response to the therapy. The one-year survival rate was 75% for retroperitoneal tumor, 65% for bladder cancer, 33% for each of renal cell carcinoma and prostatic cancer and 29% for renal pelvic and ureteral cancer. The 5-year survival rate was 48% for bladder cancer, 29% for renal pelvic and ureteral cancer, 25% for retroperitoneal tumor, and 0% for renal cell carcinoma and prostatic cancer. Subsidence of intolerable pain caused by cancer invasion was achieved in 29 of 42 patients (69.0%), indicating an improvement in patient's quality of life through pain relief.

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

The immediate therapeutic clinical efficacy and long-term outcome of hyperthermia in combination with irradiation or chemotherapeutic agent was evaluated in 46 patients with invasive bladder cancer. Radiohyperthermia was performed in 19 cases and chemohyperthermia in 27 cases. Complete response (CR) was obtained in 5 and partial response (PR) in 15 of the 46 cases. Five-year survival rates by the Kaplan-Meier method were 43.8% in the CR/PR group and 18.3% in the no change (NC)/progressive disease (PD) group, showing no difference of 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).

Adjuvant therapy with 5-fluoro-1-(2-tetrahydrofuryl)-2,4 (1H,3H)-pyrimidinedione (UFT) and Bestatin in patients with transitional cell carcinoma of the bladder--comparison between UFT therapy alone and UFT therapy in combination with Bestatin.

To prevent postoperative recurrence a randomized prospective trial was performed on 45 patients with bladder cancers by dividing them into 2 groups given either UFT therapy alone or UFT therapy in combination with Bestatin. In principle, oral administration of these drugs was initiated 4 weeks postoperatively and continued for a period of 1 year. Bestatin was given at the dose of 30 mg/day after breakfast per os, and UFT at the dose of 400 mg/day twice a day per os. After a median follow-up period of 628 days the relapse-free rate was 43.5% for the group given UFT alone and 81.8% for the group given a combination of UFT plus Bestatin, showing a significantly more favorable result in the latter group. In patients with a solitary and papillary tumor the relapse-free rate was significantly better in the UFT plus Bestatin group compared with the group of UFT alone. Accordingly, it was suggested that postoperative administration of UFT in combination with Bestatin is more effective in preventing recurrence of bladder cancer, compared with the administration of UFT alone.

Analysis of fluorescence spectra from Chinese herbal medicine for male infertility.

To clarify the contribution of Chinese herbal medicine to the treatment of male infertility, fluorescence spectra from Chinese herbal drugs at 500-700 nm with 488 nm excitation were investigated. The fluorescence spectra patterns from Hachimi-jio-gan, Gosha-jinki-gan and Hochuekki-to were similar to those from semen, seminal plasma and spermatozoa. Our previous report revealed that the concentration of spermatozoa correlated with the intensity of the emission peaks from spermatozoa, while sperm motility correlated with the emission peaks from spermatozoa and semen plasma. Thus, it was suggested that the components of these fluorescence productions in Chinese herbal medicine may contribute to clinical effects for male infertility.

A case of inverted papilloma of the ureter: is the DNA ploidy pattern associated with occurrence of transitional cell carcinoma of the bladder?

We describe herein a case of inverted papilloma of the ureter, in which transitional cell carcinoma of the bladder developed twenty-three months after nephroureterectomy. Flow cytometric analysis of formalin-fixed and paraffin-embedded archival material of the inverted papilloma revealed DNA aneuploidy pattern and relatively high percentage of S phase. Retrospectively, DNA measurement thus provided the predictive value regarding biological activity and the clinical behaviour of the present case.

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.

Fibroepithelial polyp of the verumontanum. A case report and literature review.

A case of fibroepithelial polyp of the verumontanum in a 20-year-old male is presented. The endoscopic examination revealed polypoid lesion protruding from the verumontanum, and transurethral resection of the tumour was performed. The histopathological diagnosis was fibroepithelial polyp, containing no prostatic glandular structures. As the nomenclature of the lesions is widely varying, we tried to classify polypoid or papillary lesions of the prostatic urethra by a literature review.

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).

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.

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.

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.