A Subset of Patients With Recurrent Spontaneous Abortion Is Deficient in Transforming Growth Factor β-2-Producing “Suppressor Cells” in Uterine Tissue Near the Placental Attachment Site

PROBLEM : To determine if patients with unexplained recurrent miscarriage have a deficiency of decidual immunosuppressor cells that produce transforming growth factor β type 2, as has been found in mice with abortion due to rejection and/or trophoblast failure. METHODS : Decidual biopsy specimens were taken as near to the placental attachment site as possible under ultrasound guidance from first trimester legal termination (control) patients with recurrent miscarriage and non-viable pregnancy, and from patients with sporadic missed abortion. The tissue was tested for TGFβ-2⁺ suppressor cells by in situ hybridization, immunohistochemistry, and analysis of supernatants. RESULTS : TGFβ-2-related suppressor molecules similar but not identical to those identified in pregnant mice were released by decidual lymphoid cells. Fifty percent of 14 recurrent miscarriage patients showed a lack of suppressor cells and 59% were subnormal in comparison to 20 controls and 5 sporadic miscarriage patients, where 80–85% of the patients had detectable suppressor cells. CONCLUSIONS : Suppressor cell deficiency is compatible with a role for rejection and/or trophoblast failure in some patients with recurrent miscarriage. Presence of suppressor cells in most patients with missed abortion (4/5) is compatible with an alternative cause of fetal death, similar to findings reported in genetic fetal death mice.     

Bacterial invasion into the colonic mucosa in ulcerative colitis

Abstract This study investigated interactions between mucosal lesions and bacterial invasion in ulcerative colitis using the acridine-orange staining method. In all 16 cases of ulcerative colitis, the mucosa was found to be invaded by small rods and cocci. In five of 10 controls, bacteria were seen only adhering to the mucosa and no bacteria were detected in the five remaining cases. It is suggested that the presence of bacteria in the colonic mucosa may be a factor responsible for the persistence or aggravation of ulcerative colitis.     

The Effect of Cimetidine on Natural Killer Activity of Peripheral Blood Lymphocytes of Patients with Ovarian Carcinoma

The effect of cimetidine on the natural killer (NK) activityof peripheral blood lymphocytes (PBL) of 32 patients with ovariancarcinoma was studied before and after surgery or chemotherapy.There was no significant difference in the NK activity betweennormal healthy women and patients who had been disease-freefor more than a year after initial surgery, while those in patientswith a large residual tumor after surgery were profoundly suppressed.Cimetidine stimulated the NK activity in the disease-free patientsin vivo or in Vitro. In addition, cimetidine augmented the responseto phytohemagglutinin of PBL from the disease-free patients.The NK activity of PBL of patients with a large residual tumorunder chemotherapy consisting of cisplatinum, adriamycin andcyclophosphamide, "CAP," was about half of that before initiationof chemotherapy. The inhibition of the NK activity by chemotherapywas abrogated by in vitro exposure of the PBL to cimetidine.     

Prognostic significance of vascular invasion in patients with bladder cancer who underwent radical cystectomy

BACKGROUND: The objective of this study was to determine whether vascular invasion (i.e. lymphatic and blood vessel invasion) could be a useful prognostic predictor in patients with locally invasive transitional cell carcinoma (TCC) of the bladder who underwent radical cystectomy. METHODS: This series included 114 consecutive patients undergoing radical cystectomy for primary TCC of the bladder between November 1989 and July 2003. Several clinicopathological characteristics of these patients were analyzed, focusing on the association between vascular invasion and disease recurrence after radical cystectomy. RESULTS: Lymphatic and blood vessel invasions were detected in 55 (48.2%) and 33 (29.8%) specimens, respectively. Lymphatic invasion was significantly associated with pathological stage, tumor grade, lymph node metastasis, blood vessel invasion and disease recurrence, whereas blood vessel invasion was significantly related to pathological stage, lymph node metastasis, lymphatic invasion and disease recurrence. Recurrence-free survival in patients with lymphatic invasion was significantly lower than that in those without lymphatic invasion, and a similar significant difference in recurrence-free survival was observed between patients with and without blood vessel invasion. However, multivariate analysis using the Cox proportional hazards model showed that only pathological stage and lymph node metastasis could be used as independent predictors for disease recurrence after radical cystectomy. CONCLUSIONS: Despite a significant association between several prognostic parameters, vascular invasion was not an independent predictor of disease recurrence; therefore, if there are other conventional parameters available, there might not be any additional advantage to considering the presence of vascular invasion when predicting the prognosis of patients undergoing radical cystectomy for TCC of the bladder.     

High dose chemotherapy including paclitaxel (T-ICE) combined with peripheral blood stem cell transplantation for male germ cell tumor. Preliminary report

AIM: To evaluate the feasibility and usefulness of high dose chemotherapy including paclitaxel (T-ICE) combined with peripheral blood stem cell transplantation (PBSCT) for male germ cell tumor. METHODS: Five male patients with advanced germ cell tumor underwent 1-6 courses of high dose chemotherapy including paclitaxel (T-ICE; 175 mg/m2 of paclitaxel, 1250 mg/m2 of carboplatin, 1500 mg/m2 of etoposide and 7.5 g/m2 of ifosfamide) with PBSCT after 2-3 courses of induction chemotherapy (PEB or VIP). RESULTS: In all patients, serum marker levels decreased to within the normal range by T-ICE. Two patients underwent resection of residual tumor. In one patient, viable cancer cells were detected in resected lymph node tissue and adjuvant chemotherapy was then performed. Although the follow-up period was short (7-15.5 months), four of the five patients (80%) showed no evidence of recurrent disease. No significant differences in side-effects were noted between T-ICE and conventional high dose ICE, which was previously performed in 39 patients at the Division of Urology, Kobe University Graduate School of Medicine, Japan. CONCLUSIONS: High dose chemotherapy, including T-ICE, combined with PBSCT showed an almost identical degree of side-effects as seen in previous high dose chemotherapy without paclitaxel. Although 80% of the patients showed no evidence of disease so far, the efficacy of T-ICE should be evaluated with more patients and longer follow up.     

Is a limited lymphadenectomy targeting obturator nodes alone an adequate procedure for Japanese men undergoing radical prostatectomy?

BACKGROUND: The objective of the present study was to investigate the significance of pelvic lymphadenectomy during radical prostatectomy in Japanese men with prostate cancer. METHODS: A total of 178 consecutive patients who underwent radical prostatectomy and standard pelvic lymphadenectomy targeting the external iliac nodes and obturator fossa for clinically localized prostate cancer were studied. The median observation period of this series was 18 months (range: 3-36 months). RESULTS: Lymph node metastases were detected in 13 patients; that is, positive nodes were located in the external iliac nodes alone in seven patients, the obturator fossa alone in four patients, and both external iliac nodes and obturator fossa in two patients. Of these 13 patients, all of the seven with more than one positive node demonstrated biochemical recurrence, whereas five of the six with single node involvement remained without signs of biochemical recurrence. Furthermore, a single positive node was located in the external iliac region in five of the six patients. When a group at high-risk for lymph node metastasis was defined as those meeting more than two of the following three criteria: (i) pretreatment serum prostate specific antigen value > or = 20 ng/mL; (ii) biopsy Gleason sum > or = 8; or (iii) percentage of positive biopsy core > or = 50%, the incidence of lymph node metastasis was 24.5% in the high-risk group and 0.8% in the low-risk group. CONCLUSIONS: These findings suggest that limited dissection of the obturator node alone may not be sufficient for Japanese men undergoing radical prostatectomy; therefore, we recommend performing standard pelvic lymphadenectomy targeting both the external iliac nodes and the obturator fossa for patients at high-risk of lymph node involvement.     

Predictors of prostate cancer on repeat transrectal ultrasound-guided systematic prostate biopsy

BACKGROUND: We analyzed the outcome of repeated transrectal ultrasound (TRUS)-guided systematic prostate biopsy in Japanese men whose clinical findings were suspected of prostate cancer after previous negative biopsies. METHODS: Between January 1993 and March 2002, 1045 patients underwent TRUS-guided prostate biopsy. Among them, 104 patients underwent repeat biopsy due to indications of persistent elevated serum prostate-specific antigen (PSA), abnormal digital rectal examination (DRE) or TRUS, increased PSA velocity, and/or previous suspicious biopsy findings. Several clinicopathological factors were evaluated for their ability to predict the detection of prostate cancer on repeat biopsy. RESULTS: Prostate cancer was detected in 22 of 104 patients (21.2%) who underwent repeat biopsies. PSA concentration and PSA density at both the initial and repeat biopsies, and PSA velocity in men with positive repeat biopsy were significantly greater than those in men with negative repeat biopsy. The incidence of abnormal findings in DRE and TRUS at initial biopsy in men with positive repeat biopsy was also significantly higher than that in men with negative repeat biopsy. However, neither the presence of prostatic intraepithelial neoplasia nor number of biopsy cores at initial biopsy had a significant association with the results of the repeat biopsy. Furthermore, multivariate analysis revealed that PSA and PSA density at both the initial and repeat biopsies, PSA velocity, and DRE and TRUS findings at initial biopsy were independent predictors of malignant disease on repeat biopsy. CONCLUSION: Despite an initial negative biopsy, repeat TRUS-guided biopsy should be carried out to exclude prostate cancer in cases of suspicious clinical findings, such as elevated PSA or PSA-related parameters, or abnormal findings of DRE or TRUS.     

Cerivastatin inhibits fetal calf serunvinduced DNA synthesis in cultured rat mesangial cells

SUMMARY: Inhibition of mevalonate synthesis by several statins has been shown to suppress DNA synthesis in glomerular mesangial cells. In the present study, we investigated the effect of a new statin, cerivastatin, on fetal calf serum (FCS)-induced DNA synthesis of cultured rat mesangial cells. Cultured rat mesangial cells were stimulated by 10% FCS in the presence or absence of cerivastatin and mevalonate. 5-bromo-2-deoxyuridine (BrdU) incorporation was used to assess DNA synthesis. the present study showed that 10% FCS caused marked stimulation of DNA synthesis in the mesangial cells. Cerivastatin inhibited FCS-stimulated BrdU incorporation in a dose-dependent manner. IC₅₀ was approximately 1 umol/L. Exogenous mevalonate, farnesyl pyrophosphate and geranylgeranyl pyrophosphate significantly prevented the inhibitory effect of cerivastatin on DNA replication. It appears that cerivastatin, by inhibiting the synthesis of mevalonate, may suppress DNA synthesis in the mesangial cells.     

Antitumor effect of simultaneous transfer of interleukin-12 and interleukin-18 genes and its mechanism in a mouse bladder cancer model

BACKGROUND: The objectives of this study were to evaluate the antitumor effects of the simultaneous introduction of interleukin 12 (IL-12) and IL-18 genes into a mouse bladder cancer cell line (MBT2). We intended to compare these with those of either gene alone and to investigate the mechanism of the effects induced by the transfer of IL-12 and/or IL-18 genes in this model system. METHODS: We transfected the IL-12 and/or IL-18 genes into MBT2 cells by the liposome-mediated gene transfer method. We confirmed the secretion of IL-12 and/or IL-18 by enzyme-linked immunosorbent assay. Parental (MBT2/P), IL-12-transfected (MBT2/IL-12), IL-18-transfected (MBT2/IL-18) or both IL-12- and IL-18-transfected (MBT2/Both) cells were subcutaneously or intravenously injected into syngeneic C3H mice. To analyze the mechanism of tumor rejection, these clones were subcutaneously injected into naive nude mice and those depleted with natural killer (NK) cells by antibody. RESULTS: MBT2/IL-12, MBT2/IL-18 and MBT2/Both were completely rejected when they were injected subcutaneously or intravenously into syngeneic mice. However, MBT2/IL-12, but not MBT2/IL-18, could grow in nude mice. Moreover, the antitumor effect of MBT2/IL-18 was partially abrogated when injected into nude mice of which NK cells were depleted by antibody treatment. MBT2/Both was completely rejected in both nude mice with and without NK cells. CONCLUSION: The results of the present study indicate that T cells and NK cells seem to play important roles in the antitumor effects by the secretion of IL-12 and IL-18, respectively, and MBT2/Both possesses both mechanisms.