Lipoteichoic Acids from Lactobacillus Strains Elicit Strong Tumor Necrosis Factor Alpha-Inducing Activities in Macrophages through Toll-Like Receptor 2

Lactobacilli are nonpathogenic gram-positive inhabitants of microflora. At least some Lactobacillus strains have been postulated to have health beneficial effects, such as the stimulation of the immune system. Here we examined the stimulatory effects of lactobacilli on mouse immune cells. All six heat-killed Lactobacillus strains examined induced the secretion of tumor necrosis factor alpha (TNF-α) from mouse splenic mononuclear cells, albeit to various degrees. When fractionated subcellular fractions of Lactobacillus casei were tested for NF-κB activation and TNF-α production in RAW264.7, a mouse macrophage cell line, the activity was found to be as follows: protoplast > cell wall polysaccharide-peptidoglycan complex. Both crude extracts and purified lipoteichoic acids (LTAs) from two Lactobacillus strains, L. casei and L. fermentum, significantly induced TNF-α secretion from RAW264.7 cells and splenocytes of C57BL/6, C3H/HeN, and C3H/HeJ mice but not from splenocytes of C57BL/6 TLR2^−/− mice. Lactobacillus LTA induced activation of c-Jun N-terminal kinase activation in RAW264.7 cells. Furthermore, in HEK293T cells transected with a combination of CD14 and Toll-like receptor 2 (TLR2), NF-κB was activated in response to Lactobacillus LTA. Taken together, these data suggest that LTAs from lactobacilli elicit proinflammatory activities through TLR2.     

Sigmoid neobladder in women after radical cystectomy

PURPOSE: Neobladder reconstruction using an intestinal segment is the common procedure of choice in men after cystectomy. Recently this procedure has been extended to women. We present our surgical and functional experience with the sigmoid neobladder in women. MATERIALS AND METHODS: A total of 11 women 49 to 74 years old (mean age plus or minus standard deviation 60 +/- 8.5) with transitional cell carcinoma of the bladder underwent lower urinary tract reconstruction with a modified sigmoid neobladder after nerve and urethral support sparing cystectomy. After at least 3 months voiding pattern and continence status were evaluated. Pressure flow studies and uroflowmetry were performed, the urethral pressure profile and neocystourethral angle were measured, and blood chemistry was analyzed. RESULTS: After at least 3 months complete daytime continence was achieved in 2 patients, while 8 had mild stress incontinence. At night 8 of the 11 women (72.7%) were continent with or without voiding at regular intervals. All except 1 patient voided to completion. Of the 2 patients with complete continence 1 needed clean intermittent catheterization 4 months postoperatively. Mean maximal urinary flow was 19.9 +/- 10.5 ml. per second. Excluding the woman who required catheterization mean residual urine volume was 15 +/- 13.7 ml. Postoperatively maximal urethral pressure was slightly lower and functional urethral length was about 10 mm. shorter than preoperatively. The mean neocystourethral angle was 131.9 +/- 21.7 degrees. Mean pH, bicarbonate and base excess were 7.38 +/- 0.03, 23. 48 +/- 2.34 mmol./l. and -0.92 +/- 2.50, respectively. CONCLUSIONS: After nerve and urethral support sparing cystectomy a modified sigmoid neobladder may be constructed in women to obtain satisfactory continence and voiding results.     

Clinical features and outcomes of mechanically ventilated patients with acute respiratory failure during treatment with immunosuppressive drugs

We examined clinical features and outcomes of mechanically ventilated patient (n = 11) retrospectively who had developed acute respiratory failure during treatments with immunosuppressive drugs. The mean APACHE II score was 22.6, and the mean lung injury score was 2.9. In eight patients chest X-ray and computed tomography showed interstitial pneumonia. Fungus and/or cytomegalovirus were isolated most often from patients with interstitial pneumonia. Observed mortality (72.7%) was significantly (P < 0.001) higher than predicted mortality (45.1%) in the APACHE II score. Patients, who were complicated with septic shock caused by fungus infection, showed poor mortality. These results suggest that the fungus and cytomegalovirus infections might be associated with poor prognosis in patients with acute respiratory failure during treatment with immunosuppressive drugs.     

Recovery of leukocyte function after super-high-dose chemotherapy with peripheral blood stem cell transplantation in testicular cancer patients

Leukocyte functions (superoxide production and phagocytosis) were evaluated in patients with testicular cancer who had undergone super-high-dose chemotherapy (SHDT) with peripheral blood stem cell transplantation (PBSCT). In 5 patients with advanced or relapsed testicular cancer who received 8 cycles of SHDT with PBSCT, we measured superoxide production activity by phorbol myristate acetate (PMA) stimulation, as well as phagocytic activity using latex particles before and after PBSCT. The median time to reach a leukocyte count of ≥1,000/μl was 9 days after PBSCT. Superoxide production activity was significantly decreased on day 7 compared with the pre-chemotherapy level. However, it recovered by day 12 and sustained such a level thereafter. Phagocytic activity was within the normal range on day 7 but declined slightly on days 12 and 21 compared with the pre-chemotherapy level. Our results indicate that leukocyte function and leukocyte count recover promptly following PBSCT and that PBSCT is a safe and convenient adjunctive therapy after SHDT for patients with advanced testicular cancer. Int. J. Cancer 72:39–42, 1997. © 1997 Wiley-Liss Inc.     

The brain finger protein gene (ZNF179), a member of the RING finger family,maps within the Smith-Magenis syndrome region at 17p11.2

Smith-Magenis syndrome (SMS) is caused by a microdeletion of 17p11.2 and comprises developmental and growth delay, facial abnormalities, unusual behavior and sleep problems. This phenotype may be due to haploinsufficiency of several contiguous genes. The human brain finger protein gene (ZNF179), a member of the RING finger protein family, has been isolated and mapped to 17p11.2. FISH analyses of metaphase or interphase chromosomes of 6 patients with SMS show that ZNF179 was deleted in one of the 2 homologs (17p11.2), indicating a possible association of the defect of this gene with the pathogenesis of SMS. Furthermore, using a prophase FISH ordering system, we sublocalized ZNF179 proximally to LLGL which lies on the critical region for SMS. Am. J. Med. Genet. 69:320–324, 1997. © 1997 Wiley-Liss, Inc.     

Serum matrix metalloproteinase-2 and its density in men with prostate cancer as a new predictor of disease extension

We examined whether the serum matrix metalloproteinase-2 (MMP-2) level and MMP-2 density could be predictors of the development and extension of prostate cancer. Serum samples were collected before any clinical treatment from 98 patients with prostate cancer and from 76 patients with benign prostatic hyperplasia (BPH). Control sera were obtained from 70 healthy men. The serum level of MMP-2 was determined by 1-step enzyme immunoassay. A newly defined MMP-2 density parameter was determined by dividing the serum level of MMP-2 by the prostate volume, which was measured by ultrasonography. The mean serum level of MMP-2 in prostate cancer patients was significantly higher than in the control and BPH groups. Furthermore, the serum MMP-2 levels in prostate cancer patients with metastasis were highly elevated compared with those without metastases. The MMP-2 density in pathologically organ-confined prostate cancer was significantly higher than that in BPH. There was a statistically significant difference in the MMP-2 density between pT2N0M0 and pT1N0M0 prostate cancers. Moreover, the serum MMP-2 level correlated well with the clinical course of prostate cancer with bone metastasis. Our results suggest that MMP-2 plays an important role in the development and extension of prostate cancer and that the serum level of MMP-2 and the MMP-2 density indicate prostate cancer extension and are, therefore, useful for the followup of prostate cancer patients. Int. J. Cancer (Pred. Oncol.) 79:96–101, 1998. © 1998 Wiley-Liss, Inc.     

A case of diabetic muscle infarction in Japan

Diabetic muscle infarction (DMI) is a rare complication of diabetes mellitus. We report the first recorded case in Japan. A 45-year-old Japanese woman presented with severe pain in the left antero-medial thigh. She had a 14-year history of Type 2 diabetes mellitus (DM). She had first noticed pain in her left thigh after a walk 2 weeks prior to presentation. The pain worsened progressively. She noticed a firm mass in her left thigh. T2-weighted magnetic resonance imaging (MRI) demonstrated a high-intensity signal in the muscle bulk of the anterior component of the left thigh. A needle biopsy of the mass showed necrosis. She was treated with bedrest and an antiplatelet agent. The mass disappeared 8 weeks after admission. DMI is a rare complication of poorly controlled diabetes mellitus. Twenty-seven cases with DMI have been reported in the English literature but we believe this is the first Japanese case with DMI. Copyright © 1998 John Wiley & Sons, Ltd.