Physical fitness and oral function in community-dwelling older people: a pilot study.

OBJECTIVE: The aim of the present study was to quantify the relation between physical fitness and oral function, including tongue and lip movements. BACKGROUND: Physical fitness and oral function influence quality of life and activities of daily living in older individuals. Occlusal contact and mastication performance are associated with physical fitness, but the association between tongue and lip movements and physical fitness is unclear. MATERIAL AND METHODS: Sixty-six independent community-dwelling older individuals (24 men, 42 women; mean age, 70.3 ± 5.9 years) participated in this study. Measures of physical fitness were the one-leg standing time with eyes open, the functional reach test, anteflexion, the timed up and go test, and grip strength. Measures of oral function were tongue pressure, lip pressure, tongue movement from side to side, the repetitive saliva-swallowing test (RSST), oral diadochokinesis and masticatory efficiency. Multiple regression analysis was used to quantify the relation between physical fitness and oral function. RESULTS: After adjustment for age, sex, BMI, exercise habits and number of remaining teeth, the tongue movement from side to side and/or oral diadochokinesis were chosen as significant factors in each physical fitness measurement. Furthermore, the lip pressure and masticatory efficiency were associated with handgrip strength. CONCLUSION: Oral function, including tongue and lip movements, was associated with physical fitness in older people in this study. Tongue dexterity as characterised by tongue movement from side to side and oral diadochokinesis particularly associated with physical fitness.

Circulating TNF receptor 2 is closely associated with the kidney function in non-diabetic Japanese subjects.

AIM: Chronic kidney disease (CKD) is associated with cardiovascular events. Tumor necrosis factor (TNF) and/or its receptors have been postulated to be involved in renal pathophysiology. It is unclear whether an increased TNF system activity is present before the development of apparent CKD. METHODS: Four hundred and twenty non-diabetic Japanese subjects with an estimated GFR (eGFR) greater than 60 ml/min/1.73 m(2) were recruited for measurement of the HbA1c, insulin, TNF system activity (TNF-α, soluble TNF receptor 1 (sTNF-R1) and sTNF-R2) levels and various parameters, including the lipid, high-sensitivity C-reactive protein (hsCRP), high-molecular-weight (HMW) adiponectin and leptin levels. The subjects were stratified according to the eGFR: the G1 level (eGFR ≧90 ml/min/1.73 m(2)) and the G2 level (90 ＞eGFR ≧60 ml/min/1.73 m(2)). RESULTS: Whereas no significant differences were observed in gender, body mass index (BMI), blood pressure, insulin, TNF-α, hsCRP, HMW adiponectin or leptin between the two groups, the values for age, HbA1c, triglycerides, sTNF-R1 and sTNF-R2 were significantly higher in the subjects with a G2 level of eGFR than in those with a G1 level. In contrast, the HDL cholesterol levels were significantly lower in the subjects with a G2 level than in those with a G1 level. Linear negative correlations were also observed between eGFR and age, BMI, HbA1c, triglycerides, sTNF-R1 and sTNFR2, respectively. A multiple logistic regression analysis revealed that only sTNF-R2 was associated with the presence of a G2 level of eGFR (Odds ratio 1.092, 95% CI 1.013-1.177, P=0.021). CONCLUSIONS: The circulating sTNF-R2 level is closely associated with the kidney function in non-diabetic Japanese subjects.

Smoking, white blood cell counts, and TNF system activity in Japanese male subjects with normal glucose tolerance.

BACKGROUND: Cigarette smokers have increased white blood cell (WBC) counts and the activation of tumor necrosis factor (TNF). The effect of smoking on WBC counts and TNF system activity, however, has not been separately investigated yet. SUBJECTS AND METHODS: One hundred and forty-two Japanese male subjects with normal glucose tolerance were recruited. They were stratified into two groups based on the questionnaire for smoking: one with current smokers (n = 48) and the other with current non-smokers (n = 94). Whereas no significant differences were observed in age, BMI, high molecular weight (HMW) adiponectin, and TNF-α between the two groups, current smokers had significantly higher soluble TNF receptor 1 (sTNF-R1) (1203 ± 30 vs. 1116 ± 21 pg/ml, p = 0.010) and increased WBC counts (7165 ± 242 vs. 5590 ± 163/µl, p < 0.001) and lower HDL cholesterol (55 ± 2 vs. 60 ± 1 mg/dl, p = 0.031) as compared to current non-smokers. Next, we classified 48 current smokers into two subpopulations: one with heavy smoking (Brinkman index ≥ 600) and the other with light smoking (Brinkman index < 600). RESULTS: Whereas no significant difference was observed in age, BMI, HMW adiponectin, WBC counts and TNF-α, sTNF-R1 and sTNF-R2 were significantly higher in heavy smoking group (1307 ± 44 vs. 1099 ± 30 pg/ml, p < 0.001; 2166 ± 86 vs. 827 ± 62 pg/ml, p = 0.005) than in light smoking group, whose sTNF-R1 and sTNF-R2 were similar to non-smokers (sTNF-R1: 1116 ± 15 pg/ml, p = 0.718, sTNF-R2; 1901 ± 32 pg/ml, p = 0.437). In contrast, WBC counts were significantly increased in heavy (7500 ± 324/µl, p < 0.001) or light (6829 ± 352/µl, p = 0.001) smoking group as compared to non-smokers (5590 ± 178/µl). There was no significant difference in WBC counts between heavy and light smoking group (p = 0.158). CONCLUSION: We can hypothesize that light smoking is associated with an increase in WBC counts, while heavy smoking is responsible for TNF activation in Japanese male subjects with normal glucose tolerance.

Clinical and immunological assessment of periodontal disease in Japanese leprosy patients.

Periodontitis is a chronic inflammatory disease caused by the infection of periodontopathic bacteria in dental plaque. However, an individual's susceptibility to this disease appears to be associated with multiple genetic factors, as seen in the case of leprosy. In order to gain a better understanding of the pathophysiology of periodontal disease in subjects with leprosy, we investigated the clinical features of periodontitis and the immunological responses against periodontopathic bacteria in 382 subjects with a history of leprosy and 451 age-matched control subjects. The prevalence of periodontitis and the degree of periodontal pocket depth were found to be significantly higher in leprosy patients than in age-matched controls. Furthermore, a comparison of the clinical parameters of lepromatous leprosy (L-lep) and tuberculoid leprosy (T-lep) patients showed that the probing pocket depth of L-lep patients with periodontal disease was significantly higher than that for T-lep patients. In contrast, serum IgG titers against Porphyromonas gingivalis in L-lep patients were significantly lower than in T-lep patients. These results imply that L-lep patients show more severe periodontal disease than T-lep patients or age-matched control subjects, and that low humoral immunity against P. gingivalis might be one of the genetic factors determining periodontal disease susceptibility in leprosy patients.

Human trial of liposomal lactoferrin supplementation for periodontal disease.

New approaches to periodontal health have been in strong demand in addition to conventional local plaque control. In this study, liposomal bovine lactoferrin (L-bLF) was orally administered to subjects with periodontal disease to investigate whether it could be a useful treatment. L-bLF composed of soy phosphatidylcholine was given as a supplement for four weeks in tablet form (180 mg bLF/d) to twelve subjects with multiple sites of more than 3 mm probing depth (PD). PD, bleeding on probing (BOP), gingival crevicular fluid (GCF) volume and the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and monocyte chemoattractant protein-1 (MCP-1) in GCF were evaluated for 51 sites with more than 4 mm PD in five subjects. Blood samples of all subjects were collected 0, 2 and 4 weeks after supplementation. Isolated peripheral blood mononuclear cells (PBMCs) were incubated for 24 h with or without lipopolysaccharide (LPS) (100 ng/ml) from Porphyromonas gingivalis, and TNF-α, IL-1ß, IL-6 and MCP-1 in the culture media were measured. Toll-like receptor 2 (TLR2) and TLR4 mRNA expressions of isolated PBMCs were also quantitatively analyzed using real-time reverse transcription-polymerase chain reaction (RT-PCR). The PD was significantly reduced by L-bLF supplementation, but the BOP and GCF volume were not significantly changed. The MCP-1 level in GCF was significantly reduced, while levels of other cytokines were not changed. Four-week L-bLF supplementation also showed significant decreases of LPS-induced cytokine production from PBMCs. Relative gene expressions of TLR2 and TLR4 did not change. These results suggest that L-bLF supplementation can be effective in the treatment of periodontal disease, although prospective controlled large-scale studies are required.

Comparison of the effects of three angiotensin II receptor type 1 blockers on metabolic parameters in hypertensive patients with type 2 diabetes mellitus.

OBJECTIVE: In a previous study involving 18 hypertensive patients with type 2 diabetes mellitus, we found that replacement of valsartan and candesartan by telmisartan significantly improved insulin sensitivity and significantly increased serum adiponectin levels in the patients. We investigated the effects of 3 angiotensin II type 1 receptor blockers (ARBs)-telmisartan, candesartan, and valsartan-on metabolic parameters in hypertensive patients with type 2 diabetes. METHODS: A total of 308 hypertensive patients with diabetes were enrolled in our multicentre, randomized, open-label study. The patients received 40 mg telmisartan, 8 mg candesartan, or 80 mg valsartan for 3 months, and the data of 227 patients (telmisartan: n=74, candesartan: n=79, and valsartan: n=74) were analysed. RESULTS: The systolic and diastolic blood pressures significantly decreased in all the groups at the end of the study; the decrease was comparable among the 3 groups. The changes in fasting plasma glucose, fasting insulin, glycated haemoglobin (HbA1c), total cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, adiponectin, free fatty acids, high-sensitivity C-reactive protein (hs-CRP), and plasminogen activator inhibitor-1 (PAI-1) were comparable between the 3 groups. Telmisartan and candesartan administration tended to lower urinary albumin excretion. CONCLUSIONS: Low dose telmisartan had a neutral effect on metabolic dysfunction in hypertensive patients with type 2 diabetes; the effect produced by 40 mg telmisartan was comparable with that of 8 mg candesartan and 80 mg valsartan. Failure to detect metabolic differences among the various ARB treatments could have been due to the low statistical power of the study design.

Source of plasma adrenomedullin in a patient with pheochromocytoma receiving hemodialysis.

A 45-year-old man on long-term hemodialysis (HD) was incidentally discovered to have a pheochromocytoma and underwent successful resection. This patient was normotensive, and had no symptoms suggesting pheochromocytoma. The plasma concentrations of total adrenomedullin (AM-T) and mature AM (AM-m) were higher than those in normal controls. To elucidate the source of AM, we measured plasma AM levels by immunoradiometric assay before and 3 weeks after surgery in addition to plasma adrenaline, noradrenaline and dopamine. AM expression was also assessed by immunoblot and immunohistochemical analyses on normal adrenal and tumor tissues. After surgery, elevated plasma adrenaline levels returned to the normal range; however, the levels of AM-T and AM-m remained almost the same as the preoperative values. Furthermore, although AM was expressed in both normal adrenal and tumor tissues, the AM expression level was less in tumor. In this case, it was suggested that elevation in plasma AM level might be a factor associated with normotensive blood pressure; however, adrenal pheochromocytoma was not a major source of circulating AM. To our knowledge, this is the first case of pheochromocytoma in patient with HD associated with AM in the literature.

Molecular basis for the involvement of thymidine phosphorylase in cancer invasion.

Thymidine phosphorylase (TP), also known as platelet-derived endothelial cell growth factor (PD-ECGF), has been implicated in bladder cancer angiogenesis and invasion. However, the molecular basis of its role in invasion remains unclear. We investigated the expression of TP and 10 invasion-related genes in bladder cancers from 72 randomly selected patients by real-time two-step RT-PCR assay. We found that the expression levels of TP, MMP-9, uPA, and MMP-2 were significantly higher in invasive tumors than those in superficial tumors. Also, the expression level of TP significantly correlated with that of uPA, MMP-1, MMP-9, PAI-1 and VEGF. KK47/TP cells, bladder cancer cells that overexpress TP, had a higher expression of MMP-7 and MMP-9 than KK/CV cells that express lower level of TP in hypoxic condition. PC/TP cells, prostate cancer cells that overexpress TP, also had a higher expression of MMP-1 and MMP-7 than PC/CV cells that express no detectable TP. Taken together these data indicate that TP enhances the invasion of tumor cells through the induction of invasion-related genes.

Expression of the inhibitors of apoptosis proteins in cisplatin-resistant prostate cancer cells.

Acquired multi-drug resistance remains a major obstacle in the management of prostate cancer. The objective of this study was to examine whether chemoresistance could be due in part to the expression of the inhibitors of apoptosis proteins (IAPs). We established cisplatin-resistant LNCaP sublines. We examined the effects of cisplatin on cell growth and apoptosis in LNCaP cells and LNCaP sublines by 2-(4-lodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt (WST-1) assay and Hoechst 33258 staining, and analyzed cross-resistance to adriamycin, 5-fluorouracil, taxol, taxotere, and etoposide. In addition, the expression of IAP-1, IAP-2, X-linked IAP (XIAP), neuronal apoptosis inhibitory protein, and survivin was investigated by immunoblot analysis in LNCaP sublines. Although the growth rates were reduced in a dose-dependent manner by cisplatin in LNCaP sublines, the anti-proliferative effects of cisplatin were significantly decreased in LNCaP sublines compared to LNCaP cells. Cisplatin-resistant sublines, LNCaP/C1, LNCaP/ C2, and LNCaP/C3 cells, were 6.3-, 9.1-, and 22.3-fold more resistant to cisplatin than LNCaP cells, respectively, and this resistance was paralleled with reduced induction of apoptosis. LNCaP/C3 cells showed cross-resistance to adriamycin, 5-fluorouracil, and etoposide whereas those cells exhibited no or only weak cross-resistance against taxol and taxotere. With the exception of survivin, all the IAPs were identified in LNCaP cells by immunoblot analysis. Interestingly, the expression of IAP-2, XIAP, and survivin gradually increased with the extent of cisplatin-resistance. Altered expression of IAP-2, XIAP, and survivin was involved in these phenotypes of cisplatin-resistant LNCaP sublines. IAPs may make an important contribution to the resistance to the apoptotic effect of cisplatin in prostate cancer.

Recto-peritoneal fistula following transperineal prostate biopsy.

A recto-peritoneal fistula is an extremely rare complication after prostate biopsy. We report herein on a peritonitis arising from a recto-peritoneal fistula 5 days after undergoing prostate biopsy. To our knowledge, this is the first case of recto-peritoneal fistula following transperineal needle biopsy of the prostate in the published literature.

Sp1 and Sp3 transcription factors upregulate the proximal promoter of the human prostate-specific antigen gene in prostate cancer cells.

The serum level of prostate-specific antigen (PSA) is useful as a clinical marker for diagnosis and assessment of the progression of prostate cancer, and in evaluating the effectiveness of treatment. We characterized four Sp1/Sp3 binding sites in the proximal promoter of the PSA gene. In a luciferase assay, these sites contributed to the basal promoter activity in prostate cancer cells. In an electrophoretic mobility shift assay and chromatin immunoprecipitation assay, we confirmed that Sp1 and Sp3 bind to these sites. Overexpression of wild-type Sp1 and Sp3 further upregulated the promoter activity, whereas overexpression of the Sp1 dominant-negative form or addition of mithramycin A significantly reduced the promoter activity and the endogenous mRNA level of PSA. Among the four binding sites, a GC box located at nucleotides -53 to -48 was especially critical for basal promoter activity. These results indicate that Sp1 and Sp3 are involved in the basal expression of PSA in prostate cancer cells.

Lower incidence of inguinal hernia: minilaparotomy radical retropubic prostatectomy compared with conventional technique. A preliminary report.

INTRODUCTION: The purpose of the present study was to compare the incidence of inguinal hernias after conventional and minilaparotomy (minilap) radical retropubic prostatectomy (RRP). PATIENTS AND METHODS: In this retrospective study, we review our experience with 70 consecutive patients with prostate cancer who underwent prostatectomy from April 1995 through March 2001. Of these, 35 patients had conventional RRP, and 35 patients had minilap RRP. RESULTS: Conventional RRP and minilap RRP groups were similar in body mass index (mean 24.4 and 23.5), operative time (mean 260 and 241 min), previous lower abdominal operation record (mean 37.1 and 25.7%), and post-prostatectomy anastomotic strictures (mean 11.4 and 14.3%). The volume of the estimated blood loss was significantly less for minilap RRP (mean 1,220 ml) than for conventional RRP (mean 1,666 ml; p = 0.0194). The incidence of postoperative inguinal hernias was 17.1% (6 of 35), 2.9% (1 of 35), and 3.2% (1 of 31) in conventional RRP, minilap RRP, and unoperated groups, respectively. The incidence of inguinal hernias after minilap RRP was significantly lower than after conventional RRP (p = 0.0464). Seven patients with postoperative inguinal hernias had a high incidence of postoperative strictures (42.9%), while 63 patients without hernia had a low incidence (9.5%). There was a significant difference in developing postoperative strictures between patients with hernia and those without (p = 0.0124). While postoperative stricture and operative technique were different in the hernia and hernia-free groups on univariate analysis, multivariate logistic analysis revealed that the operative technique was an independent factor for the occurrence of inguinal hernias (p = 0.0419). CONCLUSION: Minilap RRP compares favorably with conventional RRP in view of the postoperative inguinal hernia development.

Cisplatin inhibits the expression of X-linked inhibitor of apoptosis protein in human LNCaP cells.

The purpose of the present study is to investigate the role of X-linked inhibitor of apoptosis protein (XIAP) in the regulation of apoptosis induced by cisplatin in human prostate cancer cell line (LNCaP). We examined the effects of cisplatin on cell growth and apoptosis in LNCaP by 2-(4-lodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt (WST-1), flow cytometric analyses, and caspase-3 activity assay. In addition, to clarify the roles of the XIAP, we established clonal cell lines that overexpressed XIAP. The effects of cisplatin on the XIAP expression in the induction of apoptosis in LNCaP were examined by RT-PCR and immunoblot analyses. Although the growth rates were reduced in a dose- and time-dependent manner by cisplatin in LNCaP sublines, the anti-proliferative effects of cisplatin were significantly decreased in XIAP stably overexpressing cell lines. In addition, we found that cisplatin-induced apoptosis following activation of caspase-3, and that the overexpression of XIAP inhibited apoptosis by attenuating caspase-3 activity. Interestingly, treatment of LNCaP cells with 10 and 100 muM cisplatin for 48 h significantly decreased the expression of XIAP at both the protein and mRNA levels in a dose-dependent manner. Furthermore, 10-muM cisplatin treatment of LNCaP decreased XIAP mRNA and protein in a time-dependent manner. These results suggest that cisplatin induces apoptosis by the inhibition of XIAP expression, and that XIAP plays an important role in the regulation of cisplatin-induced apoptosis in LNCaP cells. The ability of cisplatin to down-regulate XIAP may be an important mechanism in chemosensitivity.

Urethral condyloma acuminata following urethral instrumentation in an elderly man.

A 70-year-old man had undergone urethral dilatation with bougie for 8 months following transurethral resection of the prostate and complained papillary masses at the urethral meatus. Physical and endoscopic examination revealed multiple tumors from the urethral meatus to the bulbous urethra. These tumors were resected transurethrally and 5-FU cream was instilled into urethra. Microscopic examination revealed urethral condyloma acuminata. Human papillomavirus types 6/11 were detected in the condylomas. As high prevalence rate of genital human papillomavirus was reported in penile skin of healthy men, urethral instrumentation including transurethral surgery might cause dissemination of penile skin human papillomavirus into the urethral lumen.

Intestinal perforation after cadaveric renal transplantation.

We performed cadaveric renal transplantation on a 46-year-old man on long-term hemodialysis. Methicillin-resistant Staphylococcus aureus (MRSA) enterocolitis occurred on the fifth postoperative day and severe intestinal ulceration and perforation followed. Subtotal abdominal colectomy and the simultaneous removal of the transplant were performed. Postoperatively, disseminated intravascular coagulopathy with pancytopenia and cerebral hemorrhagic infarction developed and the patient died 40 days later.

Repair of ileal conduit parastomal hernia by translocation of the stoma.

We repaired a recurrent ileal conduit parastomal hernia, according to Kaufman's technique, by translocating the stoma to the opposite side of the abdominal wall without laparotomy. This procedure is a simple and less invasive treatment for large parastomal hernia.

[Usefulness of lower ihfundibular length-to-diameter ratio as a predictor of lower pole stone clearance after extracorporeal shock wave lithotripsy; clinical research with two lithotriptors].

PURPOSE: Lower pole renal stones are well known to exhibit a poor stone clearance rate following extracorporeal shock wave lithotripsy (ESWL). In the present study, we analyzed several anatomical factors as predictors of lower pole stone clearance that may be used to indicate the usefulness and the universality of ESWL in such patients with two different lithotriptors. PATIENTS AND METHODS: 93 patients with a unilateral single lower pole stone of 2 cm. or less underwent ESWL using Piezolith 2500 or Medstone STS, were included in the study. An IVP was used to determine the lower infundibulopelvic angle, the caliceal pelvic height, the lower infundibular length, the lower infundibular diameter, the lower infundibular length-to-diameter ratio and the number of lower pole minor calyces. Stone-free status was assessed by a plain film with or without renal ultrasound. RESULTS: The stone clearance rate at the Piezolith 2500 group was 53.1% (34 of 64 patients), while was 51.7% (15 of 29 patients) at the Medstone STS group. In all cases, the overall stone clearance rate was 52.7% (49 of 93 patients). Age, laterality of the stone burden within the kidney and stone size were not different between the stone-free and residual stone groups. Multivariate logistic analysis revealed that length-to-diameter ratio was the most independent predictors of successful stone clearance at each group. The patients exhibited length-to-diameter ratio less than 7 achieved high stone clearance rates, greater than 72%. In contrast, the stone clearance rate was less than one third when length-to-diameter ratio was 7 or greater. Besides length-to-diameter ratio was strong prognostic factor in patients with stones 1 cm. or less and 1 to 2 cm at each group. CONCLUSION: From this study, it is apparent that successful ESWL is highly sensitive to the anatomy of the lower pole of the kidney. Especially, the lower infundibular length-to-diameter ratio is potentially useful and a universal predictor regardless of the kind of lithotriptors at least in patients with a lower pole radiopaque stone 2 cm. or less treated with ESWL.

Suppressor of cytokine signaling-1 is essential for suppressing dendritic cell activation and systemic autoimmunity.

Suppressor of cytokine signaling-1 (SOCS1/JAB) negatively regulates not only the cytokine-signaling pathway but also lipopolysaccharide (LPS)-induced macrophage activation. We found that SOCS1-deficient dendritic cells (DCs) were also hyperresponsive to interferon-gamma and interleukin-4. To define the role of SOCS1-deficient DCs in vivo, we generated mice in which the SOCS1 expression was restored in T and B cells on a SOCS1(-/-) background. In these mice, DCs were accumulated in the thymus and spleen and produced high levels of BAFF/BLyS and APRIL, resulting in the aberrant expansion of B cells and autoreactive antibody production. SOCS1-deficient DCs efficiently stimulated B cell proliferation in vitro and autoantibody production in vivo. These results indicate that SOCS1 plays an essential role in the normal DC functions and suppression of systemic autoimmunity.