Inhibitory effects of Sanguisorba officinalis root extract on HYBID (KIAA1199)-mediated hyaluronan degradation and skin wrinkling.

OBJECTIVES: Hyaluronan (HA), an important constituent of extracellular matrix in the skin, has many biological activities such as hydration that contributes to firmness and bounciness of the skin. We have reported that reduction in HA in the papillary dermis and over-expression of HYBID (HYaluronan Binding protein Involved in hyaluronan Depolymerization, alias KIAA1199 or CEMIP), a key molecule for HA degradation in skin fibroblasts, are implicated in facial skin wrinkling in Japanese and Caucasian women. However, little or no information is available for substances which inhibit the HYBID-mediated HA degradation. METHODS: Inhibition of Sanguisorba officinalis root extract and ziyuglycoside I, one of the components of Sanguisorba officinalis root extract, to the HYBID-mediated HA degradation was assessed by size-exclusion chromatography of HA depolymerized by stable transfectants of HYBID in HEK293 cells (HYBID/HEK293 cells) or normal human skin fibroblasts (Detroit 551 cells and NHDF-Ad cells). The HYBID mRNA and protein expression was examined by quantitative real-time PCR and immunoblotting in the skin fibroblasts treated with Sanguisorba officinalis root extract, and size distribution of newly produced HA was evaluated by preparing metabolically radiolabelled HA. A double-blind, randomized and placebo-controlled study was carried out in the 21 healthy Japanese women, who were topically treated with the formulation containing Sanguisorba officinalis root extract or the placebo on each side of the face including crow's foot area. RESULTS: Sanguisorba officinalis root extract, but not ziyuglycoside I, abolished HYBID-mediated HA degradation by HYBID/HEK293 cells. Sanguisorba officinalis root extract also inhibited HYBID-mediated HA degradation in skin fibroblasts by down-regulating HYBID mRNA and protein expression. Although control untreated skin fibroblasts produced polydispersed HA, the cells treated with Sanguisorba officinalis root extract produced only high-molecular-weight HA. Treatment with Sanguisorba officinalis root extract-formulated lotion significantly improved skin elasticity, and reduced skin wrinkling scores at the outer eye corner compared with the placebo formulation. CONCLUSION: Sanguisorba officinalis root extract showed an anti-HYBID-mediated HA degradation activity and anti-wrinkle activity on human facial skin, which is accompanied by the improvement in elasticity. Our study provides the possibility of a new strategy to inhibit HYBID-mediated HA degradation for anti-wrinkle care.

OBJECTIFS: l'acide hyaluronique (AH), un composant important de la matrice extracellulaire de la peau, assure de nombreuses activités biologiques, telles que l'hydratation qui contribue à la fermeté et l'élasticité de la peau. Nous avons rapporté que la réduction d'AH dans le derme papillaire et une surexpression de la protéine de liaison de l'AH impliquée dans la dépolymérisation de l'AH (HYBID, alias KIAA1199 ou CEMIP), une molécule clé de la dégradation de l'AH des fibroblastes cutanés, sont impliquées dans la formation des rides au niveau de la peau du visage chez les femmes d'origine japonaise et caucasienne. Cependant, peu ou aucune information n'est disponible concernant les substances qui inhibent la dégradation de l'AH provoquée par la protéine HYBID. MÉTHODES: l'inhibition de l'extrait de racine de la pimprenelle (Sanguisorba officinalis) et du ziyuglycoside I, l'un des composants de l'extrait de racine de Sanguisorba officinalis, sur la dégradation de l'AH provoquée par la protéine HYBID a été évaluée à l'aide d'une chromatographie par exclusion stérique de l'AH dépolymérisé par des transfectants stables de la protéine HYBID dans les cellules HEK293 (cellules HYBID/HEK293) ou les fibroblastes cutanés humains normaux (lignée cellulaire Detroit 551 et cellules des fibroblastes du derme humain chez l'adulte). L'expression de l'ARNm et de la protéine HYBID a été examinée par PCR quantitative en temps réel et par immuno-empreinte des fibroblastes cutanés traités avec de l'extrait de racine de Sanguisorba officinalis, et l'attribution des tailles des nouveaux échantillons produits de l'AH a été évaluée par préparation d'AH radiomarqué métaboliquement. Une étude en double aveugle, randomisée et contrôlée par placebo a été menée auprès des 21 femmes japonaises en bonne santé, qui ont été traitées localement avec la formulation élaborée à partir d'extraits de racine de Sanguisorba officinalis ou un placebo, sur chaque côté du visage, notamment sur la zone à pattes d'oie. RÉSULTATS: l'extrait de racine de Sanguisorba officinalis a permis d'arrêter la dégradation de l'AH provoquée par la protéine HYBID par les cellules HYBID/HEK293, mais ce n'était pas le cas du ziyuglycoside I. L'extrait de racine de Sanguisorba officinalis a également inhibé la dégradation de l'AH provoquée par la protéine HYBID des fibroblastes cutanés en diminuant l'expression de l'ARNm et des protéines HYBID. Bien que les fibroblastes cutanés témoins non traités aient produit de l'AH polydispersé, les cellules traitées aux extraits de racine de Sanguisorba officinalis ont produit uniquement de l'AH de haut poids moléculaire. Le traitement par lotion formulée à partir d'extraits de racine de Sanguisorba officinalis a amélioré de manière significative l'élasticité de la peau et réduit les scores de vieillissement du coin extérieur de la peau autour des yeux, par rapport à la formulation placebo. CONCLUSION: l'extrait de racine de Sanguisorba officinalis a démontré une action anti-dégradation de l'AH provoquée par la protéine HYBID et une activité antirides au niveau de la peau du visage humain, s'accompagnant d'une amélioration de l'élasticité. Notre étude fournit la possibilité d'une nouvelle stratégie pour inhiber la dégradation de l'AH provoquée par la protéine HYBID dans le cadre des soins antirides.

Reduction of hyaluronan and increased expression of HYBID (alias CEMIP and KIAA1199) correlate with clinical symptoms in photoaged skin.

BACKGROUND: Hyaluronan (HA) metabolism in skin fibroblasts is mediated by HYBID (hyaluronan binding protein involved in hyaluronan depolymerization, alias CEMIP and KIAA1199) and the HA synthases HAS1 and HAS2. However, photoageing-dependent changes in HA and their molecular mechanisms, and the relationship between HA metabolism and clinical symptoms in photoaged skin remain elusive. OBJECTIVES: We examined the amount, size and tissue distribution of HA and expression levels of HYBID, HAS1 and HAS2 in photoaged skin, and analysed their relationship with the degree of photoageing. METHODS: Photoageing-dependent changes of HA were investigated by studying skin biopsies isolated from photoprotected and photoexposed areas of the same donors, and the relationships between HA and photoageing symptoms such as skin wrinkling and sagging were examined. RESULTS: Skin biopsy specimens showed that the amount and size of HA are decreased in photoexposed skin compared with photoprotected skin, and this was accompanied by increased expression of HYBID and decreased expression of HAS1 and HAS2. Histologically, HA staining in the papillary dermis was decreased in photoexposed skin, showing reverse correlation with HYBID expression. HYBID expression in the photoexposed skin directly correlated with skin roughness and sagging parameters, and the reduced HA staining in the papillary dermis in the photoexposed skin positively correlated with these symptoms. CONCLUSIONS: These data demonstrate that imbalance between HYBID-mediated HA degradation and HAS-mediated HA synthesis may contribute to enhanced HA catabolism in photoaged skin, and suggest that HYBID-mediated HA reduction in the papillary dermis is related to skin wrinkling and sagging of photoaged skin.

Relationship of hyaluronan and HYBID (KIAA1199) expression with roughness parameters of photoaged skin in Caucasian women.

BACKGROUND: Hyaluronan (HA) is an important constituent of extracellular matrix (ECM) in the skin, and HA degradation mediated by HYBID (KIAA1199) is suggested to be implicated in facial skin wrinkling in Japanese women. Ethnic difference in skin wrinkle formation is known between Caucasian and Japanese women, but no information is available for the relations of HA and HYBID expression levels with skin wrinkling in Caucasian women. METHODS: The skin surface roughness at the eye corner of the Caucasian female subjects was measured, and the skin specimens biopsied from the same areas were subjected to microarray gene analysis, HA staining, and immunohistochemistry for HYBID. RESULTS: Among the ECM genes and those related to ECM metabolism, only HYBID expression levels positively correlated with the skin roughness parameters. When the skin sample groups with high expression of HYBID or low expression of HYBID were compared, the HA staining intensity and the ratio of HYBID-immunoreactive cells to total cells in the superficial dermis were significantly reduced and increased in the high-HYBID-expression group compared with the low-HYBID-expression group, respectively. CONCLUSION: Our data suggest that like Japanese women, HYBID-mediated reduction of HA in the superficial dermis is involved in the formation of wrinkles in Caucasian women.

Association of a single nucleotide polymorphism in the SH2D1A intronic region with systemic lupus erythematosus.

SH2D1A, also known as signaling lymphocytic activation molecule (SLAM)-associated protein (SAP), is an adaptor protein. Recently, it was reported that SAP deficient mice were protected from systemic lupus erythematosus (SLE). In this study, we postulated SH2D1A gene to be a candidate susceptibility gene for SLE and analyzed its association with SLE. A case-control association study was conducted on 5 tag single nucleotide polymorphisms (SNPs) in SH2D1A region in 506 Japanese female SLE patients and 330 healthy female controls. The luciferase assay was performed to determine the functional role of the SNP associated with SLE. One SNP in the intron 2, rs2049995, showed association with SLE (p=0.0110, odds ratio (OR) 1.97, 95% confidence interval (CI) 1.16-3.34, under the dominant model). The association of rs2049995 seemed to be stronger in the subset with the age of onset less than 20 years (p=0.0067, OR 2.65, 95% CI 1.28-5.46). Functional evaluation of rs2049995 showed that reporter gene activity was increased 1.9-fold for the susceptible allele compared with the resistant allele. An intronic SNP of SH2D1A is associated with SLE.

Activation of basophils by stem cell factor: comparison with insulin-like growth factor-I.

BACKGROUND: Basophils are an active participant in the pathogenesis of local inflammation in allergic diseases such as asthma, but it is not fully known how basophil activation is regulated in inflamed tissue. OBJECTIVE: In order to clarify the control mechanisms of basophil activation in chronic inflammation and at remodeling sites, we analyzed the effects of fibroblast-derived cytokines, stem cell factor (SCF), and insulin-like growth factor-I (IGF-I) on basophils. METHODS: The effects of SCF and IGF-I on degranulation and surface activation marker expression by basophils were assessed and compared. RESULTS: SCF enhanced human basophil histamine release elicited by some, but not all, secretagogues; degranulation in response to IgE- or FcepsilonRI-mediated stimulation and 12-o-tetradecanoyl-phorbol-13-acetate (TPA) was enhanced by SCF. SCF slightly enhanced ionophore A23187-induced histamine release by basophils from some donors, but it failed to affect the release elicited by monocyte chemoattractant protein-1 (MCP-1), formylmethionyl-leucyl-phenylalanine (FMLP) or C5a. The repertoire of secretagogues responsive to SCF was similar to that of IGF-I. Expression levels of both CD11b and CD69 markers were significantly enhanced by the combination of SCF and IGF-I. CONCLUSIONS: These results suggest that SCF and IGF-I may modify the activation of basophils in a similar and/or synergistic fashion. Interaction of basophils with these cytokines might be involved in the pathogenesis of local inflammation and the remodeling process in asthma.

Treatment and prognosis of patients with paraplegia or quadriplegia because of metastatic spinal cord compression in prostate cancer.

Metastatic spinal cord compression (MSCC) is a serious complication of metastatic prostate cancer (PCa). This study retrospectively evaluated patients who presented with paraplegia or quadriplegia because of MSCC of PCa. Of 847 patients with PCa who were treated between 1989 and 1998, 26 (3.1%) demonstrated paraplegia or quadriplegia because of MSCC. Characteristics, treatment efficacy, and prognosis of these patients were analyzed. In total, 15 cases became paraplegic despite androgen ablation therapy (Group I). Average time to paraplegia from initial hormonal treatment was 34 months. Out of nine cases who underwent radiation therapy (RT) to spinal lesions with/without chemotherapy, one patient became ambulatory. However, this patient subsequently had recurrent compression. Two cases had remission of paralysis. Two cases underwent laminectomy plus RT and in one case paralysis improved. MSCC was the first indication of PCa in 11 cases (Group II). Two cases underwent laminectomy plus hormone therapy and nine cases underwent hormone therapy alone. Four patients became ambulatory and two cases showed improved motor capacity. Average interval from paraplegia to death was 7.4 months in Group I and 27.1 months in Group II. However, there was no statistical difference in these two groups on disease-specific survival from the start of initial treatment. It is difficult to recover the ability to walk if paraplegia or quadriplegia occurs in PCa patients although decompression surgery plus hormone therapy seemed to impair the prognosis. Stage M1 patients with paraplegia had survival rates as good as stage M1 patients without paralysis. This should encourage an aggressive treatment approach. However, for patients with hormone-independent disease there seems to be no effective treatment and prognosis is poor.

Laparoscopic adrenalectomy for functioning adrenal tumors: clinical experiences with 38 cases and comparison with open adrenalectomy.

We reviewed 38 cases of transperitoneal or retroperitoneal laparoscopic adrenalectomy for unilateral benign functioning adrenal tumors and compared the results with those of a recent series of 36 patients undergoing an open adrenalectomy. The tumors were removed successfully in all but two cases with laparoscopy that required open laparotomy. In the other 36 cases of the laparoscopy group, mean operative time and blood loss were 225 minutes and 138 mL, respectively. Mean operative time was significantly longer for the laparoscopy group (122 minutes for open surgery: P < 0.0001), whereas mean blood loss of the laparoscopy group was almost equal to that of the open surgery group. Mean intervals to first ambulation and oral intake, and postoperative hospital stay of the laparoscopy group were significantly less than those of the open surgery group (1.4 vs 2.0 days: P = 0.014; 1.8 vs 2.9 days: P < 0.0001; and 8.5 vs 12.9 days: P < 0.0001, respectively). We conclude that laparoscopic adrenalectomy is equally effective and less invasive than open adrenalectomy. and that it should be considered as the first-choice therapy for benign adrenal tumors.

A rapid DNA probe method for detection of Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans.

BACKGROUND: The objective of the present study was to develop a rapid DNA probe method for the microbiological detection of periodontitis that can be used in dental clinics. By using the DNA probe, we also investigated the correlation between the occurrence of putative periodontopathic bacteria and clinical parameters. METHODS: This rapid DNA probe method minimizes the use of a water bath for ordinary hybridization and washing in order to shorten the total reaction time. The detection process could be completed within 2 hours. In order to evaluate the clinical application of the DNA probe, subgingival plaque samples were taken from patients with periodontitis before initial therapy. After the therapy, the patients were microbiologically and clinically evaluated. RESULTS: When the DNA probe method was compared with the culture method, the agreement was 88% for Porphyromonas gingivalis and 67% for Actinobacillus actinomycetemcomitans. A statistically significant association was found between the detection of P. gingivalis and probing depth, bleeding on probing (chi2 test: P <0.001, P <0.05). A significant association was also shown between the detection of A. actinomycetemcomitans and probing depth in patients aged 35 or older (chi2 test: P <0.001). The detection rate of A. actinomycetemcomitans was highest in teenagers. At shallow periodontal pocket sites (PD < or =3 mm) in teenagers, no P. gingivalis was found, while 22% of the sites harbored A. actinomycetemcomitans. After the therapy, the frequency of detection of P. gingivalis decreased significantly only in the clinically improved sites (chi2 test: P <0.001). CONCLUSIONS: The rapid DNA probe method appears promising as an efficient tool for rapid clinical detection of periodontopathic bacteria.

[Intra-arterial chemotherapy for invasive bladder cancer].

Between July 1993 and May 1999, 36 patients with invasive bladder cancer were treated with intra-arterial chemotherapy using cisplatin and pirarubicin, and their treatment outcome was evaluated. Clinical CR was obtained in 18 patients, PR in 13, and NC in 5, for an overall response rate of 86%. The median follow-up for evaluating patients was 24 months (2-70 months). The bladder was preserved in 13 of 18 patients showing CR and in 4 of 13 patients showing PR. The 5-year cause-specific survival rate for the 36 patients was 56%. The grade factor did not effect the survival rate significantly. Compared with stage T2, stage T3 yielded a significantly poor prognosis, especially with grade 3. Intra-arterial chemotherapy was confirmed useful as a regional treatment, but not sufficient as a systemic treatment. Thus the selection of patients for this therapy was considered to require exact staging and assessment of the effectiveness.

Three-dimensional continuation study of convection in a tilted rectangular enclosure.

A continuation method developed from a three-dimensional spectral finite element code is used to study natural convection in a tilted rectangular cavity. The cavity has its length equal to two times the side of its square cross section and it contains a fluid with a Prandtl number Pr = 1. A detailed bifurcation diagram is first obtained in the case without inclination in order to get the sequence of the different branches of solutions and determine the stable solutions. The focus is then put on the stable solutions in the inclined cavity, when the tilt occurs around its longest axis. The subtle changes induced by the tilt on the convective system are clarified. Three different stable solutions are obtained: the longitudinal roll L- solution (with the same sense of rotation as the inclination angle), which develops smoothly from zero Rayleigh number on the leading branch; the longitudinal roll L+ solution (with a sense of rotation opposite to the inclination angle), which is on a disconnected branch and is stabilized beyond a secondary bifurcation point; the oblique roll O ± solutions (corresponding to transverse roll solutions perturbed by the longitudinal flow induced by the tilt), which quickly appear beyond saddle-node points on new disconnected branches. The domain of existence of these stable solutions is eventually obtained and described in the Rayleigh number-inclination parameter space. Finally, the Nusselt number is determined as a function of the inclination at a constant Rayleigh number for the different stable solutions. The Nusselt number is maximum at an inclination of 49.55° for the leading longitudinal roll L- solution.

Neutrophil CD64 expression in the diagnosis of local musculoskeletal infection and the impact of antibiotics.

We examined the usefulness of neutrophil CD64 expression in detecting local musculoskeletal infection and the impact of antibiotics on its expression. Of 141 patients suspected of musculoskeletal infection, 46 were confirmed by microbiological culture to be infected and 95 had infection excluded. The median CD64 count of patients with localised infection was 2230 molecules per cell (interquartile range (IQR) 918 to 4592) and that of the patients without infection was 937 molecules per cell (IQR 648 to 1309) (p < 0.001). The level of CD64 correlated with the CRP level in patients with infection, but not in those without infection (r = 0.59, p < 0.01). Receiver operator characteristic curve analysis revealed that CD64 was a good predictor of local infection. When the patients were subdivided into two groups based on the administration of antibiotics at the time of CD64 sampling, the sensitivity for detecting infection was better in those who had not received antibiotics. These results suggest that measurement of CD64 expression is a useful marker for local musculoskeletal infection.

Does presence of prostate cancer affect serum testosterone levels in clinically localized prostate cancer patients?

The relationships between serum level of testosterone (T) and prostate cancer (PCa) are complex. The present study evaluated whether presence of PCa alters serum T levels. Subjects were 125 patients with clinically localized PCa treated using radical prostatectomy (RP), for whom pretreatment T levels were recorded. We investigated clinical and pathological factors such as pretreatment serum T level, age, pretreatment prostate-specific antigen, Gleason score and pathological stage. Serum T and human luteinizing hormone (LH) levels before and after RP were then compared in 118 of the 125 patients. Mean pretreatment T level was significantly higher in patients with organ-confined PCa (pT2; 4.03+/-1.50 ng ml(-1)) than in patients with nonorgan-confined cancer (pT3; 3.42+/-1.06 ng ml(-1); P=0.0438). No association existed between pretreatment serum T level and pathological Gleason score. After RP, serum T level (5.60+/-1.90 ng ml(-1)) was significantly elevated compared to preoperative level (3.89+/-1.43 ng ml(-1); P<0.0001). In parallel, significant increases were seen in postoperative serum LH level (6.86+/-3.64 ng ml(-1)) compared to preoperative level (5.11+/-2.47 ng ml(-1); P=0.0001). In contrast, differences in serum T levels according to pathological stage disappeared postoperatively (P=0.5513). Significant increases in serum T and LH levels were seen after RP, compared to preoperative levels in parallel. This study suggests that serum T levels are altered by the presence of PCa, supporting the possibility that PCa may inhibit serum T levels with negative feedback in the hypothalamic-pituitary axis.

Genetic changes in pT2 and pT3 prostate cancer detected by comparative genomic hybridization.

Prostate-specific antigen (PSA) screening has led to a remarkable increase in prostate cancer cases undergoing operative therapy. Over half of patients with locally advanced cancer (>or=pT3) develop rising PSA levels (biochemical failure) within 10 years. It is very difficult to predict which patients will progress rapidly to advanced disease following biochemical failure (BF). Therefore, a more useful prognostic factor is needed to suggest the most appropriate therapies for each patient. To determine chromosomal aberrations, we examined 30 patients with stage pT2 or pT3 primary prostate adenocarcinomas and no metastases (pN0M0) by comparative genomic hybridization (CGH). Laser capture microdissection (LCM) was used to gather cancer cells from frozen prostate specimens. Common chromosomal alterations included losses on 2q23-24, 4q26-28, 6q14-22, 8p12-22 and 13q21-31, as well as gains on 1p32-36, 6p21 and 17q21-22. Losses at 8p12-22 and 13q21-31 were observed more frequently in pT3 than pT2 tumors (P<0.05 and P<0.01, respectively). Losses at 8p12-22 were more frequent in tumors with BF (P<0.05), and those at 13q12-21 were more frequent in tumors with Gleason score (GS) 7 or more than lower GS (P<0.05). These findings suggest that losses of 8p12-22 and 13q21-31 are important determinants of prostate cancer progression.

Identification and characterization of Birt-Hogg-Dubé associated renal carcinoma.

The Birt-Hogg-Dubé (BHD) gene is responsible for BHD syndrome, a rare autosomal dominant disease, characterized by benign hair follicle tumours, spontaneous pneumothorax and renal neoplasms with diverse histology. To elucidate its involvement in the development of renal neoplasms, we examined a total of 100 sporadic renal tumours with various histological subtypes for BHD mutation by SSCP-sequencing analyses. We found one germline insertion mutation in the C8 hotspot of exon 11 (c.1733insC), which is known to have a strong association with renal tumour occurrence. The germline-mutated patient suffered from solitary renal cell carcinoma (RCC) but did not have any other BHD manifestations or family history. The tumour revealed heterogeneous cytomorphology, mainly a mixture of eosinophilic and focally clear cells with tubulopapillary architecture. In this tumour, both BHD alleles were inactivated by germline mutation concomitant with loss of heterozygosity, and the amount of BHD mRNA detected by real-time quantitative PCR (RQ-PCR) was very low. Renal tumour subtype/nephron segment-specific gene expression detected by RQ-PCR demonstrated that the tumour expressed relatively high amounts of alpha-methylacyl-CoA racemase (AMACR) and the KIT oncogene, but relatively low amounts of carbonic anhydrase IX (CA9), aquaporin 1 (AQP1), claudin 7 (CLDN7), parvalbumin (PVALB), chloride channel Kb (CLCNKB) and 11-beta-hydroxysteroid dehydrogenase 2 (HSD11B2), suggesting diverse mRNA signatures. Further clustering analysis of 88 renal tumours based on expression of these eight genes sub-classified the tumour as close to oncocytomas and chromophobe RCCs, which are considered distal nephron-associated tumours. These data suggest that somatic mutation of BHD is relatively rare in Japanese patients. The BHD-mutated RCC identified in this study, which exhibits heterogeneous biological features in both morphology and gene expression signatures, seems to deviate from our current understanding of renal tumour classification.

Acceleration of de novo cholesterol synthesis in the epidermis influences desquamation of the stratum corneum in aged mice.

Cholesterol, a component of intercellular lipids, is important for stratum corneum (SC) homeostasis, including its barrier function and desquamation. However, cholesterologenesis in the epidermis decreases under basal conditions with aging. We found that the number of horny layers in murine SC increased with the decrease of desquamation in the outermost corneocytes associated with aging. The cholesterol content decreased and the cholesterol sulfate content increased in the horny layer with aging, which resulted in an increase in the ratio of cholesterol sulfate to cholesterol. Moreover, we investigated the effects of accelerated cholesterologenesis on desquamation in aged murine skin following topical application of mevalonic acid. The ratio of cholesterol sulfate to cholesterol in aged murine SC significantly decreased following topical treatment with mevalonic acid, which resulted from an increase in cholesterol content via the acceleration of cholesterologenesis. Treatment with mevalonic acid also significantly reduced the number of cell layers in the SC along with the acceleration of desquamation, as measured by desmoglein I content, corneocyte surface area and proteinase activity. These results indicate that an improvement in the ratio of cholesterol sulfate to cholesterol content by de novo cholesterologenesis may be important for desquamation of the SC in aged epidermis.

Augmentation ileocystoplasty in patients with neurogenic bladder due to spinal cord injury or spina bifida.

STUDY DESIGN: Retrospective analysis of augmentation ileocystoplasty for neurogenic bladder. OBJECTIVES: To analyze the effects and complications of augmentation ileocystoplasty in patients with neurogenic bladder due to spinal cord injury (SCI) or spina bifida retrospectively. SETTING: Department of Urology, Kanagawa Rehabilitation Hospital, Japan. METHODS: We have treated 11 patients with neurogenic bladder due to SCI and 10 patients with spinal bifida with augmentation ileocystoplasty since 1989. The purpose of the treatment was to stop vesicoureteral reflux (VUR) and/or amelioration of urinary incontinence. In 17 of 21 cases, the antireflux operation was received simultaneously. All cases performed clean intermittent self catheterization postoperatively. RESULTS: Urinary incontinence improved in all cases and only transient recurrence of VUR was observed in the follow-up term. Complications occurred in patients with SCI, but they could be treated conservatively. CONCLUSION: Augmentation ileocystoplasty is a good treatment option for contracted bladder or VUR, which occurs in patients with neurogenic bladder.

Localization of a tumor suppressor gene associated with progression of human prostate cancer within a 1.2 Mb region of 8p22-p21.3.

Human prostate cancers frequently show loss of heterozygosity at loci on the short arm of chromosome 8. In order to take a step toward isolation of the putative tumor suppressor gene(s) on 8p via positional cloning, we performed high-resolution deletion mapping in 46 prostate cancers (stage B, 20 cases; stage C, 8 cases; endocrine therapy-resistant cancer death, 18 cases) using new 12 restriction fragment length polymorphism markers for this chromosomal region. Allelic losses were observed in 25 of the 44 cases (57%) that were informative with at least one locus. Detailed deletion mapping defined a 1.2 Mb commonly deleted region at 8p22-p21.3 flanked by markers cMSR-32 and C18-1051. A second region of common deletion was identified between C18-1312 and C18-494 at 8p21-8p11.22, suggesting that at least two tumor suppressor genes associated with prostate cancer are present on chromosome arm 8p. Allelic losses on 8p were observed more frequently in the cancer death cases (14/17, 82%) than in early-stage tumors (11/27, 40%; P < 0.01, Fisher's exact test). In two out of 7 patients for whom DNA was available from metastatic cancers as well as from normal tissues and primary tumors, the primary cancer foci had no detectable abnormality of 8p, but the metastatic tumors showed loss of heterozygosity. These results suggest that inactivation of tumor suppressor genes on 8p plays an important role in the progression of prostate cancer.