Bone resorption versus estrogen loss following oophorectomy and menopause

OBJECTIVES: To investigate if menopause and oophorectomy may represent different risk factors for bone resorption/loss. METHODS: The urinary levels of pyridinoline (Pyr) and deoxypyridinoline (D-pyr), the serum levels of type I carboxy-terminal pyridinoline cross-linked telopeptide (ICTP), and lumbar bone mineral density (BMD), were compared in 80 Japanese women after menopause or oophorectomy. These women were divided into four groups of 20 women each as follows: early postmenopausal stage (early physiologic menopause < 3 years before study entry); late postmenopausal stage (physiologic menopause > or = 3 years before study entry); early postoophorectomy stage (oophorectomy < or = 03 years before study entry); or late oophorectomy stage (oophorectomy > 3 years before study entry). RESULTS: Lumbar BMD was significantly lower in the late groups compared to their respective early groups and was lowest in the late postoophorectomy group. The ratio of D-pyr/creatinine (Cr) was not significantly different among the four groups. The ratio of Pyr/Cr was significantly higher in the early postoophorectomy subjects compared with either late group. The serum level of ICTP was significantly higher in the early postoophorectomy group compared to all other groups. CONCLUSIONS: These findings suggest that serum ICTP may be useful in detecting changes in bone resorption after oophorectomy and that women are at greater risk for bone resorption after oophorectomy than after physiologic menopause, although this difference appears to diminish with time.     

Selective regulation of T cell IL-5 synthesis by OM-01, JTE-711 and p38 MAP kinase inhibitor: independent control of Th2 cytokines, IL-4 and IL-5

BACKGROUND: Helper T cells are involved in chronic eosinophilic inflammation. Control of cytokine production seems to be an effective management. METHODS: The effect of nonactin, SB203580, a p38 MAP kinase inhibitor, and JTE-711 on the cytokine production of allergen-specific T cell clones was determined. The effect of nonactin on the airway eosinophilia was investigated using murine asthma model. RESULTS: Nonactin suppressed IL-5 synthesis by human Th cells in a dose-dependent manner without affecting IL-2 or IL-4 synthesis, and still significantly suppressed murine airway eosinophilia induced by the antigen inhalation. SB203580 and JTE-711 also selectively inhibited IL-5 synthesis in vitro. CONCLUSION: Synthesis of IL-5 by human Th cells can be differentially regulated from that of other major T cell cytokines. The in vivo effects of selective IL-5 synthesis inhibitors suggest that IL-5 is the reasonable target for the regulation of allergic disorders accompanied by eosinophilic inflammation.     

Validation of ECRHS Questionnaire in Japanese to use for nation-wide prevalence study of adult asthma]

PURPOSE: To enable international comparison of prevalence in asthma, we translated and evaluated ECRHS Questionnaire, which is introduced in GINA. Considering COPD prevalence in elder people, we added two questions to the ECRHS Questionnaire. METHOD: The Japanese edition of ECRHS Questionnaire was responded by 366 patients who were diagnosed asthma without COPD, 61 patients who were diagnosed COPD without asthma, and 137 healthy persons who were not diagnosed asthma or COPD. We analyzed the answers of the each group and evaluated the validity of the questionnaire to use for the nation-wide prevalence study of adult asthma in future. RESULTS: The question of 'Wheezing at any time in the last 12 months' had the highest Youden's index and validity to pick up asthma patients. The questions of 'Waking up with a feeling of tightness in chest at any time in the last 12 months' and 'Waking up by an attack of shortness of breath at any time in the last 12 month' had the highest specificity to pick up asthma patients. Most of the questions which were related asthma were able to be answered by asthma patients properly, but some questions were improperly answered by patients and healthy persons in elderly. The results in this study showed the less recognition of their diseases in elderly patients than younger patients and the limitation of the study with written questionnaire for elderly people. Not a few COPD patients complained wheezing or whistling in the chests as same as asthma patients in this study. CONCLUSION: We concluded that we had almost enough reliability in the Japanese edition of the ECRHS questionnaire for screening survey of asthma prevalence in Japan.     

Prevention of endotoxin shock by an antibody against leukocyte integrin {beta}2 through inhibiting production and action of TNF

Septic shock remains a serious disorder associated with highmortality. Accumulating evidence indicates that TNF is a majorand essential mediator of endotoxin shock. We report here thatadministration of an antibody against CD18 dramatically reducedendotoxin-induced shock inrabbits as revealed by preventionof severe hypotension, metabolic acidosis and a pathologicalchange suggestive of disseminated intravascular coagulationwith concomitant inhibition of elevation of plasma TNF activity.The anti-CD18 antibody also inhibited the hypotension inducedby administering recombinant TNF. Furthermore, an antibody againsta ligand for CD18 complexes, intercellular adhesion molecule-1,also prevented TNF-induced shock as well as endotoxin shockinrabbits. These observations suggest that adhesion of leukocytesto endothelium may be of primary importance in the action ofTNF as well as in the production of TNF in vivo and that theantibody against adhesion molecules could be of therapeuticbenefit in life-threatening septic shock in humans.     

Evidence of genetic heterogeneity in the autosomal recessive adult forms of limb-girdle muscular dystrophy following linkage analysis with 15q probes in Brazilian families.

The autosomal recessive limb-girdle muscular dystrophies (LGMD) represent a heterogeneous group of diseases which may be characterised by one or more autosomal loci. A gene at 15q has recently been found to be responsible for a mild form of LGMD in a group of families from the isolated island of Réunion, now classified as LGMD2. Based on results of eight out of 11 large Brazilian LGMD families of different racial background (which were informative for the closest available probe to the LGMD2 gene), we confirmed linkage to the LGMD2 gene at 15q in two of these families and exclusion in six others. These data provide the first evidence of genetic heterogeneity for the autosomal recessive limb-girdle muscular dystrophies.     

Transurethral detachment prostatectomy using a tissue morcellator for large benign prostatic hyperplasia.

OBJECTIVE: Transurethral enucleation of the prostate (TUE) is designed for complete removal of the prostate lobes. On the basis of TUE and holmium laser enucleation of the prostate, we developed a new technique of transurethral detachment prostatectomy (TUDP) using a tissue morcellator. MATERIALS AND METHODS: In TUDP, enucleation is performed with a prostate-detaching blade and the tip of a resectoscope, followed by removal of the tissue with a morcellator. This study reports our experience with TUDP in which the weight of retrieved tissue was greater than 30 g in 76 patients with benign prostate hyperplasia. RESULTS: The mean preoperative total prostate and adenoma volumes were 70.7 and 47.4 mL, respectively. The mean times required for enucleation, morcellation, and total operation time were 28.5, 14.4, and 66.3 minutes, respectively. The mean weight of removed prostate tissue was 61.1 g. The mean decreases in the levels hemoglobin and serum sodium were 1.73 mg/dL and 2.41 mEq/dL, respectively. The mean preoperative maximum flow rate (Qmax), International Prostate Symptom Score (IPSS), and quality of life score (QOL) improved from 9.8 mL/sec, 20.2, and 4.9, to 22.3 mL/sec, 3.1 and 1.2, respectively. Complications included mild morcellator-induced mucosal injury in 2 patients (2.6%), nausea in 4 patients (5.2%), transient urinary retention in 2 patients (2.6%), transient urge incontinence in 5 patients (6.4%), and urethral stricture in 2 patients (2.6%). The mean prostate volume and serum prostate-specific antigen level measured 6 months postoperatively in 46 patients were 10.68 mL and 0.89 ng/mL, respectively. CONCLUSIONS: TUDP is effective for complete removal of large prostate lobes in patients with large benign prostate hyperplasia and is associated with lower perioperative morbidity.     

Feasibility of using decades-old archival tissues in molecular oncology/epidemiology.

Archival tissues are a bountiful resource for various studies. Polymerase chain reaction permits the use of such tissues for molecular biological analyses of disease causation. However, a comprehensive study using a large number of decades-old samples (20 or more years) for molecular oncology/epidemiology has never been shown to be feasible. We have relied upon the unique tumor registry of atomic bomb survivors to show that such studies are possible using 275 hepatocellular carcinoma and 41 skin cancer cases. We used 23 relatively recent thyroid papillary carcinoma cases from persons living in the vicinity of the Chernobyl nuclear reactor accident for comparison. Degradation of DNA is severe in autopsy hepatocellular carcinoma samples but can be compensated for by decreasing the polymerase chain reaction product size. Increasing the amount of DNA that is used by a factor of 8 improved amplification efficiency from approximately 60 to 80%. Age of the samples was not as great a problem as was the source of procurement. The extracted DNA can be used for all types of assays that require polymerase chain reaction amplification, such as restriction fragment length polymorphism, single-strand conformation polymorphism, and direct sequencing.     

Immunohistochemical analysis of thymidylate synthase, p16(INK4a), cyclin-dependent kinase 4 and cyclin D1 in colorectal cancers receiving preoperative chemotherapy: significance of p16(INK4a)-mediated cellular arrest as an indicator of chemosensitivity to 5-fluorouracil

High expression of thymidylate synthase (TS) is allegedly associated with the chemoresistance to 5-fluorouracil (5-FU) in colorectal cancers. However, low TS expression does not necessarily imply chemosensitivity. Inactivation of p16(INK4a) correlates with poor prognosis in various cancers. We immunohistochemically evaluated the relationship between the expression of TS, p16(INK4a), CDK4 and cyclin D1 and the effect of 5-FU-based chemotherapy in colorectal cancers. After antigen retrieval, immunoperoxidase staining was performed on the paraffin-embedded, biopsy and surgical specimens of 37 advanced colorectal cancers preoperatively treated with peroral administration of 5-FU derivatives. As a control group, 31 colorectal cancers without preoperative treatment were analyzed. High TS expression was found in 23 (74%) of 31 tumors resected from histological non-responders and in 19 (61%) of 31 controls but in none of six responders. High p16(INK4a) expression was seen in 83% of the responders, 52% of the non-responders and 32% of the controls. The TS-low/p16(INK4a)-high phenotype was noted in 83% of the responders, but only in 3% of the non-responders (P = 0.0001). Induction of p16(INK4a) expression after chemotherapy was predominantly seen in the responders. Neither CDK4 nor cyclin D1 expression was related to the chemotherapeutic effects. In conclusion, the combination of low expression of TS and induction of p16(INK4a) after chemotherapy can be important indicators of the sensitivity to 5-FU-based chemotherapy in colorectal cancers.     

Role of nectin in organization of tight junctions in epithelial cells

BACKGROUND: In polarized epithelial cells, cell-cell adhesion forms specialized membrane structures comprised of claudin-based tight junctions (TJs) and of E-cadherin-based adherens junctions (AJs). These structures are aligned from the apical to the basal side of the lateral membrane, but the mechanism of this organization remains unknown. Nectin is a Ca2+ independent immunoglobulin-like cell-cell adhesion molecule which localizes at AJs. Nectin is associated with E-cadherin through their respective cytoplasmic tail-binding proteins, afadin and catenins, and involved in the formation of AJs in cooperation with E-cadherin. We show here that nectin is also involved in the formation of TJs. RESULTS: During the formation of the junctional complex consisting of AJs and TJs in Madin-Darby canine kidney (MDCK) cells, claudin and occludin accumulated at the apical sites of the nectin-based cell-cell adhesion sites. This accumulation of claudin and occludin was inhibited by inhibitors acting on the trans interaction of nectin. The barrier function of TJs was also impaired by the nectin inhibitors. It has been shown that a phorbol ester promotes the formation of a TJ-like structure in an E-cadherin-independent manner. This phorbol ester-induced formation of the TJ-like structure was also inhibited by the nectin inhibitors. CONCLUSIONS: These results suggest a role of the nectin-afadin system in the organization of TJs as well as AJs in epithelial cells.