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Recently, a novel transmembrane protein was found to be up-regulated in the auditory learning pathway of birds and mammals. The protein, FnTm2, was predicted to have an extracellular fibronectin III (Fn3) domain and a single transmembrane domain. By contrast to other studied Fn3 domains the extracellular domain of FnTm2 bears several cysteine residues, which are predicted to form disulfide bonds. The Fn3 domain of the FnTm2 protein was expressed in DH5-α Escherichia coli (E. coli) cells, purified and characterized by circular dichroism (CD). In order to identify binding partners to Fn3, the isolated protein was incubated with bird brain lysate for a pull down treatment. Of the proteins recognized, myelin basic protein (MBP) was identified as a bona fide partner; it was further characterized for binding to Fn3 in vitro via fluorescence spectroscopy and confirmed via isothermal calorimetry (ITC)., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Sarcoglycans are originally identified in muscle for their involvement in limb-girdle muscular dystrophies. They form a multi-meric complex (alpha-, beta-, gamma-, delta-sarcoglycan) that associates with dystrophin, dystroglycan and other proteins to constitute the larger dystrophin-glycoprotein complex at the muscle membrane. Three sarcoglycan subunits (epsilon-, beta-, delta-sarcoglycan) were previously identified in Schwann cells and shown to associate with dystroglycan and a Schwann cell-specific dystrophin isoform (Dp116) at the outermost Schwann cell membrane. Currently, little is known about the exact composition and function of the sarcoglycan complex in the peripheral nervous system. In this study, we showed that the Schwann cell sarcoglycan complex consists of epsilon-, beta-, delta-sarcoglycan and the newly identified zeta-sarcoglycan subunit. The expression of sarcoglycans precedes the onset of myelination and is induced by neurons. In sarcoglycan-deficient BIO14.6 hamsters, loss of the Schwann cell sarcoglycan complex reduces the steady state levels of alpha-dystroglycan and Dp116. Ultrastructural analysis of sciatic nerves from the mutant animals revealed altered myelin sheaths and disorganized Schmidt-Lanterman incisures indicative of myelin instability. The disruption in myelin structure increased in severity with age. Nerve conduction studies also showed subtle electrophysiological abnormalities in the BIO14.6 hamsters consistent with reduced myelin stability. Together, these findings suggest an important role of sarcoglycans in the stability of peripheral nerve myelin.

Mutations in sarcoglycans have been reported to cause autosomal-recessive limb-girdle muscular dystrophies. In skeletal and cardiac muscle, sarcoglycans are assembled into a complex on the sarcolemma from four subunits (alpha, beta, gamma, delta). In this report, we present a detailed structural analysis of sarcoglycans using deletion study, limited proteolysis and co-immunoprecipitation. Our results indicate that the extracellular regions of sarcoglycans consist of distinctive functional domains connected by proteinase K-sensitive sites. The N-terminal half domains are required for sarcoglycan interaction. The C-terminal half domains of beta-, gamma- and delta-sarcoglycan consist of a cysteine-rich motif and a previously unrecognized conserved sequence, both of which are essential for plasma membrane localization. Using a heterologous expression system, we demonstrate that missense sarcoglycan mutations affect sarcoglycan complex assembly and/or localization to the cell surface. Our data suggest that the formation of a stable complex is necessary but not sufficient for plasma membrane targeting. Finally, we provide evidence that the beta/delta-sarcoglycan core can associate with the C-terminus of dystrophin. Our results therefore generate important information on the structure of the sarcoglycan complex and the molecular mechanisms underlying the effects of various sarcoglycan mutations in muscular dystrophies.

Objective: To investigate the effects of precolposcopy counseling on women's anxiety, knowledge about colposcopy and compliance to follow-up., Methods: Two hundred and twenty women referred for colposcopy for the first time were recruited. They attended precolposcopy sessions in which written and video information were given and subsequently were randomized to have either further explanation and discussion with an experienced colposcopic nurse (study group) or no further discussion (control group). Each subject completed a Chinese version of the state-anxiety questionnaire (STAI) and a knowledge questionnaire before and immediately after the precolposcopy sessions and also before the colposcopy examination. Women's concern and opinion on the programme were also assessed. Follow-up data was compared with those who did not attend the precolposcopy sessions., Results: Women's knowledge about colposcopy significantly improved after the precolposcopy sessions. The improvement was more significant in the study group than in the control group immediately after the sessions (P = 0.003). The difference between the groups in knowledge scores remained statistically significant before colposcopic examination (P = 0.015) but the difference diminished between these two assessment points. There was no statistically significant difference between the two groups in the anxiety scores at all assessment points. Women who attended the precolposcopy sessions had a significantly higher attendance rates and better compliance to follow-up than those who did not attend the sessions., Conclusion: Precolposcopy session with explanation and discussion improves women's knowledge about colposcopy, but has negligible effects on women's anxiety before colposcopy. Provision of written and video information at the precolposcopy sessions can improve compliance to follow-up after colposcopy.

Transection of the optic nerve initiates massive death of retinal ganglion cells (RGCs). Interestingly, despite the severity of the injury, RGC loss was not observed until several days after axotomy. The mechanisms responsible for this initial lack of RGC death remained unknown. In the current study, immunohistochemical analysis revealed that caspases-3 and -9 activation in the RGCs were not detected until day 3 post-axotomy, coinciding with the onset of axotomy-induced RGC loss. Interestingly, elevated Akt phosphorylation was observed in axotomized retinas during the absence of caspase activation. Inhibiting the increase in Akt phosphorylation by intravitreal injection of wortmannin and LY294002, inhibitors of PI3K, resulted in premature nuclear fragmentation, caspases-3 and -9 activation in the ganglion cell layer. Our findings thus indicate that the PI3K/Akt pathway may serve as an endogenous regulator of caspase activation in axotomized RGCs, thereby, contributing to the late onset of RGC death following axotomy.

Objective: This study aimed to investigate the prevalence of human immunodeficiency virus (HIV) infection in women with cervical cancer and to decide whether HIV testing should be included as part of the initial work-up of invasive cervical cancer., Methods: This was a prospective case controlled study. Women with newly diagnosed cervical cancer were tested and age-matched women with benign gynecologic conditions were selected as control. Serum samples were tested for HIV I and HIV II antibodies at diagnosis and 3 months later., Results: Two hundred twenty-five consecutive patients with newly diagnosed cervical cancer and two hundred twenty-three age-matched women with benign gynaecological conditions were tested. In comparison with the control, women with cervical cancer started sexual intercourse at an earlier age and had a statistically significant higher number of sexual partners. All the HIV tests were negative. The HIV prevalence rate was estimated to be 0.0-1.6% for both groups., Conclusion: HIV screening should not be a part of the initial work-up for cervical cancer in a population with a low background prevalence.

Objective: The Bethesda system for reporting cervicovaginal cytologic diagnoses was recently revised in 2001. Pathologists are required to report not only whether the smear favors neoplastic changes, but also the origin of the abnormal cells. In this study, archival smears were reviewed to evaluate the usefulness of the new classification., Methods: Smears having atypical glandular cells taken between January 1995 and December 1997 were reviewed and subclassified according to the revised Bethesda classification. Case records were then reviewed and cases with discrepancies between the cytological evaluation and corresponding final histological diagnoses were further reviewed., Results: There were 138 smears reviewed. The mean age of the patients was 47 (range, 18 to 78). Thirty-four smears favored neoplasia and 104 favored "NOS" ("not otherwise specified"). Sixty smears favored endocervical origin and 78 endometrial origin. Forty-three patients (31%) had significant pathologies, including 12 (8.7%) patients with high-grade CIN, 2 (1.4%) with low-grade CIN, 5 (3.6%) with HPV infection, 7 (5.1%) with carcinoma of the corpus, 1 (0.7%) with cervical adenocarcinoma in situ, 4 (2.9%) with adenocarcinoma of the cervix, 3 (2.2%) with endometrial hyperplasia, and 5 (3.6%) with carcinoma of the ovary. Two (1.4%) patients had double primary female genital malignancies and 2 patients (1.4%) had extragenital malignancies. Significant correlation was found between smears "favor neoplasia" and a final diagnosis with significant pathology (chi(2) test, P < 0.05). Significant association was found between AGC favored endocervical origin and a final diagnosis with cervical diseases (chi(2) test, P < 0.05). Four of the 43 patients who had significant pathologies had lesions found during their subsequent visits and all of them had cervical smears classified as AGC "favor neoplasia"., Conclusion: AGC found on cervical smears are an indication for early and intensive investigation.

Objective: The goal of this work was to investigate the impact of music on women's anxiety and perceived pain during colposcopy examination., Methods: This was a prospective randomized study. Two hundred and twenty women referred for colposcopy for the first time were recruited. They were randomized to either the music or no-music group. Before colposcopy examination, each subject completed a Chinese version of the state anxiety questionnaire (STAI) and assessed the anticipated pain for colposcopy with a visual analog scale (VAS). Slow-rhythm music was played during colposcopy examination in the music group. Subjects in the no-music group were examined in the same setting without music. After colposcopy, each subject completed the STAI form again and assessed their pain during examination by the VAS., Results: Women in the music group experienced significantly less pain (mean VAS 3.32 [95% CI 2.86-3.78] vs 5.03 [4.54-5.52], P<0.001) and lower anxiety (mean STAI 39.36 [95% CI 37.33-41.39] vs 44.16 [41.82-46.49], P = 0.002) during colposcopy examination than women in the no-music group. On linear regression analysis, the factors significantly affecting anxiety during colposcopy were anxiety score at enrollment, pain score during colposcopy, and whether or not the women had listened to music during the colposcopy examination. The factors significantly affecting the pain scores were whether the women had listened to music during the procedure and the final anxiety scores., Conclusions: Music is a simple, inexpensive, and easily used strategy to minimize anxiety and pain during colposcopy examination.

Objective: The purpose was to explore whether health education on symptoms of ovarian cancer would aid in early detection, by examining the relationship between symptoms, coping strategies, and timing of presentation in patients with newly diagnosed ovarian cancer., Methods: Eighty women were included. A questionnaire consisting of a series of open questions was designed to collect information on the sequence of events from the onset of symptoms to the diagnosis of ovarian cancer. The Coping Response Inventory (CRI) was used to assess the coping strategies., Results: A majority (90.0%) of women with ovarian cancer did have symptoms before the diagnosis. Abdominal pain or discomfort, abdominal distension, a palpable abdominal mass, menstrual, bowel, or urinary symptoms were the commonly reported symptoms. Eight (10.0%) patients were totally asymptomatic prior to the cancer diagnosis. The presence of bowel symptoms was significantly associated with late stage disease. Most of the patients sought medical advice within 2 weeks from the onset of symptoms. There was no association between the presence of any particular symptom(s) and the timing of presentation. There was also no correlation between the coping strategies and stage of disease and timing of presentation. On average, patients with early stage disease saw one more doctor compared to patients with late stage disease before the affirmative diagnosis of ovarian cancer., Conclusion: Most patients presented early after the onset of symptoms. Health education in this regard may not be useful for early diagnosis of ovarian cancer.

We examined whether (1) a pan-caspase inhibitor, Boc-D-FMK, exerts long-term neuroprotective effects on spinal motoneurons (MNs) after root avulsion in neonatal rats and (2) whether the rescued spinal MNs regenerate their axons into a peripheral nerve (PN) graft and reinnervate a previously denervated target muscle. Eight weeks after root avulsion, 67% of spinal MNs remained in the Boc-D-FMK-treated group, whereas all MNs died in the sham control group. By 12 weeks postinjury, however, all Boc-D-FMK treated MNs died. In the regeneration experiment, a PN graft was implanted at different times after injury. The animals were allowed to survive for 4 weeks following the operation. Without caspase inhibition, MNs did not regenerate at any time point. In animals treated with Ac-DEVD-CHO, a caspase-3-specific inhibitor, and Boc-D-FMK, 44 and 62% of MNs, respectively, were found to regenerate their axons into a PN graft implanted immediately after root avulsion. When the PN graft was implanted 2 weeks after injury, however, MNs failed to regenerate following Ac-DEVD-CHO treatment, whereas 53% of MNs regenerated their axons into the graft after treatment with Boc-D-FMK. No regeneration was observed when a PN graft was implanted later than 2 weeks after injury. In the reinnervation study, injured MNs and the target biceps muscle were reconnected by a PN bridge implanted 2 weeks after root avulsion with administration of Boc-D-FMK. Eight weeks following the operation, 39% of MNs reinnervated the biceps muscle. Morphologically normal synapses and motor endplates were reformed in the muscle fibers. Collectively, these data provide evidence that injured neonatal motoneurons can survive and reinnervate peripheral muscle targets following inhibition of caspases.

Objective: The purpose was to examine the outcomes of patients with advanced ovarian cancer treated with neoadjuvant chemotherapy, with a special emphasis on the patients' quality of life (QOL)., Methods: Seventeen patients with advanced ovarian cancer were treated with neoadjuvant chemotherapy based on the extent of disease on computer tomography. All patients received combined platinum/paclitaxel chemotherapy. Debulking surgery was performed after three cycles or six cycles of chemotherapy, depending on the response to the chemotherapy. Patients' QOL was studied over time using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and was then compared with that of patients treated with conventional treatment in the previous cohort., Results: The response rate to chemotherapy assessed at three cycles was 82.4%. The rate of optimum debulking to residual disease less than 2 cm after chemotherapy was 76.9%, and 38.5% had no gross residual disease after surgery. The median overall survival was 22.9 months. The median disease-free interval was 13.3 months. The overall QOL improved after chemotherapy and this continued to improve up to 12 months. The other functional scales also showed improvements over time, apart from the initial transient deterioration in the role functioning and cognitive functioning at 3 months after chemotherapy. Patients treated with neoadjuvant chemotherapy seem to have better but statistically insignificant difference in QOL parameters than patients treated conventionally., Conclusion: Neoadjuvant chemotherapy is an alternative treatment for patients with advanced ovarian cancer in whom the chance of optimal cytoreduction is low. The patients' overall quality of life and functional status improve after neoadjuvant chemotherapy.

Objective: The aim of this study was to assess the cost-effectiveness of serial squamous cell carcinoma antigen (SCC) monitoring in the clinical setting., Methods: All patients with squamous cell carcinoma of the cervix and SCC measurement from 1994 to 1999 were reviewed. The cost of the investigations, including blood tests, X rays, and computer tomography; and clinic visits were adjusted to 2001 dollars for all cases over the 6-year study period. The effectiveness measure was the number of cases detected by SCC monitoring before the onset of clinical symptoms or abnormal physical examination findings. Altered clinical management due to early detection was considered successful., Results: Two thousand eight hundred fifty-one SCC antigen assays were performed from 384 patients. An elevated pretreatment SCC level was associated with poorer cumulative survival over time (P < 0.05). Fifty-five patients had recurrences, with 10 local and 45 distant recurrences. SCC levels were elevated in 47 patients (85%). The median lead time was 7.8 months. The cost of finding 1 recurrence was US$4750. SCC monitoring does not alter clinical management and has no advantage over clinical examination in detecting local recurrence. Most of the recurrent diseases were detected too late for curative treatment. Only 1 patient, in whom the diagnosis could have been made by clinical examination without SCC monitoring, may have potentially benefited from exenteration., Conclusion: Posttreatment SCC monitoring is not cost-effective in the absence of curative treatment for distant spread of disease.

Objective: The objective was to describe the pattern of quality of life (QOL) over time and to assess the impact of age, symptoms, disease parameters, and treatment on the overall QOL., Methods: A longitudinal study on patients with newly diagnosed gynecologic cancer using individual patients as their own control was performed. The 33-item EORTC QLQ-C30(+3) was used as the QOL measure. Patients were assessed before treatment, after completion of treatment, and at 6, 12, and 24 months. Spearman's correlation analyses were performed. A mixed effect model was fitted to the data. Bonferroni pairwise comparisons were used to analyze the different variables., Results: One hundred forty-four women completed the study. Overall QOL improved after the completion of treatment but remained the same throughout the 2 years after treatment. The individual patient's QOL before treatment was insignificant while the impact of treatment on the individual patient was significant in determining QOL after treatment. There was a strong correlation for all time points in most factors, indicating that the global health status, functional scales, and symptom scales exhibit a dependent change over time. Relief in symptoms was associated with improvements in functional scales. The scores on overall QOL were lower for younger patients and for patients treated with chemotherapy than for patients treated with surgery., Conclusions: Strategies for supportive care need to focus on symptom management. Psychosocial interventions, to be effective, should include all patients and should aim to reduce the impact of treatment on the individual patient., (Copyright 2001 Academic Press.)

Objective: The objective was to describe the change in psychosocial state over time and to identify risk factors for maladjustment in gynecologic cancer survivors. Awareness of these issues is important for planning supportive care services for cancer patients., Methods: A longitudinal prospective study of patients with newly diagnosed gynecologic cancer using individual patients as their own control was performed. Patients were interviewed after confirmation of the diagnosis and were reassessed at 6 and 18 months after completion of treatment and with no evidence of recurrent disease. Psychological adjustment was measured by self-rating on self-esteem, outlook on life, self-role, and femininity. Neuroticism and anxiety were assessed using a neuroticism score and the Hamilton Anxiety Scale. Depressive symptoms were questioned directly. Social adjustment was assessed by changes in working capacity or work status, leisure activity, marital relationship, and sexual activity., Results: Seventy-four women participated. Adjustment problems did not occur in the majority of patients. Psychosocial adjustment was different for patients receiving different types of treatments. Improvement in feminism (P = 0.050) and neuroticism (P = 0.010) was observed for patients receiving chemotherapy and deterioration was observed in patients treated with surgery. Deterioration in neuroticism was associated with lower education level (P = 0.032). With religious belief, there was better family support and more significant improvement in social activity (P = 0.038)., Conclusion: Most patients adapted well. Patients at risk for psychosocial maladjustment include those who are treated surgically, less educated, and without religious belief., (Copyright 2001 Academic Press.)

Introduction: Female urethral adenocarcinoma is extremely rare and more than one tissue of origin has been suggested other than the Skene's gland. Immunohistochemistry with cytokeratins (CK) 7 and 20 is used to define the origin of the tumor., Case Report: A 72-year-old woman presented with a 2-cm polypoid tumor at the external urethral meatus and bleeding. Wide local excision and bilateral inguinal lymphadenectomy were performed. Postoperative convalescence was uneventful. It was a poorly differentiated mucinous adenocarcinoma without direct urothelial involvement. There were focal areas of intestinal metaplasia. The tumor cells were positive for CK 7 and 20 and negative for prostate-specific antigen., Discussion: This case provides supportive evidence that mucinous urethral adenocarcinoma may arise from malignant transformation of urethritis glandularis., (Copyright 2000 Academic Press.)

Objective: The aims of this study were to assess the cost/benefit ratio for interinstitution pathology consultation (IPC) and to identify the types of specimens with little or no risk of diagnostic error in order to reduce the cost., Methods: All gynecologic oncology referrals having IPC from 1993 to 1998 were reviewed. Each case was evaluated by comparing both the original and the consulted pathology reports. A discrepancy was major if it led to treatment alteration. A minor discrepancy was defined as differences without clinical consequences. Consultation error was determined by comparison with the final diagnosis and clinical data obtained from the records. The cost per review was adjusted to 1998 dollars for all cases over the 5-year study period. Statistical data were obtained by Fisher's exact test and Pearson's correlation test., Results: Five hundred sixty-nine pathology specimens from 498 patients were analyzed in this study. The major discrepancy rate was 6.5% and the minor discrepancy rate was 12.5%. Cytological specimens accounted for no major discrepancy and 13 minor discrepancies compared to 37 major and 58 minor discrepancies in histological specimens. The difference was statistically significant (P = 0.003). Consultation errors occurred in 5 cases with no alteration of clinical care. By excluding cervical and vaginal smears and cervical biopsy specimens in cases with clinically gross tumors, the cost can be reduced by 25% with no detriment to the clinical management., Conclusions: The types of specimens that do not need consultative pathology review include (1) cervical biopsy specimens in those patients with gross tumors and (2) cervical and vaginal smears., (Copyright 1999 Academic Press.)