Evidence for an oscillatory signature in atmospheric neutrino oscillations.

Muon neutrino disappearance probability as a function of neutrino flight length L over neutrino energy E was studied. A dip in the L/E distribution was observed in the data, as predicted from the sinusoidal flavor transition probability of neutrino oscillation. The observed L/E distribution constrained nu(micro)<-->nu(tau) neutrino oscillation parameters; 1.9x10(-3)0.90 at 90% confidence level.

Limits on the neutrino magnetic moment using 1496 days of Super-Kamiokande-I solar neutrino data.

A search for a nonzero neutrino magnetic moment has been conducted using 1496 live days of solar neutrino data from Super-Kamiokande-I. Specifically, we searched for distortions to the energy spectrum of recoil electrons arising from magnetic scattering due to a nonzero neutrino magnetic moment. In the absence of a clear signal, we found micro(nu)

Search for nu(e) from the sun at Super-Kamiokande-I.

We present the results of a search for low energy nu(e) from the Sun using 1496 days of data from Super-Kamiokande-I. We observe no significant excess of events and set an upper limit for the conversion probability to nu(e) of the 8B solar neutrino. This conversion limit is 0.8% (90% C.L.) of the standard solar model's neutrino flux for total energy=8-20 MeV. We also set a flux limit for monochromatic nu(e) for E(nu(e))=10-17 MeV.

Search for supernova relic neutrinos at Super-Kamiokande.

A search for the relic neutrinos from all past core-collapse supernovae was conducted using 1496 days of data from the Super-Kamiokande detector. This analysis looked for electron-type antineutrinos that had produced a positron with an energy greater than 18 MeV. In the absence of a signal, 90% C.L. upper limits on the total flux were set for several theoretical models; these limits ranged from 20 to 130 macro nu(e) cm(-2) s(-1). Additionally, an upper bound of 1.2 macro nu(e) cm(-2) s(-1) was set for the supernova relic neutrino flux in the energy region E(nu)>19.3 MeV.

Indications of neutrino oscillation in a 250 km long-baseline experiment.

The K2K experiment observes indications of neutrino oscillation: a reduction of nu(mu) flux together with a distortion of the energy spectrum. Fifty-six beam neutrino events are observed in Super-Kamiokande (SK), 250 km from the neutrino production point, with an expectation of 80.1(+6.2)(-5.4). Twenty-nine one ring mu-like events are used to reconstruct the neutrino energy spectrum, which is better matched to the expected spectrum with neutrino oscillation than without. The probability that the observed flux at SK is explained by statistical fluctuation without neutrino oscillation is less than 1%.

Molecular analysis of inhibin A and activin A subunit gene loci in epithelial ovarian cancer.

Inhibin A (alpha-betaA) and activin A (betaA-betaA) are biochemically similar proteins that generally have opposite biologic functions. For example, while inhibin (alpha subunit) is proposed to be a tumor suppressor in some types of ovarian cancer, activin appears to stimulate tumor development. Previous reports suggest that a loss of alpha inhibin subunit expression and elevated serum activin levels are associated with human epithelial ovarian cancer (EOC). Our objective was to examine the alpha inhibin subunit gene locus on chromosome 2q for evidence of loss of heterozygosity (LOH) in cases of EOC and to correlate these results with serum activin A levels measured in the same patients. Ovarian tumor and matched healthy tissue samples were collected from 22 women with EOC. DNA was extracted and subjected to PCR analysis using 10 primers, seven from chromosome 2q (alpha inhibin subunit locus) and, as a control, three from chromosome 7p (inhibin/activin betaA subunit). In addition, each patient had a preoperative serum activin A measurement using an ELISA assay. One (1/22) case of EOC demonstrated LOH for one microsatellite marker at the alpha inhibin gene locus. Thirty-six percent (8/22) of patients had an activin A level that was increased above the normal range. We conclude that loss of heterozygosity at the inhibin/activin alpha subunit locus is not frequently associated with EOC. More direct molecular analyses of the inhibin and activin genes are warranted to rule out mutations in cases of epithelial ovarian cancer.

Caelyx/Doxil for the treatment of metastatic ovarian and breast cancer.

Caelyx/Doxil is a novel pegylated liposomal formulation of the first-generation anthracycline, doxorubicin. The pharmacokinetics of this polyethylene-glycol-coated liposome are characterized by a reduced volume of distribution, a long intravascular circulating half-life and slow plasma clearance compared with free doxorubicin. This, coupled with a small vesicular size, uniquely promotes the localization of Caelyx/Doxil at tumor sites and explains its altered toxicity profile. The FDA and EMEA have approved its use for the treatment of AIDS-related Kaposi's sarcoma and, more recently, for recurrent epithelial ovarian cancer (EOC). Numerous investigations have focused on its use in the treatment of metastatic breast cancer, as well as recurrent squamous cell cervical carcinoma, soft tissue sarcoma, squamous head and neck cancers, prostate cancers and malignant gliomas. Ongoing clinical studies of combination regimens incorporating Caelyx/Doxil will further clarify its role in the treatment of advanced solid tumors.

Solar 8B and hep neutrino measurements from 1258 days of Super-Kamiokande data.

Solar neutrino measurements from 1258 days of data from the Super-Kamiokande detector are presented. The measurements are based on recoil electrons in the energy range 5.0-20.0 MeV. The measured solar neutrino flux is 2.32+/-0.03(stat)+0.08-0.07(syst)x10(6) cm(-2) x s(-1), which is 45.1+/-0.5(stat)+1.6-1.4(syst)% of that predicted by the BP2000 SSM. The day vs night flux asymmetry (Phi(n)-Phi(d))/Phi(average) is 0.033+/-0.022(stat)+0.013-0.012(syst). The recoil electron energy spectrum is consistent with no spectral distortion. For the hep neutrino flux, we set a 90% C.L. upper limit of 40x10(3) cm(-2) x s(-1), which is 4.3 times the BP2000 SSM prediction.

Constraints on neutrino oscillations using 1258 days of Super-Kamiokande solar neutrino data.

We report the result of a search for neutrino oscillations using precise measurements of the recoil electron energy spectrum and zenith angle variations of the solar neutrino flux from 1258 days of neutrino-electron scattering data in Super-Kamiokande. The absence of significant zenith angle variation and spectrum distortion places strong constraints on neutrino mixing and mass difference in a flux-independent way. Using the Super-Kamiokande flux measurement in addition, two allowed regions at large mixing are found.

Tau neutrinos favored over sterile neutrinos in atmospheric muon neutrino oscillations.

The previously published atmospheric neutrino data did not distinguish whether muon neutrinos were oscillating into tau neutrinos or sterile neutrinos, as both hypotheses fit the data. Using data recorded in 1100 live days of the Super-Kamiokande detector, we use three complementary data samples to study the difference in zenith angle distribution due to neutral currents and matter effects. We find no evidence favoring sterile neutrinos, and reject the hypothesis at the 99% confidence level. On the other hand, we find that oscillation between muon and tau neutrinos suffices to explain all the results in hand.

Secretion of activin A in recurrent epithelial ovarian carcinoma.

OBJECTIVES: Activin A is a dimeric protein, composed of two beta-A subunits, that belongs to the TGF-beta family of growth factors. Most primary epithelial ovarian tumors (96%) synthesize and secrete activin protein in vitro and preliminary studies show that serum levels of activin are frequently elevated in women with epithelial ovarian cancer. Our objectives were to expand on studies of serum activin A levels in women with epithelial ovarian cancer and to determine whether levels of activin A correlate with the clinical course of disease. METHOD: Preoperative serum activin A levels were measured in 41 patients with epithelial ovarian cancer. In addition, serum activin A levels were measured in all available postoperative samples from the subset of these patients (n = 26) who had an elevated preoperative serum activin A level. Medical record information was used to compare each patient's serum levels of activin A to the clinical course of disease. RESULTS: Seventy-two percent of the stage III and IV patients (26/36), and none (0/5) of the stage I patients, had an elevated preoperative serum activin level. In postoperative samples, activin A levels were increased with persistent or recurrent (n = 9) stage III or IV ovarian cancer. Activin A levels dropped postoperatively and remained at or below the control level in patients in remission. CONCLUSION: Serum activin A levels correlate with recurrent or persistent disease in patients with epithelial ovarian cancer.

Ovarian cancer.

Ovarian cancer is the leading cause of death in women with pelvic malignancies. Because of the multiple histologic types of malignancy that can arise within the ovary, accurate diagnosis and staging is critical for optimal patient care. The current standard of proper surgical management followed by combination chemotherapy is outlined. In addition, risk factors, screening, prognostic factors, and the approach to the relapsed patient is discussed.

Absence of estrogen and progesterone receptors in glassy cell carcinoma of the cervix.

OBJECTIVE: To evaluate the estrogen and progesterone receptor status of glassy cell carcinoma of the cervix to assess the possible implications of hormone replacement therapy in these patients. METHODS: The estrogen and progesterone receptor status of 13 glassy cell carcinomas was evaluated by immunohistochemistry using commercial monoclonal antibodies and a streptavidin-biotin detection system. RESULTS: No immunohistochemically detectable estrogen or progesterone receptor protein was present in tumor cells, although both receptors were identified in the adjacent normal cervical tissue. CONCLUSION: The absence of estrogen and progesterone receptors in glassy cell carcinoma suggests that this tumor would not be hormonally responsive and that these patients can be safely treated with hormone replacement therapy. Further studies are indicated to confirm this observation.

S-Phase fraction, p53, and HER-2/neu status as predictors of nodal metastasis in early vulvar cancer.

OBJECTIVE: Our aim was to determine the value of the S-phase fraction, p53, and HER-2/neu status as predictors of inguinal nodal metastasis in early vulvar cancer. METHODS: The charts of 100 consecutive patients with invasive squamous cell cancer of the vulva were reviewed and a cohort of patients with clinical stage I or II disease treated primarily with radical surgery and inguinal node dissection was identified. Within this cohort, all node-positive patients were matched with node-negative controls by depth of invasion. Tumor from the 13 node-positive patients and 26 controls was then analyzed by flow cytometry and immunohistochemistry. RESULTS: The median value of the S-phase fraction was higher in tumor from patients with inguinal nodal metastasis (median, 18.2; 25th-75th percentile: 13.9-28.3) than in node-negative patients (median, 8.9; 25th-75th percentile: 5.4-15.6) (P = 0.01). The presence of the HER-2/neu immunopositivity was also found to be associated with nodal metastasis (OR 4.05, 95% CI 1.0-16.6), but we found no evidence that DNA index or the presence of p53 immunopositivity was associated with nodal metastasis. CONCLUSION: Early vulvar cancer patients with inguinal node metastasis have a significantly higher S-phase fraction and are more likely to have HER-2/neu immunopositivity when compared to those without nodal metastasis.

Multiple immunoreactive inhibin proteins in serum from postmenopausal women with epithelial ovarian cancer.

Inhibin is an ovarian protein previously shown, using a nonspecific assay, to be elevated in serum of women with ovarian cancer. However, inhibin is secreted in multiple biochemical forms, including dimeric inhibin A and B and alpha inhibin precursors (pro-alphaC), each of which can now be specifically measured. We have examined the secretion of inhibin B and pro-alphaC inhibin in serum from women with epithelial ovarian cancer (EOC) for the first time, and have compared these analytes to inhibin A and total inhibin (inhibin A + B + pro-alphaC) as potential serum markers for EOC in postmenopausal women. Of all the immunoreactive inhibin proteins studied, the best serum marker was pro-alphaC, with 22% of women with EOC having levels that exceeded the range of values in women without EOC. Since CA 125 and pro-alphaC levels were not significantly correlated, combination of these markers resulted in 87% of EOC cases having elevated preoperative serum levels, a 9% increase over CA 125 alone. These data suggest that alpha inhibin secretion, especially pro-alphaC, may be useful in addition to CA 125 as a serum marker for EOC in postmenopausal women.

Synchronous endometrioid tumors of the ovary and endometrium. A clinicopathologic study of 22 cases.

OBJECTIVE: To analyze a group of 22 patients with synchronous endometrioid tumors of the ovary and endometrium. STUDY DESIGN: A retrospective chart review was undertaken and information collected on patient age, parity, tumor grade and stage, presence of coexisting endometriosis and survival. Flow cytometry was determined from archival samples of the endometrial and ovarian tumors. RESULTS: The mean age at diagnosis was 52.8 years (range 36-71); mean parity was 1.05. With regard to the endometrial component, 68.2% were grade 1, 63.6% were stage I and, by flow cytometry, 62.5% were aneuploid. With regard to the ovarian lesions, 68.2% were grade 1, 68.2% were stage I, and 71.4% were aneuploid by flow cytometry. Twelve (54.5%) of 22 patients had pathologic evidence of coexisting endometriosis. Overall, three-year survival was 75%. All 11 patients with stage I disease at both sites were alive, without disease, at a mean follow-up of 34.9 months. CONCLUSION: Patients with synchronous endometrioid tumors of the endometrium and ovary are generally younger than reported for either endometrial adenocarcinomas or ovarian epithelial adenocarcinomas. They tend to be low grade and early stage and are frequently associated with endometriosis. Our data suggest that the survival of patients with synchronous primaries correlates with the stage of the individual tumors and that a second, synchronous primary does not adversely affect prognosis.

Malignant mixed mesodermal tumors of the ovary.

OBJECTIVE: To review the experience at Women & Infants Hospital and Hartford Hospital of patients with malignant mixed mesodermal tumors of the ovary, and to review the pertinent literature. METHODS: Fourteen cases of malignant mixed mesodermal tumors of the ovary at the two hospitals over a 5-year period were identified through their tumor registries. Demographic data, pathology, treatment, and survival rates were reviewed. RESULTS: The median survival of the patients in our series was 7 months, with 64% dead of disease in 1 year. A review of the pertinent literature indicated median survivals of 6-12 months, with more than 70% of the patients dead of disease at 1 year, despite treatment. CONCLUSION: Further investigation is needed to determine the proper management for malignant mixed mesodermal tumors of the ovary. Meanwhile, current treatment strategies should recognize the present therapeutic limitations, so as not to diminish any further the quality of life for women with this malignancy.