Weak-link Josephson Junctions Made from Topological Crystalline Insulators.

We report on the fabrication of Josephson junctions using the topological crystalline insulator Pb_{0.5}Sn_{0.5}Te as the weak link. The properties of these junctions are characterized and compared to those fabricated with weak links of PbTe, a similar material yet topologically trivial. Most striking is the difference in the ac Josephson effect: junctions made with Pb_{0.5}Sn_{0.5}Te exhibit a rich subharmonic structure consistent with a skewed current-phase relation. This structure is absent in junctions fabricated from PbTe. A discussion is given on the origin of this effect as an indication of novel behavior arising from the topologically nontrivial surface state.

Vulvar intraepithelial neoplasia (VIN 2/3): comparing clinical outcomes and evaluating risk factors for recurrence.

OBJECTIVE: To evaluate demographic and clinical characteristics associated with the development of vulvar intraepithelial neoplasia (VIN 2/3), and factors associated with recurrence. METHODS: A retrospective chart review of 303 patients with VIN 2/3 evaluated at a single institution between 1993 and 2011 was performed. Medical records were reviewed for demographic information, risk factors, treatment type, pathologic diagnosis, and recurrence/outcome information. RESULTS: Median age at diagnosis was 47 years (range 14-87). 40% of patients reported current tobacco use and 26% reported previous use. Primary treatment included excision (n=176, 59%), laser ablation (n=40, 13%), imiquimod (n=22, 7.4%), excision with laser (n=24, 8.1%), excision with imiquimod (n=10, 3.4%), and laser with imiquimod (n=3, 1.0%). 92 patients (62.6%) were noted to have positive margins, which was associated with larger tumor size (p=0.004). 87 patients (28.7%) developed recurrent disease, which was associated with smoking (p<0.001), larger lesion size (p=0.016), and positive margins (p=0.005). On univariate analysis, higher rates of recurrence were associated with laser ablation (45.0%) compared with excision (26%) or imiquimod (13.6%) (p=0.018). However, on multivariate analysis of recurrence-free survival (RFS) these therapies were equivalent when used individually, but the use of excision plus laser had an adverse impact on RFS (p<0.001). 7 patients (2.3%) recurred with invasive disease a median of 109 months (range 12-327) from initial VIN 2/3 diagnosis. CONCLUSIONS: This large cohort of women with VIN 2/3 further delineates the demographic and clinical factors associated with VIN 2/3. High rates of recurrence were noted and found to be associated with smoking, larger lesion size, and positive margins. While higher rates of recurrence were found among those treated with laser ablation, it was not inferior with respect to RFS when used alone, but the use of laser with excision was associated with decreased RFS. Our findings provide hypothesis-generating material for further research in the management of VIN2/3.

"Giant" arachnoid granulations just like CSF?: NOT!!

"Giant" AGs (>1 cm) are uncommon and can be misdiagnosed as venous sinus pathology such as a neoplasm or thrombosis. Seventeen patients with a total of 19 venous sinus AGs of >1 cm were collected from contributing authors. MR imaging was available for all AGs; CT, for 5/19; and DSA, for 7/19. Intra-AG fluid was compared with CSF in subarachnoid spaces. Nonfluid AG tissue was compared with gray matter. Diagnosis was based on imaging findings. Fluid within giant AGs did not follow CSF signal intensity on at least 1 MR image in nearly 80% (15/19) of AGs. Nine of these 15 AGs had CSF-incongruent signal intensity on ≥2 MR images. CSF-incongruent signal intensity was seen in 8/8 AGs on FLAIR, 7/10 on precontrast T1WI, 13/19 on T2WI, and 8/14 on contrast-enhanced T1WI. Nonfluid signal intensity was present in 18/19 AGs and varied from absent/hypointense (intra-AG flow voids) to gray matter isointense (stromal tissue).

Cluster intradermal DNA vaccination rapidly induces E7-specific CD8+ T-cell immune responses leading to therapeutic antitumor effects.

Intradermal administration of DNA vaccines via a gene gun represents a feasible strategy to deliver DNA directly into the professional antigen-presenting cells (APCs) in the skin. This helps to facilitate the enhancement of DNA vaccine potency via strategies that modify the properties of APCs. We have previously demonstrated that DNA vaccines encoding human papillomavirus type 16 (HPV-16) E7 antigen linked to calreticulin (CRT) are capable of enhancing the E7-specific CD+ T-cell immune responses and antitumor effects against E7-expressing tumors. It has also been shown that cluster (short-interval) DNA vaccination regimen generates potent immune responses in a minimal time frame. Thus, in the current study we hypothesize that the cluster intradermal CRT/E7 DNA vaccination will generate significant antigen-specific CD8+ T-cell infiltrates in E7-expressing tumors in tumor-bearing mice, leading to an increase in apoptotic tumor cell death. We found that cluster intradermal CRT/E7 DNA vaccination is capable of rapidly generating a significant number of E7-specific CD8+ T cells, resulting in significant therapeutic antitumor effects in vaccinated mice. We also observed that cluster intradermal CRT/E7 DNA vaccination in the presence of tumor generates significantly higher E7-specific CD8+ T-cell immune responses in the systemic circulation as well as in the tumors. In addition, this vaccination regimen also led to significantly lower levels of CD4+Foxp3+ T-regulatory cells and myeloid suppressor cells compared to vaccination with CRT DNA in peripheral blood and in tumor-infiltrating lymphocytes, resulting in an increase in apoptotic tumor cell death. Thus, our study has significant potential for future clinical translation.

Characterization of HLA-A2-restricted HPV-16 E7-specific CD8(+) T-cell immune responses induced by DNA vaccines in HLA-A2 transgenic mice.

We have recently demonstrated that linkage of DNA-encoding calreticulin to DNA-encoding human papillomavirus-16 E7 antigen strongly enhances the efficacy of DNA vaccines against E7-expressing tumors in animal models. In this study, as a prelude to clinical translation, we characterized the ability of DNA-encoding calreticulin linked to DNA-encoding E7 antigen to generate HLA-A2-restricted E7-specific CD8(+) T-cell responses in HLA-A2 (AAD) transgenic mice, as well as antitumor effects against an E7(+) HLA-A2(+) tumor cell line, TC-1/A2. Our results show that while vaccination with CRT/E7 DNA generates strong H-2D(b)-restricted E7 (amino acid (aa)49-57)-specific CD8(+) T-cell immune responses in both C57BL/6 and HLA-A2 (AAD) transgenic mice, no such responses were generated to HLA-A2-restricted epitopes in either type of mouse. In contrast, vaccination with DNA-encoding calreticulin linked to DNA encoding a mutant version of E7 with a deleted aa49-57 epitope leads to the generation of an HLA-A2-restricted E7 (aa11-20)-specific CTL response in HLA-A2 (AAD) transgenic mice. More importantly, vaccination with CRT/mtE7 (del aa49-57) DNA protects against a lethal challenge with TC-1/A2 tumor cells in HLA-A2 (AAD) transgenic mice. Furthermore, our in vitro studies demonstrate that the presence of the E7 (aa49-57) epitope does not suppress presentation of the HLA-A2-restricted E7 (aa11-20) epitope through MHC class I molecules. Thus, the predominant E7 aa49-57-specific CD8+ T-cell immune response in HLA-A2 transgenic mice vaccinated with CRT/E7 is likely due to preferred expansion of E7 aa49-57-specific CD8(+) T cells in vaccinated mice. These results highlight the importance of epitope immunodominance in the evaluation of immune responses in HLA-A2 (AAD) transgenic mice.

A combination of DNA vaccines targeting human papillomavirus type 16 E6 and E7 generates potent antitumor effects.

Human papillomavirus (HPV) infects large numbers of women worldwide and is present in more than 99% of all cervical cancers. HPV E6 and E7 are two viral oncoproteins that are consistently expressed in HPV infections and HPV-associated malignancies. We have previously developed DNA vaccines encoding calreticulin (CRT) linked either to HPV type 16 (HPV-16) E6 or to HPV-16 E7, both of which generated significant antitumor effects against E6- and E7-expressing tumors. In this study, we demonstrate that simultaneous vaccination of C57BL/6 mice or HLA-A2 transgenic mice with both CRT/E6 and CRT/E7 DNA vaccines generates significant E6- and E7-specific T-cell immune responses in vaccinated mice. Furthermore, combined vaccination with both CRT/E6 and CRT/E7 DNA generates significantly better therapeutic antitumor effects against HPV E6- and E7-expressing tumors than vaccination with either CRT/E6 DNA or CRT/E7 DNA alone. Our data suggest that it may be desirable to combine DNA vaccines targeting E6 with DNA vaccines targeting E7 to develop effective immunotherapeutic strategies for control of HPV infection and HPV-associated lesions in a clinical setting.

Polynitroxylated starch/TPL attenuates cachexia and increased epithelial permeability associated with TNBS colitis.

Free radicals play an important role in the initiation and progression of inflammatory bowel disease (IBD). Therefore, the reduction or elimination of adverse oxidant effects can provide novel therapy for IBD. Here, the antioxidant capacity and protective effects of a new class of chemically modified hetastarch (polynitroxyl starch, or PNS) plus 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl (Tempol or TPL) (PNS/TPL) were assessed in a model of colitis. The superoxide scavenging capacity of PNS/TPL-that is, the inhibition of the reduction of cytochrome c in the presence of xanthine/xanthine oxidase (X/XO)-was evaluated in vitro. The effects of PNS/TPL on X/XO-induced neutrophil endothelial adhesion in vitro were investigated. Also, this study tested the protection produced by PNS/TPL in a mouse model of trinitrobenzene sulfonic acid (TNBS)-induced colitis. PNS/TPL was given intravenously immediately before (< 30 min) and intraperitoneally at 24 and 72 hr after TNBS induction. The body weight and survival rate of the mice were checked daily. Colonic mucosal damage was assessed on the 7th day by measuring intestinal permeability to Evans blue (EB) in vivo. The ability of PNS to reoxidize bioreduced TPL was documented by whole-body electron paramagnetic resonance (EPR) detection. We found that PNS or TPL exhibits superoxide dismutase (SOD)-like activity, with approximately 2% of SOD activity occurring on a molar basis. The endothelial-neutrophil adherence induced by X/XO was significantly inhibited by PNS/TPL but not by TPL alone. PNS/TPL protected against cachexia and mortality, both usually induced by TNBS. Epithelial permeability was increased significantly in TNBS mice but was ameliorated by the administration of PNS/TPL. In conclusion, PNS/TPL may be beneficial in the treatment or prevention of IBD through its antioxidant effects, which inhibit oxidant-mediated leukocyte adhesion and injury to endothelial cells.

Infrared ellipsometry characterization of porous silicon bragg reflectors.

We investigate porous silicon Bragg reflectors in a nondestructive manner using variable angle-of-incidence infrared spectroscopic ellipsometry. In addition to the thickness, volume porosity, inhomogeneity, and optical anisotropy, properties of the solid content of the porous material are investigated in terms of dielectric function and surface chemistry. The material was found to have positive birefringence. The high sensitivity of the technique is employed to detect and identify infrared resonant absorptions related to different Si-H as well as Si-O-Si vibrational modes. The average electrical resistivity of the solid content of the porous material is determined to be 0.03 Omega cm, which is larger than the corresponding bulk value of 0.019 Omega cm. Furthermore the average carrier concentration in the porous material shows a decrease from 6.2 x 10(18) cm(-3) to 4 x 10(18) cm(-3).

Ovarian tumors of low malignant potential.

Ovarian tumors of low malignant potential (LMP) differ from epithelial ovarian carcinoma in etiology, molecular biology, and prognosis. LMP tumors are not precursor lesions to ovarian carcinoma. Treatment is primarily surgical. Women found to have an ovarian tumor of LMP should undergo removal of the involved adnexa; surgical staging; and cytoreductive surgery. Women in the reproductive years should be given the option of conservative surgery, preserving the contralateral adnexa and uterus. There is no proven benefit to adjuvant chemotherapy or radiotherapy after primary surgery. In most cases, the diagnosis of an ovarian tumor of LMP conveys good prognosis, with excellent long-term survival.

Resuscitative effects of polynitroxylated alphaalpha-cross-linked hemoglobin following severe hemorrhage in the rat.

alphaalpha-Cross-linked hemoglobin (alphaalphaHb) is an example of a hemoglobin-based oxygen carrier (HBOC) with significant cardiovascular activity. This may compromise the safety and efficacy of this HBOC by causing systemic hypertension and reducing blood flow to some organs. The present work is based on the hypothesis that incorporating antioxidant activity into an HBOC in the form of a covalently attached nitroxide may prevent these effects. We have tested this hypothesis by adding antioxidant activity to alphaalphaHb with 2,2,6,6-tetramethyl-piperidinyl-1-oxyl (Tempo) to create polynitroxylated alphaalphaHb (PN-alphaalphaHb). The new compound PN-alphaalphaHb acts as an antioxidant in our in vitro and in vivo assays. In this study urethane-anesthetized rats were hemorrhaged to a mean arterial pressure (MAP) of 35-40 mmHg and maintained for 30 min. Animals were resuscitated with solutions of (1) 10% PN-alphaalphaHb (43 mmHg), (2) 10% alphaalphaHb (43 mmHg), (3) 7.5% albumin (43 mmHg), (4) 300% Ringers lactate (RL), and (5) 0. 9% normal saline equal to the shed blood volume (SBV). Hemodynamics and regional blood circulation was measured at baseline, following hemorrhage, and at 30 and 60 min postresuscitation using a radioactive microsphere technique. Base deficit (BD) was measured at baseline, following hemorrhage, and at 60 min following resuscitative fluid infusion. Finally survival was determined as the time following resuscitation until secession of heart rhythm. Saline and 300% RL resuscitation did not improve BD, systemic hemodynamics, or regional blood circulation. PN-alphaalphaHb, alphaalphaHb, and albumin significantly improved these parameters, however, only PN-alphaalphaHb and alphaalphaHb improved survival. PN-alphaalphaHb was found to be less hypertensive than alphaalphaHb due to blunted increases in both cardiac output and systemic vascular resistance. This study demonstrates that, by using alphaalphaHb as a scaffold for polynitroxylation, improvement in vasoactivity and resuscitative efficacy may be possible. In conclusion, the addition of antioxidant activity in the form of polynitroxylation of a low molecular weight Hb (alphaalphaHb) may create a safe and efficacious resuscitative fluid.

Polynitroxyl-albumin (PNA) plus tempol attenuate lung capillary leak elicited by prolonged intestinal ischemia and reperfusion(1).

Stable nitroxyl radicals (nitroxides) are potential antioxidant drugs, and we have previously reported that linking nitroxide to biological macromolecules can improve therapeutic activity in at least two ways. First, polynitroxylated compounds such as polynitroxyl human serum albumin (PNA) are a novel class of high molecular weight, extracellular antioxidants. Second, compounds such as PNA can prolong the half-life of free (unbound, low molecular weight) nitroxides such as 4-hydroxy-2,2,6, 6-tetramethylpiperidine-N-oxyl (Tempol) in vivo. Unlike PNA, Tempol can readily access the intracellular compartment. Thus PNA can act alone in the extracellular compartment, or in concert with Tempol, to provide additional antioxidant protection within cells. In this study, we compared the abilities of PNA, Tempol, and the combination of PNA + Tempol to prevent lung microvascular injury secondary to prolonged gut ischemia (I, 120 min) and reperfusion (R, 20 min) in the rat. Pulmonary capillary filtration coefficient (K(f,c)) and lung neutrophil retention (tissue myeloperoxidase activity, MPO) were measured in normal, isolated rat lungs perfused with blood harvested from I/R rats. Blood donor rats were treated with drug during ischemia. Gut I/R resulted in a marked increase in pulmonary capillary coefficient and lung MPO. PNA + Tempol, but not PNA alone or Tempol alone, at the doses used, prevented the development of lung leak. None of the treatments had an effect on lung neutrophil retention. Anti-inflammatory therapeutic activity appeared to correlate with blood Tempol level: in the presence of PNA, blood Tempol levels were maintained in the 50-100 microM range vs. essentially undetectable levels shortly after Tempol was administered alone. In this model of lung injury secondary to prolonged gut I/R, lung capillary leak was prevented when the membrane-permeable compound Tempol was maintained in its active, free radical state by PNA.

Cervical neoplasia and repeated positivity of human papillomavirus infection in human immunodeficiency virus-seropositive and -seronegative women.

Increased risk for cervical intraepithelial neoplasia (CIN) in human immunodeficiency virus (HIV)-infected women may be explained by repeated positivity of human papillomavirus (HPV) infection facilitated by HIV infection and related immunosuppression. As part of a longitudinal study with semiannual examinations, 268 women in Baltimore, Maryland (of whom 184 were HIV+), provided 1,426 cervicovaginal lavage specimens tested for HPV DNA by a polymerase chain reaction-based assay between 1992 and 1998. HPV positivity and time to HPV clearance according to HIV serostatus and CD4+ cell count were compared using models for correlated binary data and survival analysis. Of the 187 participants who had at least one positive measurement, the probability of subsequent HPV positivity among HIV- women and HIV+ women with CD4+ > or =200 and <200 cells/microl was 47.5%, 78.7%, and 92.9% (p < 0.001). Within-women HPV results were correlated (i.e., clustered) in each group (p < 0.01). Compared with HIV-participants, the relative incidence of HPV clearance was 0.29 and 0.10 among HIV+ women with CD4+ > or =200 and <200 cells/microl (p < 0.001). At the end of follow-up, 11 women had biopsy-confirmed CIN. The association of HIV and CIN (p = 0.014) was fully explained by repeated HPV positivity induced by HIV infection (p = 0.648). Reversal of immunosuppression following potent antiretroviral therapy must be expected to have a dramatic impact on HIV-related CIN.

Reproducibility of the histopathological classification of vulvar squamous carcinoma and intraepithelial neoplasia.

Invasive vulvar carcinoma has been shown to be etiologically heterogeneous on the basis of pathological, virological, and epidemiological criteria. Human papillomavirus-related invasive vulvar carcinoma has basaloid or warty morphology and has adjacent basaloid or warty intraepithelial neoplasia. Invasive carcinoma unrelated to human papillomavirus is a keratinizing squamous carcinoma that may have adjacent squamous hyperplasia. We provided to 3 pathologists for their review and pathological diagnoses stained tissue sections from 95 patients with vulvar carcinoma. The reproducibility for grading individual categories of intraepithelial lesions was only fair (kappa values of 0.31-0.43). The reproducibility was better (moderate to good; kappa values of 0.58-0.59) for grading individual categories of invasive carcinomas. The agreements improved when the basaloid and warty categories were combined. Good agreement was achieved (kappa values of 0.55-0.79) in distinguishing human papillomavirus-related lesions from those unrelated to human papillomavirus; all three reviewers agreed on this classification for 67% of the cases. The intrareviewer agreement was of the same order as interreviewer agreement. Difficulties in differentiating between some lesions (e.g., a warty carcinoma with little atypia from a well- to moderately differentiated keratinizing squamous carcinoma) and concurrent occurrence of human papillomavirus-related lesions and those lesions unrelated to human papillomavirus in a patient may account for some of the discrepancies in the histopathological diagnoses of vulvar carcinoma.

In vivo topical EPR spectroscopy and imaging of nitroxide free radicals and polynitroxyl-albumin.

Piperidine nitroxides have considerable clinical potential, both as antioxidant therapeutic compounds and contrast agents in magnetic resonance imaging. However, their development has thus far been limited by their rapid bioreduction in vivo. Recently, it was reported that polynitroxyl albumin (PNA) can reverse the bioreduction of the reduced 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (Tempol) in the rat heart, enabling the performance of high resolution EPR imaging for prolonged time (Kuppusamy et al., Biochemistry 35, 7051-7057 (1996)). In this report, the efficacy of PNA in maintaining Tempol concentrations in vivo in mice was demonstrated, using L-band (1.25 GHz) EPR spectroscopy and imaging. The EPR signal of intravenous Tempol had a half-life of 1.0+/-0.2 min and became undetectable within 6 min. Subcutaneous Tempol, however, decayed at a slower rate (half-life, 5.0+/-0.5 min) suggesting that Tempol had been bioreduced to the corresponding hydroxylamine form, Tempol-H. Subcutaneously injected PNA restored 20% of the Tempol signal in the vicinity of the PNA deposit. In vivo topical EPR imaging demonstrated that the Tempol signal was restored at the site of PNA injection, but not at locations remote from the PNA injection site. The ability of PNA to maintain Tempol in its paramagnetic state in vivo should enable a wide range of therapeutic and diagnostic applications of piperidinyl nitroxides.

Human papillomavirus-specific serologic response in vulvar neoplasia.

Epidemiological and virological evidence suggests that invasive squamous cell carcinoma (SCC) of the vulva is etiologically heterogeneous and that basaloid or warty SCC (BWSCC) and vulvar intraepithelial neoplasia (VIN) are linked to human papillomavirus (HPV) infections while keratinizing SCC (KSCC) is a non-HPV-associated malignancy. In the present study, HPV-specific antibodies in sera of patients with BWSCC, VIN, and KSCC and of controls were examined by ELISA for antibodies reactive to HPV-16 virus-like particles (VLP) and in radioimmunoprecipitation assays for antibodies to HPV-16 E6 and E7 proteins expressed by in vitro transcription and translation. The prevalences of antibodies to HPV-16 VLPs were significantly higher in HPV-associated VIN (59.1%) and BWSCC (50.0%) than in KSCC (22.2%) and controls (18.2%). Antibodies to E6 and E7 proteins were more prevalent in BWSCC than in any other groups. Prevalence of serum antibodies to any one of the antigen preparations was significantly higher in BWSCC (64.3%) and VIN (59.1%) than in KSCC (27.8%) and controls (22.2%). Also, sera with high antibody titers were found more frequently in BWSCC and VIN cases than in controls. These data provide immunological evidence in support of the observation that VIN and BWSCC, but not KSCC, are associated with HPV infections.

Electron paramagnetic resonance imaging of rat heart with nitroxide and polynitroxyl-albumin.

Electron paramagnetic resonance (EPR) imaging utilizing stable nitroxyl radicals is a promising technique for measuring free radical distribution, metabolism, and tissue oxygenation in organs and tissues [Kuppusamy, P., Chzhan, M., Vij, K., Shteynbuk, M., Lefer, D. J., Giannella, E., & Zweier, J. L. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 3388-3392]. However, the technique has been limited by the rapid reduction of nitroxide in vivo to its hydroxylamine derivative, a diamagnetic, EPR-inactive species. In this report a novel, polynitroxylated derivative of human serum albumin is shown to be capable of reoxidizing the hydroxylamine back to nitroxide in vivo. Polynitroxyl-albumin (PNA) is shown to be effective in maintaining the signal intensity of the nitroxide 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL or TPL) in the ischemic isolated rat heart, allowing the acquisition of high-resolution three-dimensional (3D) EPR images of the heart throughout a prolonged 2.5 h period of global cardiac ischemia. In serial transverse sections of the 3D image, TPL intensity maps of the heart showed cardiac structure with submillimeter resolution. TPL intensities in coronary arteries and myocardium showed that nitroxide concentration decreases with increasing distance from large blood vessels. These results demonstrate that EPR imaging in vivo is possible using nitroxides in conjunction with PNA. In addition to its utility in the emerging technology of EPR imaging, the greatly prolonged half-life of TPL observed in the presence of PNA may facilitate the therapeutic application of nitroxides in a variety of disease processes.

Heterogeneous etiology of squamous carcinoma of the vulva.

OBJECTIVE: To correlate various previously identified risk factors, different histologic types, and the presence of human papillomaviruses (HPV) in squamous vulvar carcinomas and intraepithelial precursor lesions. METHODS: Cases of squamous vulvar carcinomas and intraepithelial precursor lesions from a case-control study were analyzed by histologic type, the presence of HPV, and HPV type. These findings were correlated with demographic and interview data. RESULTS: Significant differences (P < .001) in the prevalence of HPV DNA were noted between the following: 1) patients with high-grade vulvar intraepithelial neoplasia (VIN) (48 of 54 [88.9%]), 2) different types of squamous carcinomas, designated basaloid and warty carcinomas (18 of 21 [85.7%]), and 3) keratinizing squamous carcinoma (three of 48 [6.3%]). When the risk factor profiles for basaloid or warty carcinoma and keratinizing squamous carcinoma were compared, it was found that basaloid and warty carcinoma was significantly associated with the classical cervical cancer risk factors (lifetime number of sexual partners, age at first intercourse, abnormal Papanicolaou smears, venereal warts, low socioeconomic status, and cigarette smoking) whereas keratinizing squamous carcinoma was less strongly linked to these factors and in some cases not at all. The risk profile for VIN was similar to that of basaloid and warty carcinoma (with respect to sexual and reproductive history and smoking), although effects were weaker for some factors. CONCLUSION: The results of this study further support the view that vulvar carcinoma has two different etiologies, one related to HPV infection and one that is not.

Management of epithelial ovarian tumors of low malignant potential.

The distinct pathologic and biologic nature of ovarian tumors of low malignant potential (LMP) has been officially recognized by FIGO and the World Health Organization. LMP tumors may comprise 10% of ovarian neoplasms; they occur at a mean age of 40 years. Pregnancy, breast-feeding, and the use of oral contraceptives are protective against the development of tumors of LMP. A history of infertility and use of infertility drugs appear to increase the risk of these tumors. No association with hereditary ovarian cancer syndromes has been reported. The survival associated with these tumors is 99% at mean follow-up of 7 years for patients with stage I disease, and 92% for those with stage II and II disease. Retrospectively, more patients appear to have died from complications associated with adjuvant therapy than from progressive disease. The recommended treatment is surgical, consisting of total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymph node biopsies, peritoneal washings, and tumor debulking. In young patients with early-stage disease, conservative surgery, preserving the uterus and contralateral ovary, is acceptable. A role has not yet been established for adjuvant therapy, whether radiotherapy or chemotherapy. Laboratory investigations have not demonstrated that these tumors represent an intermediate step between benign ovarian tumors and carcinoma nor have they identified that small subset of tumors with aggressive clinical behavior. We should perhaps consider tumors of LMP in the same light as "benign" proliferative gynecologic conditions, such as endometriosis and leiomyomata.

Aircraft (ER-2) laser infrared absorption spectrometer (ALIAS) for in-situ stratospheric measurements of HCI, N(2)O, CH(4), NO(2), and HNO(3).

The Aircraft Laser Infrared Absorption Spectrometer (ALIAS) instrument is a high-resolution (0.0003 cm-(1)) scanning tunable-diode-laser spectrometer designed, tested, and flown more than 30 times on the National Aeronautics and Space Administration's high-altitude ER-2 aircraft in the Airborne Arctic Stratospheric Expedition of 1991-1992. Using long-path infrared laser absorption spectroscopy to detect optical absorptions as small as 10-(5), ALIAS provides fast, continuous in-situ measurements of key atmospheric gases, with gas detection sensitivities of tens of parts in 10(12). With four lasers and detectors in a single liquid-nitrogen Dewar, simultaneous measurements of HCI, NO(2), HNO(3), CH(4), and N(2)O are made using laser sources at 3.4-8 µm, injected into a 1-m-long, 80-pass Herriott cell.

The behavior of serous tumors of low malignant potential: are they ever malignant?

Although the literature describing the clinicopathologic features of serous borderline or low malignant potential (LMP) tumors of the ovary is extensive, the behavior of these neoplasms is not well understood. While some studies indicate a 30 to 40% mortality for advanced stage tumors, it is not clear whether this poor outcome is related to "benign" complications of the disease, such as bowel obstruction from adhesions, or to development of carcinomatosis from malignant transformation. In an effort to determine more clearly the cause of death of patients with serous LMP tumors and to assess the malignant potential of these tumors, defined by progression to invasive serous carcinoma, we reviewed 22 series, totalling 953 patients. Analysis of these studies reveals that for patients with stage I tumors, survival is 99%. For advanced stage disease, survival is 92%. Advanced-stage tumors associated with so-called invasive implants were excluded from this analysis because they were considered invasive serous carcinomas at the time of diagnosis rather than noninvasive LMP tumors. Various causes of death in patients with advanced-stage tumors include complications of the disease, complications of therapy, and, rarely, malignant transformation. Our review of 953 cases disclosed only seven (0.7%) tumors that appeared to have undergone malignant transformation, resulting in death from intraabdominal carcinomatosis. Because the rate of malignant transformation is exceedingly low and because classifying these tumors as malignant often leads to unnecessary treatment, we believe that the term low malignant potential or borderline tumor is not justified.(ABSTRACT TRUNCATED AT 250 WORDS)