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Breast tumors often show profound sensitivity to exogenous oxidative stress. Investigational agent 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F 203) induces aryl hydrocarbon receptor (AhR)-mediated DNA damage in certain breast cancer cells. Since AhR agonists often elevate intracellular oxidative stress, we hypothesize that 5F 203 increases reactive oxygen species (ROS) to induce DNA damage, which thwarts breast cancer cell growth. We found that 5F 203 induced single-strand break formation. 5F 203 enhanced oxidative DNA damage that was specific to breast cancer cells sensitive to its cytotoxic actions, as it did not increase oxidative DNA damage or ROS formation in nontumorigenic MCF-10A breast epithelial cells. In contrast, AhR agonist and procarcinogen benzo[a]pyrene and its metabolite, 1,6-benzo[a]pyrene quinone, induced oxidative DNA damage and ROS formation, respectively, in MCF-10A cells. In sensitive breast cancer cells, 5F 203 activated ROS-responsive kinases: c-Jun-N-terminal kinase (JNK) and p38 mitogen activated protein kinase (p38). AhR antagonists (alpha-naphthoflavone, CH223191) or antioxidants (N-acetyl-l-cysteine, EUK-134) attenuated 5F 203-mediated JNK and p38 activation, depending on the cell type. Pharmacological inhibition of AhR, JNK, or p38 attenuated 5F 203-mediated increases in intracellular ROS, apoptosis, and single-strand break formation. 5F 203 induced the expression of cytoglobin, an oxidative stress-responsive gene and a putative tumor suppressor, which was diminished with AhR, JNK, or p38 inhibition. Additionally, 5F 203-mediated increases in ROS production and cytoglobin were suppressed in AHR100 cells (AhR ligand-unresponsive MCF-7 breast cancer cells). Our data demonstrate 5F 203 induces ROS-mediated DNA damage at least in part via AhR, JNK, or p38 activation and modulates the expression of oxidative stress-responsive genes such as cytoglobin to confer its anticancer action.

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OBJECTIVE: To determine the predictive ability of the Jahrsdoerfer grading scale score in congenital aural atresia surgery. DESIGN: Retrospective review of medical records. SETTING: Tertiary referral center. PATIENTS: One hundred eight patients with aural atresia. MAIN OUTCOME MEASURES: Demographic data, preoperative Jahrsdoerfer score, and postoperative audiometric outcomes were reviewed. One month postoperative, 4-tone pure-tone averages and speech reception thresholds were compared between ears scoring 6 or lower, 7, and 8 or higher on the Jahrsdoerfer grading scale. The percentage of ears with a speech reception threshold of 30 dB hearing level or lower for each group was calculated and compared between groups. Individual anatomical structures on the Jahrsdoerfer grading scale were evaluated for their ability to predict postoperative audiometric success. RESULTS: Of 116 ears evaluated, postoperative 4-tone pure-tone averages and speech reception thresholds were significantly poorer in ears scoring 6 or less on the Jahrsdoerfer grading scale compared with ears scoring 7 or higher (P < .02, t test). Ears scoring 6 or less had a 45% chance of achieving a postoperative speech reception threshold of 30 dB hearing level or lower, while ears scoring 7 or higher had an 89% chance (P < .01, chi(2) test). Lack of middle ear aeration was the only anatomical factor predictive of poor audiometric outcome. CONCLUSIONS: Compared with patients with a Jahrsdoerfer score of 6 or lower, patients with a score of 7 or higher had significantly better hearing postoperatively. Middle ear aeration may be the most important predictor of postoperative hearing outcome. The Jahrsdoerfer grading scale is an invaluable tool in the preoperative evaluation of patients with congenital aural atresia.

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OBJECTIVE: To determine whether women's global self-assessment of their knowledge about hormone replacement therapy (HRT) corresponds to their performance on an explicit knowledge test about HRT and to measure associations among knowledge, personal characteristics, decision conflict, and intention to use HRT. DESIGN: Preintervention telephone survey of 156 women enrolled in a randomized, placebo-controlled trial of HRT decision aids. RESULTS: The mean rating of menopause knowledge, on a scale from 1 to 10, with 10 indicating being "extremely knowledgeable," was 5.6 (range = 0-10) and of HRT was 4.2 (range = 0-9). The mean summary score for the explicit HRT knowledge test, on a 16-point scale, was 7.8 (range = 0-15). After adjustment for demographic characteristics and exposure to a provider conversation, higher income, white race, and the provider discussion were significant correlates of knowledge. Explicit knowledge was positively correlated with self-assessed menopause knowledge and HRT knowledge (Spearman's correlation coefficient = 0.39 and 0.52, respectively; p < 0.0001). Greater knowledge was not associated with intention to use HRT 1 year later. Women who had greater knowledge reported less conflict about the HRT decision (Spearman's correlation coefficient = -0.32; p < 0.0001). CONCLUSIONS: A global question about level of knowledge is an effective clinical tool for identifying patients who are in need of additional education about HRT and menopause in this managed care population. Increased knowledge may decrease women's conflict about the HRT decision. Having had a previous conversation about menopause with a primary care provider is associated with greater knowledge about HRT.

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Two patients infected with human immunodeficiency virus (HIV) presented with persistent, large, and painful oral ulcers. Results of cultures and examination of a biopsy specimen were negative for infection and malignancy. Major aphthous-like ulcers should be considered in the differential diagnosis of oral ulcers in the HIV-infected patient.

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Despite use as constitutive protein standards to quantify mRNA, data are limited regarding alteration of cyclophilin or glyceraldehyde-3-phosphate dehydrogenase (G3PDH) in hypertension or angiotensin converting enzyme (ACE) inhibitor treatment. We assessed these standards in 6 month old Wistar-Kyoto rats (WKY, n = 16), compared to age-matched spontaneously hypertensive rats (SHR, n = 14). Additional SHR (n = 8) had received enalapril for 3 to 4 months at evaluation. Left ventricular (LV) and kidney RNA was extracted for dot blot cyclophilin and G3PDH cDNA hybridization. Cyclophilin and G3PDH mRNA densitometries were expressed as a ratio. Cyclophilin/G3PDH for the WKY, untreated SHR, and enalapril SHR were 1.56 +/- 0.33, 1.45 +/- 0.42, and 1.49 +/- 0.51, respectively, for the LV, and 1.52 +/- 0.09, 1.43 +/- 0.22, and 1.38 +/- 0.22, respectively, for the kidney. Differences were not significant. Relative expression of cyclophilin/G3PDH was unaffected by genetic SHR hypertension, or long term enalapril. Thus, either constitutive mRNA may be confidently used to index structural or functional protein responses, at the transcriptional level, in the SHR.

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High-resolution infrared spectra of sunspot umbrae have been recorded with the 1-meter Fourier transform spectrometer on Kitt Peak. The spectra contain a very large number of water absorption features originating on the sun. These lines have been assigned to the pure rotation and the vibration-rotation transitions of hot water by comparison with high-temperature laboratory emission spectra.

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OBJECTIVE: To determine the perceived needs of perimenopausal women regarding the management of menopause and the resource needs of the clinicians who treat them. SETTING: A large staff and group network model health maintenance organization (HMO) in New England. PARTICIPANTS: A random sample of 790 perimenopausal women aged 45-60 years who were members of the HMO in 1991, and a random sample of 180 clinicians in internal medicine, family practice, and obstetrics/gynecology practicing in the HMO during 1991. METHOD: Mailed surveys of women and clinicians were designed to assess possible needs and attitudes that could lead to the improvement of care for menopausal women. The chi-square test was used to determine differences in perceived needs and satisfaction levels among women with differences in self-reported menopausal status. The Kruskal-Wallis one-way analysis of variance and the Mann-Whitney U test were used in the clinician survey to test for differences among specialties and between genders. RESULTS: The key findings include that: 1) most (81%) of the women wanted to see a woman clinician, 2) many (50%) were interested in a menopause support group, 3) 30% reported that their care for menopause had been fair to poor, 4) only 55% of the primary care specialists (including internal medicine and family practice) reported high confidence in their abilities to treat menopause, compared with 68% of the obstetric/gynecology clinicians, and 5) 56% of the clinicians surveyed said that support from the HMO to their practices for the treatment of menopause was fair to poor. CONCLUSIONS: There is an opportunity for better care for perimenopausal women as reported by two sources, HMO clinicians and members. To provide this care, clinicians may need explicit guidelines as well as administrative supports such as educational materials and specialty access. Since the capability for menopausal care from clinicians in obstetrics/gynecology is perceived to be higher than that from primary care clinicians, an opportunity for cross-specialty collaboration and training may exist.

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Solar carbon monoxide spectra indicate the existence of a cool (less than 4000 kelvin) component to the solar chromosphere coexisting with the hot, bright gas at 6000 to 7000 kelvin. However, both the existence and the location of the cool component have been controversial. New high-resolution spectra show that carbon monoxide goes into emission just beyond the limb, allowing it to be probed without photospheric contamination. The cool component has temperatures as low as 3000 to 3500 kelvin and appears to cover 50 to 85 percent of the quiet solar surface. There is a steep temperature rise to normal chromospheric temperatures at a height of 900 to 1100 kilometers. Large horizontal velocities are seen, suggesting that the cool component is maintained by the supersonic adiabatic expansion of upwelling gas in overshooting granules.

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The pulmonary isozyme of rabbit angiotensin-converting enzyme (ACE) is encoded by an mRNA of about 5 kb. cDNA clones corresponding to different parts of this mRNA have been isolated and the complete nucleotide sequences of both the coding and non-coding regions of the mRNA have been determined. The encoded protein has 1309 residues with a 33 amino acids-long signal peptide at the amino terminus and a potential membrane-anchoring domain near the carboxyl terminus. There is a strong sequence homology between two regions of the rabbit cDNA and between the rabbit, human, and mouse cDNAs. Comparison of the nucleotide sequences of the 3' untranslated regions of rabbit pulmonary and testicular ACE cDNAs revealed that the testicular cDNA is nested within the pulmonary cDNA at the 3' end. A rabbit genomic clone encompassing this region was isolated and partially sequenced. It was shown that the gene contains two potential polyadenylation sites 628 bp apart within one exon. Northern analyses with an appropriate oligonucleotide probe confirmed that the proximal polyadenylation site is used exclusively for terminating the testicular mRNA whereas the distal one is used exclusively for the pulmonary mRNA. These results demonstrated that the transcription of the two mRNAs encoding the two ACE isozymes not only initiates at two alternative tissue-specific sites which are 5.7 kb apart but the mRNAs also get polyadenylated at two alternative sites which are 628 bp apart.

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Angiotensin-converting enzyme (ACE) is present in endothelial and epithelial cells of various tissues as well as in the circulating plasma. The structural relationship between the cellular and the secreted forms of ACE and the pathways to their biosynthesis have not been determined as yet mainly because of the unavailability of a natural cell line expressing ACE in tissue culture. To circumvent this problem we have permanently transfected a mouse epithelial line with an expression vector containing the recently cloned rabbit testicular ACE cDNA. Clonal derivatives of this line secreted large quantities of enzymatically active ACE. When these cells were cultured in serum-free medium, the only detectable protein in the culture medium was ACE. It has been suggested that a hydrophobic domain near the carboxyl terminus of the enzyme anchors it to the plasma membrane. To test this hypothesis we established cell lines expressing a truncated form of the active enzyme which is missing the putative anchoring domain. Pulse-chase experiments showed that the truncated ACE was secreted from the cells much faster than the native enzyme. Moreover, the secreted form of the native enzyme had a lower molecular weight than the corresponding cellular form. These results are consistent with the hypothesis that the hydrophobic domain is instrumental in keeping the enzyme cell-bound, and secretion is achieved physiologically by removal of this domain from the enzyme by a specific proteolytic cleavage.

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Primary care physicians and nurse practitioners are the initial casefinders of mental health problems and major providers of mental health treatment in the United States. However, past studies suggest that such primary care providers often neither recognize nor correctly diagnose their patients' mental disorders. This study compared an HMO's primary providers' direct assessments of the current emotional disorders of patients just seen for an outpatient medical visit with those of mental health professionals assessing the same patients with the Structured Clinical Interview for DSM III R (SCID). Using the SCID-derived diagnosis as the standard, the primary providers failed to recognize almost two-thirds of their patients with a current mental disorder. Although confident in their assessments, the primary providers were also able to correctly identify very few of the specific mental disorders most prevalent in primary medical care practice; they identified only one of the seven depressions, three of the 18 anxiety disorders, and none of the four alcohol or drug abuse disorders. Reasons for these diagnostic discrepancies, comparisons with past studies, and training to improve primary providers' diagnosis of mental disorders in their patients are discussed.

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Active Cavity Radiometer Irradiance Monitor (ACRIM) solar constant measurements from 1980 to 1986 are compared with ground-based, irradiance spectrophotometry of selected Fraunhofer lines. Both data sets were identically sampled and smoothed with an 85-day running mean, and the ACRIM total solar irradiance (S) values were corrected for sunspot blocking (S(c)). The strength of the mid-photospheric manganese 539.4-nanometer line tracks almost perfectly with ACRIM S(e), Other spectral features formed high in the photosphere and chromosphere also track well. These comparisons independently confirm the variability in the ACRIM S(e), signal, indicate that the source of irradiance is faculae, and indicate that ACRIM S(e), follows the 11-year activity cycle.

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Previous computer modeling of radiographic heel effect has shown that a simple model can give an accurate representation of heel effect for flat anode surfaces. This paper details the extension of this model to allow curved anode surfaces. A fixed-anode x-ray tube with a demountable anode was constructed and used to test the predictions of the computational model at 25 kVp using stainless-steel anodes. The computer model was also used to estimate the magnitude of the heel effect for a tungsten anode at 60 kVp. This work allows determination of the effect of anode curvature, which is an inherent feature of certain recently proposed tube designs for scanning slit radiography.

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A 32-year-old man was hospitalized 23 times in 11 years because of attacks of Mollaret's meningitis. Colchicine (0.6 mg twice daily) was administered for 15 months but failed to decrease the severity or the frequency of attacks. The prophylactic efficacy of drugs in Mollaret's meningitis is difficult to assess because episodes are unpredictable and remissions occur spontaneously. There remains no established therapy for Mollaret's meningitis.

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