Flight simulator evaluation of a novel flight instrument display to minimize the risks of spatial disorientation

BACKGROUND: Melanomas arising from the mucous membranes lining the respiratory, digestive, and genitourinary tracts are rare. Women are more commonly affected than are men, mainly because there is no male counterpart for vulvovaginal lesions. The mainstay of therapy is surgery, with little current use of adjuvant modalities in primary therapy. These lesions usually are advanced at initial presentation; consequently, the prognosis is poor, with 5-year survivals well below 50% in most series. METHODS: One hundred and nineteen patients with primary mucosal melanoma were reviewed. They represented 1.1% of the 10,393 melanoma patients seen at Duke University between 1970 and 1995. All data were obtained from the patients' clinic charts and computerized databases. RESULTS: There were 43 tumors arising from the head and neck region, 46 from the urogenital tract, and 30 from the anorectum. A female predominance was observed, with a female-to-male ratio of 2.7:1. All but five of the patients underwent resection with curative intent. Regional or distant metastases, or both, were encountered in 36 patients at the time of presentation. In patients with head and neck and urogenital tumors, local recurrences accounted for most of the treatment failures, whereas systemic recurrences were more common with tumors arising in the anorectum. The age and gender of the patient, anatomic site of origin of the tumor, clinical stage at initial presentation, and ulceration of the primary all clearly affected prognosis. Overall, the probabilities of being alive 1, 5, and 10 years after diagnosis were 80%, 29%, and 15%, respectively. CONCLUSIONS: Widely accepted classification systems are needed so that results from separate institutions can be compared adequately. Multi-institutional trials could help in delineating standardized therapeutic protocols and in establishing the potential roles of emerging modalities in the treatment of this subtype of melanoma.     

On the origin of substance P and glutamic acid decarboxylase (GAD) in the substantia nigra

Knife cuts in the frontal plane separating the anterior part of the caudate-putamen from the globus pallidus resulted in marked decreases in substances P levels in the reticular part of the substantia nigra. More caudal knife cuts were required in order to effect maximal decreases in nigral glutamic acid decarboxylase levels. Thus, there is a clear anatomical dissociation between the striatal neurons which project to the reticular part of the substantia nigra and which contain SP, and the more caudally located GAD-containing striatal and pallidal neurons, all of which travel through the globus pallidus on their way to the substantia nigra.     

Regulated Co-translational ubiquitination of apolipoprotein B100. A new paradigm for proteasomal degradation of a secretory protein

Presentation of a wild-type secretory protein, apolipoprotein B100 (apoB), to the cytosol for ubiquitin-proteasome proteolysis has been observed in HepG2 cells. A currently accepted model for proteasomal degradation of secretory proteins is retrograde translocation of the substrate polypeptides from the lumen of endoplasmic reticulum (ER) back to the cytosol. In this report, we present evidence that newly synthesized apoB becomes exposed to the cytosol and targeted to the proteasomes in a co-translational manner. Thus, after protein translation was synchronized with puromycin, partially synthesized apoB polypeptides were found to be conjugated to ubiquitin. The magnitude of co-translational ubiquitination and subsequent degradation of apoB was increased when cells were pretreated with either herbimycin A to induce cytosolic Hsp70 or with an inhibitor of microsomal triglyceride transfer protein; both treatments impede translocation of nascent apoB across the ER membrane. These treatments also decreased secretion of apoB and increased its degradation via the ubiquitin-proteasome pathway. We suggest that translocation arrest with subsequent co-translational exposure to the cytosol provides an alternative model to explain how mammalian secretory proteins can overcome topological segregation by the ER membrane and undergo degradation by the ubiquitin-proteasome pathway.     

Applicability of light absorbance as a measure of organic carbon in humic lake water

The results of statistical analysis showed that turbidity measurements at 436, 530 and 620 nm and COD data of unfiltered samples from Tjeukemeer. The Netherlands, between 1977 and 1980 were yearly significantly (P < 0.005) linearly correlated. However, the correlation coefficients and the slopes of these correlations varied irregularly.Between 1970 and 1980, the light absorbances at 250 (E₂₅₀) and 365 nm (E₃₆₅) were yearly significantly (P < 0.0005) linearly correlated with the COD of filtered samples. Apart from between 1970 and 1973, possibly due to sand-suction, this correlation of E₂₅₀ did not change from year to year and was independent of sampling stations. Therefore, E₂₅₀ is a suitable estimate of the concentration of dissolved organic carbon in eutrophic and humic Tjeukemeer water. The correlation found is almost identical to those reported for oligotrophic and humic Finnish lakes and Black Sea water.     

A descriptive study of U.S. OSHA penalties and inspection frequency for musculoskeletal disorders in the workplace

In an attempt to examine in vivo the early metabolic consequences of severe acute head injury, 1H MRS was performed in four patients from 8 to 25 h (mean 15 h) following trauma. In three of these patients, decompressive surgery was performed 4-5 h prior to the MRS. High levels of lactate (area of lactate peak >50% of the mean areas of the NAA, choline-containing, and creatine-containing compound peaks) were found at 8 h posttrauma in the one patient who was not operated on and at 10 h posttrauma in one of the patients who underwent surgery. In the other two postoperative patients, at 18 and 25 h after trauma, lactate levels were found to be low (lactate peak <20% of the mean area of the other three peaks). In the one patient who had a follow-up at 6 days and who had the largest initial lactate levels, these remained high. These findings suggest that high levels of lactate may not be an inevitable consequence of severe head injury and that similar MRS studies should be performed on each individual patient before therapies to reduce lactate are considered. There appeared to be no correlation between the relative amounts of lactate and outcome.     

Time course of chronic diazepam effects on the auditory evoked potential of the rat

We have analyzed 30 human tumor specimens (two breast, six lung, and 21 ovarian carcinomas and one malignant melanoma) for the expression of the transporter associated with antigen processing, TAP-1. Cell suspensions judged to contain negligible contamination with non-tumor cells were tested for reactivity with the antibody directed to TAP-1 in Western blot. According to these results all lysates prepared from the tumor samples contained the protein, but with considerable quantitative variations. Tumors exposed in vitro for a short time to IFN-gamma and TNF-alpha had elevated TAP-1 levels in 12 out of 30 experiments. In accordance with previous results, the tumor cell populations were heterogeneous with regard to MHC class I expression, as analyzed by indirect immunofluorescence on viable cell suspensions. Short term in vitro treatment with IFN-gamma and TNF-alpha elevated MHC class I expression in several tumors. In several mixed cultures, cytokine treated tumor cells induced cytotoxic activity in autologous or allogeneic lymphocyte populations. In vitro treatment with IFN-gamma and TNF-alpha upregulated thus the expression of MHC class I and TAP-1 in a fraction of the tumor samples. However the potentiation of the capacity to interact with T cells induced by the cytokines was not always parallel with the changes in these two parameters. It is therefore likely that the cytokine treatment induced additional changes in the tumors which contributed to their capacity to elicit the T cell response.     

Syntheses of tetra- and hexadeuterated octadecenoates

A study of the metabolism in man of cis and trans monoenoic acids required the synthesis of tetra- and hexadeutero-9-octadecenoates. Preparation of methyl 9-octadecenoate-8,8,11,11-d4 (90 mol % deuterium) by the Wittig reaction was accompanied by deuterium scattering with sodium methoxide as the base but not with alkylithium. Scattering occurred in both the aldehyde and phosphorane moieties only when the aldehyde contained deuterium on the alpha carbon. Methyl 9-octadecenoate-8,8,13,13,14-14-d6 (98 mol % deuterium) was also prepared by the Wittig reaction. The deuterated octadecenoates were formed principally as cis isomers. The trans isomers were produced by nitrogen oxide isomerization and separation on a silver ion column.