Cataracts in cichlid fish

Bilateral cataracts were detected in a group of aquarium-raised tilapia (Sarotherodon mossambicus). Vision impairment was manifested as random swimming into objects, but the fish appeared to function normally otherwise. Most of the lens was opaque, with the outer extent of the cortex and subcapsular region remaining transparent. Skeletal abnormalities, ie, deformed fins, abnormal jaws, and curvature of the spine, were observed in affected individuals. Histologically, there was progressive degeneration of the cataractous portion as the affected fish matured. Preliminary breeding experiments indicated that the condition may be inherited.     

Subunit peptide cancer vaccines targeting activating mutations of the p21 ras proto-oncogene

BACKGROUND AND OBJECTIVES: Physicians in the 1920s and 1930s began to treat patients with chronic pain syndromes using regional anesthetic techniques for both temporary and permanent block of pain pathways. The founding of the American Society of Regional Anesthesia (ASRA) in 1923 provided a unique venue for the dissemination of information concerning regional anesthesia for both surgery and chronic pain management. METHODS: The growth of chronic pain management on a national basis was assessed by using the Quarterly Cumulative Index to the Medical Literature to trace the distribution of information on regional anesthesia. From the Minutes of Meeting of the American Society of Regional Anesthesia, presented papers and the discussion that followed were analyzed. RESULTS: Inquiries into regional anesthesia during the 1920s and 1930s predominantly dealt with technique. For the first time pain papers were listed under the regional anesthesia heading in the Index. The papers presented at ASRA meetings during the period helped develop the use of regional anesthesia for both chronic pain management and surgical anesthesia. CONCLUSIONS: The ASRA was instrumental in bringing together physicians interested in regional anesthesia and pain management. During the 1930s physician anesthetists came to predominate as the organization's officers and members and helped translate the work of the ASRA into a part of the knowledge required to be a specialist physician in anesthesia.     

Bond strengths and SEM evaluation of Clearfil Liner Bond 2

PURPOSE: To evaluate a dental adhesive system that uses a single conditioning/primer agent. MATERIALS AND METHODS: Twenty-five flat enamel and dentin bonding sites were prepared to 600 grit on human molar teeth. The Clearfil Liner Bond 2 adhesive system was used to bond Clearfil AP-X composite to both enamel and dentin. After 24 hours of water storage, shear bond strengths were determined using an Instron testing machine. Fifty V-shaped cavity preparations were prepared in human molar teeth with an enamel and cementum margin. Composite restorations were placed using the new adhesive system. The teeth were stored for 24 hours, thermocycled, stained with AgNO3 , sectioned and examined for microleakage. SEM examinations were also completed to evaluate the effects of the treatment steps on enamel and dentin surfaces. RESULTS: Mean shear bond strengths for the experimental adhesive to enamel and dentin were 28.2 +/- 4.9 and 19.4 +/- 3.1 MPa. A t-test revealed that the enamel bond strength was significantly greater (P<0.05) than the dentin strength. No marginal leakage was observed from the enamel margins of the restorations. Three restorations showed minimal leakage from the cementum margins. SEM examinations showed resin penetration into both the conditioned enamel and dentin surfaces. The adhesive system produced high bond strengths to both enamel and dentin, exhibited very minimal microleakage and was easy to use.     

Purification and characterization of a lipid-mobilizing factor associated with cachexia-inducing tumors in mice and humans

A scheme is described for the purification of a lipid-mobilizing factor from a cachexia-inducing murine tumor (MAC16) using a combination of ion exchange (Mono Q), exclusion (Superose), and hydrophobic (C8) chromatography. This process yields an active material with an apparent molecular weight of 24,000 with an overall purification of 3,500 from the tumor homogenate and representing 0.005% of the total protein present. The material tends to aggregate to high molecular mass, is acidic (pI < 4), and displays heterogeneity of charge as evidenced by a broad elution profile on ion exchange and exclusion chromatography and multiple peaks on hydrophobic columns. The purified material was heat and alkali (pH 10.4) labile and activity could be completely inhibited by sulfatase, suggesting that the negative charge could arise from sulfate residues. There was no evidence that the material possessed triglyceride lipase activity. Animals transplanted with the MAC16 tumor and with a delayed weight loss contained in their serum antibodies that recognized a M(r) 24,000 band on Western blots. This material copurified with the lipid-mobilizing factor. Such antibodies were not present in the serum of mice transplanted with the MAC13 tumor, which does not induce cachexia, suggesting that the antibodies were directed to the induction of cachexia rather than the tumor itself. Urine from patients with cancer cachexia also contained a lipid-mobilizing factor which adhered to DEAE-cellulose and gave an apparent M(r) of 24,000 by exclusion chromatography. Western blotting using serum from MAC16 tumor-bearing animals showed the presence of a band of M(r) 24,000 in such fractions, which was not detected using serum from mice bearing the MAC13 tumor. This band was not present in Western blots of urine from normal subjects. The fact that serum from mice bearing the MAC16 tumor can detect the human lipid-mobilizing activity suggests a high degree of structural similarity between the two and raises the possibility that cachexia in humans may be caused by the same species as in the mouse.     

Induction of Bax-alpha precedes apoptosis in a human B lymphoma cell line: potential role of the bcl-2 gene family in surface IgM-mediated apoptosis

The members of the bcl-2 gene family are major regulators of programmed cell death, but their role in sIg-triggered apoptosis remains unclear. Using sensitive and resistant variants of the human B cell line BL-41, we studied the expression of the bcl-2 gene family during surface IgM-mediated apoptosis. We found constitutive Bcl-2 and Bcl-x expression, which remained unaltered after sIg cross-linking, in both resistant and sensitive cells. This and other experiments suggest that constitutive expression of Bcl-2 or Bcl-x alone is not sufficient to protect from activation-induced cell death in B cells. We therefore investigated Bax-alpha, the death-promoting splice variant of Bax, and found strong induction of both mRNA and protein upon sIg stimulation in sensitive cells. However, resistant subclones showed only weak expression, which was not inducible by sIg cross-linking. We provide evidence that up-regulation of Bax-alpha and the resulting imbalance of Bcl-2/Bax might be a major regulator of sIg-mediated apoptosis. Additionally, we found strong constitutive expression of Bcl-xs, the death promoting variant of Bcl-x, in sensitive cells, whereas resistant cells showed only weak Bcl-xs expression. Thus, we observed a much stronger expression of the death-promoting proteins Bax-alpha (inducible) and Bcl-xs (constitutive) in sensitive cells than in resistant cells. We therefore propose a potential role of the novel bcl-2 gene family members bcl-x and bax in surface IgM-triggered apoptosis.     

Primary traits of Eysenck's P-E-N system: three- and five-factor solutions

The Eysenck Personality Profiler (EPP), a set of 21 scales measuring primary traits hypothesized to be definers of Neuroticism, Extraversion, and Psychoticism factors, was administered to 229 adults together with the Eysenck Personality Questionnaire--Revised (H. J. Eysenck & S. B. G. Eysenck, 1991) and the Revised NEO Personality Inventory (NEO-PI-R; P. T. Costa & R. R. McCrae, 1992b). Correlations of EPP scales with NEO-PI-R facet scales provided preliminary evidence supporting the convergent and discriminant validity of the EPP scales. However, varimax and targeted validimax factor analyses suggested that some EPP scales were misclassified and that EPP scales could better be understood in terms of the 5-factor model than the intended 3-factor model.     

Determinants of early and late results of combined valve operations and coronary artery bypass grafting

BACKGROUND: Factors determining the outcome of operative correction of valvular abnormalities combined with coronary artery bypass grafting are still incompletely defined. METHODS: Determinants of early and late (more than 90 days) deaths and event-free survival were studied for combined valve operations and coronary artery bypass grafting in 741 patients using multivariate analysis. RESULTS: Ninety-day survival probability was 89% (95% confidence interval, 87% to 92%). Preoperative risk factors for early death were age, female sex, renal failure, New York Heart Association class IV or V, and mitral insufficiency. The operative risk factor was the duration of aortic cross-clamping. Five- and 10-year survival probabilities were 74% (95% confidence interval, 71% to 78%) and 43% (95% confidence interval, 36% to 50%), respectively. Preoperative risk factors for late death were age, preoperative renal failure, New York Heart Association class IV or V, vessel disease, and nonsinus rhythm. Five- and 10-year event-free survival probabilities were 57% (95% confidence interval, 53% to 61%) and 23% (95% confidence interval, 17% to 28%), respectively. Preoperative risk factors for non-event-free survival were age, female sex, reduced left ventricular function, mitral regurgitation, and pacemaker rhythm. CONCLUSION: The demographic factors of age and female sex; the comorbid condition of renal failure; the cardiac conditions of advanced New York Heart Association class, left ventricular function, mitral regurgitation, vessel disease, and cardiac rhythm; and the operative condition of ischemia time are the most important predictors of clinical outcome after combined valve operations and coronary artery bypass grafting.     

Chemotherapy in non-small cell lung cancer: a review

Lung cancer, of which non-small cell carcinoma is the most common, has been a significant therapeutic challenge for decades and will remain so for decades to come. Despite its prevalence, progress in the management of non-small cell lung cancer has been relatively slow. This is in part due to the pessimism of most physicians treating this disease, which has resulted in a relatively lackadaisical attitude with regards to clinical trials when compared to other solid tumours like breast or colorectal cancers. Nevertheless, the past decade has seen significant progress, specifically with regards to the management of locally advanced disease. Chemotherapy, though shown to be biologically active in non-small cell lung cancer, is considered an ineffective palliative tool in the setting of metastatic disease due to its toxicities and the "less than encouraging" response rates generated by the cisplatin-based combination regimen which is generally considered to be the most active currently available. The advent of new active agents such as paclitaxel and vinorelbine which are potentially less toxic may change this view. Conversely, the response rate of locally advanced disease to chemotherapy is significantly higher and this has resulted in numerous multimodality trials of neoadjuvant chemotherapy prior to surgery and/or radiation. To date, a number of randomised trials have shown that this approach can result in significant survival benefit for patients with locally advanced disease. An alternative approach makes use of the potential synergism between certain chemotherapeutic agents (such as cisplatin) and radiation when used concurrently. However, data on concurrent chemoradiotherapy in locally advanced disease have been largely based on single-arm studies and are inconclusive. Three randomised trials on concurrent chemoradiotherapy have been shown benefit for the use of combined modality in locally advanced disease. Hence, treatment of locally advanced disease should include chemotherapy as part of the combined modality approach. However, the optimal sequencing of these modalities would require well-designed randomised trials to determine.     

Altered retinoblastoma and p53 protein status in non-small cell carcinoma of the lung: potential synergistic effects on prognosis

Routinely processed pathological specimens from 119 patients with stage I and II adenocarcinomas or squamous cell carcinomas were examined by immunohistochemical analysis for altered retinoblastoma (RB) and/or p53 protein expression. Absent RB nuclear staining (RB-) indicating loss of RB function occurred in 19 (16%) of the cases studied, whereas expression of a putative mutant p53 nuclear protein (p53(+)) was found in 54 (45%) of the tumors. The median survival was 39 versus 12 months for patients with RB+ and RB- tumors, respectively (P = 0.05 by log rank analysis). Similarly, the median survival was 41 months for patients whose tumors had no expression of mutant p53 (p53(-)) compared with 24 months for individuals with p53 (+) tumors (P = 0.01). These differences in survival, however, were not statistically significant by multivariate analysis. Nevertheless, individuals with RB-/p53(+) tumors had a significantly shorter median survival (12 months) than those with RB+/p53(-) tumors (41 months), as determined by both log rank and multivariate analyses (P = 0.005 and 0.03, respectively). In addition, 66 large cell carcinomas from all stages were examined. Again, a more significant difference in survival (48 versus 8 months) was found between patients with RB+/p53(-) versus RB-/p53(+) tumors (P = 0. 006). These results suggest that RB and p53 status might be used synergistically as prognostic factors in a subset of non-small cell lung carcinomas.