Vision through cataracts

Contrast thresholds for a range of different spatial frequencies were compared with "acuity" tests for 10 subjects with uniocular senile cataract. The results indicate that the magnitude and extent of the intra-resolution limit abnormality vary dramatically in cataract subjects and that, for some subjects, vision is abnormal for objects of all sizes. This finding indicates that the present acuity evaluation of vision with cataracts is inadequate because, in some cases, it grossly overestimates the nature of the visual world of the cataract patient.     

X-Ray Structure and Crystal Lattice Interactions of the Taxol Side-Chain Methyl Ester

A colorless, parallelepiped crystal of methyl (2R,3S)-N-benzoyl-3-phenylisoserinate belonging to the space group P2_l with a = 5.414(4), b = 7.813(1), c = 17.802(7) , = 90.87(4)°, Z = 2, V = 752.9 ³, D _calc = 1.32 g cm^–3, and µ_calc = 1.02 cm^–1 was selected and the structure solved using direct methods. Refinement led to a final R = 0.079 for 819 [F _o 5(F_o)] reflections. Intermolecular hydrogen-bonding interactions are prevalent in the crystal lattice of this compound.     

Deoxy derivatives of butirosin A and 5"-amino-5"-deoxybutirosin A, aminoglycoside antibiotics resistant to bacterial 3'-phosphorylative enzymatic inactivation. Synthesis and NMR studies

3'-Deoxybutirosin A (4), 5"-amino-3', 5"-dideoxybutirosin A (6), and 5"-amino-4', 5"-dideoxybutirosin A (7) were prepared by deoxygenation of the appropriate hydroxyl in suitably protected derivatives of butirosin A, using sequentially trifluoromethylsulfonylation, displacement with benzenethiolate, and hydrogenolysis. The structures of the compounds were confirmed by NMR spectroscopy, using 13C NMR and 1H NMR at up to 600 MHz. The compounds are broad-spectrum antibiotics active against resistant microorganisms which inactivate butirosin and related aminoglycosides by 3'-phosphorylation.     

Degradation of ginseng saponins under mild acidic conditions

Ginseng saponins, ginsenosides Rg (1), Re and Rb (1), decomposed under mild acidic conditions to yield prosapogenins. The structures of the prosapogenins were investigated by (13)C-NMR spectroscopy and Rg (1)-prosapogenin II was shown to be a mixture of ginsenoside Rh (1), and its C-20 epimer, produced by hydrolysis followed by epimerization at C-20. Rg (1)-prosapogenin III, the other prosapogenin derived from ginsenoside Rg (1); was a C-25,26 hydrated derivative of Rg (1)-prosapogenin II. Re-prosapogenin II was identified as a mixture of ginsenoside Rg (2) and its C-20 epimer, and Re-prosapogenine III as a C-25,26 hydrated derivative of Re-prosapogenin II.     

Biological evaluation of Korean medicinal plants(III)

The extracts of sixty Korean plants were evaluated for their biological activities such as antitumor activities against Sarcoma 180, Leukemia SN-36 and Ehrlich ascites carcinoma, antimicrobial activities and behavioral observation in mice. The results are tabulated.     

The incidence of protrusio acetabuli in Marfan's syndrome and its relationship to bone mineral density

Twenty-one patients with Marfan's syndrome participated in a study to assess the incidence of and radiographic measurements significant for protrusio acetabuli. Our data show that the incidence of protrusio acetabuli in Marfan's syndrome is 31%. The most sensitive radiographic parameter to determine protrusio acetabuli is crossing of the acetabular line by the iliopectineal line. The presence of protrusio in Marfan's syndrome was not related to the bone mineral content of the hip and pelvis. Protrusio acetabuli in Marfan syndrome's also did not correlate with clinical symptoms. Based on our results, the presence of protrusio acetabuli alone is not an indication for early surgical intervention.     

Bioactive suture: a novel immunotherapy for head and neck cancer.

PURPOSE: We have proposed to characterize the mechanism through which bioactive surgical sutures generate a T(H)1 immune response and to define the immune-stimulating half-life of the sutures. EXPERIMENTAL DESIGN: Bioactive sutures of interferon gamma (IFNgamma), interleukin 2 (IL-2), anti-CD3/CD28, anti-CD3/CD28 + IL-2, or anti-CD3/CD28 + IFNgamma sutures were used to stimulate lymphocytes from normal donors and from head and neck cancer patients in vitro over a 24-day period. Cell supernatants were analyzed by ELISA, and T cells were phenotyped to characterize the immune response generated. Intracellular cytokine staining was performed to measure the expansion of flu-specific T cells. Electromobility shift assay and supershift assay were used to measure the intranuclear DNA binding activity of nuclear factor kappaB and its p65 subunit in T cells activated by sutures in the presence and absence of a proteasome inhibitor, MG-132. RESULTS: Anti-CD3/CD28, anti-CD3/CD28 + IL-2, or anti-CD3/CD28 + IFNgamma generated a prolonged T(H)1 immune response for 18 days in vitro. Anti-CD3/CD28 expanded flu-specific T cells. Activated T cells demonstrated enhanced CD40 ligand (CD40L) expression within 72 hours of stimulation, which stimulated other cells to secrete IL-12. Stimulated T cells demonstrated increased intranuclear expression of nuclear factor-kappaB, which was blocked by MG-132, and also reduced CD40L and IL-12 expression. CONCLUSIONS: This is the first report to demonstrate that bioactive surgical sutures can generate a prolonged T(H)1 immune response and expand flu-specific T cells. Bioactive sutures, which are primarily a T-cell stimulant, also stimulated other cells to secrete IL-12 and prolonged the immune response. Sutures may provide a novel in situ stimulating strategy for enhancing the immune system of cancer patients.     

Expression of placental growth factor gene in lung cancer.

Differences in the gene expression profiles in small cell lung cancers (SCLC) and non-small cell lung cancers (NSCLC) may explain their different clinical characteristics. The aims of this study were (1) to identify genes differentially expressed in SCLC and NSCLC using mRNA differential display, and (2) to determine the clinical relevance of such genes in lung cancer. RNA differential display using three SCLC and six non-SCLC cell lines was used to identify a differentially expressed gene. Differential expression of the gene was confirmed in additional lung cancer cell lines using RT-PCR. Immunohistochemical staining for the gene product was performed on paraffin-embedded tissue from lung cancer patients. We examined the relationship between the expression of the gene and clinical parameters, including disease stage, response to treatment and survival time. The placental growth factor (PGF) gene was identified as preferentially expressed in SCLC compared with NSCLC cell lines using mRNA differential display. Further analysis of 45 lung cancer cell lines using RT-PCR showed that the placental growth factor (PGF) gene was expressed in nine of 13 SCLC cell lines (69%) and five of 32 NSCLC cell lines (15.6%) (p < 0.001, Fisher's exact test). Immunohistochemistry using anti-PGF antibody on the paraffin blocks from lung cancer patients showed that PGF expression was significantly higher in SCLC than NSCLC tissue sections (32 vs. 5.6%, p = 0.041, Fisher's exact test). Expression of PGF protein did not correlate with disease stage, response to treatment or survival time in SCLC patients. The present study suggests there is higher expression of PGF in SCLC compared to NSCLC. It may be that higher expression of the angiogenic factor PGF contributes to differences between the progression of SCLC and NSCLC, especially in regard to the nature of SCLC metastasis.     

Cerebral atrophy in Cushing's disease

BACKGROUND: Cushing's disease causes significant pathological changes throughout the body as a result of elevated cortisol levels. Very few systematic investigations have focused on the morphologic effects of hypercortisolism on the central nervous system. The validity of using premature cerebral atrophy as a diagnostic tool for Cushing's disease remains unknown. METHODS: This study includes 63 patients with Cushing's disease who were evaluated and treated at the University of Virginia Medical Center. Radiologists randomly compared these individuals with age- and sex-matched controls in a blinded protocol, assessing the degree of cerebral atrophy on computed tomography and magnetic resonance scans. RESULTS: Patients with Cushing's disease showed significant premature atrophy when compared with controls. This trend continued after subdividing the groups based on age and duration of symptoms except in the following groups: age greater than 60, duration of symptoms less than 1 year, and symptoms lasting between 4-5 years. CONCLUSIONS: Excluding the three aforementioned groups, the hypercortisolemic state manifested in patients with Cushing's disease promotes the premature development of cerebral atrophy, which can be identified on routine radiologic imaging and may assist in the clinical diagnosis of the condition.     

Carbonic anhydrase IX expression, hypoxia, and prognosis in patients with uterine cervical carcinomas.

PURPOSE: Hypoxia is associated with adverse outcome for a number of solid tumors, including cervical carcinomas. Direct pO(2) measurement requires specialized equipment and expertise that is not generally available. Immunohistochemical measurement of intrinsic tissue markers of hypoxia is an alternative approach. Recent studies suggest that carbonic anhydrase IX (CA IX), which is regulated via hypoxia-inducible factor 1, is a useful intrinsic marker of tumor hypoxia. EXPERIMENTAL DESIGN: Biopsies were obtained from 110 patients with locally advanced cervical carcinoma treated with radiotherapy or chemoradiotherapy. Tissue sections were labeled using an immunofluorescence technique and CA IX expression in the viable tumor area measured using a semiautomated fluorescence image analysis technique. Results were compared with direct pO(2) values obtained using an Eppendorf probe and to patient outcome. Intratumoral heterogeneity of CA IX expression was examined in a subgroup of patient who underwent multiple biopsies. RESULTS: The median percentage of tumor area staining for CA IX was 3.56 (range, 0.01-58.85). CA IX staining did not correlate with the Eppendorf pO(2) measurements. Whereas the latter values were predictive of patient outcome, the CA IX levels were not. Measurement of CA IX in multiple biopsies indicated that intratumoral heterogeneity accounted for 41% of the total variance in the data set. CONCLUSIONS: In contrast to some recent studies, we did not find significant associations between CA IX expression and tumor pO(2) levels or patient outcome in locally advanced carcinomas of the cervix. Probable explanations relate to the problems of sampling error using single biopsies and the existence of biological factors other than hypoxia that influence CA IX levels.