Polyamine analogue induction of programmed cell death in human lung tumor cells

The naturally occurring polyamines putrescine, spermidine, and spermine are required for cell growth. Based on this requirement, several polyamine analogues that interfere with polyamine function and metabolism have been synthesized as antineoplastic agents. The symmetrically substituted N1,N12-bis(ethyl)spermine (BESpm), and unsymmetrically substituted N1-ethyl-N11-[(cyclopropyl)methyl]-4, 8-diazaundecane (CPENSpm) have previously been shown to cause rapid cytotoxicity of NCI H157 cells, with concurrent high induction of the polyamine catabolic enzyme spermidine/spermine N1-acetyltransferase. However, the precise mechanism(s) of the cytotoxic action of the compounds is not known. We now demonstrate that treatment with either BESpm or CPENSpm results in morphological and biochemical changes consistent with the activation of programmed cell death pathways, and that the unsymmetrically substituted CPENSpm more rapidly activates the death program. These studies suggest that the cell type-specific cytotoxicity of these polyamine analogues may be a result of their ability to selectively activate the cell death pathway in sensitive phenotypes and indicate that the relationship between the structure of the polyamine analogues and the ability to induce programmed cell death should be investigated.     

The Alabama Age-Related Macular Degeneration Grading System for donor eyes

PURPOSE: To develop a systematic method for identifying and grading age-related macular degeneration (ARMD) in human donor eyes, postmortem fundus appearance was compared with histopathologic assessment in eyes with a spectrum of age-related macular change. METHODS: Eyes without grossly visible, late ARMD were obtained from 8 cancer patients and 26 donors older than 50 years. Postmortem fundus appearance was graded for drusen and pigmentary change, using stereo color photographs. Eyes were processed and sectioned at 1 microm for histopathologic evaluation of macular retinal pigment epithelium-Bruch's membrane complex. The histologic diagnosis was compared with gross fundus appearance, clinical ophthalmic histories (n = 25), and clinical fundus photographs that were graded using the Wisconsin Age-related Maculopathy Grading System (n = 5). RESULTS: Ten eyes met histopathologic criteria for early ARMD. A similar proportion of eyes (27%-32%) was identified as affected by ARMD by other published histopathologic criteria. By choosing eyes with at least one druse larger than 125 microm in diameter or an area of pigment-clumping 500 microm in diameter that was visible in the postmortem fundus, ARMD cases were identified with 90% sensitivity and 95% specificity. CONCLUSIONS: The Alabama ARMD Grading System permits rational and standardized use of donor eyes in studies that are directed toward understanding the pathogenesis of ARMD.     

Social support and hostility as predictors of depressive symptoms in cardiac patients one month after hospitalization: a prospective study

OBJECTIVE: Hospitalization for cardiac disease is associated with an increased risk for depression, which itself confers a poorer prognosis. Few prospective studies have examined the determinants of depression after hospitalization in cardiac patients, and even fewer have examined depression within the weeks after hospital discharge. The present study assessed the prospective relations among perceptions of social support and trait hostility in predicting symptoms of depressive symptoms at 1 month after hospitalization for a diagnostic angiography in 506 coronary artery disease (CAD) patients. METHOD: A series of structural equation models 1) estimated the predictive relations of social support, hostility, and depressive symptoms while in the hospital to symptoms of depression 1 month after hospitalization, and 2) compared these relations across gender, predicted risk classification, and age. RESULTS: Social support assessed during hospitalization was independently negatively associated with depressive symptoms 1 month after hospitalization, after controlling for baseline symptoms of depression, gender, disease severity, and age. Hostility was an indirect predictor of postdischarge depressive symptomology by way of its negative relation with social support. This pattern of relations did not differ across gender, predicted risk classification, and age. CONCLUSIONS: Our findings suggest that a patient's perceived social support during hospitalization is a determinant of depressive symptoms 1 month later. The relation of social support and hostility to subsequent depressive symptoms was similar across a variety of populations.     

Dexmedetomidine and halothane produce similar alterations in electroencephalographic and electromyographic activity in cats

Hydroxylated polychlorinated biphenyls also known as biphenylols, are suspected estrogen mimics found in the environment. Various derivatization schemes were evaluated and a gas chromatography-ion trap mass spectrometry method was developed for the trifluoroacetyl derivative using MS-MS techniques for the analysis of eleven biphenylols. A time-segmented chromatographic method was developed using the respective MS-MS parameters to analyze all the eleven biphenylols in a single chromatographic run. Isomers were differentiated based on the MS-MS data of the trofluoroacetyl-biphenylol derivatives. The method was applied to detect 40 pg on-column of these compounds in a spiked egg sample which simulates a real world sample.     

Comparative analysis of breast cancer contamination in mobilized and nonmobilized hematopoietic grafts

We report a case of an 18-month-old female who presented with three supernumerary upper limbs of varying lengths on the right side. Each limb had a proximal, middle, and distal segment, and an intercalated elbow and wrist joint. A single digit was present in the superior limb, three digits in the middle limb, and two digits in the caudal-most limb. Right plagiocephaly, congenital torticollis, scoliosis involving the upper and mid thoracic region, and a hypoplastic right pectoralis major were the other abnormal features noted. Radiography showed two scapulae, humerus, a single forearm bone in each limb, and rudimentary metacarpals and phalanges. Limb duplication may rarely be encountered in parasitic conjoined twins. The role of mutagens, drugs, cellular contributions, and morphogens in the growth and differentiation of limbs has been studied in animals. It is rather difficult to deduce the time of action of the factors responsible for such a malformation.     

The development of parvalbumin and calbindin-D28k immunoreactive interneurons in kitten visual cortical areas

Calbindin-D and parvalbumin are calcium binding proteins which are found in non-overlapping subpopulations of GABA-ergic interneurons in mammalian neocortex. We studied the development of these calcium-binding proteins in interneurons of cat striate and extrastriate cortical areas which have differing patterns of connectivity and follow different developmental timetables. We examined primary visual areas 17 and 18, secondary visual area 19, medial lateral suprasylvian and lateral suprasylvian areas (MLS and LLS) and association areas 7 and the splenial visual area from the day of birth (P0) through P101. Parvalbumin-immunoreactive (ir) interneurons followed the inside-out pattern of maturation of cortical laminae. They were located only in infragranular layers at the earliest ages and were not observed in the overlying cortical plate. At 3 weeks of age, when cortical lamination is mature, parvalbumin stained cells were found in all cortical layers except layer I. The number of stained secondary and tertiary dendrites in the parvalbumin-ir interneuronal population decreased with age. This change was associated with a shift in the molecular weight of parvalbumin detected on Western blots. During the first postnatal week, the area 17/18 border contained more parvalbumin-ir neurons than other visual areas. The developmental pattern of calbindin staining differed considerably from the parvalbumin staining pattern. Very few calbindin-ir interneurons were seen in area 17 during the first 2 weeks of life. In lateral cortical areas, calbindin-ir neurons were located in cortical plate, infragranular layers of cortex and white matter/subplate. Calbindin-ir neurons increased in supragranular layers of secondary cortical areas by P7 and in area 17 by P20. In the mature cortex, the calbindin staining pattern was bilaminar, with a dense band of calbindin-ir cells in layer II and a second band in layers V-VI. There was no difference in the distribution of calbindin-ir neurons among visual areas at maturity.