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Maintenance of optimal polyamine pool levels is critical for cell survival. Intracellular polyamine depletion is usually cytostatic, whereas unregulated polyamine accumulation can result in cytotoxicity. The purpose of this work was to examine the importance of polyamine depletion in cell survival, either through increased polyamine catabolism or decreased polyamine synthesis. The polyamine analogue CHENSpm, which induces apoptosis in several cell lines, was used to examine the role of polyamine catabolism in cell survival. The susceptibility of Chinese hamster ovary cells and HCT 116 human colon cells to CHENSpm-mediated toxicity was inversely correlated with the level of polyamine oxidase (PAO) activity present in each cell type. Chinese hamster ovary cells (CHO), which contained high levels of PAO, were not growth inhibited by CBENSpm, however concomitant PAO inhibition led to a moderate growth suppression. The inhibition of the diamine exporter (DAX) in addition to PAO led to a CHENSpm-mediated cytotoxic response that was manifested as apoptosis induction. HPLC analysis of CHENSpm- treated CHO cell extracts revealed the presence of an unidentified amine that was not present when PAO was inhibited. This suggests that PAO is able to utilize CHENSpm as a substrate, and that this metabolism protects cells from CHENSpm-mediated cytotoxicity. The effect of polyamine depletion in apoptosis induced by the non-steroidal anti-inflammatory drug (NSAID) sulindac was examined in cells harboring an activated Ki-ras. Cells overexpressing Ki-ras underwent an accelerated apoptosis induction with either metabolite of sulindac, however overall toxicity was unaffected in long-term survival assays. DFMO did not affect apoptosis induction by sulindac sulfone, nor did it increase sulindac sulfone toxicity in long-term survival studies. DFMO alone was selectively cytotoxic to Ki-ras transfected clones in a dose-dependent manner. Ki-ras transfection increased c-myc expression, but had no effect on ODC steady-state mRNA levels. The downregulation of N1-spermidine/spermine acetyltransferase (SSAT) seen in Ki-ras transfected cells suggests polyamine, catabolism may protect cells from DFMO-induced cytotoxicity. These studies demonstrate that polyamine, catabolism may play an important role in cell survival under conditions of suboptimal polyamine levels.

The primary method for the diagnostic interpretation of histopathologic sections is visual analysis. However, in a small, but significant percentage of cases, histopathologists do not come to a consensus. Therefore, due to the importance of early and accurate detection of tissue changes indicative of pathology, quantitative image analysis techniques have been applied to this problem. The accurate segmentation of image structures such as cells and glands in histopathological sections, as with all "natural scenes", proves challenging. This has led to the development of an additional segmentation technique, the heuristic gradient search. Following the successful segmentation and labeling of scene objects, algorithms evaluating diagnostic clues as to the shape, size and distribution of image components were developed in order to form an overall diagnosis. A description of these diagnostic clues and the image processing techniques residing in the computer vision system used to evaluate them are presented.

The use of 153Sm-incorporated polystyrene latex particles for the external image scanning of tumors was simulated in four murine strains. Reticuloendothelial blood clearance and tissue localization of 0.5 mum and 1.0 mum fluorescent PSL was evaluated in RE-competent and RE-depressed mice following IV injection and oral particle administration. Intravenous injection of PSL revealed differences in blood clearance rates and tissue distribution patterns with respect to strain and particle size; an explanation based on genetic strain derivation is offered. RE depression in the Balb/c resulted in higher circulating blood levels of both particle sizes without affecting tissue distribution patterns; the use of dissimilarly sized particles for blocking and testing resulted in dramatic decreases in organ PSL concentrations and alterations in apparent kinetic rate constants. Balb/c blood levels of orally administered particles were increased and remained temporally constant while tissue concentrations were generally lower than IV-injected levels.

The spontaneous rate of congenital cardiac defects in the commonly used Sprague-Dawley rat has not been extensively researched. The incidence of general congenital defects has been studied thoroughly and reported as very low incidence in this rat. Teratology studies using mammalian models are of increasing importance as the number of environmental contaminants increases. It is essential to know if the spontaneous congenital cardiac defect rate of this most common mammalian model in order to plan statistically appropriate research protocols. Using a thorough and detailed method of evaluating the structure of the Sprague-Dawley fetal rat heart, 624 fetal rat hearts were examined at term, just prior of delivery. The overall incidence of spontaneous congenital cardiac defects is 2.3%. This is similar to the incidence in man and thus enhances the suitability of the Sprague-Dawley rat as a small mammalian model for research into cardiac teratogenesis.

The purpose of this study was to identify environmental and host factors that distinguish children who remain persistently uninfected from those with persistent Plasmodium falciparum infection in the village of Bancoumana, Mali (West Africa). Previous studies have shown that sickle trait (Hb AS) protects against severe disease (but not infection) due to P. falciparum. Within a village-wide cohort of 2,000 children aged 0 to 9 years, we identified and followed 181 who were persistently smear negative, 476 who persistently smear positive, and 194 who were intermittently smear positive. In addition, 2 nested case-controls studies were conducted during the 1996 and 1997 transmission seasons (June to October) to identify risk/protective factors for parasitemia. During the 2 year study period from June 1996 to June 1998, 2 children remained persistently smear negative and 26 remained persistently smear positive. However, these 2 children had high titres (≥1:160) of antibodies against asexual P. falciparum, suggesting a previous parasitemia with this parasite. Sickle cell trait (Hb AS) was associated with protection against persistent parasitemia as manifested by a prolonged time to infection (HR = 0.56; 95% CI [0.33--0.96]; p = 0.036) after controlling for antimalarial treatment, spleen size and age. In contrast, neither Hb C nor ABO blood group protected against persistent parasitemia. The relationship between MN blood group and persistent parasitemia was suggestive, but inconclusive Older children (5--9 years) were infected at a rate that was twice that of younger children (0--4 years), after controlling for antimalarial therapy, spleen size, and hemoglobin (HR = 1.98; 95% CI [1.28--3.08]; p = 0.002). Persistently negative children were of higher socioeconomic status than persistently positive children. These results suggest that children in Bancoumana are universally susceptible to P. falciparum infection. The existence of an absolute resistance to P. falciparum cannot be ruled out from this study. However, if refractoriness to P. falciparum exists in this region of Africa, its frequency must be less than 1 in 2,000 children. Further research on the biological factors associated with a delayed time to infection among sickle trait children may increase our understanding of P. falciparum interactions with human red blood cells / acase@tulane.edu

In areas with Plasmodium vivax transmission, malaria cases may represent primary infections or recurrent infections. Recurrent infections may be due to relapse (from hypnozoites), recrudescence (from persistent blood stages), or reinfection (from additional infectious mosquito bites). Because there are no clinical or parasitological criteria to distinguish among recurrent infections, a molecular strategy based on genetic polymorphic markers and the polymerase chain reaction (PCR) was developed to distinguish relapse from reinfection. Four sets of primers were designed and used in nested PCR to amplify polymorphic regions of P. vivax genes, including the fragments between Blocks 5 and 6, and Blocks 8 and 9 of the merozoite surface protein 1 (MSP1), the fragment between Regions I and II of the circumsporozoite protein (CSP), and a fragment between two conserved regions of the gametocyte blocking antigen 1 (GAM1). The combination of these four markers provided a sensitive system to characterize P. vivax and P. cynomolgi parasite types based on the pattern of their amplification products on agarose gel electrophoresis or amplicon length polymorphisms (ALPs) The hypothesis that parasites which cause relapse are indistinguishable from those that caused the initial bloodstream infection was examined using the P. cynomolgi/rhesus monkey model of human P. vivax infection. Two rhesus monkeys were infected with sporozoites of P. c. bastianellii. PCR amplification products obtained from relapses were indistinguishable from each other and from the initial bloodstream infections in terms of size (MSP1 5/6 and 8/9, and CSP markers) and DNA sequence (MSP1 5/6 and CSP markers). Therefore, demonstrating the same parasite type in the initial infection and subsequent relapses Field studies were carried out in Colombia, South America, in collaboration with Corporacion CIDEIM (Centro Internacional de Entrenamiento e Investigaciones Medicas) located in Cali. The distribution of P. vivax parasite types was examined in endemic communities (Tumaco, Buenaventura, and the Oriental Plains) in order to estimate the probability of reinfection with the same parasite type. During the study period (March 1994 to October 1996), 339 filter paper blood samples from P. vivax infected patients were analyzed by PCR, including paired blood samples (initial bloodstream infection and subsequent recurrence) obtained from ten persons with recurrent infections. (Abstract shortened by UMI.) / acase@tulane.edu

This thesis reports the results of the study of two Egyptian mummies housed at Tulane University since 1852. Background information includes an inventory of the Egyptian collection, as well as the results of research into the mummies' origin. The bodies were subject to a noninvasive, nondestructive study protocol, based on direct observation, stereoscopic microscopy and radiographic procedures Mummy 1 (Nefer Atethu, assigned name) was a subadult female who died from complications of childbirth between 12 and 16 years of age. An expansive disarticulation of the pelvic skeleton (dislocation of the symphysis pubis and symmetrical diastases of the sacroiliac joints), in the absence of any other sign of disease, supports the diagnosis. Her form of intentional mummification and degree of preservation are characteristic of the 21st dynasty (Third Intermediate Period) Mummy 2 (Got Thothi Aunk) according to the 19th century Egyptologists' research, was 'Chief of the Artificers of the Abode of Ammon,' and died during the rule of Osorkon III (23rd dynasty, 989 BCE). The unrolling of this mummy in Boston (1850) was a pivotal event that resulted in the arrival of the bodies in New Orleans a year later. Got Thothi Aunk died between 40 and 50 years of age from unknown causes. His body shows signs of osteoarthrosis, osteoporosis and chronic periodontal disease. The embalming of this body corresponds to the 21st dynasty. Further studies are recommended, with an emphasis on the preservation of these valuable bodies / acase@tulane.edu

The purpose of this study was to determine the pathogenesis and etiology of microsporidia in HIV-infected patients. All HIV-infected patients, seeking care at the Medical Center of Louisiana at New Orleans, submitting a stool specimen between October 3, 1996 and June 30, 1997 were eligible for this study. The medical charts of all eligible patients were retrospectively abstracted for demographic, clinical, and laboratory information. Logistic regression was used to determine if the presence of microsporidia in the stool were associated with persistent diarrhea or weight loss > = 10% of baseline weight six months after the index specimen, as compared to patients with cryptosporidiosis, or non-cryptosporidiosis controls. Linear regression was used to determine if the presence of microsporidia in the stool was associated with a decline in CD4 cell count. An examination of only those patients positive for microsporidia was conducted to determine the factors related to poor outcomes among these patients. A questionnaire was administered to eligible participants to determine the etiology of microsporidiosis in this population Patients with microsporidiosis were significantly more likely to have experienced chronic diarrhea and weight loss than non-cryptosporidiosis controls (OR chronic diarrhea: 2.10, [1.01, 4.38], OR weight loss: 2.23, [1.02, 5.33]). There was no significant difference between patients with cryptosporidiosis and patients with microsporidiosis with respect to the risk of chronic diarrhea or weight loss or death (OR chronic diarrhea 1.50, [0.62, 3.67], OR weight loss/death 0.94, [0.16, 1.97]). There was also no significant decline in CD4 cell count associated with microsporidiosis (-25.5 cells/dl, [-76.2, 25.1]). Factors associated with chronic diarrhea among patients with microsporidiosis included high HIV-viral load and no initiation of anti-retroviral therapy (p < 0.05). Factors associated with weight loss included very low CD4 cell count (< = 50 cells/dl) and no utilization of anti-retroviral therapy (p < 0.05). The associations between microsporidia and weight loss and chronic diarrhea indicate that microsporidia are pathogenic and may be an opportunistic pathogen In a multivariate logistic regression, well water and contact with horses were significantly associated with a stool positive for microsporidia. Rural environments and water sources should be investigated further as potential sources of microsporidia in the environment / acase@tulane.edu