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Heart weight is frequently used with other criteria at autopsy to assign hypertension as a cause of death in the absence of definitive signs of any other pathology that could have caused death. The extent to which heart weight is influential in that assignment is unknown. A major problem is to determine if heart weight is abnormal There are no universally accepted limits of heart weight in normally healthy persons. Although many studies have addressed this issue, few have been well designed and/or implemented and results are inconsistent. The purpose of this study was to determine 'normal' heart weight of healthy males aged 25-44 years who died of trauma, and to determine a criterion, based on heart weight, that classifies hearts as enlarged or not with higher sensitivity and/or specificity than the currently used criterion of 400 grams The data for this study were obtained from the Community Pathology Study, conducted in New Orleans over a ten-year period beginning in 1969. Of the 1292 male deaths that were autopsied and investigated during this time period, only the deaths due to trauma resulting from accidents, suicides, homicides, and poisoning (805 cases) were used to determine 'normal' limits of heart weight The mean heart weight of normal subjects was 363.50 $\pm$ 68.82 grams. Heart weight increased with age and there were no racial differences in each of the four five-year age groups considered; blacks tended to have lower heart weights but the differences were not statistically significant. Age, body weight, and trunk length were significant predictors of heart weight in normal persons. The upper limit of heart weight that discriminates 'normal' from 'diseased' hearts satisfactorily is 420 grams. This criterion should be used only when evidence of disease pathology is absent at autopsy, and it indicates the absence of CHD or hypertension with greater accuracy than their presence. On the basis of the findings it is believed that the actual misclassification that occurs as a result of using heart weight as a criterion to assign hypertension as a cause of death at autopsy is minimal / acase@tulane.edu

Enterotoxigenic E. coli (ETEC) are effective pathogens only if they can both colonize the small bowel of a susceptible species and produce toxin(s). The fimbrial adhesins that permit colonization of the small intestine by ETEC are highly species specific and ETEC that are human pathogens do not cause natural secretory diarrheal disease in animals. We previously identified a number of naturally occurring E. coli isolates associated with the small intestines of BALB/c mice. These isolates were shown to express chromosomally encoded, mannose resistant hemagglutination (MRHA) of human type A erythrocytes. To identify this MRHA factor, a cosmid genomic library of one of these isolates was constructed and a number of clones that express MRHA activity equivalent to that expressed by the wild type strain were identified. This MRHA operon was characterized by restriction mapping and was subcloned as a 20 kb insert in plasmid pBR325. Transpositional mutagenesis using $\lambda$::TnphoA-1 yielded a number of MRHA negative isolates containing the junction fragment between one MRHA open reading frame (orfA) and bacterial alkaline phosphatase (phoA) from TnphoA indicating that the coding product of orfA plays a critical role in the synthesis and assembly of the MRHA. A 2.2 kb plasmid (pJB71) containing an intact orfA coding sequence was subsequently identified and its nucleotide sequence was determined. A computerized sequence analysis of this plasmid indicated that the 2.2 kb insert is part of the MRHA operon which shares significant homology with E. coli papABCDEFGHIJK, prsA and prsH genes. All these genes are associated with P pili which mediate digalactoside-specific binding to human uroepithelial cells in ascending, unobstructive renal infections / acase@tulane.edu

SL3-3 murine leukemia virus (SL3) is a highly T-cell lymphomagenic retrovirus that reliably induces tumors when inoculated into newborn mice. An important genetic determinant for cell-type specificity and tumorigenic potential is shared with feline leukemia virus (FeLV). A recombinant virus, termed FS-LC, was constructed in which the determinant from FeLV was substituted for the corresponding region of SL3. FS-LC was shown to induce T-cell tumors with kinetics comparable to SL3. Thus, we concluded that the FeLV enhancer sequence can functionally substitute for that of SL3. Known oncogenes were identified as targets of insertional mutagenesis in 10% of FS-LC-induced tumors. To identify the proto-oncogenes involved in the remaining tumors, a recombinant library was constructed from DNA of an FS-LC-induced tumor. Ribosomal protein L4 was identified as a site of clonal retroviral integration using this library but no evidence was obtained that it functions as an oncogene. Finally, the immune interactions that occur during acute and chronic MuLV infection and lymphomagenesis were examined, in order to understand how malignant tumors avoid immune recognition and destruction. The role of cytokines was investigated during lymphomagenesis. Our studies indicated the presence in tumors of cytokines known to down-regulate a cell-mediated anti-tumor immune response, and the absence of cytokines known to enhance it. Data indicated that the pattern of cytokine mRNA expression seen in the end stage tumors is generated by the tumor cells. Analysis of animals infected with SL3 or with a non-tumorigenic mutant of SL3, termed Myb5, were examined longitudinally during infection in order to distinguish the immune consequences of retroviral infection per se from those associated uniquely with the malignant process. The results showed little or no difference in cytokine response to infection with SL3 or Myb5. Most interesting was the observation that IFN-gamma expression is elevated in virally-infected animals between 2 and 4 weeks post-inoculation. We concluded from this finding that the host responds immunologically to the virus, although that response uniformly fails to clear infection. The detection of IL-10 mRNA in target tissues longitudinally during infection suggested further that cytokines may provide a hospitable environment for the developing tumor / acase@tulane.edu

We evaluated the role of HIV-1 and its derived proteins in cell killing and suppression of lymphocyte blastogenic responses in vitro. Treatment of PBMC with ultraviolet light-inactivated HIV-1 (uvHIV-1) resulted in cell killing as determined by viable cell counts. Detergent disrupted preparations of uvHIV-1 (ddHIV-1), however, did not kill PBMC in culture. Furthermore, PBMC subset analysis showed that in some donors treatment with uvHIV-1 resulted in killing of CD8 positive cells in addition to CD4 positive cells, resulting in a decrease in the total numbers of CD4 and CD8 cells without affecting the CD4 to CD8 ratio. On the other hand, both uvHIV-1 and ddHIV-1 equally suppressed proliferation of PBMC and murine spleen cells in response to mitogens Our results show that PBMC treated uvHIV-1 or ddHIV-1 in the presence of PHA produce a potent suppressor of lymphocyte proliferation. The putative suppressor factor(s) is present in conditioned media of HIV-1 pretreated cultures and is protein in nature. The suppressor factor(s), however, was not produced by treatment of PBMC with various HIV-1 recombinant proteins, including gp41 (rp41), gp120 (rp120) or p24 (rp24) Recombinant p41, however, directly suppressed PHA-induced proliferation of PBMC. A synthetic peptide derived from HIV-1 gp41 (TM), referred to as CS3, representing amino acids 583-599 has previously been shown to suppress lymphocyte proliferation in response to mitogens and alloantigens. Therefore, we evaluated the ability of CS3 to induce suppressor factor(s) production. Treatment with CS3 did not induce production of suppressor factor(s) by PBMC. The suppression by CS3 may be due to a specific interaction with the cell surface Our results show that CS3 conjugated to the carrier protein human serum albumin (HSA) (CS3-HSA) binds specifically to the surface of CD4 positive cell lines and PBMC. The CS3 binding activity resides in a molecule of apparent molecular weight of approximately 44 Kd. We have further shown that presence of CS3-HSA abrogates HIV-1 mediated cell killing in vitro. CS3-HSA also inhibits HIV-1 infection in vitro, as measured by quantitation of p24 and cell surface expression of HIV-1 antigens. (Abstract shortened with permission of author.) / acase@tulane.edu