We report on the results of a large autopsy study focusing upon the hypothesis that deletion of the Alu insert in the angiotensin converting enzyme (ACE) gene is associated with: (a) greater prevalence or extent of atherosclerosis in the aorta and coronary arteries; and (b) microscopic qualities of established atherosclerotic plaques in the coronary arteries. This study was conducted in young US black (n=290) and white (n=379) males using available materials and data from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study, a multi-center cooperative autopsy study organized in 1985 to explore the relationships of known cardiovascular risk factors to atherosclerosis in victims of accidents, homicides, or suicides in the age range of 15-34 years. The results provide strong evidence that ACE genotype may not be a predictor of either the prevalence or the extent of the lesions of atherosclerosis in the right coronary artery or the aorta of young adults, an observation that confirms previous studies that estimated the prevalence and extent of atherosclerosis using coronary angiography. In addition, the results suggest that ACE genotype does not contribute to the formation of atherosclerotic lesions that have the characteristics of vulnerable plaques in the left anterior descending coronary artery of young adults.

Human cytomegalovirus (CMV) is a ubiquitous pathogen found in 40-100% of adults, and in about 1% of live births in the United States (1). It is the most common fetal and perinatal infectious organism; approx 10% of infected neonates are born with symptomatic congenital CMV disease, which is the most common cause of mental retardation and childhood deafness. CMV is a significant pathogen in immunocompromised individuals, including organ transplant recipients (2-4), and in acquired immune deficiency syndrome (AIDS) patients (5,6). Infection is characterized by latency, chronic infection, and reactivation, a progression similar to that observed in other members of the herpesvirus family. Because CMV infection is usually controlled by the host cellular immune system, primary infections can occur without obvious symptoms, and progress to latency may go unnoticed. Latent infection may persist throughout life, but primary or reactivated infection, coupled with impaired host immune response, can rapidly produce symptomatic CMV disease.

RAIONALE AND OBJECTIVES. To compare a new 7 Fr. Helix thrombectomy catheter with Amplatz thrombectomy devices (ATD) with respect to clot fragmentation efficiency, hemolytic potential, and risk for vascular trauma.MATERIALS AND METHODS. Particle size was evaluated following the maceration of 8-to-10-day-old clots, each weighing 6 +/- 0.01 g. The clots were macerated using devices of various sizes, including the 7-Fr. Helix thrombectomy catheter, the 7-Fr. over-the-wire (OTW), 8-Fr. ATD and the 6-Fr. ATD. The number of particles by weight was quantified. The 7-Fr. Helix and the 8-Fr. ATD were tested in the native iliac vein of six dogs without presence of clots. Blood samples were obtained before, during, and at 1, 3, 6, 24, and 48 hours after the procedure, to monitor the hemolytic effects. The treated iliac veins were examined histologically.RESULTS. Most of the clot was fragmented into particles < 10 mum. The mean percentage by weight of the original clot that remained as particles larger than 10 mum was 1.59% in the 7-Fr. Helix group. This was significantly less than 3.10% with the 6-Fr. ATD, 2.57% with 7-Fr. OTW and 2.44% in the 8-Fr. ATD group (< 0.01). In vivo results showed a higher plasma free hemoglobin (PFH) level starting 5 minutes after initiating the ATD activation, reaching its peak after completion of the activation, and declining afterward, with return to the baseline at 24 hours. The haptoglobin level tended to decline slightly at 10 minutes, reaching its lowest level at 24 hours, and starting to recover at 48 hours. A similar pattern of PFH and haptoglobin changes was found in both groups. There were no significant differences regarding hemolytic effect of the two tested devices. No significant changes of creatinine were observed for up to 48 hours after procedures. Focal microthrombosis was seen in two sites of two vessels treated with the 7-Fr. Helix and a focal injury of a venous valve was noted in the 8-Fr. ATD group. The media and internal elastic lamina (IEL) were intact in all cases.CONCLUSION. The newly designed 7-Fr. Helix is more effective in fragmentation in vitro clots than the 6 Fr. ATD, 7-Fr. OTW and the 8-Fr. ATD. The 7-Fr. Helix and the 8-Fr. ATD produced hemolytic effects, but they appeared to be tolerated by the animals. The in vivo results indicated that the 7-Fr. Helix appears to be as safe as the 8-Fr. ATD.

Posttransplant lymphoproliferative disorders are often accompanied by >500 Epstein-Barr virus (EBV) genome copies/10(5) lymphocytes, and they occur shortly after transplantation. Hodgkin lymphoma occurs rarely after transplantation, appearing a mean of 4.2 years posttransplant, and although Hodgkin lymphoma has strong associations with EBV, no quantitative analysis of peripheral blood EBV genome copies has been reported. A mixed cellularity Hodgkin lymphoma developed in a 17-year-old boy 4 years after a renal transplant. Serial EBV genome copy numbers from blood by competitive polymerase chain reaction had been obtained to assess for lymphoproliferative disease. Epstein-Barr virus genome copy numbers peaked at 500 copies/10(5) lymphocytes 8 months prior to Hodgkin lymphoma diagnosis but fell to 8 copies/10(5) lymphocytes at diagnosis. Reliance on EBV levels greater than 500 copies may result in delay of biopsy and diagnosis of Hodgkin disease in the posttransplant setting.

Hb G-Coushatta [beta 22(B4)Glu-->Ala] is found in geographically separated ethnic groups. Commonest along the Silk Road region of China but also present in the North American Coushatta, we sought to determine whether this variant had a unicentric or multicentric origin. We examined the haplotype of the beta-globin gene cluster in two Chinese families and in five Louisiana Coushatta heterozygous for this mutation. Chinese and Louisiana Coushatta had different haplotypes associated with the identical Hb G mutation. These haplotypes were defined by the presence of a HindIII restriction site in the (A)gamma-globin gene and AvaII restriction site in the beta-globin gene in Chinese subjects and their absence in the Louisiana Coushatta. We found a CA (C) under bar at codon beta 2 (beta-globin gene framework 1 or 2) linked to the Hb G-Coushatta gene in Chinese, and a CA (T) under bar (framework 3) in Louisiana Coushatta, indicating different beta-globin gene frameworks. Both the Hb G-Coushatta mutation (G (A) under bar A-->G (C) under bar A) and the codon 2 CA (C) under bar-->CA (T) under bar polymorphism are normal delta-globin gene sequences, suggesting the possibility of gene conversion. We conclude that Hb G-Coushatta had at least two independent origins. This could be due to separate mutations at codon beta 22 in Chinese and Louisiana Coushatta, a mutation at this codon and a beta-->delta conversion, or two beta-->delta gene conversion events.

Journal of Pediatric Gastroenterology and NutritionVolume 28, Issue 5 p. 502-505 Case Report Longitudinal Analysis of Plasma Cytomegalovirus DNA in a Child with Crohn's Disease and Cytomegalovirus Gastroenteritis Jr. John N. Udall, Corresponding Author Jr. John N. Udall n/[email protected] Department of Pediatrics, New Orleans, Louisiana Children's Hospital, New Orleans, Louisiana Louisiana State University Medical Center, New Orleans, LouisianaAddress correspondence and reprint requests to John N. Udall, Jr., M.D., Ph.D., Department of Pediatrics, Louisiana State University Medical Center, 1542 Tulane Avenue, New Orleans, LA 70112-2822.Search for more papers by this authorJames M. Hempe, James M. Hempe Department of Pediatrics, New Orleans, Louisiana Children's Hospital, New Orleans, Louisiana Louisiana State University Medical Center, New Orleans, LouisianaSearch for more papers by this authorEberhard Schmidt-Sommerfeld, Eberhard Schmidt-Sommerfeld Department of Pediatrics, New Orleans, Louisiana Children's Hospital, New Orleans, Louisiana Louisiana State University Medical Center, New Orleans, LouisianaSearch for more papers by this authorW. Douglas Scheer, W. Douglas Scheer Department of Pediatrics, New Orleans, Louisiana Department of Pathology, New Orleans, Louisiana Louisiana State University Medical Center, New Orleans, LouisianaSearch for more papers by this authorElizabeth Mannick, Elizabeth Mannick Department of Pediatrics, University of Rochester Medical Center, Rochester, New YorkSearch for more papers by this authorUwe Blecker, Uwe Blecker Dupont Hospital for Children, Wilmington, DelawareSearch for more papers by this authorHernan Correa, Hernan Correa Department of Pathology, New Orleans, Louisiana Children's Hospital, New Orleans, Louisiana Louisiana State University Medical Center, New Orleans, LouisianaSearch for more papers by this author Jr. John N. Udall, Corresponding Author Jr. John N. Udall n/[email protected] Department of Pediatrics, New Orleans, Louisiana Children's Hospital, New Orleans, Louisiana Louisiana State University Medical Center, New Orleans, LouisianaAddress correspondence and reprint requests to John N. Udall, Jr., M.D., Ph.D., Department of Pediatrics, Louisiana State University Medical Center, 1542 Tulane Avenue, New Orleans, LA 70112-2822.Search for more papers by this authorJames M. Hempe, James M. Hempe Department of Pediatrics, New Orleans, Louisiana Children's Hospital, New Orleans, Louisiana Louisiana State University Medical Center, New Orleans, LouisianaSearch for more papers by this authorEberhard Schmidt-Sommerfeld, Eberhard Schmidt-Sommerfeld Department of Pediatrics, New Orleans, Louisiana Children's Hospital, New Orleans, Louisiana Louisiana State University Medical Center, New Orleans, LouisianaSearch for more papers by this authorW. Douglas Scheer, W. Douglas Scheer Department of Pediatrics, New Orleans, Louisiana Department of Pathology, New Orleans, Louisiana Louisiana State University Medical Center, New Orleans, LouisianaSearch for more papers by this authorElizabeth Mannick, Elizabeth Mannick Department of Pediatrics, University of Rochester Medical Center, Rochester, New YorkSearch for more papers by this authorUwe Blecker, Uwe Blecker Dupont Hospital for Children, Wilmington, DelawareSearch for more papers by this authorHernan Correa, Hernan Correa Department of Pathology, New Orleans, Louisiana Children's Hospital, New Orleans, Louisiana Louisiana State University Medical Center, New Orleans, LouisianaSearch for more papers by this author First published: 01 May 1999 https://doi.org/10.1002/j.1536-4801.1999.tb02124.xRead the full textAbout ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. REFERENCES 1Söderlund C, Bratt GA, Engström L, et al. Surgical treatment of cytomegalovirus enterocolitis in severe human immunodeficiency virus infection. Report of eight cases. Dis Colon Rectum 1994; 37: 63–72. 10.1007/BF02047217 CASPubMedWeb of Science®Google Scholar 2Jonkhoff-Slok TW, Veenhoven RH, de Graeff-Meeder ER, Büller HA. An immunocompetent infant with cow's milk allergy and cytomegalovirus colitis. Eur J Pediatr 1997; 156: 528–9. 10.1007/s004310050654 CASPubMedWeb of Science®Google Scholar 3Begos DG, Rappaport R, Jain D. Cytomegalovirus infection masquerading as an ulcerative colitis flare-up: Case report and review of the literature. Yale J Biol Med 1996; 69: 323–8. CASPubMedWeb of Science®Google Scholar 4Berk T, Gordon SJ, Choi HY, Cooper HS. Cytomegalovirus infection of the colon: A possible role in exacerbations of inflammatory bowel disease. 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Quantification of human cytomegalovirus DNA in peripheral blood polymorphonuclear leukocytes of immunocompromised patients by the polymerase chain reaction. J Virol Methods 1993; 44: 45–55. 10.1016/0166-0934(93)90006-D CASPubMedWeb of Science®Google Scholar 13Emanuel D, Cunningham I, Jules-Elysee K, et al. Cytomegalovirus pneumonia after bone marrow transplantation successfully treated with the combination of ganciclovir and high-dose intravenous immune globulin. Ann Intern Med 1988; 109: 777–82. 10.7326/0003-4819-109-10-777 CASPubMedWeb of Science®Google Scholar 14Ljungman P, Engelhard D, Link H, et al. Treatment of interstitial pneumonitis due to cytomegalovirus with ganciclovir and intravenous immune globulin: Experience of European Bone Marrow Transplant Group. Clin Infect Dis 1992; 14: 831–35. 10.1093/clinids/14.4.831 CASPubMedWeb of Science®Google Scholar 15Espy MJ, Patel R, Paya CV, Smith TF. Comparison of three methods for extraction of viral nucleic acids from blood cultures. 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We compared serum lipid and apolipoprotein predictors of atherosclerosis in cases from the multicenter study, Pathobiological Determinants of Atherosclerosis in Youth (PDAY). The lipid measures included HDL cholesterol (HDL-C) and non-HDL-C, and the apolipoprotein measures included concentrations of apoA1, apoB, and Lp(a), and sizes of the apo(a) proteins. We tested whether the apolipoprotein measures predicted atherosclerotic lesions as well as the more traditional lipid measures. We estimated extent of lesions as fatty streaks or raised lesions (fibrous plaques, complicated or calcified lesions) in 3 sites: thoracic aorta, abdominal aorta, and right coronary artery. Neither apoA1 nor apoB measures were as strongly or consistently correlated with extent of lesions as the corresponding lipid measure (HDL-C and non-HDL-C, respectively). Beyond the basic model that included sex, age, race, smoking status, hypertension, and the lipid measures, apoA1 and apoB added only an average 1.3% increased explanatory ability to the model, whereas HDL-C plus non-HDL-C added an average 2.5%. The results suggest that the traditional lipid measures are more useful than apolipoprotein measures for detecting young persons at high risk of precocious atherosclerosis. Because of large racial differences, the two Lp(a)-related measures, Lp(a) concentrations and apo(a) size, were evaluated in blacks and whites separately. Under these circumstances, neither of the Lp(a)-related measures was strongly or consistently correlated with extent of lesions.

Arterial, liver, and serum specimens were collected from Greenland Inuit at autopsy and apolipoprotein E genotyping was done on 42 females (mean age = 61.3 years) and 56 males (mean age = 56.8 years). Estimates of the allele frequencies of the apo E, derived from the observed frequencies of the six common apolipoprotein E genotypes, are E2: 0.015+/-0.009; E3: 0.776+/-0.030; and E4: 0.209+/-0.029. No significant difference was found between these frequencies and those previously reported for Greenland Inuit, Canadian Inuit, or Alaska natives; however, differences were observed in comparison with frequencies reported for Japan, Norway, Sweden, USA-Blacks and USA-Whites. Anthropometric data (body mass index, panniculus adiposus thickness), blood analyte levels (total serum cholesterol, HDL-cholesterol, LDL + VLDL-cholesterol, and glycohemoglobin), and prevalence and extent of atherosclerotic lesions in the aorta and coronary arteries were analyzed for any associations with apolipoprotein E genotype. The occurrence of apolipoprotein E2 alleles are very rare and the E4 alleles are slightly more frequent in the Greenland Inuit population as compared to other populations. No significant association between apolipoprotein E genotypes and the extent of atherosclerotic lesions in the aorta and coronary arteries were found, and there does not appear to be any strong evidence for an association of either serum lipids, glycohemoglobin levels, or adiposity measurements to apolipoprotein E genotype in Greenland Inuit.

Surgical therapy for localized melanoma is highly successful. However, if melanoma spreads beyond its primary site, the results of treatment are poor. Therefore, early detection of circulating melanoma cells in the blood may be important. Currently, circulating melanoma cells are undetectable. Tyrosinase is an enzyme in the melanin synthetic pathway the expression of which is only found in melanin-producing cells. Because melanocytes are not normally found in the peripheral blood, we hypothesize that melanoma cells circulating in the peripheral blood could be detected by amplifying the tyrosinase mRNA using the reverse transcription-PCR (RT-PCR). The purpose of this study was to determine the sensitivity of a RT-PCR-based assay for tyrosinase mRNA from peripheral blood and evaluate correlations with tumor status in melanoma patients. RNA was isolated from the peripheral blood or tissue culture cells, and cDNA was prepared. DNA was amplified using RT-PCR with nested primers for tyrosinase and beta(2)-microglobulin. Serial dilution experiments using cells from the SK-MEL-28 cell line were performed in culture media and in whole blood. Twelve patients with melanoma, 10 healthy controls, and 15 patients with nonmelanoma malignancies were tested for tyrosinase expression in peripheral blood. The sensitivity of this assay was determined to be as low as 1 melanoma cell in 5 ml of whole blood. No tyrosinase was found in healthy subjects or other cancer control patients. Tyrosinase mRNA was detected in the blood of five melanoma patients (one stage II, two stage III, and two stage IV). Three of these tyrosinase-positive patients had biopsy-proven evidence of melanoma, whereas the other two had no clinical evidence of malignant disease after surgical resection. The remaining seven melanoma patients had no evidence of disease and tested negative for tyrosinase mRNA. This study suggests that a RT-PCR-based assay for the detection of tyrosinase mRNA in peripheral blood is feasible. Moreover, the presence of tyrosinase mRNA in the blood seems to correlate with the stage of melanoma. Further study and follow-up are needed to clarify the role of tyrosinase mRNA as a tumor marker for malignant melanoma.

OBJECTIVE The purpose of this study was to investigate possible relationships between lipoprotein (a) [Lp(a)] levels and NIDDM in African-Americans. The objectives were to identify associations between Lp(a) levels of subjects with and without NIDDM and to determine the influence of glycemic control, determined by GHb, and of mode of therapy on Lp(a) levels. RESEARCH DESIGN AND METHODS We studied 141 African-American subjects, 103 with NIDDM and 38 without NIDDM. Their Lp(a) levels, GHb levels, and apolipoprotein (a) [apo(a)] isoforms were determined. Clinical information, including mode of therapy (sulfonylurea, insulin, or no pharmacological therapy), date of diagnosis, and medical history, was obtained by chart review and patient interview. RESULTS There was no significant difference in median Lp(a) levels between the non-NIDDM (25.5 mg/dl) and NIDDM (24.0 mg/dl) study subjects. No statistically significant difference was found in Lp(a) levels when NIDDM patients with GHb < 12.3% were compared to those with GHb ≥ 12.3% (P = 0.096). An inverse relationship was found between apo(a) root-mean-square isoform size and Lp(a) level (r2 = 0.091, P = 0.0035). Analysis of the cases by mode of therapy indicates that there is evidence of an increased median level of Lp(a) in African-Americans with NIDDM on insulin therapy relative to those on sulfonylurea (34.0 vs. 16.0 mg/dl; P = 0.013) and to nondiabetic subjects (34.0 vs. 25.5 mg/dl; P = 0.043). CONCLUSIONS We conclude that the level of plasma Lp(a) is higher in African-Americans with NIDDM who are being treated with insulin when compared to those on sulfonylurea therapy and to those who are non-NIDDM subjects, and this does not seem to be due to genetic variance or method bias.

A significant difference in breast cancer survival between blacks and whites has been observed in the United States. Biological variation between races has been suggested to explain the difference. We investigated the difference by comparing the prognostic value of p53 alterations (mutations and protein accumulation) between black and white breast cancer patients. Black, but not white, patients with p53 mutations had a significantly poorer survival than those without p53 mutations (p < 0.05). In contrast, white, but not black, patients having tumors with p53 protein accumulation tended to have a poorer survival than those without accumulation of p53 protein (p = 0.058). Among patients who died of breast cancer, blacks were often to have p53 mutations without protein accumulation, and whites frequently had p53 protein accumulation without mutations. The racial disparities in the associations of p53 alterations with breast cancer survival could have clinical implications in terms of treatment management.

Arterial, liver, and serum specimens were collected from 130 Alaska Natives who underwent forensic necropsy (mean age, 36.9 years; age range, 9-85 years; 38 females and 92 males). Based upon the observed frequencies of the six common apo E genotypes, the estimates of the relative frequencies of the corresponding alleles in the population are 0.020 +/- 0.009 for E2, 0.787 +/- 0.026 for E3 and 0.193 +/- 0.025 for E4. Analysis showed significant differences, by apo E genotype, in the extent of total surface lesion involvement in both the right and left coronary arteries. In all but the abdominal aorta, the pattern of lesion involvement by genotype is consistent with a decrease in lesions for genotypes with the E2 allele and an increase in lesions for the genotypes with the E4 allele, relative to the E3 homozygotes. After adjustment for low + very low density lipoprotein cholesterol (LDL + VLDL-C), the differences fell below statistically significant levels. Analysis by genotype of total serum cholesterol, high density lipoprotein cholesterol (HDL-C) and LDL + VLDL-C showed no statistically significant differences in analyte levels among genotypes. However, evidence is seen of a pattern in which total cholesterol and VLDL + LDL-C is less in genotypes with the E2 allele and greater in those with the E4 allele. We conclude that there does appear to be an effect by apo E genotype upon extent of atherosclerosis in the coronary arteries of Alaska Natives and this effect is likely due to the previously reported effect of apo E polymorphisms on serum cholesterol, particularly LDL + VLDL-C.

A significant black/white difference in breast cancer prognosis has been observed in the United States. Alterations of p53 tumor suppressor gene in breast cancer have been associated with poor prognosis. This study was designed to test the hypothesis that p53 gene alterations are related to the difference in prognosis between black and white breast cancer patients. Formalin-fixed paraffin-embedded breast tissue blocks were available from 45 black and 47 white patients for PCR-single strand conformation polymorphism analysis and DNA sequencing. The types of p53 gene alterations were compared between blacks and whites. Associations between p53 gene alterations and survival were also evaluated. Three missense, 2 nonsense, 1 microdeletion, 1 intron, and 4 silent mutations were detected in blacks, while 7 missense, 1 microdeletion, 1 silent mutation, and 3 polymorphisms were observed in whites. Among the point mutations, G:C to A:T transitions at non-CpG sites were found in 80.0% of blacks (8 of 10) and 62.5% of whites (5 of 8). Significantly poorer survival associated with p53 gene alterations was observed for blacks (P = 0.012), but not for whites. Black patients with p53 alterations had a significant 4-5-fold excess risk of death from breast cancer than those without p53 alterations. Adjustment for stage, age, tumor histopathology, receptor status, and adjuvant treatment did not change the excess risk. The findings suggest that the types of p53 gene alterations may contribute to the racial difference in breast cancer survival.

It has been postulated that chronic atrophic gastritis, intestinal metaplasia, and dysplasia are precancerous stages of stomach tumorigenesis. We investigated the timing of p53 alterations in these events of gastric tumorigenesis. Each of 12 cases of archived tissue containing precancerous and cancerous lesions were selected for the detection of p53 alterations. Accumulation of p53 protein was detected by immunohistochemistry. Exons 5 to 8 of p53 gene were examined for mutations by polymerase chain reaction-single strand conformation polymorphism and DNA sequencing. p53 immunoreactivity was detected in 60% of the dysplasia cases and in 60% of the cases with carcinomas. p53 gene alterations were found in 37.5% of the metaplasia cases, 58.3% of the dysplasia cases, and 66.7% of the cases with carcinomas. In 71% of the cases, mutations were shown as G:C-->A:T transition. We conclude that mutation of the p53 gene is an early event in stomach tumorigenesis.