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Biomedical subjects

J Peterson

Publications and source records attributed to J Peterson.

At least 127 records · Page 7Linked to original sources

Identification of axial ligands of cytochrome c552 from Nitrosomonas europaea.

Cytochrome c552 from Nitrosomonas europaea was analyzed by visible, EPR and MCD spectroscopies. The visible and MCD data show that histidine and methionine are the axial ligands to the heme iron of the ferric protein. The EPR spectrum of the cytochrome shows an atypical highly axial low spin (HALS) type signal with g-values that make it difficult to identify the axial ligands. These results reinforce the value of near-infrared MCD spectroscopy for assigning ligands in ferric heme systems and point out the difficulties in using only EPR spectroscopy for the same purpose. The description of another c-cytochrome exhibiting a HALS-type EPR signal will eventually be helpful in explaining the physical basis for this unusual signal.

Circular Dichroism↗

Ventricular fibrillation induced by low-energy shocks from programmable implantable cardioverter-defibrillators in patients with coronary artery disease.

Many of the newest implantable cardioverter-defibrillators (ICDs) provide the option of programmable low-energy cardioversion for monomorphic ventricular tachycardia (VT). Whereas these devices may provide less myocardial damage and increased comfort in patients receiving frequent shocks for VT, the proarrhythmic effects of low-energy cardioversion from ICDs in patients with structural heart disease are not clear. The purpose of this study was to determine prospectively the per-patient incidence of ventricular fibrillation (VF) induction after low-energy cardioversion of VT by ICDs in patients with coronary artery disease. The estimated cardioversion energy requirement was determined during the course of routine predischarge ICD testing in 40 patients with newly implanted ICDs. Two groups of patients were identified during determination of the cardioversion energy requirement: (1) a non-VF group consisting of 26 of 40 patients (65%) without VF induced by low-energy shock and, (2) a VF group consisting of 14 of 40 patients (35%) who developed VF during low-energy cardioversion. There was no difference between the 2 groups in terms of patient age, sex, concurrent antiarrhythmic drug therapy, VT cycle length, or type of ICD system implanted. Compared with the non-VF group, the VF group was more likely to have both a lower ejection fraction (25 +/- 5% vs 33 +/- 8%; p = 0.005) and a cardioversion energy requirement > 2 J (79 vs 27%; p = 0.005). Our results suggest that low-energy cardioversion is associated with a high per-patient risk of VF induction, and the risk is higher in patients with poorer left ventricular function and, possibly, higher cardioversion energy requirement.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Long-term prognosis after peri-operative cardiac complications.

UNLABELLED: The objective was to document the 5 year prognosis of patients who had cardiac complications after non-cardiac surgery. DESIGN: 5-year follow-up of 218 patients originally enrolled in a prospective study to identify risks factors for peri-operative complications. SETTING: an academic medical center. Participants were hypertensives and diabetics who underwent elective surgery between 1982 and 1985. In the original study, patients were evaluated pre-operatively, monitored intra-operatively by an independent observer, and followed daily for 7 days post-operatively according to a standard surveillance protocol. Outcomes were judged by assessors blinded to the pre-operative status and intra-operative course. Patients were interviewed at 3 and 5 years post-operatively. Patients with post-operative cardiac complications had significantly higher rates of overall mortality, mortality attributable to cardiac causes (MI, CHF, arrest), and mortality attributable to other cardiovascular causes (stroke, renal failure) than patients without cardiac complications. For example, at 5 years 11% of those patients without post-operative cardiac complications had cardiac deaths, in contrast to 45% of those patients with post-operative cardiac complications. Proportional hazards analysis demonstrated that post-operative cardiac complications remained a significant predictor of cardiac (p < 0.001) and cardiovascular (p < 0.0001) mortality controlling for pre-operative cardiac disease, other non-cardiovascular comorbid diseases, age, sex, diabetes, and pre-operative renal insufficiency or stroke. Similarly, patients with post-operative non-fatal cardiac complications had higher rates of cardiac or cardiovascular events during the 5 year follow-up period. We conclude that post-operative cardiac complications have a significant adverse long-term prognostic impact comparable to the prognostic impact of myocardial infarction, ischemia or congestive failure in the non-operative setting. Understanding these events could be an important factor in identifying patients at high risk for subsequent peri-operative complications.

Aged↗

Validation of a combined comorbidity index.

The basic objective of this paper is to evaluate an age-comorbidity index in a cohort of patients who were originally enrolled in a prospective study to identify risk factors for peri-operative complications. Two-hundred and twenty-six patients were enrolled in the study. The participants were patients with hypertension or diabetes who underwent elective surgery between 1982 and 1985 and who survived to discharge. Two-hundred and eighteen patients survived until discharge. These patients were followed for at least five years post-operatively. The estimated relative risk of death for each comorbidity rank was 1.4 and for each decade of age was 1.4. When age and comorbidity were modelled as a combined age-comorbidity score, the estimated relative risk for each combined age-comorbidity unit was 1.45. Thus, the estimated relative risk of death from an increase of one in the comorbidity score proved approximately equal to that from an additional decade of age. The combined age-comorbidity score may be useful in some longitudinal studies to estimate relative risk of death from prognostic clinical covariates.

Age Factors↗

Interactions between the bud emergence proteins Bem1p and Bem2p and Rho-type GTPases in yeast.

The SH3 domain-containing protein Bem1p is needed for normal bud emergence and mating projection formation, two processes that require asymmetric reorganizations of the cortical cytoskeleton in Saccharomyces cerevisiae. To identify proteins that functionally and/or physically interact with Bem1p, we screened for mutations that display synthetic lethality with a mutant allele of the BEM1 gene and for genes whose products display two-hybrid interactions with the Bem1 protein. CDC24, which is required for bud emergence and encodes a GEF (guanine-nucleotide exchange factor) for the essential Rho-type GTPase Cdc42p, was identified during both screens. The COOH-terminal 75 amino acids of Cdc24p, outside of the GEF domain, can interact with a portion of Bem1p that lacks both SH3 domains. Bacterially expressed Cdc24p and Bem1p bind to each other in vitro, indicating that no other yeast proteins are required for this interaction. The most frequently identified gene that arose from the bem1 synthetic-lethal screen was the bud-emergence gene BEM2 (Bender and Pringle. 1991. Mol. Cell Biol. 11:1295-1395), which is allelic with IPL2 (increase in ploidy; Chan and Botstein, 1993. Genetics. 135:677-691). Here we show that Bem2p contains a GAP (GTPase-activating protein) domain for Rho-type GTPases, and that this portion of Bem2p can stimulate in vitro the GTPase activity of Rho1p, a second essential yeast Rho-type GTPase. Cells deleted for BEM2 become large and multinucleate. These and other genetic, two-hybrid, biochemical, and phenotypic data suggest that multiple Rho-type GTPases control the reorganization of the cortical cytoskeleton in yeast and that the functions of these GTPases are tightly coupled. Also, these findings raise the possibility that Bem1p may regulate or be a target of action of one or more of these GTPases.

Adaptor Proteins, Signal Transducing↗

Age-sensitive T cell phenotypes covary in genetically heterogeneous mice and predict early death from lymphoma.

We have assessed several age-sensitive indicators of immune status in young (i.e., 6 to 11-month-old) mice of a genetically heterogeneous population to see if these varied in parallel and to determine if one or more of the status indices predicted life span or cancer incidence. We report that the number of memory (i.e., CD44hi) T cells within the CD8 subset is correlated with number of memory cells in the CD4 population, and inversely correlated with the number of naive (i.e., CD45RBhi) CD4 cells at both 6 and 11 months of age, suggesting that the conversion of naive to memory cells may occur at similar rates in both T cell subsets. Mice that ranked high in the proportion of memory T cells (within the CD4 and CD8 pools) at 6 months of age tended to retain their ranking at 11 months, suggesting that the pace or extent of memory cell formation may be a consistent trait that distinguishes mice at least within a genetically heterogeneous population. Mice that at 6 months of age exhibited high levels of CD4 or CD8 memory T cells, low levels of naive CD4 cells, or low levels of T cells able to proliferate in response to Con A and IL-2 were found to be significantly more likely than their littermates to die within the first 18 months of life. Cases of follicular cell lymphoma, lymphocytic and lymphoblastic lymphoma, and hepatic hemangiosarcoma were seen within the group of mice dying at early ages.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Native oligomeric human immunodeficiency virus type 1 envelope glycoprotein elicits diverse monoclonal antibody reactivities.

We synthesized and purified a recombinant human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoprotein, lacking the gp120/gp41 cleavage site as well as the transmembrane domain, that is secreted principally as a stable oligomer. Mice were immunized with separated monomeric and oligomeric HIV-1 Env glycoproteins to analyze the repertoire of antibody responses to the tertiary and quaternary structure of the protein. Hybridomas were generated and assayed for reactivity by immunoprecipitation of nondenatured Env protein. A total of 138 monoclonal antibodies (MAbs) were generated and cloned, 123 of which were derived from seven animals immunized with oligomeric Env. Within this group, a significant response was obtained against the gp41 ectodomain; 49 MAbs recognized epitopes in gp41, 82% of which were conformational. The influence of conformation on gp120 antigenicity was less pronounced, with 40% of the anti-gp120 MAbs binding to conformational epitopes, many of which blocked CD4 binding. Surprisingly, less than 7% of the MAbs derived from mice immunized with oligomeric Env recognized the V3 loop. In addition, MAbs to linear epitopes in the C-terminal domain of gp120 were not obtained, suggesting that this region of the protein may be partially masked in the oligomeric molecule. A total of 15 MAbs were obtained from two mice immunized with monomeric Env. Nearly half of these recognized the V3 loop, suggesting that this region may be a less predominant epitope in the context of oligomeric Env than in monomeric protein. Thus, immunization with oligomeric Env generates a large proportion of antibodies to conformational epitopes in both gp120 and gp41, many of which may be absent from monomeric Env.

Amino Acid Sequence↗

Correlates of condom use among black, Hispanic, and white heterosexuals in San Francisco: the AMEN longitudinal survey. AIDS in Multi-Ethnic Neighborhoods survey.

We examined correlates of condom use among heterosexual whites, blacks, and Hispanics (ages 20-45 years) with an human immunodeficiency virus (HIV) risk factor in a community-based longitudinal sample (San Francisco; n = 716). Lag models were used to examine hypothesized antecedents of condom use at wave 2. High levels of condom use were associated with labeling one's sexual behavior as risky for HIV infection, high levels of condom enjoyment and commitment to use condoms, good sexual communication practices, gender (trend), and marital status. The results support the need for wide-ranging intervention programs that stimulate people to make personal risk assessments, teach basic sexual skills, and direct those in need of intensive help to appropriate agencies.

Adult↗

Transgenic hepatocarcinogenesis in the rat.

Although transgenic hepatocarcinogenesis has been accomplished in the mouse with a number of genetic constructs targeting the oncogene to expression primarily in the liver, no example of this process has yet been developed in the rat. Because our understanding of the multistage nature of hepatocarcinogenesis is most advanced in the rat, we have developed a strain of transgenic rats carrying the promoter-enhancer sequences of the mouse albumin gene linked 5' to the simian virus-40 T antigen gene. A line of transgenic rats bearing this transgene has been developed from a single founder female. Five to six copies of the transgene, possibly in tandem, occur within the genome of the transgenic animals, which are maintained by heterozygous matings. Livers of transgenic animals are histologically normal after weaning; at 2 months of age, small foci of vacuolated cells appear in this organ. By 4 months of age, all animals exhibit focal lesions and nodules consisting primarily of small basophilic cells, many of which exhibit considerable cytoplasmic vacuolization. Mating of animals each bearing the transgene results in rats with a demyelinating condition that develops acutely in pregnant females and more chronically in males. Ultrastructural studies of these cells indicate that the vacuoles contain substantial amounts of glycogen, with the cells resembling hepatoblasts. Malignant neoplasms with both a glandular and a hepatoblastoma/hepatocellular carcinoma pattern arise from the nodules. Enzyme and immunohistochemical studies of all lesions reveal many similarities in gene expression to comparable lesions in rats subjected to chemically induced hepatocarcinogenesis, with certain exceptions. The placental form of glutathione-S-transferase is absent from all lesions in the transgenic animal, as is the expression of connexin 32. A significant number of lesions express serum albumin, and many, but not all, exhibit the T antigen. Lesions expressing the T antigen also contain stainable amounts of the p53 gene product; by contrast, normal hepatocytes express only very low levels of the T antigen within their nuclei and no demonstrable p53. All of the animals develop hepatic lesions, and approximately one-third also develop adenomas and carcinomas derived from the islet cells of the pancreas. Although there are differences in the morphology, biology, and genetic expression in early and late hepatic lesions in this strain of transgenic rat, many similarities also occur, making this a potential model system with which to study the interactions of environmental factors with a genetic program for hepatocarcinogenesis.

Animals↗

The "hustle": socioeconomic deprivation, urban drug trafficking, and low-income, African-American male gender identity.

OBJECTIVE: Drug trafficking seems to be both prevalent and associated with considerable morbidity and mortality among inner-city African-American males. Survey data has indicated the possible importance of economic need in the rapid emergence of drug trafficking in this population. In the present study, an historical-cultural approach is used to examine this economic relationship further and to explore the role that drug trafficking plays in a society that has permitted its successful and rapid growth. METHODOLOGY: Data were obtained from interviews of approximately 600 African-Americans residing in inner-city neighborhoods in Washington, DC and Baltimore during nine drug- and acquired immunodeficiency syndrome-related studies conducted over 4 years. RESULTS AND CONCLUSIONS: From the perspective of the study participants, the need to provide economic support for one's family as well as to achieve some sense of status, respect, and reputation among one's peers are two core constructs of masculine identity in the United States. The historical and worsening inequities in access to economic resources and power by African-American males are viewed as significantly reducing the opportunity for economic success through more social or legal enterprises. Pursuit of nonmainstream activities (such as drug trafficking) is perceived as offering an opportunity for economic advancement and for establishing a power base for individuals who have been denied access to mainstream opportunities.

Adolescent↗

Characterization of heme c peptides by mass spectrometry.

Liquid secondary ion mass spectrometry, also called fast atom bombardment mass spectrometry, has been used to determine proteolytic hydrolysis sites for peptides derived from c-type cytochromes that contain covalently attached heme c. An unexpected fragmentation occurs that breaks the covalent thioether bonds between the heme and the peptide, and the heme fragment further rearranges to give rise to an intense ion at m/z of 617 that corresponds to protonated iron protoporphyrin IX. The observation of this ion fragment can be used to unambiguously identify the presence of authentic heme c in peptides or peptide mixtures at the subnanomole level.

Amino Acid Sequence↗

Magnetization of fast and slow oxidized cytochrome c oxidase.

Oxidized cytochrome c oxidase can now be prepared either to react rapidly (fast) or to react slowly (slow) with cyanide [Baker, G.M., Noguchi, M., & Palmer, G. (1987) J. Biol. Chem. 262, 595-604]. Slow oxidized cytochrome c oxidase is also characterized by an integer spin g = 12 EPR signal which is absent in the fast form. The saturation magnetization of two samples of both forms of cytochrome oxidase has been studied at four applied magnetic fields (0.3125, 1.25, 2.5, and 5.0 T) over a temperature range from 2 to 200 K using a superconducting susceptometer. The saturation magnetization data of the two preparations are readily distinguished. The data for the coupled cytochrome a3: CuB site of both preparations are most simply interpreted as exhibiting S = 2 paramagnetism with D = +13 cm-1 for the fast and D = -7 cm-1 for the slow forms, respectively. However, there is some indication that the fast form is a mixture of both S = 2 and S = 1 paramagnetic species while the slow form is only S = 2.

Animals↗

High-calcium diet in spontaneously hypertensive rats: intervention with calcium antagonist verapamil.

A number of studies have shown an antihypertensive effect for high-calcium diets, but others have found no effect or, even a prohypertensive effect. Because of these disparate results, studies were conducted in spontaneously hypertensive rats (SHR) fed either a normal calcium diet (1.0% calcium) or a high-calcium diet (4.0% calcium) with or without verapamil HCl (50 mg/kg body weight) from ages 5 to 12 weeks. Systolic blood pressure (SBP) and heart rate (HR) were measured by indirect tail cuff method. During the analysis of the electrolytes and vasoactive hormones monitored in this study, it was found that rats fed high-calcium diet had significantly elevated serum ionized and total calcium and calcium excretion. Systolic blood pressure for the verapamil-normal calcium diet (week 5, 148 +/- 4 mm Hg; week 7, 162 +/- 4 mm Hg) did not differ significantly from that of normal calcium diet (week 5, 152 +/- 2 mm Hg; week 7, 160 +/- 1 mm Hg). The high-calcium diet potentiated the development of hypertension, i.e., SBP was (157 +/- 2 mm Hg) on the 5th week and (174 +/- 4 mm Hg) on the 7th week. Conversely, verapamil high-calcium diet prevented the development of hypertension (week 5, SBP was 139 +/- 4 mm Hg; week 7, SBP was 146 +/- 3 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Diffusion imaging of experimental allergic encephalomyelitis.

Diffusion-weighted magnetic resonance imaging (MRI) was compared with T2-weighted MRI in longitudinal studies of experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis, in five monkeys (Macaca fascicularis). In a region of the brain that had highly directional myelinated fibers (internal capsule) sequential changes were identified on diffusion-weighted images on and before the day these changes were detected on conventional T2-weighted images. Changes were also identified on diffusion-weighted images in brain areas that did not develop T2-weighted abnormalities. This result suggests that diffusion-weighted image intensities are sensitive to pathologic conditions of the brain that can not be seen on T2-weighted images.

Animals↗

Membranous glomerulonephritis in association with hepatitis C virus infection.

Two bone marrow transplant recipients are described who developed nephrotic syndrome in association with hepatitis C virus (HCV) infection. Renal biopsies of both patients revealed stage I membranous glomerulonephritis. Detection of HCV genome was performed by nonisotopic in situ hybridization and reverse transcriptase polymerase chain reaction on paraffin-embedded renal biopsy specimens. Hepatitis C virus genome was detected by reverse transcription nested polymerase chain reaction on the RNA extracted from 15 5-microns paraffin sections. However, HCV genome was not revealed by nonisotopic in situ hybridization, which was likely due to the low copy number of HCV genomes present. These studies suggest that chronic HCV infection is associated with membranous glomerulonephritis.

Adult↗

Comparison of hepatocyte phenotypes at the glutathione transferase and albumin loci in Sprague-Dawley and Nagase analbuminemic rats and F1 progeny after initiation and promotion.

Hepatocarcinogenesis was examined in an initiation--promotion protocol with a single initiating dose of 7,12-dimethylbenz[a]anthracene (DMBA) followed by promotion with phenobarbital (PB) in the Nagase analbuminemic rat (NA), the Sprague-Dawley rat (SD) and their F1 crosses. All rats received a 70% partial hepatectomy, followed at 24 h by 30 mg DMBA/kg body wt or the solvent. After a 2 week recovery following surgery, half of the solvent control and initiated groups received either basal diet or promotion with 0.05% PB mixed into the basal NIH-07 diet. After 12 weeks of promotion, the rats were killed and the livers perfused and fixed in situ with paraformaldehyde. Liver slices were paraffin embedded and stained for the placental isozyme of glutathione S-transferase (PGST). The number of altered hepatic foci (AHF) expressing PGST per liver was determined by quantitative stereology and used as an endpoint for comparison of initiation in the rat strains. The NA rat had a lower response to this initiation-promotion protocol than did the SD rat. The F1 progeny of the male NA and female SD rats were more similar to the NA parent in their responsiveness to initiation, whereas the F1 progeny of the female NA and male SD were similar to the SD parent in this respect. Putative mutagenesis and carcinogenesis were examined in the F1 progeny of the female NA and male SD rat. In these rats, serial liver sections were stained either for albumin to detect putative mutations at that locus, or PGST to identify putatively initiated hepatocytes. In the NA/SD F1, the number of single hepatocytes with a putative mutation at the albumin locus was the same (3.7 x 10(5)/liver) as those expressing a common marker of preneoplasia (PGST). The number of AHF expressing PGST was approximately 5% that of the single cells exhibiting an altered expression of albumin or PGST, indicating a possible quantitative correlation between initiation and mutation in vivo when individual hepatocytes with altered gene expression were counted. These studies also suggest that only a subpopulation of the putatively initiated hepatocytes expands clonally in the presence of the promoting agent, PB. The progeny of the female NA rat crossed with the SD male rat appears to provide a useful model in which to compare mutation and carcinogenesis simultaneously in vivo.

9,10-Dimethyl-1,2-benzanthracene↗