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Biomedical subjects

J Ackerman

Publications and source records attributed to J Ackerman.

At least 19 recordsLinked to original sources

The weak interdomain coupling observed in the 70 kDa subunit of human replication protein A is unaffected by ssDNA binding.

Replication protein A (RPA) is a heterotrimeric, multi-functional protein that binds single-stranded DNA (ssDNA) and is essential for eukaryotic DNA metabolism. Using heteronuclear NMR methods we have investigated the domain interactions and ssDNA binding of a fragment from the 70 kDa subunit of human RPA (hRPA70). This fragment contains an N-terminal domain (NTD), which is important for hRPA70-protein interactions, connected to a ssDNA-binding domain (SSB1) by a flexible linker (hRPA70(1-326)). Correlation analysis of the amide (1)H and (15)N chemical shifts was used to compare the structure of the NTD and SSB1 in hRPA70(1-326) with two smaller fragments that corresponded to the individual domains. High correlation coefficients verified that the NTD and SSB1 maintained their structures in hRPA70(1-326), indicating weak interdomain coupling. Weak interdomain coupling was also suggested by a comparison of the transverse relaxation rates for hRPA70(1-326) and one of the smaller hRPA70 fragments containing the NTD and the flexible linker (hRPA70(1-168)). We also examined the structure of hRPA70(1-326) after addition of three different ssDNA substrates. Each of these substrates induced specific amide (1)H and/or (15)N chemical shift changes in both the NTD and SSB1. The NTD and SSB1 have similar topologies, leading to the possibility that ssDNA binding induced the chemical shift changes observed for the NTD. To test this hypothesis we monitored the amide (1)H and (15)N chemical shift changes of hRPA70(1-168) after addition of ssDNA. The same amide (1)H and (15)N chemical shift changes were observed for the NTD in hRPA70(1-168) and hRPA70(1-326). The NTD residues with the largest amide (1)H and/or (15)N chemical shift changes were localized to a basic cleft that is important for hRPA70-protein interactions. Based on this relationship, and other available data, we propose a model where binding between the NTD and ssDNA interferes with hRPA70-protein interactions.

Amides↗

Reflections on validity and epistemology in a study of working relations between deaf and hearing professionals.

In this article, a research study that examined the working relationships between Deaf and hearing professionals in health and educational services in the United Kingdom is addressed. These service providers worked in bilingual organizations where both British Sign Language and English were used and in which Deaf people's identity as a cultural-linguistic minority was accepted. The focus of this article is on issues of validity and epistemology that arose for the Deaf and hearing research team in the course of this study. In particular, it examines the influence of identity attributions on the research process for researchers operating within a context of historical oppression, minority language use and legitimization of research knowledge, and challenges to the interpretative analysis used in the study that arose from the dynamics of majority-minority power relations in the wider social world.

Communication↗

Reconstruction of the severely atrophic maxilla in a young adult with periodontosis.

Reconstruction of the atrophic maxilla in a young adult presents unique challenges. This article describes reconstruction in a 30-year-old patient using a two-stage procedure. Bilateral maxillary sinus augmentations with simultaneous corticocancellous grafting to the anterior maxilla and alveolar ridge were performed. Eight endosseous implant fixtures were subsequently placed into the maxilla after a five-month healing phase. Six months later the implants were uncovered, healing abutments placed and a maxillary vestibuloplasty performed. The rationale behind this treatment and a review of the literature are discussed.

Adult↗

Effect of normal ageing on the sites of aortic bifurcation and inferior vena cava confluence: a CT study.

The object of this retrospective study was to determine the sites of abdominal aortic bifurcation and inferior vena cava confluence in relation to age and sex. The study group comprised 180 subjects (90 males and 90 females) divided into 9 groups by age (in decades). The positions of the aortic bifurcation and the inferior vena cava confluence were evaluated by CT, and linear regression models were fitted to the data. The positions of the aortic bifurcation and venous confluence showed a highly significant downward shift with increasing age (p = 0.0001). The shift was more pronounced in women. The mean site of the aortic bifurcation for the whole group was at lower L4 (range, upper L3 to upper S1); in males, it was at upper L4 (range, upper L3 to upper L5), and in females at lower L4 (range, upper L3 to upper S1). The mean site of the venous confluence for the whole group was at disc L4-L5 (range, lower L3 to upper S1); in males, it was at disc L4-L5 (range, upper L4 to disc L5-S1), and in females at disc L4-L5 (range, lower L3 to upper S1). Thus, the aorta and the inferior vena cava can extend as low as the level of S1. These data are of relevance in laparoscopic procedures, especially in laparoscopic lumbar discectomy.

Adolescent↗

Suspended rocking cradles, positional asphyxia, and sudden infant death.

OBJECTIVE: To describe the risk of unexpected death in infants who are placed in suspended rocking cardles. MAIN OUTCOME MEASURES: Ten cases of sudden infant death and 5 cases of infant asphyxia with successful resuscitation reported to the Consumer Product Safety Commission were analyzed. The death scene investigation reports and autopsy material were made available for evaluation. All 15 cases implicated a suspended head-to-toe rocking cradle. RESULTS: Infants were aged 3 months or younger and were found in the facedown prone position when discovered. The cradle was tilted at greater than 5 degrees, and the head was wedged at one end of the cradle. A locking pin was not used in 14 cases. Ten of the 15 infants died. The autopsy reports listed sudden infant death syndrome as the cause of death. CONCLUSIONS: Suspended rocking cradles represent a potentially lethal sleeping environment and should not be used without a locking pin in place. Infants should be placed in the supine position for sleep.

Asphyxia↗

IS outlook '96: predictions & predilections. Roundtable discussion.

Musings from some of the leading national and international HIT organizations make it clear that the need for a computer-based patient record is approaching the critical point. Half of our respondents identified the CPR as the single most important technology in 1996. One of our participants goes so far as to say that the era prior to the electronic medical record will one day be remembered as the "paper age." Progress in the development of standards--crucial to the CPR--could be dramatic this year, say experts from two of the major standards organizations. For a look at these issues and others, including key government policies to watch this year, read on.

Computer Communication Networks↗

The role of p53 mutations in bilateral breast carcinoma.

Mutations of the tumor suppressor gene p53 have been implicated in certain familial cases of breast cancer. We examined a series of 38 cases of nonfamilial bilateral breast cancer using antibodies CM1 and DO7 to p53 wild-type and mutant protein (Novocastra Laboratories) by the avidin-biotin-peroxidase complex method. The two antibodies reacted similarly. Mutant p53 protein was detected in 17 of 76 (22%) tumors but in only 3 of 38 (8%) paired tumors. There were no significant differences in p53 expression between synchronous (< 12 mos) and metachronous tumors (29% vs 17%, P = 0.09) or between first and second tumors (14% vs 26%, P = 0.29). Mutant p53 was detected bilaterally in one metachronous and two synchronous cases, which were amplified and sequenced and two synchronous cases, which were amplified and sequenced by polymerase chain reaction and single strand confirmation polymorphism. One synchronous case showed a bilateral mutation in exon 2-3; the other had a bilateral mutation in exon 8-9. In the metachronous case, a mutation could be demonstrated in only one breast. Analysis of all tumors demonstrated that when p53 protein is overexpressed in the first tumor, there is a 60% probability of overexpression in the second, whereas if absent from the first, it is unlikely to be present in the second. These data suggest that p53 mutations do not play a major role in the pathogenesis of bilateral disease in most women.

Adult↗

Competition turns to United Healthcare for technology edge. Interview by Carolyn Dunbar and Michael L. Laughlin.

Joel Ackerman serves as director of advanced technologies for Minneapolis-based ProviderLink, an electronic claims software subsidiary of United Healthcare Corporation. United Healthcare is a managed-care company that owns and operates 19 fee-for-service and capitated health maintenance organizations in 15 states serving almost two million members. In addition, United Healthcare has subsidiary operations selling services to more than 80 other Blue Cross Blue Shield plans and indemnity and HMOs--including its competitors. These services include managing departments such as pharmacy, providing specialized contract clinics like mental health or chemical dependency, performing utilization-review services, and providing computer outsourcing such as enrollment and electronic claims processing. Ackerman has been involved in both American National Standards Institute (ANSI) efforts and the Health and Human Service's Workgroup on Electronic Data Interchange (WEDI).

Administrative Personnel↗

Anti-CD4 mediates clonal anergy during transplantation tolerance induction.

Depletion of CD4+ cells using anti-CD4 monoclonal antibodies leads to allograft tolerance. Here we show that anti-CD4-mediated tolerance to pancreatic islets of Langerhans transplanted from an A/J (IEk) donor to a diabetic C57B1/6 (B6) (IE-) recipient occurs in the absence of clonal deletion of the potentially IE-reactive V beta 11+ T cells. Instead, a state of clonal anergy is induced in both the CD4+V beta 11+ and CD8+V beta 11+ T cell subsets. This clonal anergy can be partially overcome in vitro by the addition of recombinant interleukin 2.

Animals↗

Effect of maternal administration of thyrotropin-releasing hormone or DN1417 on functional and morphologic fetal rabbit lung maturation and duration of survival after premature delivery.

Though maternal treatment with thyrotropin-releasing hormone (TRH) for prevention of hyaline membrane disease has been utilized, precise mechanisms of TRH in accelerating fetal lung maturation remain unclear. We studied the effect of maternally administered TRH or DN1417 (an analog of TRH) on functional and morphologic fetal rabbit lung maturation and the duration of survival after premature delivery. Because DN1417 retains the neurotransmitter but not the neuroendocrine effects of TRH, this study enables us to determine which of these effects was responsible for enhancement of lung maturation. TRH or DN1417 (0.2 mg/kg/dose) or saline was injected intravenously into New Zealand White rabbit does 48, 36, 24, 12 and 2 h prior to sacrifice on day 27 of gestation. Functional pulmonary maturity was assessed by pressure-volume hysteresis, and morphologic maturity was assessed by histologic technique. Maternal administration of TRH or DN1417 enhanced both functional and morphologic fetal lung maturation as well as the duration of neonatal survival after premature delivery. We propose that the effect of TRH in fetal lung maturation is due to neurotransmitter rather than neuroendocrine effects.

Animals↗