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W Schaffner

Publications and source records attributed to W Schaffner.

At least 217 records · Page 12Linked to original sources
PubMed1988

Sensitivity, specificity, and predictive value of body surface cultures in a neonatal intensive care unit.

We analyzed 24,584 cultures obtained from 3371 infants during a three-year period to determine how frequently body surface culture isolates matched those obtained subsequently from body fluids. The sensitivity, specificity, and predictive values of surface cultures were calculated daily for the two weeks up to and including the day that a body fluid culture was obtained. Isolates from cultures of material from the ear canal, nasopharynx, axilla, umbilicus, groin, rectum, stomach, and endotracheal tube were rarely the same as those recovered from blood or fluids of the cerebrospinal, joint, pleural, pericardial, and peritoneal spaces. With a frequency of sepsis of 3.3% among patients in our neonatal intensive care unit, the optimum sensitivity, specificity, and positive predictive values of surface cultures were 56%, 82%, and 7.5%, respectively. These values did not improve substantially for any specific times of surface cultures prior to sepsis, for anatomic sites cultured, or for pathogens recovered. We conclude that surface cultures are of limited value in predicting the etiology of sepsis in neonates.

Algorithms↗
PubMed1988

Failure of hospitals to promote the use of child restraint devices.

Motor vehicle accidents are the leading cause of death in children. In 1977, Tennessee adopted the nation's first law requiring the use of child restraint devices (CRDs), but despite extensive promotional efforts, a majority of young children still travel unrestrained. We surveyed all acute-care hospitals in Tennessee to determine their policies regarding CRDs. Of 109 hospitals with obstetric services, 28 (26%) had a policy calling for discharged newborns to be transported in CRDs; only seven (5%) of 128 pediatric services had such a policy. It is time for hospitals and professional organizations to adopt policies to ensure that the parents of every child discharged from an obstetric or pediatric unit are educated concerning CRD use laws and are able to comply with them. Pediatricians should consider incorporating "discharge in child restraint device" into their routine discharge orders.

Accidents, Traffic↗
PubMed1988

Metal binding 'finger' structures in the glucocorticoid receptor defined by site-directed mutagenesis.

The glucocorticoid receptor and the other members of the steroid receptor super-family share a highly conserved, cysteine-rich region which coincides with the DNA binding/transactivating domain. It has been postulated that this region is folded into two 'zinc finger' structures, similar to those originally reported for the transcription factor TFIIIA. The first potential finger domain contains four conserved cysteines and one conserved histidine, while the second contains five conserved cysteines. Using site-directed mutagenesis, we have analysed the consequences of altering the proposed finger-like structures. Our results show that most of the mutations affecting the conserved cysteines result in a total loss of glucocorticoid receptor function. In one important exception, however, a conserved cysteine (Cys500) is dispensable for glucocorticoid receptor activity and therefore cannot be involved in complexing a metal ion to form a finger structure. Moreover, the replacement of either Cys476 or Cys482 by His residues maintains partial in vivo activity of the glucocorticoid receptor, while their exchange for an alanine or serine residue, respectively, eliminates receptor function. These results support, at a genetic level, the involvement of cysteines of the glucocorticoid receptor DNA binding domain in metal ion complexation and define the candidate residues involved in such coordination.

Amino Acid Sequence↗
PubMed1988

A large outbreak of mumps in the postvaccine era.

During a county-wide mumps outbreak in Nashville, Tennessee, 332 cases of mumps were identified at a public high school (attack rate, 18.8%). A pep rally 17 d before the peak of the outbreak at a single public high school may have provided an opportunity for point-source exposure. A case-control study demonstrated that vaccine efficacy was 75% (we used provider-verified records and excluded students with a history of mumps disease). Although school records were nonuniform, mumps immunization status was correct, compared with provider-verified records, in at least 85% of both cases and controls. Parental reports were much less reliable. The cost of the outbreak was estimated at $154/case. Receiving mumps vaccine at a vaccine clinic held after the outbreak had peaked was associated with a decrease in risk of mumps disease. Thus, these clinics may have a role in the control of such outbreaks.

Adolescent↗
PubMed1988

Sp1 transcription factor binds DNA and activates transcription even when the binding site is CpG methylated.

In vertebrates, a negative correlation between gene activity and CpG methylation of DNA, notably in the promoter region, is well established. Therefore, it is conceivable that differential binding of transcription factors to methylated versus unmethylated binding sites is crucial for gene activity. Since the consensus binding site of transcription factor Sp1 contains a central CpG, we have investigated the binding of Sp1 factor to unmethylated and synthetically CpG-methylated DNA. A strong Sp1 binding site was methylated on both strands at two CpG positions, located in the center and at the periphery of the recognition sequence. Our studies show that neither binding in vitro, nor transcription in vivo and in vitro are affected by methylation of the Sp1 binding site. We discuss the possibility that binding of Sp1 factor, which is often associated with promoters of housekeeping genes, prevents CpG methylation.

Animals↗
PubMed1988

AIDS awareness in the conduct of radiologic procedures: guidelines to safe practice.

The epidemic of the acquired immunodeficiency syndrome (AIDS) has affected all geographic regions of the United States. Indeed, it is likely that a majority of U.S. hospitals have cared for patients who are infected with the human immunodeficiency virus (HIV), the virus that causes AIDS. More than 46,000 individuals with HIV infection have fulfilled the strict diagnostic criteria for AIDS (1). All of these patients with AIDS have been seriously ill and have been hospitalized, often multiple times and for prolonged periods. Another, larger group patients with HIV infection has had another form of the disease, the so-called AIDS-related complex. Many of these patients have also spent time in hospitals. An even larger group of individuals has been infected with HIV but has remained asymptomatic to date. Some of these persons have been admitted to hospitals or have received outpatient diagnostic procedures for intercurrent medical or dental complaints that were unrelated to their asymptomatic HIV infection. At the time of their medical evaluation, some of these asymptomatic individuals were known to have a positive HIV antibody test. It is likely, however, that the serologic status of the majority of asymptomatically infected patients was unknown. Thus, by now a very large number of health-care personnel in the United States, including diagnostic radiology staff, have assisted in the care of HIV-infected patients.

Acquired Immunodeficiency Syndrome↗
PubMed1987

OVEC, a versatile system to study transcription in mammalian cells and cell-free extracts.

We have developed a vector, OVEC ("oligonucleotide vector") to study DNA sequences involved in the regulation of transcription in mammalian cells. This vector is equally suitable for studying expression in vivo after transfection into cells, or for transcription studies in vitro with cell-free extracts. Putative cis-acting DNA segments from enhancers or promoters can be inserted at a position immediately upstream of the TATA box and coding sequence of the rabbit beta-globin gene. A regulatory DNA segment can be tested by itself or in conjunction with an enhancer located either in an adjacent upstream position, or downstream of the beta-globin gene. S1 nuclease mapping can be used to study transcription from circular and linear templates and run-off transcription in vitro is also feasible. Transcripts from a reference globin gene with a small deletion around the transcription initiation site can be measured with the same S1 nuclease probe and thus serve as an internal standard. We demonstrate the usefulness of OVEC by inserting either short oligonucleotides comprising a metal responsive enhancer element, or the SV40 enhancer, directly upstream of the TATA box. Both constructs yield high levels of correctly initiated transcripts in a transient expression assay in HeLa cells. In a HeLa cell nuclear extract the SV40 enhancer stimulates transcription 40-fold.

Animals↗
PubMed1987

An outbreak of organic dust toxic syndrome in a college fraternity.

An explosive outbreak of a febrile respiratory illness occurred among members of a college fraternity. The preponderant signs and symptoms were muscle aches, cough, and low-grade fever. All illnesses occurred within 1.3 to 13 hours of attendance at a party where there was a dense airborne dust from straw that had been laid on the floor. Of the 67 fraternity members who attended the party and answered a questionnaire, 55 became ill (attack rate, 82%). Risk of illness was higher for those who spent more time at the party. Duration of illness ranged from 4.5 hours to seven days. Results of serological studies did not demonstrate an allergic or viral cause for these illnesses. The clinical and epidemiologic features of this outbreak were characteristic of organic dust toxic syndrome, an acute respiratory illness caused by inhalation of molds growing on hay, silage, or other agricultural products.

Adult↗
PubMed1987

Psychotropic drug use and the risk of hip fracture.

To assess the risk of hip fracture associated with the use of four classes of psychotropic drugs, we performed a case-control study of 1021 patients with hip fractures and 5606 controls among elderly Medicaid enrollees. Persons treated with hypnotics-anxiolytics having short (less than or equal to 24 hours) elimination half-lives had no increased risk of hip fracture. By contrast, a significantly increased risk was associated with current use of hypnotics-anxiolytics having long (greater than 24 hours) elimination half-lives (odds ratio, 1.8; 95 percent confidence interval, 1.3 to 2.4), tricyclic antidepressants (odds ratio, 1.9; 95 percent confidence interval, 1.3 to 2.8), and antipsychotics (odds ratio, 2.0; 95 percent confidence interval, 1.6 to 2.6). The risk increased in relation to the doses of drugs in these three classes. An analysis for possible confounding by dementia did not alter the results. Previous but noncurrent use of drugs in these classes conferred no increase in risk. Although a cause-and-effect relation was not proved, these data support the hypothesis that the sedative and autonomic effects of psychotropic drugs increase the risk of falling and fractures in elderly persons. The results suggest the need for studies of this association in other populations and for evaluation of newer psychotropic drugs with fewer undesirable sedative and autonomic effects.

Accidental Falls↗
PubMed1987

Cell type-specificity elements of the immunoglobulin heavy chain gene enhancer.

A strong transcriptional enhancer was created by oligomerization of a short segment from the immunoglobulin heavy chain (IgH) enhancer. This segment was analyzed in parallel for biological activity in vivo and factor binding in vitro. In transfection experiments the oligomerized segment stimulates transcription in a cell type-specific manner similar to the entire IgH enhancer. Transfections of mutants identified two sequence motifs whose integrity is required for efficient and cell type-specific activity of this enhancer. The first is a sequence suggested previously to be bound by a factor in vivo, and the second is a highly conserved decanucleotide which also occurs in Ig variable gene promoters. The ability of these two sequence motifs to bind proteins in vitro was tested by band shift assays. Under our in vitro conditions we could not detect proteins binding to the in vivo footprint region. However, we found protein factors binding to the decanucleotide. A ubiquitous form of this factor is present in every cell line analyzed. Additional variants are detected exclusively in cells where the IgH enhancer and the segment thereof are active. Elimination of the decanucleotide motif is not only a strong down mutation in vivo but also abolishes binding of all factor variants in vitro. Thus our data suggest that the two enhancer motifs analyzed are involved in positive rather than negative control of transcription.

Base Sequence↗
PubMed1987

A transcriptional enhancer located between adult beta-globin and embryonic epsilon-globin genes in chicken and duck.

We have detected a transcriptional enhancer sequence downstream from the adult beta-globin (beta A-globin) genes of chicken and duck. DNA segments from the beta-globin coding and flanking sequences were cloned into expression vectors containing the SV40 promoter linked to either the T antigen gene or the cat gene. The expression of these genes was measured in a chicken erythroid cell line transfected with the recombinant plasmids. We found that segments located about 400 bp downstream from the poly(A) site of both the chicken and duck beta A-globin genes (and about 1.5 kb upstream from the embryonic epsilon-globin gene) stimulate transcription of the test genes about five-fold. In chicken essentially the same segment was also found by others to act as an erythroid cell-specific enhancer [Hesse et al., Proc. Natl. Acad. Sci. USA 83 (1986) 4312-4316; Choi and Engel, Nature 323 (1986) 731-734]. The sequence containing this enhancer is conserved in evolution. A high degree of homology, reaching 84% in a segment 180 bp in length, was found between chicken and duck despite an evolutionary divergence of 70 myr.

Animals↗
PubMed1987

The SV40 enhancer can be dissected into multiple segments, each with a different cell type specificity.

The SV40 enhancer is known to be active in a wide variety of tissues and species. It contains a number of sequence motifs that can be bound by protein factors and whose integrity is essential for full enhancer activity. We have individually analyzed three synthetic oligonucleotides derived from sequences present within the SV40 enhancer: two oligonucleotides contain variants of the enhancer "core" sequence (designated corePVUII and coreC) and the third represents a region containing a decanucleotide homology to the immunoglobulin promoters/enhancers (designated SPHI). The oligonucleotides were multimerized and linked to a beta-globin test gene. Transcripts of the test gene were analyzed following transient expression in 10 cell lines representing a broad spectrum of tissues. We show that each of the three short segments can individually act as an enhancer when present in multiple copies. None of these enhancers is ubiquitously active; however, each shows activity in a distinctive subpopulation of cell lines. This cell type specificity is most remarkable in the case of the two oligonucleotide segments containing the core sequences. One of these is primarily active in CV-1 cells, whereas the other exhibits a cell type specificity identical to that of the entire enhancer, possibly identifying it as the most important sequence element within the native SV40 enhancer. Our data suggest that a particular cell type specificity is typical for individual enhancer segments, and that enhancers of differing specificity can be assembled from the individual sequence motifs by combining them in different patterns.

Animals↗
PubMed1987

A purine-rich DNA sequence motif present in SV40 and lymphotropic papovavirus binds a lymphoid-specific factor and contributes to enhancer activity in lymphoid cells.

The enhancer of simian virus 40 (SV40) is active in a wide variety of tissues and hosts and thus has been called a general enhancer. Previous work has established that this region contains a number of subsegments, each with a different cell type specificity. By analyzing enhancer deletion mutants of SV40 with a restricted cell type specificity, we have identified a purine-rich DNA motif (Pu box) that is essential for activity of the mutant enhancer in lymphoid cells and also obtained evidence for an independent element that confers activity in kidney CV-1 cells. The Pu box element is positively regulated since binding of a cognate factor(s) was only observed in lymphoid cell extracts. The Pu box is also present in the 63-bp enhancer repeat of lymphotropic papovavirus (LPV), and competition experiments show that the SV40 and LPV sequences bind the same factor(s). Thus, the Pu box is likely to be a major determinant of the lymphotropic host range of LPV. In SV40, however, the Pu box is one of several enhancer elements with different cell specificities. We suggest that such an arrangement reflects a diversification strategy of SV40 to maximize its chance of adaptation to various types of host cells.

Animals↗