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Biomedical subjects

C Schaefer

Publications and source records attributed to C Schaefer.

34 records · Page 2Linked to original sources
PubMed1989

Directionality of DnaA protein/DNA interaction. Active orientation of the DnaA protein/dnaA box complex in transcription termination.

The complex of DnaA protein with its 9 bp consensus binding site, the dnaA box 5'-TT(A/T)T(A/C)CA(A/C)A, blocks transcribing RNA polymerase. In a model system, the rate of transcription was monitored distal to the dnaA box 5'-TTTTCCACA by the expression of a reporter gene. DnaA-dependent transcription termination occurred irrespective of whether the dnaA box region was or was not translated. Only the dnaA box orientation 5'-TTTTCCACA on the non-coding strand, but not the reverse orientation, was active in termination. This suggests that DnaA protein contacts only one strand of the DNA duplex. Oligonucleotide-directed mutation of a dnaA box present within the dnaA coding region resulted in increased expression of dnaA. This demonstrates that DnaA protein-directed transcription termination is an element of the autoregulation of the dnaA gene.

Amino Acid Sequence↗
PubMed1989

In vivo targets of recombinant human tumour necrosis factor-alpha: blood flow, oxygen consumption and growth of isotransplanted rat tumours.

The impact of recombinant human tumour necrosis factor-alpha (1 microgram kg-1 to 1 mg kg-1; 6.6 x 10(6) U mg protein-1) on blood flow, oxygen consumption and growth of a moderately TNF-sensitive rat tumour (DS-carcinosarcoma) was studied. Tumour growth was stimulated at low TNF doses (1 and 10 micrograms kg-1) and significantly retarded at higher TNF dose levels (0.1 and 1 mg kg-1). Growth changes were concomitant with variations in oxygen consumption, lactate release and acidification of the metabolic micromilieu. Both single and repeated application of low TNF doses (1-10 micrograms kg-1 i.v.) increased tumour perfusion whereas single administration of high TNF dose levels (0.1-1 mg kg-1 i.v.) reduced tumour blood flow. After repeated application of high TNF doses tumours shrank to such small sizes that perfusion measurements could not be performed within the observation period of two weeks. It is concluded that TNF effects on solid tumours are at least partially mediated by changes in tumour perfusion. Thus, an altered tumour sensitivity towards other treatment modalities, e.g. irradiation, chemotherapy or hyperthermia, can be expected after TNF therapy. A beneficial TNF effect would critically depend on the dose level employed and on the sequence and timing of various combination regimes.

Animals↗
PubMed1989

Sociocultural factors in puerperal infectious morbidity among Navajo women.

From 1980 to 1982, a sample of 968 pregnant Navajo women in New Mexico was enrolled in a prospective study of biologic and sociocultural factors in puerperal infectious morbidity. Past studies have independently implicated both genital infection and psychosocial stressors in perinatal complications, but, to the authors' knowledge, no previous work has concurrently investigated the interactive effects of genital pathogens and psychosocial processes. Endocervical cultures for Mycoplasma hominis and Chlamydia trachomatis were obtained during prenatal visits, and structured interviews were conducted assessing social support and the degree of cultural traditionality, in this context a proxy measure of acculturative stress. The incidences of postpartum fever, endometritis, and premature rupture of membranes were significantly associated with the concurrence of two factors: the presence of genital tract M. hominis and a highly traditional cultural orientation. When demographic and conventional obstetric risk factors were controlled for, women with both M. hominis and high traditionality experienced infectious complications at a rate twice that of women with either factor alone. Among the plausible explanations for this result is the possibility that acculturative stress undermines physiologic resistance to infectious genital tract disease.

Adolescent↗
PubMed1989

Effects of tumor necrosis factor-alpha on tumor blood flow and hyperthermic treatment.

The impact of recombinant human tumor necrosis factor-alpha (rhTNF-alpha), given alone or in combination with local hyperthermia, on perfusion and growth of a moderately rhTNF-alpha-sensitive rat tumor (DS-carcinosarcoma) was investigated. DS-carcinosarcomas were implanted into the hind foot dorsum of Sprague-Dawley rats. Tumor blood flow (TBF) was measured with the krypton-85 clearance technique. Treatment with either tumor necrosis factor-alpha (0.1-1.0 mg/kg) or hyperthermia (43.3 and 44.3 degrees C, 40 min) can decrease the perfusion of malignant tumors. The TBF reduction was fully established 2 h after rhTNF-alpha injection and lasted for at least 4 h. The application of local hyperthermia (T greater than 42 degrees C) 3 h after rhTNF-alpha administration further diminished tumor blood flow. Volume growth of the tumors was monitored during repeated treatment. rhTNF-alpha (0.2 and 1.0 mg/kg i.v.) combined with hyperthermia (43.3 and 44.3 degrees C, 40 min, starting 3 h after rhTNF-alpha injection) were given every third day from the fifth to the 20th day after tumor implantation. Monotherapies retarded tumor growth in a dose-dependent manner. Combined treatment was superior to either monotherapy leading to local tumor control in 40-50% of the animals treated. It is concluded that local hyperthermia can enhance the efficacy of rhTNF-alpha treatment by further reducing tumor perfusion.

Animals↗
PubMed1989

[The effect of recombinant human tumor necrosis factor alpha on malignant tumors in vivo. Physiopathologic basis for clinical oncology].

Effects of Recombinant Human Tumor Necrosis Factor-alpha on Malignant Tumors in vivo/Pathophysiological fundamentals for clinical oncology. The impact of recombinant human tumor necrosis factor-alpha (rhTNF-alpha; 6.6.10(6) U/mg protein) on growth, metabolism and perfusion of isotransplanted rat tumors (DS-carcinosarcomas) was investigated. Tumor growth was stimulated at low TNF doses (1 and 10 micrograms/kg), and significantly retarded at higher TNF dose levels (0.1 and 1.0 mg/kg). Growth changes were paralleled by variations in perfusion and metabolism. A reduced tumor blood flow enhanced the efficacy of a subsequent heat treatment. From these results, important implications for the clinical use of rhTNF-alpha are obvious (e.g., possible growth stimulation, timing of a combination therapy with other tumor treatment modalities).

Animals↗
PubMed1988

Functions of the DnaA protein of Escherichia coli in replication and transcription.

The function of DnaA protein as a replisome organizer in the initiation of DNA replication is reviewed. A model is presented showing the construction of two basic types of DnaA-dependent replication origin. New data demonstrate that the dnaA box-DnaA protein complex is a transcription terminator. Only one orientation of the dnaA box results in termination of transcription. Mutation of the dnaA box within the dnaA reading frame shows that DnaA-mediated transcription termination has a role in the autoregulation of the dnaA gene.

Amino Acid Sequence↗
PubMed1988

Termination of the Escherichia coli asnC transcript. The DnaA protein/dnaA box complex blocks transcribing RNA polymerase.

Genes clockwise of oriC, the Escherichia coli replication origin (oriC-mioC-asnC), show anticlockwise transcription. The intergenic region between mioC and asnC contains both a terminator and a consensus DnaA-protein-binding site (dnaA box). We analysed termination in this region using galK expression to monitor for transcription. About 50% of the asnC transcripts were not terminated, and about 25% terminated at the asnC terminator. We found that the DnaA protein/dnaA box complex acts as a terminator of transcription for about 25% of the transcripts. Its efficiency could be increased by raising the level of DnaA protein, or it could be inactivated by deletion in the dnaA box or by thermal denaturation of the DnaA protein.

Bacterial Proteins↗
PubMed1987

Human recombinant interleukin 1 beta has no effect on intracellular calcium or on functional responses of human neutrophils.

The effect of human recombinant interleukin 1 beta (rIL 1 beta) on human neutrophils was examined. rIL 1 beta, even at concentrations of 100 ng/ml (100 half-maximal T cell stimulating U/ml) did not change significantly the intracellular free calcium concentration, [Ca++]i, whereas the control stimulus, fmet-leu-phe, significantly elevated [Ca++]i. rIL 1 beta also failed to stimulate production of superoxide, degranulation of lysosomal enzymes, phagocytosis of bacterial particles, chemotaxis, or chemokinesis of human neutrophils. This is substantial evidence that superphysiologic concentrations of interleukin 1 have no direct effect on [Ca++]i, as well as on functional responses of neutrophils.

Adult↗
PubMed1986

Social and cultural factors in pregnancy complications among Navajo women.

A population of 968 pregnant Navajo women was followed in a prospective study conducted from 1980 to 1983 at the Indian Health Service Hospitals in Gallup and Crownpoint, New Mexico. The purpose of the study was to examine social and cultural influences on obstetric and neonatal complications. The extent of traditional cultural practices and the availability of social support were ascertained in structured interviews completed during each woman's first prenatal visit. In a subsample of women, the occurrence of stressful life events was also measured during a final prenatal visit in the third trimester of pregnancy. Controlling for a variety of conventional risk factors and other potential confounders, traditional women sustained complications at a rate greater than twice that of the least traditional, most acculturated women (approximate relative risk = 2.1; p = 0.001). Social support and life events were modestly associated with maternal complications (approximate relative risk = 0.7, 0.8, respectively; p = 0.07), with poorer outcomes found among those with low social support and low numbers of life events. It is proposed that the relationship of maternal complications to all three sociocultural variables--traditionality, social support, and life events--may reflect the influences of social isolation on the course and outcomes of pregnancy.

Adolescent↗
PubMedDate not supplied

The complex of oriC DNA with the DnaA initiator protein.

We describe several experimental approaches relating to the early steps in the initiation of DNA replication at oriC. 1) A matrix is given which enables calculatation of the relative affinity of DnaA boxes for DnaA protein; 2) base changes within single Dna A boxes in oriC have little effect on oriC function; 3) mutations which change the distance between DnaA boxes inactivate oriC, but changes by one helical turn (+ and -) result in near wild-type oriC activity; 4) a Fis binding site was located at oriC coordinates 206-220; 5) KMnO4 probing demonstrates Dna-A-dependent unwinding in the left part of oriC in vivo and in vitro.

Bacterial Proteins↗
PubMedDate not supplied

Life event questionnaires for measuring presumptive stress.

Cumulative stress from the impact of life events has become an important variable in psychosomatic and psychological research. This article provides both short and long life events questionnaires that add to incidence information the remoteness or recency in time of a given experience. In the weight assignment system that leads to a single presumptive stress score, events remote in time have less influence than recent events. The reliability of weight assignment was checked in subject groups that differed by sex, age, and status. Women weighted life events as more stressful than did men; other differences in groups were less important. In spite of the sex differential, review of these data suggests use of the same weight assignments for all subgroups rather than differential weighting by sex and age. Reliability was also checked by test and retest methods in contrast to common sense expectation, a disappointingly low level of reliability was found. The implications for investigative use of life events questionnaires are discussed.

Adult↗
PubMedDate not supplied

[Promoting airbags:Evaluation of a public health intervention aimed at federal election candidates].

During the 1988 federal election campaign, the Directors of Community Health Departments throughout Québec met with the candidates of the three national political parties. The objectives of this intervention were to inform the candidates on the importance of regulating the installation of airbags in motor vehicles and to elicit from them a commitment to take initiatives in that direction once elected into office. This report assesses the effect of this intervention on the candidates of the Québec City region. After the intervention, two-thirds of candidates had developed a strongly favourable opinion of airbags. A majority, including 11 of the 13 Conservatives who were elected, committed themselves in writing to lobby in support of airbags. Despite this commitment, these Members of Parliament made little progress during the year following the election.

Automobiles↗