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Biomedical subjects

W Schaffner

Publications and source records attributed to W Schaffner.

At least 253 records · Page 14Linked to original sources
PubMed1985

The effects of calcitonin on central neurons in the rat.

The effects of salmon calcitonin on central neurons were studied in anesthetized rats. Calcitonin applied iontophoretically consistently inhibited spontaneous activity in half of the neurons tested in the anterior hypothalamic nucleus and subthalamus but had virtually no effect on cortical and thalamic neurons. Calcitonin also inhibited glutamate-evoked activity in the neurons tested. Calcitonin administered into the brain ventricular system led to a marked decrease in spontaneous discharge of hypothalamic cells in the majority of cells tested. The onset of this response began within 20 and 30 min of calcitonin application.

Animals↗
PubMed1985

Food-borne streptococcal pharyngitis in a hospital pediatrics clinic.

After a potluck luncheon, more than half the staff of a hospital pediatrics clinics became ill. Group A Streptococcus (M precipitin, nontypable; T agglutination type, 8/25; and serum opacity reaction, positive) was isolated from 12 of the 20 ill persons. Food-consumption analysis implicated a rice dressing as the vehicle of transmission. The dressing was prepared by a clinic employee in whom pharyngitis had developed three weeks before the luncheon. This is an unusual outbreak in that the implicated food product was not institutionally or commercially prepared and was not preponderantly composed of milk, eggs, or meat.

Disease Outbreaks↗
PubMed1985

Enhancer activity correlates with the oncogenic potential of avian retroviruses.

Avian retroviruses lacking an oncogene, such as Rous-associated virus 1 (RAV-1), RAV-2, and td mutants of Rous sarcoma virus (RSV), can nevertheless cause leukemias and other neoplastic diseases. During this process, viral DNA integrates near a cellular proto-oncogene, such as c-myc, and thus de-regulates its expression. The virus RAV-0, on the other hand, is known to be non-oncogenic even in long-term in vivo infections of domestic chickens. The major difference between oncogenic and non-oncogenic viruses is found within the U3 region of the long terminal repeat (LTR) which is known to harbor the promoter and enhancer elements. We therefore wanted to see whether viral oncogenicity was correlated with enhancer activity. Using a variety of techniques (including the SV40 'enhancer trap' from which we obtained RSV-SV40 recombinant viruses), we demonstrate that a strong enhancer exists within the LTRs of both RSV and RAV-1. In contrast, no enhancer is present in RAV-0, although RAV-0 has functional promoter elements. Our data therefore strongly support a concept of oncogenesis by enhancer insertion.

Animals↗
PubMed1985

A transcription enhancer in the Herpesvirus saimiri genome.

Herpesvirus saimiri, an oncogenic agent of New World primates, has a linear double-stranded DNA genome of approximately 155 kb. To test its genome for the presence of a transcription enhancer, we have mixed randomly fragmented H. saimiri DNA with non-infectious, linear SV40 DNA lacking the 72-bp repeat enhancer region (the so-called SV40 enhancer trap) and co-transfected this DNA mixture into monkey CV-1 cells. Viable SV40-like viruses were generated by intracellular ligation/repair processes with short H. saimiri DNA fragments. One recombinant, SVHS-2, had integrated a 377-bp enhancer segment from the righthand region of the H. saimiri genome, 7 kb upstream of DNA sequences encoding an immediate-early mRNA. This enhancer sequence is contained within the non-repetitive portions of the viral genome known to be preserved episomally in all lymphoid tumor cell lines. Further recombinant viruses (SVHS-14, SVHS-7, and SVHS-8) essentially contain subsets of the 377-bp insert. Unlike in the previous enhancer trap experiments, where heterologous enhancers were incorporated without any sequence alterations, SVHS-14 and SVHS-7 have suffered short internal deletions of a very similar segment of the H. saimiri insert. This renders the enhancer more active, implying that the deleted segment, while it may have a role in the herpesvirus infection cycle, exerts a negative effect within the isolated enhancer.

Antigens, Viral, Tumor↗
PubMed1985

Cell-type preference of immunoglobulin kappa and lambda gene promoters.

Immunoglobulin gene constant regions are known to be associated with strictly tissue-specific enhancer elements. Until recently the promoter of the variable region, which becomes linked to the constant region by somatic rearrangement, could have been viewed as a passive recipient of the enhancer stimulus. Here we show that the promoters of the immunoglobulin kappa and lambda light chain genes are approximately 20-30 times more active in lymphoid cells than in non-lymphoid cells. To avoid the problem of differential mRNA stability upon transfection of immunoglobulin genes into non-lymphoid cells we have constructed chimeric genes. All kappa mRNA sequences were progressively deleted to fuse the kappa gene promoter to a globin gene coding body. A similar chimeric gene was constructed with the promoter of the lambda gene. The cell-type preference of the promoter may be exploited during B-lymphocyte differentiation to regulate the immunoglobulin gene promoter independently from the enhancer.

Animals↗
PubMed1985

High frequency of homologous recombination in mammalian cells between endogenous and introduced SV40 genomes.

We have detected a high frequency of homologous recombination between introduced and chromosomal DNA in mammalian cells. Linear enhancerless SV40 DNA has been transfected into monkey cells that have either one (COS1 cells) or five to seven (COS7 cells) copies of the SV40 early region stably integrated into their genome. Enhancer-containing wild-type SV40 DNA is formed as a result of homologous recombination of the introduced DNA with chromosomal DNA. Up to 25% of the successfully transfected cells produce wild-type virus within 48 hr after transfection. The highest levels of wild-type virus were produced from transfections of molecules that contained a double-strand break at positions of uninterrupted homology with the chromosomal template. This SV40/COS cell system provides a rapid assay for recombination between introduced and genomic DNA.

Animals↗
PubMed1985

A very strong enhancer is located upstream of an immediate early gene of human cytomegalovirus.

A strong transcription enhancer was identified in the genomic DNA (235 kb) of human cytomegalovirus (HCMV), a ubiquitous and severe pathogen of the herpesvirus group. Cotransfection of enhancerless SV40 DNA with randomly fragmented HCMV DNA yielded two SV40-HCMV recombinant viruses that had incorporated overlapping segments of HCMV DNA to substitute for the missing SV40 enhancer. Within HCMV, these enhancer sequences are located upstream of the transcription initiation site of the major immediate-early gene, between nucleotides -118 and -524. Deletion studies with the HCMV enhancer, which harbors a variety of repeated sequence motifs, show that different subsets of this enhancer can substitute for the SV40 enhancer. The HCMV enhancer, which seems to have little cell type or species preference, is severalfold more active than the SV40 enhancer. It is the strongest enhancer we have analyzed so far, a property that makes it a useful component of eukaryotic expression vectors.

Base Sequence↗
PubMed1985

A long and complex enhancer activates transcription of the gene coding for the highly abundant immediate early mRNA in murine cytomegalovirus.

Using the simian virus 40 "enhancer trap" approach, we have identified a transcription enhancer located just upstream of the major immediate early gene of murine cytomegalovirus. This enhancer has several striking properties. (i) Together with the enhancer of human cytomegalovirus, it is the strongest transcription enhancer found to date. (ii) It is an extremely long enhancer, spanning greater than 700 base pairs. (iii) It consists of a rather complex pattern of sequence repeats, the longest of which is 181 base pairs. Also, several types of short sequence motifs are scattered throughout the enhancer in monomeric, heterodimeric, or homodimeric (palindromic) form. These motifs have been identified to be components of other enhancers and promoters, and they are presumably binding sites for specific nuclear factors. Our analysis suggests that enhancers are composed of a modular arrangement of short conserved sequence motifs and that enhancer strength is correlated with the redundancy of these motifs.

Animals↗
PubMed1985

The detection of penicillin-resistant pneumococci. The compliance of hospital laboratories with recommended methods.

Isolations of pneumococci with diminished susceptibility to penicillin have been reported with increasing frequency in recent years. The first reported isolations of such organisms in Tennessee occurred in December 1982, and prompted a survey of acute-care hospitals to determine the methods being used to test pneumococcal isolates for penicillin susceptibility. All 77 acute-care hospitals in Tennessee with 100 or more beds were surveyed. Eighteen (23%) did not test the penicillin susceptibility of any pneumococcal isolates obtained from blood or cerebrospinal fluid. Thirty-eight hospitals (49%) tested some or all such isolates, but did not perform the tests in accord with established standards; 21 (27%) properly tested all such isolates. There was no correlation between the proper testing of pneumococcal isolates for penicillin susceptibility and the mode of governance, numbers of beds, or medical school affiliations of the respondent hospitals. It is recommended that appropriate pneumococcal isolates be tested for penicillin susceptibility. Such testing is most reliably performed by the disk diffusion method, using a 1-microgram oxacillin disk.

Adult↗
PubMed1985

Factors associated with early demise in nursing home residents: a case control study.

A case-control study was performed to identify factors differentiating nursing home residents who die within 12 months of admission (decedents) and those who survive for at least four years (survivors). Using Tennessee Medicaid data, 49 decedent/survival pairs admitted during the same year were matched for age, race, sex, nursing home, and diagnosis. There were no significant differences between the decedent and survivor groups in demographic factors, sensory impairments, physical handicaps, or number of drugs prescribed. Assessments of the ability to perform activities of daily living were found to be strongly associated with survival, providing a valuable prognostic tool. The authors suggest that personnel providing care for patients of advanced age would benefit from instruction in making such assessments.

Activities of Daily Living↗
PubMed1985

Tularemia: a 30-year experience with 88 cases.

Drawing upon our experience with 88 cases and a survey of the English literature, we reviewed the clinical, pathophysiological, and epidemiological aspects of tularemia. Tularemia can be thought of as two syndromes--ulceroglandular and typhoidal. This dichotomy simplifies earlier nomenclature and emphasizes the obscure typhoidal presentation. Clinical manifestations suggest that the two syndromes reflect differences in host response. In ulceroglandular tularemia the pathogen appears to be well contained by a vigorous inflammatory reaction. Pneumonia is less common and the patient's prognosis is good. In typhoidal disease there are few localizing signs; pneumonia is more common; and the mortality without therapy is much higher, suggesting that the host response is somehow deficient. Francisella tularensis is an extremely virulent pathogen capable of initiating infection with as few as 10 organisms inoculated subcutaneously. During an incubation period of 3 to 6 days the host responds first with polymorphonuclear leukocytes and then macrophages. Granulocytes are unable to kill the pathogen without opsonizing antibody leaving cellular immunity to play the major role in host defense. One to 2 weeks after infection, a vigorous T-lymphocyte response can be detected in vitro with lymphocyte blast transformation assays and in vivo with an intradermal skin test, which, unfortunately, is not commercially available. Humoral immunity, often used as a diagnostic modality, appears 2 to 3 weeks into the illness. Cellular immunity is long-lasting, accounting for the common reoccurrence of localized disease upon repeated exposures to the pathogen. There are no symptoms that distinguish the ulceroglandular from the typhoidal syndrome. A pulse-temperature dissociation is seen in less than half of the patients. The location of ulcers and enlarged lymph nodes give a clue to the likely vector since lesions located on the upper extremities are more commonly associated with mammalian, and those of the head and neck and lower extremities with arthropod, vectors. Pharyngitis, pericarditis, and pneumonia can complicate both syndromes, although the latter is much more common in typhoidal disease. Hepatitis, usually of a mild degree, is common and occasionally erythema nodosum is seen. No specific laboratory tests characterize tularemia, and cultures of the pathogen are often difficult to obtain because of the special growth requirements of Francisella tularesis and the inability of many clinical laboratories to handle the dangerous pathogen.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1984

Unrearranged immunoglobulin lambda variable region is transcribed in kappa-producing myelomas.

Most cell lines which secrete immunoglobulin kappa chains retain their lambda light chain genes in the germline configuration. We report that the lambda variable (V lambda) region is nevertheless transcribed in such kappa-secreting cells at a steady-state level of 1-10 RNA molecules per cell. These transcripts are developmentally regulated since they are not detectable in cell lines representative of earlier stages of B-lymphocyte differentiation. Therefore, the same cellular components which recognize and activate the unrearranged V lambda segment may also regulate the expression of the productive immunoglobulin genes. V lambda transcripts are initiated at the lambda gene cap site, include the variable region, and extend approximately 175 nucleotides into the adjacent spacer DNA. The transcripts are polyadenylated, properly spliced and transported into the cytoplasm. Interestingly, the spacer sequence contains an open reading frame which extends the V lambda coding region for an additional 37 amino acids. It is likely that V lambda transcripts are translated into an elongated protein which may play a regulatory role in B-lymphocyte differentiation.

Amino Acid Sequence↗
PubMed1984

The use and efficacy of child restraint devices. The Tennessee experience, 1982 and 1983.

The Tennessee Child Passenger Protection Act, mandating the use of child restraint devices for children younger than 4 years, took effect in 1978. In the years 1978 through 1983, eighty-one children younger than 4 years died in Tennessee traffic accidents; only two were in child restraint devices. During this period, as child restraint device use rose from 8% to more than 30%, the number of deaths among children younger than 4 years declined more than 50%. Analysis of supplemental accident reports filed in investigations of motor vehicle accidents involving children younger than 4 years during 1982 and 1983 showed that child restraint devices are highly effective in preventing death and in preventing or reducing injury. Children not in child restraint devices were 11 times more likely to die in an accident than children in child restraint devices. Children traveling in the arms of an adult were exposed to a risk of injury or death comparable to that of children left entirely unrestrained.

Accident Prevention↗
PubMed1984

An SV40 "enhancer trap" incorporates exogenous enhancers or generates enhancers from its own sequences.

We have transfected monkey CV-1 cells with non-infectious, linear SV40 DNA, lacking the 72 bp repeat enhancer region. Infectious virus was recovered from this "enhancer trap" upon cotransfection with enhancer DNA segments from various viruses, notably a truncated polyoma enhancer that was integrated as a dimer. Cotransfection of the "enhancer trap" with fragmented DNA of mouse, monkey, or human origin yielded no recombinant virus with integrated cellular sequences, with one possible exception. In some transfection experiments without added viral enhancer DNA, SV40 variants were generated that have a segment of their flanking "late" DNA duplicated to substitute for the deleted 72 bp repeat. In one variant, an 88 bp duplication creates a strong enhancer from this nonenhancing DNA region. Both the polyoma enhancer fragment and the spontaneously created enhancers lack the alternating purines-pyrimidines or "CACA box" suggested to be characteristic for enhancer elements and show only limited homology to the "GTGG(AAATTT)G box."

Animals↗