Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 22
Filter
1.
Biologicals ; 38(4): 511-21, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20537552

ABSTRACT

In October 2009, The International AIDS Vaccine Initiative (IAVI) convened a satellite symposium entitled 'Replicating Viral Vectors for use in AIDS Vaccines' at the AIDS Vaccine 2009 Conference in Paris. The purpose of the symposium was to gather together researchers, representatives from regulatory agencies, and vaccine developers to discuss issues related to advancement of replication-competent viral vector- based HIV vaccines into clinical trials. The meeting introduced the rationale for accelerating the development of replicating viral vectors for use as AIDS vaccines. It noted that the EMEA recently published draft guidelines that are an important first step in providing guidance for advancing live viral vectors into clinical development. Presentations included case studies and development challenges for viral vector-based vaccine candidates. These product development challenges included cell substrates used for vaccine manufacturing, the testing needed to assess vaccine safety, conducting clinical trials with live vectors, and assessment of vaccination risk versus benefit. More in depth discussion of risk and benefit highlighted the fact that AIDS vaccine efficacy trials must be conducted in the developing world where HIV incidence is greatest and how inequities in global health dramatically influence the political and social environment in developing countries.


Subject(s)
AIDS Vaccines/immunology , Acquired Immunodeficiency Syndrome/immunology , Genetic Vectors/genetics , HIV Infections/immunology , AIDS Vaccines/genetics , Acquired Immunodeficiency Syndrome/prevention & control , Clinical Trials as Topic , HIV Infections/prevention & control , Humans , Research Report , Virus Replication
2.
Biologicals ; 36(5): 277-86, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18555698

ABSTRACT

At the International AIDS Society Conference on Pathogenesis, Treatment and Prevention held in Sydney, Australia, in July 2007, the International AIDS Vaccine Initiative (IAVI) convened a satellite symposium entitled 'Accelerating the Development of Replicating Viral Vectors for AIDS Vaccines.' Its purpose was to highlight the rationale for accelerating the development of replicating viral vectors for use as vaccines against HIV-1, and to bring together vaccine scientists, regulatory officials, and public health specialists from industrialized and developing nations to discuss the major issues facing the development and testing of replicating viral vector-based vaccines.


Subject(s)
AIDS Vaccines/genetics , AIDS Vaccines/immunology , Genetic Vectors/genetics , Virus Replication , Animals , Clinical Trials as Topic , Humans , Societies, Medical , Time Factors
3.
J Virol ; 75(2): 910-20, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11134304

ABSTRACT

Protein-encoding nucleotide sequences of the N, P, M, F, H, and L genes were determined for a low-passage isolate of the Edmonston wild-type (wt) measles virus and five Edmonston-derived vaccine virus strains, including AIK-C, Moraten, Schwarz, Rubeovax, and Zagreb. Comparative analysis demonstrated a high degree of nucleotide sequence homology; vaccine viruses differed at most by 0. 3% from the Edmonston wt strain. Deduced amino acid sequences predicted substitutions in all viral polypetides. Eight amino acid coding changes were common to all vaccine viruses; an additional two were conserved in all vaccine strains except Zagreb. Comparisons made between vaccine strains indicated that commercial vaccine lots of Moraten and Schwarz had identical coding regions and were closely related to Rubeovax, while AIK-C and Zagreb diverged from the Edmonston wt along slightly different paths. These comparisons also revealed amino acid coding substitutions in Moraten and Schwarz that were absent from the closely related reactogenic Rubeovax strain. All of the vaccine viruses contained amino acid coding changes in the core components of the virus-encoded transcription and replication apparatus. This observation, combined with identification of noncoding region nucleotide changes in potential cis-acting sequences of the vaccine strains (C. L. Parks, R. A. Lerch, P. Walpita, H.-P. Wang, M. S. Sidhu, and S. A. Udem, J. Virol. 75:921-933, 2001), suggest that modulation of transcription and replication plays an important role in attenuation.


Subject(s)
Genome, Viral , Measles virus/genetics , Viral Proteins/chemistry , Viral Proteins/genetics , Amino Acid Sequence , Amino Acid Substitution , Animals , Genes, Viral , Humans , Measles Vaccine , Measles virus/chemistry , Measles virus/classification , Measles virus/pathogenicity , Molecular Sequence Data , Mutation , Reverse Transcriptase Polymerase Chain Reaction , Sequence Analysis, DNA , Vaccines, Attenuated
4.
J Virol ; 75(2): 921-33, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11134305

ABSTRACT

The noncoding sequence of five Edmonston vaccine viruses (AIK-C, Moraten, Rubeovax, Schwarz, and Zagreb) and those of a low-passage Edmonston wild-type (wt) measles virus have been determined and compared. Twenty-one nucleotide positions were identified at which Edmonston wt and one or more vaccine strains differed. The location of some of these nucleotide substitutions suggests that they may influence the efficiency of mRNA synthesis, processing, and translation, as well as genome replication and encapsidation. Five nucleotide substitutions were conserved in all of the vaccine strains. Two of these were in the genomic 3'-terminal transcriptional control region and could affect RNA synthesis or encapsidation. Three were found within the 5'-untranslated region of the F mRNA, potentially altering translation control sequences. The remaining vaccine virus base changes were found in one to four vaccine strains. Their genomic localization suggests that some may modify cis-acting regulatory domains, including the Kozak consensus element of the P and M genes, the F gene-end signal, and the F mRNA 5'-untranslated sequence.


Subject(s)
Genome, Viral , Measles Vaccine , Measles virus/genetics , RNA, Untranslated/analysis , 5' Untranslated Regions/genetics , Base Sequence , DNA, Intergenic , Gene Expression Regulation, Viral , Genes, Regulator , Humans , Measles/virology , Molecular Sequence Data , Sequence Analysis, DNA , Transcription, Genetic , Viral Proteins/genetics
5.
J Virol ; 73(5): 3560-6, 1999 May.
Article in English | MEDLINE | ID: mdl-10196245

ABSTRACT

Rescue of negative-stranded RNA viruses from full-length genomic cDNA clones is an essential technology for genetic analysis of this class of viruses. Using this technology in our studies of measles virus (MV), we found that the efficiency of the measles virus rescue procedure (F. Radecke et al., EMBO J. 14:5773-5784, 1995) could be improved by modifying the procedure in two ways. First, we found that coculture of transfected 293-3-46 cells with a monolayer of Vero cells increased the number of virus-producing cultures about 20-fold. Second, we determined that heat shock treatment increased the average number of transfected cultures that produced virus another two- to threefold. In addition, heat shock increased the number of plaques produced by positive cultures. The effect of heat shock on rescue led us to test the effect on transient expression from an MV minireplicon. Heat shock increased the level of reporter gene expression when either minireplicon DNA or RNA was used regardless of whether complementation was provided by cotransfection with expression plasmids or infection with MV helper virus. In addition, we found that MV minireplicon gene expression could be stimulated by cotransfection with an Hsp72 expression plasmid, indicating that hsp72 likely plays a role in the effect of heat shock.


Subject(s)
DNA, Viral , Gene Expression Regulation, Viral , Heat-Shock Response/physiology , Measles virus/genetics , Animals , Cell Line, Transformed , Chlorocebus aethiops , Genes, Viral , HSP72 Heat-Shock Proteins , HeLa Cells , Heat-Shock Proteins/genetics , Heat-Shock Proteins/metabolism , Humans , Replicon , Vero Cells
6.
Proc Natl Acad Sci U S A ; 95(18): 10734-9, 1998 Sep 01.
Article in English | MEDLINE | ID: mdl-9724773

ABSTRACT

Brain serotonin (5-HT) has been implicated in a number of physiological processes and pathological conditions. These effects are mediated by at least 14 different 5-HT receptors. We have inactivated the gene encoding the 5-HT1A receptor in mice and found that receptor-deficient animals have an increased tendency to avoid a novel and fearful environment and to escape a stressful situation, behaviors consistent with an increased anxiety and stress response. Based on the role of the 5-HT1A receptor in the feedback regulation of the 5-HT system, we hypothesize that an increased serotonergic neurotransmission is responsible for the anxiety-like behavior of receptor-deficient animals. This view is consistent with earlier studies showing that pharmacological activation of the 5-HT system is anxiogenic in animal models and also in humans.


Subject(s)
Anxiety/genetics , Receptors, Serotonin/genetics , Animals , Base Sequence , Behavior, Animal , Brain/metabolism , DNA Primers , Female , Genotype , Male , Mice , Mice, Inbred BALB C , Mice, Knockout , Receptors, Serotonin, 5-HT1
7.
J Virol ; 71(12): 9600-7, 1997 Dec.
Article in English | MEDLINE | ID: mdl-9371624

ABSTRACT

Multiple binding sites for the transcription factors MAZ and Sp1 within the adenovirus type 5 major late promoter have been identified by DNase I protection studies. In the proximal region of the promoter, both MAZ and Sp1 interact with GC-rich sequences flanking the TATA box. Two MAZ binding sites are centered at -18 and -36 relative to the transcriptional initiation site. Sp1 bound only to the -18 GC-rich sequence. Several sites of interaction were also evident in the distal region of the promoter. Both MAZ and Sp1 interacted with a sequence centered at -166, and MAZ bound weakly to an additional site centered at -130. Overexpression of MAZ or Sp1 activated expression from the major late promoter in transient expression assays. Mutational analysis of the GC-rich sequences in the major late promoter suggested that a primary target of MAZ activation is the GC-rich sequences flanking the TATA sequence, whereas Sp1 requires the distal GC-rich sequence elements to stimulate gene expression. This activation is enhanced by the adenovirus E1A protein, and evidence for interaction between E1A and both transcription factors was obtained by using an immunoprecipitation assay. Activation by MAZ and Sp1 also was observed in transfection studies using the complete adenovirus type 5 genome as the target. Increased levels of late mRNA from both the L1 and L5 regions were observed when MAZ or Sp1 expression plasmids were transfected with viral DNA. Unexpectedly, activation of the major late promoter by MAZ and Sp1 was detected irrespective of whether the viral DNA could replicate.


Subject(s)
Promoter Regions, Genetic , Sp1 Transcription Factor/metabolism , Transcription Factors/metabolism , Transcriptional Activation , Zinc Fingers , Adenoviridae/genetics , Adenovirus E1A Proteins/metabolism , Base Sequence , Binding Sites , Cell Line, Transformed , DNA, Viral , DNA-Binding Proteins , HeLa Cells , Humans , Molecular Sequence Data , TATA Box
8.
J Biol Chem ; 271(8): 4417-30, 1996 Feb 23.
Article in English | MEDLINE | ID: mdl-8626793

ABSTRACT

The structure and function of the 5'-flanking region of the mouse and human serotonin 1a receptor gene have been analyzed by RNA 5' end mapping, DNA-protein interaction, and transient expression assays. A large number of mRNA 5' termini, detected by mapping 5' ends from mouse brain RNA, were found dispersed over a region of about 700 base pairs flanking the receptor coding sequence. Consistent with the apparently heterogeneous pattern of transcription initiation, the flanking DNA sequence lacked typical TATA box elements and was rich in guanine and cytosine. The mouse and human 5'-flanking sequences were 63% homologus and similarly organized. A guanine-cytosine-rich DNA sequence motif related to the sequence 5'-GGGG(C/A)GGGG-3' was repeated within the 5'-flanking region and located at or near several mRNA 5' ends. This DNA sequence motif bound to proteins in a crude HeLa cell nuclear extract. A cDNA encoding a protein that interacts with this sequence was cloned and found to be the MAZ (Pur-1, Zif87) protein. The interaction between MAZ and the receptor gene 5'-flanking region proximal to the protein coding sequence was examined by DNase I footprinting, and four sites of MAZ interaction were identified. Three of the four MAZ binding sites also were shown to interact with transcription factor Sp1. Overproduction of MAZ or Sp1 in transient transfection assays increased expression directed by the human 5'-flanking sequence, although MAZ was substantially more effective. This result suggests that MAZ and Sp1 both participate in regulating expression from the serotonin 1a receptor gene promoter, and it raises the possibility that MAZ may act at a variety of promoters through the guanosine-cytosine-rich sequences generally thought to serve as binding sites for the Sp1 family of transcription factors. Analysis of one of the guanosine-cytosine-rich DNA sequences also revealed that it can serve as a transcription initiator sequence in vitro. This initiator sequence differs from previously characterized initiators and may represent a new class of this transcriptional control sequence.


Subject(s)
Promoter Regions, Genetic , Receptors, Serotonin/genetics , Repetitive Sequences, Nucleic Acid , Sp1 Transcription Factor/metabolism , Transcription Factors/metabolism , Animals , Base Composition , Base Sequence , Binding Sites , Cell Line , Cloning, Molecular , Consensus Sequence , Cytosine , DNA-Binding Proteins , Guanine , HeLa Cells , Humans , L Cells , Mice , Molecular Sequence Data , Receptors, Serotonin/biosynthesis , Receptors, Serotonin, 5-HT1 , Recombinant Proteins/biosynthesis , Regulatory Sequences, Nucleic Acid , Sequence Homology, Nucleic Acid , TATA Box , Transfection , Zinc Fingers
9.
Virology ; 194(1): 128-36, 1993 May.
Article in English | MEDLINE | ID: mdl-8480416

ABSTRACT

We report that transcription of the adenovirus type 5 E1b gene is activated substantially in cis by sequences located between positions -362 and -49 with respect to the RNA start site. DNA fragments consisting of the -362 to -49 sequences, or subsets thereof, were inserted into a reporter plasmid containing a minimal E1b promoter (positions -48 to +14) joined to the Escherichia coli cat gene. In the presence of cotransfected E1a and E1b genes in trans, CAT enzyme synthesis in transfected KB cells was stimulated about 20-fold by sequences from -362 to -49 (XY) in cis and to a lesser extent by sequences from either -362 to -128 (X) or -127 to -49 (Y). Adenoviruses were isolated lacking the X, Y, or XY sequences and KB cells were infected with one of the mutants, as well as wild-type virus to provide E1a and E1b in trans. Deletion of both X and Y resulted in a 20-fold reduction in early E1b RNA and a 12-fold reduction in late RNA. Deletion of X or Y alone produced up to 5-fold reductions in early or late E1b RNA accumulation. In vitro DNA-protein interactions in the Y sequence were revealed by modification of the procedure used for previous detection of X region footprints. These data indicate that X and Y sequences, which include E1a protein coding and 3' untranslated DNA, also participate in DNA-protein interactions necessary for high levels of E1b promoter activity. The presence of such overlapping genetic elements raises the interesting possibility that functional E1a and E1b mRNAs must be synthesized from separate templates.


Subject(s)
Adenoviridae/genetics , Adenovirus E1B Proteins/genetics , Gene Expression Regulation, Viral , Genes, Viral/genetics , Transcription, Genetic , Adenoviridae/growth & development , Amino Acid Sequence , Chloramphenicol O-Acetyltransferase/analysis , Chloramphenicol O-Acetyltransferase/genetics , Chromosome Mapping , DNA, Recombinant , DNA-Binding Proteins/metabolism , Deoxyribonuclease I/metabolism , Models, Genetic , Molecular Sequence Data , RNA, Viral/biosynthesis , RNA, Viral/isolation & purification , Regulatory Sequences, Nucleic Acid/genetics , Transfection
10.
Nucleic Acids Res ; 19(25): 7155-60, 1991 Dec.
Article in English | MEDLINE | ID: mdl-1766875

ABSTRACT

Under appropriate conditions, specific double-stranded DNA product was generated after amplification of genomic DNA sequences in a polymerase chain-like reaction that contained only a single primer. This type of amplification reaction was performed with a variety of primers and substrate DNAs. In addition to nonspecific heterogeneous products, 5 of 11 primers reproducibly directed synthesis of double-stranded DNA that corresponded to the region of the template that contained the authentic primer annealing site. Three of these amplified products were cloned and their ends were sequenced. All three contained a copy of the primer at both 5' ends, and the position of one of the primers represented the authentic primer binding site. In each case, the location of the second copy of the primer indicated that it had initially hybridized to a partially homologous sequence in the template DNA. This single primer reaction makes it possible to amplify and clone a DNA region of unknown sequence that is adjacent to a known DNA sequence. One of the single primer reaction products described here included sequence to the 5' side of the coding region of a serotonin receptor gene that contained a functional promoter.


Subject(s)
Cloning, Molecular/methods , Receptors, Serotonin/genetics , Adenoviridae/genetics , Base Sequence , Chloramphenicol O-Acetyltransferase/genetics , Chloramphenicol O-Acetyltransferase/metabolism , HeLa Cells , Humans , Molecular Sequence Data , Oligodeoxyribonucleotides/genetics , Polymerase Chain Reaction , Promoter Regions, Genetic/genetics
11.
J Health Care Mark ; 11(3): 61-8, 1991 Sep.
Article in English | MEDLINE | ID: mdl-10116319

ABSTRACT

Investor-owned walk-in centers are a recent innovation in ambulatory care. The authors surveyed private practice primary care physicians about their marketing strategies before and after the advent of a local walk-in center. Respondents were more likely to report that they accepted walk-ins and that they advertised in the latter than in the former time period. Findings are discussed in the framework of previous predictions about the impact of walk-in centers on the delivery of care in traditional primary care practice settings.


Subject(s)
Ambulatory Care Facilities/statistics & numerical data , Marketing of Health Services/methods , Physicians, Family/statistics & numerical data , Private Practice/trends , Ambulatory Care Facilities/economics , Appointments and Schedules , Catchment Area, Health/economics , Catchment Area, Health/statistics & numerical data , Chi-Square Distribution , Economic Competition/statistics & numerical data , Fees, Medical , Health Facilities, Proprietary/economics , Health Facilities, Proprietary/statistics & numerical data , Marketing of Health Services/statistics & numerical data , Marketing of Health Services/trends , Massachusetts , Private Practice/economics , Private Practice/statistics & numerical data , Surveys and Questionnaires
12.
QRB Qual Rev Bull ; 17(4): 120-5, 1991 Apr.
Article in English | MEDLINE | ID: mdl-1852433

ABSTRACT

Several aspects of quality of care at one chain of freestanding ambulatory health care walk-in centers were evaluated. Those areas for which data were available--medical record review, physician credentials, and patient satisfaction--suggest that for primary acute episodic care, HSMMI walk-in centers provided care comparable to that which would have been received in traditional health care settings. In fact, HSMMI offices were found to be similar in organizational structure and appeared very much like private physicians' offices in management, staffing, patient flow, and physician performance. The corporation's QA program evolved from a series of informal managers' meetings (in 1986), to a detailed and structured program involving a CEO and regional medical directors by the end of 1990. The exact way in which HSMMI's new emphasis on formal quality-of-care assessment and assurance will affect patient care will be seen as the program fully matures. The issue of the proper relationship between money and medicine remains a problem. As health services organizations are increasingly influenced by market forces and consumers have ever-higher expectations, patients and physicians alike want to be sure that high-quality health care remains the first priority. Although this is an issue for all providers, it is much more visible in proprietary offices, making physicians as well as the public uneasy. For this reason, HSMMI's burden of proof regarding quality may be higher--particularly within the medical community--than the burden on traditional private practice physicians.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Ambulatory Care Facilities/standards , Quality Assurance, Health Care/organization & administration , Adolescent , Adult , Consumer Behavior/statistics & numerical data , Evaluation Studies as Topic , Health Facilities, Proprietary/standards , Humans , Massachusetts , Medical Records/standards , Physicians/standards , United States
13.
Med Care ; 29(1): 72-86, 1991 Jan.
Article in English | MEDLINE | ID: mdl-1986180

ABSTRACT

This article examines the quality of acute episodic care for five diagnostic categories amenable to one-visit diagnosis and treatment at the nation's largest chain of investor-owned ambulatory care centers. A total of 803 medical records were audited for five common conditions and measured against specific protocols. In four of the five diagnostic categories studied--pharyngitis, otitis media, vaginitis, and use of tetanus immunization--42-97% of patients received care that met or exceeded the standards set by a panel of practicing academic physicians. In follow-up of an incidental high blood pressure reading, however, study physicians met the standard only 24% of the time. Some overprescribing and overtreatment with immunizations were detected. As far as comparison is possible to other studies, results suggest that care in this setting falls within the range of experience that has been reported for other types of practices. In spite of direct economic incentives to increase volume, little evidence was found of overuse of ancillary tests or unnecessary scheduling of repeat visits.


Subject(s)
Ambulatory Care Facilities/standards , Health Facilities, Proprietary/standards , Outcome and Process Assessment, Health Care , Acute Disease , Adolescent , Adult , Aged , Child , Female , Humans , Hypertension/diagnosis , Male , Massachusetts , Middle Aged , New Hampshire , Otitis Media/diagnosis , Otitis Media/therapy , Pharyngitis/diagnosis , Pharyngitis/therapy , Tetanus/prevention & control , Vaccination , Vaginitis/diagnosis , Vaginitis/therapy
14.
J Ambul Care Manage ; 14(1): 66-77, 1991 Jan.
Article in English | MEDLINE | ID: mdl-10113467

ABSTRACT

In sum, people go to a walk-in office for quick, convenient service, and overall they are happy with their experience. Although we cannot generalize from this case study of one chain of walk-in centers to walk-ins nationally, results from other studies of walk-in patient populations are approximately similar to ours.


Subject(s)
Ambulatory Care Facilities/statistics & numerical data , Patient Acceptance of Health Care/statistics & numerical data , Boston , Diagnosis-Related Groups , Health Facilities, Proprietary/statistics & numerical data , Sampling Studies , Socioeconomic Factors , Surveys and Questionnaires
15.
J Virol ; 64(6): 2780-7, 1990 Jun.
Article in English | MEDLINE | ID: mdl-2139894

ABSTRACT

A cis-dominant mutation in the adjacent E1a gene disrupted the accumulation of adenovirus type 5 E1b mRNA during the early phase of infection. Steady-state levels of cytoplasmic and nuclear E1b RNAs in cells infected with dl312, a strain that lacks the E1a TATA box, cap site, and much of the coding sequence, were reduced 5- to 10-fold even when the E1a activator was provided in trans. The strain was defective for early E1b RNA synthesis but not for E1b RNA made late or during prolonged incubation in the presence of an inhibitor of DNA replication. The defect in E1b RNA synthesis could not be attributed to the E1a promoter sequences missing in dl312 DNA. If the E1a protein-coding region contains cis-acting regulatory sequences, they are not part of the previously mapped E1b transcriptional control region and may represent additional regulatory elements that ensure prompt and efficient E1b expression during the early phase of infection.


Subject(s)
Gene Expression Regulation, Viral , Genes, Dominant , Genes, Viral , Oncogene Proteins, Viral/genetics , RNA, Messenger/genetics , RNA, Viral/genetics , Transcription, Genetic , Adenovirus Early Proteins , Cell Nucleus/metabolism , Humans , KB Cells , Mutation , Promoter Regions, Genetic , RNA, Messenger/isolation & purification , RNA, Viral/isolation & purification , Restriction Mapping
16.
N Engl J Med ; 322(15): 1059-63, 1990 Apr 12.
Article in English | MEDLINE | ID: mdl-2320066

ABSTRACT

Health Stop is a major chain of ambulatory care centers operating for profit. Until 1985 its physicians were paid a flat hourly wage. In the middle of that year, a new compensation plan was instituted to provide doctors with financial incentives to increase revenues. Physicians could earn bonuses the size of which depended on the gross incomes they generated individually. We compared the practice patterns of 15 doctors, each employed full time at a different Health Stop center in the Boston area, in the same winter months before and after the start of the new arrangement. During the periods compared, the physicians increased the number of laboratory tests performed per patient visit by 23 percent and the number of x-ray films per visit by 16 percent. The total charges per month, adjusted for inflation, grew 20 percent, mostly as a result of a 12 percent increase in the average number of patient visits per month. The wages of the seven physicians who regularly earned the bonus rose 19 percent. We conclude that substantial monetary incentives based on individual performance may induce a group of physicians to increase the intensity of their practice, even though not all of them benefit from the incentives.


Subject(s)
Ambulatory Care Facilities/organization & administration , Health Facilities, Proprietary/organization & administration , Health Facility Administration , Personnel Management/economics , Physician Incentive Plans/economics , Practice Patterns, Physicians'/statistics & numerical data , Boston , Data Collection , Income/statistics & numerical data , Office Visits/statistics & numerical data
17.
Health Care Manage Rev ; 15(3): 47-57, 1990.
Article in English | MEDLINE | ID: mdl-2398002

ABSTRACT

This article describes physicians at a major chain of investor-owned free-standing walk-in centers and reports on their job satisfaction. They derived satisfaction from a sense of autonomy and the corporation's reliable provision of staff and supplies. Their job dissatisfaction results from the corporate emphasis on generating revenue and the lack of opportunity for professional interaction with colleagues.


Subject(s)
Ambulatory Care Facilities/standards , Job Satisfaction , Physicians/statistics & numerical data , Adult , Attitude of Health Personnel , Boston , Career Choice , Decision Making, Organizational , Female , Humans , Interprofessional Relations , Male , Middle Aged , Physician-Patient Relations , Physicians/psychology , Salaries and Fringe Benefits , Surveys and Questionnaires
18.
Soc Sci Med ; 28(1): 59-67, 1989.
Article in English | MEDLINE | ID: mdl-2648594

ABSTRACT

The decline in infant mortality now occurring in the developing world assures a growing population of older persons with a chronic disease morbidity burden that is predictable and costly. The health needs and related social requirements of the elderly are not always well met even in countries where resources are substantial. In the developing world, this morbidity burden can quickly overwhelm fragile and often underfinanced health infrastructures already unable to meet fully the prevention and treatment needs of a younger population with relatively low-cost, easy-to-prevent, easy-to-treat illnesses. Inappropriate application of costly technology could easily result, accompanied by diversion of resources from existing primary-care services, and paradoxically poor service to the emerging aging population. This paper examines the dilemma, and spells out the issues by examining several chronic diseases in detail. We conclude with suggestions for a policy-oriented research agenda aimed at the development of affordable and humane approaches to the health needs of aging populations, and the prevention and care of chronic diseases in the developing world.


Subject(s)
Chronic Disease/economics , Developing Countries , Health Services for the Aged/economics , Aged , Aging , Child , Chronic Disease/therapy , Health Policy , Humans , Life Expectancy/trends
19.
J Virol ; 62(1): 54-67, 1988 Jan.
Article in English | MEDLINE | ID: mdl-3334751

ABSTRACT

Genetic analysis of the transcriptional control sequences of the E1b gene of adenovirus type 5 identified two regions that stimulated specific transcription by whole cell extracts from uninfected cells. The first region, located within 50 nucleotides (position -50) 5' to the transcription initiation (cap) site, contains a G+C-rich consensus-binding site (GC box) for the transcription factor Sp1 and a TATA box. Unambiguous stimulatory activity of the second region, between positions -358 and -127, was observed only in the absence of the GC box. DNase I protection experiments (footprinting) with crude nuclear extracts from uninfected cells revealed multiple DNA-protein interactions at the control region. Proximal to the initiation site, both the GC box and the cap site were protected; however, protection of the TATA box was not observed. In the distal region, four protein-binding sites, designated I through IV, were located between positions -250 and -120. Three of the four mapped in protein-coding sequences of the adjacent E1a gene. Sites I and II were 5' to position -218 whereas sites III and IV were 3' to position -218. This finding was consistent with results of the transcriptional analysis indicating that subsets of the distal region were sufficient for stimulation of transcription in vitro in the absence of the GC box. Within the boundaries of site I, a 10-base-pair protected sequence was similar to one located 5' to the adenovirus E1a, E2a, E3, E4, E2 late, and polypeptide IX transcription initiation sites. Sequences within the boundaries of the other three sites were similar to those within other viral and cellular enhancers.


Subject(s)
Adenoviruses, Human/genetics , DNA-Binding Proteins/physiology , Genes, Viral , Regulatory Sequences, Nucleic Acid , Transcription Factors/physiology , Transcription, Genetic , Base Sequence , Binding Sites , DNA Mutational Analysis , Deoxyribonuclease I , Gene Expression Regulation , Molecular Sequence Data , Nuclear Proteins/physiology , Promoter Regions, Genetic , RNA, Viral/genetics
20.
Virus Res ; 7(1): 69-82, 1987 Feb.
Article in English | MEDLINE | ID: mdl-2436393

ABSTRACT

A small DNA fragment containing the simple sequence [GGC]10 from the long repeat of herpes simplex virus type 1 (HSV-1) DNA hybridized to cellular DNA and polyadenylated RNA from different mammalian species. The number and intensity of blot hybridization signals were increased in human compared with rodent and simian nucleic acids. The hybridization was blocked specifically by human 28S ribosomal DNA, which shares only the GGC repeats with the herpes simplex virus DNA. These data indicate that GGC repeats were common components of cellular DNA and were expressed in mRNA. Blot hybridization analysis of viral RNA from the HSV-1 gene regions encompassing the GGC repeats revealed abundant stable mRNAs from portions of the virus genome not previously analyzed in detail and indicated that the viral GGC sequence was not expressed in stable cytoplasmic mRNA.


Subject(s)
DNA, Viral/genetics , DNA/genetics , Nucleic Acid Hybridization , RNA, Messenger/genetics , Simplexvirus/genetics , Animals , Cricetinae , Haplorhini , Mice , Poly A/genetics , RNA/genetics , RNA, Viral/genetics , Repetitive Sequences, Nucleic Acid , Transcription, Genetic
SELECTION OF CITATIONS
SEARCH DETAIL
...