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Biomedical subjects

D M Morens

Publications and source records attributed to D M Morens.

At least 37 records · Page 2Linked to original sources
PubMed1995

Thoughts on the relevance of medical history.

Clinicians are, by their very nature, historians--a question remains as to whether and how the history of medicine should be studied as a subject. In recent years medical educators have increasingly answered this question by deleting medical history from the curriculum. But this may be a mistake: among other things of value, medical history provides a much-needed perspective of medical knowledge, and a pigeon holer into which essential new facts--basic, clinical, whatever--can be filed without getting lost. But linear learning, the piling-on of facts, is more likely to bring exhaustion than comprehension.

Hawaii↗
PubMed1994

"Thucydides syndrome" reconsidered: new thoughts on the "Plague of Athens".

A recently published theory (N Engl J Med 1985;313:1027-30) argues that the famous Athenian epidemic of 430 B.C. was caused by a combination of influenza and toxin-producing staphylococci (the "Thucydides syndrome"). Although it is accepted by some medical authorities, and ostensibly supported by identification of modern cases, the theory's plausibility has not been carefully examined. The authors used an epidemiologic approach supplemented by historical and clinical observations to examine the likelihood that a "Thucydides syndrome" could have caused the Athenian epidemic. Arguing against the influenza theory are epidemiologic and clinical features of the disease, mathematical models of the spread of influenza, and empirical observations of epidemic influenza in premodern populations of known size and crowding. The authors conclude that neither influenza nor a "Thucydides syndrome" could have produced the Athenian epidemic. Epidemiologic features suggest either a zoonotic or vectorborne disease, a disease associated with an environmental source, or a respiratory infection with unusual alternative mechanisms of spread.

Disease Outbreaks↗
PubMed1994

Prospective study of cigarette smoking and the risk of developing idiopathic Parkinson's disease.

A 26-year follow-up study of 8,006 men enrolled in the Honolulu Heart Program examined the effect of cigarette smoking on the risk of developing idiopathic Parkinson's disease. Cases were identified through an ongoing search of hospital records and by the review of death certificates and medical records of local neurologists. Men who had smoked cigarettes at any time prior to study enrollment in 1965 had a reduced risk of developing idiopathic Parkinson's disease (relative risk = 0.39). Examination of smoking by pack-years revealed an apparent dose-response effect on the risk of idiopathic Parkinson's disease, but not on the age of onset. Coffee drinking was also associated with reduced risk, apparently because of its association with cigarette smoking. Although the detrimental health effects of cigarette smoking would far outweight any possible protective effect for smoking and Parkinson's disease, the association of smoking with apparent protection may contribute to understanding the underlying pathogenetic mechanisms.

Aged↗
PubMed1994

Antibody-dependent enhancement of infection and the pathogenesis of viral disease.

Antibody-dependent enhancement of infection (ADE) is an in vitro serological phenomenon--or a group of phenomena--in which viral infection of susceptible cells is modified by the addition of virus-reactive antibody. Evidence suggests that ADE reflects immunologic processes that occur in vivo. Various severe and even fatal viral conditions of humans and animals, including dengue shock syndrome, the "early-death phenomenon" in experimental infections of immune animals, and other vaccine- and immunoglobulin-modified conditions, have been attributed to ADE by some researchers. ADE has caused great concern in relation to the development of vaccines against dengue virus and human immunodeficiency virus. More data are urgently needed on the mechanisms and determinants of ADE and on its alleged role in disease pathogenesis and in vaccine-associated phenomena.

Age Factors↗
PubMed1994

Epidemiologic characteristics of leprosy reactions.

An 8-year prospective study of a cohort of 176 newly diagnosed leprosy patients was conducted to examine the possible influence of age, sex, multidrug therapy (MDT), and duration of illness on the risk of either type 1 or type 2 reactions. Patients were enrolled over a 5-year period (1984-1989) and followed for a minimum of 3 years. All reactions studied were severe enough to warrant hospital admission. Overall, 45% of this cohort developed a reaction; 32% of patients considered at risk developed type 1 reactions, and 37% of patients considered at risk developed type 2 reactions. Despite the predominance of men among the leprosy patients, type 1 reactions occurred with significantly greater frequency in women, and did not appear to be influenced by age of onset of leprosy. Individuals experiencing one type 1 reaction were not likely to experience a recurrence, suggesting that the immunologic mechanisms of this reaction may be limited or regulated by genetic or immunologic factors. Type 2 reactions, on the other hand, occurred with equal frequency in both males and females, but were highly associated with onset of leprosy in the second decade of life. Individuals who experienced type 2 reactions often had one or more recurrence of the reaction. No increased risk was seen for either reaction with longer duration of leprosy or longer duration of treatment. The mechanisms by which these differences relate to the pathogenesis of leprosy reactions remains unclear, but future studies of clinical and immunological parameters of leprosy reactions may benefit from stratification of data by gender and age of onset of leprosy in addition to the routine grouping of results by leprosy classification.

Adolescent↗
PubMed1992

Use of recombinant fusion proteins and monoclonal antibodies to define linear and discontinuous antigenic sites on the dengue virus envelope glycoprotein.

Sixteen overlapping fragments of the dengue-2 virus envelope (E) protein, expressed as trpE-E fusion products in Escherichia coli, were used to map the epitopes defined by a panel of 20 monoclonal antibodies (MAbs) by immunoblotting. Using this technique, the amino acid sequence of six antigenic domains on the E protein was characterized. Nonneutralizing MAbs were found to define either linear-specific, subcomplex-specific (amino acids 22-58), and complex-specific (amino acids 304-332) epitopes or a subcomplex conformational-dependent epitope requiring the presence of two closely linked amino acid sequences from the E protein, 60-97 and 298-397. Neutralizing MAbs, however, defined either group-reactive epitopes present on two overlapping domains (amino acids 60-135; amino acids 60-205) or type-, subcomplex-, complex-, subgroup-, and group-specific determinants (amino acids 298-397). These neutralizing epitopes were all found to be dependent upon disulfide bridges. Our results suggest that the maintenance of a topographical arrangement of discontinuous antigenic domains in the flavivirus E-protein is necessary to induce neutralizing and protective antibodies.

Amino Acid Sequence↗
PubMed1992

Severe streptococcal infections in historical perspective.

The recent unexplained increase in severe streptococcal diseases in the United States and Great Britain is compared to the 1825-1885 pandemic of fatal scarlet fever. Although scarlet fever may not be representative of all severe streptococcal disease, it was the only one reliably identified in the 19th century. The epidemiology of scarlet fever during the 19th century pandemic suggests the following features of the disease; cocirculation of both virulent and less-virulent streptococcal strains eliciting cross-immunity; circulation of hyperendemic prevalent strains in urban centers of developed nations, with periodic spillovers to rural areas and developing nations; and protection of infants from infection (but not from fatal disease once infection occurred) by the transfer of maternal antibodies via the placenta, breast milk, or both. The 19th century data suggest that efforts to prevent severe streptococcal diseases should begin with better characterization of the epidemiology of streptococcal disease, a task entailing identification of streptococcal virulence factors and measurement of their distribution among isolates from individuals with streptococcal diseases and in open populations.

Global Health↗
PubMed1991

The "fourth disease" of childhood: reevaluation of a nonexistent disease.

Observed and described between 1884 and 1900, "fourth disease" (Dukes disease) followed measles, scarlet fever, and rubella as the fourth clinically characterized childhood exanthem. Like rubella ("third disease") and erythema infectiosum ("fifth disease"), accepted by the medical community at about the same time, the existence of fourth disease was initially controversial. Over the following decades descriptions of hundreds of cases, outbreaks, and laboratory studies were published in the indexed medical literature. Unlike rubella and fifth disease, however, fourth disease was not subsequently proven to exist by either epidemiologic criteria or isolation of an etiologic agent. By the 1930s, it was infrequently recognized and by the 1960s had been dropped from textbooks. In this study, the authors use epidemiologic methods to reevaluate published data on English schoolchildren from 1892 to 1900 upon which the original fourth disease claim of Dukes was based. The authors conclude that fourth disease never existed. Reinterpretation of the original data suggests that cases can be completely explained as misdiagnosed rubella and scarlet fever. Misidentification of fourth disease is attributed to failures in the critical abilities of the medical and scientific communities at the time. The implications of erroneously identifying a nonexistent disease suggest that modern scientific approaches to disease identification are sound.

Child↗
PubMed1991

Growth of dengue type 2 virus isolates in human peripheral blood leukocytes correlates with severe and mild dengue disease.

We tested three dengue type 2 (DEN-2) isolates from children with clinically apparent but mild secondary dengue infections, and 10 isolates from children with moderately severe dengue hemorrhagic fever, and noted significant growth differences in peripheral blood leukocytes, but not in C6/36 cells. We also observed cytopathic effects in C6/36 cells that correlated with disease severity. These preliminary observations suggest the possibility that viral factors, whether surface antigens, attachment sites for entry into leukocytes, or intrinsic replication properties in human mononuclear phagocytes, might contribute to enhanced DEN infection and to the severity of the disease.

Child↗
PubMed1990

Measurement of antibody-dependent infection enhancement of four dengue virus serotypes by monoclonal and polyclonal antibodies.

Although its underlying mechanisms are poorly understood, data comparing each of the four dengue virus serotypes suggest that in vitro antibody-dependent infection enhancement is a reproducible and measurable phenomenon related to other serological measures of antibody-virus binding. Information characterizing infection enhancement may provide clues to disease pathogenesis for dengue and other viruses that exhibit antibody-enhanced infection. We propose criteria for the detection and quantification of in vitro antibody-dependent enhancement of flavivirus infection based on observations using all four dengue virus serotypes, macrophage-like cell lines and human peripheral blood monocytes, and various immune sera and monoclonal antibodies. It is proposed that antibody-dependent infection enhancement is defined by the following findings: (i) significantly increased virus production is measured in quantitative assays at different points on the growth curve; (ii) assays of the virus output of cells infected with mixtures of constant amounts of virus and serial dilutions of the pre-existing antibody source produce characteristic 'enhancement profiles' of rising and falling virus output over at least a 10(-3)-fold dilution range; (iii) for each enhancing antibody source the dilution producing maximal infection enhancement is related to other serological measures of binding to the envelope, or another virus component; (iv) infection enhancement is detected with different antibody sources and virus strains (when available) tested over a range of m.o.i.; (v) other causes of enhanced virus production are ruled out.

Animals↗
PubMed1987

Study of the distribution of antibody-dependent enhancement determinants on dengue 2 isolates using dengue 2-derived monoclonal antibodies.

Dengue 2 (DEN-2) strains isolated from children during the 1980 metropolitan Bangkok epidemic were shown to possess antigenic homogeneity when studied for determinants mediating antibody-dependent infection enhancement using DEN-2 monoclonal antibodies. All isolates possessed multiple enhancing determinants, but those associated with mild and severe dengue syndromes could not be distinguished. Either the basis of disease severity in dengue is more complex than the mere presence or absence of virus epitopes involved in enhanced infection or enhancing epitopes have differences not detected in this system with monoclonal antibodies raised to the same serotype.

Animals↗
PubMed1987

Disease severity-related antigenic differences in dengue 2 strains detected by dengue 4 monoclonal antibodies.

Low-passage epidemic Thai isolates of dengue 2 (DEN-2) were distinguished on the basis of associated disease severity by detection of virus determinants involved in enhanced macrophage infection when incubated with a panel of monoclonal antibodies derived from a DEN-4 strain associated with grade II dengue hemorrhagic fever (DHF). DEN-2 strains associated with DHF typically had multiple determinants that were involved in antibody-dependent enhancement of infection, whereas those associated with uncomplicated disease had few. These data provide further evidence that in epidemic areas where DHF is associated with prior circulation of low-level monotypic antibody, severe dengue disease could represent antibody-enhanced infection of human monocytes/macrophages.

Animals↗
PubMed1987

Profiles of antibody-dependent enhancement of dengue virus type 2 infection.

Antibody-dependent infection enhancement (ADE) was studied with P-388D1 mouse macrophage-like cells, 21 dengue virus type 2 (DEN-2) strains, and 8 monoclonal antibodies reactive with flavivirus group-specific or dengue serotype-specific determinants. Testing a constant number of virions against serial dilutions of antibody for their ability to infect P-388D1 cells, a reproducible 'enhancement profile' was observed. The profile was characterized by (1) appearance, peak, decline, and disappearance of infection enhancement when antibody-containing ascitic fluids were diluted beyond the neutralizing endpoint, and (2) evolution over an approximate 10,000-fold dilutional range. The profiles were similar regardless of whether viruses were complexed with antibody at flavivirus group or serotype determinants, but the antibody dilution at which infection enhancement was maximal varied with the neutralization titer of the antibody. Neutralization and antibody-dependent enhancement of dengue infection appear to be biological outcomes of interactions between antibodies and single viral epitopes at different antibody: virus ratios.

Animals↗
PubMed1987

Dengue 4 virus monoclonal antibodies identify epitopes that mediate immune infection enhancement of dengue 2 viruses.

Nineteen monoclonal antibodies produced to dengue type 4 virus (DEN-4) strain 4328-S were tested for their ability to mediate antibody-dependent infection enhancement (ADE) with seven DEN-2 strains in P-388D1 mouse macrophage-like cells. In this first study of the distribution of enhancing epitopes on multiple DEN-2 strains reacted with monoclonal antibodies to a different serotype (DEN-4), DEN-4 monospecific antibodies produced ADE with DEN-2 viruses, indicating the presence of DEN-4-like determinants on DEN-2 viruses. Analysis differentiated at least one and possibly more DEN-2 strain subgroups, one of which (isolates AHF-110 and AHF-191) was previously identified by DEN-2 monoclonal antibody analysis. The study demonstrates the heterogeneous distribution of dengue complex and DEN-4 epitopes on DEN-2 strains. Monoclonal antibodies are valuable tools for study of the biology of ADE and its relation to dengue shock syndrome.

Animals↗