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Biomedical subjects

E Schwartz

Publications and source records attributed to E Schwartz.

At least 73 records · Page 4Linked to original sources
PubMed1998

Imported severe falciparum malaria in Israel.

Malaria remains an overwhelming problem in tropical developing countries, with 300 to 500 million new cases and 1.5 to 3.5 million deaths per year. Malaria is a potentially life-threatening disease for travelers to the tropics. Imported malaria is an important clinical problem in nonendemic areas of the world because of increasing numbers of travelers, overseas workers, and immigrants from endemic areas. According to the World Health Organization's criteria, the recognition of one or more of the following clinical features should raise the suspicion of severe malaria: cerebral malaria (unrousable coma), severe anemia (hemoglobin <5 g/dL), renal failure (serum creatinine >3 mg/dL), pulmonary edema or adult respiratory distress syndrome, hypoglycemia (glucose <40 mg/dL), circulatory collapse or shock, disseminated intravascular coagulation, repeated generalized convulsions, acidosis (pH <7.25), macroscopic hemoglobinuria, hyperparasitemia (>5 percent of the erythrocytes infested by parasites), or jaundice (bilirubin >3 mg/dL). Although only a small proportion of patients with malaria develops severe manifestations, these patients require the most urgent and intensive care. Mortality among patients with cerebral malaria, even when treated in modern intensive care units, exceeds 30%, and when complicated by the adult respiratory distress syndrome, it may approach 80%. Among travelers, mortality remains a serious issue because of failure to obtain and use preventive measures, delay in seeking medical attention, and misdiagnosis.

Adult↗
PubMed1998

Transcriptional regulation of Alcaligenes eutrophus hydrogenase genes.

Alcaligenes eutrophus H16 produces a soluble hydrogenase (SH) and a membrane-bound hydrogenase (MBH) which catalyze the oxidation of H2, supplying the organism with energy for autotrophic growth. The promoters of the structural genes for the SH and the MBH, PSH and PMBH, respectively, were identified by means of the primer extension technique. Both promoters were active in vivo under hydrogenase-derepressing conditions but directed only low levels of transcription under condition which repressed hydrogenase synthesis. The cellular pools of SH and MBH transcripts under the different growth conditions correlated with the activities of the respective promoters. Also, an immediate and drastic increase in transcript pool levels occurred upon derepression of the hydrogenase system. Both promoters were dependent on the minor sigma factor sigma 54 and on the hydrogenase regulator HoxA in vivo. PSH was stronger than PMBH under both heterotrophic and autotrophic growth conditions. The two promoters were induced at approximately the same rates upon derepression of the hydrogenase system in diauxic cultures. The response regulator HoxA mediated low-level activation of PSH and PMBH in a heterologous system.

Alcaligenes↗
PubMed1998

Fibrillin containing elastic microfibrils support platelet adhesion under dynamic shear conditions.

The vascular subendothelium contains macromolecular structures called microfibrils. Type VI collagen is one protein found in microfibrils that supports platelet adhesion and aggregation and we have previously evaluated the roles of platelet receptors and vWf involved in these processes under physiological shear conditions. Here we investigate the ability of fibrillin containing elastic microfibrils to support mural thrombus formation. Our results show that elastic microfibril surfaces support platelet adhesion under low shear conditions at a level similar to collagen VI tetramers. However, the degree of aggregation on the elastic microfibril surface is much higher. Both adhesion and aggregation were shown to be mediated by the GPIIb-IIIa platelet receptor. Elastic microfibrils do not support the formation of mural thrombi under high shear conditions. These results suggest roles for both collagen VI and fibrillin containing elastic microfibrils in modulating the platelet response to blood vessel injury.

Actin Cytoskeleton↗
PubMed1997

Improving stereological estimates for the volume of structures identified in three-dimensional arrays of spatial data.

Investigators frequently measure the volumes of anatomic structures. These volumes can answer important scientific questions such as whether a structure differs between two groups, which structures a disease affects, or how the size of a structure relates to its function. Magnetic resonance (MR) imaging, X-ray computed tomography and confocal microscopy are used more and more frequently in anatomic studies; each yields information that is spatially organized as a three-dimensional array. We describe how to improve an efficient stereological technique for estimating the volumes of structures that are identifiable in these arrays. As an example, we apply the technique to measuring brain volumes by MR imaging. We then show how the results of the technique may be used for solving a typical problem in experimental design. This technique is applicable to a wide range of experimental problems. We discuss its limitations and offer some suggestions and observations relating to its use.

Aged↗
PubMed1997

Models which explain the inhibition of reverse transcriptase by HIV-1-specific (thio)carboxanilide derivatives.

The (thio)carboxanilide derivatives are potent and selective inhibitors of HIV-1 reverse transcriptase (RT) and have a favourable antiviral activity spectrum. To understand better their mode of action, and to provide a structural basis for further improvement, models of RT complexed with four (thio)carboxanilide inhibitors (UC781, UC10, UC38 and UC84) have been constructed based on the X-ray structure of RT complexed with 9-chloro-TIBO. In the models, the protein conformation is similar to that of the RT-TIBO complex and the complexes are stabilised by hydrogen bonding between the inhibitors and the main chain oxygen of Lys101. Significant hydrophobic interactions include those with Leu100, Val106, Val179, Tyr188, Phe227, Leu234, and His235. The thiocarboxanilides UC781 and UC10 also make important hydrophobic interactions with Trp229. The models are consistent with the inhibitors' relative antiviral potencies and the observed resistance data. They further predict that mutations to Phe227, Trp229, or Leu234 might confer resistance. Since these are not observed, some constraining structural or functional role for these residues in the active enzyme is suggested.

Anilides↗
PubMed1997

An overview of the malaria situation in Zanzibar.

Zanzibar is composed of two neighbouring islands with about a 1.1 million inhabitants in 2600 square kilometers. Both islands are located off the northeastern coast of the Tanzanian mainland. Zanzibar is a typical malaria endemic area. About a third of all blood samples currently examined for malaria in Zanzibar are positive to Plasmodium falciparum. Previous attempts failed to significantly improve the malaria situation in Zanzibar due to administrative problems, antimalarial drug and DDT resistance. We visited Zanzibar in order to evaluate the magnitude of the malaria problem and the medical logistics. This paper reviews the results of the visit, past and present attempts to eliminate malaria and our conclusions regarding Zanzibar as a model site for attempts to eradicate malaria.

Antimalarials↗
PubMed1997

Molecular analysis of a compound heterozygote for hypoprothrombinemia and dysprothrombinemia (-G 7248/7249 and ARG 340 TRP).

Hypoprothrombinemia is an uncommon hereditary coagulation defect characterized by low levels of biologically active prothrombin. Automated fluorescence-based DNA sequence analysis of amplified genomic DNA was used to define prothrombin gene regions from a patient with severe functional hypoprothrombinemia and little detectable prothrombin antigen. Two changes that alter amino acid sequence were observed: a deletion of one nucleotide (-G, 7248/7249) in exon 8 of one allele, causing a frameshift at codon 249/250 that results in premature termination of translation; and a C --> T change resulting in the substitution of tryptophan (TGG) for arginine (CGG) at amino acid 340 in exon 10 of the prothrombin gene. Computer modeling of the thrombin molecule confirmed that arginine 340 is located at the surface of the thrombin molecule, which points to the aqueous solvent. As tryptophan is a highly hydrophobic amino acid, the Arg --> Trp change may be associated with instability of the thrombin molecule.

Adult↗
PubMed1997

The significance of subendothelial von Willebrand factor.

von Willebrand factor (vWf) serves to bridge between receptors on the platelet cytoplasmic membrane and the extracellular matrix. In addition to circulating in plasma, vWf is deposited into the extracellular matrix of the subendothelium where it is associated with type VI collagen microfibrils, but not with the elastin-associated microfibrils which are present in the deepest portion of the subendothelium at the zone of the internal elastic lamina. The reaction of platelets to type VI collagen in flow systems is qualitatively different from the shear rate dependent adhesion and aggregation response which is observed with fibrillar type I collagen, exhibiting a response only at low shear rates. The adhesion response to type VI collagen is dependent upon vWf, GP Ib and the GP IIb-IIIa complex. Platelets exposed to purified fibrillin-containing elastin-associated microfibrils adhere and aggregate at low shear rates; this response appears to involve GP IIb-IIIa but not GP Ib. The data are consistent with the hypothesis that type VI collagen is a physiologically relevant binding site for vWf in subendothelium.

Animals↗
PubMed1996

Expression studies of delta-globin gene alleles associated with reduced hemoglobin A2 levels in Greek Cypriots.

We previously identified five delta-globin gene alleles associated with reduced hemoglobin (Hb) A2 (Trifillis, P., Ioannou, P., Schwartz, E., and Surrey, S. (1991) Blood 78, 3298-3305). We have now evaluated functional consequences of the changes after expression in COS-1 cells to monitor effects on RNA splicing. In addition, variant Hb A2 tetramers were expressed in yeast to assess effects of amino acid changes on oxygen binding and stability to heat and mechanical agitation. The G --> T change at codon 27 and the A --> G change in IVS-2 both affect RNA splicing, whereas the C --> T change at codon 97 and the AT deletion in IVS-2 have no effect. Oxygen equilibrium curves of the Hb A2 variants expressed in yeast were similar to that of wild type Hb A2. None of the three variant Hb A2 tetramers (Thr --> Ile at codon 4 (Hb deltaT4I), Ala --> Ser at codon 27 (Hb deltaA27S), and Arg --> Cys at codon 116 (Hb deltaR116C)) showed decreased heat stability compared with Hb A2, whereas the Hb deltaT4I variant showed highest instability to mechanical agitation. Co-expression in yeast of alpha-globin chain and the delta-chain variant containing a Leu --> Pro change at codon 141 yielded no identifiable tetramers, suggesting lack of assembly or severe tetramer instability. These studies show the probable cause for decreased Hb A2 for two alleles is due to defective splicing, whereas decreased protein stability, increased tetramer association with red cell membranes, increased interdisulfide bond formation of delta-chains, which inhibits assembly with alpha-chains, and/or reduced assembly is suggested for the other three alleles.

Alleles↗
PubMed1996

Polymerization of three hemoglobin A2 variants containing Val6 and inhibition of hemoglobin S polymerization by hemoglobin A2.

To understand determinants for hemoglobin (Hb) stability and Hb A2 inhibition of Hb S polymerization, three Valdelta6 Hb A2 variants (Hb A2 deltaE6V, Hb A2 deltaE6V,deltaQ87T, and Hb A2 deltaE6V, deltaA22E,deltaQ87T) were expressed in yeast, and stability to mechanical agitation and polymerization properties were assessed. Oxy forms of Hb A2 deltaE6V and Hb A2 deltaE6V,deltaQ87T were 2- and 1.6-fold, respectively, less stable than oxy-Hb S, while the stability of Hb A2 deltaE6V,deltaA22E,deltaQ87T was similar to that of Hb S, suggesting that Aladelta22 and Glndelta87 contribute to the surface hydrophobicity of Hb A2. Deoxy Hb A2 deltaE6V polymerized without a delay time, like deoxy Hb F gammaE6V, while deoxy Hb A2 deltaE6V,deltaQ87T and deoxy Hb A2 deltaE6V,deltaA22E,deltaQ87T polymerized after a delay time, like deoxy Hb S, suggesting that beta87 Thr is required for the formation of nuclei. Deoxy Hb F gammaE6V,gammaQ87T showed no delay time and required a 3.5-fold higher concentration than deoxy Hb S for polymerization, suggesting that Thr effects on Valdelta6 Hb A2 and Valgamma6 Hb F variants are different. Mixtures of deoxy Hb S/Hb A2 deltaE6V,deltaQ87T polymerized, like deoxy Hb S, while polymerization of Hb S/Hb A2 deltaE6V mixtures was inhibited, like Hb S/Hb F gammaE6V mixtures. These results suggest alpha2betaSdelta6 Val, 87 Thr hybrids and Hb A2 deltaE6V,deltaQ87T participate in Hb S nucleation, while only 50% of alpha2betaSdelta6 Val hybrids and none of the Hb A2 deltaE6V participate. These findings are in contrast to those of mixtures of Hb S with Hb F gammaE6V or Hb F gammaE6V,Q87T, which both inhibit Hb S polymerization. Our results also suggest participation in nucleation of some alpha2betaSdelta hybrids in A2S mixtures but not alpha2betaSgamma hybrids in FS mixtures.

Animals↗
PubMed1996

Efferent neurons of the lateral line system and their innervation of lateral line branches in a euteleost and an osteoglossomorph.

The efferent neurons of the lateral line system of the euteleost Aplocheilus lineatus and the osteoglossomorph Pantodon buchholzi, both surface feeding fish, were examined by neuronal tract tracing. Besides horse-radish peroxidase, fluorescent dextrans were used as tracers to allow simultaneus visualization of projections from different lateral line branches. Labeled efferent neurons were found in nuclei situated in the medulla ventral of ventricle IV. This position resembles the octa-volateralis efferent nucleus of previous studies. The number of labeled cells in the efferent nucleus is low in both species. Most neurons were found ipsilaterally to the application site, some along the midline and only very few contralaterally. The size of efferent cells differs distinctly between Aplocheilus, possessing small cell-bodies (length 16.5 microm), and Pantodon, which has very large efferent cells (length 47.0 micron). Efferent axon bundles course rostrally in both species, leaving the brain at the level of the anterior lateral line nerve. Only Aplocheilus has in addition lateral axon bundles leaving the brain at the level of the posterior lateral line nerve. After application of one fluorescent tracer to the lateral ramus and a different fluorescent tracer to the superficial ophtalmic ramus in a given animal, double-labeling of efferent cells hardly ever occurs. If the neuromasts I and IV of the dorsal skull of Pantodon are applied with one fluorescent tracer each, approximately 10% of centrally labeled cells are double-labeled. Considering the results of double-labeling, the concept of a differential innervation of lateral line branches is supported and discussed.

Animals↗
PubMed1996

Developmental analysis of GFAP immunoreactivity in the cerebellum of the meander tail mutant mouse.

It is thought that Bergmann glial fibers assist in the inward migration of granule cells. Model systems in which there is a perturbation of either the migrating cells or the glial cell population have been useful in understanding the migratory process. In the meander tail mutant mouse, the anterior cerebellar region is agranular, whereas the posterior cerebellum is relatively unaffected by the mutation. This study presents a qualitative analysis of the development of cerebellar radial glia in mea/mea and +/mea mice aged from postnatal day 0 to adult, using an antibody against the glia specific antigen, glial fibrillary acidic protein. The results indicate a slight delay in the onset of immunoreactivity in the mea/mea cerebellum and abnormal glial formation in the anterior and posterior regions by postnatal day 5. At postnatal day 11, the full complement of labeled fibers appears to be present and although they appear abnormal in formation, they eventually reach the surface and terminate in oddly shaped and irregularly spaced endfeet. In adult mea/mea and +/mea mice, as compared to the early postnatal stages, there is a significant reduction in GFAP immunoreactive fibers. Cresyl violet stained adult mea/mea sections revealed the presence of ectopic granule cells in radial columns and small clumps at the surface of and within the molecular layer of the caudal cerebellum. Quantitative analyses revealed a 4- to 5-fold increase in the number of ectopic granule cells in lobule VIII of the mea/mea when compared with the +/mea cerebellum. These results suggest that the radial glia in the mea/mea cerebellum exhibit some uncharacteristic morphologies, but that these abnormalities are most likely the consequence of environmental alterations produced by the mutant gene.

Age Factors↗
PubMed1996

Three stages of medical dialogue.

The negative consequences of physicians' failure to establish and maintain personal relationships with patients are at the heart of the "humanistic crisis" in medicine. To resolve this crisis, a new model of doctor-patient interaction is proposed, based on the ideas of Martin Buber's philosophy of dialogue. This model shows how the physician may successfully combine the personal (I-Thou) and impersonal (I-It) aspects of medicine in three stages. These "Three Stages of Medical Dialogue" include: 1. An Initial Personal Meeting stage, which initiates the doctor-patient relationship and involves mutual confirmation; 2. An Examination stage, which requires a shift from a personal to an impersonal style of interaction; 3. An Integration Through Dialogue or "Healing Through Meeting" Stage, which involves the integration of the impersonal medical data into the ongoing dialogue between doctor and patient, as a basis for shared decision-making. The use of the model, as well as common failures of doctor-patient dialogue are discussed.

Aged↗
PubMed1996

Peeling agents and irritants, unlike tretinoin, do not stimulate collagen synthesis in the photoaged hairless mouse.

Tretinoin has been shown to stimulate the synthesis of collagen in photo-aged human and hairless mouse skin. It has been suggested that this partial reversal of photodamage by tretinoin is a consequence of low-grade inflammation. The purpose of this study was to compare the effect of tretinoin with a number of irritants and peeling agents on collagen synthesis. Hairless mice were irradiated thrice weekly for 10 weeks with UVB. In the 10-week postirradiation period, the mice were treated topically five times per week with tretinoin (0.05%), glycolic acid (10%), benzalkonium chloride (1.0%), sodium lauryl sulfate (5%), croton oil (5%) and the water - propylene glycol vehicle. Microscopic measurements showed that the tretinoin-induced zone of new collagen was twice the depth of that induced by irritants or vehicle. The salt-soluble collagen content was determined by HPLC analysis of hydroxyproline levels. Type III procollagen was quantified by radioimmunoassay. Tretinoin-treated skin had increased amounts of collagen and type III procollagen whereas irritant- and peeling agent-treated skins were similar to vehicle-treated controls. Immunofluorescence studies were confirmatory. These results demonstrate that these agents, unlike tretinoin, do not have the capacity to enhance collagen synthesis. Therefore, it is likely that the effect of tretinoin does not depend upon irritation.

Animals↗
PubMed1996

Dengue fever among travelers.

PURPOSE: The present paper describes the epidemiology and clinical manifestations of dengue fever in a nonendemic population of travelers. PATIENTS AND METHODS: Clinical manifestations, epidemiologic information, and laboratory findings are described for a series of 18 Israeli travelers who tested serologically positive for dengue. RESULTS: All the patients in the series contracted the disease in Southeast Asia, mostly in Thailand; 30% had to be evacuated due to severe morbidity. The clinical symptoms in travelers somewhat differ from the classical description among endogenous populations. High fever, chills, extreme fatigue, and severe headaches were prevalent. Other symptoms considered to be typical of dengue fever, such as myalgia, arthralgia, rash, biphasic fever, were uncommon. Laboratory findings were marked leukopenia, usually accompanied by lymphopenia, thrombocytopenia, liver function impairment, and hyponatremia. Some hemorrhagic phenomena were manifest despite it being the first exposure, without mortality. CONCLUSIONS: Dengue fever among the nonimmune has a somewhat different manifestation from that reported for the Southeast Asian population. Although it is a significant cause for morbidity and hospitalization, it is underestimated as a factor affecting traveler's health. More efforts should be expended in developing an effective vaccine.

Adult↗
PubMed1996

Relationship between Fc receptor IIA polymorphism and infection in children with sickle cell disease.

OBJECTIVE: Despite penicillin prophylaxis and vaccination, infection with encapsulated organisms remains a leading cause of morbidity and death in children with sickle cell disease. The role of Fc receptors in the clearance of encapsulated organisms is well documented. The His(H)-Arg(R) polymorphism at amino acid 131 of the Fc gamma RIIA receptor alters binding affinity for human IgG2 and influences infection with encapsulated organisms in children without sickle cell disease. We hypothesized that the genotype for high-affinity human IgG2 binding (H/H131) is underrepresented in children with sickle cell disease who had encapsulated organism infection. DESIGN: We studied 60 black children with sickle cell disease from four participating centers who had a history of encapsulated organism infection. Genomic DNA from peripheral blood was subjected to amplification by polymerase chain reaction and to sequence analysis for identification of the Fc gamma RIIA genotype, and the genotype distribution was then compared with our data from ethnically matched control subjects. RESULTS: Contrary to our hypothesis, the H/H131 genotype was overrepresented in all individuals (p = 0.046) and in particular in the 11 individuals with a history of Haemophilus influenzae type b infection (64% H/H131, 27% H/R131, 9% R/R131; p = 0.002), in comparison with ethnically matched control subjects (14% H/H131, 60% H/R131, 26% R/R131). In the 51 individuals with a history of Streptococcus pneumoniae infection, the genotype distribution was not statistically significantly different from that of the control population. CONCLUSIONS: The H/H131 Fc gamma RIIA genotype is overrepresented in black children with sickle cell disease and a history of H. influenzae type b infection but not in those with S. pneumoniae infection.

Adolescent↗