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Biomedical subjects

E Schwartz

Publications and source records attributed to E Schwartz.

At least 55 records · Page 3Linked to original sources
PubMed1999

Hepatitis E virus infection in travelers.

Hepatitis E virus (HEV) is a major cause of clinical hepatitis in regions of endemicity, affecting primarily young adults and travelers to these areas. We present 5 cases of acute HEV infection in travelers and review 143 cases of HEV infection found by a literature search that were contracted in areas of endemicity. Fulminant hepatitis occurred in 2.7% of the reported cases; 2 of these were fatal. The destination of most of the travelers with acute HEV infection was the Indian subcontinent. The overall risk of contracting HEV infection for travelers appears to be lower than the risk for hepatitis A virus infection. Pregnant women and individuals with underlying liver disease may be a risk for severe infection.

Acute Disease↗
PubMed1999

Primaquine as prophylaxis for malaria for nonimmune travelers: A comparison with mefloquine and doxycycline.

Malaria prophylaxis for travelers is a controversial issue. The commonly used regimens are associated with side effects, low compliance, or low efficacy, which have raised concern regarding their use. In addition, they are inefficient against the tissue stage of the parasite and thus do not prevent relapses of Plasmodium vivax infection. Primaquine is aimed at the pre-erythrocytic stage and thus may be a potential causal-prophylactic treatment that can abolish the need for long postexposure therapy. During 1995-1998, we followed retrospectively travelers who joined rafting trips to an area in Ethiopia where both P. vivax and Plasmodium falciparum are hyperendemic. Of the 106 travelers who received primaquine, 5.7% developed malaria; of the 19 doxycycline recipients, 53% developed malaria; and of the 25 mefloquine recipients, 52% developed P. vivax malaria (>/=3 months after return from the area of endemicity). Primaquine was well tolerated, and only 1 withdrawal from therapy (due to gastrointestinal symptoms) was reported. Primaquine was shown to be a safe and effective prophylactic drug against both P. falciparum malaria and P. vivax malaria in travelers.

Adult↗
PubMed1999

Steady-state mRNA levels of interleukin-1, integrins, cJun, and cFos in hairless mouse skin during short-term chronic UV exposure and the effect of topical tretinoin.

We have proposed that UV activation of cytokine and integrin signaling pathways may initiate the photoaging process and that one of the effects of tretinoin treatment may be to alter the cytokine and integrin patterns. In previous results, steady-state mRNA levels of interleukin-1alpha, tumor necrosis factor alpha, transforming growth factor beta, collagenase, stromelysin, collagen, and integrins (alpha1 and alpha2) were increased in the skin of hairless mice that were either UV treated or concurrently treated with UV followed by topical tretinoin for 5 weeks. The aim of this study was to focus on the expression of alpha1, alpha2 and alpha5 integrins, IL-1alpha, IL-1beta, cJun, and cFos at an earlier time point (3 weeks). Animals were UV irradiated thrice weekly for 3 weeks and were treated topically with either 0.05% tretinoin or the vehicle immediately after each exposure. Total RNA was prepared and used in RT-PCR with radiolabeled dCTP and specific primers. UV slightly increased steady-state mRNA levels for alpha1, alpha2 and alpha5 integrins whereas UV + tretinoin increased their expression (3-, 2- and 7-fold respectively). Steady-state mRNA levels for IL-1alpha, IL-1beta and cJun were increased with UV (3-, 12- and 6-fold respectively) and with UV + tretinoin (6-, 7- and 9-fold respectively). In contrast, cFos expression was unchanged. In situ staining for IL-1alpha mRNA was slightly more abundant in mice treated for 3 weeks with UV and UV + tretinoin than in controls whereas 5 weeks of UV + tretinoin treatment gave strongly positive staining. Results are consistent with cytokines and integrins mediating the effects of UV on the skin, with modulation of these effects by tretinoin.

Administration, Topical↗
PubMed1999

Positive transcriptional feedback controls hydrogenase expression in Alcaligenes eutrophus H16.

The protein HoxA is the central regulator of the Alcaligenes eutrophus H16 hox regulon, which encodes two hydrogenases, a nickel permease and several accessory proteins required for hydrogenase biosynthesis. Expression of the regulatory gene hoxA was analyzed. Screening of an 8-kb region upstream of hoxA with a promoter probe vector localized four promoter activities. One of these was found in the region immediately 5' of hoxA; the others were correlated with the nickel metabolism genes hypA1, hypB1, and hypX. All four activities were independent of HoxA and of the minor transcription factor sigma(54). Translational fusions revealed that hoxA is expressed constitutively at low levels. In contrast to these findings, immunoblotting studies revealed a clear fluctuation in the HoxA pool in response to conditions which induce the hox regulon. Quantitative transcript assays indicated elevated levels of hyp mRNA under hydrogenase-derepressing conditions. Using interposon mutagenesis, we showed that the activity of a remote promoter is required for hydrogenase expression and autotrophic growth. Site-directed mutagenesis revealed that P(MBH), which directs transcription of the structural genes of the membrane-bound hydrogenase, contributes to the expression of hoxA under hydrogenase-derepressing conditions. Thus, expression of the hox regulon is governed by a positive feedback loop mediating amplification of the regulator HoxA. These results imply the existence of an unusually large (ca. 17,000-nucleotide) transcript.

Alcaligenes↗
PubMed1999

Gln --> Arg 191 polymorphism of paraoxonase and Parkinson's disease.

We investigated the Gln --> Arg 191 polymorphism in paraoxonase (PON1) in St. Petersburg population, in three clinically differentiated groups of patients with Parkinson's disease (PD) and in the symptomatic tremor group. A new approach for Gln --> Arg 191 PON1 polymorphism genotyping is suggested. No significant differences in the groups studies as compared to the controls was observed.

Aged↗
PubMed1998

Generation of a tropoelastin mRNA variant by alternative polyadenylation site selection in sun-damaged human skin and ultraviolet B-irradiated fibroblasts.

The goal of this research was to delineate the post-transcriptional mechanisms responsible for the increased elastin synthesis characteristic of sundamaged skin. In this study, a unique molecular variant of the tropoelastin mRNA transcript was identified in human sundamaged skin that was derived from the usage of an alternate polyadenylation site. Nonsolar exposed human skin expressed one tropoelastin mRNA species whereas sundamaged human skin expressed the primary tropoelastin mRNA and a larger, alternate tropoelastin mRNA formed from the utilization of a second polyadenylation site. Cultured human skin fibroblasts expressed both tropoelastin transcripts and in vitro UV treatment increased the amount of the unique tropoelastin mRNA. Hairless mouse skin (normal and UV treated) expressed the primary tropoelastin transcript although UV irradiation increased the length of its poly (A) tail two-fold. Therefore, UV radiation may stimulate elastin production by affecting polyadenylation site selection and the poly (A) tail length of tropoelastin mRNA.

Aged↗
PubMed1998

-245 bp of 5'-flanking region from the human platelet factor 4 gene is sufficient to drive megakaryocyte-specific expression in vivo.

Platelet factor 4 (PF4) serves as a lineage-specific marker of megakaryocyte development. We previously identified two positively acting sequences in the human platelet factor 4 (hPF4) gene promoter that synergized to drive high-level luciferase reporter gene expression in vitro. Using portions of the hPF4 5'-flanking region linked to the lacZ reporter gene, we observed in this investigation that constructs with -245 bp of 5'-flanking region were more active than constructs with -2 kb of 5'-flanking region in vitro. We created two independent transgenic mouse lines with a -245-bp hPF4/lacZ construct. Cells from these mice were tested for beta-galactosidase (beta-gal) expression at the mRNA level by Northern blot and semiquantitative reverse transcription polymerase chain reaction (RT-PCR) and at the protein level by immunohistochemistry assay. Mice from one line showed beta-gal expression specifically in all megakaryocytes of all ploidy classes from bone marrow and in platelets. Expression level was comparable to that driven by the 1.1-kb rat PF4 promoter in other transgenic mouse lines. Those in the second line showed no beta-gal expression in megakaryocytes, platelets, or any of the eight organs tested. The -245-bp hPF4 promoter is capable of driving reporter gene expression in a megakaryocyte-specific manner in transgenic mice. The small size of this megakaryocyte-specific promoter is compatible with that required in some viral vectors and may provide a model for targeting gene expression to megakaryocytes.

Animals↗
PubMed1998

A naturally occurring mutation in Fc gamma RIIA: a Q to K127 change confers unique IgG binding properties to the R131 allelic form of the receptor.

Fc gamma RIIa is widely expressed on hematopoietic cells. There are two known allelic polymorphic forms of Fc gamma RIIa, Fc gamma RIIa-R131 and Fc gamma RIIa-H131, which differ in the amino acid at position 131 in the second lg-like domain. In contrast to Fc gamma RIIa-R131, Fc gamma RIIa-H131 binds hlgG2 but not mIgG1, and this differential binding has clinical implications for host defense, autoimmune disease, immunohematologic disease, and response to therapeutic monoclonal antibodies. We identified a novel Fc gamma RIIA genotype in a healthy individual homozygous for Fc gamma RIIA R/R131 in whom a C to A substitution at codon 127 changes glutamine (Q) to lysine (K) in one of the two Fc gamma RIIA genes. This individual's homozygosity for Fc gamma RIIA-R/R131 leads to the prediction that the receptors on her cells would not bind hIgG2. Monocyte and neutrophil phagocytosis of hIgG2-opsonized erythrocytes was significantly higher (P < .05) for cells from this K/Q127, R/R131 individual than for Q/Q127, R/R131 donors. Platelet aggregation stimulated by an mIgG1 anti-CD9 antibody in this individual was significantly different (P < .05) from Q/Q127, H/R131 and Q/Q127, H/H131 donors and similar to Q/Q127, R/R131. Our data show that the K127/R131 receptors have a unique phenotype, binding both hIgG2 and mIgG1. Further functionally significant mutations in human Fc gamma receptors and possible novel mechanisms for inherited differences in disease susceptibility should be sought with unbiased screening methods.

Alleles↗
PubMed1998

Prevalence of Lithuanian mutation among St. Petersburg Jews with familial hypercholesterolemia.

We used polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis to detect LDL receptor gene defects in the St. Petersburg population. We have found a deltaG197 mutation in several patients of Jewish origin. The mutation named is shown to be responsible for one-third (7/23) of familial hypercholesterolemia (FH) cases in St. Petersburg Jews and absent in patients of Russian descent. The prevalence of a deltaG197 mutation in St. Petersburg Jews is consistent with its origin in Lithuania or Poland. The deltaG197 mutation can be easily detected in polyacrylamide minigels because of formation of specific heteroduplexes during PCR with DNA of heterozygous patients. Taken together with high prevalence of the mutation in St. Petersburg Jews, this observation provides an opportunity for DNA diagnostics of FH in this ethnic group.

DNA Mutational Analysis↗
PubMed1998

Age as a risk factor for myocardial infarction in Leiden mutation carriers.

A single factor V gene G-A mutation (Arg506Gln) underlying activated protein C (APC) resistance is a common risk factor for venous thromboembolism. It is still unclear whether the factor V Leiden predisposes patients to arterial thrombosis and myocardial infarction (MI). To determine a correlation between the factor V Leiden mutation and MI in different age categories, DNA samples from 287 patients with "early" and "late" MI were investigated. As control groups 373 young subjects (mean age 11 years) and 110 elderly ones (mean age 80 years) were studied. We found a significant difference in mutant allele distribution in the "late" MI group compared to the "early" MI group (chi2 = 9.86, OR = 13,7, P < 0.005) and the control group of elderly subjects (chi2 = 5.92, OR = 8.6, P < 0.02). The mean age of MI patients carrying the Leiden mutation was 72 years, i.e., 12 years higher than the mean age of all investigated MI patients (60 years). Thus, we found a statistically significant correlation between MI and factor V Leiden mutation in elderly subjects.

Adolescent↗
PubMed1998

Ultraviolet B radiation increases steady-state mRNA levels for cytokines and integrins in hairless mouse skin: modulation by topical tretinoin.

Chronically sun-damaged human skin has a wrinkled, aged appearance as a result of alterations in the dermal extracellular matrix. Secondary effectors such as cytokines and integrins may mediate the effects of UV radiation on the skin by regulating the synthesis of metalloproteinases and structural proteins including collagen. The aim of this study was to semi-quantify the steady-state mRNA levels of interleukin-1 alpha, tumor necrosis factor alpha, transforming growth factor beta, collagenase, stromelysin, collagen, and integrins (alpha, and alpha2) in the skin of hairless mice that were either treated with UV or concurrently treated with UV and topical tretinoin for 5 weeks. Total RNA was extracted from the skin of the mice, reverse transcribed to cDNA, and amplified by the polymerase chain reaction in the presence of 32P-dCTP using gene-specific primers. Results were normalized relative to glyceraldehyde-3-phosphate dehydrogenase levels. Steady-state mRNA levels of the cytokines and integrins were increased by UV radiation. Concurrent UV and topical tretinoin treatment superinduced the expression of interleukin-1, increased alpha 1, and decreased alpha 2 integrin expression. Immunofluorescence analysis showed increased dermal localization of beta 1 integrin in UV and tretinoin treated skin. These results suggest that cytokines and integrins may be involved in the mechanism of photo-damage.

Administration, Topical↗
PubMed1998

Transgenic mice with elevated level of CuZnSOD are highly susceptible to malaria infection.

Copper/zinc superoxide dismutase (CuZnSOD) catalyses the conversion of O2.- into H2O2. Constitutive overexpression of CuZnSOD in cells and animals creates an indigenous oxidative stress that predisposes them to added insults. In this study, we used transgenic CuZnSOD (Tg-CuZnSOD) mice with elevated levels of CuZnSOD to determine whether overexpression of CuZnSOD affected the susceptibility of these mice to plasmodium infection. Acute malaria is associated with oxidative stress, mediated by redox-active iron released from the infected RBC. Two independently derived Tg-CuZnSOD lines showed higher sensitivity than control mice to infection by Plasmodium berghei (P. berghei), reflected by an earlier onset and increased rate of mortality. Nevertheless, while Tg-CuZnSOD mice were more vulnerable than control mice, the levels of parasitemia were comparable in both strains. Moreover, treatment of infected red blood cells (RBC) with oxidative stress inducers, such as ascorbate or paraquat, reduced the viability of parasites equally in both transgenic and control RBC. This further confirms that increased CuZnSOD does not support plasmodia development. The data are consistent with the possibility that the combination of increased redox-active iron and elevated H2O2 in the plasmodium-infected Tg-CuZnSOD mice, led to an enhanced Fenton's reaction-mediated HO. production, and the resulting oxidative injury renders the transgenic mice more vulnerable to parasite infection.

Animals↗
PubMed1998

New aspects of malaria imported from Ethiopia.

We describe a high incidence of Plasmodium vivax malaria among travelers returning from Ethiopia, who all took the recommended prophylaxis. Three groups of 7-11 nonimmune travelers received mefloquine (250 mg weekly), beginning 1-2 weeks prior to departure and continuing for 4 weeks after their return. A fourth group mistakenly took inadequate prophylaxis and is presented for comparison. Vivax malaria occurred at a rate of up to 50% in the first three groups; nearly all patients became ill 3 months after exposure. In the fourth group, primary attacks of both falciparum and vivax malaria occurred within 1 month of return, at an incidence of 50%. The use of mefloquine prevented Plasmodium falciparum infection, but a very high rate of relapses of P. vivax infection occurred. The complexity of prophylaxis for malaria in an area with a high rate of both P. falciparum and P. vivax infections and the urgent need for effective causal prophylaxis are discussed.

Animals↗
PubMed1998

The prevalence of hepatitis A antibodies among Israeli travellers and the economic feasibility of screening before vaccination.

BACKGROUND: Hepatitis A (HA) is the most common vaccine-preventable disease among travellers. The probability of contracting the disease depends on the endemicity in both the destination and country of origin of the traveller. The introduction of the new highly effective but expensive inactivated HA vaccine necessitates a re-evaluation of HA prevention policy. In highly developed countries all travellers require vaccination. In highly endemic areas the entire population is immune. In Israel, HA seroprevalence declined from 94% in the early 1970s to < 60% in the mid 1980s. Living in a country in which the HA endemicity is changing, we studied the current situation of HA seroprevalence among travellers and the cost-benefit of screening for HA IgG before vaccination. METHODS: Israeli travellers of all ages, (range 22-74 years) expecting to spend a considerable time abroad presented to the travel clinic for pre travel advice and vaccination. A brief medical history was taken, including history of jaundice. Blood for HA IgG testing was drawn. RESULTS: In the present study, 389 Israeli travellers were screened for HA IgG. Overall, 46% were seropositive: 26% in the 21-30 group (n = 102); 37% in the 31-40 group (n = 145); 62% in the 41-50 group (n = 62); and 79% in the > 50 group (n = 80). CONCLUSIONS: In countries where hepatitis A endemicity is changing, an evaluation of seroprevalence and then a cost benefit calculation should be made. In Israel, assuming a current cost of $130 for vaccination and $30 for the IgG test, it is economically valid to screen Israeli travellers > 30 years old for HAV IgG before vaccination. A formula is presented for calculating the cost benefit ratio in any country, based on local endemicity according to age group.

Adult↗
PubMed1998

Simultaneous amoebic liver abscess and hepatitis A infection.

Hepatitis A virus (HAV) infection and amoebic liver abscess have an identical mode of transmission (fecal-oral route) and similar epidemiology. Either of these diseases might be considered in patients presenting with clinical signs and symptoms of liver disease in areas of the world where hepatitis and Entamoeba histolytica are endemic. The following two cases describe patients with simultaneous infection of HAV and amoebic liver abscess. This report emphasizes the role of dual infection in patients from endemic areas. It also challenges the assumption that jaundice in patients with amoebic liver abscess is due to amoebic hepatitis, rather than co-infection with viral hepatitis.

Acute Disease↗