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Biomedical subjects

S Reed

Publications and source records attributed to S Reed.

At least 19 recordsLinked to original sources
PubMed2001

The potency and durability of DNA- and protein-based vaccines against Leishmania major evaluated using low-dose, intradermal challenge.

DNA- and protein- based vaccines against cutaneous leishmaniasis due to Leishmania major were evaluated using a challenge model that more closely reproduces the pathology and immunity associated with sand fly-transmitted infection. C57BL/6 mice were vaccinated s.c. with a mixture of plasmid DNAs encoding the Leishmania Ags LACK, LmSTI1, and TSA (AgDNA), or with autoclaved L. major promastigotes (ALM) plus rIL-12, and the mice were challenged by inoculation of 100 metacyclic promastigotes in the ear dermis. When challenged at 2 wk postvaccination, mice receiving AgDNA or ALM/rIL-12 were completely protected against the development of dermal lesions, and both groups had a 100-fold reduction in peak dermal parasite loads compared with controls. When challenged at 12 wk, mice vaccinated with ALM/rIL-12 maintained partial protection against dermal lesions and their parasite loads were no longer significantly reduced, whereas the mice vaccinated with AgDNA remained completely protected and had a 1000-fold reduction in dermal parasite loads. Mice vaccinated with AgDNA also harbored few, if any, parasites in the skin during the chronic phase, and their ability to transmit L. major to vector sand flies was completely abrogated. The durable protection in mice vaccinated with AgDNA was associated with the recruitment of both CD8(+) and CD4(+) T cells to the site of intradermal challenge and with IFN-gamma production by CD8(+) T cells in lymph nodes draining the challenge site. These data suggest that under conditions of natural challenge, DNA vaccination has the capacity to confer complete protection against cutaneous leishmaniasis and to prevent the establishment of infection reservoirs.

Animals↗
PubMed2001

The second stage of labor and stress urinary incontinence.

OBJECTIVE: This study was undertaken to investigate the potential association between prolonged second stage of labor and stress urinary incontinence. STUDY DESIGN: A retrospective, population-based study was performed. A random, case-controlled sample of 85 cases and 88 controls was identified by means of a standard computerized patient database. Subjects were identified by International Classification of Diseases, Ninth Revision codes, and medical records were reviewed. The median follow-up time from delivery was 7.8 years for cases and 7.2 years for controls. Multiple logistic regression was performed to test for an association between stress urinary incontinence and variables of interest. RESULTS: The data suggest that for all women who labored the length of the second stage of labor for the first delivery was not associated with stress urinary incontinence (odds ratio, 1.07; P =.42; 95% confidence interval, 0.9-1.3). However, forceps delivery was associated with a significant increase in stress urinary incontinence risk (odds ratio, 10.4; P =.04; 95% confidence interval, 1.2-93.4). CONCLUSION: Length of second stage of labor was not associated with stress urinary incontinence. However, the odds of having a later diagnosis of stress urinary incontinence was 10 times higher for women who underwent forceps delivery.

Adult↗
PubMed2001

Low-resistance endometrial arterial flow in the exclusion of ectopic pregnancy revisited.

The objective of this study was to evaluate the efficacy of endometrial arterial flow in the exclusion of ectopic pregnancy. From October 1997 to June 1999, 66 women with elevated beta-human chorionic gonadotropin titers and clinical indications of ectopic pregnancy were evaluated by endovaginal sonography. Women with a gestational sac containing an embryo, a yolk sac, or both were excluded from the study. Doppler ultrasonography was performed in the remaining cases when a definite intrauterine pregnancy could not be visualized. In all cases the thermal index was kept to less than 1.0, consistent with as-low-as-reasonably-achievable principles. Trophoblastic flow was defined as a resistive index of less than 0.6 within the endometrium. Statistical analysis was performed using a 2-tailed t test. Twenty women had ectopic pregnancies; 33 had spontaneous pregnancy losses; and 13 had normal intrauterine pregnancies. A total of 29 women had endometrial trophoblastic flow: 11 of 13 with intrauterine pregnancies, 1 of 20 with ectopic pregnancies, and 17 of 33 with spontaneous pregnancy losses. The negative predictive value for the presence of endometrial low-resistance flow for excluding ectopic pregnancy was 97%. The presence of low-resistance arterial endometrial flow can be a useful sign in diagnosing an early intrauterine pregnancy and decreasing the probability that an ectopic pregnancy is present, particularly in patients with otherwise normal ultrasonographic findings.

Adult↗
PubMed2000

Circulating levels of sTNFR and discrepancy between cytotoxicity and immunoreactivity of TNF-alpha in patients with visceral leishmaniasis.

OBJECTIVES: To study the influence of soluble tumour necrosis factor (TNF) receptors (sTNFR) on bioactivity and immunoreactivity of TNF-alpha in patients with visceral leishmaniasis (Kala-azar) and to examine the association between circulating levels of sTNFR type I and type II with clinical manifestations of the disease. METHODS: Ten patients with Kala-azar were enrolled. Plasma samples for TNF-alpha and sTNFR were obtained on days 0, 7 and 21-28 of antimonial therapy. Bioactivity of TNF-alpha was measured by cytotoxicity to L-929 cells and immunoreactivity by enzyme-linked immunosorbent assay (ELISA). sTNFR-I and sTNFR-II were measured by ELISA. RESULTS: Measured by ELISA, TNF-alpha was detected at baseline in all patients (range from 22.3 to 163 pg/mL) and showed a linear decline over time on therapy (r = -0.49, P = 0.007). In contrast, when measured by cytotoxicity assay, TNF-alpha was detected in only one patient at baseline (193 pg/mL) and in four patients at the end of therapy (38.7, 95, 133 and 232 pg/mL) and there was no linear association between TNF-alpha and duration of therapy (r = -0.18, P = 0.45). sTNFR-I and sTNFR-II were detected in all patients before therapy. There was a strong positive correlation between plasma concentrations of sTNFR-I and sTNFR-II (r = 0.8, P = 0.006). Levels of sTNFR-I and sTNFR-II declined exponentially with time on therapy. CONCLUSIONS: We concluded that sTNFR-I and sTNFR-II are related to disease activity in patients with Kala-azar and that these circulating receptors may interfere with the biological activity of TNF-alpha in patients with Kala-azar.

Animals↗
PubMed2000

Increasing frequency of dental patients in the urban ED.

This study examined the spectrum and frequency of dental disorders presenting to an urban ED. Data were retrospectively collected on all patients presenting with dental complaints between January 1, 1987 and December 31, 1995. Data included age, date and time of presentation, diagnosis, triage acuity and disposition. Of the 3,943 charts reviewed, 1,892 (48%) patients required emergent oral surgery management and 2,051 (52%) emergency physician management only. The frequency of dental patients increased from 4.4/1,000 total ED patients in 1987 to 11.5/1,000 in 1995 (P < .05). The rate of emergent dental trauma, emergent nontraumatic dental care, and nonemergent nontraumatic dental care increased similarly during the study period. There was no significant difference by day of week, but a significantly greater number of nonemergent patients presented between 7:00 a.m. and 3:00 p.m. (72%). The incidence of dental patients presenting to the ED increased significantly between 1987 and 1995. Approximately one-half did not require specialist consultation and could potentially have been managed by a primary care dental practitioner.

Adolescent↗
PubMed2000

Molecular epidemiology of Entamoeba spp.: evidence of a bottleneck (Demographic sweep) and transcontinental spread of diploid parasites.

Entamoeba histolytica causes amebic colitis and liver abscess in developing countries such as Mexico and India. Entamoeba dispar is morphologically identical but is not associated with disease. Here we determined the ploidy of E. histolytica and developed PCR-based methods for distinguishing field isolates of E. histolytica or E. dispar. Fluorescence in situ hybridization showed that E. histolytica trophozoites are diploid for five "single-copy" probes tested. Intergenic sequences between superoxide dismutase and actin 3 genes of clinical isolates of E. histolytica from the New and Old Worlds were identical, as were those of E. dispar. These results suggest a bottleneck or demographic sweep in entamoebae which infect humans. In contrast, E. histolytica and E. dispar genes encoding repeat antigens on the surface of trophozoites (Ser-rich protein) or encysting parasites (chitinase) were highly polymorphic. chitinase alleles suggested that the early axenized strains of E. histolytica, HM-1 from Mexico City, Mexico, and NIH-200 from Calcutta, India, are still present and that similar E. dispar parasites can be identified in both the New and Old Worlds. Ser-rich protein alleles, which suggested the presence of the HM-1 strain in Mexico City, included some E. histolytica genes that predicted Ser-rich proteins with very few repeats. These results, which suggest diversifying selection at chitinase and Ser-rich protein loci, demonstrate the usefulness of these alleles for distinguishing clinical isolates of E. histolytica and E. dispar.

Actins↗
PubMed2000

Analysis of 16S rRNA and 51-kilodalton antigen gene and transmission in mice of Ehrlichia risticii in virgulate trematodes from Elimia livescens snails in Ohio.

Operculate snails (the family Pleuroceridae: Elimia livescens) were collected between June and October 1998 from a river in central Ohio where repeated cases of Potomac horse fever (PHF) have occurred. Of collected snails, consistently 50 to 80% carried a combination of cercariae and sporocysts of digenetic virgulate trematodes. The trematodes obtained from each snail were pooled and tested for Ehrlichia risticii, the agent of PHF, by nested PCR using primers specific to the 16S rRNA gene. Out of a total of 209 trematode pools, 50 pools were found to be positive by PCR. The DNA sequence of the 16S rRNA gene identified in one trematode pool was identical to that of the type strain of E. risticii, and the sequence of the gene identified in another pool differed from that of the type strain by 1 nucleotide. Comparison of the deduced amino acid sequence of the partial 51-kDa antigen gene from various sources revealed that Maryland, Ohio (except Ohio 081), and Kentucky strains are in a cluster distinct from the sequences obtained from sources in California and Oregon. Ohio 081 was shown previously by antigenic composition analysis to be distinct from other groups. However, all sequences examined were not segregated according to their sources: horse blood or infected trematodes. E. risticii was found to be transmittable from trematodes to mice and was subsequently passaged from infected mice to additional mice, as determined by PCR analysis. Our findings suggest the evolution of E. risticii in the natural reservoir in separate geographic regions and persistent infection of trematode populations with E. risticii during summer and early fall. The study also suggests that the mouse can be used to isolate E. risticii from the infected trematode.

Amino Acid Sequence↗
PubMed1999

Direct induction of cyclin D2 by Myc contributes to cell cycle progression and sequestration of p27.

Ectopic expression of Myc induces Cdk2 kinase activity in quiescent cells and antagonizes association of p27(kip1) with Cdk2. The target gene(s) by which Myc mediates this effect is largely unknown. We now show that p27 is rapidly and transiently sequestered by cyclin D2-Cdk4 complexes upon activation of Myc and that cyclin D2 is a direct target gene of Myc. The cyclin D2 promoter is repressed by Mad-Max complexes and de-repressed by Myc via a single highly conserved E-box element. Addition of trichostatin A to quiescent cells mimics activation of Myc and induces cyclin D2 expression, suggesting that cyclin D2 is repressed in a histone deacetylase-dependent manner in quiescent cells. Inhibition of cyclin D2 function in established cell lines, either by ectopic expression of p16 or by antibody injection, inhibits Myc-dependent dissociation of p27 from Cdk2 and Myc-induced cell cycle entry. Primary mouse fibroblasts that are cyclin D2-deficient undergo accelerated senescence in culture and are not immortalized by Myc; induction of apoptosis by Myc is unimpaired in such cells. Our data identify a downstream effector pathway that links Myc directly to cell cycle progression.

3T3 Cells↗
PubMed1999

High-density lipoprotein: multipotent effects on cells of the vasculature.

The epidemiological evidence showing a strong inverse correlation between the level of plasma high-density lipoprotein (HDL) and the incidence of heart disease suggests that HDL has a protective effect against cardiovascular disease. The mechanism of this protective effect has been the raison d'etre for much research. The ability of HDL to mediate cholesterol efflux from peripheral tissues has been used to explain the cardioprotective effect of HDL. However, there is little direct evidence to suggest that in subjects with low plasma levels of HDL the rate of cholesterol efflux from peripheral tissues is significantly reduced. This observation suggested that HDL may be mediating its protective effect through other mechanisms. This review provides an account of the burgeoning evidence that HDL has many effects on cellular processes, in addition to the effects on cholesterol efflux, and will illustrate the multipotency of this lipoprotein.

Acute-Phase Proteins↗