Search PubMed⌕ Search

Biomedical subjects

J M Roberts

Publications and source records attributed to J M Roberts.

At least 37 records · Page 2Linked to original sources
PubMed2001

Critical realism and the dialectic.

A prominent strand within both sociological and social theory has been concerned to develop a 'systems approach' with which to explore social life. One of the most original contributions to a systems approach has arisen within critical realism. In particular critical realism demonstrates that it is possible to abstract the causal powers of different objects of analysis to examine their interaction within concrete and contingent 'open systems'. The recent dialectical turn of critical realism develops this systems approach in a much more rigorous manner. However, in this paper I argue that the (dialectical) critical realist mode of abstraction ultimately fails to embed concepts and categories internally within the specific ideological and historical forms of social relations. Or rather, critical realists do not seek to develop concepts that reflect the self-movement of a historical and contradictory essence. This self-movement is what I prefer to call a 'system'. Consequently critical realists are led to separate method from system in theory construction and such a separation leads to a problematic dualist mode of theorizing. I make these observations from a Hegelian-Marxist position.

Group Processes↗
PubMed2001

Homocysteine and cellular fibronectin are increased in preeclampsia, not transient hypertension of pregnancy.

OBJECTIVE: The objective of this study was to confirm that endothelial dysfunction is present in preeclampsia and absent in transient hypertension of pregnancy, and to determine whether the cardiovascular risk factor homocysteine is associated with the degree of endothelial dysfunction. METHODS: We measured cellular fibronectin (as a marker of endothelial injury) and total plasma homocysteine in samples collected at the time of admittance to labor and delivery in 17 women with preeclampsia (increased blood pressure, proteinuria, and hyperuricemia), 16 women with transient hypertension of pregnancy (only increased blood pressure), and 34 normal pregnant women. Each subject with preeclampsia was matched by prepregnancy body mass index, race, and gestational age at delivery to one subject with transient hypertension of pregnancy and two controls. RESULTS: Cellular fibronectin was found to be significantly increased in women with preeclampsia compared to subjects with transient hypertension of pregnancy or normal pregnant women (22.9 +/- 14.1 microg/mL versus 10.9 +/- 5.4 and 10.1 +/- 6.2 microg/mL, respectively, p<0.0001). Similarly, total plasma homocysteine was also significantly increased in the women with preeclampsia compared to subjects with transient hypertension of pregnancy or normal pregnant women (8.3 +/- 2.5 microM versus <5.5 +/- 2.2 and 5.4 +/- 3.4 microM respectively, p<0.01). However, contrary to our hypothesis, there was no apparent association between cellular fibronectin and homocysteine. CONCLUSIONS: The increased concentrations of homocysteine observed in preeclampsia are not a general feature of all hypertensive complications of pregnancy. Furthermore, endothelial dysfunction is present in preeclampsia and is not evident in transient hypertension of pregnancy. However, the apparent endothelial dysfunction in preeclampsia is not explained by the increase in homocysteine concentrations observed.

Female↗
PubMed2001

Mishandling of copper by albumin: role in redox-cycling and oxidative stress in preeclampsia plasma.

OBJECTIVE: To test the hypothesis that enhanced oxidative stress during pregnancies complicated by preeclampsia is associated with improper copper (Cu) binding by plasma albumin, resulting in enhanced Cu redox-cycling activity and that altered Cu binding, in turn, is caused by interactions of excessive amounts of free fatty acids with albumin. STUDY DESIGN: We studied binding and redox-cycling activity of Cu in 17 normal pregnancy and 17 preeclampsia plasma samples. Binding of exogenous Cu in plasma samples was quantified indirectly using spectrophotometric measurements of its complex with a specific chelator of Cu(I), bathocuproine disulfonate. Redox-cycling activity of Cu in plasma samples was estimated by electron paramagnetic resonance (EPR) spectroscopy of ascorbate radicals formed during one-electron oxidation of ascorbate by redox-active catalytic Cu. Formation of Cu/albumin complexes in model systems in the presence and absence of fatty acids was studied using EPR spectroscopy of Cu(II)/albumin. RESULTS: We found that preeclampsia plasma (as compared to normal pregnancy plasma) (1) displays elevated endogenous ascorbate redox-cycling that is normalized by a Cu(II) chelator, cuprizone I, (2) has lowered capacity to bind and redox-regulate exogenously added Cu, and (3) responds to treatment with fatty-acid-free albumin by diminished ascorbate oxidizing activity. Conversely, addition of free fatty acid (oleic acid) to normal pregnancy plasma sample yields increased ascorbate redox-cycling activity. Our model experiments showed that Cu-dependent redox-cycling activity of purified human serum albumin is significantly increased by excess free fatty acids. CONCLUSION: Mishandling of Cu by albumin contributes to oxidative stress in preeclampsia. Cu chelators may represent promising mechanism-based antioxidants to attenuate oxidative stress in preeclampsia.

Adult↗
PubMed2001

Enzyme immunoassay detection of antigen-specific immunoglobulin g antibodies in longitudinal serum samples from patients with cryptosporidiosis.

Cryptosporidium parvum is a protozoan parasite that causes diarrheal illness in a wide range of mammalian hosts, including humans. Characteristic serum immunoglobulin G (IgG) antibody responses to antigens in the 27- and 17-kDa size ranges have been shown to develop after infection, and several enzyme-linked immunosorbent assay (ELISA) and Western blot assay formats have been used to measure these IgG levels in human serum. Using a collection of serial samples from laboratory-confirmed cryptosporidiosis patients, we compared the results obtained by using two new ELISAs with those obtained with two different Western blot assays. When assayed with the large-format Western blot, 97% of the 67 patients had a demonstrable antibody response on at least one occasion. The Cp23 ELISA correctly identified 93% of the samples that had a 27-kDa response by Western blot and 100% of the negative samples. The Triton antigen ELISA detected 77% of the samples that had a 17-kDa response by Western blot and 88% of the negative samples. The sensitivity of the Triton antigen assay was higher for samples collected between 16 and 92 days after the onset of symptoms (96%). The minigel-format Western blot did not compare favorably with the large-format blot for the detection of antibodies to the 27-kDa antigen (71% sensitivity). A half-life of about 12 weeks was estimated for antibodies to both the 27- and 17-kDa antigens. We believe the Cp23 and Triton antigen ELISAs will be useful in epidemiologic studies of the prevalence of Cryptosporidium infection in the population.

Adult↗
PubMed2001

Longitudinal study of natural immune responses to the Plasmodium falciparum apical membrane antigen (AMA-1) in a holoendemic region of malaria in western Kenya: Asembo Bay Cohort Project VIII.

We investigated the development and maintenance of proliferative and antibody responses to apical membrane antigen-1 (AMA-1) epitopes in a holoendemic area of western Kenya. Young children (< 10 years), older children (10-17 years), and adults (> or = 18 years) were followed longitudinally for antibody and T-cell responses at 3 time points with an interval of 3-4 months. The proliferative responses against the AMA-1 T epitopes (PL171, PL172, PL173, PL186, PL191, and PL192) were not stable during follow-up; however, response to mycobacterial antigen PPD was highly stable. The responder frequencies were similar in all 3 time points except for epitope PL192. The younger and older children responded more frequently to T-cell epitopes, but the differences were not significant. A positive proliferative response to PL191 was associated with a significantly lower risk of parasitemia at subsequent follow-up (relative risk, 0.5; P = 0.03). The presence of antibody response to B epitopes PL169, PL170, PL173, PL187, and PL192 in one time point was associated with a subsequent response (P = 0.0001-0.008) suggesting a stable response. Younger (P = 0.046) and older children (P = 0.017) more frequently responded to epitope PL169 than did adults, and adults responded more frequently to PL187 than did younger children (P = 0.009). Responses to AMA-1 T-cell epitopes were short lived, and antibody responses were relatively stable.

Adolescent↗
PubMed2001

Malaria control in Bungoma District, Kenya: a survey of home treatment of children with fever, bednet use and attendance at antenatal clinics.

OBJECTIVE: To lay the basis for planning an improved malaria control programme in Bungoma District, Kenya. METHODS: By means of a cluster sample household survey an investigation was conducted into the home management of febrile children, the use of bednets, and attendance at antenatal clinics. FINDINGS: Female carers provided information on 314 recently febrile children under 5 years of age, of whom 43% received care at a health facility, 47% received an antimalarial drug at home, and 25% received neither. Of the antimalarial treatments given at home, 91% were started by the second day of fever and 92% were with chloroquine, the nationally recommended antimalarial at the time. The recommended dosage of chloroquine to be administered over three days was 25 mg/kg but the median chloroquine tablet or syrup dosage given over the first three days of treatment was 15 mg/kg. The total dosages ranged from 2.5 mg/kg to 82 mg/kg, administered over one to five days. The dosages were lower when syrup was administered than when tablets were used. Only 5% of children under 5 years of age slept under a bednet. No bednets had been treated with insecticide since purchase. At least two antenatal visits were made by 91% of pregnant women. CONCLUSIONS: Carers are major and prompt providers of antimalarial treatment. Home treatment practices should be strengthened and endorsed when prompt treatment at a health facility is impossible. The administration of incorrect dosages, which proved common with chloroquine, may occur less frequently with sulfadoxine-pyrimethamine, as its dosage regimen is simpler. High levels of utilization of antenatal clinics afford the opportunity to achieve good coverage with presumptive intermittent malaria treatments during pregnancy, and to reach the goal of widespread bednet use by pregnant women and children by distributing nets during antenatal clinic visits.

Antimalarials↗
PubMed2000

Dendritic cell elimination as an assay of cytotoxic T lymphocyte activity in vivo.

We show in this paper that the survival of antigen-loaded dendritic cells in vivo may be used as a sensitive readout of CTL activity. We have previously shown that dendritic cells labeled with the fluorescent dye CFSE and injected sub-cutaneously into mice migrate spontaneously to the draining lymph node where they persist for several days. In the presence of effector CTL responses, dendritic cells loaded with specific antigen rapidly disappear from the draining lymph node. In this paper we extend the above observations and set up a simple and sensitive method to reveal CTL activity in individual mice in vivo. Dendritic cells were labeled with two different fluorochromes, loaded with antigen or left untreated, and mixed together before injection into mice. We show that only the dendritic cells loaded with specific antigen were cleared from the draining lymph node, while dendritic cells not loaded with antigen remained unaffected. Cytotoxic responses generated by immunization with peptide-loaded dendritic cells, or by infection with influenza virus, could be revealed using this method. Comparison of the differential survival of dendritic cells populations mixed together also allowed us to accurately evaluate the disappearance of dendritic cells, irrespective of variability in the injection site and other parameters. Given the ability of dendritic cells to efficiently take up and present complex antigens, nucleic acids and apoptotic bodies, this method may also allow the evaluation of cytotoxic activity against antigens that are not characterized in terms of peptide epitopes.

Animals↗
PubMed2000

Prostitution and the sex discrepancy in reported number of sexual partners.

One of the most reliable and perplexing findings from surveys of sexual behavior is that men report substantially more sexual partners than women do. We use data from national sex surveys and studies of prostitutes and their clients in the United States to examine sampling bias as an explanation for this disparity. We find that prostitute women are underrepresented in the national surveys. Once their undersampling and very high numbers of sexual partners are factored in, the discrepancy disappears. Prostitution's role in the discrepancy is not readily apparent because men are reluctant to acknowledge that their reported partners include prostitutes.

Female↗
PubMed2000

Immunotherapy with dendritic cells and tumor major histocompatibility complex class I-derived peptides requires a high density of antigen on tumor cells.

Immunization with dendritic cells and unfractionated MHC class I-binding peptides derived from autologous tumor cells has been shown to induce effective antitumor immunity. However, the importance of the relative abundance of tumor peptides on the surface of tumor cells is not known. We have addressed this question using peptides isolated from three tumor cell lines transfected with a minigene encoding amino acids 33-41 of the lymphocytic choriomeningitis virus glycoprotein (LCMV(33-41)). The three cell lines expressed different levels of MHC class I molecules and had different abilities to stimulate proliferation of LCMV(33-41)-specific T cells in vitro. We found that antitumor immune responses were best elicited by immunizing mice with dendritic cells and synthetic LCMV(33-41) peptide. Peptide preparations from a given tumor cell line conferred protection against challenge with the same tumor cell line. However, protective immunity to a different tumor could be induced only if the cell line used for peptide preparation presented a high relative proportion of LCMV(33-41) in association with MHC class I. Our results suggest that multiple peptide epitopes are required for the induction of an effective antitumor immune response using MHC class I-binding peptides from tumor cells. Also, the ability to induce an antitumor immune response appears to correlate with the proportion, rather than the absolute amount, of tumor-specific peptide in the mixture used for immunization.

Animals↗
PubMed2000

Giardiasis surveillance--United States, 1992-1997.

PROBLEM/CONDITION: Giardia intestinalis, the organism that causes the gastrointestinal illness giardiasis, is the most commonly diagnosed intestinal parasite in public health laboratories in the United States. In 1992, the Council of State and Territorial Epidemiologists assigned giardiasis an event code that enabled states to begin voluntarily reporting surveillance data on giardiasis to CDC. REPORTING PERIOD: This report includes data that were reported from January 1992 through December 1997. DESCRIPTION OF THE SYSTEM: The National Giardiasis Surveillance System includes data about reported cases of giardiasis from participating states. Because most states were already collecting data on occurrence of giardiasis, the assignment of an event code to giardiasis has allowed voluntary reporting of these data to CDC via the National Electronic Telecommunications System for Surveillance. RESULTS: Since 1992, the number of states reporting cases of giardiasis to CDC has risen from 23 to 43. The annual number of giardiasis cases reported has ranged from 12,793 in 1992 to 27,778 in 1996. In 1997, cases per 100,000 state population ranged from 0.9 to 42.3, with 10 states reporting >20.0 cases per 100,000 population and a national average of 9.5 cases per 100,000 population. In 1997, New York State, including New York City, reported the highest number of cases (3,673, or 20.3 cases per 100,000 population), accounting for 14.5% of cases nationally; however, Vermont reported the highest incidence rate in 1997 (42.3 cases per 100,000 population). Both states have active surveillance systems in place for giardiasis. Cases have an approximately equal sex distribution. Nationally, rates were the highest among children aged 0-5 years, followed closely by persons aged 31-40 years. In these two age groups, most cases were reported during late summer and early fall--an indication that transmission occurred during the summer. INTERPRETATION: This report documents the first nationwide look at epidemiologic parameters and disease burden estimates for giardiasis in the United States. Transmission occurs in all major geographic areas of the country. The seasonal peak in age-specific case reports coincides with the summer recreational water season and might reflect the heavy use by young children of communal swimming venues (e.g., lakes, rivers, swimming pools, and water parks)--a finding consistent with Giardia's low infectious dose, the high prevalence of diaper-aged children in swimming venues, the extended periods of cyst shedding that can occur, and Giardia's environmental resistance. Estimates based on state surveillance data indicate that as many as 2.5 million cases of giardiasis occur annually in the United States. PUBLIC HEALTH ACTION: Giardiasis surveillance provides data to educate public health practitioners and health-care providers about the scope and magnitude of giardiasis in the United States. These data can be used to establish research priorities and to plan future prevention efforts.

Adolescent↗
PubMed2000

A multiyear prospective study of the risk factors for and incidence of diarrheal illness in a cohort of Peace Corps volunteers in Guatemala.

BACKGROUND: Diarrheal illness is the most common medical disorder among travelers from developed to developing countries and is common among expatriate residents in developing countries. OBJECTIVE: To assess the risk factors for and incidence of diarrheal illness among Americans living in a developing country. DESIGN: Prospective longitudinal study. SETTING: Rural Guatemala. PATIENTS: Cohort of 36 Peace Corps volunteers. MEASUREMENTS: Collection of daily dietary and symptom data for more than 2 years; identification by multivariate Poisson regression analyses of risk factors for clinically defined episodes of diarrheal illness. RESULTS: The 36 Peace Corps volunteers in this study had 307 diarrheal episodes (median, 7 per person), which lasted a median of 4 days (range, 1 to 112) and a total of 10.1% of the 23 689 person-days in the study. The incidence density (episodes per person-year) was 4.7 for the study as a whole, 6.1 for the first 6-month period, 5.2 for the second 6-month period, and 3.6 thereafter. Statistically significant risk factors for diarrheal illness included drinking water whose source (for example, the tap) and, therefore, quality, was unknown to the person; eating food prepared by a Guatemalan friend or family; eating food at a small, working-class restaurant; eating fruit peeled by someone other than a Peace Corps volunteer; drinking an iced beverage; and eating ice cream, ice milk, or flavored ices. The relative risks comparing the presence of these exposures during the first 6-month period overseas with their absence during the second year of residence ranged from 1.90 to 2.67, and the summary attributable risk percentage (that is, the percentage of diarrheal episodes that could be ascribed to the exposures) was 75.4%. Exposures generally were riskier if they occurred during travel elsewhere in Guatemala rather than in the person's usual work area. CONCLUSIONS: Diarrheal illness of mild-to-moderate severity continued to occur throughout Peace Corps service but decreased in incidence as length of stay increased. Various dietary behaviors increased the risk for diarrheal illness, which suggests that avoidance of potentially risky foods and beverages is beneficial.

Adult↗
PubMed2000

Subdividing atypical glandular cells of undetermined significance according to the Australian modified Bethesda, system: analysis of outcomes.

BACKGROUND: The Australian modification of the Bethesda system (TBS) for reporting endocervical cellular abnormalities differs from TBS in having a "high grade" category for prediction of adenocarcinoma in situ (AIS), an "inconclusive" category requiring that AIS be excluded (AISEX), and a "low grade" category (Enatyp) for when only minor changes are seen in endocervical cells. METHODS: From subsequent follow-up, the authors evaluated the proportion of histologically confirmed high grade lesions (squamous, glandular, or endometrial) in each cytologic reporting category, for cases in which no concurrent squamous abnormality was also predicted. RESULTS: From information was available for 95.9% of 172 AIS predictions, 81.5% of 119 AISEX predictions, and 89.0% of 237 reports of Enatyp. The histologic positive predictive values for high grade lesions were 95.7% for AIS, 71.1% for AISEX, and 7.1% for Enatyp. In the first 2 categories, a minority of lesions proved to be purely squamous (3.8% for AIS and 33.3% for AISEX), whereas in the Enatyp category 87.0% were squamous only. CONCLUSIONS: Compared with TBS, the Australian terminology for reporting of endocervical abnormalities better reflects the risk of underlying high grade abnormalities and may result in more appropriate management recommendations. For Enatyp reports, which constitute over 85% of reported endocervical abnormalities, repeat cytology should be considered appropriate management. However, cone biopsy should be the investigative method of choice for women with reports of AIS and AISEX.

Adenocarcinoma↗
PubMed2000

CD8+ T cell-dependent elimination of dendritic cells in vivo limits the induction of antitumor immunity.

The fate of dendritic cells (DC) after they have initiated a T cell immune response is still undefined. We have monitored the migration of DC labeled with a fluorescent tracer and injected s.c. into naive mice or into mice with an ongoing immune response. DC not loaded with Ag were detected in the draining lymph node in excess of 7 days after injection with maximum numbers detectable approximately 40 h after transfer. In contrast, DC that had been loaded with an MHC class I-binding peptide disappeared from the lymph node with kinetics that parallel the known kinetics of activation of CD8+ T cells to effector function. In the presence of high numbers of specific CTL precursors, as in TCR transgenic mice, DC numbers were significantly decreased by 72 h after injection. The rate of DC disappearance was extremely rapid and efficient in recently immunized mice and was slower in "memory" mice in which memory CD8+ cells needed to reacquire effector function before mediating DC elimination. We also show that CTL-mediated clearance of Ag-loaded DC has a notable effect on immune responses in vivo. Ag-specific CD8+ T cells failed to divide in response to Ag presented on a DC if the DC were targets of a pre-existing CTL response. The induction of antitumor immunity by tumor Ag-loaded DC was also impaired. Therefore, CTL-mediated clearance of Ag-loaded DC may serve as a negative feedback mechanism to limit the activity of DC within the lymph node.

Animals↗
PubMed2000

Differential requirement for CD80 and CD80/CD86-dependent costimulation in the lung immune response to an influenza virus infection.

The CD28 costimulatory pathway is critical to T cell activation. Blockade of the interaction of CD28 with its ligands CD80 and CD86 using CTLA4-Ig has been proposed as a therapy for a number of immune-based disorders. We have used a murine model of influenza virus infection to study the role of CD28-dependent costimulation in the development of antiviral immune responses. In vivo treatment with CTLA4-Ig to block the interaction of CD28 with CD80 and CD86 reduced virus-specific cytotoxicity and IFN-gamma production by bronchoalveolar lavage fluid CD8+ T lymphocytes in vitro. It also resulted in decreased numbers of virus-specific CD8+ T lymphocytes in the bronchoalveolar lavage fluid, lung, and spleen and lowered virus-specific Ab titers. Mice treated with CTLA4-Ig were able to control and clear the virus infection, but this was delayed compared with controls. Treatment with Y100F-Ig, a mutant form of CTLA4-Ig which selectively binds to CD80 and blocks the CD28-CD80 interaction leaving CD28-CD86 binding intact, did not affect Ab production, spleen cytotoxic precursors, or clearance of virus. However, Y100F-Ig treatment had a clear effect on lung effector cell function. Secretion of IFN-gamma by bronchoalveolar lavage fluid CD8+ T lymphocytes in vitro was decreased, and the number of virus-specific CD8+ T lymphocytes in the bronchoalveolar lavage fluid and lungs of infected mice was reduced. These results indicate that CD28-dependent costimulation is important in the antiviral immune response to an influenza virus infection. The individual CD28 ligand, CD80, is important for some lung immune responses and cannot always be compensated for by CD86.

Abatacept↗
PubMed2000

Interval nodes: the forgotten sentinel nodes in patients with melanoma.

BACKGROUND: Any sentinel lymph node that receives lymph drainage directly from a primary melanoma site, regardless of its location, may contain metastatic disease. This is true even if the sentinel node does not lie in a recognized node field. Interval (in-transit) nodes that lie along the course of a lymphatic vessel between a primary melanoma site and a recognized node field are sometimes seen during lymphatic mapping for sentinel node biopsy. If drainage to such interval nodes is ignored by the surgeon during sentinel node biopsy, metastatic melanoma will be missed in some patients. HYPOTHESIS: When lymph drains directly from a cutaneous melanoma site to an interval node, that sentinel node has the same chance of harboring micrometastatic disease as a sentinel node in a recognized node field. DESIGN: Preoperative lymphoscintigraphy with technetiumTc 99m antimony trisulfide colloid was performed to define lymphatic drainage patterns and, since 1992, to locate the sentinel lymph nodes for surgical biopsy or for permanent skin marking of their location with point tattoos. SETTING: Melanoma unit of a university teaching hospital. PATIENTS: A total of 2045 patients with cutaneous melanoma were studied in 13 years. RESULTS: Interval nodes were found in 148 patients (7.2%). The incidence of interval nodes varied with the site of the primary melanoma. Interval nodes were more common with melanomas on the trunk than with those on the lower limbs. Micrometastatic disease was found in 14% of interval nodes that underwent biopsy as sentinel nodes. This incidence is similar to that found in sentinel nodes located in recognized node fields, confirming the potential clinical importance of interval nodes. CONCLUSIONS: Interval nodes should be removed surgically along with any additional sentinel nodes in standard node fields if the sentinel node biopsy procedure is to be complete. In some patients, an interval node will be the only lymph node that contains metastatic disease.

Female↗