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Biomedical subjects

D Rosenberg

Publications and source records attributed to D Rosenberg.

At least 19 recordsLinked to original sources

Human nerve growth factor protects common marmosets against autoimmune encephalomyelitis by switching the balance of T helper cell type 1 and 2 cytokines within the central nervous system.

Multiple sclerosis is a demyelinating disorder of the central nervous system (CNS), in which an immune attack directed against myelin constituents causes myelin destruction and death of oligodendrocytes, the myelin-producing cells. Here, the efficacy of nerve growth factor (NGF), a growth factor for neurons and oligodendrocytes, in promoting myelin repair was evaluated using the demyelinating model of experimental allergic encephalomyelitis (EAE) in the common marmoset. Surprisingly, we found that NGF delayed the onset of clinical EAE and, pathologically, prevented the full development of EAE lesions. We demonstrate by immunocytochemistry that NGF exerts its antiinflammatory effect by downregulating the production of interferon gamma by T cells infiltrating the CNS, and upregulating the production of interleukin 10 by glial cells in both inflammatory lesions of EAE and normal-appearing CNS white matter. Thus, NGF, currently under investigation in human clinical trials as a neuronal trophic factor, may be an attractive candidate for therapy of autoimmune demyelinating disorders.

Animals

Proliferation of hepatic lineage cells of normal C57BL and interleukin-6 knockout mice after cocaine-induced periportal injury.

The cellular response to periportal liver injury, induced by phenobarbital feeding and cocaine injection, is used to compare the restitutive proliferation of hepatocytes, cholangiocytes, and oval cells in the livers of normal control to those of interleukin-6 (IL-6) knockout mice. After this injury hepatocytes in noninjured middle and central zones start to proliferate first, followed by proliferation of cholangiocytes and intraportal oval cells. Proliferation of all cell types peaks at 2 days, but oval cells continue to proliferate and differentiate through days 4 and 6 as they reconstitute the necrotic zone. By day 10, the injured zone is completely repaired, and no dividing cells remain. During the first 3 to 4 days after injury, the number of proliferating hepatocytes, cholangiocytes, and sinusoidal cells is lower in IL-6 knockout mice than in normal mice, whereas the number of dividing oval cells is higher. However, overall repair of the injury is accomplished in the same time period in both groups. During repair of the periportal zone, oval cells acquire differentiation markers of hepatocytes as they cross the zone of injury. In conclusion, the phenobarbital/cocaine injury model is useful to study restitutive proliferation of mouse liver cell lineages. The proliferative response in IL-6 knockout mice shows that IL-6 is not required for proliferation of liver cells; timely repair of liver injury occurs in both normal and IL-6 knockout mice. Increased proliferation of oval cells in IL-6 knockout mice may compensate for the lower proliferation of other liver cell types.

Alanine Transaminase

[Pseudotumoral subacute osteomyelitis: a series of 41 children].

PURPOSE OF THE STUDY: To confirm that subacute osteomyelitis in children is a real entity, and give the main characteristics of this disease MATERIAL AND METHODS: We reviewed 41 cases as well as the litterature. RESULTS: Pain without fever was the only constant symptom. The erythrocyte sedimentation rate was increased slightly. XRays were the most important investigation, showing a geode in the metaphysis or more rarely in the epiphysis evoking a benign bone tumor in a child. DISCUSSION: The treatment was most often surgical: scraping permits the isolation of the microbe in 50 per cent of cases (staphylococcus most often) and usualy leady to recovery. CONCLUSION: This form of osteomyelitis is relatively frequent and must be discussed in front of a cystic tumoral image of the child's long bone.

Adolescent

Validity of self-reported pregnancy delivery weight: an analysis of the 1988 National Maternal and Infant Health Survey. NMIHS Collaborative Working Group.

This study examined the validity of self-reported delivery weight among 3,518 respondents to the 1988 National Maternal and Infant Health Survey. Self-reported delivery weight was ascertained from a mail survey administered during the postpartum period. Measured delivery weight was obtained by abstraction of medical records from the hospital of delivery. On average, a woman's reported delivery weight was 2.82 pounds (1 pound = 0.45 kg) less than her measured delivery weight (p < 0.001). The level of underreporting increased significantly with increases in prepregnancy body mass index, current body mass index, pregnancy weight gain, and weight change from delivery to recall. Reporting error also increased among women who were non-White, less educated, and unmarried; whose pregnancy was unintended; and who initiated prenatal care late, responded late to the survey questionnaire, became pregnant again before responding, and reported a delivery weight ending in zero. When reported delivery weight was used to calculate weight gain and was categorized into typical weight gain categories, 30-40% of women were classified incorrectly. An empirical evaluation of how this misclassification might impact epidemiologic analyses indicated that associations between weight gain and birth weight were attenuated when weight gain was based on reported delivery weight rather than on measured delivery weight.

Adolescent

Expression of biologically active atrial natriuretic factor following intrahepatic injection of a replication-defective adenoviral vector in dogs.

Atrial natriuretic factor (ANF) is a potent natriuretic, diuretic, and vasoactive hormone produced and released by atrial cardiomyocytes. We investigated whether adenovirus-mediated ANF gene delivery to dogs leads to a sustained increase in circulating ANF levels resulting in long-lasting biological effects. An adenoviral vector containing the canine ANF cDNA under the control of the Rous sarcoma virus 3' long terminal repeat (AdRSV-ANF) was injected via the intrahepatic route to nonvaccinated 2-month-old dogs. In the first group of four dogs injected with AdRSV-ANF (10(10.2) TCID50), a short-lived increase in plasma ANF concentrations not associated with biological effects occurred 8-10 days after the injection, as compared with four control dogs injected with an adenovirus encoding a luciferase reporter gene (AdRSV-luc). In a second series of experiments, six dogs received AdRSV-ANF at a dose of 10(10) TCID50 and a replication-defective type 5 adenovirus harboring a modified VAI gene (Ad-VAr) at the same dose. Sustained increases in plasma ANF concentrations and urinary cGMP excretion starting on day 2 and persisting until day 20 were seen, as well as concomitant elevations in natriuresis and diuresis, a transient increase in cardiac output, and a delay in body weight gain, as compared with control dogs injected with AdRSV-luc/Ad-VAr. These results show that adenovirus-mediated ANF gene expression can lead to systemic biological effects in dogs, a finding of potential relevance for the treatment of cardiovascular diseases and sodium-retaining disorders.

Adenoviridae

Networks of persons with syphilis and at risk for syphilis in Louisiana: evidence of core transmitters.

BACKGROUND AND OBJECTIVES: Differences in sociodemographic attributes and healthcare access may explain differences in regional sexually transmitted disease rates but don't fully explain why syphilis persists disproportionately in certain populations. GOAL OF THIS STUDY: To understand the behavioral epidemiology of syphilis, we conducted a social network analysis of persons with syphilis and their contacts and developed and applied a definition of core transmitters. STUDY DESIGN: We interviewed 10 index persons with primary or secondary untreated syphilis and 80 of their named sexual and social contacts. RESULTS: Fourteen (16%) of 90 interviewed persons met the definition of core transmitters, 9 of whom had past or current syphilis. The other interviewed persons had only moderately risky behaviors. Seventy-eight (42%) of the network sexual contacts were connected directly or indirectly to a core transmitter. CONCLUSION: This analysis suggests that syphilis transmission is maintained by a community with a small percentage of high-risk persons centrally placed amidst a larger group with moderately risky behavior.

Adult

Identification of a signal sequence necessary for the unconventional secretion of Engrailed homeoprotein.

BACKGROUND: Engrailed-1 and Engrailed-2 are homeoproteins--transcription factors implicated in the morphogenesis of discrete structures. Engrailed proteins have a role in patterning the midbrain-hindbrain region and are expressed in the nuclei of rat embryo midbrain-hindbrain cells. We have previously found that both endogenous and exogenously expressed Engrailed proteins also associate with membrane regions implicated in signal transduction and secretion. Within total membrane fractions, a small proportion of Engrailed--about 5%--is protected against proteinase K proteolysis, suggesting that Engrailed has access to a luminal compartment. Together with our finding that homeodomains and homeoproteins can be internalized by live cells, these observations suggest that Engrailed might act as a polypeptidic messenger. In order to investigate this possibility, we looked to see if Engrailed could be secreted. RESULTS: Engrailed expressed in COS cells can be recovered in abutting primary neurons and this is dependent on a short sequence in its homeodomain distinct from 'classical' secretion signals. This sequence, which overlaps with the sequence necessary for Engrailed internalization and which is highly conserved among homeoproteins, is the first example of an 'unconventional' sequence necessary for secretion. Less than 50% of total intracellular Engrailed is secreted and there is a correlation between secretion and access to the membrane compartment where the protein is protected against proteinase K. CONCLUSIONS: Our results lend weight to the proposal that Engrailed, and possibly other homeoproteins, might act as intercellular polypeptidic messengers.

Animals

Measuring satisfaction among low-income women: a prenatal care questionnaire.

OBJECTIVE: To evaluate the reliability and construct validity of a prenatal care satisfaction scale. METHOD: A prenatal care satisfaction scale that included six dimensions of care based on the literature was tested during a telephone interview with 101 first-time African-American and Mexican-American mothers 18 and over who receive Medicaid. RESULTS: The scale exhibited high reliability (Cronbach's alpha = 0.95), as well as good construct validity. The correlation between the scale and rating of the quality of care overall was 0.74 (p < 0.001); the correlation between the scale and whether the women would recommend this provider to a friend was 0.67 (p < 0.001). Results from correlation and factor analysis suggested a different set of dimensions than those described in the literature. CONCLUSION: The 22-question satisfaction with prenatal care scale has excellent reliability and construct validity and taps six established dimensions of satisfaction, including the art of care, technical quality, access, physical environment, availability, and efficacy. The multidimensional scale allows for alternative groupings of the domains of satisfaction as our understanding of prenatal care satisfaction increases.

Adolescent

Health care characteristics associated with women's satisfaction with prenatal care.

OBJECTIVES: The objective of this study was to explore the relation between prenatal care characteristics and satisfaction among Medicaid recipients. METHODS: African-American (n = 75) and Mexican-American (n = 26) nonadolescent primiparous pregnant women who had at least three prenatal care visits participated in a 25-minute telephone survey that asked them about satisfaction with prenatal care (art of care, technical quality, physical environment, access, availability and efficacy); prenatal care characteristics (practitioner attributes, service availability, and features of the delivery of care); and, personal characteristics (sociodemographics, health status and behaviors, and pregnancy-related variables). Univariate and multivariable analyses were conducted to explore the relations between personal characteristics and satisfaction and between care characteristics and satisfaction. RESULTS: For the overall sample, the following prenatal care characteristics were associated with increased satisfaction: having procedures explained by the provider, short waiting times at the prenatal care site, the availability of ancillary services, and reporting that the prenatal care practitioner was male. When examining the data by ethnicity, whether the provider explained procedures was the most important determinant of satisfaction for both African-American and Mexican-American women. CONCLUSIONS: Knowledge of the care characteristics that impact low-income pregnant women's satisfaction can be utilized to alter service delivery to increase use of prenatal care and ultimately to improve perinatal outcomes.

Adult

Decreased caudate volume in neuroleptic-naive psychotic patients.

OBJECTIVE: Previous studies, mostly involving neuroleptic-treated patients, have suggested enlarged basal ganglia size in schizophrenia. The authors sought to examine basal ganglia volume in neuroleptic-naive psychotic patients. METHOD: Magnetic resonance imaging volumetric studies were conducted in newly diagnosed neuroleptic-naive schizophrenic and non-schizophrenic psychotic patients and in matched healthy comparison subjects. RESULTS: Both patient groups had bilaterally reduced caudate, but not putamen, volumes, compared to the healthy subjects, after adjustment for intracranial volume. CONCLUSIONS: Decreases in caudate volume in newly diagnosed psychotic patients may be related to the primary pathophysiology of these disorders; prior observations of increased caudate volume may reflect effects of neuroleptic treatment.

Adult

6-[18F]fluoro-L-m-tyrosine: metabolism, positron emission tomography kinetics, and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine lesions in primates.

The tracer 6-[18F]fluoro-L-m-tyrosine (FMT) was studied with regard to its biochemistry and kinetics, as well as its utility in evaluating brain dopaminergic function in primates before and after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment using positron emission tomography (PET). Plasma analysis of FMT and its F18-labeled metabolites 6-fluoro-3-hydroxyphenylacetic acid (FPAC) and 6-fluoro-3-hydroxyphenylethylamine (FMA) during PET scanning enabled kinetic analysis of FMT uptake. A separate study examined brain FMT metabolism in MPTP-naive monkeys euthanized 60 or 120 min after FMT injection. Almost 60% of total plasma F-18 activity was associated with FPAC and FMA 120 min after FMT injection. The FMT signal accumulated preferentially in dopaminergic areas such as caudate and putamen. This bilateral FMT signal was disrupted after unilateral intracarotid artery (ICA) MPTP infusion which reduced ipsilateral striatal activity. A three compartment three kinetic rate constant model for FMT uptake revealed reduced FMT decarboxylation (k3) in ipsilateral caudate and putamen after unilateral MPTP although a further decrease was not evident after intravenous MPTP. FPAC was the major F-18 species in all brain regions except in cerebellum where FMT was predominant 60 min post-mortem. FPAC was most concentrated in dopaminergic areas whereas lower levels occurred in areas containing few dopamine terminals. These data demonstrate preferential FMT metabolism and F-18 retention in dopaminergic tissue and support the use of FMT to evaluate normal and abnormal dopaminergic function.

Animals

Magnetic resonance imaging and spectroscopy in offspring at risk for schizophrenia: preliminary studies.

1. Studies of first-degree relatives of persons with schizophrenia provide an opportunity to characterize risk factors for the development of this illness. In this report the authors will provide preliminary data from an ongoing study of neurobiological alterations in the offspring of schizophrenia patients. 2. A series of offspring of schizophrenic patients (OS) were compared with age and sex matched healthy controls (HC) without psychiatric history in first degree relatives on psychiatric, volumetric Magnetic Resonance Imaging (MRI) of whole brain and proton Magnetic Resonance Spectroscopy (1H MRS) evaluations of the ventral prefrontal cortex. 3. Compared with HC group, high risk subjects had reduced left amygdala volume, enlarged third ventricular volume, and smaller overall brain volume. 4. 1H MRS studies showed a trend for decreased NAA/choline ratios in the anterior cingulate region in the OS group as compared to HC subjects. 5. Follow-up studies of these subjects are needed to confirm the predictive value of these measures for future emergence of schizophrenia in subjects at risk for this illness.

Adolescent

Prospective recruitment of women receiving prenatal care from diverse provider arrangements: a potential strategy.

OBJECTIVES: This study describes the use of a Medicaid managed care list to prospectively recruit into a research project pregnant women receiving care from a variety of providers. METHOD: A list of women enrolled in Medicaid managed care was used to recruit pregnant African-American and Latina women into a study of prenatal care satisfaction. Due to privacy concerns, the researchers were not able to directly access names from the list. Instead, a managed care contract agency sent recruitment letters to 1009 pregnant African-American and Latina Medicaid recipients. Response rates by ethnicity and several other key variables are calculated. The biases associated with this method of recruiting pregnant women from a variety of providers are discussed. RESULTS: Thirty-five percent of the women contacted returned consent forms and agreed to have researchers approach them; the response rate for African-American women was 43% and for Latinas was 29% (p < 0.0001). Respondents were younger and later in their pregnancies than nonrespondents, but did not differ from them by zip code of residence. The women recruited into the study obtained prenatal care from a diverse group of providers. CONCLUSIONS: While the use of a prospectively generated list of pregnant Medicaid recipients to recruit low-income pregnant women into a research study may be associated with some selection bias, the potential cost savings, decreased effort, and diminished recall bias may make their use a feasible sampling alternative, particularly when the researcher desires to recruit women seeking care from a variety of provider arrangements.

Adolescent

Going mainstream.

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