Oculomotor findings in preterm children with periventricular leukomalacia. A connection between lesions in the periventricular area and eye motility disorders?
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Biomedical subjects
Publications and source records attributed to L Jacobson.
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Interleukin-1 (IL-1) and interleukin-6 (IL-6) are thought to play a role in mediating weight loss, net protein catabolism, anorexia, and fever after infection or injury. Because IL-1 and IL-6 can be synthesized in the brain and have been shown to be increased in central nervous system (CNS) infections, we investigated the metabolic consequences of prolonged CNS exposure to these cytokines. At equivalent doses, intracerebroventricular infusion of IL-1, but not IL-6, caused negative nitrogen balance, weight loss, and anorexia. Intracerebroventricular infusion of IL-1 also caused adrenocortical activation, as indicated by increased adrenal weight and plasma corticosterone, and decreased thymus weight. However, clamping plasma glucocorticoids at low levels by adrenalectomy and corticosterone pellet replacement did not attenuate IL-1-induced losses of body weight and nitrogen. We conclude that centrally produced IL-1 could play an important role in the metabolic alterations associated with CNS injury or infection and that these effects may not be solely attributable to increased secretion of glucocorticoids.
Immunoprecipitation of human acetylcholine receptor (AChR) is used in the diagnostic assay for myasthenia gravis (MG). We compared human AChR derived from TE671 cells, which express fetal-type AChR, with AChR from TE671-epsilon cells, which we have engineered to express adult-type AChR. Some low-titer MG sera distinguished strikingly between the two subtypes. Four out of seven MG sera that had equivocal titers in standard assays gave positive titers with TE671-epsilon AChR, whereas only one out of seven gave a positive titer with TE671 cells. The new cell line provides a greater concentration of adult AChR than can be obtained from normal human muscle and increases the sensitivity of the diagnostic assay.
Molecular epidemiological studies of populations at high risk for liver cancer have shown that hepatitis B virus (HBV) and aflatoxin B1 (AFB1) exposure are two major risk factors for this disease. These etiological agents, combined with nutritional deficiencies, are important for the initiation and promotion of liver cancer in various parts of the world. In Qidong, People's Republic of China, liver cancer accounts for 10% of all adult deaths, and both HBV and AFB1 exposures are common. To study temporal and possible chemical-viral interactions in people, serum samples were collected during a longitudinal study designed to measure aflatoxin molecular biomarkers in residents of Daxin Township, Qidong City, People's Republic of China. In this study, the temporal modulation of aflatoxin adduct formation with albumin over multiple lifetimes of serum albumin was examined in both HBV-positive and HBV-negative people in two periods: September-December 1993 (wave 1) and June-September 1994 (wave 2). During the 12-week monitoring period of wave 1, 120 individuals (balanced by gender and HBV status) provided a total of 792 blood samples. AFB1-albumin adducts were detected in all but one of the serum samples. The range of binding detected by RIA in the Daxin population was 0.17-4.39 pmol AFB11/mg albumin with an overall mean +/- SD of 1.51 +/- 0.21 pmol AFB11/mg albumin. The mean +/- SD for weeks 0, 2, 4, 6, 8, 10 and 12 of wave 1 were 1.21 +/- 0.41, 1.58 +/- 0.70, 1.36 +/- 0.52, 1.71 +/- 0.44, 1.18 +/- 0.60, 2.00 +/- 0.59, and 1.68 +/- 0.34 pmol AFB1/mg albumin, respectively. During wave 2, 103 individuals from wave 1 provided a total of 396 blood samples collected monthly over wave 2, with mean +/- SD aflatoxin-albumin adduct levels of 1.19 +/- 0.37, 0.85 +/- 0.45, 0.89 +/- 0.28, and 0.61 +/- 0.15 pmol AFB1/mg albumin. Using linear regression models, the mean aflatoxin-albumin adduct levels increased (P < 0.05) during the 12 weeks of wave 1 and decreased (P < 0.05) over the 4 months of wave 2. Neither HBV surface antigen status nor gender modified either the baseline mean or the temporal trend. High-performance liquid chromatography confirmation was done on a subset of serum samples, and the results show an excellent association between the immunoassay data and high-performance liquid chromatography. Taken together, these data demonstrate that AFB1-albumin is a sensitive and specific biomarker for assessing exposure to this carcinogen in the population in Qidong.
Are taking an overdose and undergoing termination of pregnancy linked? In one practice this study has identified a significant association between the two events. If this finding is supported more widely, could one event act as a risk marker for the second?
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To study pathogenic T helper cells in myasthenia gravis (MG) reacting against the acetylcholine receptor (AChR), we have previously selected five CD4+ T cell lines/clones from MG patients (or healthy controls) against full-length recombinant human AChR alpha subunit (alpha 1-437); these can all recognize AChR solubilized from human muscle. Recently, T cells selected with pooled AChR subunit synthetic peptides have shown greater heterogeneity than above. Hoping to validate that, we have characterized three MG and six control T cell lines selected with pooled peptides (averaging 33 residues long) covering the alpha subunit sequence; recurring responses to three particular peptides each showed preferred HLA class II restrictions--p75-115/DR4, p138-167/DR4, and p309-344/DR3 (or DR52a). However, none of three lines from MG patients recognized p138-167--even one from a previous responder to this epitope in full-length alpha 1-437; otherwise they resembled those from controls. Moreover, no peptide-selected line responded significantly to whole AChR, alpha 1-437, or even to shorter polypeptides sharing one terminus with the peptide, suggesting specificity for epitopes not naturally processed by APCs from blood. Of 20 sublines maintained with individual peptides, at least 10 responded to independently synthesized overlapping sequences, but four others depended on contaminants in the original peptides. A single line did recognize one longer polypeptide, but only after tryptic digestion; the processing of this cryptic epitope was evidently the limiting factor here rather than its concentration or the T cell sensitivity. Therefore, while synthetic peptides are essential for mapping epitopes, assessment of the pathogenic MG T cell repertoire requires full-length Ag processed naturally.
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The body responds to stress by activation of the hypothalamic-pituitary-adrenal (HPA) axis and release of glucocorticoids. Glucocorticoid production in the adult regulates carbohydrate and amino-acid metabolism, maintains blood pressure, and restrains the inflammatory response. In the fetus, exogenous glucocorticoids accelerate maturation of lung and gastrointestinal enzyme systems and promote hepatic glycogen deposition. Corticotropin-releasing hormone (CRH), a 41-amino-acid neuropeptide produced in the paraventricular nucleus of the hypothalamus and many regions of the cerebral cortex, has been implicated in both the HPA axis and behavioural responses to stress. To define the importance of CRH in the response of the HPA axis to stress and fetal development, we have constructed a mammalian model of CRH deficiency by targeted mutation in embryonic stem (ES) cells. We report here that corticotropin-releasing hormone-deficient mice reveal a fetal glucocorticoid requirement for lung maturation. Postnatally, despite marked glucocorticoid deficiency, these mice exhibit normal growth, fertility and longevity, suggesting that the major role of glucocorticoid is during fetal rather than postnatal life.
This study assesses second-year medical students' views of the nurse and compares them to those commonly held by the lay public. Using a modified version of the American Nurses Association National Commission's "Nursing Implementation Project Survey," views of the role of the registered professional nurse were elicited from second-year medical students in 1992 (n = 38), 1993 (n = 50), and 1994 (n = 70) during workshops designed for them to enhance nurse-physician collegiality. Misconceptions about the nursing profession and the scope of the nurse's role to ensure positive patient outcomes, were elucidated. Medical students welcomed opportunities within the curriculum to redefine their conceptions of the image of registered professional nurses. Nurses' advanced professional capabilities and interdisciplinary collegiality deserve continued attention throughout the medical school curriculum.
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A czar was born when President Clinton named Kristine M. Gebbie to be his national AIDS policy coordinator. But a year later, under unrelenting fire from AIDS activists, Gebbie resigned. Her departure underscores the trouble that some activists have had shifting from the outsider's game to the insider's.