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Biomedical subjects

M Kennedy

Publications and source records attributed to M Kennedy.

At least 109 records · Page 6Linked to original sources

Tumor necrosis factor-alpha is not essential in endotoxin induced eye inflammation: studies in cytokine receptor deficient mice.

OBJECTIVE: Anterior uveitis frequently occurs in association with specific systemic inflammatory diseases. Interleukin 1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) have been implicated in the pathogenesis of these diseases. We evaluate the need for these cytokines in a model of anterior uveitis. METHODS: Endotoxin was injected into the vitreous of mice deficient in IL-1 receptor type I, TNF receptors p55 and p75, both IL-1R1 and TNFR p55, or controls. Eyes were harvested after 24 h for histology and IL-6 bioassays or after 3 h for reverse transcriptase-polymerase chain reaction analysis of mRNA for specific cytokines or enzymes. RESULTS: No significant difference in the number of infiltrating cells was found in TNFR p55/p75 deficient mice compared to controls in any of 4 separate experiments or in the combined data (p = 0.8). The number of infiltrating cells was significantly reduced in 2 of 4 experiments with IL-1R1 deficient mice (p < 0.001 based on combined data from 4 studies). IL-1R1/TNFR p55 deficient mice had a reduction in infiltrating cells in 2 of 3 experiments (p < 0.001 based on combined data from all studies). IL-6 levels were not significantly reduced in either of 2 experiments with TNFR p55/p75 deficient mice, but were reduced in one of 2 experiments with IL-1R1-/- mice (p = 0.02) and in one experiment with IL-1R1/TNFR p55 deficient mice (p = 0.01). In response to endotoxin, all 3 receptor deficient lines increased mRNA levels for IL-1-alpha, IL-10, TNF-alpha, IL-1 receptor antagonist, and inducible nitric oxide synthase. CONCLUSIONS: IL-1 appears to have a more pivotal role in endotoxin induced uveitis than TNF-alpha, although neither cytokine is essential. Deletion of receptors for both cytokines has the most consistent effect, which is in accord with the hypothesis that these cytokines are, at least in part, functionally redundant.

Animals↗

A common precursor for primitive erythropoiesis and definitive haematopoiesis.

The generation of blood cells, haematopoiesis, in the mouse embryo begins with the development of primitive nucleated erythroid cells in the yolk sac followed by the appearance of precursors for multiple definitive haematopoietic lineages. The later developing lineages arise from multipotential stem cells, but the relationship of primitive erythroid cells to these other haematopoietic populations is unknown. Using an in vitro embryonic stem (ES) cell differentiation system, we show that primitive erythrocytes and other haematopoietic lineages arise from a common multipotential precursor that develops within embryoid bodies generated from differentiated ES cells. In response to vascular endothelial growth factor and c-kit ligand these precursors give rise to colonies containing immature cells (blasts) expressing marker genes characteristic of haematopoietic precursors. Many blast colonies also expressed betaH1 and beta major globins but not Brachyury, a mesodermal marker. Kinetic analysis demonstrated that the blast colony-forming cells represent a transient population, preceding the establishment of the primitive erythroid and other lineage-restricted precursors. This precursor population may represent the earliest stage of embryonic haematopoietic commitment.

Animals↗

Conversion of desulforedoxin into a rubredoxin center.

Rubredoxin and desulforedoxin both contain an Fe(S-Cys)4 center. However, the spectroscopic properties of the center in desulforedoxin differ from rubredoxin. These differences arise from a distortion of the metal site hypothesized to result from adjacent cysteine residues in the primary sequence of desulforedoxin. Two desulforedoxin mutants were generated in which either a G or P-V were inserted between adjacent cysteines. Both mutants exhibited optical spectra with maxima at 278, 345, 380, 480, and 560 nm while the low temperature X-band EPR spectra indicated highspin Fe3+ ions with large rhombic distortions (E/D = 0.21-0.23). These spectroscopic properties are distinct from wild type desulforedoxin and virtually identical to rubredoxin.

Cysteine↗

The effect of the source of transfused blood on the rate of consumption of transfused red blood cells in pregnancies affected by red blood cell alloimmunization.

OBJECTIVE: Our purpose was to compare the rate of consumption of maternally donated red blood cells with the rate of red blood cells from volunteers in fetuses affected by red blood cell alloimmunization. STUDY DESIGN: The rate of hemoglobin decline was calculated in 293 fetal transfusions in 52 pregnancies, in 43 patients affected by red blood cell alloimmunization from 1987 to 1996. Fifty-eight transfusions were excluded from analysis. Hemoglobin decline was stratified by gestational age. The rates of consumption were compared with use of unpaired t tests. RESULTS: The rates of hemoglobin decline (in grams per deciliter per day) were 18 to 24 weeks, 0.47 volunteer and 0.38 maternal (p = 0.174); 25 to 28 weeks 0.41 volunteer, 0.34 maternal (p = 0.46); 29 to 32 weeks, 0.35 volunteer, 0.33 maternal; > or = 33 weeks, 0.37 volunteer, 0.25 maternal, p = 0.048). Hemoglobin decline was less for the maternal donation group than for the volunteer donation group throughout gestation, becoming significant only in fetuses at > or = 33 weeks. CONCLUSION: In the red blood cell-alloimmunized fetus, there is less consumption of maternal than of volunteer red blood cells. This difference reaches a statistical significance only in late gestation.

Blood Donors↗

Anti-M isoimmunization: management and outcome at the Ohio State University from 1969 to 1995.

OBJECTIVE: To review the management strategies and outcome in gravidas with anti-M isoimmunization over the past 26 years at The Ohio State University. METHODS: Data collected from 115 pregnancies found to have anti-M antibody at The Ohio State University from September 1969 through February 1996 were reviewed retrospectively. We analyzed indirect antiglobulin tests, amniotic fluid with spectrophotometric examination, direct antiglobulin tests, M antigen status, antepartum course, and perinatal outcome. RESULTS: Anti-M antibody was found in 90 women who had 115 pregnancies over 26 years. Among those with positive indirect antiglobulin tests, 104 pregnancies had titers at or below 1:4. Only one patient with an initial low titer experienced more than a three-fold increase to 1:64. Two women underwent a total of eight amniocenteses when titers were at or above 1:128. Forty-two (60%) of the 70 infants tested were positive for M antigen. Nine infants required phototherapy. Eight of these infants were delivered preterm. There was an increase in the number of women seen with anti-M antibody in pregnancy at our institution, with nearly 10% of all gravidas with a positive antibody screen having anti-M alloantibodies. There were no cases of hemolytic disease of the newborn, mild or severe. CONCLUSION: The prevalence of anti-M isoimmunization may be increasing. The incidence of severe hemolytic disease of the newborn due to anti-M is extremely low. We found no cases in our review of 115 pregnancies, although there have been several cases of severe hemolytic disease of the newborn reported. If anti-M is detected in pregnancy, the titer is low (no more than 1:4), and there is no history of prior pregnancy complications suggesting a hemolytic disease process, we recommend no further testing other than an indirect antiglobulin test at 28 weeks to look for the emergence of other alloantibodies. However, if the initial titer is elevated or there is a concerning obstetric history, serial titers should be performed and amniocenteses reserved for rising titers.

Antibodies, Anti-Idiotypic↗

Interleukin 15.

Explore the source record for details and available documents.

Animals↗

Reversible oligohydramnios in a pregnancy with angiotensin-converting enzyme inhibitor exposure.

The use of angiotensin-converting enzyme inhibitors during pregnancy has been associated with poor fetal outcomes, including oligohydramnios, renal tubular dysplasia, cranial malformations, and fetal death. A 35-year-old woman with chronic hypertension was treated with the angiotensin-converting enzyme inhibitor benazepril until 27 weeks' gestation, when severe oligohydramnios was noted. After hospitalization for bed rest, fetal surveillance, and discontinuation of the agent, amniotic fluid rapidly reaccumulated, and a healthy infant was delivered at term. Although the use of angiotensin-converting enzyme inhibitors should be avoided during pregnancy, patients whose fetuses are inadvertently exposed in utero need not be given a uniformly poor prognosis. Oligohydramnios induced by the use of angiotensin-converting enzyme inhibitors during pregnancy may be reversible if the agent is discontinued. This case underscores the need for obstetricians to review carefully the medication regimens of all pregnant women and to be familiar with generic and proprietary names of medications to avoid the use of potentially harmful agents during pregnancy.

Adult↗

Nutritional support for patients with intellectual disability and nutrition/dysphagia disorders in community care.

Patients with intellectual disability and neurological handicaps associated with swallowing difficulties are vulnerable to dehydration and undernutrition. Some patients are severely undernourished, a condition which is usually associated with recurrent food aspiration and respiratory infections. Underweight patients are usually provided with adequate dietary protein by carers: their low energy intakes reflect inadequate intakes of fat and carbohydrate. Many patients gain weight following the provision of easily assimilated energy-dense fat- and sugar-containing foods. Where these measures fail, the provision of a percutaneous endoscopic gastrostomy (PEG) tube may be life-saving. Optimal supervision of patients with severe nutrition/dysphagia problems requires a support network linking carers at home or in community care facilities with the primary health care team and the local district general hospital.

Anthropometry↗

Indicators of abuse or neglect in preschool children's drawings.

1. Research designed to examine the systematic ability of children's drawings to disclose abuse or neglect has been equivocal. 2. The use of art to understand preschool-aged children is particularly advantageous because very young children usually are not able to communicate their feelings clearly. 3. The study shows that the family drawings of abused or neglected preschool children can be differentiated from those of children not identified as abused or neglected.

Art Therapy↗