Biomedical subjects
Publications and source records attributed to J Hamilton.
A rise in the rate of hospital admissions for patients with COPD has led to the development of nurse-led home care. A study in which a nurse-led team provided domiciliary treatment with ongoing follow-up, was found to be cost-effective and reduced the need for hospital care.
Neuronal membranes are highly enriched with docosahexaenoic acid (22:6n-3), and its content can be altered by ethanol consumption. We have previously reported that the 22:6n-3 status in membrane affects the biosynthesis of phosphatidylserine (PS), a phospholipid class which contains an exceptionally high proportion of 22:6n-3. The aim of the present study is to investigate the effect of chronic ethanol exposure on PS accumulation in relation to the 22:6n-3 status. C-6 glioma cells were enriched with 25 microM 22:6n-3 for 48 h and the PS accumulation was first evaluated in comparison to nonenriched cells as well as cells enriched with arachidonic acid (20:4n-6). Electrospray liquid chromatography-mass spectrometry analysis revealed that cells treated with 22:6n-3 showed significantly higher accumulation of PS in comparison to nonenriched or 20:4n-6-enriched cells, primarily due to an increase of 1-stearoyl-2-docosahexaenoyl-glycerophosphoserine (18:0,22:6-PS). Chronic ethanol exposure selectively affected the accumulation of PS in 22:6n-3-enriched cells. After cells were exposed to 20 or 50 mM ethanol for 4 wk, accumulation of 18:0,22:6-PS upon 22:6n-3 supplementation was significantly lower, resulting in a drastic reduction of total PS. Concomitantly, ethanol-treated cells showed lower incorporation of serine in comparison to control cells. From these data, it was concluded that supplementation of cells with 22:6n-3 promotes the accumulation of PS and chronic ethanol treatment diminishes this effect at least in part through impaired serine incorporation processes. Attenuated accumulation of 22:6n-3 in PS and the reduction of PS thus may have significant implications in pathophysiological effects of ethanol, especially in tissues with abundant 22:6n-3.
This third report from a longitudinal study of lesbian families presents data obtained from interviews with mothers of five-year-old children conceived by donor insemination. Results indicated that 87% of the children related well to peers, 18% had experienced homophobia from peers or teachers, and 63% had grandparents who frankly acknowledged their grandchild's lesbian family. Of the original couples, 31% had divorced. Of the remainder, 68% felt that their child was equally bonded to both mothers. Concerns of lesbian families are discussed.
BACKGROUND & AIMS: This study aimed to determine whether brief psychodynamic-interpersonal (PI) psychotherapy is more efficacious than a psychological control for patients with chronic, intractable functional dyspepsia (FD), and whether patients with abnormal gastric function respond differently than those with normal gastric function. METHODS: Ninety-five consecutive patients with chronic symptoms of FD who had failed to respond to conventional pharmacologic treatments were approached. Thirty-seven received PI psychotherapy, and 36 the control condition (supportive therapy). Patients completed self-report questionnaires before and after treatment and 12 months later. The patients' gastroenterologists, who were blind to the study groups, conducted independent ratings before and after treatment. Forty-nine patients also underwent a radioisotope gastric emptying study. An intention-to-treat analysis was used with baseline scores as covariates. RESULTS: At the end of treatment, there were significant advantages for PI psychotherapy compared with controls for the gastroenterologists' (P = 0.002) and patients' total symptom score (P = 0.015). One year after treatment, the symptomatic scores were similar. However, a subanalysis showed that PI therapy was superior to the control condition at 1 year, when patients with severe heartburn were excluded. There was no difference in outcome between patients with normal and abnormal gastric emptying. CONCLUSIONS: PI therapy may have both short- and long-term effects in patients with dyspepsia, but further evaluation is required. Its cost-effectiveness needs to be determined.
Hepatic ischemia-reperfusion (I/R) is an important cause of organ dysfunction in the critically ill. With reperfusion, Kupffer cells release pro-inflammatory cytokines that promote endothelial cell (EC) expression of adhesion molecules such as intercellular adhesion molecule (ICAM)-1, facilitating neutrophil (PMN) infiltration. Studies suggest hypertonic saline (HTS) might exert beneficial effects on development of organ injury following shock on the basis of reduced PMN-EC interactions. We hypothesized that HTS alters expression of EC ICAM-1 and thus minimizes PMN-mediated injury. To test our hypothesis, we used an in vivo model of hepatic I/R and an in vitro model of activated EC. Rats underwent 30 min of hepatic ischemia after pretreatment with HTS (7.5% NaCl, 4cc/kg ia) or normal saline (NS). At 4 h reperfusion, plasma was taken for aspartate aminotransferase (AST) and liver tissue was harvested for assessment of hepatic ICAM-1 mRNA by Northern blot analysis. Human umbilical vein endothelial cells (HUVECs) were activated by lipopolysaccharide (LPS) and exposed to hypertonic medium (350-500 mOsM). HUVEC ICAM-1 protein was measured by cell ELISA and ICAM-1 mRNA by Northern blot analysis. HTS prevented hepatic I/R injury as measured by AST. AST of shams was 282.6+/-38.1 IU/L. I/R following NS pretreatment caused significant injury (AST 973.8+/-110.9 IU/L) compared to sham (SM) (P < 0.001). Pretreatment with HTS exerted significant protection following I/R with an AST of 450.9+/-56.3 IU/L (P < 0.05). There was no significant difference in AST levels between SM and HTS groups. Reduced hepatic injury after HTS and I/R was accompanied by inhibition of I/R-induced hepatic ICAM-1 mRNA expression compared to NS treated animals (P < 0.01). Similarly, hypertonicity inhibited HUVEC LPS-induced ICAM-1 protein (LPS: 1.86+/-0.19 absorbance units; 400 mOsM +/- LPS: 1.45+/-0.14 absorbance units; 450 mOsM + LPS: 1.02+/-0.19 absorbance units, P < 0.001) and mRNA expression. Thus, hypertonicity modulates endothelial ICAM-1 expression as one possible protective mechanism against I/R injury.
DNA replication in the human beta-globin locus is subject to long-distance regulation. In murine and human erythroid cells, the human locus replicates in early S phase from a bidirectional origin located near the beta-globin gene. This Hispanic thalassemia deletion removes regulatory sequences located over 52 kb from the origin, resulting in replication of the locus from a different origin, a shift in replication timing to late S phase, adoption of a closed chromatin conformation, and silencing of globin gene expression in murine erythroid cells. The sequences deleted include nuclease-hypersensitive sites 2 to 5 (5'HS2-5) of the locus control region (LCR) plus an additional 27-kb upstream region. We tested a targeted deletion of 5'HS2-5 in the normal chromosomal context of the human beta-globin locus to determine the role of these elements in replication origin choice and replication timing. We demonstrate that the 5'HS2-5-deleted locus initiates replication at the appropriate origin and with normal timing in murine erythroid cells, and therefore we conclude that 5'HS2-5 in the classically defined LCR do not control replication in the human beta-globin locus. Recent studies also show that targeted deletion of 5'HS2-5 results in a locus that lacks globin gene expression yet retains an open chromatin conformation. Thus, the replication timing of the locus is closely correlated with nuclease sensitivity but not globin gene expression.
Elevated circulating levels of an endogenous ouabain (EO) have been associated with essential hypertension. To investigate structure-activity relationships relevant to blood pressure, we infused either ouabain, ouabagenin, digoxin or digitoxin at 30 microg/kg/day in normal Sprague Dawley rats. After five weeks, the ouabain and ouabagenin infused rats were hypertensive, whereas blood pressures declined below their vehicle controls in rats infused with digoxin or digitoxin. In a second study, mean blood pressures were 118.5+/-1.7 mmHg in rats infused with ouabain (15 microg/kg/day) on day 35 vs. 98.3+/-1.8 and 100.3+/-1.1 mmHg in the digoxin (30 microg/kg/day) and vehicle infused groups (both p<0.005 vs. ouabain), respectively. Plasma and kidney levels of ouabain immunoreactivity were increased 4-8 fold in ouabain infused rats while blood pressure and plasma levels of ouabain returned to normal one week following discontinuation of the steroid infusion. In rats with ouabain-dependent hypertension, secondary infusions of digoxin or digitoxin (30 microg/kg/day) normalized blood pressure even though circulating ouabain remained elevated. In digoxin infused rats, neither blood pressure nor kidney digoxin immunoreactivity was raised whereas plasma digoxin was increased. Collectively, the results show that the hemodynamic effects of these sodium pump inhibitors differ dramatically during prolonged administration and that tissue rather than circulating levels of these agents appear to better explain their effects on blood pressure. These studies suggest that sodium pump inhibition is not the exclusive mediator of the hemodynamic effects of these cardiac glycosides and demonstrate the presence of structure-specific mechanisms that regulate their tissue levels and effects on long-term blood pressure.
Researchers studying cellulase enzymes for the economical production of fuel ethanol envision cellulose as the carbon source. However, submerged Trichoderma reesei cultures grown on cellulose exhibit high run-to-run variability. Thus, an investigation of 30 batch cellulase production experiments was instrumental in determining fermentation conditions that improved enzyme titers, yields, and productivities. Eighteen of the 30 batch experiments experienced minimal process upsets and were classified into eight groups based on agitation rate, gas sparge rate, and the use of oxygen supplementation. Comparing corn steep liquor with yeast extract/peptone also tested the effect of different sources of nitrogen in the media. Average 7-d enzyme titers were doubled from 4 to 8 FPU/mL primarily by increasing aeration.
This article describes fiber optic and electrochemical pH sensors that could become part of a therapeutic arsenal to quickly and aggressively treat stroke victims as well as people who have suffered brain trauma. The fiber optic sensor design was based on the immobilization of a pH-sensitive dye, seminaphthorhodamine-1 carboxylate (SNARF-1C), onto the end of a 125-microm-diameter silica optical fiber using the sol-gel method. A miniature bench-top fluorimeter system was developed for use with the optical fiber to obtain pH measurements. The electrochemical sensor was based on sputter-coated iridium oxide thin films. Linear and reproducible responses for both sensors were obtained in human blood with pH varying between 6.8 ato 8.0, which encompasses the clinically relevant range. In vivo studies were also performed and results indicated that both types of sensors tracked pH with very little drift.
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Subcutaneous myxoid liposarcoma (ML) is exceedingly rare, with only two or three cases having been reported. Lipoblastoma (LB), a rare fatty tumor that arises in infants and children, is unknown after adolescence. In contrast to ML, LB is often superficial. The two tumors can be difficult to distinguish due to many histologic similarities. We examined a 0.9 cm superficial subcutaneous nodule from the dorsal neck of a 48 year old man that had been growing slowly. Three and one half years later, a 0.4 cm palpable recurrent nodule was excised from the scar. The patient is now free of disease at 7.5 years. Because of these unusual features, we performed clinicopathologic, immunohistochemical and molecular analysis of this unusual tumor to decide if this represented a rare cutaneous ML or an unprecedented example of LB in an adult. The primary featured a thick fibrous pseudocapsule with foci of lymphocytes and infiltrating nests of semi-mature fetal-appearing adipocytic tissue. This surrounded a more immature cellular-but-cytologically-bland myxoid tissue featuring stellate cells and signet lipoblasts. There were fibrous sep at the periphery and the vasculature was rather inconspicuous. The 0.4 cm diameter recurrence was distinctly lobular and had minute satellite nodules. It was composed of uniform fetal-appearing bland myxoid lipoblastic tissue featuring signet ring lipoblasts surrounded by a few spindle cells. In both tumors, lipoblasts expressed S-100 protein. In the primary, 5% of the lesional cells were FXIIIa+ dendritic stromal histiocytes while in the recurrence, 15% of the lesional cells were FXIIIa+ dendritic cells. CD34 stained only scattered small capillaries. The Ki67 proliferation index was 1% in the primary and 3% in the recurrence. RT-PCR assay for TLS/FUS-CHOP fusion transcripts was negative despite three repeat tests performed on paraffin sections of the primary tumor in the presence of good m-RNA internal controls. We reviewed the clinicopathologic and cytogenetic features of ML and LB. Based on this review and on the growth pattern, anatomic features and molecular data from the present case, we conclude that this tumor may represent the first reported case of adult LB.
In this second report from a longitudinal study of lesbian families in which the children were conceived by donor insemination, interviews yielded the following data: Most couples shared parenting co-equally; the majority felt closer to their family of origin; adoptive co-mothers felt greater legitimacy as parents; biology and nurture received the same ratings for mother-child bonding; and political and legal action had increased among many participants. The impact of these findings and that of homophobia on lesbian family life are discussed.
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