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Biomedical subjects

J Barrett

Publications and source records attributed to J Barrett.

At least 235 records · Page 13Linked to original sources

The effect of hypertonic saline resuscitation on bacterial translocation after hemorrhagic shock in rats.

Translocation of enteric bacteria occurs in rats after hemorrhagic shock. A proposed mechanism involves intestinal mucosal injury by hypoperfusion. Recent work suggests that moderate hypovolemia causes gut arteriolar constriction, which is ameliorated by hypertonic saline resuscitation. Bacterial translocation should, therefore, be reduced when hypertonic saline (HS) is used as the resuscitative fluid. Seventy-eight Sprague-Dawley rats were anesthetized and subjected to 30 minutes of hemorrhagic shock (systolic blood pressure 30 to 50 mm Hg) through a modified Wigger's model. Resuscitation was performed with either shed blood (B), 3% HS + 1/2B (1:1), or with 7.5% HS + 1/2B (1:1). Spleen, liver, and mesenteric lymph nodes were sent for quantitative culture 24 hours later. Translocation occurred if enteric organisms were cultured from at least one organ. Statistical analysis used the Fisher exact test. Compared to autotransfusion, hemodilutional resuscitation from hemorrhagic shock with hypertonic saline resulted in a significant reduction in bacterial translocation (p values were 0.03 and 0.04 for 3% and 7.5% hypertonic saline, respectively). The reduction in translocation after hypertonic saline resuscitation may be the consequence of microcirculatory alterations preventing gut hypoperfusion.

Animals↗

A novel NADPH/NADH-dependent aldehyde reduction enzyme isolated from the tapeworm Moniezia expansa.

An aldehyde reduction enzyme has been purified from the cytosol of the tapeworm, Moniezia expansa, by chromatofocusing and Reactive-Red chromatography. The enzyme is monomeric (subunit 34 kDa) and can utilise NADH and NADPH as co-factors. Substrates of the enzyme include alkanals, alka-2,4-dienals and alk-2-enals, established secondary products of lipid peroxidation. The enzyme reduced methylglyoxal, another possible natural substrate (M. expansa lacks glyoxalase I activity). The parasite enzyme may help form a final line of defence against cytotoxic aldehydes arising from host immune initiated lipid peroxidation.

Alcohol Oxidoreductases↗

In vivo characterisation of 3-iodo-6-methoxybenzamide 123I in humans.

3-Iodo-6-methoxybenzamide (123I-IBZM), a new Dopamine D2 receptor ligand, was used in conjunction with SME 810 brain tomography to study six subjects (one normal volunteer, four schizophrenics and one DAT patient). Initial Dynamic SPET was followed by multislice SPET. High-resolution images of the D2 receptor distribution in the basal ganglia were obtained. The specific binding in D2 receptors of the basal ganglia is highest from 2-4 h p.i. Patients on anti-psychotic drugs showed significantly lower specific binding. Dopamine D2 brain receptor availability in man may now be studied with SPET. Continuous data acquisition with single slice tomography is particularly important in the study of this type of radiotracers.

Adult↗

Relative distribution of glutathione transferase, glyoxalase I and glyoxalase II in helminths.

Glutathione transferase, glyoxalase I and glyoxalase II activities were not evenly distributed among the major helminth groups. Intestinal cestodes and digeneans had higher glutathione transferase activity than parasitic nematodes. High glyoxalase II activity was found in cestodes and digeneans but no glyoxalase I was detectable. Glyoxalase I and II were both detected in nematodes. These results are discussed in relation to the enzymes' suggested role in protection against secondary lipid peroxidation products.

Animals↗

Sphingomyelin synthesis in Fasciola hepatica.

Whole worms and/or homogenates of F. hepatica incorporate label from cytidine-5-diphospho[methyl-14C]choline,[1-14C]palmitoylCoA,[U- 14C]serine,[2-14C]methionine, [U-14C]glycine, [U-14C]threonine and [U-14C]aspartate into the various intermediates of sphingomyelin synthesis (ketosphinganine, sphinganine, sphingosine, ceramide and sphingomyelin). This suggests that sphingomyelin synthesis in F. hepatica occurs by a pathway similar to that found in mammals. However, there is some evidence that in F. hepatica 3-ketosphinganine may be N-acylated prior to reduction and dehydrogenation.

Amino Acids↗

Detoxification reactions of Fasciola hepatica cytosolic glutathione transferases.

Acidic/neutral glutathione (GSH) transferase forms have been isolated from Fasciola hepatica by a combination of GSH-affinity chromatography and chromatofocusing. Approximately 10-25% of the activity failed to interact with the GSH-affinity matrix when applied from crude cytosolic preparations. Following partial purification by chromatofocusing this GSH transferase activity did subsequently bind to the affinity matrix. The F. hepatica GSH transferases had catalytic activity with secondary lipid peroxidation products, the latter being possible natural substrates. The enzymes also interacted with a number of hydrophobic ligands including haematin and substituted phenol-based anthelmintics.

Animals↗

Bone marrow transplantation for genetic disorders.

In 1967, a congenital disorder, severe combined immune deficiency disease, (SCID), was the first condition to be successfully corrected by bone marrow transplantation (BMT) from a histocompatible matched sibling donor. Since then the number of inherited disorders in which BMT has been used has been greatly extended. In preface, it should be stressed that BMT represents only one aspect of the management of genetic disorders which includes first and foremost detection and prevention by antenatal screening. Enzyme replacement treatment and the development of genetic engineering techniques to correct the underlying fault are being actively explored. However, reliable screening programmes are only feasible in a minority of disorders, of which thalassaemia is an example. Enzyme replacement treatment has been largely unsuccessful, and despite considerable advances in the understanding of gene regulation, at present BMT represents the only practice capable of correcting genetic disorders and improving the quality of life of affected individuals.

Bone Marrow Transplantation↗

Symptomatology of late-life minor depression among primary care patients.

Patients of four general internists and four family physicians were interviewed by two psychiatrists to identify those suffering from depressive disorders. Nineteen elderly (60 years of age and older) patients and 22 younger (between 18 and 59 years of age) patients met Research Diagnostic Criteria (RDC) for minor depressive disorder, and 73 elderly and 79 younger patients had no psychiatric disorder. In general, the elderly depressed medical outpatients and the younger depressed medical outpatients had similar symptomatology, as did the elderly and nonelderly medical outpatients without psychiatric disorders.

Adult↗

Relative bradycardia in patients with isolated penetrating abdominal trauma and isolated extremity trauma.

A relative bradycardia is sometimes seen in patients with hemorrhagic shock. The phenomenon of relative bradycardia in civilian patients with isolated penetrating abdominal trauma and isolated severe extremity trauma who presented to an urban trauma center was studied retrospectively. Relative bradycardia was defined as a pulse rate of less than 100 with a concomitant systolic blood pressure of less than 100 mm Hg. There were 256 patients with isolated penetrating abdominal trauma and 938 patients with isolated severe extremity trauma. The incidence of relative bradycardia was 3.1% (eight of 256) in the group with abdominal trauma and 1.8% (17 of 938) in the group with extremity trauma. A pulse rate less than 100 was documented in 35.2% of all patients presenting with a systolic blood pressure less than 100 mm Hg (25 of 71). A pulse rate of less than 100 was documented in 45.8% of all patients presenting with a systolic blood pressure less than 90 mm Hg (11 of 24). No increased mortality was seen in the patients who evidenced relative bradycardia. The effect of intraperitoneal bleeding on the normal tachycardic response to hemorrhage also was studied. After controlling for volume status using various operational definitions of shock, no statistically significant (P less than .01) difference in pulse rates was noted between patients with isolated penetrating abdominal trauma and isolated extremity trauma. This result suggests that the previously theorized vagal-mediated bradycardia unique to intraperitoneal bleeding may not exist.

Abdominal Injuries↗

Blocking factors and the isolation of glutathione transferases from Hymenolepis diminuta (Cestoda: Cyclophyllidea).

Four acidic glutathione (GSH) transferase forms were isolated from the cytosol of the adult cestode Hymenolepis diminuta by hydroxylapatite chromatography, glutathione-affinity chromatography and chromatofocusing, pH 7-5. The enzymes were dimers of subunit size approximately 24 kDa and accounted for at least 3% of the total soluble protein. The major GSH transferase had limited catalytic activity but may interact with a range of ligands and function as a binding/passive detoxification protein. An endogenous factor interfered with the binding of the crude cytosolic GSH transferase activity to glutathione-dependent affinity matrices but, following partial purification, the GSH transferase activity successfully interacted with the glutathione affinity matrix.

Animals↗

Glutathione transferase in helminths.

The helminth glutathione (GSH) transferases are present as isoenzymes but fail to show a clear biochemical homology to any of the three mammalian GSH transferase families. GSH transferase is one of the major detoxification systems found in helminths, particularly high levels being found in cestodes and digeneans. Helminth GSH transferases bind a range of anthelmintics but there is limited evidence that the enzymes can conjugate anthelmintics with glutathione. Other natural substrates of helminth GSH transferase may be secondary products of lipid peroxidation including lipid hydroperoxides and reactive carbonyls. Lipid peroxidation can arise via free radicals produced by host immuno-effector cells and helminth GSH transferase may help form a defence system against immune-mediated damage. GSH transferase has also been identified as a protective antigen in schistosomiasis.

Animals↗

Unrelated donor marrow transplantation between 1977 and 1987 at four centers in the United Kingdom.

Retrospectively we analyzed the histocompatibility data and clinical results of bone marrow transplantation in 51 patients who received marrow from unrelated donors (UD) from 1977 to 1987 at one of four UK BMT centers. We compared the results with those obtained in 51 transplants carried out at the same centers using HLA-identical (ID) sibling donors. Of the UD/recipient pairs 32 (63%) were serologically identical for HLA A, B, and DR antigens, and 37% showed varying degrees of mismatch. UD-BMT primary diagnoses were: severe aplastic anemia or Fanconi's anemia (n = 17), acute leukemia (n = 11), chronic myeloid leukemia (n = 21), and other conditions (n = 2). T cell depletion of the graft was associated with a significant improvement in survival in both UD and ID-BMT. Graft failure was more common in recipients of UD than of ID transplants (13 [25%] vs. 5 [10%] P = 0.05) but there was no significant difference in the frequency of acute or chronic graft-versus-host disease. Actuarial survival was superior for recipients of ID transplants (UD vs. ID: 49% vs. 78%, respectively, at 3 months; 32% vs. 63% at one year). Reduced survival for recipients of UD-BMT was confirmed in case control regression analysis (relative risk 3.0, P = 0.01). Nevertheless in patients whose only alternative is a partially mismatched family donor we think that UD-BMT is justified.

Bone Marrow Transplantation↗

The effect of sleep/wake state on nocturnal melatonin excretion.

Twenty-four hour patterns of urinary 6-sulphatoxymelatonin excretion were monitored in eight healthy adult subjects in two bed rest constant routines, one with normal nocturnal sleep and one with continuous wakefulness. The implementation of dim light "constant routines" enabled the effect of the sleep wake/state on melatonin to be tested without the confounding effects of body activity and normal room lighting. In both conditions 6-sulphatoxymelatonin excretion was significantly higher during the nighttime hours (2200-1000) than during the daytime hours (1000-2200) producing averages of 80% and 78.5% of the total 24 hour output in the sleep and wakeful conditions, respectively. The large differences between subjects in nocturnal melatonin excretion (38 to 150 nmol) were highly consistent between the two conditions. There were no differences between the nocturnal wakeful and sleep conditions in total nighttime melatonin excretion nor in the nighttime percentage of the 24 hour total melatonin excretions. Therefore, the sleep/wake state alone had no effect on nocturnal melatonin excretion. On the other hand, a significant correlation between the nighttime melatonin percentage and sleep length suggested the need to investigate further the relation between the amplitude of the melatonin circadian rhythm and sleep length and quality.

Adult↗

An amino-terminal c-myc domain required for neoplastic transformation activates transcription.

The product of the c-myc proto-oncogene is a nuclear phosphoprotein whose normal cellular function has not yet been defined. c-Myc has a number of biochemical properties, however, that suggest that it may function as a potential regulator of gene transcription. Specifically, it is a nuclear DNA-binding protein with a short half-life, a high proline content, segments that are rich in glutamine and acidic residues, and a carboxyl-terminal oligomerization domain containing the leucine zipper and helix-loop-helix motifs that serve as oligomerization domains in known regulators of transcription, such as C/EBP, Jun, Fos, GCN4, MyoD, E12, and E47. In an effort to establish that c-Myc might regulate transcription in vivo, we sought to determine whether regions of the c-Myc protein could activate transcription in an in vitro system. We report here that fusion proteins in which segments of human c-Myc are linked to the DNA-binding domain of the yeast transcriptional activator GAL4 can activate transcription from a reporter gene linked to GAL4-binding sites. Three independent activation regions are located between amino acids 1 and 143, a region that has been shown to be required for neoplastic transformation of primary rat embryo cells in cooperation with a mutated ras gene. These results demonstrate that domains of the c-Myc protein can function to regulate transcription in a model system and suggest that alterations of Myc transcriptional regulatory function may lead to neoplastic transformation.

Amino Acid Sequence↗

Detoxification of secondary products of lipid peroxidation in the cytosol of a mouse fibroblast cell line.

A cytosolic fraction prepared from a mouse fibroblast cell line reduced secondary products of lipid peroxidation, including alkenals, alkanals, alk-2-enals, and alka-2,4-dienals, using NADH or NADPH. An alternative route for detoxification of alk-2-enals and alka-2,4-dienals in the cell line cytosol was via glutathione conjugation. The major glutathione transferase in the cell line cytosol was partially characterized by glutathione-agarose chromatography and chromatofocusing. High glutathione peroxidase activity suggested that the enzyme was an alpha family glutathione transferase. The major glutathione transferase also efficiently catalyzed the conjugation of alk-2-enals and alka-2,4-dienals with glutathione.

Animals↗

Extension of reproductive suppression by pheromonal cues in subordinate female marmoset monkeys, Callithrix jacchus.

Pheromonal signals from the dominant female marmoset monkey were implicated in maintaining the suppression of LH secretion and ovulation in socially subordinate females. When subordinate, and reproductively suppressed, female marmoset monkeys were removed from their group without scent contact with their dominant females, subordinate females in control group 1 (N = 8) and control group 2 (N = 5), ovulated 10.8 +/- 1.4 days and 10.4 +/- 0.8 days respectively (mean +/- s.e.m.) after separation. Subordinate females (N = 8) removed from their dominant female and group, but maintained in scent contact only with their dominant females, showed a delay in the onset of ovulation (31.0 +/- 6.4 days) compared with control groups 1 and 2. Plasma LH concentrations of subordinate females during the scent transfer phase were lower than in controls without scent transfer and comparable to those seen whilst the females were subordinates in groups. Contact of subordinate females with olfactory stimuli from dominant females therefore maintains the suppression of both LH secretion and ovulation in socially subordinate female marmosets. Such pheromonal cues provide evidence of a quantifiable link between dominant female marmosets and the maintenance of physiological suppression of reproduction in their female subordinates.

Animals↗

Overcoming potential pitfalls in the use of Medicare data for epidemiologic research.

We used Medicare data bases and US Census data to address two questions critical to the use of Medicare files for epidemiologic research. First, we examined the degree to which the population enrolled in the Medicare program is similar to the elderly resident population of the United States, as estimated by the US Census. We found small differences in the total population estimates but substantial differences by age and race. Second, we found that among Medicare enrollees, physician claims identify a small proportion of hip fracture cases which are not documented in the hospital discharge files. This proportion varies by age, region, and state within the United States. Calculation of rates based on Medicare hospital discharge data, and probably other hospital discharge data sets as well, must take these limitations into account. Use of all available Medicare data files can overcome these limitations.

Aged↗