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Biomedical subjects

R T White

Publications and source records attributed to R T White.

At least 19 recordsLinked to original sources
PubMed2000

Altered patterns of gene expression in response to myocardial infarction.

The use of cDNA microarrays has made it possible to simultaneously analyze gene expression for thousands of genes. Microarray technology was used to evaluate the expression of >4000 genes in a rat model of myocardial infarction. More than 200 genes were identified that showed differential expression in response to myocardial infarction. Gene expression changes were monitored from 2 to 16 weeks after infarction in 2 regions of the heart, the left ventricle free wall and interventricular septum. A novel clustering program was used to identify patterns of expression within this large set of data. Unique patterns were revealed within the transcriptional responses that illuminate changes in biological processes associated with myocardial infarction.

Animals↗
PubMed2000

Obstacles to a randomised controlled trial of intensive dynamic psychotherapy: an account of the New South Wales Section of Psychotherapy outcomes project.

OBJECTIVE: This paper examines the obstacles to a randomised controlled trial (RCT) of intensive dynamic psychotherapy (IDP) by reference to the fate of the New South Wales Section of Psychotherapy outcomes project. METHOD: Planning was complete and the final research protocol was about to be implemented when funding difficulties led to suspension of the project. The opinions of the research subcommittee regarding the main obstacles to the ultimate success of the project are now analysed in the expectation that better research strategies will follow. RESULTS: With hindsight, six of the eight members of the research subcommittee reported that the project was not feasible. By choice of questionnaire items they identified the greatest threats to a successful trial as: standardisation of the procedures, termination at 24 months, the availability of funding and the choice of treatment procedures. The most frequently volunteered concerns related to the enlistment and cooperation of the trial therapists (5), standardisation of the experimental therapy (3), probable shortfall in trial subjects (3) and the availability of funding (2). CONCLUSIONS: The most powerful general obstacles to success of the project related to the standardisation of procedures and the failure to maintain sufficient cooperation of trial therapists. The protocol required IDP therapists to terminate procedures at 24 months, which contradicted their usual practices and led to some alienation from the project. Amendments to the protocol might improve the possibility of a successful trial. However, one might also conclude that it is premature to attempt a naturalistic RCT of IDP.

Adult↗
PubMed1997

Measurement of autobiographical recall.

The finding by Huffman and Weaver (1996) of no support for the hypothesis that personal episodic recall involves visual imagery may be a consequence of their method of assessment. Further research which employs more measures than simply number of events recalled and which gives subjects longer time to respond is needed.

Autobiographies as Topic↗
PubMed1995

Jumping from a general hospital.

Jumping is the most common reported means of suicide in general hospitals. There have been no published reviews of suicides of nonpsychiatric inpatients since 1980. We describe 12 subjects who, between January 1980 and January 1992, jumped from a large general teaching hospital. Eight of them succumbed, providing a rate of suicide of 1.7 per 100,000 admissions. There were three clinical subgroups: those admitted after suicide attempts, the acutely delirious, and the chronically medically ill. Factors appearing frequently in the third subgroup were pain, dyspnea, transient confusion, poor prognosis, and recent adverse news. When we compared the hospital jumpers with 30 nonfatal jumpers who attended our Emergency Department, the medical and psychiatric profiles differed in the frequency of medical illnesses, advancing age, male gender, and absence of preexisting psychiatric illness. Proximity and ease of access to balconies and windows appeared to be highly relevant to the prevention of hospital jumping.

Adolescent↗
PubMed1995

Characterization of the promoter of human pulmonary surfactant protein B gene.

Pulmonary surfactant protein B (SP-B) is required for normal surfactant function and for survival at birth. To further study SP-B gene expression, we sequenced genomic clones and examined promoter activity of SP-B DNA fragments by transient transfection. A plasmid construct containing human SP-B fragment -1039/+431 linked to chloramphenicol acetyltransferase (CAT) reporter gene was readily expressed in H441 cells, which are derived from a human lung adenocarcinoma, but was < 4% as active in Hep G2, HeLa, and Calu 6 cell lines. SP-B promoter activity in H441 cells was orientation dependent and increased by linked Rous sarcoma virus (RSV) enhancer and was stronger than for thymidine kinase (tk) and RSV promoters. Deletional mapping of the 5' flanking region with exonuclease III suggested nonspecific negative (-811/-1039)- and positive (-453/-641)-control regions and a cell-specific enhancer region at -208 to -54. When a fragment from -403 to -35 base pairs (bp) was placed upstream or downstream of tkCAT, in either orientation, expression in H441 cells but not other cell lines was increased 4- to 28-fold relative to tkCAT. Deletional analysis of the 3' terminus indicated a requirement for at least 7 bp 3' of the transcription start site. Promoter activity was strongly inhibited in a dose-dependent fashion by phorbol ester, with responsiveness mapped to bp -208/-54, but was not responsive to glucocorticoid.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

CD36 is a receptor for oxidized low density lipoprotein.

The oxidation of low density lipoprotein (LDL) in the arterial wall is thought to contribute to human atherosclerotic lesion formation, in part by the high affinity uptake of oxidized LDL (OxLDL) by macrophages, resulting in foam cell formation. We have utilized cloning by expression to identify CD36 as a macrophage receptor for OxLDL. Transfection of a CD36 clone into 293 cells results in the specific and high affinity binding of OxLDL, followed by its internalization and degradation. An anti-CD36 antibody blocks 50% of the binding of OxLDL to platelets and to human macrophage-like THP cells. Furthermore, like mouse macrophages, 293 cells expressing CD36 recognize LDL which has been oxidized only 4 h, whereas more extensive oxidation of the LDL is required for recognition by the other known OxLDL receptors, the acetylated LDL (AcLDL) receptor and Fc gamma RII-B2. CD36 may play a role in scavenging LDL modified by oxidation and may mediate effects of OxLDL on monocytes and platelets in atherosclerotic lesions.

Animals↗
PubMed1993

Characterization of the cow stomach lysozyme genes: repetitive DNA and concerted evolution.

Cow stomach lysozyme genes have evolved in a mosaic pattern. The majority of the intronic and flanking sequences show an amount of sequence difference consistent with divergent evolution since duplication of the genes 40-50 million years ago. In contrast, exons 1, 2, and 4 and immediately adjacent intronic sequences differ little between genes and show evidence of recent concerted evolution. Exon 3 appears to be evolving divergently. The three characterized genes vary from 5.6 to 7.9 kilobases in length. Different distributions of repetitive DNA are found in each gene, which accounts for the majority of length differences between genes. The different distributions of repetitive DNA in each gene suggest the repetitive elements were inserted into each gene after the duplications that give rise to these three genes and provide additional support for divergent evolution for the majority of each gene. The observation that intronic and flanking sequences are evolving divergently suggests that the concerted evolution events involved in homogenizing the coding regions of lysozyme genes involve only one exon at a time. This model of concerted evolution would allow the shuffling of exon-sized pieces of information between genes, a phenomenon that may have aided in the early adaptive evolution of stomach lysozyme.

Animals↗
PubMed1992

A macrophage Fc receptor for IgG is also a receptor for oxidized low density lipoprotein.

The internalization of oxidized low density lipoprotein (OxLDL) by macrophages is hypothesized to contribute to foam cell formation and eventually to atherosclerotic lesion formation. OxLDL is a ligand for the acetylated low density lipoprotein (AcLDL) receptor, however, our data show that this receptor accounts for less than half of OxLDL uptake by mouse macrophages, suggesting additional receptors for OxLDL. We have developed a novel expression cloning strategy in order to isolate clones encoding OxLDL receptors. In addition to the AcLDL receptor, we isolated a molecular clone for a structurally unrelated receptor capable of mediating the high affinity uptake of OxLDL following transfection into cells. This receptor has been identified as the mouse Fc gamma RII-B2, a member of a family of receptors known to mediate immune complex uptake through recognition of the Fc region of IgG. The uptake of OxLDL by cells transfected with the Fc gamma RII-B2 clone is not blocked by AcLDL but is blocked by the anti-Fc gamma RII monoclonal antibody, 2.4G2.

Animals↗
PubMed1992

Human adipsin is identical to complement factor D and is expressed at high levels in adipose tissue.

A cDNA for human adipsin was isolated and shown to encode a protein sharing 98% amino acid sequence similarity with the protein sequence previously determined for purified natural human complement factor D. Like mouse adipsin, recombinant human adipsin displays the enzymatic activity of human complement factor D, cleaving complement factor B only when B is complexed with activated complement component C3. We conclude that human adipsin is equivalent to complement factor D and that adipsin is the homologue of factor D in rodents. Adipose tissue is a major site of synthesis of human adipsin/complement factor D mRNA, but unlike the case in rodents, human adipsin mRNA is also expressed in monocytes/macrophages. The data presented here, demonstrating the equivalence of human adipsin to complement factor D and its high level of expression in fat, suggest a previously unsuspected role for adipose tissue in immune system biology.

Adipose Tissue↗
PubMed1990

Interferon-gamma and synthesis of surfactant components by cultured human fetal lung.

We examined the effects of interferon-gamma (IFN-gamma) on development of the surfactant system in alveolar epithelial cells of fetal lung. Explants of second-trimester human fetal lung were cultured for 1 to 6 days in serum-free medium containing recombinant human IFN-gamma (0.03 to 30 ng/ml) and/or dexamethasone (10 or 100 nM). Treatment for 3 days with IFN-gamma alone, dexamethasone alone, and IFN plus dexamethasone increased the content of surfactant protein A (SP-A, 28 to 36 kD) by approximately 3-, 2.5-, and 10-fold, respectively. The biphasic response pattern of SP-A to dexamethasone (stimulation initially and inhibition with continued culture) was not altered by the presence of IFN-gamma. IFN-gamma also stimulated accumulation of SP-A mRNA (2.7-fold at 24 h) but did not affect the levels of mRNAs for surfactant protein B (18 kD) and surfactant protein C (5 kD). To assess the effect of IFN-gamma on synthesis of surfactant lipids, we determined the content of phosphatidylcholine, the rate of labeled choline incorporation into phosphatidylcholine, saturation of newly synthesized phosphatidylcholine, and the activity of fatty acid synthetase, a glucocorticoid-inducible enzyme. Treatment of explants for 5 days with IFN-gamma had no effect on these parameters. Studies by light and electron microscopy revealed little difference between control and IFN-treated explants with regard to cell viability and epithelial cell differentiation. We conclude that IFN-gamma has a selective stimulatory effect on SP-A among surfactant components.(ABSTRACT TRUNCATED AT 250 WORDS)

Choline↗
PubMed1989

Studies of the structure of lung surfactant protein SP-A.

SP-A, a glycoprotein of pulmonary surfactant, consists of an NH2-terminal domain containing a collagen-like sequence and a COOH-terminal domain with sequence homology to several Ca2(+)-dependent lectins. We have compared the size, thermal stability, and secondary structure of recombinant SP-A, the product of a fibroblast line transfected with a single human gene encoding SP-A, with natural SP-A isolated from canine and human lungs. Our results suggest both recombinant and natural SP-A are assembled as large oligomers. More variability in the degree of oligomerization was observed with recombinant human SP-A than with natural canine SP-A. As shown by collagenase digestion, the full assembly of protein subunits was dependent on an intact collagen-like domain. The cysteines in the noncollagen domain of SP-A form intrachain bonds between residues 135-226 and 204-218. The circular dichroism spectra of both recombinant and natural SP-A were consistent with the presence of a collagen-like triple helix. As determined by the change in ellipticity at 205 nm, the thermal transition temperatures of canine, natural human, and recombinant SP-A were 51.5, 52.3, and 42.0 degrees C, respectively. These results suggest differences in the assembly and stability of the natural and recombinant proteins.

Amino Acid Sequence↗
PubMed1989

Regulation of messenger RNAs for the hydrophobic surfactant proteins in human lung.

The pulmonary surfactant proteins SP-B (8,000 D) and SP-C (4,000 D) accelerate surface film formation by surfactant phospholipids. We used cDNA probes to examine regulation of these proteins in human fetal lung. The mRNAs were detectable at 13 wk gestation and increased to approximately 50% (SP-B) and approximately 15% (SP-C) of adult levels at 24 wk. The mRNAs were detected only in lung of 11 dog tissues examined. When human fetal lung was cultured as explants without hormones, SP-B mRNA increased and SP-C mRNA decreased. Exposure for 48 h to glucocorticoids, but not other steroids, increased both SP-B mRNA (approximately 4-fold) and SP-C mRNA (approximately 30-fold) vs. controls. Half-maximal stimulation occurred with 1 nM dexamethasone and 300 nM cortisol for SP-B mRNA and at three- to fivefold higher concentrations for SP-C mRNA. Both stimulation and its reversal on removal of hormone were more rapid for SP-B than for SP-C. Terbutaline and forskolin increased SP-B mRNA but not SP-C mRNA. Levels of both mRNAs were much higher in type II cells than fibroblasts prepared from explants. Thus, the genes for SP-B and SP-C are expressed in vivo before synthesis of both SP-A (28,000-36,000 D) and surfactant lipids. Glucocorticoid induction of SP-B and SP-C mRNAs in type II cells appears to be receptor mediated but may involve different mechanisms.

Animals↗
PubMed1988

Glucocorticoids both stimulate and inhibit production of pulmonary surfactant protein A in fetal human lung.

Pulmonary surfactant is a mixture of phospholipids and proteins which stabilizes lung alveoli and prevents respiratory failure. The surfactant-associated protein of Mr = 28,000-36,000 (SP-A) influences the structure, function (film formation), and metabolism of surfactant. We have characterized glucocorticoid regulation of SP-A and SP-A mRNA in explants of fetal human lung. The time course of response to dexamethasone was biphasic, with early stimulation and later inhibition of SP-A accumulation. Maximal induction of SP-A occurred with 3-10 nM dexamethasone and approximately 300 nM cortisol for 72 hr, and stimulation diminished at higher concentrations. SP-A mRNA accumulation was maximally stimulated at 24-48 hr of exposure to dexamethasone (10 nM) and was generally inhibited by 4-6 days. Stimulation was also observed with cortisone and corticosterone but not with sex steroids, suggesting a receptor-mediated process. When explants were exposed to cortisol for only 24 hr, SP-A content was transiently increased above the level in continuously treated tissue and subsequently was similar to control. The content of SP-A and its mRNA was also increased by dibromo-cAMP, terbutaline, and forskolin, and effects were approximately additive with those of dexamethasone. However, elevated in tracellular cAMP did not alter the biphasic time course or dose-response patterns of dexamethasone. We propose that glucocorticoids have both stimulatory and inhibitory effects on SP-A gene expression. This biphasic regulation is not consistent with generalized toxic effects, product-feedback inhibition, or receptor down-regulation, and it appears to be specific for SP-A among the various surfactant components.

Adult↗