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Biomedical subjects

D Stark

Publications and source records attributed to D Stark.

At least 37 records · Page 2Linked to original sources
PubMed2000

Patched represses the Hedgehog signalling pathway by promoting modification of the Smoothened protein.

Hedgehog (Hh) signalling plays a central role in many developmental processes in both vertebrates and invertebrates [1]. The multipass membrane-spanning proteins Patched (Ptc) [2-4] and Smoothened (Smo) [5-7] have been proposed to act as subunits of a putative Hh receptor complex. According to this view, Smo functions as the transducing subunit, the activity of which is blocked by a direct interaction with the ligand-binding subunit, Ptc [8]. Activation of the intracellular signalling pathway occurs when Hh binds to Ptc [8-11], an event assumed to release Smo from Ptc-mediated inhibition. Evidence for a physical interaction between Smo and Ptc is so far limited to studies of the vertebrate versions of these proteins when overexpressed in tissue culture systems [8,12]. To test this model, we have overexpressed the Drosophila Smo protein in vivo and found that increasing the levels of Smo protein per se was not sufficient for activation of the pathway. Immunohistochemical staining of wild-type and transgenic embryos revealed distinct patterns of Smo distribution, depending on which region of the protein was detected by the antibody. Our findings suggest that Smo is modified to yield a non-functional form and this modification is promoted by Ptc in a non-stoichiometric manner.

Animals↗
PubMed2000

Sequence of PHA synthase gene from two strains of Rhodospirillum rubrum and in vivo substrate specificity of four PHA synthases across two heterologous expression systems.

A 3.0-kb genomic fragment has been isolated from Rhodospirillum rubrum (ATCC 25903) that contains an open reading frame (ORF) with strong homology to other known polyhydroxyalkanoate (PHA) synthase genes. This ORF has lower homology to the R. rubrum strain Ha PHA synthase than would be expected within the same species. We have conducted a series of heterologous expression studies evaluating the in vivo substrate specificity of PHA synthase genes from Rhodobacter sphaeroides, Ralstonia eutropha (formerly Alcaligenes eutrophus), Thiocystis violacea, and Nocardia corrallina, within the PHA-synthase-negative hosts, Ralstonia eutropha DSM541 and Pseudomonas putida GpP104. The N. corrallina PHA synthase incorporated the highest percentage of C5 monomers in the polymer when fermented in medium supplemented with 0.1% heptanoate as the sole carbon source. When the T. violacea and R. sphaeroides were expressed in the PHA-negative host DSM541, a greater percentage of C5 monomer was observed in the polymer as compared to the expression of the PHA synthase of R. eutropha, when the transconjugants were fermented in medium supplemented with 0.4% propionate. Evaluation for preference of medium-chain-length monomers demonstrated the flexibility of the N. corrallina, T. violacea, and R. eutropha synthase genes to polymerize a copolyester composed of short- and medium-chain-length monomers when the respective transconjugants were fermented in medium supplemented with 0.5% octanoate. These studies demonstrate that the PHA synthase from N. corrallina, T. violacea, and R. eutropha are able to polymerize a copolyester composed of short- and medium-chain-length monomers, while the PHA synthase from R. sphaeroides lacks this ability and only produces a short-chain-length polymer. These observations suggest that the composition of the PHA from the PHA-producing organisms does not necessarily reflect the inherent specificity of the PHA synthase.

Acyltransferases↗
PubMed1999

Quality of life instruments in oncology.

The objective of this article is to aid clinicians in understanding the current state of the development and application of quality of life (QOL) instruments as outcome measures in cancer clinical research and practice. As a result of the achievements of the past two decades, the concept of QOL has been defined and many reliable and valid measurement tools have been developed. The two main approaches to QOL assessment, psychometric-based and utility-based, are discussed together with a brief description of the strategies for meaningful interpretation of QOL profiles. QOL measures in oncology have the potential to be used to study populations in randomised clinical trials, to aid patient-clinician interactions in routine practice and to support policy decision making and economic evaluation of healthcare provision.

Clinical Trials as Topic↗
PubMed1997

Exercise training by individuals with predialysis renal failure: cardiorespiratory endurance, hypertension, and renal function.

The purpose of this study was to determine the effects of 4 months of exercise training (ET) on cardiorespiratory function and endurance, blood pressure, muscle strength, hematology, blood lipids, and renal function in individuals with chronic renal failure (CRF) who were not yet on dialysis. Sixteen subjects were recruited to volunteer for participation in this study, but only eight completed all study phases. Subjects were first evaluated before and after a 2-month baseline (BL1 and BL2), after 4 months of ET, and again after 2 months of detraining (DT). ET did not change hematology, blood lipids, or echocardiographic measurements of left ventricular function and mass. Resting systolic and diastolic blood pressures decreased significantly from BL after the ET (146 +/- 15.7/87 +/- 9 mm Hg to 124 +/- 17.5/78 +/- 9.5 mm Hg; P < 0.02), and then increased significantly after DT (139 +/- 14.7 mm Hg and 87 +/- 9.9 mm Hg; P < 0.01). Peak oxygen consumption (pVO2) changed significantly during the study (1.3 +/- 0.3 L/min, 1.5 +/- 0.3 L/min, and 1.4 +/- 0.3 L/min for BL2, ET, and DT, respectively; P < 0.02), as did the VO2 at the ventilatory threshold (0.65 +/- 0.18 L/min, 0.92 +/- 0.19 L/min, and 0.68 +/- 0.23 L/min for BL2, ET, and DT, respectively; P < 0.01). Knee flexion peak torque increased after ET (43.4 +/- 25.6 Nm to 51.0 +/- 30.5 Nm; P < 0.02). GFR, as measured by creatinine clearance, continued to deteriorate during the course of the study (25.3 +/- 12.0 mL/min, 21.8 +/- 13.2 mL/min, and 21.8 +/- 13.2 mL/min for BL2, ET, and DT, respectively; P < 0.001). Individuals with predialysis CRF who undergo ET improve in functional aerobic capacity, muscular strength, and blood pressure.

Adult↗
PubMed1996

Receptor isoform specificity in a cellular response to retinoic acid.

The effects of retinoic acid on cell proliferation, differentiation and patterning are thought to be mediated by the various retinoic acid receptors. Different receptor types are encoded by distinct genes (alpha, beta, and gamma), whereas various isoforms within each type are encoded by splicing variants resulting from the use of alternative promoters. The only region that differs between isoforms is the N-terminal A region containing a transcriptional activating domain. It has been proposed that these alternative A regions confer distinct activities on the receptors, thus allowing each to mediate specific effects of retinoic acid, but it has been difficult to demonstrate such isoform specificity as most cells express a number of different retinoic acid receptors. In an attempt to test whether different isoforms can mediate distinct biological effects we are focusing on retinoic-acid-dependent growth inhibition of newt limb cells. We have constructed chimaeric receptors in which the retinoic acid binding domain of each of five newt retinoic acid receptors has been replaced with a thyroid hormone (T3) binding domain. These constructs were introduced individually into cells whose growth rate was then measured in the presence of T3. The chimaeric alpha 1 receptor mediated T3-dependent inhibition of proliferation that was comparable to that given by retinoic acid, whereas the alpha 2 isoform had no activity in this assay, nor did the delta 1A, delta 1B and Delta 2 receptors. When the A region was deleted from the alpha 1 chimaera it remained a potent T3-dependent transcriptional activator, but no longer mediated T3-dependent growth inhibition. In contrast, when the A region of alpha 1 was transferred to a delta chimaeric receptor, the resulting molecule was fully active in T3-dependent growth inhibition. This is the first direct evidence for isoform specificity in a biological response to retinoic acid, and demonstrates that the specificity of this response is confined to the A region.

Alternative Splicing↗
PubMed1996

A prospective, randomized controlled trial of inpatient versus outpatient continence programs in the treatment of urinary incontinence in the female.

Seventy-four patients presenting with a mixed pattern of urinary symptoms were randomly allocated to undergo either inpatient or outpatient continence programs as initial treatment, without prior urodynamic investigation. Both programs consisted of physiotherapy, bladder retraining, fluid normalization, dietary advice and general support and advice. Nine out of 39 in the outpatient group and 8 out of the 35 of the inpatient group failed to complete the study. There was a significant decrease in frequency, nocturia, number of incontinent episodes and visual analog scores for both groups. In addition the outpatients had a significant reduction in loss on pad testing, and a significantly greater improvement in their visual analog score. In each group 63% were cured or improved to the extent that they did not require further treatment. Staff costs per outpatient were half those for an inpatient. We conclude that outpatient conservative treatment as detailed above is a successful first-line treatment of urinary incontinence in women. It is as successful and possibly better than inpatient treatment, and is significantly cheaper.

Adult↗
PubMed1996

Cross-training between cycling and running in untrained females.

OBJECTIVE: The purpose of the study was to evaluate the cross-training response between running and cycling in untrained females. EXPERIMENTAL DESIGN: The following study involved a pretest, post-test, 3 x 3 factorial design. SETTING: Training (4 days-week-1, 10 weeks, 70-80% heart rate reserve) occurred at the Center for Exercise and Applied Human Physiology. Exercise testing occurred at the Veterans Hospital, Exercise Laboratory. PATIENTS AND PARTICIPANTS: Subjects included healthy, untrained females aged 18-25 years, (N = 18). INTERVENTION: Subjects were assigned to one of three (n = 6) training groups (run = R, cycle = C, both run and cycle = RC) matched on pre-training CE VO2max results. MEASURES: Graded treadmill run (TR) and cycle ergometer (CE) tests were performed on each subject to determine a mode specific VO2max and the lactate threshold (LT). Graded arm ergometer (AE) was performed to determine VO2max and heart rate and blood lactate at 20 and 40 Watts (W). Testing occurred prior to (0T), after 5 (5T) and after 10 weeks of training (10T). Body fat testing (hydrodensitometry at residual lung volume) was performed at 0T and 10T. RESULTS: TR and CE VO2max as well as TR and CE VO2 at the LT improved throughout the 10 weeks, regardless of training group. Although there were no changes in VO2max or blood lactate levels during AE, submaximal heart rates were significantly reduced over the 10 weeks, regardless of training group. CONCLUSIONS: These results indicate that the aerobic benefits of either run, cycle or combined run and cycle training are similar in untrained females. The LT and AE heart rate data demonstrate that improvements in VOmax due to ten weeks of training are a result of pronounced peripheral and moderate central adaptations.

Adipose Tissue↗
PubMed1995

[Animal experiment studies on the influence of fatty infiltration of liver cells on tissue relaxation times and signal changes in magnetic resonance tomography].

Using a spectrometer (n = 60) in vitro and MRT imaging (n = 8) in vivo, we studied the influence of fatty changes of liver cells on the relaxation times of the liver (two animal models of fatty liver disease/orotic acid, L-ethionine). Induction of fatty degeneration of the liver by means of an orotic acid diet resulted in pure deposition of fat in the liver without any histological or serological proof of inflammatory changes. Although accumulation of triglyceride in the liver reduced the T1 relaxation time only relatively slightly (-15%), there was good correlation (r = 0.88) between fat content and T1. There was also good correlation (r = 0.92) between T2 and histological fat content. Inflammatory changes besides fatty deposition were seen both serologically and histologically in the L-ethionine model, so that the fatty content did not correlate with T1. In-vivo MRT imaging showed that spin-echo sequences are inappropriate for diagnosing fatty infiltration of the liver despite the relaxation time changes produced by the fatty deposition. On the other hand, chemical-shift imaging sequences are very sensitive to identify fatty deposits, and are also independent of any additionally existing inflammatory changes.

Alanine Transaminase↗
PubMed1995

[Atypical focal fatty liver].

Focal fatty liver disease can cause difficulties in the differential diagnosis by ultrasound, CT, and MRI. This case report describes the atypical findings of focal spared areas of fatty liver disease in association with inflammatory changes, which were thought to be malignant focal liver lesions.

Adult↗
PubMed1992

Ophthalmology in the undergraduate curriculum. A review in Queensland.

Three hundred and sixty-nine postal questionnaires related to the content and teaching of the undergraduate medical course were sent to Queensland city and provincial ophthalmologists, general practitioners, physicians and surgeons. The return rate was 53%. The views of the four groups were similar in most respects. The majority of respondents thought that ophthalmology should be taught as a separate course. They stated visits to operating theatre and eye casualty unit should be included in the course. Ophthalmologists and general practitioners stated the course should be longer, physicians thought it should remain the same length and surgeons felt less time should be dedicated to the teaching of ophthalmology. Topic areas regarded as essential were the acute care areas: trauma; glaucoma; infection; use of an ophthalmoscope; acute visual loss; and red eye. Squint was also regarded as an essential area by ophthalmologists.

Curriculum↗
PubMed1991

Moving muscles with microchips, mathematics and models: an update on the 'reverse' model.

This paper reviews the current status of our computer model for the management of strabismus and its future direction. Vector analysis was first used in the 1950s for the assessment of strabismus. Robinson's model was the first computer simulation of ocular motility. Using physiological principles and anatomical approximations, Robinson's model sought to predict the strabismic pattern to be expected from a given injury. The Kault/Stark 'reverse' model works in the opposite direction, to first simulate the given strabismic pattern and then advise the surgery required to restore orthophoria. The surgeon is able to 'trial' various operations and compare the expected postoperative results. An automated system is currently being developed to ease the difficulty in measuring the position of the eyes in all nine positions of gaze. This paper includes three illustrative case reports.

Adolescent↗
PubMed1989

An automated system of strabismus management. A direct approach using a "reverse" model.

Until now computer models of strabismus have consisted of lengthy calculations based on oculomotor physiology. Such models have been able to demonstrate the pattern of strabismus that would arise from any given muscle abnormality and/or operation. However, it has been difficult to use such models to guide strabismus surgery because the surgeon requires a model that works in the opposite direction. The surgeon requires a model whose input is the pattern of strabismus and output is the muscle operation required. Such a model is described here. Instead of consisting of calculations based on physiology the new model consists of a store of most of the information capable of being generated by an existing strabismus model together with an efficient search procedure. In this paper the potential of the new model is demonstrated by its application to a case of paralytic strabismus.

Diagnosis, Computer-Assisted↗
PubMed1988

Dermabrasion of traumatic tattoos: simple, inexpensive, effective.

In this article we describe the use of an electrosurgical cautery tip scratch pad for the treatment of traumatic (adventitious) tattoos. This inexpensive item is available in most surgical operating rooms. The pad is flexible yet firm and obviates the need for power equipment. Most important, the technique is simple, easy to learn, and highly effective.

Blast Injuries↗
PubMed1986

Abnormal in vivo metabolism of apolipoprotein E4 in humans.

Apolipoprotein E (apoE) is important in modulating the catabolism of remnants of triglyceride-rich lipoprotein particles. It is a polymorphic protein with the three common alleles coding for apoE2, apoE3, and apoE4. ApoE3 is considered the normal isoform, while apoE4 is associated both with hypercholesterolemia and type V hyperlipoproteinemia. We quantitated the kinetics of metabolism of apoE4 in 19 normolipidemic apoE3 homozygotes and 1 normolipidemic apoE4 homozygote, and compared this with the metabolism of apoE3 in 12 normolipidemic apoE3 homozygotes. In the apoE3 homozygous subjects, apoE4 was catabolized twice as fast as apoE3, with a mean plasma residence time of 0.37 +/- 0.01 d (+/- SEM) and 0.73 +/- 0.05 (P less than 0.001), respectively. When plasma was fractionated into the lipoprotein subclasses, the greatest amount of labeled apoE4 was present on very low density lipoproteins, while the largest fraction of labeled apoE3 was associated with high density lipoproteins. The plasma apoE concentration was decreased in an apoE4 homozygote compared with the apoE3 homozygotes (3.11 mg/dl vs. 4.83 +/- 0.35 mg/dl). The reduced apoE4 concentration was entirely due to a decreased apoE4 residence time in the apoE4 homozygote (0.36 d vs. 0.73 +/- 0.05 d for apoE3 in apoE3 homozygotes). These results indicate that apoE4 is kinetically different than apoE3, and suggest that the presence of apoE4 in hypercholesterolemic and type V hyperlipoproteinemic individuals may play an important pathophysiological role in the development of these dyslipoproteinemias.

Adolescent↗
PubMed1985

Magnetic resonance imaging in hypertrophic cardiomyopathy.

Gated magnetic resonance imaging (MRI) was performed using a 0.35-Tesla cryogenic system in 14 patients with hypertrophic cardiomyopathy (HC) in order to define the site and extent of abnormal wall thickness. These studies were compared with 2-dimensional (2-D) echocardiograms. Gated magnetic resonance imaging studies in 12 normal volunteers were used for comparison. In normal subjects and in patients with HC, the sharp demarcation of the myocardial wall permitted measurement of wall thickness. The thickness of the septal and posterolateral walls in normal subjects was 10.2 +/- 0.4 mm (+/- standard deviation) and 10.8 +/- 0.5 mm, respectively, whereas septal thickness in all but 1 patient with HC was 15.0 mm or greater. In patients with HC, septal and posterolateral wall thickness were 2.2 +/- 0.8 cm and 1.3 +/- 0.17 cm, respectively, by MRI. The 2-D echocardiographic measurements for septal and posterolateral walls were 2.4 +/- 0.6 cm and 1.4 +/- 0.7 cm, respectively. The severity and distribution of abnormal wall thickness were comparable on 2-D echo and MRI. Gated MRI is an effective and completely noninvasive technique for demonstrating the presence, site and extent of abnormal wall thickness in HC. The large field of view, ability to image directly in multiple planes, and discrete blood-endocardial interfaces are advantages for cardiovascular imaging.

Adult↗