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Biomedical subjects

D Platt

Publications and source records attributed to D Platt.

At least 55 records · Page 3Linked to original sources

Fibronectin mRNA (FN-V95+) is increased in the liver of old Sprague-Dawley rats: effect of food restriction.

Because fibronectin (FN) mRNA has been shown to be increased in the brain of old rats and during in vivo and in vitro aging of both endothelial cells and fibroblasts, it was of interest to determine what effect age and caloric restriction have on the ability of liver cells to express FN mRNA. The prevalence of fibronectin mRNA containing the alternatively spliced variant V95 (FN-V95) was examined by RNA gel blot hybridization in the liver of 10-mo, 18-mo, 30-mo ad lib-fed (AL) and 30-mo food-restricted (FR) rats. The transcripts coding for FN-V95 mRNA were well expressed in the liver of 10-mo and 18-mo-old rats. The hybridization signal then increased (1.3-fold, p < .05) in the liver of 30-mo AL rats vs 10-mo-old rats. However, the prevalence of FN-V95 mRNA was dramatically decreased (approximately 4.5-fold, p < .01) in the liver of 30-mo food-restricted rats as compared to 30-mo-old AL rats. The distribution of FN-V95 mRNA was also investigated by non-radioactive in situ hybridization (ISH) on liver frozen sections. The hybridization signal for FN-V95 mRNA was evenly distributed among liver cells of 10-mo and 18-mo-old rats, while weak hybridization signals were sparsely scattered on liver sections derived from 30-mo-old FR rats. In contrast, strong hybridization signals showing a localized distribution were detected on liver sections obtained from 30-mo-old AL rats. Histologic examination of cryostat sections also revealed a massive accumulation of lipid droplets in the liver of 30-mo-old AL rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Proteoglycan metabolism of equine articular cartilage and its modulation by insulin-like growth factors.

The effect of human recombinant insulin-like growth factor 1 (rhIGF-1) on proteoglycan (PG) metabolism of full thickness equine articular cartilage explants was investigated. PG synthesis was stimulated at all ages, but higher concentrations of rhIGF-1 were required for maximal stimulation of adult cartilage. There were no changes in the hydrodynamic size, electrophoretic heterogeneity or composition of proteoglycans isolated from rhIGF-1-stimulated cartilage. rhIGF-1 reduced the rate of turnover of both newly synthesized and endogenous proteoglycans in all ages of cartilage investigated. The structure of proteoglycan fragments retained within the matrix and those released into the culture medium was unaffected by IGF-1 stimulation, suggesting that this peptide is a key regulator of the proteoglycan composition of equine articular cartilage extracellular matrix.

Aging↗

The event-related P300 potential approach to cognitive functions of nondemented patients with cerebral and peripheral arteriosclerosis.

OBJECTIVES: To detect subtle cognitive dysfunction in non-demented patients with either cerebral (cAD) or peripheral (pAD) arteriosclerotic disease, and to evaluate in these patients the effects on cognitive functions of carotid endarterectomy and bypass surgery, respectively. DESIGN: Case-control study. SETTING: Tertiary care referral center. PARTICIPANTS: Eighty consecutive patients with moderate to high-grade stenosis of the internal carotid artery (ICA) (mean age +/- SD, 62 +/- 8 years), 53 patients with stenoses of the peripheral arteries (60 +/- 10 years), and 80 healthy volunteers (58 +/- 15 years) enrolled in a study on healthy aging. Cerebral and peripheral arteriosclerotic disease was verified by digital subtraction angiography, and all patients were screened for confounding effects of concomitant diseases. MAIN OUTCOME MEASURES: Cognitive functions by event-related visual P300 potentials. RESULTS: Patients with cAD showed prolonged P300 latencies and reduced P300 amplitudes, whereas pAD patients had reduced P300 amplitudes only. On an individual scale, 25% of cAD patients, but only 6% of pAD patients, revealed P300 abnormalities. In the cAD, but not in the pAD patients, the P300 latencies were especially prolonged in the older patients, but other factors such as sex, cerebral symptoms, degree of ICA stenosis, and premorbid intelligence did not play any role in either group. Within 1 to 2 weeks of surgery, the P300 latencies shortened in both cAD and pAD patients with high initial values. CONCLUSIONS: As demonstrated by P300 potentials, even nondemented arteriosclerotic patients reveal signs of subtle cognitive dysfunction affecting especially the older cAD patient. In the short-term, carotid endarterectomy presumably improves cognitive functions unspecifically in nondemented patients with a higher initial degree of P300 abnormality.

Adult↗

Fibrin degeneration product concentrations (D-dimers) in the course of ageing.

D-dimers, cross-linked fibrin split products, have been found to be an indicator of thromboembolic disease and may predict, as fibrinogen or other factors of hemostasis, a higher risk of cerebro- and cardiovascular diseases. D-dimers rose with advancing age in healthy elderly subjects and reached values well above the upper limit of the normal test values. The increase is considered to be the result of several causes, i.e. higher fibrinogen concentrations in the elderly, a slower urinary excretion, more frequent fibrin generation, (occult) diseases, risk factors, inflammatory reactions and degenerative vascular damage. In the elderly, moderately elevated D-dimers are therefore an unspecific finding. The specificity of the D-dimer test for diagnosing thromboembolic diseases can be expected to be lower than in young subjects.

Adolescent↗

Influence of age, treadmill running, and food restriction on plasma fibrinogen concentration and expression of gamma chain mRNA in female Sprague-Dawley rats.

Plasma fibrinogen concentration and expression of mRNA encoding the gamma-chain of fibrinogen were determined in female Sprague-Dawley rats aged 10, 21 and 30 months. Both parameters increased significantly with age in a parallel fashion. Food restriction was able to reduce the age-dependent increase of both plasma concentration and gene expression to levels below young controls. On the other hand, long-term treadmill running failed to influence the plasma fibrinogen concentration. From these results we conclude that the plasma fibrinogen concentration increases with age due to an increased fibrinogen biosynthesis.

Aging↗

Palliative therapies in elderly cancer patients.

Palliative therapy in elderly cancer patients deserves special attention because of differences between young and elderly cancer patients. In elderly patients, the treatment produces more adverse effects and the disease is cured less frequently, but the prognosis is usually better than in young patients with cancer. In the elderly population, cancer is seen more frequently than in the young population, yet elderly patients are less frequently included in trials. It is obvious that the results obtained from the treatment of young cancer patients do not necessarily apply to elderly cancer patients. The existing lack of formal data for the management of elderly cancer patients justifies 5 distinctive steps: collection of individual information; review of the available and appropriate knowledge; definition and specification of treatment goals; selection of treatment tools; and assessment of outcome. Following these steps will lead to coordination of oncology and palliative medicine.

Adult↗

CQI: using the Hoshin planning system to design an orientation process.

The Hoshin planning system, developed in Japan after World War II, includes management tools intended specifically for planning new processes. There are seven tools, which can be used individually or in any combination: affinity diagrams, interrelationship digraphs, systematic diagrams, matrix diagrams, process decision program charts, arrow diagrams and prioritization matrices. The radiology department at Carson-Tahoe Hospital formed a CQI team to improve the training of front office clerks. The team quickly discovered that a new orientation program was needed and decided to use Hoshin tools to create one. Using the tools, the team identified and prioritized all relevant factors, described specific tasks needed to complete the planning process and how long each would take, anticipated problems, and assigned areas of responsibility to members of the team. Each time the team grew weary or discouraged, the clarity and organization afforded by the tools helped them feel productive and in control of the process. The team was amazed at the creative ideas they generated through this 3-month-long process. Not only did they develop and implement a new orientation program, they also cultivated a stronger sense of pride and confidence in their work and each other.

Inservice Training↗

Complete primary sequence of equine cartilage link protein deduced from complementary DNA.

Investigation of the structure of the equine articular cartilage link protein (LP) from individuals ranging in age from 1 to 15 years identified 3 distinct isoforms having molecular weights of 46,000, 43,000 and 41,000. The relative amounts of each of the 3 isoforms altered with age. The largest form did not change with age; however, amounts of the Mr 43,000 and 41,000 forms increased with increasing age. The results suggested that an accumulation, in the extracellular matrix of cartilage, of these 2 smaller products may have arisen from proteolytic cleavage. The complete amino acid sequence of the protein core was determined from complementary DNA products prepared by polymerase chain reaction amplification of cartilage LP mRNA. The sequence had 96% similarity with human LP and with that of other species for which the primary structure has been determined. This high degree of sequence conservation and the isoform data indicate that extracellular processing of LP occurs by similar mechanisms in various species. At the transcription level, equine chondrocytes were found to express LP as 2 abundant mRNA of 5.0 and 3.0 kb, and a smaller mRNA of 1.5 kb. Processing of the LP m RNA in horses, thus, appears to be similar to that found in other species investigated, an although multiple transcripts are present, the coding region remains unaltered and only 1 protein product is made.

Aging↗

Fibrinogen and aging.

Plasma fibrinogen concentration is becoming widely accepted as a risk factor for cardio- and cerebrovascular disease. In order to evaluate its age-dependency, plasma fibrinogen and several other blood components were determined in 156 persons (23-96 years). In 116 participants, living on their own and rating themselves as healthy, fibrinogen increased by 26 mg/dL and decade. After exclusion of persons with pathological laboratory findings and risk factors, fibrinogen still rose by 25 mg/dL per decade, thereby reaching concentrations above 320 mg/dL in 81% of those older than 65 years. In prospective studies, these values were found to be associated with an augmented cardio- and cerebrovascular risk. In this investigation, the age-dependent rise of fibrinogen was more pronounced than that of blood glucose or cholesterol. Increasing fibrinogen may reflect a multitude of processes, such as (occult) acute phase reactions, risk factors, subclinical degeneration of vascular endothelium, or a more frequent activation of coagulation and fibrinolysis, with interleukin 6 (IL-6) as a possible mediator.

Adult↗

An investigation of the proteoglycan metabolism of mature equine articular cartilage and its regulation by interleukin-1.

The effect of human recombinant interleukin-1 beta (rhIL-1 beta) on proteoglycan metabolism was investigated in cultures of full thickness explants of articular cartilage from horses 3-21 years of age. Proteoglycan synthesis was inhibited at all ages but no alteration in the hydrodynamic size or electrophoretic heterogeneity was observed in proteoglycan isolated from rhIL-1 beta stimulated cartilage. The sulphation pattern of the newly synthesised proteoglycan molecules was, however, significantly affected by the presence of the peptide regulatory factor. Interleukin-1 had no effect on the rate of turnover of newly synthesised or endogenous proteoglycans in mature equine articular cartilage and did not influence the structure of proteoglycan fragments released into the culture medium. These observations suggest that IL-1, released into synovial fluid during inflammation, may modify the proteoglycan composition of normal equine cartilage not by stimulating catabolic enzymes capable of degrading the resident proteoglycans but by promoting the deposition of a reduced number of newly synthesised proteoglycan molecules of abnormal composition.

Animals↗

[Pharmacokinetics and -dynamics of calcium antagonists in the elderly].

The therapeutic effect of a drug is determined by various properties and parameters. Both dose and pharmacodynamics determine the amount of active agent or its metabolites--and thus their effects--at the site of action. With increasing age, both pharmacodynamics and pharmacokinetics can change. Differences in action in old age may be due to changes in the number and sensitivity of binding sites or to other physiological changes associated with aging. Pharmacokinetics processes (clearance, distribution) are commonly affected by aging. Clinico-pharmacological studies involving calcium antagonists, for example verapamil, diltiazem and nifedipine, have been performed in the elderly by a number of authors.

Age Factors↗