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D Platt

Publications and source records attributed to D Platt.

At least 73 records · Page 4Linked to original sources
PubMed1993

Structure-function relationship of a recombinant human galactoside-binding protein.

A galactoside-binding lectin (hL-31) containing a collagen-like sequence was identified in human tumor cells. It was found to be the homologue of the IgE-binding protein, the macrophage cell-surface Mac-2 antigen, and the murine CBP35, RL-29, and mL-34 lectins. Here we report on the expression in Escherichia coli and functional analysis of recombinant hL-31 (rhL-31). The rhL-31 was purified in one step through an asialofetuin affinity column. The rhL-31 was reactive to anti-lectin antibodies and retained its lactose-dependent hemagglutination of trypsin-treated glutaraldehyde-fixed rabbit erythrocytes. The rhL-31 elutes from an affinity column as a 31-kDa monomer and undergoes homodimerization at relatively high protein concentrations, comparable to those used to mediate hemagglutination. Electron microscopy showed that the rhL-31 appears as a Y-shaped structure. Lactoperoxidase-catalyzed iodination of murine tumor cell-surface proteins followed by collagenase treatment revealed that the lectin is probably a peripheral membrane protein whereby both the amino and the carboxy termini are exposed on the outer cell membrane. These results point to the membrane disposition and orientation of the lectin and suggest a mechanism for a structure-function relationship of lectin activity.

Amino Acid Sequence↗
PubMed1993

[Peculiarities of drug therapy in the elderly].

OBJECTIVES: Old people (over 70) are often treated with drugs. With respect to the indications for drug treatment, pharmacokinetics and pharmacodynamics, as well as undesired adverse drug reactions, there are a number of points peculiar to old age. MAJOR INFORMATION: The usefulness of so-called geriatric drugs in the treatment of age-associated disorders continues to be controversial. The proportionate reduction in fat-free body mass leads to a change in drug distribution volumes, which can have an influence on the half-life of the substances concerned. While the perfusion of the liver and kidneys diminishes, effects on drug metabolism tend to be due to disease rather than aging processes. In old age, the incidence of side effects of medication is increased-the main cause of this, however, being the greater number of medicaments taken simultaneously, and not age in itself. A generally passive attitude towards treatment of the old patient is, however, not justified. CONCLUSIONS: In old age, too, the general rule applies: as few drugs as possible, but then used selectively. Therapeutic regimens should be regularly checked and the results of treatment critically evaluated; a specific search should be made for adverse reactions.

Aged↗
PubMed1993

Effects of exercise on myocardial adenylate cyclase and Gi alpha expression in senescence.

The present study investigated the influence of physical training on alterations leading to reduced adenosine 3',5'-cyclic monophosphate (cAMP) formation in aged myocardium. Senescent (28-mo-old) rats underwent a moderate treadmill exercise program and were compared with sedentary controls. In myocardial membranes from aged rats, isoprenaline-stimulated adenylate cyclase activity (AC) was reduced compared with that in young animals and was accompanied by an increase of pertussis toxin substrates (17.5%) and an increased amount of immunodetectable inhibitory guanine nucleotide-binding proteins (Gi alpha; 72%). Physical training reduced the amount of Gi alpha proteins (30-35%) in young and old animals and enhanced only isoprenaline-stimulated AC in the aged rats, and basal and 5'-guanylylimidodiphosphate [Gpp(NH)p]- as well as isoprenaline-stimulated AC in young rats. Physical training or aging had no effect on the number of beta-adrenoceptors or m-cholinoceptors or on forskolin-stimulated AC in either group. The amount of immunodetectable stimulatory guanine nucleotide-binding proteins (Gs alpha) using an antiserum raised against the COOH-terminal peptide of Gs alpha (RMHLRQYELL) was unchanged in either condition. It is concluded that enhanced Gi alpha expression might be one mechanism leading to depressed cAMP formation in aged myocardium. Depressed AC and increased Gi alpha can be partially reversed by physical training, especially in young myocardium. Gi alpha might serve as a regulator of cardiac AC in a variety of physiological and pathophysiological situations in the absence of beta-adrenoceptor changes.

Adenylate Cyclase Toxin↗
PubMed1993

The event-related P300 potential analysis of cognitive human brain aging: a review.

Event-related P300 potentials are closely reflecting cognitive functions such as stimulus evaluation time (P300 latency) and task relevance (P300 amplitude). Hence, both their potential clinical application for detecting slight cognitive disturbances and an increasing interest in the aging of cognitive human brain functions resulted in a growing number of studies on age-related P300 changes. Although there are converging lines of evidence that aging results in prolongations of P300 latencies, reductions of P300 amplitudes and a more equipotential P300 scalp distribution, the amount of these changes and the best fit for the P300-age interactions, respectively, remain still controversial. In general, these P300 alterations obviously reflect only minor cognitive changes during normal aging. For their clinical application, however, it is necessary to obtain an age-matched normative database. Furthermore, the increased P300 variability in the elderly has to be reduced--as far as possible--by appropriate simple P300 paradigms which should be preferentially applied in longitudinal analyses to differentiate normal from pathological aging of cognitive functions. Finally, additional cross-correlational analyses between the P300 and morphological as well as neurobiochemical data are needed. By these means, our knowledge about age-related changes of cognitive brain functions should be considerably enlarged.

Adolescent↗
PubMed1992

High-performance liquid chromatographic method for the determination of alprazolam in plasma using the column-switching technique.

A reversed-phase high-performance liquid chromatographic method is described for the quantitative determination of alprazolam in the plasma of geriatric patients in the presence of 4-hydroxyalprazolam, alpha-hydroxyalprazolam, bromazepam, oxazepam, lorazepam, clobazam, desmethylclobazam, diazepam and desmethyldiazepam. The procedure is based on the enrichment of alprazolam on a PRP-1 pre-column, followed by the transfer of the compound in a forflush mode to the analytical column. Alprazolam can be quantified reliably down to a minimum concentration of 1 ng/ml of plasma.

Aged↗
PubMed1992

[Intensive care medicine in advanced age from the viewpoint of the internist].

BASIC REMARKS: The percentage of elderly patients in ICUs has doubled over the last 20 years; in the case of the over-seventy-year-olds it is at present about 30%. MAJOR DISCUSSION POINTS: The mean length of stay in the ICU and hospital, and the average costs incurred, are not significantly higher in the case of the elderly. With increasing age, mortality rises steadily, being about 20% for geriatric patients in the ICU, 37% in hospital, and 52, cumulative, after one year. Nevertheless, elderly patients benefit in particular from intensive care. Their relative mortality rate in comparison with the general population of the same age is only slightly elevated. In view of the very high mortality following cardiopulmonary resuscitation of geriatric patients, it would make good sense to limit the indication in particular cases. Quality of life after discharge from ICU care and thereafter is appreciably lower in comparison with younger patients, but acceptance of intensive care is very good among elderly patients, too. As a study we carried out in our "toxicological" ICU showed, prognostic scoring systems for the elderly are not particularly reliable, and the geriatric skills and the knowledge of the physician weigh heavier. CONCLUSIONS: We consider intensive care in the elderly to be both beneficial and efficient, for despite an increase in the mortality rate, a satisfactory quality of life is achieved.

Aged↗
PubMed1992

Dynamics of gene expression for microtubule-associated protein MAP1B, embryonic alpha-tubulin and late neural beta-tubulin mRNAs in the hippocampus of aged rats.

In the present study we characterized the developmental changes in the prevalence of mRNA coding for microtubule-associated protein, MAP1B, embryonic alpha-tubulin and late neural beta-tubulin in rat hippocampus and forebrain from 1 to 720 days of age using RNA gel-blot analysis. We find that (i) the microtubule-associated protein, MAP1B, signal was relatively abundant at early postnatal stages when compared with mature animals. The hybridization signal in the 24-month-old rats was was approximately 1.7 times that observed in 6-month-old rats. (ii) Embryonic alpha-tubulin and late neural beta-tubulin were differentially regulated during rat brain development. This regulation is characterized by a dramatic decrease in the amount of alpha-tubulin after day-1 and a coincident increase in the production of late neural beta-tubulin. Both messages became stabilized at moderate levels during the subsequent developmental stages. However, the averaged signal for beta-tubulin was then approximately 1.8-fold increased in 24- vs. 6-month-old rats. These results are consistent with hypothesis of an age-associated increase in reactive synaptogenesis where the healthy neurons sprout new connections to compensate for neuronal loss occurring in neighboring neurons.

Aging↗
PubMed1992

Modulation of the lung colonization of B16-F1 melanoma cells by citrus pectin.

CONTEXT: Studies have shown that the galactoside-containing simple sugars and anti-galactoside-binding lectin antibodies may affect experimental tumor cell metastasis. However, the limited number of reagents used thus far necessitate further observations. PURPOSE: Natural citrus pectin (CP) and pH-modified CP (MCP), rich in galactose residues, were used to study the involvement of carbohydrates containing galactoside residues in cellular interaction in vitro and in lung colonization in vivo of B16-F1 melanoma cells. METHODS: B16-F1 melanoma cells were incubated with various concentrations of CP and MCP. Their ability to form homotypic aggregation in vitro and tumor lung colonization in vivo in 8-week-old female C57BL/6 mice was then analyzed. RESULTS: The CP binds to the surface of B16-F1 melanoma cells; this binding can be inhibited by lactose at a concentration of 0.15 M. Intravenous injection of the murine B16-F1 melanoma cells with the natural CP resulted in a significant increase (up to threefold) in the appearance of tumor colonies in the lung and in increased homotypic aggregation properties of the cells, while injection of MCP significantly decreased B16-F1 experimental metastasis (greater than 90%). CONCLUSIONS: Tumor galactoside-binding proteins mediate cellular recognition by linking oligosaccharides with terminal D-galactoside residues on adjacent cells. Successful interference with such a process with MCP may lead to a reduced ability to form tumor cell emboli and metastasis. IMPLICATIONS: These findings imply that the galactose-containing carbohydrate side chains of CP might mimic or compete with the natural ligand(s) of the tumor galactoside-binding protein (gal-lectin) and thus affect cellular interactions relevant for metastasis.

Animals↗
PubMed1992

The influence of hydrochlorothiazide on the pharmacokinetics of enalapril in elderly patients.

In a randomized, cross-over, single-dose study of 19 elderly hypertensive patients (aged 62-84 y, SBP greater than 160 mmHg, DBP greater than 100 mmHg, creatinine clearance 11-93 ml.min-1) we have studied the pharmacokinetics of the angiotensin converting enzyme (ACE) inhibitor enalapril after a single oral dose of either 10 mg enalapril or 10 mg enalapril + 25 mg hydrochlorothiazide. The pharmacokinetics of enalapril were unaffected by hydrochlorothiazide, but there was a significant reduction in renal clearance and a significant increase in AUC(0-24 h) of enalaprilat after hydrochlorothiazide, resulting in higher serum concentrations of the active drug. This was independent of the individual degree of renal impairment and might be due either to an initial reduction of GFR by hydrochlorothiazide or to interference with the tubular secretion of enalaprilat. The relationships between serum enalaprilat and serum ACE activity were similar after both treatments, both consistent with a value for Ki of enalaprilat of about 0.1 nmol.l-1. Thus, serum ACE activity was not affected by hydrochlorothiazide but completely reflected the pharmacokinetics of enalaprilat in both treatments.

Administration, Oral↗
PubMed1992

Decortication and striatal mRNA: increases of mRNA for fibronectin, but not of NCAM or alpha-1 tubulin.

Ipsilateral frontal cortex lesions damaged the corticostriatal input. Northern hybridization analysis showed increases in fibronectin (FN) mRNA, but not changes in mRNA for neural cell adhesion molecule (NCAM), neuro-filament-68 (NF-68) or alpha-tubulin (alpha-1T) 72 h post-lesion. In situ hybridization resolved a different spatial-temporal distribution. The superficial cell layer beneath the wound cavity showed transient elevations of FN mRNA that peaked at 72 h post-lesion. However, in the ipsilateral striatum, FN mRNA was maximal at later times than in the wound cavity, at 240 h post-lesion. Changes in NCAM and alpha-tubulin mRNAs in response to decortication occur only around the wound cavity but not in the deafferentated striatum. The different time courses of mRNA revealed by Northern blot analysis and in situ hybridization are most probably due to contamination of the ipsilateral striatum at dissection with superficial tissue adjacent to the wound cavity. These results suggest that cellular responses to ipsilateral decortication consist of two phases: (i) a wound healing process; and (ii) striatal responses to deafferentation.

Animals↗
PubMed1991

Garlic.

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Aged↗