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R J Maxwell

Publications and source records attributed to R J Maxwell.

At least 109 records · Page 6Linked to original sources
PubMed1981

Dry column method for the quantitative extraction and simultaneous class separation of lipids from muscle tissue.

A method for lipid isolation is presented that is alternative to the traditional chloroform/methanol extraction methods. This new method allows lipid isolation by solvent elution of a dry column composed of a tissue sample, anhydrous sodium sulfate, and Celite 545 diatomaceous earth ground together. To isolate total lipids, the dry column is eluted with a mixture of dichloromethane/methanol (90:10, v/v). Alternatively, the lipids may be isolated and simultaneously separated into neutral and polar fractions by a sequential elution procedure; neutral lipids free of polar lipids are eluted first with dichloromethane, followed by elution of polar lipids with the dichloromethane/methanol (90:10) mixture. The two dry column methods-isocratic or sequential elution-were compared with the traditional chloroform/methanol methods by gravimetric, thin layer chromatographic and phosphorus analyses.

Animals↗
PubMed1980

Determination of total fat in meat and meat products by a rapid, dry column method.

A rapid, dry column method is proposed for determining fat in meat and meat products. Unlike AOAC procedures 24.005 and 24.006, this procedure measures total rather than crude fat. A 5 g sample is blended with anhydrous sodium sulfate in a mortar and is then reduced to a fine powder with Celite 545. The fat is eluted on a glass column, using dichloromethane-methanol (9+1). Solvent is removed from the eluate, and the resulting residue is weighed to calculate total fat of the sample. A determination takes 2.5 hr or less. Fat levels ranged from 7 to 90% in 15 meat samples. Quadruplicate determinations by this method and duplicate determinations by 24.005(a) yielded overall means of 29.9 and 29.3% fat, respectively. Repeatability was 0.3% fat. The 0.6% mean difference is significant (P = 0.05) and represents a more complete extraction of polar lipids by the proposed method. Results of determinations by this method are compared with results by an accepted but laborious chloroform/methanol procedure for total fat recovery. Overall means and standard deviations of replicate determinations on 4 meats containing 4-30% fat were 12.8 +/- 0.1 with this method and 12.7 +/- 0.1 with the reference method.

Animals↗
PubMed1979

Doomed status: observations on the segregation of impaired old people.

The antecedents and consequences of the segregation of severely impaired old people within institutions is a problem that deserves more research attention than it has so far received. Given that such segregation exists and that it has some positive benefits for both staff and residents in homes for the aged, it is proposed that there exist among administration and ward staff impulses to avoid the mentally impaired aged, and that these impulses are part of a more general phylogenetic residue. Many animals show avoidance reactions in the presence of strange objects or strange conspecific individuals, and the more advanced the animal, the more disturbed he seems to be. It is suggested that the segregation of impaired old people consigns them to a doomed role, rather than a sick role, and that the process operates largely through the impact of the activation of the emergency team and the withdrawal of community support and can result in the death of the individual, partly by means of suggestion. Examples of sudden unexplained deaths are drawn from material on simpler societies.

Aged↗
PubMed1979

Larger ear replica for KEMAR manikin.

A larger external ear replica for use on a KEMAR manikin has been developed to meet the needs of hearing aid designers and other manikin users. The ear was selected from the 24 subject sample used by Burkhard and Sachs (1975) as the basis for the original ear development. Ear dimensions were chosen to be two standard deviations larger than the existing ear. A mirroring technique was used to give right and left ears with nearly identical properties. Responses of the manikin with the new ears are given and compared with responses with the original ears.

Ear, External↗
PubMed1977

Biogenesis of mitochondria 48: mikamycin resistance in Saccharomyces cerevisiae--a mitochondrial mutation conferring resistance to an antimycin A-like contaminant in mikamycin.

Commercial preparations of mikamycin have been shown to act as both inhibitors of mitochondrial protein synthesis and respiration. These preparations are shown to consist of two major streptogramin components (mikamycin A and mikamycin B) and a number of minor components. The major streptogramin components which inhibit mitochondrial protein synthesis in vitro are without effect in vivo due to whole cell impermeability to these compounds. A minor antimycin A-like component is the active compound in mikamycin preparations which inhibits growth of yeast cells on ethanol. The site of this inhibition is at the level of respiratory Comples III. The mitochondrial [mik 1-r] mutation confers resistance to this minor growth inhibitory component and cross resistance to antimycin A. For clarity the designation mik 1 has therefore been renamed ana 1 to denote the mitochondrial determinant conferring resistance to antimycin A. Genetic and physical mapping studies localise the ana 1 determinant in the region of mitochondrial DNA specifying cytochrome b. It is proposed that the ana 1 locus is part of a gene specifying a membrane component of Complex III.

Anti-Bacterial Agents↗
PubMedDate not supplied

Effect of immobilization on the penicillin binding and reactivity properties of DD-peptidase from Streptomyces R61.

An affinity gel matrix containing an enzyme (DD-peptidase) with specific beta-lactam binding properties was characterized with respect to its binding and reactivity behavior with penicillin. The data show that immobilization of DDP by reaction with the enzymes susceptible amino groups resulted in changes in catalytic activity on a tripeptide substrate, penicillin binding efficiency and pH stability of drug binding. Properties unaffected by immobilization were the drug-enzyme complex stability, binding reaction mechanism, drug selectivity and method of complex desorption. The affinity of DDP for penicillin-G was investigated by surface plasmon resonance. These characteristics were compared with those of the soluble enzyme. Conditions for elution of the bound drug were determined and a method for immobilizing Streptomyces DDP by which its binding site structure is sustained was also evaluated.

Carbon Radioisotopes↗
PubMedDate not supplied

Genetic programming for classification and feature selection: analysis of 1H nuclear magnetic resonance spectra from human brain tumour biopsies.

Genetic programming (GP) is used to classify tumours based on 1H nuclear magnetic resonance (NMR) spectra of biopsy extracts. Analysis of such data would ideally give not only a classification result but also indicate which parts of the spectra are driving the classification (i.e. feature selection). Experiments on a database of variables derived from 1H NMR spectra from human brain tumour extracts (n = 75) are reported, showing GP's classification abilities and comparing them with that of a neural network. GP successfully classified the data into meningioma and non-meningioma classes. The advantage over the neural network method was that it made use of simple combinations of a small group of metabolites, in particular glutamine, glutamate and alanine. This may help in the choice of the most informative NMR spectroscopy methods for future non-invasive studies in patients.

Artificial Intelligence↗
PubMedDate not supplied

Classification of tumour 1H NMR spectra by pattern recognition.

1H spectra of tumours or normal tissues, which include signals from all hydrogen-containing metabolites, are too complex for the human eye to interpret. We have studied 58 1H spectra from perchloric acid extracts of three normal tissues (liver, kidney and spleen) and five rat tumours (GH3 pituitary, fibrosarcoma, Morris Hepatomas 7777 and 9618a and Walker carcinosarcoma). Instead of editing them or quantifying individual metabolites, we have used statistical pattern recognition techniques to classify them into groups. This automatic, objective method differentiated spectra from normal and malignant rat tissue biopsies, and from different types of cancer. It seems likely that this technique can be applied to human tissues and thus used for cancer diagnosis.

Animals↗
PubMedDate not supplied

Non-invasive MRS in new anticancer drug development.

In the rational development of anticancer drugs it is important to employ all the available pharmacological information. Early clinical trials provide an opportunity for hypothesis testing. MRS techniques have the potential to provide valuable data on the preclinical and clinical pharmacokinetics and pharmacodynamics of drugs non-invasively. Here we illustrate advantages and pitfalls of MRS using studies of two fluorine-containing cancer drugs: a beta,beta-difluoro analogue of the alkylating agent chlorambucil and a fluorinated derivative of the nitroimidazole misonidazole, Ro 07-0741. Limitations include signal quenching via protein binding and inadequate sensitivity for more potent drugs like beta,beta-difluorochlorambucil; but fluoromisonidazole was shown to accumulate in tumours and shows promise as a chemical probe for tumour hypoxia, detectable by 19F MRS.

Animals↗
PubMedDate not supplied

In vivo and ex vivo magnetic resonance spectroscopy as applied to pharmacokinetic studies with anticancer agents: a review.

The potential role of MRS in studying the pharmacokinetics of anticancer drugs is reviewed. In vivo and ex vivo MRS has been used extensively in studies with fluoropyrimidines. Results from preclinical models have demonstrated that biochemical modulation of 5-fluorouracil metabolism can be demonstrated by MRS. The more general potential of MRS is illustrated by studies with the antifolate CB3988 (C2-desamino-C2-methyl-N10-propargyl-2'-trifluoromethyl-5,8-dideazafolic acid). Studies in mice and rats have shown that hepatobiliary clearance and renal elimination can be measured non-invasively by MRS. Comparison of half-lives derived from MRS and high performance liquid chromatography data gave reasonable agreement. In addition, MRI was used to localize drug-derived material within the abdominal cavity. The application of ex vivo MRS is illustrated by studies on the urinary excretion of platinum complexes. 1H-MRS has been used to demonstrate the presence of the cyclobutanedicarboxylate leaving group, both free and platinum bound, in the urine of patients treated with carboplatin. With iproplatin 195Pt NMR has been used to demonstrate in vivo reduction of this Pt(IV) complex to Pt(II) complexes. Finally, the application of MRS to the study of the molecular pharmacology of alkylating agents (a nitrogen mustard and N-methyl-N-nitrosourea) is discussed.

Alkylating Agents↗
PubMedDate not supplied

An assessment of 31P MRS as a method of measuring pH in rat tumours.

The contribution of extracellular components to the measurement of pHMRS of a variety of rat tumours (nitrosomethyl urea induced mammary tumours, GH3 prolactinomas, Hepatoma 9618a, UA hepatomas and Walker sarcomas) has been assessed. Acid extractable P(i) was between 2.6 and 12.5 mumol/G wet wt depending on tumour type, and of this 53 +/- 4.8% (mean +/- SEM) was MRS-visible. The P(i) content of tumour exudate was 2-3 mM, of interstitial fluid (sampled from a micropore chamber incorporated within a tumour) 1.7 mM, and of blood plasma 1.95 mM. The mean extracellular volumes of the tumours, measured by distribution of 3H2O and [14C]inulin, were 49-55% depending on tumour type and were at least twice that found in normal liver. Calculations suggested that for most tumours with an extracellular volume not exceeding 55%, at least 65% of the P(i)(MRS) signal was derived from intracellular P(i), and thus that pH(MRS) is a measure of pHi. For each tumour type, pHMRS was measured both in 'pulse-acquire' mode at 1.9 T which may include signals from surrounding tissue, and in localized mode at 4.7 T where the signal came uniquely from tumour tissue. The steady state pHMRS was either neutral or on the alkaline side of neutrality (pH range 7.04-7.37). Raised lactate content and decreased buffering capacity (compared to normal tissues) accompanied these neutral to alkaline pH values.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Pattern recognition of 31P magnetic resonance spectroscopy tumour spectra obtained in vivo.

Pattern recognition has been applied to the analysis of in vivo 31P NMR spectra. Using four different classes of tumour and three types of normal tissue, cluster analysis and artificial neural networks were successful in separating and classifying the majority of samples analysed. Although the phosphomonoester and P(i) regions appeared to be the most important spectral features, data representing the entire 31P spectrum were required for best separation of the tumour and tissue classes.

Animals↗
PubMedDate not supplied

Applications of magnetic resonance in model systems: cancer therapeutics.

The lack of information regarding the metabolism and pathophysiology of individual tumors limits, in part, both the development of new anti-cancer therapies and the optimal implementation of currently available treatments. Magnetic resonance [MR, including magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and electron paramagnetic resonance (EPR)] provides a powerful tool to assess many aspects of tumor metabolism and pathophysiology. Moreover, since this information can be obtained nondestructively, pre-clinical results from cellular or animal models are often easily translated into the clinic. This review presents selected examples of how MR has been used to identify metabolic changes associated with apoptosis, detect therapeutic response prior to a change in tumor volume, optimize the combination of metabolic inhibitors with chemotherapy and/or radiation, characterize and exploit the influence of tumor pH on the effectiveness of chemotherapy, characterize tumor reoxygenation and the effects of modifiers of tumor oxygenation in individual tumors, image transgene expression and assess the efficacy of gene therapy. These examples provide an overview of several of the areas in which cellular and animal model studies using MR have contributed to our understanding of the effects of treatment on tumor metabolism and pathophysiology and the importance of tumor metabolism and pathophysiology as determinants of therapeutic response.

Animals↗
PubMedDate not supplied

From hydralazine to CGRP to man?

Attempts to selectively reduce tumour blood flow have, in the past, concentrated on the use of hydralazine. However, although this vasodilator can be highly effective in experimental animals, it is only at such high concentration as to result in a severe and clinically unacceptable reduction in systemic blood pressure. At clinically acceptable levels, the drug appears to produce a small increase in tumour blood flow. We have used the techniques of magnetic resonance spectroscopy as indicators of metabolism and blood flow in a search for vasoactive drugs that would produce an effective reduction in tumour blood flow without causing severe hypotension or other serious side effects. Single injections of either prazosin or CGRP are shown to be substantially more effective than hydralazine in causing a reduction in tumour blood flow without massive reduction in blood pressure. Even more effective was CGRP given by continuous infusion. In this case a three-fold reduction in tumour blood flow could be obtained with a reduction of only 15-20% in systemic blood pressure. All these studies, however, have been made with transplanted animal tumours. Using high-dose hydralazine and primary tumours that were either radiation or chemically induced, we obtained a success rate of only about a 35% in causing selective reduction in blood flow. In contrast, in a transplanted tumour line derived from one of the non-responding radiation-induced primary lesions, the success rate was about 95%, consistent with the majority of animal studies using transplanted tumours.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

ESCA depth profiling studies of borosilicate glass containers.

This article discusses the results of studies that utilized Electron Spectroscopy for Chemical Analysis (ESCA), a surface analytical technique, in conjunction with Ar+ ion milling, a method of depth profiling, to examine some borosilicate glass containers. The ESCA depth profiling experiments involved several elemental analyses (Na, Ba, O, B, Si, Al, and C) for both the product-contact surface and various depths (0.01-0.30 micron) beneath the surface. Untreated vials, (NH4)2SO4 treated vials, and (NH4)2SO4 treated ampoules were analyzed in this study. The experiments included both unprocessed and processed containers as well as vials and ampoules that were exposed to various aqueous media (H2O, pH = 8 buffer, and pH = 10 buffer) for congruent to 6 months at room temperature. Assuming the samples were representative of most (NH4)2SO4 treated and untreated containers, the results indicate that ESCA depth profiling studies can distinguish an (NH4)2SO4 treated container from an untreated one for unprocessed and processed containers as well as containers that are exposed to aqueous media. In general, treated samples were unaffected by processing and long-term, room-temperature exposure to H2O or a pH = 8 buffer. In contrast, washing and sterilizing operations led to significant changes in the surface and near near surface composition of untreated containers, and six-month, room-temperature exposure to H2O or a pH = 8 buffer resulted in some additional changes. Also, the data indicated glass dissolution had occurred for both treated and untreated containers that had been processed and exposed to pH = 10 media. Finally, the results suggested that significant differences in the surface/near surface composition can lead to significant differences in the extractable behavior of borosilicate glass containers.

Argon↗