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Biomedical subjects

A M Gordon

Publications and source records attributed to A M Gordon.

At least 109 records · Page 6Linked to original sources
PubMed1984

Activation of ADP-ribosyltransferase in polyamine-depleted mammalian cells.

Mammalian fibroblasts were cultured in the presence of alpha-methylornithine and/or methylglyoxal bis(guanylhydrazone), which inhibit the synthesis of polyamines. This led to a decrease in the cellular content of the polyamines spermine and spermidine by up to 60% when the cells were grown in the presence of both drugs together. The activity of the chromatin-associated enzyme ADP-ribosyltransferase was enhanced 2-3-fold in the drug-treated cells when measured in cells subsequently rendered permeable to exogenous NAD+, the substrate for the transferase. This is a novel and surprising observation, since the transferase is invariably activated by the addition of polyamines to a suitable incubation system such as permeabilized cells, isolated nuclei or the purified enzyme. We found no evidence that the activation was due to the appearance of DNA strand breaks, by using a variety of procedures including both neutral [the 'nucleoid' technique of Cook & Brazell [(1975) J. Cell Sci. 19, 261-279; (1976) J. Cell Sci. 22, 287-302]] and alkaline sucrose-gradient centrifugation and gel electrophoresis, suggesting that this therefore may not be the only means of regulating the activity of ADP-ribosyltransferase and that polyamines may have a role to play in this regard in vivo.

Adenosine Diphosphate Ribose↗
PubMed1984

Calcium sensitivity is modified by contraction.

This paper summarizes three lines of experimental evidence showing that crossbridge interaction affects calcium sensitivity and probably also affects calcium binding. Evidence is presented that this is a true hysteresis, not just a slow approach to equilibrium. In barnacle single muscle fibers injected with aequorin to monitor intracellular Ca, a long duration stimulus under voltage clamp conditions can produce a long duration calcium transient and force record which both approach steady levels. However, if the stimulus is briefly elevated to transiently produce a higher force early in the contraction, the same steady state Ca level can eventually maintain a higher steady force. Thus Ca sensitivity is modified. In "skinned" barnacle muscle activated by Ca in the presence of buffered Ca, MgATP, and pH, force was measured in split, detergent treated fiber while it was transferred consecutively between solutions which were relaxing, submaximal contracting, maximal contracting, the same submaximal contracting, and finally relaxing. The submaximal contracting solution produced more force when stepping down in Ca concentration (as in relaxation) than when stepping up. Extending the time in the initial submaximal contracting solution did not result in more force. Thus, the force-pCa relationship shows marked hysteresis. The same phenomenon was seen in frog and mammalian muscle fibers. These experiments confirm the findings that contraction modifies Ca sensitivity. In the barnacle single muscle fiber preparation (under both voltage clamp and controlled length conditions), phasic (400 msec) depolarization leads to a calcium transient and a twitch contraction. Releasing the muscle to allow it to shorten rapidly during the declining phase of the calcium transient causes the force to fall and leads to extra Ca in the sarcoplasm. Rapidly stretching the muscle produces the opposite effect. The extra Ca probably comes from a myofilament Ca activating site. Thus, a length change (force change) affects Ca binding.

Aequorin↗
PubMed1984

Muscle calcium transient. Effect of post-stimulus length changes in single fibers.

We examined the effects of post-stimulus length changes on voltage-clamped, aequorin-injected single muscle fibers from the barnacle Balanus nubilus. Extra light (extra calcium) is seen when the fiber is allowed to shorten (a small percentage) during the declining phase of the calcium transient. The opposite is observed when the fiber is stretched. Increasing the extent of shortening increases the amount of extra calcium, as does decreasing the temperature. The extra calcium probably comes from the myofilaments and not from the sarcoplasmic reticulum because (a) there is a strong correlation between the extra calcium and the level of activation; (b) there is a strong correlation between the extra calcium and the amount of force redeveloped after a length change; and (c) the time course of the appearance of the extra calcium is intermediate between that of the free calcium concentration and that of force. We suggest (a) that the calcium binding to the activating myofibrillar proteins is sensitive to muscle length or muscle force, and (b) that there is a pool of bound calcium (activating calcium) that waxes and wanes with a time course intermediate between the free calcium concentration and force.

Animals↗
PubMed1984

Effects of hypertonic solutions on contraction of frog tonic muscle fibers.

The influence of solution hypertonicity on contraction was studied in small bundles of tonic muscle fibers from the iliofibularis muscle of the frog Rana pipiens. Muscles were activated with high-K+ solutions that had osmolalities which were increased with tris(hydroxymethyl)aminomethanepropionate. Peak potassium contracture force decreased monotonically with tonicity and was zero in solutions with 2.5 or 3 times the osmolality of control Ringer. Contracture force at all tonicities studied (less than or equal to 3 X Ringer) was increased by increasing Ca2+ in the media 10-fold (to 20 mM) and/or by adding caffeine (10-20 mM). Nevertheless, this potentiated force also was diminished as tonicity increased. Force of single, mechanically skinned tonic fibers taken from these bundles was activated by Ca2+ over the same concentration range as that of twitch fibers. Moreover, maximal Ca2+-activated force, normalized per cross-sectional area, was similar in skinned tonic and twitch fibers. As was shown previously in twitch fibers, maximal Ca2+-activated force was decreased when ionic strength was increased. These data suggest that, as with twitch fibers, increased tonicity depresses contraction of tonic fibers by increasing the intracellular ionic strength, which in turn inhibits the ability of the contractile apparatus to generate force. Unlike twitch fibers, however, disruption of the excitation-contraction coupling process probably plays a more significant role in the action of hypertonicity on tonic fibers.

Animals↗
PubMed1983

Hysteresis in the force-calcium relation in muscle.

Calcium ions activate muscle contraction. The mechanism depends on the calcium sensitivity of the proteins that regulate contraction. Evidence is presented for the reverse phenomenon, where contraction modulates calcium sensitivity. Increasing the force level increased calcium sensitivity in intact fibers showing that the relation between force and calcium is not unique. A particular calcium concentration can maintain a higher force level than it can create. The results were confirmed in skinned fiber experiments. Transient reduction of the force led to a transient reduction in calcium binding, suggesting a simple mechanism for the hysteresis.

Aequorin↗
PubMed1983

Drugs and delinquency. A ten year follow-up of drug clinic patients.

The addiction and conviction status of 60 male patients who presented to a London drug clinic in 1970 was re-examined 10 years later. Eleven of the patients had died. Three-quarters of the survivors had been abstinent for five years and one quarter were still addicted in this time. Ninety-seven per cent had received a court conviction by 1981 and 83 per cent were convicted during follow-up. Neither hospital treatment, receipt of a clinic prescription nor imprisonment was associated with eventual abstinence. Poor outcome, in combined terms of continued addiction and re-conviction, related to early parental loss, poor academic achievement, conviction before drug use, longer imprisonment and a high conviction rate. Criminality emerges as the predominant and continuing expression of deviancy in these drug clinic patients.

Adult↗
PubMed1982

Nutritional status of Cuban refugees: a field study on the health and nutriture of refugees processed at Opa Locka, Florida.

A field study was conducted to evaluate the nutritional status of newly arrived Cuban refugees. The protocol consisted of socioeconomic, clinical, anthropometric, laboratory, and dietary investigations. A total of 138 refugees was studied at Opa Locka, Fl. The results revealed that 25% of children suffered from malnutrition mostly of the first degree. Second degree malnutrition was rare and cases of third degree malnutrition or infantile kwashiorkor were not found. Obesity was found in 17% of women. Of adults 25% had significantly low adipose tissue stores. Lean body mass was estimated by anthropometry and found to be adequate in 88% of adults. Fifteen percent of adults and 12% of children had anemia. The foods most frequently consumed by the refugees in Cuba were bread, eggs, rice, and garbanzo (chick peas). Fruits and vegetables were not consumed in Cuba daily by the majority of the refugees.

Adolescent↗
PubMed1982

Glucocorticoid-induced atrophy is not due to impaired excitability of rat muscle.

We explored the possibility that glucocorticoid-induced muscle weakness and atrophy resulted from impaired muscle membrane excitability. Male Sprague-Dawley rats received intramuscular injections of dexamethasone, cortisone acetate (equivalent anti-inflammatory doses), or saline for up to 28 days. Temporal patterns of change in muscle mass, twitch and tetanic tension, and membrane potential, cable parameters, and excitability were studied in vitro in the extensor digitorum longus (EDL), soleus (SOL), omohyoid (OMO), caudofemoralis (CF), and the sternomastoid muscles (membrane potential only). the membrane properties of EDL fibers were also studied in vivo (pentobarbital anesthesia). The relative severity of atrophy was OMO greater than CF greater than EDL greater than SOL. Reduction in twitch or tetanic tension never preceded atrophy. The twitch and tetanic tension (per g muscle) increased with glucocorticoid treatment. There were no significant changes in the time course of the twitch or tetanus. Dexamethasone produced more severe atrophy and force reduction than did cortisone acetate. Glucocorticoid treatment produced a depolarization of EDL muscle fibers measured in vitro at 23 degrees C, but this did not appear to be physiologically significant because EDL fibers studied in vivo were not depolarized and had normal action potential amplitudes and thresholds. Glucocorticoid treatment did not change the membrane resistance or capacitance. We conclude that glucocorticoid treatment did not produce muscle weakness by impairing sarcolemmal excitability or excitation-contraction coupling, but that the weakness resulted from muscle atrophy.

Animals↗
PubMed1981

Enteral nutritional support: guidelines for feeding tube selection and placement.

Enteral nutritional support is an important and effective means of providing needed nutrients to patients. Four levels of support can be defined. Most patients are able to eat the diet prescribed for them (level 1), but some require forced nutritional support given by nasogastric (level 2) or nasoenteral (level 3) feeding tubes or by gastroenterostomy (level 4). Selection of the appropriate tube from among the many commercially available types with different features is important to minimize the risk of medical complications. How the tube is placed depends on whether the patient can or will cooperate. Proper positioning of the tube can be checked without an x-ray film by determining if four criteria have been met in a specified order.

Enteral Nutrition↗