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Biomedical subjects

M J Jackson

Publications and source records attributed to M J Jackson.

At least 217 records · Page 12Linked to original sources

Release of intracellular enzymes from an isolated mammalian skeletal muscle preparation.

An isolated skeletal muscle preparation is described which has been used to study the efflux of enzymes in response to contractile activity, metabolic poisons and detergent treatment. In both fast and slow muscles contractile activity caused a release of lactate dehydrogenase and creatine kinase that reached a peak 1-2 h after the end of stimulation. There was very little release during the 30 min stimulation period whether the muscles were under aerobic or hypoxic conditions. Incubation of the muscles with cyanide and iodoacetate caused a similar delayed release of enzyme. Disruption of cell membranes with detergent treatment caused an entirely different and very rapid pattern of enzyme release. Enzyme release from the fatigued isolated muscle preparations appears to be initiated as a consequence of phosphorylcreatine or ATP depletion. The relevance of this to release of muscle enzymes after activity in vivo is discussed.

Animals↗

Mechanism of action of ATP on intestinal epithelial cells. Cyclic AMP-mediated stimulation of active ion transport.

ATP, ADP and AMP but not adenosine increased cyclic AMP in dispersed enterocytes prepared from guinea pig small intestine. This action of ATP was augmented by IBMX and was reproduced by App(NH)p or App(CH2)p. ATP also increased the formation of cyclic [14C]AMP in enterocytes that had been preincubated with [14C]adenine. Gpp(NH)p and NaF each caused persistent activation of adenylate cyclase in plasma membranes from enterocytes and ATP caused significant augmentation of this persistent activation. In addition to increasing cellular cyclic AMP and augmenting Gpp(NH)p and NaF-stimulated persistent activation of adenylate cyclase, ATP increased the Isc across mounted strips of small intestine and inhibited net absorption of fluid and electrolytes in segments of everted small intestine. These results indicate that intestinal epithelial cells possess a receptor that interacts with ATP and other adenine nucleotides and that receptor occupation by ATP causes activation of adenylate cyclase, increased cyclic AMP and changes in active ion transport across intestinal mucosa.

1-Methyl-3-isobutylxanthine↗

Zinc and carbonic anhydrase III distribution in mammalian muscle.

Zinc and carbonic anhydrase III measurement in human and rat muscle extracts indicate that: 1. About one fifth of zinc in human soleus is associated with carbonic anhydrase III isozyme, and even higher levels of zinc and carbonic anhydrase III are found in rat soleus, where about one half of the zinc is in carbonic anhydrase III. Other muscle was also analysed in a similar way, (see text). Heart is notable in containing lower levels of zinc but negligible carbonic anhydrase III. 2. Treatment of muscle with water or phosphate solutions showed that all the carbonic anhydrase III was water extractable, whereas significant zinc remained bound, but was partially extractable by phosphate solutions. 3. Dialysis of muscle extracts showed that whilst some zinc was dialysable, there was no significant contribution from the carbonic anhydrase III in the dialysed extract. EDTA enhanced the release of dialysable zinc from muscle extract. These findings are discussed in relation to muscle disease.

Animals↗

Tissue zinc levels as an index of body zinc status.

Dietary depletion of zinc was found to result in a 30% decrease in the total body zinc content of experimental rats when compared with control animals. In the depleted animals there was no decrease in the zinc content of hair, skin, heart or three different skeletal muscles although the levels in plasma, liver, bone, and testes were significantly reduced. The analysis of tissues from three patients suffering from disturbance of zinc metabolism suggest that man reacts to zinc deficiency in a similar way. These findings indicate that for a simple screening test of zinc status, analysis of the plasma zinc concentration remains the single most useful measurement.

Animals↗

Transport of weak bases across rat gastric mucosa in vivo and in vitro.

The transport of weak bases (pKa values 1.4 through 10.3) across in vitro and in vivo preparations of rat gastric mucosa have been compared. Asymmetric movements were observed in all cases, and the in vitro and in vivo data showed similar profiles of relation between the degrees of asymmetry and the pKa values of transported compounds. These profiles could be described by an equation based on a three-compartment model system, but it was necessary to postulate two such systems in parallel to give a satisfactory fit to the full range of pKa values tested. One system (I) is analogous to that described previously in small intestine. The properties of this system [(Pi/Pni)a = 2.5 x 10(-3), (Pi/Pni)b = 7.0 x 10(-1)] suggested that the intermediate compartment is a subepithelial extracellular compartment in which an alkaline pH is maintained [pHx = 8.5]. The second system (II) is the opposite polarity [(Pi/Pni)a = 1 x 10(0), (Pi/Pni)b = 3 x 10(-1)], and this system may be represented by the acidic lumen of the gastric tube [pHx = 2.0]. The principal differences between the in vivo and in vitro data could be ascribed to poor stirring of the luminal bulk phase in the in vivo situation. It was concluded that the determinants of weak base transport identified in studies with in vitro preparations are pertinent to the absorptive and secretory processes that occur in the intact stomach.

Animals↗

Weak-acid transport in the small intestine: discrimination in the lamina propria.

Studies on the intestinal transport of weak acids suggest that the subepithelial tissues exhibit a modest, but significant, ability to discriminate between the ionized and nonionized forms. This suggestion has been tested directly in experiments using an in vitro preparation of rat small intestine from which the epithelial cells were removed, but in which the structural and functional integrity of the subepithelial tissues was maintained. Studies on the effects of potential difference on the fluxes of weak acids in this preparation showed that the ratio of permeabilities for the ionized and nonionized species (Pi/Pni) was indeed less than one, and of a magnitude comparable to the value suggested by analysis of transport in the intact tissue. (Pi/Pni) for the subepithelial tissue decreased as pH was increased, and the discriminatory properties of the tissue were abolished [(Pi/Pni)=1] on treatment with the cationic macromolecule polyethyleneimine (PEI). These observations suggested that the discriminatory properties of the subepithelial tissues were determined by fixed anionic sites, and morphological studies with PEI indicated that such sites were concentrated in the region of the basement membrane.

Animals↗

Zinc absorption in the rat.

1. A method of studying zinc absorption in rats has been developed in which binding of radioactive Zn to the intestinal mucosa and absorption into the carcass was determined at different times after administration by stomach tube. 2. This technique has been used to evaluate different hypotheses concerning the control of Zn absorption and to examine the processes by which this occurs. 3. The proportion of radioactive Zn absorbed into the carcass was found to be dependent on the Zn status of the animals but that found within the small intestinal wall was independent of this, indicating the existence of two mechanisms of Zn absorption. 4. One of these two mechanisms has been shown to be induced by a low dietary Zn content while the other was shown to be insensitive to this. This latter mechanism predominated in rats of normal dietary Zn, status and a study of the characteristics of this process indicated that the quantity of Zn absorbed was proportional to the dietary Zn content over the normal range of intake. This implies that normally Zn homeostasis in rats is achieved through variations in Zn excretion. The additional mechanism of Zn absorption only becomes fully active at levels of dietary Zn below 0.24 MUMOL/g diet.

Animals↗

A severe 'stasis eczema', associated with low plasma zinc, treated successfully with oral zinc.

We describe a case of non-ulcerating severe stasis eczema in an elderly female associated with a low plasma zinc and which responded to treatment with oral supplements. The dermatological changes were not accompanied by oedema and were most marked over the lower legs and ankles, with patchy erythematous lesions extending to the inner thighs, over the dorsal surface of both hands and the forearms. There was some excoriation and a degree of lichenification. These lesions were intensely pruritic and resolved almost completely following treatment with oral zinc sulphate (220 mg daily) on two separate occasions.. Histological appearances of biopsy material included those of stasis eczema but there was also a marked degree of parakeratosis. The cause of the low plasma zinc was not identified.

Aged↗

Cellular mechanisms of ion transport associated with osmotic gradients in rat small intestine.

1. The electrical potential difference, short-circuit current, tissue conductance, and fluxes of sodium and chloride were measured in rat small intestine in an in vitro chamber preparation in the presence and absence of 100 mM-mannitol on either the mucosal or serosal surface. 2. Mucosal mannitol generally decreased potential difference, short-circuit current, and tissue conductance while serosal mannitol increased the electrical variables. 3. Mucosal mannitol decreased unidirectional movement of sodium and chloride but did not change the net transport of these ions. The change in short-circuit current was therefore ascribed to changes in fluxes of ions other than sodium and chloride. 4. Serosal mannitol increased the unidirectional fluxes of sodium, but not the new transport of this ion. The transport of chloride increased only in the serosal to mucosal direction yielding a net secretion of chloride equal to the change in short-circuit current. 5. The changes in potential difference and short-circuit current caused by mucosal mannitol were dependent on the presence of sodium. The changes due to serosal mannitol were dependent on both sodium and chloride. 6. Changes in undirectional transport of ions, small non-electrolytes, and water due to an osmotic gradient were attributed to changes in the dimension of the lateral intercellular spaces observed in earlier studies. 7. No evidence suggesting that the electrical changes due to the mannitol gradients could be attributed to diffusive or convective flows of fluid, but instead the changes were ascribed to perturbations in the cellular transport mechanisms.

Animals↗

Weak electrolyte permeation in alimentary epithelia.

The potential significance of ionized species in weak electrolyte absorption or secretion has been reexamined using a mathematical model that represents the epithelium as a system of parallel ion-permeable and ion-impermeable channels. An important determinant of weak electrolyte movement in this system is the ratio of ionized and nonionized permeabilities (Pi/Pni). This variable, which has been termed the discrimination coefficient, interacts with the degree of ionization in determining the contributions of ionized and nonionized species to the transepithelial movement of a weak electrolyte. Calculations based on the model suggest that ionized species may contribute significantly to the absorption or secretion of many common weak electrolytes. It is concluded that the frequently made assumption that ionized species do not contribute significantly to transepithelial movements of weak electrolytes in the alimentary tract is not generally valid. Further work is required to delineate the quantitative determinants of discrimination in alimentary epithelia, and two methods for evaluation of epithelial discrimination coefficients are described.

Absorption↗

Transport mechanisms for narcotics and narcotic antagonists in alimentary epithelia.

A study has been made of the transport of seven morphine analogs across short-circuited preparations of rat gastric mucosa, small intestine and colon in vitro. Net secretory transport of all of the compounds tested was observed in the experiments with stomach. In the intestine the weaker bases were not transported but the more ionized compounds were secreted; in the colon, the stronger bases were transported in the absorptive direction. These transport processes were not dependent on transmural gradients of pH and in some cases the pattern of transport was maintained in the presence of adverse pH gradients. Studies on the effects of concentration and of interactions between concurrently transported compounds provided no evidence for carrier-mediated mechanisms. It was suggested that these observations are explicable in terms of a double membrane system.

Animals↗

Transport of benzylpenicillin in gastrointestinal epithelia of the rat in vitro.

A steady-state net absorptive movement of benzylpenicillin across rat small intestine was observed in the absence of transmural gradients of electrochemical potential. The transport process was dependent on tissue metabolism and the presence of sodium, but no evidence of a saturable rate-limiting step was observed. Voltage-clamp studies showed that the transintestinal movement of benzylpenicillin varied with the electric potential across the tissue. It was found that a mathematical model based on a series three-compartment system yielded a good quantitative description of benzylpenicillin transport in the short-circuited condition and of the voltage-dependence of the transport process. A net absorptive movement of benzylpenicillin was also observed in studies on rat stomach in vitro, but on the colon a net secretory movement occurred. It was suggested that the gastric and colonic transport processes may be described in terms similar to those of the small intestine and that the variations of the direction of transport reflect differences in the pattern of acid-base metabolism in tissue.

Animals↗

Surgical prosthetic splints as an adjunct in treating facial fractures.

Surgical splints are a valuable adjunct in managing certain mandible and maxillary fractures. Of the various splint materials, acrylic is the easiest, fastest, and least expensive. Acrylic splints are rigid, strong, easily adjusted and repaired, translucent, lightweight, and tolerated well by the oral mucosa. Splints are beneficial not only in the edentulous adult, but also in the child with deciduous dentition and in the patient with a partial dentition. Splints are helpful in managing fractures of the symphysis, parasymphyseal region, body, and alveolar ridges of the mandible, sagittal fractures of the hard palate, and severely comminuted mandible fractures. Construction of acrylic splints is simple and rapid if the surgeon uses the services of a dentist or a dental laboratory.

Acrylates↗