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Biomedical subjects

R J Stark

Publications and source records attributed to R J Stark.

At least 37 records · Page 2Linked to original sources
PubMed1982

Ionophore A23187 can mimick the changes in membrane permeability that occur during acetylcholine-stimulation of pancreatic acinar secretion.

Acetylcholine (ACh) released from vagal terminals increases the permeability of the pancreatic acinar membrane to Na+ and Ca2+ ions. In this report, we compare the induced changes in intracellular Na+ and Ca2+ electrode potentials (ENa and ECa) due to ACh-stimulation of acini with those observed during stimulation with the calcium ionophore, A23187, which mimicks the action of ACh on pancreatic secretion. Stimulation with ACh concentrations varying from 10(-8) to 10(-5) M and with A23187 concentrations of 10(-6) and 10(-5) M caused parallel increases in cytosolic Ca2+ and Na+ ([Ca]i, [Na]i). The magnitude of the increases in [Ca]i and [Na]i due to A23187-stimulation further indicate that when presented with a calcium challenge the acinar cells continue to regulate [Ca]i close to physiological levels and suggest that the observed increases in ionized calcium could reflect much larger increases in complexed Ca2+. ACh-stimulation following removal of either extracellular Na+ or Ca2+ ions, eliminated the intracellular increases found when the removed ions is present, but did not affect the increases usually found with the other ion. The independence of the permeability changes to either the presence of Ca2+ or Na+ indicates the ACh-induced currents carried by Na+ and Ca2+ are also independent. The selective translocation of Na+ and Ca2+ during acetylcholine-stimulation in a manner analogous to the changes observed when ionophore A23187 was used as stimulus, indicates the ability of the activated acinar membrane to function as an ionophore.

Acetylcholine↗
PubMed1982

Spinal metastases. A retrospective survey from a general hospital.

One hundred and thirty-one patients presenting to a general hospital with neurological symptoms deriving from spinal metastases were reviewed. The primary site of tumour was the lung in 33 per cent, breast in 28 per cent, other sites in 25 per cent and unknown in 14 per cent. Haematological malignancies were excluded. In 47 per cent of cases the spinal metastasis produced the first evidence of malignant disease. Spinal or radicular pain was the initial complaint in 69 per cent of cases, followed by the appearance of neurological symptoms. Leg weakness usually preceded sphincter disturbance, and was the commonest reason for referral. Spinal cord compression occurred in 106 patients, 10 had compression of conus medullaris or cauda equina and 15 had evidence of radicular compression only. Plain x-rays of the spine were abnormal in 84 per cent of patients, and in 94 per cent of those with carcinoma of the breast. The results of treatment by radiotherapy alone were retrospectively compared with those of surgical decompression (with or without radiotherapy). There was no significant difference between these results for immediate response to treatment or for long-term outcome. The best predictor of outcome was the site of primary tumour. Only 17 per cent of patients with lung cancer responded well to treatment and only 2 per cent were alive one year after treatment; 51 per cent of patients with breast cancer responded well and 36 per cent were alive at one year. Surgical treatment is considered preferable in cases in which the diagnosis of cancer is not proven, when there is a possibility of neural compression by diseased bone rather than soft tumour tissue and when the area has previously been irradiated. These groups accounted for about 60 per cent of our patients. Radiotherapy alone may be preferred if multiple lesions are demonstrated. In other cases a therapeutic decision is required. The availability of neurosurgical and radiotherapeutic facilities will be a factor. There is no clear evidence from our figures or from the literature of a difference between results obtained by radiotherapy alone and those with surgical decompression followed by irradiation. The choice of treatment will depend upon the particular requirements of each individual parent.

Female↗
PubMed1982

Mitochondrial encephalomyopathies: biochemical studies in two cases revealing defects in the respiratory chain.

We describe two patients with mitochondrial myopathies who presented with complex multisystem diseases predominantly affecting the central nervous system. In both cases the disease ran a fluctuating clinical course, eventually leading to profound impairment of intellectual function. In Case 1 dementia was associated with optic atrophy, absent pupillary responses, impaired eye movements and generalized dystonic rigidity without evidence of weakness or loss of muscle bulk. In Case 2 myoclonus preceded the onset of ataxia, generalized weakness and mental confusion by several years. Biochemical studies on isolated muscle mitochondria revealed defects in the mitochondrial respiratory chain which were located at NADH-CoQ reductase in Case 1, and at cytochrome b in Case 2. This study illustrates the potential value of muscle biopsy in the diagnosis of unusual and otherwise unexplained cerebral syndromes in man, even in the absence of muscle weakness.

Biopsy↗
PubMed1982

Effect of ionophore A23187 on cytosolic Ca2+ and enzyme secretion.

As the ionophore A23187 is believed to act by increasing cytosolic Ca2+ ([Ca]i), it offers a mechanism for experimentally controlling [Ca]i. Ca2+-selective microelectrodes were employed to examine the effect of A23187 on [Ca]i and the role of [Ca]i in acinar secretion. The mean [Ca]i in acinar cells of the mouse pancreas was determined to be 0.43 +/- 0.03 microM. When the ionophore was added to the saline bathing the acinar cells, 10(-6) M A23187 depolarized the membrane potential (Em) by 5.2 +/- 0.3 mM and the intracellular Ca-electrode potential (ECs) by 9.8 +/- 0.6 while 10(-5) M A23187 depolarized Em by 7.4 +/- 0.3 mV and ECs by 14.1 +/- 0.8. These changes in potentials reflect an increase in [Ca]i to 0.62 +/- 0.03 microM with 10(-6) M and 0.73 +/- 0.05 microM with 10(-5) M A23187. The increase in [Ca]i observed with 10(-6) M A23187 was similar to that found with concentrations of acetylcholine (Ach) that produced maximal enzyme secretion, whereas the increase in [Ca]i with 10(-5) M was similar in magnitude to that observed with ACh concentration that inhibited or reduced secretion. Measurements of amylase release during 30 min exposure of A23187 produced an 88.4% increase in amylase activity over basal levels with 10(-6) M and little or no change with (10(-5) M, indicating that the ionophore influences secretion through changes in [Ca]i in a manner analogous to the natural secretagogue ACh. This report establishes that acinar secretion occurs only within a narrow range of [Ca]i activities and suggests intracellular increases in both "bound" and "free" calcium may occur during cell activation.

Acetylcholine↗
PubMed1982

Intracellular Na+ and K+ activities during insulin stimulation of rat soleus muscle.

The action of insulin on the resting membrane potential (Em) and intracellular sodium and potassium activities (aNa, aK) of rat soleus muscle fibers was determined by direct intracellular measurements of aNa, aK, and Em using Na-selective, K-selective, and conventional microelectrodes. The use of these microelectrodes allowed us to continuously monitor these parameters in the same fiber. Although we were able to accurately measure aNa and aK and continuously monitor their levels throughout periods of insulin stimulation of up to 20 min duration, we were unable to detect any significant change in Em, aNa, or aK. Varying the concentration of insulin or extracellular glucose failed to alter our observations. These results indicate that the action of insulin on the sarcolemma and subsequent increase in glucose transport must result from some mechanism independent of a change in membrane potential or intracellular sodium or potassium activity.

Animals↗
PubMed1982

Stimulation of pancreatic acinar secretion: increases in cytosolic calcium and sodium.

Na+-selective and Ca2+-selective microelectrodes were used to examine the ionic mechanisms regulating acetylcholine (ACh) stimulation of pancreatic secretion. The cytosolic concentrations of free ionized Na+ and Ca2+ ([Na]i, [Ca]i) were determined in unstimulated acinar cells to be 10.5 +/- 0.4 mM and 0.43 +/- 0.03 microM, respectively. By measuring the induced changes in intracellular Ca2+, Na+, and membrane potentials (ECa, ENa, Em), we were able to demonstrate that 5 X 10(-8) M ACh depolarized Em by 4.3 +/- 0.2 mV and increased [Na]i and [ca]i to 12.2 +/- 0.3 mM and 0.58 +/- 0.02 microM, respectively. Stimulation with ACh at concentrations ranging from 10(-8) to 10(-5) M increased [Ca]i from 0.4 microM to between 0.5 and 1.0 microM. Amylase release reached a maximum at 10(-7) M ACh stimulation and progressively decreased at higher concentrations of stimulus. Increasing the stimulus above an optimal concentration appears to reduce or inhibit enzyme release. These experiments provide direct evidence supporting the concept that acinar cell secretion is triggered by increases in [Ca]i and of calcium's ability to act as primary intracellular mediator. Stimulation after removal of extracellular Ca2+ eliminated the increase in [ca]i that is usually observed in secreting cells, while producing the normal depolarization of Em and increase in [Na]i. These studies demonstrate the increases in [Ca]i are derived from an increase in membrane permeability to Ca2+ and the ability of ACh to depolarize the Em by a transmembrane movement of Na+ that is independent of the change in intracellular Ca2+.

Acetylcholine↗
PubMed1981

Hand wasting in spondylotic high cord compression: an electromyographic study.

Conventional and single-fiber electromyographic studies in two patients with a wasted hand associated with spondylotic narrowing of the spinal canal at C3-4 and C5-6 revealed changes that were most severe in the hand muscles (C8, T1) and moderately severe in the extensor digitorum communis (C7), but relatively spared the C5 and C6 myotomes. This gradation of abnormality within the cervical cord is consistent with stagnant hypoxia secondary to venous congestion.

Aged↗
PubMed1981

Cerebral compression by myeloma.

A patient presented with right hemiparesis, dysphasia and a large, palpable, left frontoparietal mass arising from the calvarial diploe. A diagnosis of multiple myeloma was made on radiological and biochemical grounds, together with bone marrow examination. Few cases of cerebral compression by a massive plasmacytoma have been reported, but in some surgical management produced clinical deterioration. The present case was treated with radiotherapy and chemotherapy, with satisfactory results.

Aged↗
PubMed1981

Transmembrane and transepithelial movement of calcium during stimulus-secretion coupling.

Electrophysiological studies were undertaken to determine the transmembrane and transepithelial changes in free Ca2+ concentration that occur during serotonin-induced secretion in the salivary glands of the blowfly, Phormia regina. Ca-selective and conventional microelectrodes were used to measure intracellular and luminal Ca2+ concentrations ([Ca]L), serosal membrane and transepithelial potentials (Em, Etr), and their changes during serotonin (5-hydroxytryptamine, 5HT)-induced salivary secretion. The effect of stimulus concentration on these parameters and enzyme release was also determined. Previous studies provided evidence that serosal stimulation with 10(-8) M 5HT caused a hyperpolarization of Em and short phasic two- to threefold increases in [Ca]i. In these studies, higher concentrations of 5HT (10(-7) M) resulted in depolarization of Em by 13 +/- 1.2 mV and of ECa by 64 +/- 2.1 mV, a dramatic increase in [Ca]i, and a decrease in enzyme release. In addition, serotonin (10(-8) M) reduced the normal spontaneous Etr (+19.6 +/- 1 mV) to near zero while causing an increase in [Ca]L from 1.3 +/- 0.3 X 10(-5) mM to 2.0 +/- 0.1 X 10(-3) mM, a concentration isomolar with that of the bathing medium. These results provide direct electrochemical evidence that, during stimulus-secretion coupling of the salivary epithelial cells, the neurohormone serotonin controls the secretory response by the regulation of intracellular Ca2+ and induces transepithelial transport of Ca2+, thereby suggesting that, during secretion, the neurohormone causes the salivary gland to behave as a "leaky epithelium" by activating the paracellular shunt pathways.

Animals↗
PubMed1980

Calcium regulation during stimulus-secretion coupling: continuous measurement of intracellular calcium activities.

Accurate measurements of intracellular calcium activities in salivary gland epithelial cells of the insect Phormia regina were obtained with microelectrodes in which N,N'-di(11-ethoxycarbonyl)undecyl-N,N'-4,5-tetramethyl-3,6-dioxaoctane diacid diamide wsa incorporated in a liquid membrane system. When calibrated in solutions approximating the ionic concentration of the cell interior, these microelectrodes gave rapid stable responses that were linear functions of the logarithm of calcium activities and were not affected by potassium, sodium and magnesium. Continuous monitoring of calcium activities during serotonin-induced saliva release provided direct evidence of hormonal influence on transmembrane calcium movement and spontaneous regulation of intracellular calcium by stimulated cells.

Animals↗
PubMed1980

Insulin does not act by causing a change in membrane potential or intracellular free sodium and potassium concentration of adipocytes.

The influence of insulin on the intracellular free sodium and potassium ion concentrations ([Na+]i, [K+]i) and resting membrane potential of rat epididymal adipocytes was examined to determine its potential for mediating insulin's action on other cellular processes. Direct intracellular measurements of [Na+]i, [K+]i, and the resting membrane potential were made using ion-selective and conventional microelectrodes. The use of these microelectrodes enabled us to continuously monitor these parameters in the same cell before, during, and after periods of insulin stimulation of up to 20-min duration. The electrical potentials measured in these experiments remained unchanged when the cells were stimulated with insulin (0.01, 0.1, or 1.0 mU/ml). Varying the extracellular glucose concentration had no effect on these results. Our results provide the first direct measurement of [Na+]i and [K+]i in adipose tissue and clearly demonstrate that the response to insulin's association with its receptors on the cell surface and subsequent action on hexose transport and cellular metabolism does not involve a change in membrane potential or intracellular sodium and potassium ions.

Adipose Tissue↗
PubMed1979

Spasticity due to phenytoin toxicity.

A young epileptic presented with spasticity as well as ataxia, diplopia and nystagmus; his serum phenytoin level was very high. All the abnormal signs disappeared after withdrawal of phenytoin. Spasticity, hyperreflexia, and clonus are features of phenytoin intoxication, present in this case, which are not commonly seen, and which have rarely been mentioned previously in the literature.

Adult↗
PubMed1979

Eosinophilc polymyositis.

A case of eosinophilic polymyositis is reported. Tender muscle swelling was followed by proximal weakness, creatinine kinase elevation, and electromyographic features typical of polymyositis. Severe myocarditis, pericarditis and heart failure were present. Muscle biopsy specimen showed active myositis with eosinophil infiltrate. Unlike previous cases, blood eosinophils count was normal. The clinical response to corticosteroids was excellent, and a relapse occurring as steroid dose was lowered responded rapidly to an increased dose of prednisolone. Eosinophilic polymyositis may be a component of a general systemic illness with prominent cardiac involvement.

Adult↗
PubMed1979

Supranuclear ophthalmoplegia with basilar artery aneurysms.

In two patients, large aneurysms of the basilar artery produced a supranuclear gaze paresis, involving horizontal gaze in one case and vertical gaze in the other. In both cases the diagnosis was suggested by computed tomography and confirmed by vertebral angiography. Autopsy findings in one case confirmed the diagnosis. Although supranuclear gaze palsies must reflect damage to structures deep within the brain stem, these cases illustrate that an extrinsic lesion may produce such damage indirectly. Basilar artery aneurysm should be considered in patients presenting with supranuclear gaze paresis and long tract signs.

Aged↗
PubMed1978

Polymyositis presenting with severe weakness involving only one arm.

A woman presented with severe weakness and wasting involving only one arm. A definite diagnosis was not made until almost six years later when she developed proximal weakness in the legs as well, and a muscle biopsy showed changes of polymyositis. Asymmetry of weakness in polymyositis has been noted previously in the literature, but is rare. In previous reports asymmetry as marked as in the present case has not been noted.

Arm↗