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Biomedical subjects

J M Russell

Publications and source records attributed to J M Russell.

At least 19 recordsLinked to original sources
PubMed1992

Initial combination chemotherapy with cisplatin, methotrexate and vinblastine in locally advanced transitional cell carcinoma--response rate and pitfalls. MRC Subgroup in Advanced Bladder Cancer (on behalf of the MRC Urological Working Party).

A total of 51 patients with locally advanced transitional cell carcinoma of the bladder were entered into a phase II study to evaluate the effect of initial cisplatin (100 mg/m2, Day 2) combined with methotrexate (30 mg/m2, Days 1 and 8) and vinblastine (4 mg/m2, Days 1 and 8). Of 44 evaluable patients, 25 (57%) achieved an objective response of their primary bladder tumour (complete response (CR): 4 patients; partial response (PR): 21 patients); 30 of the 36 patients with micturition disturbances obtained relief. Toxicity was acceptable, but dose modifications due to haematological or renal toxicity were required in 153 of the 690 drug courses. Non-protocol dose modifications were performed 45 times. The experience gained in this trial emphasises the need for improved co-operation between urologists, radiologists and clinical oncologists in such multicentre phase II studies. Difficulties were observed in adhering to dose modification rules, assessing pre-treatment tumour size (due to variation in quality of measure and in timing relative to initial transurethral resection (TUR)) and defining response to chemotherapy (due to failure to perform mandatory investigations at the right time). This study also illustrates that the accepted criteria for assessing response in the primary bladder tumour are difficult to apply in practice and that the results of any study using this indicator lesion require caution in their interpretation.

Aged↗
PubMed1991

Identification of the phosphorylation sites in elongation factor-2 from rabbit reticulocytes.

The sites in eukaryotic elongation factor eEF-2 phosphorylated by the Ca2+/calmodulin-dependent eEF-2 kinase in vitro have been identified. The kinase catalysed the rapid incorporation of one mol of phosphate per mol eEF-2 and the slower incorporation of a second mol. All the phosphorylation sites in eEF-2 are contained in the CNBr fragment corresponding to residues 22-155. Tryptic digestion of phosphorylated eEF-2 yielded 3 phosphopeptides, one being unique to monophosphorylated eEF-2. The phosphorylation sites were identified as threonine residues 56 and 58, the former being more rapidly phosphorylated. Ala-Gly-Glu-Thr-Phe-Thr56-Asp-Thr58-Arg. The same sites are labelled in eEF-2 isolated from reticulocyte lysates.

Amino Acid Sequence↗
PubMed1991

Florid refractory schizophrenias that turn out to be treatable variants of HLA-associated narcolepsy.

Narcolepsy in which the hallucinatory component is unusually prominent may lead to the development of an illness indistinguishable from the schizophrenic syndrome. Psychotic symptoms dominate the symptomatology, so that the primary illness is obscured. Five patients are described for whom conventional antipsychotic drugs were ineffectual, but for whom treatment with stimulants produced substantial improvement. The diagnosis of narcolepsy was confirmed by Human Leukocyte Antigen typing and sleep laboratory testing. These results support the "REM intrusion" hypothesis of the causation of schizophrenia in as many as 7% of a series of schizophrenic patients. Implications for diagnosis and treatment are discussed.

Adult↗
PubMed1991

Successful methods for arterial blood gas interpretation.

Understanding acid-base disturbances is essential in the care of the critically ill patient. Through a systematic evaluation of patient symptoms and arterial blood gas values, patient care can be improved. These formulas can be effective tools for the nurse to use in the care of patients with acid-base imbalances.

Blood Gas Analysis↗
PubMed1990

Type IV flexor digitorum profundus avulsion.

Flexor digitorum profundus avulsions, are well-documented injuries occasionally associated with a distal phalanx fragment. While the injury may involve primarily either tendon or bone, a rarely observed variant combines both tendon and bone avulsions. A type IV variant seen after two sequential injuries is described.

Adult↗
PubMed1990

Osmotic stimulation of Na(+)-K(+)-Cl- cotransport in squid giant axon is [Cl-]i dependent.

The effects of increasing extracellular osmolality on unidirectional Cl- fluxes through the Na(+)-K(+)-Cl- cotransporter were studied in internally dialyzed squid giant axons. Hyperosmotic seawater stimulated bumetanide-sensitive Cl-influx at 150 mM intracellular Cl- concentration ([Cl-]i), whereas Cl- efflux was unaffected under comparable ionic conditions. Stimulation of bumetanide-sensitive Cl- influx was proportional to the increase in extracellular osmolality. Bumetanide-sensitive Cl- influx began to increase after a latency of approximately 20 min after a stepwise increase of extracellular osmolality and continued to increase for at least 70 min. The increased bumetanide-sensitive Cl- influx measured after 65 min of exposure to hyperosmotic external fluid was a function of the intracellular Cl- concentration; stimulation by hyperosmotic external fluids was observed at physiological [Cl-]i levels (greater than 100 mM) but not at lower [Cl-]i levels. Under both normo- and hyperosmotic conditions, intracellular Cl- inhibited Na(+)-K(+)-Cl- cotransport influx in a concentration-dependent manner. However, in hyperosmotic seawater, the dose dependence of inhibition by intracellular Cl- was shifted to higher [Cl-]i values. Therefore, we conclude that hyperosmotic extracellular fluids stimulate influx via the Na(+)-K(+)-Cl- cotransport by resetting the relation between [Cl-]i and transport activity.

Animals↗
PubMed1990

Binding of bumetanide to microsomes from optic ganglia of the squid, Loligo pealei.

Saturable high-affinity binding of [3H] bumetanide [dissociation constant (KD) = 80 nM] was measured in microsomal membranes prepared from squid optic ganglia. Under control conditions, the maximal specific binding of labeled bumetanide (Bmax) was approximately 6-7 pmol/mg protein. Binding had a higher relative affinity for bumetanide than for furosemide and depended on the presence of Cl- and K+, but not Na+, in the incubation media. In the case of K+, [3H]bumetanide binding was half-saturated at [K+] = 100 mM. The Cl- effect was biphasic. At [Cl-] between 0 and 150 mM, [3H]bumetanide binding increased with increasing [Cl-]. However, when [Cl-] was increased above 150 mM, [3H]bumetanide binding was progressively reduced. ATP acted as a nonessential activator [mean affinity constant (K0.5) approximately 1 microM] of the ion-dependent [3H]bumetanide binding by increasing the apparent binding capacity. The activation by ATP did not require Mg2+. Other adenosine analogues also stimulated the binding of bumetanide.

Adenine Nucleotides↗
PubMed1990

Self-medication by women attending a genitourinary medicine clinic.

A questionnaire was completed by 103 symptomatic women attending a busy, walk-in genitourinary medicine clinic in London before seeing a doctor. This questionnaire asked about the patients' own diagnosis of symptoms, previous remedies and their source. The answers were compared to their past history and current diagnosis. Of symptomatic women 56% had used a self-administered remedy prior to attending the clinic. This was significantly associated with a history of a previous episode of genital infection which had produced similar symptoms to the current problem. Forty-three percent of those who used self-medication reported some improvement in symptoms and more than 50% tolerated longer than 10 days of symptoms before attending the clinic.

Female↗
PubMed1989

Familial aggregation of blood pressure and anthropometric variables in patrilocal households.

Fifty-three households in a small Indian fishing community were surveyed for blood pressure, pulse rate, and anthropometric measurements (height, weight, and three skinfolds). In addition to nuclear family relationships, correlations for extended family members and in-laws living within a common household were estimated by maximum likelihood. Based on likelihood ratio tests, the hypothesis that correlations among genetically unrelated pairs from the same household are zero is rejected for systolic blood pressure. Among genetically related individuals, the degree of relationship does not affect the magnitude of the blood pressure correlations. For the anthropometric measurements, family resemblance is significant only for first-degree relatives, except that the correlation for uncle-child pairs is significant for subscapular skinfold, and brother-in-law-sister-in-law pairs resemble each other for height and weight. The results suggest that common household environment is a significant determinant of blood pressure but not fatness in this population.

Blood Pressure↗
PubMed1988

Intracellular Ca2+ does not activate the SITS-sensitive anion transporter in barnacle muscle.

By means of the intracellular dialysis technique, we have measured 36Cl efflux from single barnacle muscle fibers and compared the effects of raising intracellular ionized calcium concentration [( Ca2+]i) to the effects of lowering intracellular pH (pHi). Lowering pHi by 1 unit or less resulted in a 20-fold stimulation of 36Cl efflux which occurred relatively rapidly and which could be inhibited by 90-95% by 4-acetamido-4'-isothio-cyanostilbene-2,2'-disulfonic acid (SITS). In contrast, raising [Ca2+]i as much as 250-fold resulted in a relatively small increase of 36Cl efflux. The small increase occurred after a long latency, developed slowly and could not be blocked or prevented by treatment with SITS. We conclude that the increase of the SITS-sensitive 36Cl efflux caused by a fall of pHi is not mediated by a rise of [Ca2+]i.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1988

pH-sensitive activation of the intracellular-pH regulation system in squid axons by ATP-gamma-S.

The regulation of intracellular pH (pHi) is essential for normal cell function, and controlled changes in pHi may play a central role in cell activation. Sodium-dependent Cl-HCO3 exchange is the dominant mechanism of pHi regulation in the invertebrate cells examined, and also occurs in mammalian cells. The transporter extrudes acid from the cell by exchanging extracellular Na+ and HCO3- (ref. 9) (or a related species) for intracellular Cl- (refs 3, 4). It is blocked by the stilbene derivatives DIDS (4,4'-diisothiocyano-stilbene-2,2'-disulphonate, ref. 10) and SITS (4-acetamido-4'-isothiocyano-stilbene-2,2'-disulphonate, ref. 3), and has a stoichiometry of two intracellular H+ neutralized for each Na+ taken up and each Cl- extruded by the axon. Because the inwardly-directed Na+ concentration gradient is sufficiently large to energize both the HCO3- influx and Cl- efflux, this electroneutral exchanger could be a classic secondary active transporter, thermodynamically independent of ATP hydrolysis. However, at least in the squid axon, the exchanger has an absolute requirement for ATP (ref. 3). Thus, a major unresolved issue is whether this Na-dependent Cl-HCO3 exchanger stoichiometrically hydrolyses ATP (the pump hypothesis), or whether ATP activates the transporter by a mechanism such as phosphorylation or simple binding (the activation hypothesis). We have now explored the role of ATP in pHi regulation by dialysing axons with the ATP analogue ATP-gamma-S. In many systems, ATP-gamma-S is an acceptable substrate for protein kinases, whereas the resulting thiophosphorylated proteins are not as readily hydrolysed by phosphatases as are phosphorylated proteins. Our results rule out the pump hypothesis, and show that the basis of the axon's ATP requirement is the pH-dependent activation (by, for instance, phosphorylation or ATP binding) of the exchanger itself, or of an essential activator.

Adenosine Triphosphate↗
PubMed1988

A plasma membrane-enriched preparation from giant barnacle muscle fibers.

We describe a procedure for obtaining a highly enriched plasma membrane (sarcolemmal) preparation from muscle fibers of the giant barnacle (Balanus nubilus). The sarcolemmal-enriched portion migrated as a light fraction (F1) at the 10-24% sucrose interface. This fraction displayed saturable ouabain binding (Kd = 0.119 microM) that was enriched 10 times compared to that in the original homogenate. F1 was also prepared using muscle fibers previously labeled with 1,2-ditritio-1,2(2,2'-disulfo-4,4'-diisothiocyano)diphenylet hane, disodium salt [( 3H]-H2DIDS). F1 was enriched 25-fold in [3H]H2DIDS binding sites with respect to the homogenate. Ca2+-ATPase and succinic dehydrogenase-activities were low in F1, as was oxalate-supported Ca2+ uptake. Compared to membranes of sarcoplasmic reticulum origin, F1 was enriched in sarcolemma membranes by about 45-fold while it was enriched approximately 30-fold over mitochondrial membranes. Thus, F1 provides an extremely pure source of external muscle membranes.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1988

The interaction of intracellular Mg2+ and pH on Cl- fluxes associated with intracellular pH regulation in barnacle muscle fibers.

The intracellular dialysis technique was used to measure unidirectional Cl- fluxes and net acid extrusion by single muscle fibers from the giant barnacle. Decreasing pHi below normal levels of 7.35 stimulated both Cl- efflux and influx. These increases of Cl- fluxes were blocked by disulfonic acid stilbene derivatives such as SITS and DIDS. The SITS-sensitive Cl- efflux was sharply dependent upon pHi, increasing approximately 20-fold as pHi was decreased from 7.35 to 6.7. Under conditions of normal intracellular Mg2+ concentration, the apparent pKa for the activation of Cl- efflux was 7.0. We found that raising [Mg2+]i, but not [Mg2+]o, had a pronounced inhibitory effect on both SITS-sensitive unidirectional Cl- fluxes as well as on SITS-sensitive net acid extrusion. Increasing [Mg2+]i shifted the apparent pKa of Cl- efflux to a more acid value without affecting the maximal flux that could be attained. This relation between pHi and [Mg2+]i on SITS-sensitive Cl- efflux is consistent with a competition between H ions and Mg ions. We conclude that the SITS-inhibitable Cl- fluxes are mediated by the pHi-regulatory transport mechanism and that changes of intracellular Mg2+ levels can modify the activity of the pHi regulator/anion transporter.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1988

Vanadate and fluoride effects on Na+-K+-Cl- cotransport in squid giant axon.

The effects of vanadate and fluoride on the Na+-K+-Cl- cotransporter of the squid giant axon were assessed. In axons not treated with these agents, intracellular dialysis with ATP-depleting fluids caused bumetanide-inhibitable 36Cl influx to fall with a half time of approximately 16 min. In the presence of either 40 microM vanadate or 5 mM fluoride, the decay of bumetanide-inhibitable 36Cl influx was significantly slowed; half time for vanadate-treated axons is 45 min and for fluoride-treated axons is 37 min. These agents are not exerting their effects on Na+-K+-Cl- cotransport by influencing the rate of ATP depletion of the axon, since they had no effect on the ATP hydrolysis rate of an optic ganglia homogenate. We therefore suggest that these data support the hypothesis that Na+-K+-Cl- cotransport in squid axons is regulated by a phosphorylation-dephosphorylation mechanism and that vanadate and fluoride reduce the rate of dephosphorylation by inhibiting a protein phosphatase.

Adenosine Triphosphate↗