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Biomedical subjects

E R Brown

Publications and source records attributed to E R Brown.

At least 37 records · Page 2Linked to original sources
PubMed1999

Sex difference in the relationship of calcium and magnesium excretion to glycaemic control in type 1 diabetes mellitus.

In order to assess the variability and possible causes of calcium and magnesium losses in diabetes mellitus, urinary calcium and magnesium excretion were monitored six monthly over a 3-year period in 108 stable, type 1 diabetic patients who were having assessment of their clinical status and glycaemic control over the same period. In the patients studied the ranges of excretion of both calcium and magnesium were considerably wider than our non-diabetic reference ranges but the within subject variation in excretion was high. However, using mean values obtained over the study period, a direct relationship was observed between the excretion of both calcium and magnesium and HbA1 in female patients (P < 0.01) but not in males who had similar HbA1 values. The urinary excretion of calcium and magnesium did not relate to any of the other clinical or biochemical indices measured, including body mass index, daily insulin dose, retinal status or albumin excretion. It is suggested that, in poorly controlled patients, females may have a greater risk than males of developing the complications associated with chronic calcium and magnesium loss.

Adult↗
PubMed1998

Preservation of cholinergic activity and prevention of neuron death by CEP-1347/KT-7515 following excitotoxic injury of the nucleus basalis magnocellularis.

We have identified a class of small organic molecules, derived from the indolocarbazole K-252a, that promote the survival of cultured neurons. However, many of these indolocarbazoles inhibit protein kinase C and neurotrophin-activated tyrosine kinase receptors. These kinase inhibitory activities may limit the utility of these compounds for neurological disorders. A bis-ethyl-thiomethyl analogue of K-252a, CEP-1347/KT-7515, has been identified that lacks protein kinase C and tyrosine kinase receptor inhibitory activities, yet retains the ability to promote survival of cultured neurons, including cholinergic neurons derived from the basal forebrain. In the present studies, CEP-1347/KT-7515 was assessed for neurotrophic activity on basal forebrain neurons of in vivo rats following excitotoxic insult. Ibotenate infusion into the nucleus basalis magnocellularis reduced levels of choline acetyltransferase activity in the cortex, as well as reduced numbers of choline acetyltransferase-immunoreactive and retrogradely (FluoroGold)-labelled cortically-projecting neurons in the nucleus basalis. Systemically administered CEP-1347/KT-7515 attenuated the loss of cortical choline acetyltransferase activity and the loss of the number of choline acetyltransferase-immunoreactive and retrogradely-labelled FluoroGold neurons in the nucleus basalis. Moreover, CEP-1347/KT-7515 ameliorated the loss of cortical choline acetyltransferase if administration was initiated one day, but not seven days post-lesion. Together, these results demonstrate that CEP-1347/KT-7515 protects damaged cortically-projecting basal forebrain neurons from degeneration. Thus, CEP-1347/KT-7515 may have therapeutic potential in neurodegenerative diseases, such as Alzheimer's disease, in which basal forebrain cholinergic neurons degenerate.

Animals↗
PubMed1998

Metabolic screening.

Mandated, universal metabolic screening has been an effective tool for the early identification of infants with metabolic disorders, particularly those amenable to improved outcome with dietary management or medication. Although the availability of diagnosis long before symptoms occur may be useful to preclude expensive diagnostic evaluation when the subtle early symptoms begin and may allow for genetic counseling and testing in affected families, many concerns have been raised regarding the psychologic impact of presymptomatic diagnosis of diseases that are either fatal or for which no effective treatment is available. Before mass screening is initiated, careful pilot studies need to be done to evaluate sensitivity and specificity as well as the impact of early identification on infant outcome.

Humans↗
PubMed1997

K+ accumulation and K+ conductance inactivation during action potential trains in giant axons of the squid Sepioteuthis.

1. During action potential trains in giant axons from the squid Sepioteuthis, decline of the peak level of the undershoot potential was observed. The time course of the decline of the undershoot could be fitted with a three-exponential function with time constants of approximately 25, approximately 400 and approximately 7,000 ms, respectively. 2. When the osmolarity of the external solution was doubled by adding glucose (1.2 M), the fast component of undershoot decline, but not the medium and slow components, was significantly reduced. 3. Under voltage clamp in high osmolarity solutions where K+ accumulation was completely removed, repeated depolarizing pulses at 40 Hz (designed to mimic a train of action potentials) elicited K+ currents whose peak value declined. The decline is consistent with inactivation of the K+ conductance (gK). The decline of gK was fitted by a two-exponential function with time constants of approximately 400 and approximately 7,000 ms, respectively. 4. Interventions designed to modify Schwann cell physiology, such as high frequency stimulation (100 Hz, 2 min), externally applied ouabain (100-500 microM), L-glutamate (100 microM), ACh (100 microM), Co2+ (5mM), Ba2+ (2mM), or removal of external Ca2+ by EGTA, had no significant effects on the fast, medium or slow components of undershoot decline. 5. The results suggest that the fast component of undershoot decline represents K+ accumulation in the space between Schwann cell and axolemma. The medium and slow components are the result of axonal gK inactivation. Schwann cells appear to be involved in K+ clearance only to the extent that they provide an efficient physical pathway for the clearance of K+ by extracellular diffusion.

Action Potentials↗
PubMed1997

Hypophysiotropic CRF neurons display a sustained immediate-early gene response to chronic stress but not to adrenalectomy.

Immediate-early genes (IEGs) are now widely used to identify neurons acutely activated by extracellular stimuli. Though challenge-induced IEG expression is typically transient, examples of sustained elevation have been reported, including in hypothalamic magnocellular neurosecretory neurons of osmotically challenged rats. Another chronic stimulus, adrenalectomy (ADX), targets parvocellular neurosecretory neurons in the paraventricular nucleus of the hypothalamus (PVH), resulting in a persistent elevation in the synthesis and secretion of corticotropin-releasing factor (CRF). In the present study we used hybridization histochemical methods to compare the effects of ADX on the induction over time of two independent IEG markers, c-fos and NGFI-B, in hypophysiotropic CRF neurons. The induction of both c-fos and NGFI-B mRNA was greatest 3 to 6 after ADX, diminished by 12 h, and no longer detectable at 24, 48, 72 h, or 6 days after surgery. Immunohistochemical analyses using a Fos-specific N-terminally directed antiserum also revealed Fos immunoreactivity (-ir) in the PVH at early time points (3 h), but not later than 12 h after ADX. Combined immuno- and hybridization histochemistry on tissue from 3 h ADX rats localized Fos-ir and NGFI-B mRNA to parvocellular CRF-expressing neurons, the majority of which expressed both Fos and NGFI-B. These early IEG responses, however, were not paralleled by increases in CRF mRNA, which was not significantly elevated until 48 h after ADX. In the chronically ADX rat, CRF neurons are capable of c-fos expression since animals subjected to an acute injection of hypertonic saline 5 days after ADX displayed a robust induction of Fos-ir in the parvocellular PVH. Furthermore, a chronic challenge, insulin-induced hypoglycemia, provoked comparable c-fos mRNA and protein expression in CRF neurons in the PVH of ADX and sham-operated rats, which was observed both acutely (2 h) and chronically (5 days) after the onset of hypoglycemia. The maintenance of Fos expression in parvocellular CRF neurons following chronic hypoglycemia, but not ADX, suggests an involvement of distinct signaling pathways in the maintenance of hypophysiotropic neuron responses to chronic steroid withdrawal and stress.

Adrenalectomy↗
PubMed1997

Contribution of PKC to beta-hexosaminidase-induced airway smooth muscle proliferation.

beta-Hexosaminidases (Hex) A and B promote mitogenesis via airway smooth muscle (ASM) mannose receptor. The objective of this study was to elucidate the contribution of protein kinase C (PKC) in Hex-induced mitogenesis in ASM cells (ASMC). Exposure of ASMC to Hex caused increases in both the calcium-dependent and the calcium-independent PKC activities. Both downregulation of PKC and PKC inhibitors staurosporine and calphostin C diminished Hex-induced DNA synthesis and cell number. Hex-induced DNA synthesis was enhanced by a diacylglycerol kinase inhibitor, R-59022, which was blocked by calphostin C. These data suggest that activation of PKC in part mediates Hex-induced mitogenesis in ASMC.

Animals↗
PubMed1997

Evaluation of Bionike one-step tests for the detection of drugs of abuse in urine.

Bionike one-step tests were used to screen urine samples for amphetamines, methamphetamines, benzodiazepines, cannabinoids, methadone and opiates, and results were compared with those obtained using enzyme multiplied immunoassay technique d.a.u. assays. Taking into consideration different threshold levels and possible differences in cross-reactivities, there was good agreement between the methods. Results of Bionike tests correlated well with amphetamines, methadone and opiates detected in urine using gas chromatography-mass spectrometry. Bionike methods are rapid, simple to use, and relatively inexpensive for on-site testing of individual drugs or groups of drugs in urine.

Amphetamine↗
PubMed1997

Different excitation-contraction coupling mechanisms exist in squid, cuttlefish and octopod mantle muscle

Excitation-contraction (EC) coupling was studied in central zone mantle muscle fibres of a squid (Alloteuthis subulata), a cuttlefish (Sepia officinalis) and an octopod (Eledone cirrhosa). Thin slices of muscle were used for twitch experiments and enzymatic isolation of single fibres for whole-cell patch-clamp studies. The current required for a supramaximal twitch response during direct stimulation of muscle slices was lower for squid than for cuttlefish. In squid, but not in cuttlefish, the current-response relationship was independent of slice thickness (range 0.1-0.5 mm). Twitches of squid and cuttlefish slices were reversibly abolished by removal of extracellular Ca2+. In squid, but not in cuttlefish, the current-response relationship was Na+-dependent, and in the absence of Na+ higher current strengths were required to generate a supramaximal response. In whole-cell voltage-clamp experiments on isolated muscle fibres from squid, cuttlefish and Eledone cirrhosa, a sustained inward current was recorded upon depolarisation. This current was blocked by 5 mmol l-1 Co2+ and suppressed by 10 micromol l-1 nifedipine. In squid, an additional inward fast-activating transient current was seen which was blocked by 2 micromol l-1 tetrodotoxin and depolarised holding potentials. The fast current represents a voltage-activated Na+ channel, and the slow currents represent L-type Ca2+ channels. We conclude that squid possess a specialised rapid EC coupling mechanism in central zone fibres that is absent in cuttlefish and Eledone cirrhosa.

Journal Article↗