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Biomedical subjects

M E Brown

Publications and source records attributed to M E Brown.

At least 73 records · Page 4Linked to original sources
PubMed1987

Age-related recurrence of basal forebrain lesion-induced cholinergic deficits.

Lesions of basal forebrain cholinergic nuclei projecting in neocortex have recently been employed as an animal model for the cholinergic deficits in Alzheimer's disease. However, unlike Alzheimer's patients, whose deterioration appears to be progressive and irreversible, basalis lesioned rats usually recover both behaviorally and neurochemically within several months after the lesion. We now demonstrate that this recovery may be a function of the age of the rat and that cholinergic deficits re-occur in the aged rat. Choline acetyltransferase (ChAT) activity and [3H]hemicholinium-3 ([3H]HCh-3) binding are reduced in cortex ipsilateral to ibotenic acid lesions in the 12-month postlesion rat following an initial recovery to normal levels by about 3 months postlesion. The recurrence of decrease of cholinergic markers is not a consequence of a non-specific age-related decline since the activity of glutamic acid decarboxylase remains constant between 3 and 12 months postlesion.

Age Factors↗
PubMed1987

Monitoring the bioenergetics of cardiac allograft rejection using in vivo P-31 nuclear magnetic resonance spectroscopy.

Monitoring human cardiac allograft rejection is currently accomplished by endomyocardial biopsy. Available noninvasive methods for identifying rejection have lacked the necessary sensitivity or specificity, or both, for routine clinical application. In vivo phosphorus-31 (P-31) nuclear magnetic resonance (NMR) spectroscopy has been used for monitoring phosphorus metabolism in both animal models and humans. In the present study this technique was employed as a noninvasive means to assess the bioenergetic processes that occur during cardiac allograft rejection in a rat model. Brown Norway rat hearts were transplanted subcutaneously into the anterior region of the neck of Lewis rat recipients (allografts). Control isografts employed Lewis donors and recipients. Phosphocreatine to inorganic phosphate (PCr/Pi), phosphocreatine to beta-adenosine triphosphate (PCr/ATP beta), beta-adenosine triphosphate to inorganic phosphate (ATP beta/Pi) ratios and pH of the transplanted hearts were monitored using surface coil P-31 NMR spectroscopy (at 4.7 tesla) daily for 7 days. To allow recovery from the compromise induced by the surgical procedure, the measurements obtained on day 2 were taken as a baseline. PCr/Pi was unchanged or increased in the isografts but decreased continually in allografts, with the difference becoming significant by day 4 when compared with levels in day 2 allografts (p less than 0.005) and by day 3 when compared with levels in the isograft group (p less than 0.05). PCr/ATP beta in isografts did not change throughout the study; however, allografts demonstrated a significant decrease as early as day 3 (p less than 0.01), although a significant difference between isografts and allografts did not become manifest until day 4 (p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1987

A mathematical method for analysing plasmid stability in micro-organisms.

A mathematical model describing the instability of plasmids in micro-organisms has been developed. The model is based on the assumption that the overall causes of plasmid instability are described by the segregational instability of the plasmid, R (i.e. the rate at which plasmid-free cells are generated from plasmid-bearing cells), and the growth rate difference, d mu (i.e. the difference in growth rate between plasmid-free and plasmid-bearing cells). A method for determining the values of R and d mu (accompanied by 95% confidence limits) for any plasmid-bearing micro-organism is described. This method is based on the observation that, depending on the plasmid, various exponential patterns of plasmid instability are observed. The stability of Escherichia coli 1B373(pMG169), where d mu much greater than R, and E. coli RV308(pHSG415), where R much greater than d mu, are analysed in order to demonstrate the method.

Escherichia coli↗
PubMed1987

Investigation of the effect of growth environment on the stability of low-copy-number plasmids in Escherichia coli.

The stability of a low-copy-number plasmid, pHSG415, in Escherichia coli, was investigated in batch and continuous culture. The plasmid was unstable in batch culture, but was significantly stabilized by growth in continuous culture with phosphate, nitrogen or potassium limitation. However, the plasmid was very unstable when grown in continuous culture with sulphate limitation. These results contrast with those obtained with multicopy plasmids such as pBR322, which is particularly unstable in carbon- or phosphate-limited continuous culture. The effect of growth rate on the stability of E. coli(pHSG415) grown in continuous culture with glucose limitation was also investigated. The plasmid was significantly more stable in cells grown at higher growth rates. The segregational instability (R) of the plasmid and the difference in growth rate between plasmid-free and plasmid-bearing cells (dmu) were calculated for each condition using the method of Cooper et al. (accompanying paper: Journal of General Microbiology 133, 1871-1880). It was found that the primary cause of the loss of pHSG415 from the cell population was the segregational instability of the plasmid.

Carbon↗
PubMed1987

Phorbol esters and A23187 regulate Na+-K+-pump activity in pancreatic acinar cells.

To clarify the subcellular mechanisms that mediate stimulation of Na+-K+-pump activity in pancreatic acinar cells by cholinergic agonists, we examined the effects of the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) and the Ca2+ ionophore A23187 on [3H]ouabain binding to dispersed guinea pig pancreatic acinar cells under conditions in which binding reflects the average rate of pump cycling. The phorbol ester more than doubled Na+-K+-pump activity as did the diacylglycerol analogue, 1-oleoyl-2-acetolyl-sn-3-glycerol. A23187 increased pump activity by a maximum of 31% at 0.3 microM but was progressively inhibitory at higher concentrations. The stimulatory effects of TPA and A23187 were additive, although either secretagogue elicited a less than additive response when added together with a maximally effective concentration of the cholinergic agonist, carbachol. Removal of extracellular Ca2+ had little effect on the pump response to TPA and did not reduce the maximal effect of A23187 but abolished the inhibitory effect seen at high ionophore concentrations in Ca2+-containing medium. These results indicate that both Ca2+ and protein kinase c are involved in regulating Na+-K+-pump activity in the pancreatic acinar cell.

Adenosine Triphosphate↗
PubMed1986

Regulation of muscarinic acetylcholine receptors in cultured guinea pig pancreatic acini.

Regulation of muscarinic receptors in cultured guinea pig pancreatic acini was investigated by assessing the effects of cholinergic agonists on binding of [N-methyl-3H]scopolamine [( 3H]NMS) and on amylase release. Freshly dispersed acini bound [3H]NMS with a Kd of 74 pM and a maximal binding level (Bmax) of 908 fmol/mg DNA. Carbachol (CCh) stimulated amylase secretion and inhibited [3H]NMS binding. Incubation of acini for 30 min with 0.1 mM CCh decreased the subsequent efficacy of CCh in stimulating amylase release by threefold but had no effect on its potency. In contrast, amylase release in response to cholecystokinin octapeptide (CCK-8) was not altered by CCh preincubation. [3H]NMS binding to acini was decreased only 15-20% after 30-min incubation with CCh. However, culture of acini with 0.1 mM CCh decreased [3H]NMS binding by 50% at 3-4 h and by 85-90% at 24 h. This decrease was attributable primarily to a reduction in Bmax. [3H]NMS binding also was decreased to a similar extent by the cholinergic agonists bethanechol and methacholine but not by other secretagogues. The decrease in antagonist binding induced by CCh was dose dependent, with the IC50, 5.8 microM, approximating the EC50 for amylase release, 4.3 microM. Culture of acini for 24 h with CCh abolished subsequent amylase release in response to CCh but not to CCK-8. When CCh was removed from the culture medium after 24 h and acini recultured in its absence, [3H]NMS binding increased with a half-time for recovery of 20-24 h; this recovery was blocked by cycloheximide.(ABSTRACT TRUNCATED AT 250 WORDS)

Amylases↗
PubMed1986

Long-latency auditory event-related potentials in epilepsy.

Long latency auditory event-related potentials have been shown to change in patients with cerebral dysfunction. Some seizure patients with no evidence of brain damage or mental retardation show altered interictal cognitive and memory function. Long-latency auditory event-related potentials to tone stimulation were recorded in nineteen control subjects and seventeen patients with complex partial or partial and secondarily generalized seizures who had no evidence of brain damage, retardation, or drug intoxication, and whose seizures were controlled when studied. The latencies of N2 and P3 components were significantly longer in seizure patients than control subjects, and the P3 waveform was significantly greater in amplitude in epileptics. These findings suggest that cognitive event-related potentials are affected by partial epilepsy. The changes may be related to the recently reported involvement of the hippocampus in ERP generation, or to loss or alteration of modulatory functions, possibly cholinergic in nature, in the temporal lobe consequent upon epileptogenesis.

Adult↗
PubMed1985

Desensitization with human (recombinant DNA) insulin.

A 34-year-old woman developed gestational diabetes and was treated with insulin (beef-pork and beef) and oral therapy at various periods. She developed an insulin allergy; however, attempts at desensitization with the commercially available purified pork insulin desensitization kit (Eli Lilly Co.) were not successful. Reactivity to human (recombinant DNA) insulin as well as elevated IgE levels and eosinophilia were also demonstrated. A second desensitization attempt with human (recombinant DNA) insulin using a protocol developed by the authors was successful. This report discusses a desensitization procedure using human insulin in an insulin-allergic patient.

Adult↗
PubMed1985

Computerized spectral analysis of the interictal EEG in epilepsy.

Eight seizure patients without encephalopathy, frequent seizures, brain lesion, or medication intoxication had significant slowing of alpha-frequency activity, as compared to nonepileptic controls, that was evident in compressed spectral analysis but not in standard EEG. Those patients with cognitive or behavioral problems or taking more than one antiepileptic medication had a greater degree of slowing. Differences between seizure patients with and without cognitive or behavioral symptoms, and between specific antiepileptic drugs, were suggested but could not be assigned significance due to small numbers. The findings suggest that interictal changes in brain function that are not revealed by standard EEG may relate to observed changes in interictal behavior and cognition, and that computerized spectral analysis of the interictal EEG may be of value in the assessment of seizure patients before and during therapy.

Adolescent↗
PubMed1981

Effect of monensin sodium on the performance and proportions of rumen volatile fatty acids of Friesian bulls.

The effect of including monensin sodium at a dose rate of 40 mg/kg in the diet of Friesian bulls (mean initial liveweight 158 kg) fed a barley-based diet ad libitum was assessed in terms of growth rate, feed intake, feed and energy conversion efficiency and the concentration and molar proportions of ruminal volatile fatty acids over a 157-day period. Mean daily feed dry matter intake for the treated group (5.4 kg) was 24 per cent lower than the control group (7.1 kg). The treated group grew at a significantly slower rate than the control animals although feed conversion efficiency was improved by the treatment. A comparison with the results of other workers suggested that the dose rate used had been too high. There were no significant differences in the molar proportions of volatile fatty acids in rumen fluid as a result of monensin usage. While many workers have shown increases in the molar proportions of propionic acid the fact that the control group in this experiment had a very high value (48 per cent) may explain the lack of response.

Administration, Oral↗
PubMed1980

Transient elevation of serum thyroid hormone concentration after initiation of replacement therapy in myxedema.

Measurements of thyroid hormone concentrations in serum are commonly used to determine the proper dose of hormone replacement. We have noted that early in the course of thyroxine (T4) replacement in myxedema, serum T4 concentrations may be transiently elevated before reaching a lower "steady-state" level. This observation is illustrated in a study of six patients. Serum T4, free thyroxine index, and triiodothyronine (T3) rose to peak concentrations at 2 to 6 weeks, 35% to 120% above the values achieved 4 to 8 months later. Values were transiently in the thyrotoxic range in five of the six patients. This phenomenon is most likely due to a decrease in the metabolic clearance rate of the absorbed hormone associated with hypometabolism. Thus, serum T4 and T3 concentrations during the first 6 months of therapy do not reflect the optimal dose of T4 replacement on a long-term basis.

Adolescent↗
PubMed1980

Measuring dimensions of the quality of care in small community residences.

Techniques previously used to assess the quality of care in large institutions (cf. Raynes, Pratt, & Roses, 1979) were adapted for a similar study of seven small community residences. Five areas were assessed: daily management practices, the physical environment, resident community involvement, staff-to-resident speech, and staff attitudes. Interitem correlations within each scale were generally high, and validity comparisons between the community residences and the larger institutions of Raynes et al. (1979) showed that scores on the measures were generally superior in the group homes. These dimensions of the caretaking environment varied independently of one another, clearly indicating the need for differentiated evaluation techniques.

Adolescent↗