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P Butler

Publications and source records attributed to P Butler.

At least 73 records · Page 4Linked to original sources
PubMed1994

Coordinate pulsatile insulin secretion by chronic intraportally transplanted islets in the isolated perfused rat liver.

In the present studies we sought to address the following questions: do chronically transplanted intrahepatic islets (IHI-Tx) secrete insulin in a coordinate pulsatile manner, and, if so, is reestablishment of this coordinate pulsatility a function of time after transplantation? We studied isolated perfused livers at 10 mM glucose from 27 rats rendered diabetic with streptozotocin and then transplanted with approximately 2 x 10(3) islets, 2 (n = 5), 7 (n = 5), 30 (n = 5), and 200 (n = 12) d after transplantation. 12 out of 12 of the 200-d IHI-Tx secreted insulin in coordinate pulses (frequency 3.9 +/- 0.3 pulses/h, amplitude 15.2 +/- 2.4 nmol/min). In contrast, one out of five 2-d, zero out of five 7-d, and one out of five 30-d IHI-Tx showed pulsatile insulin secretion. Insulin secretion was markedly greater (76 +/- 13 vs 13 +/- 3 nmol/min, P < 0.0001) in the 200-d versus early IHI-Tx. Pentobarbital 25 micrograms/ml had no effect on total (13.9 +/- 3.9 vs 15.9 +/- 3.9 nmol/min), nonpulsatile (12.9 +/- 3.5 vs 14.1 +/- 3.3 nmol/min), or pulsatile (pulse amplitude 17.6 +/- 4.5 vs 20.0 +/- 4.2 nmol/min, pulse frequency 4.1 +/- 0.3 vs 4.0 +/- 0.7 pulses/h) insulin secretion. Using synaptophysin, islet innervation was documented in 12 out of 12 200-d IHI-Tx but in none of the early IHI-Tx. We conclude that established (approximately 200 d) IHI-Tx secrete insulin in a coordinate pulsatile manner and that establishment of coordinate pulsatile insulin secretion by IHI-Tx is accompanied by increased total insulin secretion and is associated with islet reinnervation.

Animals↗
PubMed1994

THE USE OF HEART RATE TO ESTIMATE OXYGEN CONSUMPTION OF FREE-RANGING BLACK-BROWED ALBATROSSES DIOMEDEA MELANOPHRYS

Heart rates (fh) and rates of oxygen consumption (V(dot)O2) were measured in eight black-browed albatrosses (Diomedea melanophrys) when walking on a treadmill, with the aim of using fh to predict V(dot)O2 in free-ranging albatrosses. The resulting relationship between the variables was: V(dot)O2 (ml min-1) = [0.0157fh (beats min-1)]1.60, r2=0.80, P<0.001. In addition to the calibration procedure, six of the albatrosses were injected with doubly labelled water (DLW), and fh and V(dot)O2 were monitored continuously over a 3 day period while the birds were held in a respirometer. During the 3 day period, the birds were walked for up to 3&shy;4 h day-1 in bouts lasting approximately 0.5 h. The heart rate data were used to estimate the metabolic rates of these birds using the above regression. Estimates of metabolic rate derived from fh, DLW and respirometry did not differ (ANOVA; P=0.94), primarily because of the variance between individual birds. There was also no significant difference between the different estimates obtained from the different equations used to calculate energy expenditure from the DLW technique (ANOVA; P=0.95). Mean estimates of V(dot)O2 from fh under active and inactive conditions differed from measured values of V(dot)O2 by -5.9 % and -1.7 % respectively. In addition, the estimates of V(dot)O2 from fh at different walking speeds did not differ significantly from the measured values. It appears that, in the black-browed albatross, fh is as good a predictor of the mean metabolic rate of free-ranging birds as DLW or time&shy;energy budgets combined with either respirometry or DLW. However, the method should be applied to as many individuals and as many instances of a particular behaviour as possible. The heart rate technique offers potential for much more detailed analyses of the daily energy budgets of these birds, and over much longer periods, than has previously been possible.

Journal Article↗
PubMed1993

Autoimmune disease and molecular mimicry: an hypothesis.

Helper T lymphocytes are normally only stimulated to initiate an immune reaction through the recognition of peptides bound to class II major histocompatibility complex (MHC) molecules. Class II MHC molecules are constitutively expressed on antigen-presenting cells which play a critical role in the initiation of immune responses. In disease states, however, other cells often express class II MHC molecules inappropriately. This article suggests an hypothesis for the pathogenesis of autoimmune diseases based on molecular mimicry. The mimicry described is between microbial or viral peptides presented by antigen-presenting cells and self peptides presented inappropriately on a target tissue. This leads to helper T cells, stimulated by peptides derived from infectious organisms, initiating an autoimmune attack on the target tissue.

Amino Acid Sequence↗
PubMed1993

M2 mitochondrial antibodies and urinary rough mutant bacteria in patients with primary biliary cirrhosis and in patients with recurrent bacteriuria.

Primary biliary cirrhosis (PBC) patients have a higher incidence of recurrent urinary tract infection and an increased prevalence of rough forms (mutants) of E. coli in their stool samples than other chronic liver disease patients. PBC patients exhibit autoantibody reactivity against mitochondria, the most common antigen (M2) being a family of antigens with the major components having approximate molecular weights of 74, 56, 52 and 48 kD. Cross-reactivity between M2 antigen components and corresponding antigenic bands of bacteria has been demonstrated with PBC sera. Patients with recurrent urinary tract infections, all of whom had normal liver function and were taking prophylactic antibiotic treatment, had weak anti-mitochondrial antibody (AMA) reactivity (69%), with reactivity against the 74-kD antigen alone being the most common. When antibody to the 74-kD band was eluted, it was found to cross-react with bacterial membrane fractions. In the controls, 12/77 chronic liver disease patients and 2/24 normals possessed AMA. Rough forms of bacteria were found in the urine of patients with significant bacteriuria: 39% PBC, 5.3% chronic liver disease and 41% of the recurrent urinary tract infection group. M2 antibodies may be induced by urinary organisms in 'normal' women with recurrent bacteriuria and in females with PBC.

Autoantibodies↗
PubMed1993

A double blind randomised trial of low power laser treatment in rheumatoid arthritis.

OBJECTIVES: To define the value of low power laser treatment in small joint rheumatoid arthritis. METHODS: Twenty five women with active disease were recruited. The metacarpophalangeal and proximal interphalangeal joints of one hand were treated with 12 J/cm2 for 30 s with a gallium-aluminium-arsenate laser. The other hand received a sham laser treatment designed so that neither therapist nor patient could distinguish the active laser from the sham laser. Each patient received 12 treatments over four weeks. The following parameters were measured: pain as assessed by visual analogue scale; range of joint movements; grip strength; duration of early morning stiffness, joint circumference, Jebsen's hand assessment; drug usage; total swollen joint counts; Arthritis Impact Measurement Scales; three phase bone scans; haematological and serological tests. RESULTS: A total of 72% of patients reported pain relief but this reduction was reported equally in both hands. No significant changes were seen in other clinical, functional, scintigraphic, or laboratory features. Neither patients nor staff were able to detect which hand was treated with the active laser. CONCLUSION: When this specific laser and dose regimen was used, low power laser treatment had no objective effect on patients with rheumatoid arthritis. It did appear to produce analgesia through a powerful placebo effect.

Adult↗
PubMed1993

Hepatic and extrahepatic insulin action in humans: measurement in the absence of non-steady-state error.

The isotope dilution technique has been extensively used to assess insulin action in humans. To determine if nonsteady state (NSS) has led to erroneous estimates of hepatic and extrahepatic insulin sensitivity, we measured glucose turnover in healthy subjects during infusion of insulin at rates of 0.25, 0.6, and 2.0 mU.kg-1.min-1. Turnover was calculated using Steele's traditional NSS equations [fixed-effective volume (pV) method] as well as with methods [radioactive infused glucose (hot-GINF) or variable pV] designed to minimize NSS error. In contrast to the fixed-pV method, both the hot-GINF and variable-pV methods indicated that several hours were required for suppression of hepatic glucose release at all insulin concentrations and that small increases in plasma insulin (approximately 100 pmol/l) had comparable effects on glucose disappearance and hepatic glucose release. Nevertheless, despite these differences, when turnover during the final hour of the insulin infusions was plotted vs. the prevailing insulin concentration, all three methods yielded similar insulin dose-response curves for suppression of hepatic glucose release. Thus despite previous errors in measurement of glucose turnover, the widely accepted belief that the human liver is exquisitely sensitive to small changes in insulin is correct.

Adult↗
PubMed1992

Use of chromosomal gene fusions to investigate the role of repetitive DNA in regulation of genes involved in lipopolysaccharide biosynthesis in Haemophilus influenzae.

The lic3 locus of Haemophilus influenzae consists of four open reading frames. The derived amino acid sequences of orf2 and orf4 exhibit homology to Escherichia coli GalE and AdK, respectively. The functions of orf1 and orf3 remain unknown. orf1 contains multiple tandem repeats of the tetrameric DNA sequence CAAT near the 5' end. Two possible translational starts (ATG1 and ATG2) lie upstream. We have used lacZ fusions to investigate whether changes in the number of CAAT repeats in conjunction with differential usage of the upstream frames control the expression of lic3-orf1. Phase-variable expression of lacZ was observed for individual colonies and could be related to variable numbers of CAAT repeats. Of the three possible upstream frames, only one, containing the more downstream of the two possible ATG start codons (ATG2), is used for strong expression of lacZ. Utilization of the more upstream ATG (ATG1) or ATG2 was observed with medium-level expression, while utilization of any of the three possible frames was observed when lacZ was expressed at low to undetectable levels, indicating that other mechanisms may affect expression. To investigate this, lacZ was fused in frame with ATG2 of lic3-orf1, with concomitant deletion of the repeats. Phase-variable expression was still observed, supporting the view that an alternative level of control operates in conjunction with the repeat mechanism.

Amino Acid Sequence↗
PubMed1992

Use of [3-3H]glucose and [6-14C]glucose to measure glucose turnover and glucose metabolism in humans.

[3-3H]glucose is frequently used to measure glucose turnover in humans. If fructose 6-phosphate-fructose 1,6-diphosphate cycling (Fpc) is negligible in both liver and muscle, then [3-3H]- and [6-14C]glucose (corrected for Cori cycle activity) should provide equivalent measures of glucose turnover. In addition, if glycogenolysis is fully suppressed, then [14C]lactate specific activity should equal that of [6-14C]glucose from which it was derived, and oxidation of [6-14C]glucose, as measured by rate of generation of 14CO2, should equal total glucose oxidation (i.e., that derived from intra- and extracellular pools) as measured by indirect calorimetry. To address these questions, glucose turnover was measured simultaneously with [3-3H]- and [6-14C]glucose in the basal state and in presence of low (approximately 200 pM) and high (approximately 750 pM) insulin concentrations. Glucose turnover rates measured with [3-3H]- and [6-14C]glucose were equivalent at all insulin concentrations, indicating that Fpc had no detectable effect on measurement of glucose appearance. [14C]lactate specific activity was lower (P less than 0.01) than that of [6-14C]glucose in the basal state but not during either low- or high-dose insulin infusion, implying that all lactate was derived from extracellular glucose. On the other hand, glucose oxidation as measured by rate of generation of 14CO2 was lower (P less than 0.05) than glucose oxidation as measured by indirect calorimetry during both insulin infusions, implying either that suppression of glycogenolysis was not complete in all tissues or that one or both of these techniques do not accurately measure glucose oxidation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

The influence of needle size on post-myelography headache: a controlled trial.

This study aimed to test the hypothesis that the use of fine rather than larger calibre needles for myelography reduces the incidence of post-procedural headache. 160 patients were randomized in a prospective controlled trial of 22 gauge versus 26 gauge needles. The incidence and overall severity of headache as measured at 1, 4 and 21 days after myelography was not significantly different in the two groups.

Female↗
PubMed1991

Effects of chronic systemic insulin delivery on insulin action in dogs.

The metabolic consequences of the prolonged systemic insulin delivery associated with human pancreas transplantation have not been precisely defined. To determine if systemic insulin delivery in the absence of immunosuppressive agents results in alterations in hepatic or extrahepatic insulin action, three groups of dogs were studied 2 months after either a sham operation or after their pancreatic venous drainage was severed and anastomosed to the inferior vena cava or portal vein (sham, peripheral and portal groups, respectively). The pattern of venous drainage was documented by measuring vena cava and portal insulin concentrations before and after glucose injection. Systemic insulin concentrations were higher (p less than 0.05) in the peripheral group than in the portal group both following a 14-h fast and after intravenous glucose. During a hyperinsulinaemic euglycaemic clamp (1 mU.kg-1.min-1), glucose utilization (measured using [6(3)H]glucose) was slightly lower (p = 0.07) in the peripheral than in the portal group. Hepatic glucose release was equal in all groups. Carbon dioxide incorporation into glucose (an estimate of gluconeogenesis) was higher in the portal than peripheral group in the fasted state but not during insulin infusion. Plasma concentrations and flux rates of fatty acids and amino acids did not differ between groups. We conclude that chronic systemic insulin delivery results in a) systemic but not portal hyperinsulinaemia, b) a minimal impairment in insulin-stimulated glucose uptake, without altering insulin-induced suppression of hepatic glucose release, and c) no effect on fatty acid or amino acid turnover.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Digital subtraction angiography (DSA) of the extracranial cerebral vessels: a direct comparison between intravenous and intra-arterial DSA.

Fifty patients being investigated for ischaemic cerebrovascular disease underwent both intravenous digital subtraction angiography (IV-DSA) and intra-arterial arch digital subtraction angiography (arch-DSA) to enable a direct comparison to be made between the two techniques. The overall quality of the images obtained by arch-DSA was better than that obtained by IV-DSA, but there was no significant difference between the number and gradation of stenoses detected by the two techniques. No significant stenosis was missed by IV-DSA and the technique was found to be sufficiently accurate for it to be used as a screening procedure for carotid bifurcation stenoses suitable for carotid endarterectomy. The advantages and limitations of both techniques are discussed.

Adult↗