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Biomedical subjects

B Dean

Publications and source records attributed to B Dean.

At least 109 records · Page 6Linked to original sources
PubMed1989

Ferritin subunits in livers of siderotic mice.

The major ferritin species of mouse liver has been resolved by SDS-PAGE into two bands similar to the H and L subunits of rat liver ferritin with the L subunit predominating. Amino acid sequencing has confirmed the major, faster-migrating component as L chain. An additional, electrophoretically fast, minor ferritin was isolated from siderosome-containing subcellular fractions. In denaturing gels it gave a single 'F' subunit band of about 17 kDa, significantly smaller than the L and H subunits (about 20 and 21 kDa respectively). A small fragment isolated from the fast ferritin was sequenced. It corresponds to a 19-residue C-terminal peptide cleaved from L subunits in the assembled molecules. The F subunit must be derived from L subunits by loss of this peptide, and is not the expression product of a different gene. 'Fast' ferritins of siderotic mice and rats are thus analogous.

Amino Acid Sequence↗
PubMed1989

Dopamine uptake by platelets is selective, temperature dependent and not influenced by the dopamine-D1 or dopamine-D2 receptor.

The human platelet, which takes up and releases dopamine, has been proposed as a peripheral model for the study of dopaminergic neurons in the central nervous system (CNS). In addition, the platelet has been shown to possess membrane components with pharmacological properties similar to the dopamine-D1 (DA-D1) and D2 (DA-D2) receptor on dopaminergic neurons. We have therefore studied the specificity of the platelet uptake system for dopamine and, as dopamine uptake comprises both internalised and membrane bound dopamine, the contribution of the DA-D1 and DA-D2 receptor to the uptake of dopamine has been assessed. Significant uptake of 3H-dopamine by platelet rich plasma (PRP) occurred after 10 min incubation at 37 degrees C, uptake being maximal after 90 min. In contrast, at 4 degrees C no uptake of 3H-dopamine occurred up to 60 mins incubation but at 20 degrees C was approximately 8% of the 60 min uptake at 37 degrees C. The neurotransmitters serotonin and dopamine inhibited dopamine uptake by platelets in a dose dependent manner. Uptake of dopamine appeared to be via two systems, one of high affinity with low capacity and the other of lower affinity but high capacity. In contrast, noradrenaline, adrenaline, acetylcholine, gamma-aminobutyric acid and histamine (10 microM) had no effect on dopamine uptake by platelets. The DA-D1 receptor antagonist SCH 23390 (10 microns) and the DA-D2 receptor antagonists (10 microM) spiperone, domperidone and (+)-butaclamol did not significantly affect dopamine uptake by platelets. In addition, ouabain and desipramine (100 microM) inhibited dopamine uptake by 21% and 24% respectively whilst reserpine and imipramine (100 microM) increased uptake by 14% and 15%. We therefore conclude that platelets take up dopamine via a selective, temperature dependent mechanism. Our data also suggest that dopamine uptake by platelets does not involve the DA-D1 or DA-D2 receptor.

Biological Transport↗
PubMed1989

Double-blind controlled trial of azathioprine in children with newly diagnosed type I diabetes.

A double-blind controlled trial of azathioprine (2 mg.kg-1.day-1) was conducted with 49 patients aged 2-20 yr (mean 10.8 yr) who had newly diagnosed type I (insulin-dependent) diabetes. Patients were randomly assigned to receive either azathioprine (n = 24) or placebo (n = 25) for 12 mo, beginning within the 20-day period after diagnosis. Baseline clinical and metabolic characteristics did not differ between the two groups. No patient experienced complete remission, defined as restoration of normal carbohydrate tolerance without other treatment. Partial remission, defined as good metabolic control (hemoglobin A1c less than or equal to 7.9%, preprandial blood glucose less than or equal to 8 mM with an insulin dose of less than 0.5 U.kg-1.day-1), occurred in 10 placebo (40%) and 7 azathioprine (29%) patients at 6 mo and in 4 placebo (16%) and 4 azathioprine (17%) patients at 12 mo (differences not significant). Fasting plasma C-peptide was significantly greater in the azathioprine-treated group at 3 and 6 mo, but this difference was not sustained. C-peptide responses to a standard meal and the frequency of islet cell and insulin antibodies did not differ between the two groups over the 12-mo period. Azathioprine caused no significant side effects. We conclude that in the dosage used, and despite early effects on endogenous insulin secretion, azathioprine alone does not influence the remission phase in children with newly diagnosed type I diabetes.

Azathioprine↗
PubMed1989

Poison center utilization in nosocomial toxicologic exposures: a prospective study.

Accidental toxicologic exposures that occur within health care facilities (HCF's) have the potential to increase morbidity and mortality, as well as enhance medicolegal liability. By contacting the poison center immediately on recognition of these events, health care providers may ultimately lessen eventual toxic effects through appropriate intervention. Exposures of this nature reported to the poison center over a twelve month period were collected and tabulated for specific occurrences. Six categories of therapeutic misadventure were delineated: Right patient/wrong medication (18%); Right patient, right medication/wrong dose or route (16%); Lack of patient education (2%); Proximity of potentially harmful substances to confused persons (54%); and Incorrect equipment management (4%). This study seeks to increase awareness of poison center ability to assist in management of the "therapeutic misadventure."

Adult↗
PubMed1988

Chromatography of serum on Sep-pak C18 corrects falsely elevated vitamin D metabolite levels measured by protein binding assay.

Using a commercial kit method we obtained a vitamin D metabolite level within the normal range in a patient with biopsy-proven osteomalacia. This suggested that the ethanol extraction method employed had not removed serum factors known to falsely elevate the measurement of vitamin D metabolites. We therefore compared the levels measured after ethanol extraction and after purification by chromatography on Sep-pak C18 or Sephadex LH-20. Vitamin D metabolite levels after ethanol extraction of sera correlated with, but were higher than, those after chromatography on Sep-pak C18 cartridges (r = 0.84; 134 +/- 76 vs 76 +/- 46 nmol/l: mean +/- SD; p less than 0.01). Results were similar after chromatography on Sep-pak C18 and Sephadex LH-20 (r = 0.95; 79 +/- 46 vs 68 +/- 41 nmol/l). Sera from 5 patients (4 with osteomalacia, 1 with chronic pancreatitis/malabsorption) had vitamin D metabolite levels in the normal range after ethanol extraction but had low levels after Sep-pak C18 chromatography; four of these sera also had low levels after chromatography on Sephadex LH-20. These findings indicate that chromatography of serum on Sep-pak C18 cartridges corrects falsely elevated vitamin D metabolite levels measured by protein binding assay.

Adult↗
PubMed1988

A study of iron complexation in a swine model.

The treatment of iron poisoning consists of supportive care and efforts to remove or retard the absorption of iron from the gastrointestinal tract. A standard but rarely challenged treatment is to render the unabsorbed iron less soluble by complexing it with bicarbonate or phosphate solution. Another therapy is the use of oral deferoxamine. Bicarbonate and phosphate therapy are known to be associated with adverse outcomes if used inappropriately. Is their use justified? To closely simulate a potentially toxic iron overdose in a 24-month-old child, a swine model was used. Twenty fasted castrated male pigs weighing an average of 14.6 kg (+/- 3.0 kg) were orally dosed with 300 mg/kg FeSO4 (60 mg Fe/kg) and randomly placed into 1 of 4 treatment groups receiving 50 ml of distilled water (control), 5% sodium bicarbonate, 5% sodium dihydrogen phosphate, or deferoxamine (10 g). Sequential serum iron levels were obtained at 0, 1, 2, 4, and 6 hr. There were no significant differences in the absorption of iron, as reflected by serum iron concentrations, in the bicarbonate and phosphate groups when compared to the control group (p greater than 0.05). Deferoxamine therapy reduced iron serum concentrations, ie iron absorption, significantly (p less than 0.05) when compared to the control, bicarbonate and phosphate groups. This study provides evidence that efforts to form digestive tract complexation of iron with bicarbonate or phosphate are of no value.

Administration, Oral↗
PubMed1988

MR imaging of pericallosal lipoma.

Early pathologic reports of corpus callosal lipoma described a consistent relationship between the lipoma and the dorsal surface of the corpus callosum, particularly when the lipoma is not associated with corpus callosal agenesis. MR imaging, especially T1-weighted sagittal acquisitions, exquisitely demonstrated this anatomic relationship in three relatively asymptomatic patients. Therefore, in most cases, a lipoma of the corpus callosum is more accurately described as a pericallosal lipoma. In one individual, common associated findings (partial agenesis of the corpus callosum and choroid plexus lipoma) were also noted. Surgical therapy is usually not indicated because symptoms are generally not related and the anterior cerebral artery is often encased by the lipoma.

Adult↗
PubMed1988

Accidental childhood poisoning: influence of the type of caretaker on etiology and risk.

The primary audience of poison prevention programs is the parent(s) of children less than 6 years of age. Literature review reveals few references assessing other caretakers as risk factors in childhood poisoning. The frequency and severity of calls to the poison center by nonparental caretakers was studied. A total of 4,205 poisoning cases involving children under 6 years of age were analyzed. In 11.9% of the cases the caretaker at the time of exposure was someone other than the parents and the site of the exposure was other than the child's home. Of the 3,702 cases where the exposure occurred while the child was supervised by the parents in their home, 90.2% were treated in the home and 72.4% required dilution only. Grandparents represented 39.6% of caretakers other than the parents. In these cases 44.6% required treatment beyond dilution, indicating more serious exposures in this group. Ingestion of cardiovascular drugs occurred in 12.3% of calls from grandparents as opposed to 0.7% of calls initiated by parents. Poisoning exposures involving children under six years of age, where the caretaker is other than the parents, and the site is other than the child's home, are often more serious. Poison prevention information programs are needed to reduce the risk factors among this group.

Accidents, Home↗
PubMed1988

Adolescent poisoning: a comparison of accidental and intentional exposures.

The fact that intentional drug and toxic substance use/abuse by adolescents has dramatically increased during the past 2 decades often overshadows the knowledge that adolescents also suffer accidental poisonings as well. A 1-year retrospective analysis of 1,879 poison exposures involving children 13 to 17 years of age revealed 894 (47.6%) were due to accidental circumstances and 945 (50.2%) were intentional in nature. Nonpharmaceuticals were involved in 63.5% of all accidental adolescent poisonings versus 36.5% involving various drugs. Intentional nonpharmaceutical exposures were 17.5% compared to total intentional adolescent poisonings, while 82.5% involved drugs. Site of exposure was the child's own home in 1,252 (66.7%) cases, school in 201 (10.8%), the workplace in 35 (1.9%), and other/unknown sites accounted for 387 (20.6%) poisonings. Poisoning by ingestion accounted for 1,408 (74.9%) of the adolescent exposures, inhalations 147 (7.8%), ocular 219 (11.5%), and dermal 110 (5.8%). Management at the nearest health care facility (HCF) was necessary in 1,252 (66.6%) of the poisonings versus 627 (33.4%) who were treated in non-HCF environments. Regional poison centers must be cognizant that accidental as well as intentional poisoning can occur with adolescents. Distinct viable prevention strategies should be developed to address these problems.

Accidents↗
PubMed1987

Isolation of a post-binding inhibitor of insulin action from the sera of non-insulin-dependent diabetics.

We have reported that sera from a majority of patients with non-insulin-dependent diabetes mellitus (NIDDM) inhibit insulin-stimulated lipogenesis (3-3H-glucose conversion to 3H-lipid) in rat adipocytes to a greater extent than control sera or sera from patients with insulin-dependent diabetes mellitus (IDDM). This effect was apparently due to a circulating, low molecular weight (Mr) substance soluble in acid/ethanol and resistant to proteases. We now describe the further characterization of this inhibitor isolated uniquely from NIDDM sera. Size exclusion chromatography of acid/ethanol extracts of sera on a Bio-Rad P2 column revealed the presence of a Mr 300-400 inhibitor of insulin-stimulated lipogenesis in 32 (70%) of 46 NIDDM sera but not in 9 IDDM or 12 control sera. NIDDM sera that contained the low Mr inhibitor had significantly elevated haemoglobin A1c levels compared with those without the inhibitor (14.1 +/- 2.6% vs 11.5 +/- 2.7%, p less than 0.001). In rat adipocytes, the low Mr inhibitor at a dilution equivalent to 1:40 unextracted serum, reduced maximal insulin-stimulated lipogenesis by 33%, 14C-6-glucose oxidation by 70% and 14C-1-glucose oxidation by 25%. In contrast, insulin-stimulated 2-deoxy-D-(1-3H) glucose uptake was unaffected. In the presence of the inhibitor, insulin sensitivity (insulin dose required for half-maximal response) was unchanged for lipogenesis but decreased for 14C-6-glucose oxidation and increased for 14C-1-glucose oxidation. In the presence of control sera, the low Mr inhibitor decreased basal lipogenesis (a measure of serum insulin-like activity) and its effect on insulin-stimulated lipogenesis was unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1986

A high prevalence of diabetes in a rural village in Papua New Guinea.

The prevalence of glucose intolerance was determined in a sample of 192 adults (34% of the adult population) from Wanigela in rural Central Province, Papua New Guinea. This centre was chosen to compare the high prevalence rates previously found in residents from this village who had become urbanized in Port Moresby. The age- and sex-standardised rates for abnormal glucose tolerance in Wanigela were significantly lower than those recorded in the urban community. However, the crude rates of 8.9% for diabetes and 5.7% for impaired glucose tolerance are among the highest reported for rural populations in the Pacific. These results strongly suggest that a genetic predisposition to glucose intolerance is present in this ethnic group, and argue for the early adoption of primary prevention programmes as the process of development encroaches rapidly upon the traditional lifestyles of previously isolated communities in Papua New Guinea.

Adolescent↗
PubMed1986

Fasting plasma insulin. A risk factor for abnormal electrocardiogram in Maltese residents of Australia.

Analysis of atherogenic risk factors in 493 Maltese-born residents of Melbourne showed that after adjustment for the effects of age, fasting plasma insulin was the only factor with a highly significant (p = less than 0.001) association with electrocardiogram abnormalities suggestive of atherosclerotic coronary artery disease. Absence of peripheral arterial pulses was not correlated with abnormal electrocardiogram but was significantly associated with both age and smoking. Elevation of plasma insulin appears to be a significant risk factor for atherosclerotic heart disease.

Adolescent↗
PubMed1985

Structural homology between mouse liver and horse spleen ferritins.

Mouse liver ferritin is composed almost exclusively of polypeptide chains similar in molecular mass (22 kDa) to that characteristic of the major chain (H) found in heart ferritin isolated from human, horse or rat. In these species the predominant polypeptide of liver (L) is smaller (about 20 kDa). Here we show that mouse liver and horse spleen ferritins and apoferritins exhibit extensive structural homology as judged by the similarity in the diffraction patterns of their crystals grown from cadmium sulphate solutions. Implications of this finding are discussed.

Animals↗
PubMed1985

Insulin resistance, acanthosis nigricans, and polycystic ovaries associated with a circulating inhibitor of postbinding insulin action.

A 21-yr-old moderately obese woman with hirsutism, acanthosis nigricans, and oligomenorrhoea was diagnosed as having polycystic ovary syndrome. Despite hyperinsulinemia, binding of insulin to her red cells was within the range for normal, young adult subjects. Her serum did not bind or degrade [125I]insulin or alter its binding to fat cells, and was negative for insulin receptor antibodies. However, her serum caused a dose-dependent inhibition of insulin-stimulated lipogenesis (conversion of [3-3H]glucose to [3H]lipid) in rat fat cells significantly greater than that produced with control serum (relative potency, 3.5:1) and (at a 1:20 dilution) markedly impaired the response of both lipogenesis and 2-deoxy-D-glucose uptake to maximum concentrations of insulin. After the patient was treated with clomiphene for 4 months, her menses resumed, hair growth slowed, fasting blood glucose and plasma insulin concentrations decreased, and serum inhibitory activity decreased to the control range. Serum inhibitory activity was stable to freezing and thawing and to heating at 56 C for 30 min, and could be extracted into acid-ethanol. By dialysis, its mol wt was below 1000, whereas by ultracentrifugation, it was above 3500; both high and low mol wt forms were detected after Sephadex G-50 gel chromatography of serum, suggesting that the inhibitor was of low mol wt but loosely bound to a higher mol wt component in serum. These findings indicate that insulin resistance in this patient with acanthosis nigricans and polycystic ovaries could be attributed to a circulating low mol wt inhibitor of postbinding insulin action.

Acanthosis Nigricans↗
PubMed1985

Increase in remission rate in newly diagnosed type I diabetic subjects treated with azathioprine.

Azathioprine (2 mg/kg) was given, in addition to routine insulin treatment, to alternate patients presenting with recent-onset type I diabetes. Treated (N = 13) and untreated (N = 11) patients did not differ significantly at diagnosis with respect to age, duration of symptoms, body weight, blood glucose, hemoglobin A1c, or presence of ketosis. Eight patients were treated for 12 mo, three elected to stop treatment at 6 mo, and treatment was stopped in two because of side effects. Seven treated patients had a remission compared with one untreated patient. At 12 mo these seven patients were distinguished by significantly higher basal and glucagon-stimulated levels of C-peptide (1.98 +/- 0.52 and 3.88 +/- 0.34 micrograms/L, respectively) compared with the other six treated patients (0.93 +/- 0.52 and 1.32 +/- 0.85 microgram/L, respectively), and by the persistence of islet cell cytoplasmic antibodies. Remissions were not sustained in the 1-2 yr after treatment, although relapsed patients required less insulin for control. These results corroborate those from nonrandomized trials using cyclosporine and suggest that protracted treatment with nonspecific immunosuppressive drugs may be necessary to avert insulin dependence.

Adolescent↗
PubMed1984

Glucose tolerance and mortality in diabetes mellitus in Maltese-born residents of Victoria.

In view of the recognized high prevalence of diabetes mellitus in Malta compared with Australia, 75 g oral glucose tolerance tests were performed on 396 Maltese-born residents of Melbourne. Eighteen (4.5%) were found to have diabetes mellitus and 19 (4.8%) were found to have impaired glucose tolerance by current criteria. Glucose tolerance was correlated with family history of diabetes, with age, with obesity and with parity in women, but not with length of residence in Australia. Analysis of statistical data of death certification showed that Maltese-born residents of Victoria had a higher age-specific mortality from both diabetes mellitus and ischaemic heart disease than did Victorian Italian-born residents or the total Victorian population. This was most marked in women. The results suggest that Maltese immigrants to Australia after years of residence, still run a higher risk of becoming affected with diabetes mellitus or ischaemic heart disease than the average for the Australian population. The relative importance of genetic and environmental factors involved in this difference should be the subject of continuing study in the future.

Adolescent↗