Silent myocardial ischaemia: characteristics and management.
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Coronary Disease↗
Biomedical subjects
T J Higgins
Publications and source records attributed to T J Higgins.
Infection control in general dental practice. Results of a postal survey of 600 registered dental practitioners in New South Wales.
A postal survey of 600 dental practitioners in New South Wales was conducted in 1986 to establish a data base on current infection control protocols as they apply to everyday dental practice. Three hundred and sixty-three replies (60 per cent) were returned, representing approximately 16 per cent of Australian Dental Association members in New South Wales (1987).
Communicable Disease Control↗
Clinical experience with lisinopril. Observations on safety and tolerability.
The safety and tolerability of lisinopril (1.25-160 mg daily) were assessed in 3,270 patients (2,688 hypertensives and 582 patients with congestive heart failure (CHF] and 280 healthy subjects. The duration of therapy ranged from a single dose to 43 months; 438 patients received lisinopril for at least 12 months (mean 20 months). In the hypertensive population, the most frequent adverse events reported were headache, dizziness, cough, nausea, diarrhoea and fatigue, although not all of these events were thought to be related to lisinopril; 6.1% discontinued lisinopril due to adverse clinical events, most commonly cough and nausea. Twelve hypertensive patients died (0.45%), but most of these were not receiving lisinopril at the time of death and none was considered to be drug-related. In CHF patients, the most frequently reported adverse events were dizziness, dyspnoea, diarrhoea, hypotension and fatigue. Again, not all of these reports were considered to be drug-related. Therapy was withdrawn in 9.6% of patients--hypotension, dizziness, diarrhoea and rash being the most frequent reasons. Fifty-three CHF patients died (9.1%) and in three cases death was considered to be related to lisinopril therapy. Hypotension, orthostatic effects or dizziness following the initial dose of lisinopril occurred infrequently (in 1.3% of the hypertensive group, including those receiving hydrochlorothiazide, and in 4.8% of CHF patients). Changes in laboratory parameters were generally minor and seldom resulted in discontinuation of therapy. Long-term treatment of hypertension and CHF with lisinopril for at least 3 years confirms that the drug is well tolerated. Overall, the side-effect profile is very similar to that of other ACE inhibitors with regard to class-specific effects. However, taste disturbance was rarely observed.
Adult↗
Monitoring the fate of dietary proteins in rumen fluid using gel electrophoresis.
1. When fractionated by sodium dodecylsulphate-polyacrylamide gel electrophoresis (SDS-PAGE), strained rumen fluid from sheep fed on pelleted lucerne (Medicago sativa) hay showed no major protein components that stain with Coomassie Blue. This feature made it possible to monitor the fate of individual polypeptides within a protein mixture incubated in rumen fluid in vitro. 2. Extracts from a number of seed meals (sunflower (Helianthus annuus), lupin (Lupinus angustifolius), rape (Brassica napus) and pea (Pisum sativum L.)), as well as casein and bovine serum albumin, were examined in this system. The protein components of each seed type showed a wide range of resistances to degradation. One protein in pea seeds (pea albumin 1), which is particularly rich in cysteine, was almost as resistant to rumen degradation as bovine serum albumin. 3. Analysis of synthetic-fibre-bag experiments by SDS-PAGE showed that the rate of loss of total protein from solid meal residues does not provide an index of the resistance of individual protein components of the meal to rumen degradation. While there was no qualitative change in the protein profile of residual pea-seed meal inside a synthetic-fibre bag, there was considerable variation in the rate at which individual, solubilized protein components were degraded in the surrounding rumen fluid.
Animals↗
A monoclonal antibody with reactivity to asialo GM1 and murine natural killer cells.
A monoclonal antibody (MAb) was prepared by the fusion of murine SP2-O myeloma cells with BALB/cByJ spleen cells that were immunized with the glycolipid asialo GM1 adsorbed to naked Salmonella. The specificity of the IgM antibody obtained was defined using various glycolipids, cell extracts and saccharides in ELISA assays and thin-layer chromatography (TLC) immunoblots. The non-reducing terminal galactose is the immunodominant residue for this antibody; however, there is undetectable reactivity to free galactose, galactosylceramide or compounds with an alpha-linked galactose. The SH-34 antibody specifically lyses asialo GM1-expressing macrophages in the presence of complement and removes NK cells in vitro from spleen cell populations. When the specificity of the MAb was compared to that of a commercially available rabbit antiserum to asialo GM1, it was found that both cross-reacted with GM1 and asialo GM3 at high antibody concns; however, the MAb did not bind asialo GM2 while the rabbit antiserum showed substantial reactivity to this glycolipid. It is anticipated that this MAb will be useful for the study of murine and rat natural killer cells.
Animals↗
The efficacy and tolerability of antihypertensive treatment based on atenolol in the prevention of stroke and the regression of left ventricular hypertrophy.
Nine hundred and thirty nine moderate to severe hypertensive patients were treated with a combination of atenolol, a beta 1 selective receptor blocker, diuretics and where required, additional vasodilator therapy to achieve adequate blood pressure (BP) control. Patients were followed up for a period of 10.2 years (mean 6.1 years). Amassed clinical exposure amounted to 5465 patient years. Mean BP fell from 183.0 +/- 1.0/109.2 +/- 0.5 mmHg to 145.1 +/- 0.6/89.3 +/- 0.3 mmHg and treatment resulted in a significant regression of the electrocardiographic signs of left ventricular hypertrophy (LVH). Side effects of treatment were consistent with those expected from a regime comprising a combination of a beta 1 selective hydrophilic beta-blocker, diuretics and vasodilators. Reported side effects appeared to diminish with time; were more common in the elderly than in the young and increased in frequency as the dose of atenolol increased. Biochemical disturbance was minimal. Total mortality (n = 91) and mortality from myocardial infarction (n = 40) were positively related to treated systolic blood pressure (SBP). A J-shaped curvilinear relationship between treated diastolic blood pressure (DBP) and death rate from myocardial infarction has been shown. Although the number of deaths from stroke was small (n = 21), there appeared to be a positive relationship with treated DBP: by contrast the data suggest that in the elderly, lowering SBP to below about 140 mmHg might be associated with an increased incidence of death from stroke.
Adolescent↗
Gene structure, protein structure, and regulation of the synthesis of a sulfur-rich protein in pea seeds.
Two low molecular weight pea seed albumins (Mr approximately 6000 and approximately 4000) have been characterized by protein, cDNA, and gene sequencing. Both proteins are encoded by separate regions of the same mRNA species. The initial translation product is a preproprotein from which a signal sequence is removed co-translationally. The resultant proprotein (PA1) is then cleaved post-translationally to yield the mature form of the two albumins (PA1a and PA1b). Comparison of cDNA and protein sequences suggests that at least four different PA1 genes are expressed in the pea genome. Both PA1a and PA1b have an unusually high cysteine content (7.5 and 16.2%, respectively). Pea seeds developing under suboptimal levels of sulfur nutrient supply contain reduced levels of PA1 mRNA and accumulate greatly reduced levels of PA1a and PA1b in the mature seed. In vitro transcription studies showed that this reduced level of PA1 mRNA resulted from reduced post-transcriptional stability rather than an altered rate of transcription of the PA1 gene. In contrast, during normal seed development, the level of PA1 mRNA seems to be under transcriptional control. Sequence comparisons reveal some homology between PA1 and a number of low molecular weight proteins from seeds of a wide range of mono- and dicotyledonous plants.
Albumins↗
Actinobacillus endocarditis.
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Actinobacillus↗
Current concepts in periodontal diseases.
Periodontal diseases are common oral diseases that afflict all humans to some degree. The major aetiological agent is dental plaque--the complex microflora which forms on teeth in the absence of effective oral hygiene. The interaction of the microbial flora and the periodontal tissues produces an inflammatory response and tissue breakdown. Recent information has categorized periodontal diseases on the basis of increased knowledge about the particular microorganisms associated with the different clinical conditions. In addition, the important role of host defences, in particular the phagocytic cellular elements, has allowed for a better understanding of the pathological processes. This knowledge is contributing towards the development of rational and effective therapy for all forms of periodontal diseases. Because of the widespread occurrence of periodontal diseases and their potential relationships to systemic conditions, it is important that medical practitioners should be able to recognize, and be conversant with methods of treatment of, these diseases.
Acute Disease↗
Transcriptional and post-transcriptional regulation of storage protein gene expression in sulfur-deficient pea seeds.
We have used in vitro transcription in isolated pea nuclei to determine whether the expression of genes for the seed storage proteins legumin and vicilin is regulated transcriptionally or post-transcriptionally in response to changing sulfur status in the developing seed. During the first 48 h of recovery from S deficiency, transcription of legumin genes increased by two-fold whereas the level of legumin mRNA increased 20-fold in the same period. Vicilin gene transcription decreased during recovery, consistent with a gradual decrease in mRNA levels. We conclude that regulation of legumin mRNA levels in response to changing S status is post-transcriptional, whereas that of vicilin mRNA is transcriptional. In contrast, during normal plant development the expression of both of these gene families appears to be under transcriptional control.
Gene Expression Regulation↗
Murine antibody response to the glycolipid asialo GM1 adsorbed to Salmonella.
The murine antibody response to the asialo GM1 adsorbed to stripped Salmonella was studied. IgM and IgG responses were obtained which did not fall to baseline within 200 days after the initial immunization. The antisera from the experimental group showed strong reactivity to asialo GM1 and measureable amounts of activity to asialo GM2. Sera from control animals receiving Salmonella alone also reacted to asialo GM2. Additional experiments showed that the anti-asialo GM1 and the anti-asialo GM2 activities were the result of separate antibody populations. Antisera from an early bleed of the experimental group showed specific lysis of asialo GM1 bearing macrophages; however, later bleeds from both experimental and control groups lysed asialo GM1 expressing and normal macrophages equally. These results suggest an autoimmunity had been generated. The suitability of this protocol for generating specific antiserum and immunizing in preparation for generating monoclonal antibodies is discussed.
Animals↗
Influence of Sulfur Nutrition on Developmental Patterns of Some Major Pea Seed Proteins and Their mRNAs.
In addition to the marked reduction in legumin synthesis and legumin mRNA levels reported earlier (Chandler, Higgins, Randall, Spencer 1983 Plant Physiol 71: 47-54), pulse labeling of S-deficient Pisum sativum L. seeds showed that a high relative level of total vicilin (vicilin plus convicilin) synthesis was maintained throughout the entire phase of protein accumulation, whereas in nondeficient seeds vicilin synthesis is largely confined to the first half of this phase. Fractionation of pulse-labeled proteins on Na-dodecylsulfate-polyacrylamide gels showed that the synthesis of the M(r) 50,000 family of vicilin polypeptides was increased and greatly extended in S-deficient seeds whereas that of convicilin was slightly reduced. Other changes apparent from pulse-labeling experiments include a depression, to different degrees, in the synthesis of three major albumin polypeptides.The level of the mRNAs for seven major seed proteins was followed throughout development of control and sulfur-deficient seeds. In all cases, the changes in each mRNA closely reflected the pattern of synthesis of its corresponding polypeptide seen by pulse labeling. S-deficient seeds showed an elevated level of M(r) 50,000 vicilin mRNA which remained high throughout seed formation, whereas legumin mRNA levels were greatly reduced at all stages of development.When S-deficient plants were given an adequate supply of sulfate midway through seed development, there was a shift toward the protein synthesis profile characteristic of healthy plants. The synthesis of legumin and two albumins rapidly increased and the synthesis of M(r) 50,000 vicilin declined more slowly. Similar responses were seen in detached, S-deficient seeds supplied directly with adequate sulfate.
Journal Article↗
Pyogenic dental infections--a retrospective analysis.
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Abscess↗
Simplified fluorometric assay for sphingosine bases.
A simplified procedure for fluorometric determination of sphingosine bases is presented. Nitrogenous bases are reacted with fluorescamine and then extracted into a lower phase solvent, obviating the need to transfer the reaction products prior to quantitation. Consequently, the entire procedure may be carried out in a single set of screw-capped reaction tubes. Chloroform was found to be the best solvent of those tested for the maximal extraction of derivatized sphingosine bases with negligible extraction of nitrogenous contaminants derived from phospholipids and amino sugars. The simplified method retains excellent sensitivity and selectivity and allows for simultaneous processing of large numbers of samples. Furthermore, quantitation of glycolipid-derived hexosamine can be obtained by measuring the fluorescence of the aqueous phase after partitioning.
Chloroform↗
The biosynthesis and primary structure of pea seed lectin.
Isolation of pea lectin from immature seeds, together with in vivo pulse-chase labeling and in vitro translation of RNA from such seeds, all gave results which indicated strongly that pea lectin is initially synthesized as a large precursor (pre-pro-form) (Mr = 25,000) which is cleaved both co- and post-translationally to yield the alpha and beta subunits of mature lectin. Two overlapping cDNA plasmids complementary to lectin mRNA were sequenced. They coded for both beta and alpha subunits of lectin, in the orientation beta leads to alpha from the NH2 terminus, together with a hydrophobic NH2-terminal leader sequence and included a 3' untranslated region of 124 nucleotides. In the appropriate reading frame, no stop codon was found between the coding sequences for the beta and alpha subunits, confirming the synthesis of pea lectin via a pre-pro-form. The entire pea lectin sequence showed a high degree of homology with the published amino acid sequences of lectins from lentil, broad bean, and, to a lesser extent, with concanavalin A from jack bean. Sequence variation occurred mainly in those regions thought not to be involved in metal- and sugar-binding or in the formation of beta-pleated sheets.
Amino Acid Sequence↗
Intracellular sites of synthesis and processing of lectin in developing pea cotyledons.
The biosynthesis and processing of pea lectin was studied in developing pea cotyledons by a combination of pulse-chase experiments using 14C-aminoacids and subcellular fractionation of the homogenates. Lectin polypeptides were isolated on immunoaffinity gels and fractionated on sodium dodecyl sulfate-polyacrylamide gels followed by fluorography. Whether made in vivo or in an in vitro chain completion system containing polysomes still attached to microsomal membranes, newly synthesized lectin had an Mr of 23,000. In vivo labeling showed that radioactive lectin first associates with the rough endoplasmic reticulum and is then sequestered into the lumen of the endoplasmic reticulum. Pulse-chase experiments showed that it is chased out of the endoplasmic reticulum considerably more slowly than the storage proteins and accumulates in the protein bodies, initially as a polypeptide of Mr = 23,000. This pro-lectin is processed in the protein bodies to its mature form with polypeptides of Mr = 17,000 and 6,000. Pea lectin is synthesized throughout the protein accumulation phase of seed formation with maximum levels of synthesis and of mRNA approximately half-way through this period.
Endoplasmic Reticulum↗
The effects of cyanide and iodoacetate intoxication and ischaemia on enzyme release from the perfused rat heart.
Isolated rat hearts perfused in the presence of iodoacetate show inhibition of glycolysis and release enzymes into the perfusate. Hearts perfused with cyanide, a mitochondrial inhibitor, show acceleration of glycolysis and no enzyme release. The adenine nucleotide content of the iodoacetate, but not the cyanide-perfused hearts was reduced. These results indicate that the membranes were permeable in the former treatment group. The adenylate energy charge and the ATP content of both the cyanide and iodoacetate treatment groups were similar but, as the extent of enzyme release was quite different, it appears that the energy state of the cell was not the prime factor controlling membrane integrity. Isolated perfused hearts were rendered ischaemic by placing a one-way ball valve in the aortic outflow tract. ATP concentration declined, as did ADP after an initial rise of short duration. AMP concentrations rose as the time of ischaemia increased. At the time at which enzyme release was first determined, the intracellular total adenine nucleotide content began to decline, suggesting that the membrane had become permeable to both small and large molecules. Glycolysis was stimulated by the hypoxia induced in the preparation and then this increase became inhibited. The point at which this inhibition was observed was also the point at which membrane permeability was evident. Taken together, the data from these experiments suggest that the energy derived from the activity of the glycolytic pathway may be important to the heart for maintenance of membrane function, particularly in ischaemia.
Adenine Nucleotides↗
Regulation of Legumin Levels in Developing Pea Seeds under Conditions of Sulfur Deficiency: Rates of Legumin Synthesis and Levels of Legumin mRNA.
It was shown previously that when peas (Pisum sativum L.) are grown with suboptimal sulfur supply the level of legumin (the more S-rich of the two major seed storage proteins) in the mature seed is selectively reduced (Randall, Thomson, Schroeder, 1979 Aust J Plant Physiol 6: 11-24). This paper reports a study of the cellular mechanisms involved in regulating legumin synthesis under these conditions. Pulse and pulse-chase labeling experiments were carried out with excised, immature cotyledons from normal and S-deficient plants. Legumin was isolated from cotyledon extracts by immunochromatography, and the proportion of legumin synthesis relative to total protein synthesis was determined. Results showed that reduced legumin accumulation could largely be accounted for by a greatly reduced level of legumin synthesis (80-88% reduction) rather than by a major increase in legumin breakdown.Legumin mRNA levels were assayed by two methods. In vitro translation of polysomal RNA from cotyledons of normal and S-deficient plants indicated a reduction of 60 to 70% in synthesis of legumin-related products by preparations from S-deficient plants. A legumin cDNA clone was constructed, characterized, and used to measure the levels of legumin mRNA in polysomal and total RNA preparations from developing cotyledons. Legumin mRNA levels were reduced by 90% in preparations from S-deficient plants.When restored to an adequate S supply, S-deficient plants (or pods taken from such plants) recovered normal levels of legumin synthesis (in vivo and in vitro) and of legumin mRNA. These results indicate that reduced legumin accumulation under conditions of S deficiency is primarily a consequence of reduced levels of legumin mRNA.
Journal Article↗